
@article{langfelder2008,
  title = {{{WGCNA}}: An {{R}} Package for Weighted Correlation Network Analysis},
  shorttitle = {{{WGCNA}}},
  author = {Langfelder, Peter and Horvath, Steve},
  year = 2008,
  month = dec,
  journal = {BMC Bioinformatics},
  volume = {9},
  number = {1},
  pages = {559},
  issn = {1471-2105},
  doi = {10.1186/1471-2105-9-559},
  urldate = {2024-10-10},
  copyright = {http://creativecommons.org/licenses/by/2.0},
  langid = {english},
  file = {C:\Users\706194\Zotero\storage\7B9GXQ94\Langfelder og Horvath - 2008 - WGCNA an R package for weighted correlation network analysis.pdf}
}



@article{chen2024,
  author = {Chen, Li-Pang and Qiu, Bangxu},
  title = {SIMEXBoost: An R package for Analysis of High-Dimensional Error-Prone Data Based on Boosting Method},
  journal = {The R Journal},
  year = {2024},
  note = {https://doi.org/10.32614/RJ-2023-080},
  doi = {10.32614/RJ-2023-080},
  volume = {15},
  issue = {4},
  issn = {2073-4859},
  pages = {5-20}
}


@article{chentsao2024,
    author = {Chen, Li-Pang and Tsao, Hui-Shan},
    title = {GUEST: an R package for handling estimation of graphical structure and multiclassification for error-prone gene expression data},
    journal = {Bioinformatics},
    volume = {40},
    number = {12},
    pages = {btae731},
    year = {2024},
    month = {12},
    abstract = {In bioinformatics studies, understanding the network structure of gene expression variables is one of the main interests. In the framework of data science, graphical models have been widely used to characterize the dependence structure among multivariate random variables. However, the gene expression data possibly suffer from ultrahigh-dimensionality and measurement error, which make the detection of network structure challenging and difficult. The other important application of gene expression variables is to provide information to classify subjects into various tumors or diseases. In supervised learning, while linear discriminant analysis is a commonly used approach, the conventional implementation is limited in precisely measured variables and computation of their inverse covariance matrix, which is known as the precision matrix. To tackle those challenges and provide a reliable estimation procedure for public use, we develop the R package GUEST, which is known as Graphical models for Ultrahigh-dimensional and Error-prone data by the booSTing algorithm. This R package aims to deal with measurement error effects in high-dimensional variables under various distributions and then applies the boosting algorithm to identify the network structure and estimate the precision matrix. When the precision matrix is estimated, it can be used to construct the linear discriminant function and improve the accuracy of the classification.The R package is available on https://cran.r-project.org/web/packages/GUEST/index.html.},
    issn = {1367-4811},
    doi = {10.1093/bioinformatics/btae731},
    url = {https://doi.org/10.1093/bioinformatics/btae731},
    eprint = {https://academic.oup.com/bioinformatics/article-pdf/40/12/btae731/61035112/btae731.pdf},
}


@article{chen2022,
  title = {{{BOOME}}: {{A Python}} Package for Handling Misclassified Disease and Ultrahigh-Dimensional Error-Prone Gene Expression Data},
  shorttitle = {{{BOOME}}},
  author = {Chen, Li-Pang},
  year = 2022,
  month = oct,
  journal = {PLOS ONE},
  volume = {17},
  number = {10},
  pages = {e0276664},
  publisher = {Public Library of Science},
  issn = {1932-6203},
  doi = {10.1371/journal.pone.0276664},
  urldate = {2026-03-23},
  abstract = {In gene expression data analysis framework, ultrahigh dimensionality and measurement error are ubiquitous features. Therefore, it is crucial to correct measurement error effects and make variable selection when fitting a regression model. In this paper, we introduce a python package BOOME, which refers to BOOsting algorithm for Measurement Error in binary responses and ultrahigh-dimensional predictors. We primarily focus on logistic regression and probit models with responses, predictors, or both contaminated with measurement error. The BOOME aims to address measurement error effects, and employ boosting procedure to make variable selection and estimation.},
  langid = {english},
  file = {C:\Users\chidimmpe\Zotero\storage\S8DP9L8G\Chen - 2022 - BOOME A Python package for handling misclassified disease and ultrahigh-dimensional error-prone gen.pdf}
}



@article{berin_resistance_2019,
	title = {Resistance training for hot flushes in postmenopausal women: A randomised controlled trial.},
	volume = {126},
	rights = {Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.},
	issn = {1873-4111 0378-5122},
	doi = {10.1016/j.maturitas.2019.05.005},
	abstract = {{OBJECTIVES}: To investigate the effect of 15 weeks of resistance training on the frequency of moderate to severe hot flushes in postmenopausal women. {STUDY}  {DESIGN}: Postmenopausal women with at least 4 moderate or severe hot flushes or  night sweats per day day were randomized to a 15-week resistance training  intervention or unchanged physical activity. Participants did not exercise  regularly at baseline and had not used any therapy for hot flushes two months  prior to study entry. The resistance training was performed three times per week  and the program contained 8 exercises performed with 8-12 repetitions in 2 sets.  Loads were set individually from eight-repetition maximum-strength tests and  increased progressively. {MAIN} {OUTCOME} {MEASURES}: The primary outcome was change in  mean moderate or severe hot flushes per day from baseline to week 15, assessed  with symptom diaries. Secondary outcomes included change in hot flush score and  time spent on physical activity. {RESULTS}: Between November 19, 2013, and October  26, 2016, 65 women were enrolled; 58 completed the trial and were included in the  analyses. The mean age was 55 and the mean number of moderate or severe hot  flushes per day at baseline was 7.1; there were no baseline differences between  groups. The frequency of hot flushes decreased more in the intervention group  than in the control group (mean difference -2.7, 95\% {CI} -4.2 to -1.3). The mean  percentage change was -43.6\% (-56.0 to -31.3) in the intervention group and -2.0\%  (-16.4-12.4) in the control group. {CONCLUSION}: A 15-week resistance-training  program decreased the frequency of moderate and severe hot flushes among  postmenopausal women and could be an effective and safe treatment option to  alleviate vasomotor symptoms.},
	pages = {55--60},
	journaltitle = {Maturitas},
	shortjournal = {Maturitas},
	author = {Berin, Emilia and Hammar, Mats and Lindblom, Hanna and Lindh-Åstrand, Lotta and Rubér, Marie and Spetz Holm, Anna-Clara},
	date = {2019-08},
	pmid = {31239119},
	note = {Place: Ireland},
	keywords = {*Postmenopause, *Resistance Training, Exercise, Female, Hot flashes, Hot Flashes/*therapy, Humans, Menopause, Middle Aged, Randomised controlled trial, Resistance training, Women},
}

@article{maestre-cascales_gradual_2022,
	title = {Gradual Strength Training Improves Sleep Quality, Physical Function and Pain in Women with Fibromyalgia.},
	volume = {19},
	issn = {1660-4601 1661-7827},
	doi = {10.3390/ijerph192315662},
	abstract = {{BACKGROUND}: Fibromyalgia ({FM}) is characterized by chronic and generalized musculoskeletal pain. There is currently no cure for {FM}, but alternative  treatments are available. Among them, gradual strength training programs ({ST})  which on daily activities are a valid option to improve some of the pronounced  symptoms of {FM} that affect quality of life, such as fatigue, pain, sleep quality,  and physical function. However, there is a need for more information on optimal  training programs to improve anxiety and fatigue symptoms. {AIM}: To analyze the  effects of a 24-week gradual and progressive {ST} on sleep quality, fatigue, pain  domains, physical function, and anxiety-state. {METHODS}: 41 women with {FM}  participated in the 24 weeks of intervention based on gradual and progressive {ST}.  Two, 60 min, training sessions per week were con-ducted. Participants were  evaluated before the {ST} program (week 0), in week 12 and at the end of the {ST}  program (week 24). The Revised Fibromyalgia Impact Questionnaire was used to  assess sleep quality and fatigue scales. Anxiety-state was evaluated with the  State Anxiety Inventory, and pain domains by means of the Brief Pain Inventory.  Senior Fitness Test was used for physical function measurements. One-way analysis  of variance ({ANOVA}) was applied to assess the mean differences between phases,  and Spearman's correlations were used to assess the associations between physical  and psychological symptoms, and physical function. {RESULTS}: The results  demonstrated that 24 weeks of {ST} improves physical function, sleep quality and  pain domains (p ≤ 0.05). Higher anxiety and pain interference scores were related  to worsening physical function. {CONCLUSIONS}: Gradual {ST} significantly improves  sleep quality, pain, and physical function, but not anxiety and fatigue.},
	number = {23},
	journaltitle = {International journal of environmental research and public health},
	shortjournal = {Int J Environ Res Public Health},
	author = {Maestre-Cascales, Cristina and Castillo-Paredes, Antonio and Romero-Parra, Nuria and Adsuar, José Carmelo and Carlos-Vivas, Jorge},
	date = {2022-11-25},
	pmid = {36497737},
	pmcid = {PMC9793755},
	note = {Place: Switzerland},
	keywords = {Female, Humans, *Fibromyalgia/psychology, *Resistance Training/methods, exercise, Fatigue/etiology/therapy/diagnosis, fibromyalgia, functionality, pain, Pain, physical fitness, Quality of Life, resistance training, sleep, Sleep Quality},
}

@article{ghafouri_vastus_2023,
	title = {The Vastus Lateralis Muscle Interstitium Proteome Changes after an Acute Nociception in Patients with Fibromyalgia Compared to Healthy Subjects-A  Microdialysis Study.},
	volume = {11},
	issn = {2227-9059},
	doi = {10.3390/biomedicines11010206},
	abstract = {Fibromyalgia ({FM}) is a complex disorder and a clinical challenge to diagnose and treat. Microdialysis is a valuable tool that has been used to investigate the  interstitial proteins and metabolites of muscle in patients with fibromyalgia.  The implantation of the catheter in the muscle causes acute tissue trauma and  nociception. The aim of this study was to investigate acute proteome changes in  the vastus lateralis muscle in women fibromyalgia patients ({FM}) and healthy  subjects ({CON}). A further aim was to study if a 15-week resistance exercise  program in {FM} had any influence on how chronic painful muscle responds to acute  nociception. Twenty-six women patients with {FM} and twenty-eight {CON} were included  in this study. A microdialysis catheter (100 kilo Dalton cut off, membrane 30 mm)  was inserted in the vastus lateralis muscle, and samples were collected every 20  min. Subjects rated pain before catheter insertion, directly after, and every 20  min of sample collection. Dialysate samples from time points 0-120 were pooled  and considered trauma samples due to the catheter insertion. The samples were  analyzed with nano-liquid chromatography-tandem mass spectrometry ({nLC}-{MS}/{MS}).  Advanced multivariate data analysis was used to investigate protein profile  changes between the groups. Multivariate data analysis showed significant  ({CV}-{ANOVA} p = 0.036) discrimination between {FM} and {CON} based on changes in 26  proteins. After the 15-week exercise intervention, the expression levels of the  15 proteins involved in muscle contraction, response to stimulus, stress, and  immune system were increased to the same expression levels as in {CON}. In  conclusion, this study shows that microdialysis, in combination with proteomics,  can provide new insights into the interstitial proteome in the muscle of {FM}. In  response to acute nociception, exercise may alter the innate reactivity in {FM}.  Exercise may also modulate peripheral muscle proteins related to muscle  contraction, stress, and immune response in patients with {FM}.},
	number = {1},
	journaltitle = {Biomedicines},
	shortjournal = {Biomedicines},
	author = {Ghafouri, Bijar and Matikhan, Daria and Christidis, Nikolaos and Ernberg, Malin and Kosek, Eva and Mannerkorpi, Kaisa and Gerdle, Björn and Wåhlén, Karin},
	date = {2023-01-13},
	pmid = {36672714},
	pmcid = {PMC9856129},
	note = {Place: Switzerland},
	keywords = {biomarkers, chronic pain, interstitial fluid, muscle proteome, painful muscle},
}

@article{larsson_resistance_2015,
	title = {Resistance exercise improves muscle strength, health status and pain intensity in fibromyalgia--a randomized controlled trial.},
	volume = {17},
	issn = {1478-6362 1478-6354},
	doi = {10.1186/s13075-015-0679-1},
	abstract = {{INTRODUCTION}: Fibromyalgia ({FM}) is characterized by persistent widespread pain, increased pain sensitivity and tenderness. Muscle strength in women with {FM} is  reduced compared to healthy women. The aim of this study was to examine the  effects of a progressive resistance exercise program on muscle strength, health  status, and current pain intensity in women with {FM}. {METHODS}: A total of 130  women with {FM} (age 22-64 years, symptom duration 0-35 years) were included in  this assessor-blinded randomized controlled multi-center trial examining the  effects of progressive resistance group exercise compared with an active control  group. A person-centred model of exercise was used to support the participants'  self-confidence for management of exercise because of known risks of  activity-induced pain in {FM}. The intervention was performed twice a week for 15  weeks and was supervised by experienced physiotherapists. Primary outcome measure  was isometric knee-extension force (Steve Strong®), secondary outcome measures  were health status ({FIQ} total score), current pain intensity ({VAS}), 6MWT,  isometric elbow-flexion force, hand-grip force, health related quality of life,  pain disability, pain acceptance, fear avoidance beliefs, and patient global  impression of change ({PGIC}). Outcomes were assessed at baseline and immediately  after the intervention. Long-term follow up comprised the self-reported  questionnaires only and was conducted after 13-18 months. Between-group and  within-group differences were calculated using non-parametric statistics.  {RESULTS}: Significant improvements were found for isometric knee-extension force  (p = 0.010), health status (p = 0.038), current pain intensity (p = 0.033), 6MWT  (p = 0.003), isometric elbow flexion force (p = 0.02), pain disability (p =  0.005), and pain acceptance (p = 0.043) in the resistance exercise group (n = 56)  when compared to the control group (n = 49). {PGIC} differed significantly (p =  0.001) in favor of the resistance exercise group at post-treatment examinations.  No significant differences between the resistance exercise group and the active  control group were found regarding change in self-reported questionnaires from  baseline to 13-18 months. {CONCLUSIONS}: Person-centered progressive resistance  exercise was found to be a feasible mode of exercise for women with {FM}, improving  muscle strength, health status, and current pain intensity when assessed  immediately after the intervention. {TRIAL} {REGISTRATION}: {ClinicalTrials}.gov  identification number: {NCT}01226784, Oct 21, 2010.},
	pages = {161},
	number = {1},
	journaltitle = {Arthritis research \& therapy},
	shortjournal = {Arthritis Res Ther},
	author = {Larsson, Anette and Palstam, Annie and Löfgren, Monika and Ernberg, Malin and Bjersing, Jan and Bileviciute-Ljungar, Indre and Gerdle, Björn and Kosek, Eva and Mannerkorpi, Kaisa},
	date = {2015-06-18},
	pmid = {26084281},
	pmcid = {PMC4489359},
	note = {Place: England},
	keywords = {Female, Humans, Middle Aged, Quality of Life, *Health Status, Adult, Exercise Therapy/methods, Fibromyalgia/diagnosis/epidemiology/*rehabilitation, Muscle Strength/*physiology, Pain Measurement/*methods, Pain/diagnosis/epidemiology/*rehabilitation, Relaxation Therapy/methods, Resistance Training/*methods, Single-Blind Method, Young Adult},
}

@article{xie_effects_2022,
	title = {Effects of resistance exercise on blood glucose level and pregnancy outcome in patients with gestational diabetes mellitus: a randomized controlled trial.},
	volume = {10},
	rights = {© Author(s) (or their employer(s)) 2022. Re-use permitted under {CC} {BY}-{NC}. No commercial re-use. See rights and permissions. Published by {BMJ}.},
	issn = {2052-4897},
	doi = {10.1136/bmjdrc-2021-002622},
	abstract = {{INTRODUCTION}: To date, the effects of resistance exercise on diabetes-related parameters (blood glucose level and insulin use) and pregnancy outcome in  participants with gestational diabetes mellitus ({GDM}) have not been compared with  those of aerobic exercise. To investigate the effect of resistance exercise  versus aerobic exercise on blood glucose level, insulin utilization rate, and  pregnancy outcome in patients with {GDM}. {RESEARCH} {DESIGN} {AND} {METHODS}: From  December 2019 to December 2020, 100 pregnant women with {GDM} were selected and  divided into a resistance exercise group (49 patients) and an aerobic exercise  group (51 patients) randomly. The aerobic exercise group received an aerobic  exercise intervention, while the resistance exercise group received a resistance  exercise intervention. Both groups received exercise intervention for 50-60 min,  3 times per week, lasting for 6 weeks. In addition, patients in both groups  received the same routine care, including personalized dietary intervention,  online education, and school courses for pregnant women. {RESULTS}: The blood  glucose level in the resistance exercise group and the aerobic exercise group was  lower after the intervention than before the intervention (p{\textless}0.05). After the  intervention, no significant differences were observed in the fasting blood  glucose level, insulin utilization rate, and incidence of adverse pregnancy  outcomes between the two groups (p{\textgreater}0.05); however, significant differences were  noted in 2-hour postprandial blood glucose level and exercise compliance between  the two groups (p{\textless}0.05), with the resistance exercise group showing better  outcomes than the aerobic exercise group. {CONCLUSIONS}: Resistance exercise is  more compliant for pregnant women with {GDM} than aerobic exercise; hence, it is  necessary to popularize resistance exercise in this specific population group.  Long-term effects of resistance exercise should be evaluated in future studies.  {TRIAL} {REGISTRATION} {NUMBER}: {ChiCTR} 1900027929.},
	number = {2},
	journaltitle = {{BMJ} open diabetes research \& care},
	shortjournal = {{BMJ} Open Diabetes Res Care},
	author = {Xie, Yaping and Zhao, Huifen and Zhao, Meijing and Huang, Huibin and Liu, Chunhong and Huang, Fengfeng and Wu, Jingjing},
	date = {2022-04},
	pmid = {35383101},
	pmcid = {PMC8984031},
	note = {Place: England},
	keywords = {*Resistance Training, Exercise, Female, Humans, *Diabetes, Gestational/epidemiology, blood glucose, Blood Glucose, diabetes, gestational, education, nursing, exercise therapy, Pregnancy, Pregnancy Outcome},
}

@article{villareal_aerobic_2017,
	title = {Aerobic or Resistance Exercise, or Both, in Dieting Obese Older Adults.},
	volume = {376},
	issn = {1533-4406 0028-4793},
	doi = {10.1056/NEJMoa1616338},
	abstract = {{BACKGROUND}: Obesity causes frailty in older adults; however, weight loss might accelerate age-related loss of muscle and bone mass and resultant sarcopenia and  osteopenia. {METHODS}: In this clinical trial involving 160 obese older adults, we  evaluated the effectiveness of several exercise modes in reversing frailty and  preventing reduction in muscle and bone mass induced by weight loss. Participants  were randomly assigned to a weight-management program plus one of three exercise  programs - aerobic training, resistance training, or combined aerobic and  resistance training - or to a control group (no weight-management or exercise  program). The primary outcome was the change in Physical Performance Test score  from baseline to 6 months (scores range from 0 to 36 points; higher scores  indicate better performance). Secondary outcomes included changes in other  frailty measures, body composition, bone mineral density, and physical functions.  {RESULTS}: A total of 141 participants completed the study. The Physical  Performance Test score increased more in the combination group than in the  aerobic and resistance groups (27.9 to 33.4 points [21\% increase] vs. 29.3 to  33.2 points [14\% increase] and 28.8 to 32.7 points [14\% increase], respectively;  P=0.01 and P=0.02 after Bonferroni correction); the scores increased more in all  exercise groups than in the control group (P{\textless}0.001 for between-group  comparisons). Peak oxygen consumption (milliliters per kilogram of body weight  per minute) increased more in the combination and aerobic groups (17.2 to 20.3  [17\% increase] and 17.6 to 20.9 [18\% increase], respectively) than in the  resistance group (17.0 to 18.3 [8\% increase]) (P{\textless}0.001 for both comparisons).  Strength increased more in the combination and resistance groups (272 to 320 kg  [18\% increase] and 288 to 337 kg [19\% increase], respectively) than in the  aerobic group (265 to 270 kg [4\% increase]) (P{\textless}0.001 for both comparisons). Body  weight decreased by 9\% in all exercise groups but did not change significantly in  the control group. Lean mass decreased less in the combination and resistance  groups than in the aerobic group (56.5 to 54.8 kg [3\% decrease] and 58.1 to 57.1  kg [2\% decrease], respectively, vs. 55.0 to 52.3 kg [5\% decrease]), as did bone  mineral density at the total hip (grams per square centimeter; 1.010 to 0.996 [1\%  decrease] and 1.047 to 1.041 [0.5\% decrease], respectively, vs. 1.018 to 0.991  [3\% decrease]) (P{\textless}0.05 for all comparisons). Exercise-related adverse events  included musculoskeletal injuries. {CONCLUSIONS}: Of the methods tested, weight  loss plus combined aerobic and resistance exercise was the most effective in  improving functional status of obese older adults. (Funded by the National  Institutes of Health; {LITOE} {ClinicalTrials}.gov number, {NCT}01065636 .).},
	pages = {1943--1955},
	number = {20},
	journaltitle = {The New England journal of medicine},
	shortjournal = {N Engl J Med},
	author = {Villareal, Dennis T. and Aguirre, Lina and Gurney, A. Burke and Waters, Debra L. and Sinacore, David R. and Colombo, Elizabeth and Armamento-Villareal, Reina and Qualls, Clifford},
	date = {2017-05-18},
	pmid = {28514618},
	pmcid = {PMC5552187},
	note = {Place: United States},
	keywords = {*Resistance Training, Female, Humans, Single-Blind Method, *Frail Elderly, Aged, Body Composition, Bone Density, Combined Modality Therapy, Exercise Therapy, Exercise/*physiology, Male, Obesity/diet therapy/physiopathology/*therapy, Oxygen Consumption, Weight Loss/physiology},
}

@article{lebouthillier_efficacy_2017,
	title = {The efficacy of aerobic exercise and resistance training as transdiagnostic interventions for anxiety-related disorders and constructs: A randomized  controlled trial.},
	volume = {52},
	rights = {Copyright © 2017 Elsevier Ltd. All rights reserved.},
	issn = {1873-7897 0887-6185},
	doi = {10.1016/j.janxdis.2017.09.005},
	abstract = {Evidence supports exercise as an intervention for many mental health concerns; however, randomized controlled investigations of the efficacy of different  exercise modalities and predictors of change are lacking. The purposes of the  current trial were to: (1) quantify the effects of aerobic exercise and  resistance training on anxiety-related disorder (including anxiety disorders,  obsessive-compulsive disorder, and posttraumatic stress disorder) status,  symptoms, and constructs, (2) evaluate whether both modalities of exercise were  equivalent, and (3) to determine whether exercise enjoyment and physical fitness  are associated with symptom reduction. A total of 48 individuals with  anxiety-related disorders were randomized to aerobic exercise, resistance  training, or a waitlist. Symptoms of anxiety-related disorders, related  constructs, and exercise enjoyment were assessed at pre-intervention and weekly  during the 4-week intervention. Participants were further assessed 1-week and  1-month post-intervention. Both exercise modalities were efficacious in improving  disorder status. As well, aerobic exercise improved general psychological  distress and anxiety, while resistance training improved disorder-specific  symptoms, anxiety sensitivity, distress tolerance, and intolerance of  uncertainty. Physical fitness predicted reductions in general psychological  distress for both types of exercise and reductions in stress for aerobic  exercise. Results highlight the efficacy of different exercise modalities in  uniquely addressing anxiety-related disorder symptoms and constructs.},
	pages = {43--52},
	journaltitle = {Journal of anxiety disorders},
	shortjournal = {J Anxiety Disord},
	author = {{LeBouthillier}, Daniel M. and Asmundson, Gordon J. G.},
	date = {2017-12},
	pmid = {29049901},
	note = {Place: Netherlands},
	keywords = {Female, Humans, Middle Aged, Resistance training, Adult, Young Adult, Aged, Male, Adolescent, Aerobic exercise, Anxiety disorders, Anxiety Disorders/*therapy, Exercise Therapy/*methods, Exercise/*psychology, Mental Health, Randomized controlled trial, Resistance Training/methods, Stress Disorders, Post-Traumatic/therapy, Transdiagnostic, Treatment Outcome, Uncertainty},
}

@article{frontera_aging_2000,
	title = {Aging of skeletal muscle: a 12-yr longitudinal study.},
	volume = {88},
	issn = {8750-7587 0161-7567},
	doi = {10.1152/jappl.2000.88.4.1321},
	abstract = {The present study examines age-related changes in skeletal muscle size and function after 12 yr. Twelve healthy sedentary men were studied in 1985-86 (T1)  and nine (initial mean age 65.4 +/- 4.2 yr) were reevaluated in 1997-98 (T2).  Isokinetic muscle strength of the knee and elbow extensors and flexors showed  losses (P {\textless} 0.05) ranging from 20 to 30\% at slow and fast angular velocities.  Computerized tomography (n = 7) showed reductions (P {\textless} 0.05) in the  cross-sectional area ({CSA}) of the thigh (12.5\%), all thigh muscles (14.7\%),  quadriceps femoris muscle (16.1\%), and flexor muscles (14. 9\%). Analysis of  covariance showed that strength at T1 and changes in {CSA} were independent  predictors of strength at T2. Muscle biopsies taken from vastus lateralis muscles  (n = 6) showed a reduction in percentage of type I fibers (T1 = 60\% vs. T2 = 42\%)  with no change in mean area in either fiber type. The capillary-to-fiber ratio  was significantly lower at T2 (1.39 vs. 1. 08; P = 0.043). Our observations  suggest that a quantitative loss in muscle {CSA} is a major contributor to the  decrease in muscle strength seen with advancing age and, together with muscle  strength at T1, accounts for 90\% of the variability in strength at T2.},
	pages = {1321--1326},
	number = {4},
	journaltitle = {Journal of applied physiology (Bethesda, Md. : 1985)},
	shortjournal = {J Appl Physiol (1985)},
	author = {Frontera, W. R. and Hughes, V. A. and Fielding, R. A. and Fiatarone, M. A. and Evans, W. J. and Roubenoff, R.},
	date = {2000-04},
	pmid = {10749826},
	note = {Place: United States},
	keywords = {Humans, Middle Aged, Aged, Male, Aging/*physiology, Capillaries/growth \& development/physiology, Elbow Joint/physiology, Isometric Contraction, Knee Joint/physiology, Longitudinal Studies, Muscle Development, Muscle Fibers, Skeletal/cytology/physiology, Muscle, Skeletal/blood supply/growth \& development/*physiology, Time Factors, Tomography, X-Ray Computed},
}

@article{angulo_physical_2020,
	title = {Physical activity and exercise: Strategies to manage frailty.},
	volume = {35},
	rights = {Copyright © 2020. Published by Elsevier B.V.},
	issn = {2213-2317},
	doi = {10.1016/j.redox.2020.101513},
	abstract = {Frailty, a consequence of the interaction of the aging process and certain chronic diseases, compromises functional outcomes in the elderly and  substantially increases their risk for developing disabilities and other adverse  outcomes. Frailty follows from the combination of several impaired physiological  mechanisms affecting multiple organs and systems. And, though frailty and  sarcopenia are related, they are two different conditions. Thus, strategies to  preserve or improve functional status should consider systemic function in  addition to muscle conditioning. Physical activity/exercise is considered one of  the main strategies to counteract frailty-related physical impairment in the  elderly. Exercise reduces age-related oxidative damage and chronic inflammation,  increases autophagy, and improves mitochondrial function, myokine profile,  insulin-like growth factor-1 ({IGF}-1) signaling pathway, and insulin sensitivity.  Exercise interventions target resistance (strength and power), aerobic, balance,  and flexibility work. Each type improves different aspects of physical  functioning, though they could be combined according to need and prescribed as a  multicomponent intervention. Therefore, exercise intervention programs should be  prescribed based on an individual's physical functioning and adapted to the  ensuing response.},
	pages = {101513},
	journaltitle = {Redox biology},
	shortjournal = {Redox Biol},
	author = {Angulo, Javier and El Assar, Mariam and Álvarez-Bustos, Alejandro and Rodríguez-Mañas, Leocadio},
	date = {2020-08},
	pmid = {32234291},
	pmcid = {PMC7284931},
	note = {Place: Netherlands},
	keywords = {Exercise, Humans, Aged, Exercise Therapy, *Frailty/therapy, *Sarcopenia/prevention \& control, Adaptation, Physiological, Aging, Frail Elderly, Frailty, Multicomponent intervention, Oxidative stress, Physical activity},
}

@article{ruple_comparisons_2022,
	title = {Comparisons between skeletal muscle imaging techniques and histology in tracking midthigh hypertrophic adaptations following 10 wk of resistance training.},
	volume = {133},
	issn = {1522-1601 0161-7567},
	doi = {10.1152/japplphysiol.00219.2022},
	abstract = {This study had two aims. Aim1 was to determine the agreement between midthigh vastus lateralis ({VL}) cross-sectional area measured by ultrasound ({mCSA}({US}))  versus magnetic resonance imaging ({mCSA}({MRI})) at a single time point, and the  ability of each to detect hypertrophic changes. Aim2 was to assess the  relationships between pre- and posttraining changes in thigh lean mass determined  by dual-energy X-ray absorptiometry ({DXA}), {VL} {mCSA}({US}), ultrasound-determined {VL}  thickness ({VL}(Thick)), and {VL} mean myofiber cross-sectional area ({fCSA}) with  changes in {VL} {mCSA}({MRI}). Twelve untrained males (age: 20 ± 1 yr, {BMI}: 26.9 ± 5.4  kg/m(2); n = 12) engaged in a 10-wk resistance training program (2×/week) where  right midthigh images and {VL} biopsies were obtained before and 72 h following the  last training bout. Participants' {VL} {mCSA}({MRI}) (P = 0.005), {DXA} thigh lean mass  (P = 0.015), and {VL}(Thick) (P = 0.001) increased following training, whereas {VL}  {mCSA}({US}) and {fCSA} did not. For Aim1, {mCSA}({US}) demonstrated excellent concordance  [concordance correlation coefficients ({CCC}) = 0.830] with {mCSA}({MRI}), albeit  {mCSA}({US}) values were systematically lower compared with {mCSA}({MRI}) (mean bias:  -2.29 cm(2)). In addition, {PRE}-to-{POST} {VL} {mCSA} changes between techniques  exhibited good agreement ({CCC} = 0.700; mean bias: -1.08 cm(2)). For Aim2,  moderate, positive correlations existed for pre-to-post changes in {VL} {mCSA}({MRI})  and {DXA} thigh lean mass (r = 0.580, P = 0.048), {mCSA}({US}) (r = 0.622, P = 0.031),  and {VL}(Thick) (r = 0.520, P = 0.080). A moderate, negative correlation existed  between {mCSA}({MRI}) and {fCSA} (r = -0.569, P = 0.054). Our findings have multiple  implications: 1) resistance training-induced hypertrophy was dependent on the  quantification method, 2) ultrasound-determined {mCSA} shows good agreement with  {MRI}, and 3) tissue-level changes poorly agreed with mean {fCSA} changes and this  requires further research.{NEW} \& {NOTEWORTHY} This is the first study to  comprehensively examine how different midthigh muscle imaging techniques and  histology compare with one another in participants that performed 10 weeks of  resistance training. Our study suggests that histology results show poor  agreement with results yielded from other common muscle imaging techniques, and  researchers should be aware of this limitation.},
	pages = {416--425},
	number = {2},
	journaltitle = {Journal of applied physiology (Bethesda, Md. : 1985)},
	shortjournal = {J Appl Physiol (1985)},
	author = {Ruple, Bradley A. and Smith, Morgan A. and Osburn, Shelby C. and Sexton, Casey L. and Godwin, Joshua S. and Edison, Joseph L. and Poole, Christopher N. and Stock, Matt S. and Fruge, Andrew D. and Young, Kaelin C. and Roberts, Michael D.},
	date = {2022-08-01},
	pmid = {35771220},
	note = {Place: United States},
	keywords = {*Resistance Training, Humans, Adult, Young Adult, Male, dual-energy X-ray absorptiometry, histology, Hypertrophy, {MRI}, muscle, Muscle, Skeletal/diagnostic imaging/physiology, Quadriceps Muscle/diagnostic imaging, Thigh/diagnostic imaging, ultrasound},
}

@article{mobley_biomarkers_2018,
	title = {Biomarkers associated with low, moderate, and high vastus lateralis muscle hypertrophy following 12 weeks of resistance training.},
	volume = {13},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0195203},
	abstract = {We sought to identify biomarkers which delineated individual hypertrophic responses to resistance training. Untrained, college-aged males engaged in  full-body resistance training (3 d/wk) for 12 weeks. Body composition via dual  x-ray absorptiometry ({DXA}), vastus lateralis ({VL}) thickness via ultrasound,  blood, {VL} muscle biopsies, and three-repetition maximum (3-{RM}) squat strength  were obtained prior to ({PRE}) and following ({POST}) 12 weeks of training. K-means  cluster analysis based on {VL} thickness changes identified {LOW} [n = 17; change  (mean±{SD}) = +0.11±0.14 cm], modest ({MOD}; n = 29, +0.40±0.06 cm), and high ({HI}; n  = 21, +0.69±0.14 cm) responders. Biomarkers related to histology, ribosome  biogenesis, proteolysis, inflammation, and androgen signaling were analyzed  between clusters. There were main effects of time ({POST}{\textgreater}{PRE}, p{\textless}0.05) but no  cluster×time interactions for increases in {DXA} lean body mass, type I and {II}  muscle fiber cross sectional area and myonuclear number, satellite cell number,  and macronutrients consumed. Interestingly, {PRE} {VL} thickness was {\textasciitilde}12\% greater in  {LOW} versus {HI} (p = 0.021), despite {POST} values being {\textasciitilde}12\% greater in {HI} versus  {LOW} (p = 0.006). However there was only a weak correlation between {PRE} {VL}  thickness scores and change in {VL} thickness (r2 = 0.114, p = 0.005). Forced post  hoc analysis indicated that muscle total {RNA} levels (i.e., ribosome density) did  not significantly increase in the {LOW} cluster (351±70 ng/mg to 380±62, p =  0.253), but increased in the {MOD} (369±115 to 429±92, p = 0.009) and {HI} clusters  (356±77 to 470±134, p{\textless}0.001; {POST} {HI}{\textgreater}{POST} {LOW}, p = 0.013). Nonetheless, there was  only a weak association between change in muscle total {RNA} and {VL} thickness (r2 =  0.079, p = 0.026). {IL}-1β {mRNA} levels decreased in the {MOD} and {HI} clusters  following training (p{\textless}0.05), although associations between this marker and {VL}  thickness changes were not significant (r2 = 0.0002, p = 0.919). In conclusion,  individuals with lower pre-training {VL} thickness values and greater increases  muscle total {RNA} levels following 12 weeks of resistance training experienced  greater {VL} muscle growth, although these biomarkers individually explained only  {\textasciitilde}8-11\% of the variance in hypertrophy.},
	pages = {e0195203},
	number = {4},
	journaltitle = {{PloS} one},
	shortjournal = {{PLoS} One},
	author = {Mobley, Christopher B. and Haun, Cody T. and Roberson, Paul A. and Mumford, Petey W. and Kephart, Wesley C. and Romero, Matthew A. and Osburn, Shelby C. and Vann, Christopher G. and Young, Kaelin C. and Beck, Darren T. and Martin, Jeffrey S. and Lockwood, Christopher M. and Roberts, Michael D.},
	date = {2018},
	pmid = {29621305},
	pmcid = {PMC5886420},
	note = {Place: United States},
	keywords = {*Resistance Training, Humans, Adult, Young Adult, Body Composition, Muscle Fibers, Skeletal/cytology/physiology, Hypertrophy, *Biomarkers, *Exercise, Androgens/metabolism, Cluster Analysis, Gene Expression, Micronutrients, Muscle Strength, Muscle, Skeletal/*anatomy \& histology/diagnostic imaging/*physiology, Ribosomes, Satellite Cells, Skeletal Muscle/cytology/physiology, Self Report, Signal Transduction, Ultrasonography},
}

@article{pender_effects_2023,
	title = {The Effects of Intradialytic Exercise on Key Indices of Sarcopenia in Patients With End-stage Renal Disease: A Systematic Review of Randomized Controlled  Trials.},
	volume = {5},
	rights = {© 2023 Published by Elsevier Inc. on behalf of American Congress of Rehabilitation Medicine.},
	issn = {2590-1095},
	doi = {10.1016/j.arrct.2022.100252},
	abstract = {{OBJECTIVE}: To evaluate the effects of intradialytic exercise ({IDE}) (exercise performed during dialysis) on sarcopenia and quality of life ({QoL}) in patients  with end-stage renal disease ({ESRD}). {DATA} {SOURCES}: A comprehensive search of 7  electronic databases was performed to identify randomized controlled trials  measuring the effects of {IDE} in adults with {ESRD}. Searches were limited to the  English language. {STUDY} {SELECTION}: Included studies were randomized controlled  trials that measured the effects of {IDE} in adults with {ESRD}. Comparator groups  received usual care or low-intensity sham interventions. Outcomes of interest  were muscle mass, strength, physical function, and {QoL}. Papers were independently  screened for eligibility by 2 authors, and any discrepancies resolved by a third  author. {DATA} {EXTRACTION}: One author extracted the data from the included studies.  Data were compared and discussed across the team members. Two authors  independently assessed risk of bias using the Cochrane Risk of Bias 2 tool.  Quality was assessed using the van Tulder scale and a narrative synthesis was  conducted. Best evidence synthesis was used to structure the reviews findings.  {DATA} {SYNTHESIS}: Fourteen studies were included in this review (n=837). While risk  of bias was found high in 11 studies, demonstrating mainly selection,  performance, and detection bias, the best evidence synthesis indicated strong  evidence of resistance training improving muscle mass (16\%-4.2\%) and strength  (45\%-18\%), and moderate evidence of combined exercise improving strength (37\%),  and various physical function scores. {CONCLUSIONS}: Overall, there is strong  evidence of resistance exercise, with moderate evidence of combined exercise,  improving sarcopenia-related muscle and strength loss, and {QoL} in end-stage  kidney disease. Adequately powered, good quality studies are required to  determine the optimal exercise prescription to maximize outcomes.},
	pages = {100252},
	number = {1},
	journaltitle = {Archives of rehabilitation research and clinical translation},
	shortjournal = {Arch Rehabil Res Clin Transl},
	author = {Pender, Daniel and {McGowan}, Ellen and {McVeigh}, Joseph G. and {McCullagh}, Ruth},
	date = {2023-03},
	pmid = {36968168},
	pmcid = {PMC10036234},
	note = {Place: United States},
	keywords = {Exercise, Quality of life, Renal dialysis, Renal insufficiency, Sarcopenia},
}

@article{busch_resistance_2013,
	title = {Resistance exercise training for fibromyalgia.},
	volume = {2013},
	issn = {1469-493X 1361-6137},
	doi = {10.1002/14651858.CD010884},
	abstract = {{BACKGROUND}: Fibromyalgia is characterized by chronic widespread pain that leads to reduced physical function. Exercise training is commonly recommended as a  treatment for management of symptoms. We examined the literature on resistance  training for individuals with fibromyalgia. Resistance training is exercise  performed against a progressive resistance with the intention of improving muscle  strength, muscle endurance, muscle power, or a combination of these. {OBJECTIVES}:  To evaluate the benefits and harms of resistance exercise training in adults with  fibromyalgia. We compared resistance training versus control and versus other  types of exercise training. {SEARCH} {METHODS}: We searched nine electronic databases  (The Cochrane Library, {MEDLINE}, {EMBASE}, {CINAHL}, {PEDro}, Dissertation Abstracts,  Current Controlled Trials, World Health Organization ({WHO}) International Clinical  Trials Registry Platform, {AMED}) and other sources for published full-text  articles. The date of the last search was 5 March 2013. Two review authors  independently screened 1856 citations, 766 abstracts and 156 full-text articles.  We included five studies that met our inclusion criteria. {SELECTION} {CRITERIA}:  Selection criteria included: a) randomized clinical trial, b) diagnosis of  fibromyalgia based on published criteria, c) adult sample, d) full-text  publication, and e) inclusion of between-group data comparing resistance training  versus a control or other physical activity intervention. {DATA} {COLLECTION} {AND}  {ANALYSIS}: Pairs of review authors independently assessed risk of bias and  extracted intervention and outcome data. We resolved disagreements between the  two review authors and questions regarding interpretation of study methods by  discussion within the pairs or when necessary the issue was taken to the full  team of 11 members. We extracted 21 outcomes of which seven were designated as  major outcomes: multidimensional function, self reported physical function, pain,  tenderness, muscle strength, attrition rates, and adverse effects. We evaluated  benefits and harms of the interventions using standardized mean differences ({SMD})  or mean differences ({MD}) or risk ratios or Peto odds ratios and 95\% confidence  intervals ({CI}). Where two or more studies provided data for an outcome, we  carried out a meta-analysis. {MAIN} {RESULTS}: The literature search yielded 1865  citations with five studies meeting the selection criteria. One of the studies  that had three arms contributed data for two comparisons. In the included  studies, there were 219 women participants with fibromyalgia, 95 of whom were  assigned to resistance training programs. Three randomized trials compared 16 to  21 weeks of moderate- to high-intensity resistance training versus a control  group. Two studies compared eight weeks of progressive resistance training  (intensity as tolerated) using free weights or body weight resistance exercise  versus aerobic training (ie, progressive treadmill walking, indoor and outdoor  walking), and one study compared 12 weeks of low-intensity resistance training  using hand weights (1 to 3 lbs (0.45 to 1.36 kg)) and elastic tubing versus  flexibility exercise (static stretches to major muscle groups).Statistically  significant differences ({MD}; 95\% {CI}) favoring the resistance training  interventions over control group(s) were found in multidimensional function  (Fibromyalgia Impact Questionnaire ({FIQ}) total decreased 16.75 units on a  100-point scale; 95\% {CI} -23.31 to -10.19), self reported physical function (-6.29  units on a 100-point scale; 95\% {CI} -10.45 to -2.13), pain (-3.3 cm on a 10-cm  scale; 95\% {CI} -6.35 to -0.26), tenderness (-1.84 out of 18 tender points; 95\% {CI}  -2.6 to -1.08), and muscle strength (27.32 kg force on bilateral concentric leg  extension; 95\% {CI} 18.28 to 36.36).Differences between the resistance training  group(s) and the aerobic training groups were not statistically significant for  multidimensional function (5.48 on a 100-point scale; 95\% {CI} -0.92 to 11.88),  self reported physical function (-1.48 units on a 100-point scale; 95\% {CI} -6.69  to 3.74) or tenderness ({SMD} -0.13; 95\% {CI} -0.55 to 0.30). There was a  statistically significant reduction in pain (0.99 cm on a 10-cm scale; 95\% {CI}  0.31 to 1.67) favoring the aerobic groups.Statistically significant differences  were found between a resistance training group and a flexibility group favoring  the resistance training group for multidimensional function (-6.49 {FIQ} units on a  100-point scale; 95\% {CI} -12.57 to -0.41) and pain (-0.88 cm on a 10-cm scale; 95\%  {CI} -1.57 to -0.19), but not for tenderness (-0.46 out of 18 tender points; 95\% {CI}  -1.56 to 0.64) or strength (4.77 foot pounds torque on concentric knee extension;  95\% {CI} -2.40 to 11.94). This evidence was classified low quality due to the low  number of studies and risk of bias assessment. There were no statistically  significant differences in attrition rates between the interventions. In general,  adverse effects were poorly recorded, but no serious adverse effects were  reported. Assessment of risk of bias was hampered by poor written descriptions  (eg, allocation concealment, blinding of outcome assessors). The lack of a priori  protocols and lack of care provider blinding were also identified as methodologic  concerns. {AUTHORS}' {CONCLUSIONS}: The evidence (rated as low quality) suggested  that moderate- and moderate- to high-intensity resistance training improves  multidimensional function, pain, tenderness, and muscle strength in women with  fibromyalgia. The evidence (rated as low quality) also suggested that eight weeks  of aerobic exercise was superior to moderate-intensity resistance training for  improving pain in women with fibromyalgia. There was low-quality evidence that 12  weeks of low-intensity resistance training was superior to flexibility exercise  training in women with fibromyalgia for improvements in pain and multidimensional  function. There was low-quality evidence that women with fibromyalgia can safely  perform moderate- to high-resistance training.},
	pages = {CD010884},
	number = {12},
	journaltitle = {The Cochrane database of systematic reviews},
	shortjournal = {Cochrane Database Syst Rev},
	author = {Busch, Angela J. and Webber, Sandra C. and Richards, Rachel S. and Bidonde, Julia and Schachter, Candice L. and Schafer, Laurel A. and Danyliw, Adrienne and Sawant, Anuradha and Dal Bello-Haas, Vanina and Rader, Tamara and Overend, Tom J.},
	date = {2013-12-20},
	pmid = {24362925},
	pmcid = {PMC6544808},
	note = {Place: England},
	keywords = {Exercise, Female, Humans, Adult, Resistance Training/*methods, Fibromyalgia/*rehabilitation, Randomized Controlled Trials as Topic},
}

@article{murton_resistance_2013,
	title = {Resistance exercise and the mechanisms of muscle mass regulation in humans: acute effects on muscle protein turnover and the gaps in our understanding of chronic  resistance exercise training adaptation.},
	volume = {45},
	rights = {Copyright © 2013. Published by Elsevier Ltd.},
	issn = {1878-5875 1357-2725},
	doi = {10.1016/j.biocel.2013.07.005},
	abstract = {Increasing muscle mass is important when attempting to maximize sports performance and achieve physique augmentation. However, the preservation of  muscle mass is essential to maintaining mobility and quality of life with aging,  and also impacts on our capacity to recover from illness. Nevertheless, our  understanding of the processes that regulate muscle mass in humans during  resistance exercise training, chronic disuse and rehabilitation training  following atrophy remains very unclear. Here, we report on some of the recent  developments in the study of those processes thought to be responsible for  governing human muscle protein turnover in response to intense physical activity.  Specifically, the effects of acute and chronic resistance exercise in healthy  volunteers and also in response to rehabilitation resistance exercise training  following muscle atrophy will be discussed, with discrepancies and gaps in our  understanding highlighted. In particular, ubiquitin-proteasome mediated muscle  proteolysis (Muscle Atrophy F-box/Atrogin-1 and Muscle {RING} Finger 1),  translation initiation of muscle protein synthesis (mammalian target of rapamycin  signaling), and satellite cell mediated myogenesis are highlighted as pathways of  special relevance to muscle protein metabolism in response to acute resistance  exercise. Furthermore, research focused on quantifying signaling and molecular  events that modulate muscle protein synthesis and protein degradation under  conditions of chronic resistance training is highlighted as being urgently needed  to improve knowledge gaps. These studies need to include multiple time-point  measurements over the course of any training intervention and must include  dynamic measurements of muscle protein synthesis and degradation and sensitive  measures of muscle mass. This article is part of a Directed Issue entitled  Molecular basis of muscle wasting.},
	pages = {2209--2214},
	number = {10},
	journaltitle = {The international journal of biochemistry \& cell biology},
	shortjournal = {Int J Biochem Cell Biol},
	author = {Murton, A. J. and Greenhaff, P. L.},
	date = {2013-10},
	pmid = {23872221},
	note = {Place: Netherlands},
	keywords = {*Resistance Training, Humans, Exercise/*physiology, Signal Transduction, Adaptation, Physiological/physiology, Animals, Muscle atrophy, Muscle protein turnover, Muscle Proteins/*metabolism, Muscle rehabilitation, Muscle, Skeletal/*metabolism/pathology, Muscular Atrophy/*metabolism/pathology, Protein Biosynthesis, Resistance exercise training},
}

@article{stokes_molecular_2020,
	title = {Molecular Transducers of Human Skeletal Muscle Remodeling under Different Loading States.},
	volume = {32},
	rights = {Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.},
	issn = {2211-1247},
	doi = {10.1016/j.celrep.2020.107980},
	abstract = {Loading of skeletal muscle changes the tissue phenotype reflecting altered metabolic and functional demands. In humans, heterogeneous adaptation to loading  complicates the identification of the underpinning molecular regulators. A  within-person differential loading and analysis strategy reduces heterogeneity  for changes in muscle mass by ∼40\% and uses a genome-wide transcriptome method  that models each {mRNA} from coding exons and 3' and 5' untranslated regions  ({UTRs}). Our strategy detects ∼3-4 times more regulated genes than similarly sized  studies, including substantial {UTR}-selective regulation undetected by other  methods. We discover a core of 141 genes correlated to muscle growth, which we  validate from newly analyzed independent samples (n = 100). Further validating  these identified genes via {RNAi} in primary muscle cells, we demonstrate that  members of the core genes were regulators of protein synthesis. Using  proteome-constrained networks and pathway analysis reveals notable relationships  with the molecular characteristics of human muscle aging and insulin sensitivity,  as well as potential drug therapies.},
	pages = {107980},
	number = {5},
	journaltitle = {Cell reports},
	shortjournal = {Cell Rep},
	author = {Stokes, Tanner and Timmons, James A. and Crossland, Hannah and Tripp, Thomas R. and Murphy, Kevin and {McGlory}, Chris and Mitchell, Cameron J. and Oikawa, Sara Y. and Morton, Robert W. and Phillips, Bethan E. and Baker, Steven K. and Atherton, Phillip J. and Wahlestedt, Claes and Phillips, Stuart M.},
	date = {2020-08-04},
	pmid = {32755574},
	pmcid = {PMC7408494},
	note = {Place: United States},
	keywords = {Exercise, Humans, Adult, Young Adult, Adolescent, Signal Transduction, Protein Biosynthesis, atrophy, Gene Expression Regulation, Gene Regulatory Networks, growth, human, hypertrophy, Muscle Fibers, Skeletal/metabolism, Muscle, Skeletal/growth \& development/*physiology, Organ Size, protein synthesis, protein turnover, Proteome/metabolism, resistance exercise, {RNA}/metabolism, skeletal muscle, transcriptome, unloading, untranslated region, Weight-Bearing},
}

@article{cruz-jentoft_sarcopenia_2010,
	title = {Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People},
	volume = {39},
	issn = {0002-0729},
	url = {https://doi.org/10.1093/ageing/afq034},
	doi = {10.1093/ageing/afq034},
	abstract = {The European Working Group on Sarcopenia in Older People ({EWGSOP}) developed a practical clinical definition and consensus diagnostic criteria for age-related sarcopenia. {EWGSOP} included representatives from four participant organisations, i.e. the European Geriatric Medicine Society, the European Society for Clinical Nutrition and Metabolism, the International Association of Gerontology and Geriatrics—European Region and the International Association of Nutrition and Aging. These organisations endorsed the findings in the final document.The group met and addressed the following questions, using the medical literature to build evidence-based answers: (i) What is sarcopenia? (ii) What parameters define sarcopenia? (iii) What variables reflect these parameters, and what measurement tools and cut-off points can be used? (iv) How does sarcopenia relate to cachexia, frailty and sarcopenic obesity?For the diagnosis of sarcopenia, {EWGSOP} recommends using the presence of both low muscle mass + low muscle function (strength or performance). {EWGSOP} variously applies these characteristics to further define conceptual stages as ‘presarcopenia’, ‘sarcopenia’ and ‘severe sarcopenia’. {EWGSOP} reviewed a wide range of tools that can be used to measure the specific variables of muscle mass, muscle strength and physical performance. Our paper summarises currently available data defining sarcopenia cut-off points by age and gender; suggests an algorithm for sarcopenia case finding in older individuals based on measurements of gait speed, grip strength and muscle mass; and presents a list of suggested primary and secondary outcome domains for research.Once an operational definition of sarcopenia is adopted and included in the mainstream of comprehensive geriatric assessment, the next steps are to define the natural course of sarcopenia and to develop and define effective treatment.},
	pages = {412--423},
	number = {4},
	journaltitle = {Age and Ageing},
	shortjournal = {Age and Ageing},
	author = {Cruz-Jentoft, Alfonso J. and Baeyens, Jean Pierre and Bauer, Jürgen M. and Boirie, Yves and Cederholm, Tommy and Landi, Francesco and Martin, Finbarr C. and Michel, Jean-Pierre and Rolland, Yves and Schneider, Stéphane M. and Topinková, Eva and Vandewoude, Maurits and Zamboni, Mauro},
	urldate = {2023-04-02},
	date = {2010-07-01},
}

@article{frontera_skeletal_2015,
	title = {Skeletal muscle: a brief review of structure and function.},
	volume = {96},
	issn = {1432-0827 0171-967X},
	doi = {10.1007/s00223-014-9915-y},
	abstract = {Skeletal muscle is one of the most dynamic and plastic tissues of the human body. In humans, skeletal muscle comprises approximately 40\% of total body weight and  contains 50-75\% of all body proteins. In general, muscle mass depends on the  balance between protein synthesis and degradation and both processes are  sensitive to factors such as nutritional status, hormonal balance, physical  activity/exercise, and injury or disease, among others. In this review, we  discuss the various domains of muscle structure and function including its  cytoskeletal architecture, excitation-contraction coupling, energy metabolism,  and force and power generation. We will limit the discussion to human skeletal  muscle and emphasize recent scientific literature on single muscle fibers.},
	pages = {183--195},
	number = {3},
	journaltitle = {Calcified tissue international},
	shortjournal = {Calcif Tissue Int},
	author = {Frontera, Walter R. and Ochala, Julien},
	date = {2015-03},
	pmid = {25294644},
	note = {Place: United States},
	keywords = {Humans, Muscle, Skeletal/*anatomy \& histology/*metabolism},
}

@article{sexton_skeletal_2023,
	title = {Skeletal Muscle {DNA} Methylation and {mRNA} Responses to a Bout of Higher versus Lower Load Resistance Exercise in Previously Trained Men.},
	volume = {12},
	issn = {2073-4409},
	doi = {10.3390/cells12020263},
	abstract = {We sought to determine the skeletal muscle genome-wide {DNA} methylation and {mRNA} responses to one bout of lower load ({LL}) versus higher load ({HL}) resistance  exercise. Trained college-aged males (n = 11, 23 ± 4 years old, 4 ± 3 years  self-reported training) performed {LL} or {HL} bouts to failure separated by one  week. The {HL} bout (i.e., 80 Fail) consisted of four sets of back squats and four  sets of leg extensions to failure using 80\% of participants estimated  one-repetition maximum (i.e., est. 1-{RM}). The {LL} bout (i.e., 30 Fail) implemented  the same paradigm with 30\% of est. 1-{RM}. Vastus lateralis muscle biopsies were  collected before, 3 h, and 6 h after each bout. Muscle {DNA} and {RNA} were  batch-isolated and analyzed using the 850k Illumina {MethylationEPIC} array and  Clariom S {mRNA} microarray, respectively. Performed repetitions were significantly  greater during the 30 Fail versus 80 Fail (p {\textless} 0.001), although total training  volume (sets × reps × load) was not significantly different between bouts (p =  0.571). Regardless of bout, more {CpG} site methylation changes were observed at 3  h versus 6 h post exercise (239,951 versus 12,419, respectively; p {\textless} 0.01), and  nuclear global ten-eleven translocation ({TET}) activity, but not global {DNA}  methyltransferase activity, increased 3 h and 6 h following exercise regardless  of bout. The percentage of genes significantly altered at the {mRNA} level that  demonstrated opposite {DNA} methylation patterns was greater 3 h versus 6 h  following exercise ({\textasciitilde}75\% versus {\textasciitilde}15\%, respectively). Moreover, high percentages  of genes that were up- or downregulated 6 h following exercise also demonstrated  significantly inversed {DNA} methylation patterns across one or more {CpG} sites 3 h  following exercise (65\% and 82\%, respectively). While 30 Fail decreased {DNA}  methylation across various promoter regions versus 80 Fail, transcriptome-wide  {mRNA} and bioinformatics indicated that gene expression signatures were largely  similar between bouts. Bioinformatics overlay of {DNA} methylation and {mRNA}  expression data indicated that genes related to "Focal adhesion," "{MAPK}  signaling," and "{PI}3K-Akt signaling" were significantly affected at the 3 h and 6  h time points, and again this was regardless of bout. In conclusion, extensive  molecular profiling suggests that post-exercise alterations in the skeletal  muscle {DNA} methylome and {mRNA} transcriptome elicited by {LL} and {HL} training bouts  to failure are largely similar, and this could be related to equal volumes  performed between bouts.},
	number = {2},
	journaltitle = {Cells},
	shortjournal = {Cells},
	author = {Sexton, Casey L. and Godwin, Joshua S. and {McIntosh}, Mason C. and Ruple, Bradley A. and Osburn, Shelby C. and Hollingsworth, Blake R. and Kontos, Nicholas J. and Agostinelli, Philip J. and Kavazis, Andreas N. and Ziegenfuss, Tim N. and Lopez, Hector L. and Smith, Ryan and Young, Kaelin C. and Dwaraka, Varun B. and Frugé, Andrew D. and Mobley, Christopher B. and Sharples, Adam P. and Roberts, Michael D.},
	date = {2023-01-09},
	pmid = {36672198},
	pmcid = {PMC9856538},
	note = {Place: Switzerland},
	keywords = {*Resistance Training, Humans, Adult, Young Adult, Male, resistance exercise, *{DNA} Methylation/genetics, {DNA} methylation, {DNA}/metabolism, Muscle, Skeletal/metabolism, Phosphatidylinositol 3-Kinases/metabolism, {RNA}, Messenger/genetics/metabolism, training volume, transcriptomics},
}

@article{molmen_vitamin_2021,
	title = {Vitamin D(3) supplementation does not enhance the effects of resistance training in older adults.},
	volume = {12},
	rights = {© 2021 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley \& Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting  Disorders.},
	issn = {2190-6009 2190-5991},
	doi = {10.1002/jcsm.12688},
	abstract = {{BACKGROUND}: Lifestyle therapy with resistance training is a potent measure to counteract age-related loss in muscle strength and mass. Unfortunately, many  individuals fail to respond in the expected manner. This phenomenon is  particularly common among older adults and those with chronic diseases (e.g.  chronic obstructive pulmonary disease, {COPD}) and may involve endocrine variables  such as vitamin D. At present, the effects of vitamin D supplementation on  responses to resistance training remain largely unexplored. {METHODS}: Ninety-five  male and female participants (healthy, n = 71; {COPD}, n = 24; age 68 ± 5 years)  were randomly assigned to receive either vitamin D(3) or placebo supplementation  for 28 weeks in a double-blinded manner (latitude 61°N, September-May).  Seventy-eight participants completed the {RCT}, which was initiated by 12 weeks of  supplementation-only (two weeks with 10 000 {IU}/day, followed by 2000 {IU}/day),  followed by 13 weeks of combined supplementation (2000 {IU}/day) and supervised  whole-body resistance training (twice weekly), interspersed with testing and  measurements. Outcome measures included multiple assessments of muscle strength  (n(variables)  = 7), endurance performance (n = 6), and muscle mass (n = 3, legs,  primary), as well as muscle quality (legs), muscle biology (m. vastus lateralis;  muscle fibre characteristics, transcriptome), and health-related variables (e.g.  visceral fat mass and blood lipid profile). For main outcome domains such as  muscle strength and muscle mass, weighted combined factors were calculated from  the range of singular assessments. {RESULTS}: Overall, 13 weeks of resistance  training increased muscle strength (13\% ± 8\%), muscle mass (9\% ± 8\%), and  endurance performance (one-legged, 23\% ± 15\%; whole-body, 8\% ± 7\%), assessed as  weighted combined factors, and were associated with changes in health variables  (e.g. visceral fat, -6\% ± 21\%; [{LDL}](serum) , -4\% ± 14\%) and muscle tissue  characteristics such as fibre type proportions (e.g. {IIX}, -3\% points), myonuclei  per fibre (30\% ± 65\%), total {RNA}/{rRNA} abundances (15\%/6-19\%), and transcriptome  profiles (e.g. 312 differentially expressed genes). Vitamin D(3) supplementation  did not affect training-associated changes for any of the main outcome domains,  despite robust increases in [25({OH})D](serum) (∆49\% vs. placebo). No conditional  effects were observed for {COPD} vs. healthy or pre-{RCT} [25({OH})D](serum) . In  secondary analyses, vitamin D(3) affected expression of gene sets involved in  vascular functions in muscle tissue and strength gains in participants with high  fat mass, which advocates further study. {CONCLUSIONS}: Vitamin D(3)  supplementation did not affect muscular responses to resistance training in older  adults with or without {COPD}.},
	pages = {599--628},
	number = {3},
	journaltitle = {Journal of cachexia, sarcopenia and muscle},
	shortjournal = {J Cachexia Sarcopenia Muscle},
	author = {Mølmen, Knut Sindre and Hammarström, Daniel and Pedersen, Karianne and Lian Lie, Anne Cecilie and Steile, Ragnvald B. and Nygaard, Håvard and Khan, Yusuf and Hamarsland, Håvard and Koll, Lise and Hanestadhaugen, Marita and Eriksen, Atle Lie and Grindaker, Eirik and Whist, Jon Elling and Buck, Daniel and Ahmad, Rafi and Strand, Tor A. and Rønnestad, Bent R. and Ellefsen, Stian},
	date = {2021-06},
	pmid = {33788419},
	pmcid = {PMC8200443},
	note = {Place: Germany},
	keywords = {*Resistance Training, Female, Humans, Middle Aged, Aged, Male, *Cholecalciferol/therapeutic use, Cholecalciferol, Dietary Supplements, Muscle plasticity, Strength training, Vitamin D, Vitamins},
}

@article{molmen_chronic_2021,
	title = {Chronic obstructive pulmonary disease does not impair responses to resistance training.},
	volume = {19},
	issn = {1479-5876},
	doi = {10.1186/s12967-021-02969-1},
	abstract = {{BACKGROUND}: Subjects with chronic obstructive pulmonary disease ({COPD}) are prone to accelerated decay of muscle strength and mass with advancing age. This is  believed to be driven by disease-inherent systemic pathophysiologies, which are  also assumed to drive muscle cells into a state of anabolic resistance, leading  to impaired abilities to adapt to resistance exercise training. Currently, this  phenomenon remains largely unstudied. In this study, we aimed to investigate the  assumed negative effects of {COPD} for health- and muscle-related responsiveness to  resistance training using a healthy control-based translational approach.  {METHODS}: Subjects with {COPD} (n = 20, {GOLD} {II}-{III}, {FEV}(1predicted) 57 ± 11\%, age  69 ± 5) and healthy controls (Healthy, n = 58, {FEV}(1predicted) 112 ± 16\%, age  67 ± 4) conducted identical whole-body resistance training interventions for  13 weeks, consisting of two weekly supervised training sessions. Leg exercises  were performed unilaterally, with one leg conducting high-load training (10RM)  and the contralateral leg conducting low-load training (30RM). Measurements  included muscle strength (n(variables) = 7), endurance performance  (n(variables) = 6), muscle mass (n(variables) = 3), muscle quality, muscle  biology (m. vastus lateralis; muscle fiber characteristics, {RNA} content including  transcriptome) and health variables (body composition, blood). For core outcome  domains, weighted combined factors were calculated from the range of singular  assessments. {RESULTS}: {COPD} displayed well-known pathophysiologies at baseline,  including elevated levels of systemic low-grade inflammation ([c-reactive  protein](serum)), reduced muscle mass and functionality, and muscle biological  aberrancies. Despite this, resistance training led to improved lower-limb muscle  strength (15 ± 8\%), muscle mass (7 ± 5\%), muscle quality (8 ± 8\%) and  lower-limb/whole-body endurance performance (26 ± 12\%/8 ± 9\%) in {COPD}, resembling  or exceeding responses in Healthy, measured in both relative and numeric change  terms. Within the {COPD} cluster, lower {FEV}(1predicted) was associated with larger  numeric and relative increases in muscle mass and superior relative improvements  in maximal muscle strength. This was accompanied by similar changes in hallmarks  of muscle biology such as {rRNA}-content↑, muscle fiber cross-sectional area↑, type  {IIX} proportions↓, and changes in {mRNA} transcriptomics. Neither of the core  outcome domains were differentially affected by resistance training load.  {CONCLUSIONS}: {COPD} showed hitherto largely unrecognized responsiveness to  resistance training, rejecting the notion of disease-related impairments and  rather advocating such training as a potent measure to relieve pathophysiologies.  {TRIAL} {REGISTRATION}: {ClinicalTrials}.gov {ID}: {NCT}02598830. Registered November 6th  2015, https://clinicaltrials.gov/ct2/show/{NCT}02598830.},
	pages = {292},
	number = {1},
	journaltitle = {Journal of translational medicine},
	shortjournal = {J Transl Med},
	author = {Mølmen, Knut Sindre and Hammarström, Daniel and Falch, Gunnar Slettaløkken and Grundtvig, Morten and Koll, Lise and Hanestadhaugen, Marita and Khan, Yusuf and Ahmad, Rafi and Malerbakken, Bente and Rødølen, Tore Jørgen and Lien, Roger and Rønnestad, Bent R. and Raastad, Truls and Ellefsen, Stian},
	date = {2021-07-06},
	pmid = {34229714},
	pmcid = {PMC8261934},
	note = {Place: England},
	keywords = {*Resistance Training, Humans, Middle Aged, Aged, Muscle Strength, Strength training, *Pulmonary Disease, Chronic Obstructive, Anabolic resistance, {COPD}, Cross-Sectional Studies, Exercise Tolerance, Muscle, Skeletal, Pathophysiology, Skeletal muscle, Training load},
}

@article{westcott_resistance_2012,
	title = {Resistance training is medicine: effects of strength training on health.},
	volume = {11},
	issn = {1537-8918 1537-890X},
	doi = {10.1249/JSR.0b013e31825dabb8},
	abstract = {Inactive adults experience a 3\% to 8\% loss of muscle mass per decade, accompanied by resting metabolic rate reduction and fat accumulation. Ten weeks of resistance  training may increase lean weight by 1.4 kg, increase resting metabolic rate by  7\%, and reduce fat weight by 1.8 kg. Benefits of resistance training include  improved physical performance, movement control, walking speed, functional  independence, cognitive abilities, and self-esteem. Resistance training may  assist prevention and management of type 2 diabetes by decreasing visceral fat,  reducing {HbA}1c, increasing the density of glucose transporter type 4, and  improving insulin sensitivity. Resistance training may enhance cardiovascular  health, by reducing resting blood pressure, decreasing low-density lipoprotein  cholesterol and triglycerides, and increasing high-density lipoprotein  cholesterol. Resistance training may promote bone development, with studies  showing 1\% to 3\% increase in bone mineral density. Resistance training may be  effective for reducing low back pain and easing discomfort associated with  arthritis and fibromyalgia and has been shown to reverse specific aging factors  in skeletal muscle.},
	pages = {209--216},
	number = {4},
	journaltitle = {Current sports medicine reports},
	shortjournal = {Curr Sports Med Rep},
	author = {Westcott, Wayne L.},
	date = {2012-08},
	pmid = {22777332},
	note = {Place: United States},
	keywords = {Humans, *Health Status, Adult, Resistance Training/*methods, Aging/*physiology, Muscle, Skeletal/*physiology, Physical Fitness/*physiology},
}

@article{kirkman_resistance_2022,
	title = {Resistance exercise for cardiac rehabilitation.},
	volume = {70},
	rights = {Copyright © 2022 Elsevier Inc. All rights reserved.},
	issn = {1873-1740 0033-0620},
	doi = {10.1016/j.pcad.2022.01.004},
	abstract = {Lean mass abnormalities are highly prevalent in patients referred for cardiac rehabilitation ({CR}). As such, current guidelines recommend incorporating  resistance exercise ({RE}) into the exercise prescription of Phase {II}-{IV} {CR}. The  effects of {RE} on health-related outcomes in patients with cardiovascular ({CV})  disease ({CVD}) have not been extensively investigated in comparison to aerobic  exercise, the traditional modality of exercise implemented in {CR}. The purpose of  this review is to highlight the growing prevalence of lean mass abnormalities  such as dynapenia and sarcopenia in {CVD} and briefly outline the contributing  pathophysiology of these impairments as potential targets for {RE} training. An  update on the current evidence pertaining to the effects of {RE} on exercise  capacity, skeletal muscle strength, body composition, {CV} health, and quality of  life in {CR} patient populations is provided. The current recommendations for {RE}  training in {CR} are discussed. Future directions for research and clinical  practice in this field are highlighted, and included the need to identify the  most efficacious principles of resistance training for different health related  outcomes in {CVD}, as well as the suggested drive towards a 'personalized medicine'  approach to exercise prescription in {CR}.},
	pages = {66--72},
	journaltitle = {Progress in cardiovascular diseases},
	shortjournal = {Prog Cardiovasc Dis},
	author = {Kirkman, Danielle L. and Lee, Duck-Chul and Carbone, Salvatore},
	date = {2022-02},
	pmid = {35122871},
	pmcid = {PMC8930531},
	note = {Place: United States},
	keywords = {*Resistance Training, Exercise, Humans, Resistance training, Quality of Life, Exercise Therapy, Sarcopenia, *Cardiac Rehabilitation, *Cardiovascular Diseases/diagnosis/epidemiology, Cardiac rehabilitation, Cardiovascular disease},
}

@article{lee_effect_2012,
	title = {Effect of physical inactivity on major non-communicable diseases worldwide: an analysis of burden of disease and life expectancy.},
	volume = {380},
	issn = {1474-547X 0140-6736},
	doi = {10.1016/S0140-6736(12)61031-9},
	abstract = {{BACKGROUND}: Strong evidence shows that physical inactivity increases the risk of many adverse health conditions, including major non-communicable diseases such as  coronary heart disease, type 2 diabetes, and breast and colon cancers, and  shortens life expectancy. Because much of the world's population is inactive,  this link presents a major public health issue. We aimed to quantify the eff ect  of physical inactivity on these major non-communicable diseases by estimating how  much disease could be averted if inactive people were to become active and to  estimate gain in life expectancy at the population level. {METHODS}: For our  analysis of burden of disease, we calculated population attributable fractions  ({PAFs}) associated with physical inactivity using conservative assumptions for  each of the major non-communicable diseases, by country, to estimate how much  disease could be averted if physical inactivity were eliminated. We used  life-table analysis to estimate gains in life expectancy of the population.  {FINDINGS}: Worldwide, we estimate that physical inactivity causes 6\% (ranging from  3·2\% in southeast Asia to 7·8\% in the eastern Mediterranean region) of the burden  of disease from coronary heart disease, 7\% (3·9-9·6) of type 2 diabetes, 10\%  (5·6-14·1) of breast cancer, and 10\% (5·7-13·8) of colon cancer. Inactivity  causes 9\% (range 5·1-12·5) of premature mortality, or more than 5·3 million of  the 57 million deaths that occurred worldwide in 2008. If inactivity were not  eliminated, but decreased instead by 10\% or 25\%, more than 533 000 and more than  1·3 million deaths, respectively, could be averted every year. We estimated that  elimination of physical inactivity would increase the life expectancy of the  world's population by 0·68 (range 0·41-0·95) years. {INTERPRETATION}: Physical  inactivity has a major health eff ect worldwide. Decrease in or removal of this  unhealthy behaviour could improve health substantially. {FUNDING}: None.},
	pages = {219--229},
	number = {9838},
	journaltitle = {Lancet (London, England)},
	shortjournal = {Lancet},
	author = {Lee, I.-Min and Shiroma, Eric J. and Lobelo, Felipe and Puska, Pekka and Blair, Steven N. and Katzmarzyk, Peter T.},
	date = {2012-07-21},
	pmid = {22818936},
	pmcid = {PMC3645500},
	note = {Place: England},
	keywords = {Female, Humans, *Exercise, *Cost of Illness, Breast Neoplasms/*epidemiology, Colonic Neoplasms/*epidemiology, Coronary Disease/*epidemiology, Diabetes Mellitus, Type 2/*epidemiology, Global Health, Life Expectancy, Life Tables, Risk Factors},
}

@article{deane_transcriptomic_2021,
	title = {Transcriptomic meta-analysis of disuse muscle atrophy vs. resistance exercise-induced hypertrophy in young and older humans.},
	volume = {12},
	rights = {© 2021 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley \& Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting  Disorders.},
	issn = {2190-6009 2190-5991},
	doi = {10.1002/jcsm.12706},
	abstract = {{BACKGROUND}: Skeletal muscle atrophy manifests across numerous diseases; however, the extent of similarities/differences in causal mechanisms between atrophying  conditions in unclear. Ageing and disuse represent two of the most prevalent and  costly atrophic conditions, with resistance exercise training ({RET}) being the  most effective lifestyle countermeasure. We employed gene-level and network-level  meta-analyses to contrast transcriptomic signatures of disuse and {RET}, plus young  and older {RET} to establish a consensus on the molecular features of, and  therapeutic targets against, muscle atrophy in conditions of high socio-economic  relevance. {METHODS}: Integrated gene-level and network-level meta-analysis was  performed on publicly available microarray data sets generated from young  (18-35 years) m. vastus lateralis muscle subjected to disuse (unilateral limb  immobilization or bed rest) lasting ≥7 days or {RET} lasting ≥3 weeks, and  resistance-trained older (≥60 years) muscle. {RESULTS}: Disuse and {RET} displayed  predominantly separate transcriptional responses, and transcripts altered across  conditions were mostly unidirectional. However, disuse and {RET} induced directly  inverted expression profiles for mitochondrial function and translation  regulation genes, with {COX}4I1, {ENDOG}, {GOT}2, {MRPL}12, and {NDUFV}2, the central hub  components of altered mitochondrial networks, and {ZMYND}11, a hub gene of altered  translation regulation. A substantial number of genes (n = 140) up-regulated  post-{RET} in younger muscle were not similarly up-regulated in older muscle, with  young muscle displaying a more pronounced extracellular matrix ({ECM}) and  immune/inflammatory gene expression response. Both young and older muscle  exhibited similar {RET}-induced ubiquitination/{RNA} processing gene signatures with  associated {PWP}1, {PSMB}1, and {RAF}1 hub genes. {CONCLUSIONS}: Despite limited opposing  gene profiles, transcriptional signatures of disuse are not simply the converse  of {RET}. Thus, the mechanisms of unloading cannot be derived from studying muscle  loading alone and provides a molecular basis for understanding why {RET} fails to  target all transcriptional features of disuse. Loss of {RET}-induced {ECM}  mechanotransduction and inflammatory profiles might also contribute to suboptimal  ageing muscle adaptations to {RET}. Disuse and age-dependent molecular candidates  further establish a framework for understanding and treating disuse/ageing  atrophy.},
	pages = {629--645},
	number = {3},
	journaltitle = {Journal of cachexia, sarcopenia and muscle},
	shortjournal = {J Cachexia Sarcopenia Muscle},
	author = {Deane, Colleen S. and Willis, Craig R. G. and Phillips, Bethan E. and Atherton, Philip J. and Harries, Lorna W. and Ames, Ryan M. and Szewczyk, Nathaniel J. and Etheridge, Timothy},
	date = {2021-06},
	pmid = {33951310},
	pmcid = {PMC8200445},
	note = {Place: Germany},
	keywords = {*Resistance Training, Humans, Aged, Hypertrophy, Resistance exercise training, Muscle, Skeletal, Ageing, Gene-level analysis, Mechanotransduction, Cellular, Muscular Atrophy/genetics, Network analysis, Skeletal muscle disuse, Transcriptome, Transcriptomic meta-analysis},
}

@article{lim_evidence-based_2022,
	title = {An Evidence-Based Narrative Review of Mechanisms of Resistance Exercise-Induced Human Skeletal Muscle Hypertrophy.},
	volume = {54},
	rights = {Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Sports Medicine.},
	issn = {1530-0315 0195-9131},
	doi = {10.1249/MSS.0000000000002929},
	abstract = {Skeletal muscle plays a critical role in physical function and metabolic health. Muscle is a highly adaptable tissue that responds to resistance exercise ({RE};  loading) by hypertrophying, or during muscle disuse, {RE} mitigates muscle loss.  Resistance exercise training ({RET})-induced skeletal muscle hypertrophy is a  product of external (e.g., {RE} programming, diet, some supplements) and internal  variables (e.g., mechanotransduction, ribosomes, gene expression, satellite cells  activity). {RE} is undeniably the most potent nonpharmacological external variable  to stimulate the activation/suppression of internal variables linked to muscular  hypertrophy or countering disuse-induced muscle loss. Here, we posit that despite  considerable research on the impact of external variables on {RET} and hypertrophy,  internal variables (i.e., inherent skeletal muscle biology) are dominant in  regulating the extent of hypertrophy in response to external stimuli. Thus,  identifying the key internal skeletal muscle-derived variables that mediate the  translation of external {RE} variables will be pivotal to determining the most  effective strategies for skeletal muscle hypertrophy in healthy persons. Such  work will aid in enhancing function in clinical populations, slowing functional  decline, and promoting physical mobility. We provide up-to-date, evidence-based  perspectives of the mechanisms regulating {RET}-induced skeletal muscle  hypertrophy.},
	pages = {1546--1559},
	number = {9},
	journaltitle = {Medicine and science in sports and exercise},
	shortjournal = {Med Sci Sports Exerc},
	author = {Lim, Changhyun and Nunes, Everson A. and Currier, Brad S. and {McLeod}, Jonathan C. and Thomas, Aaron C. Q. and Phillips, Stuart M.},
	date = {2022-09-01},
	pmid = {35389932},
	pmcid = {PMC9390238},
	note = {Place: United States},
	keywords = {*Resistance Training, Humans, Mechanotransduction, Cellular, Exercise/physiology, Hypertrophy/metabolism, Muscle, Skeletal/physiology},
}

@article{houben_resistance_2023,
	title = {Resistance Exercise Training Increases Muscle Mass and Strength in Prostate Cancer Patients on Androgen Deprivation Therapy},
	volume = {55},
	issn = {0195-9131},
	url = {https://journals.lww.com/acsm-msse/Fulltext/2023/04000/Resistance_Exercise_Training_Increases_Muscle_Mass.2.aspx},
	abstract = {Purpose

This study aimed to assess the effects of 20 wk resistance exercise training with or without protein supplementation on body composition, muscle mass, muscle strength, physical performance, and aerobic capacity in prostate cancer patients receiving androgen deprivation therapy ({ADT}).

Methods

Sixty prostate cancer patients receiving {ADT} were randomly assigned to perform 20 wk of resistance exercise training with supplementation of 31 g whey protein ({EX} + {PRO}, n = 30) or placebo ({EX} + {PLA}, n = 30), consumed immediately after exercise and every night before sleep. A separate control group ({CON}, n = 36) only received usual care. At baseline and after 20 wk, body composition (dual-energy x-ray absorptiometry), muscle mass (computed tomography scan), muscle strength (1-repetition maximum strength tests), physical performance (Timed Up and Go Test, 30-Second Chair Stand Test, and Stair Climb Test), aerobic capacity (cardiopulmonary exercise test), and habitual dietary intake (food diary) were assessed. Data were analyzed using a two-factor repeated-measures {ANOVA}.

Results

Over time, muscle mass and strength increased in {EX} + {PRO} and {EX} + {PLA} and decreased in {CON}. Total fat mass and fat percentage increased in {EX} + {PRO} and {CON}, but not in {EX} + {PLA}. Physical performance did not significantly change over time in either group. Aerobic capacity was maintained in {EX} + {PLA}, but it decreased in {EX} + {PRO} and {CON}. Habitual protein intake (without supplements) averaged {\textgreater}1.0 g·kg body weight−1·d−1, with no differences over time or between groups.

Conclusions

In prostate cancer patients, resistance exercise training counteracts the adverse effects of {ADT} on body composition, muscle mass, muscle strength, and aerobic capacity, with no additional benefits of protein supplementation.},
	number = {4},
	journaltitle = {Medicine \& Science in Sports \& Exercise},
	author = {{HOUBEN}, {LISANNE} H. P. and {OVERKAMP}, {MAARTEN} and {VAN} {KRAAIJ}, {PUCK} and {TROMMELEN}, {JORN} and {VAN} {ROERMUND}, {JOEP} G. H. and {DE} {VRIES}, {PETER} and {DE} {LAET}, {KEVIN} and {VAN} {DER} {MEER}, {SASKIA} and {MIKKELSEN}, {ULLA} R. and {VERDIJK}, {LEX} B. and {VAN} {LOON}, {LUC} J. C. and {BEIJER}, {SANDRA} and {BEELEN}, {MILOU}},
	date = {2023},
	keywords = {{AEROBIC} {CAPACITY}, {BODY} {COMPOSITION}, {HORMONE} {THERAPY}, {PHYSICAL} {PERFORMANCE}, {PROTEIN} {SUPPLEMENTATION}},
}

@article{nunes_what_2021,
	title = {What influence does resistance exercise order have on muscular strength gains and muscle hypertrophy? A systematic review and meta-analysis.},
	volume = {21},
	issn = {1536-7290},
	doi = {10.1080/17461391.2020.1733672},
	abstract = {The objectives of this paper were to: (a) systematically review studies that explored the effects of exercise order ({EO}) on muscular strength and/or  hypertrophy; (b) pool their results using a meta-analysis; and (c) provide  recommendations for the prescription of {EO} in resistance training ({RT})  programmes. A literature search was performed in four databases. Studies were  included if they explored the effects of {EO} on dynamic muscular strength and/or  muscle hypertrophy. The meta-analysis was performed using a random-effects model  with Hedges' g effect size ({ES}). The methodological quality of studies was  appraised using the {TESTEX} checklist. Eleven good-to-excellent methodological  quality studies were included in the review. When all strength tests, that is,  both in multi-joint ({MJ}) and single-joint ({SJ}) exercises were considered, there  was no difference between the {EOs} ({ES} = -0.11; p = 0.306). However, there was a  difference between the {MJ}-to-{SJ} and {SJ}-to-{MJ} orders for strength gains in the {MJ}  exercises, favouring starting the exercise session with {MJ} exercises ({ES} = 0.32;  p = 0.034), and the strength gains in the {SJ} exercises, favouring starting the  exercise session with {SJ} exercises ({ES} = -0.58; p = 0.032). No significant effect  of {EO} was observed for hypertrophy combining site-specific and indirect measures  ({ES} = 0.03; p = 0.862). In conclusion, increases in muscular strength are the  largest in the exercises performed at the beginning of an exercise session. For  muscle hypertrophy, our meta-analysis indicated that both {MJ}-to-{SJ} and {SJ}-to-{MJ}  {EOs} may produce similar results.},
	pages = {149--157},
	number = {2},
	journaltitle = {European journal of sport science},
	shortjournal = {Eur J Sport Sci},
	author = {Nunes, João Pedro and Grgic, Jozo and Cunha, Paolo M. and Ribeiro, Alex S. and Schoenfeld, Brad J. and de Salles, Belmiro F. and Cyrino, Edilson S.},
	date = {2021-02},
	pmid = {32077380},
	note = {Place: England},
	keywords = {Humans, Muscle Strength/*physiology, Resistance Training/*methods, Hypertrophy, Muscle, Skeletal/*physiology, Muscle contraction, muscle growth, muscle strength, pre-exhaustion, strength training},
}

@article{da_boit_sex_2016,
	title = {Sex differences in the response to resistance exercise training in older people},
	volume = {4},
	issn = {2051-817X},
	url = {https://pubmed.ncbi.nlm.nih.gov/27354538},
	doi = {10.14814/phy2.12834},
	abstract = {Resistance exercise training is known to be effective in increasing muscle mass in older people. Acute measurement of protein metabolism data has indicated that the magnitude of response may differ between sexes. We compared adaptive responses in muscle mass and function to 18 weeks resistance exercise training in a cohort of older ({\textgreater}65 years) men and women. Resistance exercise training improved knee extensor maximal torque, 4 m walk time, time to complete five chair rises, muscle anatomical cross-sectional area ({ACSA}) and muscle quality with no effect on muscle fat/water ratio or plasma glucose, insulin, triacylglycerol, {IL}-6, and {TNF}-α Differences between sexes were observed for knee extensor maximal torque and muscle quality with greater increases observed in men versus women (P {\textless} 0.05). Maximal torque increased by 15.8 ± 10.6\% in women and 41.7 ± 25.5\% in men, whereas muscle quality increased by 8.8 ± 17.5\% in women and by 33.7 ± 25.6\% in men. In conclusion, this study has demonstrated a difference in the magnitude of adaptation, of some of the outcome measures employed, in response to 18 weeks of resistance exercise training between men and women. The mechanisms underlying this observation remain to be established.},
	pages = {e12834},
	number = {12},
	journaltitle = {Physiological reports},
	shortjournal = {Physiol Rep},
	eprinttype = {pubmed},
	eprint = {27354538},
	author = {Da Boit, Mariasole and Sibson, Rachael and Meakin, Judith R and Aspden, Richard M and Thies, Frank and Mangoni, Arduino A and Gray, Stuart Robert},
	date = {2016-06},
	note = {Place: United States},
	keywords = {*Resistance Training, Female, Humans, exercise, Aged, Male, Aging, *Adaptation, Physiological, Blood Glucose/metabolism, Insulin/blood, Interleukin-6/blood, muscle adaptation, Muscle, Skeletal/growth \& development/metabolism/*physiology, Sex Factors, sexual dimorphism, Torque, Triglycerides/blood, Tumor Necrosis Factor-alpha/blood},
}

@article{hurst_resistance_2022,
	title = {Resistance exercise as a treatment for sarcopenia: prescription and delivery.},
	volume = {51},
	rights = {© The Author(s) 2022. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email:  journals.permissions@oup.com.},
	issn = {1468-2834 0002-0729},
	doi = {10.1093/ageing/afac003},
	abstract = {Sarcopenia is a generalised skeletal muscle disorder characterised by reduced muscle strength and mass and associated with a range of negative health outcomes.  Currently, resistance exercise ({RE}) is recommended as the first-line treatment  for counteracting the deleterious consequences of sarcopenia in older adults.  However, whilst there is considerable evidence demonstrating that {RE} is an  effective intervention for improving muscle strength and function in healthy  older adults, much less is known about its benefits in older people living with  sarcopenia. Furthermore, evidence for its optimal prescription and delivery is  very limited and any potential benefits of {RE} are unlikely to be realised in the  absence of an appropriate exercise dose. We provide a summary of the underlying  principles of effective {RE} prescription (specificity, overload and progression)  and discuss the main variables (training frequency, exercise selection, exercise  intensity, exercise volume and rest periods) that can be manipulated when  designing {RE} programmes. Following this, we propose that an {RE} programme that  consists of two exercise sessions per week and involves a combination of upper-  and lower-body exercises performed with a relatively high degree of effort for  1-3 sets of 6-12 repetitions is appropriate as a treatment for sarcopenia. The  principles of {RE} prescription outlined here and the proposed {RE} programme  presented in this paper provide a useful resource for clinicians and exercise  practitioners treating older adults with sarcopenia and will also be of value to  researchers for standardising approaches to {RE} interventions in future sarcopenia  studies.},
	number = {2},
	journaltitle = {Age and ageing},
	shortjournal = {Age Ageing},
	author = {Hurst, Christopher and Robinson, Sian M. and Witham, Miles D. and Dodds, Richard M. and Granic, Antoneta and Buckland, Charlotte and De Biase, Sarah and Finnegan, Susanne and Rochester, Lynn and Skelton, Dawn A. and Sayer, Avan A.},
	date = {2022-02-02},
	pmid = {35150587},
	pmcid = {PMC8840798},
	note = {Place: England},
	keywords = {*Resistance Training, Humans, Aged, resistance exercise, Muscle, Skeletal, muscle strength, *Sarcopenia/therapy, exercise prescription, Muscle Strength/physiology, older people, physical performance, Prescriptions, sarcopenia},
}

@article{davidsen_high_2011,
	title = {High responders to resistance exercise training demonstrate differential regulation of skeletal muscle {microRNA} expression.},
	volume = {110},
	issn = {1522-1601 0161-7567},
	doi = {10.1152/japplphysiol.00901.2010},
	abstract = {{MicroRNAs} ({miRNA}), small noncoding {RNA} molecules, may regulate protein synthesis, while resistance exercise training ({RT}) is an efficient strategy for stimulating  muscle protein synthesis in vivo. However, {RT} increases muscle mass, with a very  wide range of effectiveness in humans. We therefore determined the expression  level of 21 abundant {miRNAs} to determine whether variation in these {miRNAs} was  able to explain the variation in {RT}-induced gains in muscle mass. Vastus  lateralis biopsies were obtained from the top and bottom ∼20\% of responders from  56 young men who undertook a 5 day/wk {RT} program for 12 wk. Training-induced  muscle mass gain was determined by dual-energy X-ray absorptiometry, and fiber  size was evaluated by histochemistry. The expression level of each {miRNA} was  quantified using {TaqMan}-based quantitative {PCR}, with the analysis carried out in  a blinded manner. Gene ontology and target gene profiling were used to predict  the potential biological implications. Of the 21 mature {miRNAs} examined, 17 were  stable during {RT} in both groups. However, {miR}-378, {miR}-29a, {miR}-26a, and {miR}-451  were differentially expressed between low and high responders. {miR}-378, {miR}-29a,  and {miR}-26a were downregulated in low responders and unchanged in high  responders, while {miR}-451 was upregulated only in low responders. Interestingly,  the training-induced change in {miR}-378 abundance was positively correlated with  muscle mass gains in vivo. Gene ontology analysis of the target gene list of  {miR}-378, {miR}-29a, {miR}-26a, and {miR}-451, from the weighted cumulative context  ranking methodology, indicated that {miRNA} changes in the low responders may be  compensatory, reflecting a failure to "activate" growth and remodeling genes. We  report, for the first time, that {RT}-induced hypertrophy in human skeletal muscle  is associated with selected changes in {miRNA} abundance. Our analysis indicates  that {miRNAs} may play a role in the phenotypic change and pronounced intergroup  variation in the {RT} response.},
	pages = {309--317},
	number = {2},
	journaltitle = {Journal of applied physiology (Bethesda, Md. : 1985)},
	shortjournal = {J Appl Physiol (1985)},
	author = {Davidsen, Peter K. and Gallagher, Iain J. and Hartman, Joseph W. and Tarnopolsky, Mark A. and Dela, Flemming and Helge, Jørn W. and Timmons, James A. and Phillips, Stuart M.},
	date = {2011-02},
	pmid = {21030674},
	note = {Place: United States},
	keywords = {Humans, Adult, Resistance Training/*methods, Young Adult, Male, Adolescent, Muscle, Skeletal/*physiology, Physical Fitness/*physiology, Gene Expression Profiling, Gene Expression Regulation/*physiology, {MicroRNAs}/genetics/*metabolism, Muscle Proteins/*genetics/metabolism},
}

@article{gyenis_genome-wide_2023,
	title = {Genome-wide {RNA} polymerase stalling shapes the transcriptome during aging},
	issn = {1546-1718},
	url = {https://doi.org/10.1038/s41588-022-01279-6},
	doi = {10.1038/s41588-022-01279-6},
	abstract = {Gene expression profiling has identified numerous processes altered in aging, but how these changes arise is largely unknown. Here we combined nascent {RNA} sequencing and {RNA} polymerase {II} chromatin immunoprecipitation followed by sequencing to elucidate the underlying mechanisms triggering gene expression changes in wild-type aged mice. We found that in 2-year-old liver, 40\% of elongating {RNA} polymerases are stalled, lowering productive transcription and skewing transcriptional output in a gene-length-dependent fashion. We demonstrate that this transcriptional stress is caused by endogenous {DNA} damage and explains the majority of gene expression changes in aging in most mainly postmitotic organs, specifically affecting aging hallmark pathways such as nutrient sensing, autophagy, proteostasis, energy metabolism, immune function and cellular stress resilience. Age-related transcriptional stress is evolutionary conserved from nematodes to humans. Thus, accumulation of stochastic endogenous {DNA} damage during aging deteriorates basal transcription, which establishes the age-related transcriptome and causes dysfunction of key aging hallmark pathways, disclosing how {DNA} damage functionally underlies major aspects of normal aging.},
	journaltitle = {Nature Genetics},
	shortjournal = {Nature Genetics},
	author = {Gyenis, Akos and Chang, Jiang and Demmers, Joris J. P. G. and Bruens, Serena T. and Barnhoorn, Sander and Brandt, Renata M. C. and Baar, Marjolein P. and Raseta, Marko and Derks, Kasper W. J. and Hoeijmakers, Jan H. J. and Pothof, Joris},
	date = {2023-01-19},
}

@article{he_role_2018,
	title = {Role of {lncRNAs} in aging and age-related diseases},
	volume = {1},
	issn = {2475-0360},
	url = {https://pubmed.ncbi.nlm.nih.gov/31942494},
	doi = {10.1002/agm2.12030},
	abstract = {Aging is progressive physiological degeneration and consequently declined function, which is linked to senescence on both cellular and organ levels. Accumulating studies indicate that long noncoding {RNAs} ({lncRNAs}) play important roles in cellular senescence at all levels-transcriptional, post-transcriptional, translational, and post-translational. Understanding the molecular mechanism of {lncRNAs} underlying senescence could facilitate interpretation and intervention of aging and age-related diseases. In this review, we describe categories of known and novel {lncRNAs} that have been involved in the progression of senescence. We also identify the {lncRNAs} implicated in diseases arising from age-driven degeneration or dysfunction in some representative organs and systems (brains, liver, muscle, cardiovascular system, bone pancreatic islets, and immune system). Improved comprehension of {lncRNAs} in the aging process on all levels, from cell to organismal, may provide new insights into the amelioration of age-related pathologies and prolonged healthspan.},
	pages = {158--175},
	number = {2},
	journaltitle = {Aging medicine (Milton (N.S.W))},
	shortjournal = {Aging Med (Milton)},
	eprinttype = {pubmed},
	eprint = {31942494},
	author = {He, Jieyu and Tu, Chao and Liu, Youshuo},
	date = {2018-07-30},
	note = {Place: Australia},
	keywords = {age‐related diseases, long noncoding {RNAs}, senescence},
}

@article{adusumalli_increased_2019,
	title = {Increased intron retention is a post-transcriptional signature associated with progressive aging and Alzheimer's disease.},
	volume = {18},
	rights = {© 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley \& Sons Ltd.},
	issn = {1474-9726 1474-9718},
	doi = {10.1111/acel.12928},
	abstract = {Intron retention ({IR}) by alternative splicing is a conserved regulatory mechanism that can affect gene expression and protein function during adult development and  age-onset diseases. However, it remains unclear whether {IR} undergoes spatial or  temporal changes during different stages of aging or neurodegeneration like  Alzheimer's disease ({AD}). By profiling the transcriptome of Drosophila head cells  at different ages, we observed a significant increase in {IR} events for many genes  during aging. Differential {IR} affects distinct biological functions at different  ages and occurs at several {AD}-associated genes in older adults. The increased  nucleosome occupancy at the differentially retained introns in young animals  suggests that it may regulate the level of {IR} during aging. Notably, an increase  in the number of {IR} events was also observed in healthy older mouse and human  brain tissues, as well as in the cerebellum and frontal cortex from independent  {AD} cohorts. Genes with differential {IR} shared many common features, including  shorter intron length, no perturbation in their {mRNA} level, and enrichment for  biological functions that are associated with {mRNA} processing and proteostasis.  The differentially retained introns identified in {AD} frontal cortex have higher  {GC} content, with many of their {mRNA} transcripts showing an altered level of  protein expression compared to control samples. Taken together, our results  suggest that an increased {IR} is an conserved signature that is associated with  aging. By affecting pathways involved in {mRNA} and protein homeostasis, changes of  {IR} pattern during aging may regulate the transition from healthy to pathological  state in late-onset sporadic {AD}.},
	pages = {e12928},
	number = {3},
	journaltitle = {Aging cell},
	shortjournal = {Aging Cell},
	author = {Adusumalli, Swarnaseetha and Ngian, Zhen-Kai and Lin, Wei-Qi and Benoukraf, Touati and Ong, Chin-Tong},
	date = {2019-06},
	pmid = {30868713},
	pmcid = {PMC6516162},
	keywords = {Humans, Animals, human, Transcriptome, aging, Aging/*genetics, Alzheimer Disease/*genetics/pathology, Alzheimer’s disease, Brain/pathology, Drosophila, Intron retention, Introns/*genetics, Mice, mouse},
}

@article{mariotti_deterioration_2022,
	title = {Deterioration of the human transcriptome with age due to increasing intron retention and spurious splicing},
	url = {http://biorxiv.org/content/early/2022/03/14/2022.03.14.484341.abstract},
	doi = {10.1101/2022.03.14.484341},
	abstract = {Adult aging is characterized by a progressive deterioration of biological functions at physiological, cellular and molecular levels, but its damaging effects on the transcriptome are not well characterized. Here, by analyzing splicing patterns in ∼1,000 human subjects sampled across multiple tissues, we found that splicing fidelity declines with age. Most prominently, genuine introns fail to be spliced out, manifesting as a broad surge in intron retention, and this is exacerbated by the increase in diverse spurious exon-exon junctions with age. Both of these effects are prominently detected in the majority of human tissues. Collectively, they result in the progressive deterioration of the active transcriptome, wherein functional {mRNAs} are increasingly diluted with non-functional splicing isoforms. We discuss the concept of “splicing damage” and formulate methods to quantify it. Using these tools, we show that splicing damage increases both with age and with the incidence of diseases. Altogether, this work uncovers transcriptome damage as a critical molecular indicator of human aging and healthspan.Competing Interest {StatementThe} authors have declared no competing interest.},
	pages = {2022.03.14.484341},
	journaltitle = {{bioRxiv}},
	author = {Mariotti, Marco and Kerepesi, Csaba and Oliveros, Winona and Mele, Marta and Gladyshev, Vadim N.},
	date = {2022-01-01},
}

@article{van_dam_genefriends_2015,
	title = {{GeneFriends}: a human {RNA}-seq-based gene and transcript co-expression database.},
	volume = {43},
	rights = {© The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.},
	issn = {1362-4962 0305-1048},
	doi = {10.1093/nar/gku1042},
	abstract = {Co-expression networks have proven effective at assigning putative functions to genes based on the functional annotation of their co-expressed partners, in  candidate gene prioritization studies and in improving our understanding of  regulatory networks. The growing number of genome resequencing efforts and  genome-wide association studies often identify loci containing novel genes and  there is a need to infer their functions and interaction partners. To facilitate  this we have expanded {GeneFriends}, an online database that allows users to  identify co-expressed genes with one or more user-defined genes. This expansion  entails an {RNA}-seq-based co-expression map that includes genes and transcripts  that are not present in the microarray-based co-expression maps, including over  10,000 non-coding {RNAs}. The results users obtain from {GeneFriends} include a  co-expression network as well as a summary of the functional enrichment among the  co-expressed genes. Novel insights can be gathered from this database for  different splice variants and {ncRNAs}, such as {microRNAs} and {lincRNAs}.  Furthermore, our updated tool allows candidate transcripts to be linked to  diseases and processes using a guilt-by-association approach. {GeneFriends} is  freely available from http://www.{GeneFriends}.org and can be used to quickly  identify and rank candidate targets relevant to the process or disease under  study.},
	pages = {D1124--1132},
	issue = {Database issue},
	journaltitle = {Nucleic acids research},
	shortjournal = {Nucleic Acids Res},
	author = {van Dam, Sipko and Craig, Thomas and de Magalhães, João Pedro},
	date = {2015-01},
	pmid = {25361971},
	pmcid = {PMC4383890},
	keywords = {Humans, *Databases, Genetic, *Gene Expression Profiling, *Gene Regulatory Networks, *Sequence Analysis, {RNA}, Internet, {RNA}, Untranslated/*metabolism},
}

@article{marttila_ageing-associated_2020,
	title = {Ageing-associated changes in the expression of {lncRNAs} in human tissues reflect a transcriptional modulation in ageing pathways.},
	volume = {185},
	rights = {Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.},
	issn = {1872-6216 0047-6374},
	doi = {10.1016/j.mad.2019.111177},
	abstract = {Ageing-associated changes in the protein coding transcriptome have been extensively characterised, but less attention has been paid to the non-coding  portion of the human genome, especially to long non-coding {RNAs} ({lncRNAs}). Only a  minority of known {lncRNAs} have been functionally characterised; however, a  handful of these {lncRNAs} have already been linked to ageing-associated processes.  To gain more information on the effects of ageing on {lncRNAs}, we identified from  {GTEx} data {lncRNAs} that show ageing-associated expression patterns (age-{lncRNAs})  in 29 human tissues in 20-79-year-old individuals. The age-{lncRNAs} identified  were highly tissue-specific, but the protein coding genes co-expressed with the  age-{lncRNAs} and the functional categories associated with the age-{lncRNAs} showed  significant overlap across tissues. Functions associated with the age-{lncRNAs},  including immune system processes and transcription, were similar to what has  previously been reported for protein coding genes with ageing-associated  expression pattern. As the tissue-specific age-{lncRNAs} were associated with  shared functions across tissues, they may reflect the tissue-specific fine-tuning  of the common ageing-associated processes. The present study can be utilised as a  resource when selecting and prioritising {lncRNAs} for further functional analyses.},
	pages = {111177},
	journaltitle = {Mechanisms of ageing and development},
	shortjournal = {Mech Ageing Dev},
	author = {Marttila, Saara and Chatsirisupachai, Kasit and Palmer, Daniel and de Magalhães, João Pedro},
	date = {2020-01},
	pmid = {31706952},
	pmcid = {PMC6961210},
	keywords = {Female, Humans, Middle Aged, Adult, Aged, Male, Aging, *Gene Expression Profiling, *Aging/genetics/immunology, *Transcriptome, Databases, Nucleic Acid, Down-Regulation, Gene Regulatory Networks/physiology, Genome, Human, {lncRNA}, Molecular Sequence Annotation, {ncRNA}, Organ Specificity/*genetics, {RNA}, Long Noncoding/*analysis, Transcription, Genetic/*physiology, Transcriptomics, Up-Regulation},
}

@article{stokes_transcriptomics_2023,
	title = {Transcriptomics for clinical and experimental biology research: hang on a seq},
	volume = {4},
	pages = {2200024},
	number = {2},
	journaltitle = {Advanced Genetics},
	author = {Stokes, Tanner and Cen, Haoning Howard and Kapranov, Philipp and Gallagher, Iain J. and Pitsillides, Andrew A. and Volmar, Claude-Henry and Kraus, William E. and Johnson, James D. and Phillips, Stuart M. and Wahlestedt, Claes},
	date = {2023},
	note = {{ISBN}: 2641-6573
Publisher: Wiley Online Library},
}

@article{nederveen_skeletal_2016,
	title = {Skeletal muscle satellite cells are located at a closer proximity to capillaries in healthy young compared with older men},
	volume = {7},
	pages = {547--554},
	number = {5},
	journaltitle = {Journal of cachexia, sarcopenia and muscle},
	author = {Nederveen, Joshua P. and Joanisse, Sophie and Snijders, Tim and Ivankovic, Victoria and Baker, Steven K. and Phillips, Stuart M. and Parise, Gianni},
	date = {2016},
	note = {{ISBN}: 2190-5991
Publisher: Wiley Online Library},
}

@article{mayhew_eukaryotic_2011,
	title = {Eukaryotic initiation factor 2B epsilon induces cap‐dependent translation and skeletal muscle hypertrophy},
	volume = {589},
	pages = {3023--3037},
	number = {12},
	journaltitle = {The Journal of physiology},
	author = {Mayhew, David L. and Hornberger, Troy A. and Lincoln, Hannah C. and Bamman, Marcas M.},
	date = {2011},
	note = {{ISBN}: 0022-3751
Publisher: Wiley Online Library},
}

@article{stec_ribosome_2016,
	title = {Ribosome biogenesis may augment resistance training-induced myofiber hypertrophy and is required for myotube growth in vitro},
	volume = {310},
	pages = {E652--E661},
	number = {8},
	journaltitle = {American Journal of Physiology-Endocrinology and Metabolism},
	author = {Stec, Michael J. and Kelly, Neil A. and Many, Gina M. and Windham, Samuel T. and Tuggle, S. Craig and Bamman, Marcas M.},
	date = {2016},
	note = {{ISBN}: 0193-1849
Publisher: American Physiological Society Bethesda, {MD}},
}

@article{lavin_muscle_2021,
	title = {Muscle transcriptional networks linked to resistance exercise training hypertrophic response heterogeneity.},
	volume = {53},
	issn = {1531-2267 1094-8341},
	doi = {10.1152/physiolgenomics.00154.2020},
	abstract = {The skeletal muscle hypertrophic response to resistance exercise training ({RT}) is highly variable across individuals. The molecular underpinnings of this  heterogeneity are unclear. This study investigated transcriptional networks  linked to {RT}-induced muscle hypertrophy, classified as 1) predictive of  hypertrophy, 2) responsive to {RT} independent of muscle hypertrophy, or 3) plastic  with hypertrophy. Older adults (n = 31, 18 F/13 M, 70 ± 4 yr) underwent 14-wk {RT}  (3 days/wk, alternating high-low-high intensity). Muscle hypertrophy was assessed  by pre- to post-{RT} change in mid-thigh muscle cross-sectional area ({CSA})  [computed tomography ({CT}), primary outcome] and thigh lean mass [dual-energy  X-ray absorptiometry ({DXA}), secondary outcome]. Transcriptome-wide poly-A {RNA}-seq  was performed on vastus lateralis tissue collected pre- (n = 31) and post-{RT} (n =  22). Prediction networks (using only baseline {RNA}-seq) were identified by  weighted gene correlation network analysis ({WGCNA}). To identify Plasticity  networks, {WGCNA} change indices for paired samples were calculated and correlated  to changes in muscle size outcomes. Pathway-level information extractor ({PLIER})  was applied to identify Response networks and link genes to biological  annotation. Prediction networks (n = 6) confirmed transcripts previously  connected to resistance/aerobic training adaptations in the {MetaMEx} database  while revealing novel member genes that should fuel future research to understand  the influence of baseline muscle gene expression on hypertrophy. Response  networks (n = 6) indicated {RT}-induced increase in aerobic metabolism and reduced  expression of genes associated with spliceosome biology and type-I myofibers. A  single exploratory Plasticity network was identified. Findings support that  interindividual differences in baseline gene expression may contribute more than  {RT}-induced changes in gene networks to muscle hypertrophic response  heterogeneity. Code/Data:  https://github.com/kallavin/{MASTERS}\_manuscript/tree/master.},
	pages = {206--221},
	number = {5},
	journaltitle = {Physiological genomics},
	shortjournal = {Physiol Genomics},
	author = {Lavin, Kaleen M. and Bell, Margaret B. and {McAdam}, Jeremy S. and Peck, Bailey D. and Walton, R. Grace and Windham, Samuel T. and Tuggle, S. Craig and Long, Douglas E. and Kern, Philip A. and Peterson, Charlotte A. and Bamman, Marcas M.},
	date = {2021-05-01},
	pmid = {33870722},
	pmcid = {PMC8424535},
	note = {Place: United States},
	keywords = {*Resistance Training, Female, Humans, Aged, Male, resistance exercise, skeletal muscle, Muscle, Skeletal/physiology, muscle growth, *Gene Regulatory Networks, Absorptiometry, Photon, network biology, {RNA}-seq, Skeletal Muscle Enlargement/*genetics},
}

@article{trewin_long_2022,
	title = {Long non-coding {RNA} Tug1 modulates mitochondrial and myogenic responses to exercise in skeletal muscle},
	volume = {20},
	pages = {164},
	number = {1},
	journaltitle = {{BMC} biology},
	author = {Trewin, Adam J. and Silver, Jessica and Dillon, Hayley T. and Della Gatta, Paul A. and Parker, Lewan and Hiam, Danielle S. and Lee, Yin Peng and Richardson, Mark and Wadley, Glenn D. and Lamon, Séverine},
	date = {2022},
	note = {{ISBN}: 1741-7007
Publisher: Springer},
}

@article{kang_ppp1r1b-lncrna_2020,
	title = {Ppp1r1b-{lncRNA} inhibits {PRC}2 at myogenic regulatory genes to promote cardiac and skeletal muscle development in mouse and human},
	volume = {26},
	pages = {481--491},
	number = {4},
	journaltitle = {Rna},
	author = {Kang, Xuedong and Zhao, Yan and Van Arsdell, Glen and Nelson, Stanley F. and Touma, Marlin},
	date = {2020},
	note = {{ISBN}: 1355-8382
Publisher: Cold Spring Harbor Lab},
}

@article{zheng_integrated_2021,
	title = {Integrated analysis of long non-coding {RNAs} ({lncRNAs}) and {mRNA} expression profiles identifies {lncRNA} {PRKG}1-{AS}1 playing important roles in skeletal muscle  aging.},
	volume = {13},
	issn = {1945-4589},
	doi = {10.18632/aging.203067},
	abstract = {This study aimed to identify long non-coding {RNAs} ({lncRNAs}) involving in the skeletal muscle aging process. Skeletal muscle samples from old and young  subjects were collected for {lncRNA}-sequencing. Differentially expressed genes  ({DEGs}) and {DElncRNAs} between young and old groups were identified and a  co-expression network was built. Further, a dexamethasone-induced muscle atrophy  cell model was established to characterize the function of a critical {lncRNA}. A  total of 424 {DEGs}, including 271 upregulated genes and 153 downregulated genes as  well as 152 {DElncRNAs} including 76 up-regulated and 76 down-regulated {lncRNAs}  were obtained. Functional analysis demonstrated that the {DEGs} were significantly  related to immune response. Coexpression network demonstrated {lncRNA} {AC}004797.1,  {PRKG}1-{AS}1 and {GRPC}5D-{AS}1 were crucial {lncRNAs}. Their expressions were further  validated by {qRT}-{PCR} in human skeletal muscle and the muscle atrophy cell model.  Further in vitro analysis suggested that knock-down of {PRKG}1-{AS}1 could  significantly increase cell viability and decrease cell apoptosis. {qRT}-{PCR} and  western blot analyses demonstrated that knock-down of {PRKG}1-{AS}1 could increase  the expression of {MyoD}, {MyoG} and Mef2c. This study demonstrated that {lncRNAs} of  {GPRC}5D-{AS}1, {AC}004797.1 and {PRKG}1-{AS}1 might involve the aging-associated disease  processes.},
	pages = {15044--15060},
	number = {11},
	journaltitle = {Aging},
	shortjournal = {Aging (Albany {NY})},
	author = {Zheng, Yan and Liu, Ting and Li, Qun and Li, Jie},
	date = {2021-05-29},
	pmid = {34051073},
	pmcid = {PMC8221296},
	note = {Place: United States},
	keywords = {Female, Humans, Middle Aged, Adult, Young Adult, Aged, Male, Adolescent, Muscle, Skeletal/*metabolism/pathology, Gene Expression Regulation, Gene Regulatory Networks, {RNA}, Messenger/genetics/metabolism, Aging/*genetics, *Gene Expression Profiling, Aged, 80 and over, Apoptosis/genetics, Cell Survival/genetics, Dexamethasone, differentially expressed genes, Gene Ontology, long non-coding {RNAs}, Models, Biological, Muscular Atrophy/genetics/pathology, {MyoD} Protein/metabolism, {PRKG}1-{AS}1, Reproducibility of Results, {RNA}-Seq, {RNA}, Long Noncoding/genetics/*metabolism, skeletal muscle aging},
}

@article{li_functional_2021,
	title = {Functional significance of gain-of-function H19 {lncRNA} in skeletal muscle differentiation and anti-obesity effects},
	volume = {13},
	pages = {137},
	number = {1},
	journaltitle = {Genome medicine},
	author = {Li, Yajuan and Zhang, Yaohua and Hu, Qingsong and Egranov, Sergey D. and Xing, Zhen and Zhang, Zhao and Liang, Ke and Ye, Youqiong and Pan, Yinghong and Chatterjee, Sujash S.},
	date = {2021},
	note = {{ISBN}: 1756-994X
Publisher: Springer},
}

@article{fukada_exerciseresistance_2021,
	title = {Exercise/resistance training and muscle stem cells},
	volume = {36},
	pages = {737--744},
	number = {4},
	journaltitle = {Endocrinology and Metabolism},
	author = {Fukada, So-ichiro and Nakamura, Ayasa},
	date = {2021},
	note = {Publisher: Korean Endocrine Society},
}

@article{raue_transcriptome_2012,
	title = {Transcriptome signature of resistance exercise adaptations: mixed muscle and fiber type specific profiles in young and old adults.},
	volume = {112},
	issn = {1522-1601 8750-7587 0161-7567},
	doi = {10.1152/japplphysiol.00435.2011},
	abstract = {This investigation examined the effects of acute resistance exercise ({RE}), progressive resistance training ({PRT}), and age on the human skeletal muscle  Transcriptome. Two cohorts of young and old adults [study A: 24 yr, 84 yr (n =  28); study B: 25 yr, 78 yr (n = 36)] were studied. Vastus lateralis biopsies were  obtained pre- and 4 h post-{RE} in conjunction with the 1st and 36th (last)  training session as part of a 12-wk {PRT} program in study A, whereas biopsies were  obtained in the basal untrained state in study B. Additionally, the muscle fiber  type specific ({MHC} I and {MHC} {IIa}) Transcriptome response to {RE} was examined in a  subset of young and old women from study A. Transcriptome profiling was performed  using {HG} U133 Plus 2.0 Arrays. The main findings were 1) there were 661 genes  affected by {RE} during the 1st and 36th training bout that correlated with gains  in muscle size and strength with {PRT} (termed the Transcriptome signature of  resistance exercise adaptations); 2) the {RE} gene response was most pronounced in  fast-twitch ({MHC} {IIa}) muscle fibers and provided additional insight into the  skeletal muscle biology affected by {RE}; 3) skeletal muscle of young adults is  more responsive to {RE} at the gene level compared with old adults and age also  affected basal level skeletal muscle gene expression. These skeletal muscle  Transcriptome findings provide further insight into the molecular basis of  sarcopenia and the impact of resistance exercise at the mixed muscle and fiber  type specific level.},
	pages = {1625--1636},
	number = {10},
	journaltitle = {Journal of applied physiology (Bethesda, Md. : 1985)},
	shortjournal = {J Appl Physiol (1985)},
	author = {Raue, Ulrika and Trappe, Todd A. and Estrem, Shawn T. and Qian, Hui-Rong and Helvering, Leah M. and Smith, Rosamund C. and Trappe, Scott},
	date = {2012-05},
	pmid = {22302958},
	pmcid = {PMC3365403},
	note = {Place: United States},
	keywords = {*Resistance Training, Female, Humans, Adult, Young Adult, Aged, Male, Time Factors, Gene Expression Regulation, Sex Factors, Aging/*genetics, Aged, 80 and over, *Gene Expression Profiling/methods, Adaptation, Physiological/genetics, Age Factors, Biopsy, Least-Squares Analysis, Linear Models, Muscle Fibers, Skeletal/*metabolism, Myosin Heavy Chains/genetics, Myosin Type I/genetics, Oligonucleotide Array Sequence Analysis, Quadriceps Muscle/*metabolism, Skeletal Muscle Myosins/genetics},
}

@article{timmons_multiple_2015,
	title = {Multiple sources of bias confound functional enrichment analysis of global-omics data},
	volume = {16},
	pages = {1--3},
	journaltitle = {Genome biology},
	author = {Timmons, James A. and Szkop, Krzysztof J. and Gallagher, Iain J.},
	date = {2015},
	note = {Publisher: Springer},
}

@article{robinson_enhanced_2017,
	title = {Enhanced protein translation underlies improved metabolic and physical adaptations to different exercise training modes in young and old humans},
	volume = {25},
	pages = {581--592},
	number = {3},
	journaltitle = {Cell metabolism},
	author = {Robinson, Matthew M. and Dasari, Surendra and Konopka, Adam R. and Johnson, Matthew L. and Manjunatha, S. and Esponda, Raul Ruiz and Carter, Rickey E. and Lanza, Ian R. and Nair, K. Sreekumaran},
	date = {2017},
	note = {{ISBN}: 1550-4131
Publisher: Elsevier},
}

@article{lindholm_human_2014,
	title = {The human skeletal muscle transcriptome: sex differences, alternative splicing, and tissue homogeneity assessed with {RNA} sequencing},
	volume = {28},
	pages = {4571--4581},
	number = {10},
	journaltitle = {The {FASEB} Journal},
	author = {Lindholm, Malene E. and Huss, Mikael and Solnestam, Beata W. and Kjellqvist, Sanela and Lundeberg, Joakim and Sundberg, Carl J.},
	date = {2014},
	note = {{ISBN}: 0892-6638
Publisher: Wiley Online Library},
}

@article{kulkarni_metformin_2020,
	title = {Metformin alters skeletal muscle transcriptome adaptations to resistance training in older adults.},
	volume = {12},
	issn = {1945-4589},
	doi = {10.18632/aging.104096},
	abstract = {Evidence from clinical trials and observational studies suggests that both progressive resistance exercise training ({PRT}) and metformin delay a variety of  age-related morbidities. Previously, we completed a clinical trial testing the  effects of 14 weeks of {PRT} + metformin ({metPRT}) compared to {PRT} with placebo  ({plaPRT}) on muscle hypertrophy in older adults. We found that metformin blunted  {PRT}-induced muscle hypertrophic response. To understand potential mechanisms  underlying the inhibitory effect of metformin on {PRT}, we analyzed the muscle  transcriptome in 23 {metPRT} and 24 {plaPRT} participants. {PRT} significantly  increased expression of genes involved in extracellular matrix remodeling  pathways, and downregulated {RNA} processing pathways in both groups, however,  metformin attenuated the number of differentially expressed genes within these  pathways compared to {plaPRT}. Pathway analysis showed that genes unique to {metPRT}  modulated aging-relevant pathways, such as cellular senescence and autophagy.  Differentially expressed genes from baseline biopsies in older adults compared to  resting muscle from young volunteers were reduced following {PRT} in {plaPRT} and  were further reduced in {metPRT}. We suggest that although metformin may blunt  pathways induced by {PRT} to promote muscle hypertrophy, adjunctive metformin  during {PRT} may have beneficial effects on aging-associated pathways in muscle  from older adults.},
	pages = {19852--19866},
	number = {20},
	journaltitle = {Aging},
	shortjournal = {Aging (Albany {NY})},
	author = {Kulkarni, Ameya S. and Peck, Bailey D. and Walton, R. Grace and Kern, Philip A. and Mar, Jessica C. and Windham, Samuel T. and Bamman, Marcas M. and Barzilai, Nir and Peterson, Charlotte A.},
	date = {2020-10-18},
	pmid = {33071237},
	pmcid = {PMC7655218},
	note = {Place: United States},
	keywords = {*Resistance Training, Female, Humans, Aged, Male, Treatment Outcome, Time Factors, Adaptation, Physiological, Gene Expression Regulation, Gene Regulatory Networks, strength training, Gene Expression Profiling, aging, Alabama, Double-Blind Method, exercise-drug interaction, gene expression, Hypoglycemic Agents/*therapeutic use, Kentucky, metformin, Metformin/*therapeutic use, Quadriceps Muscle/*drug effects/growth \& development/metabolism, Skeletal Muscle Enlargement/*drug effects, Transcriptome/*drug effects},
}

@article{nishida_tissue-_2015,
	title = {Tissue- and case-specific retention of intron 40 in mature dystrophin {mRNA}},
	volume = {60},
	issn = {1435-232X},
	url = {https://doi.org/10.1038/jhg.2015.24},
	doi = {10.1038/jhg.2015.24},
	abstract = {The dystrophin gene, which is mutated in Duchenne muscular dystrophy ({DMD}), comprises 79 exons that show multiple alternative splicing events. Intron retention, a type of alternative splicing, may control gene expression. We examined intron retention in dystrophin introns by reverse-transcription {PCR} from skeletal muscle, focusing on the nine shortest (all {\textless}1000 bp), because these are more likely to be retained. Only one, intron 40, was retained in {mRNA}; sequencing revealed insertion of a complete intron 40 (851 nt) between exons 40 and 41. The intron 40 retention product accounted for 1.2\% of the total product but had a premature stop codon at the fifth intronic codon. Intron 40 retention was most strongly observed in the kidney (36.6\%) and was not obtained from the fetal liver, lung, spleen or placenta. This indicated that intron retention is a tissue-specific event whose level varies among tissues. In two {DMD} patients, intron 40 retention was observed in one patient but not in the other. Examination of splicing regulatory factors revealed that intron 40 had the highest guanine–cytosine content of all examined introns in a 30-nt segment at its 3′ end. Further studies are needed to clarify the biological role of intron 40-retained dystrophin {mRNA}.},
	pages = {327--333},
	number = {6},
	journaltitle = {Journal of Human Genetics},
	shortjournal = {Journal of Human Genetics},
	author = {Nishida, Atsushi and Minegishi, Maki and Takeuchi, Atsuko and Niba, Emma Tabe Eko and Awano, Hiroyuki and Lee, Tomoko and Iijima, Kazumoto and Takeshima, Yasuhiro and Matsuo, Masafumi},
	date = {2015-06-01},
}

@article{angarola_splicing_2021,
	title = {Splicing alterations in healthy aging and disease},
	volume = {12},
	pages = {e1643},
	number = {4},
	journaltitle = {Wiley Interdisciplinary Reviews: {RNA}},
	author = {Angarola, Brittany Lynn and Anczuków, Olga},
	date = {2021},
	note = {{ISBN}: 1757-7004
Publisher: Wiley Online Library},
}

@article{sanchez-escabias_co-transcriptional_2022,
	title = {Co-transcriptional splicing efficiency is a gene-specific feature that can be regulated by {TGFβ}},
	volume = {5},
	issn = {2399-3642},
	url = {https://doi.org/10.1038/s42003-022-03224-z},
	doi = {10.1038/s42003-022-03224-z},
	abstract = {Differential splicing efficiency of specific introns is a mechanism that dramatically increases protein diversity, based on selection of alternative exons for the final mature {mRNA}. However, it is unclear whether splicing efficiency of introns within the same gene is coordinated and eventually regulated as a mechanism to control mature {mRNA} levels. Based on nascent chromatin-associated {RNA}-sequencing data, we now find that co-transcriptional splicing ({CTS}) efficiency tends to be similar between the different introns of a gene. We establish that two well-differentiated strategies for {CTS} efficiency exist, at the extremes of a gradient: short genes that produce high levels of pre-{mRNA} undergo inefficient splicing, while long genes with relatively low levels of pre-{mRNA} have an efficient splicing. Notably, we observe that genes with efficient {CTS} display a higher level of mature {mRNA} relative to their pre-{mRNA} levels. Further, we show that the {TGFβ} signal transduction pathway regulates the general {CTS} efficiency, causing changes in mature {mRNA} levels. Taken together, our data indicate that {CTS} efficiency is a gene-specific characteristic that can be regulated to control gene expression.},
	pages = {277},
	number = {1},
	journaltitle = {Communications Biology},
	shortjournal = {Communications Biology},
	author = {Sánchez-Escabias, Elena and Guerrero-Martínez, José A. and Reyes, José C.},
	date = {2022-03-28},
}

@article{molmen_chronic_2021-1,
	title = {Chronic obstructive pulmonary disease does not impair responses to resistance training.},
	volume = {19},
	issn = {1479-5876},
	doi = {10.1186/s12967-021-02969-1},
	abstract = {{BACKGROUND}: Subjects with chronic obstructive pulmonary disease ({COPD}) are prone to accelerated decay of muscle strength and mass with advancing age. This is  believed to be driven by disease-inherent systemic pathophysiologies, which are  also assumed to drive muscle cells into a state of anabolic resistance, leading  to impaired abilities to adapt to resistance exercise training. Currently, this  phenomenon remains largely unstudied. In this study, we aimed to investigate the  assumed negative effects of {COPD} for health- and muscle-related responsiveness to  resistance training using a healthy control-based translational approach.  {METHODS}: Subjects with {COPD} (n = 20, {GOLD} {II}-{III}, {FEV}(1predicted) 57 ± 11\%, age  69 ± 5) and healthy controls (Healthy, n = 58, {FEV}(1predicted) 112 ± 16\%, age  67 ± 4) conducted identical whole-body resistance training interventions for  13 weeks, consisting of two weekly supervised training sessions. Leg exercises  were performed unilaterally, with one leg conducting high-load training (10RM)  and the contralateral leg conducting low-load training (30RM). Measurements  included muscle strength (n(variables) = 7), endurance performance  (n(variables) = 6), muscle mass (n(variables) = 3), muscle quality, muscle  biology (m. vastus lateralis; muscle fiber characteristics, {RNA} content including  transcriptome) and health variables (body composition, blood). For core outcome  domains, weighted combined factors were calculated from the range of singular  assessments. {RESULTS}: {COPD} displayed well-known pathophysiologies at baseline,  including elevated levels of systemic low-grade inflammation ([c-reactive  protein](serum)), reduced muscle mass and functionality, and muscle biological  aberrancies. Despite this, resistance training led to improved lower-limb muscle  strength (15 ± 8\%), muscle mass (7 ± 5\%), muscle quality (8 ± 8\%) and  lower-limb/whole-body endurance performance (26 ± 12\%/8 ± 9\%) in {COPD}, resembling  or exceeding responses in Healthy, measured in both relative and numeric change  terms. Within the {COPD} cluster, lower {FEV}(1predicted) was associated with larger  numeric and relative increases in muscle mass and superior relative improvements  in maximal muscle strength. This was accompanied by similar changes in hallmarks  of muscle biology such as {rRNA}-content↑, muscle fiber cross-sectional area↑, type  {IIX} proportions↓, and changes in {mRNA} transcriptomics. Neither of the core  outcome domains were differentially affected by resistance training load.  {CONCLUSIONS}: {COPD} showed hitherto largely unrecognized responsiveness to  resistance training, rejecting the notion of disease-related impairments and  rather advocating such training as a potent measure to relieve pathophysiologies.  {TRIAL} {REGISTRATION}: {ClinicalTrials}.gov {ID}: {NCT}02598830. Registered November 6th  2015, https://clinicaltrials.gov/ct2/show/{NCT}02598830.},
	pages = {292},
	number = {1},
	journaltitle = {Journal of translational medicine},
	shortjournal = {J Transl Med},
	author = {Mølmen, Knut Sindre and Hammarström, Daniel and Falch, Gunnar Slettaløkken and Grundtvig, Morten and Koll, Lise and Hanestadhaugen, Marita and Khan, Yusuf and Ahmad, Rafi and Malerbakken, Bente and Rødølen, Tore Jørgen and Lien, Roger and Rønnestad, Bent R. and Raastad, Truls and Ellefsen, Stian},
	date = {2021-07-06},
	pmid = {34229714},
	pmcid = {PMC8261934},
	note = {Place: England},
	keywords = {*Resistance Training, Humans, Middle Aged, Aged, Muscle Strength, Strength training, *Pulmonary Disease, Chronic Obstructive, Anabolic resistance, {COPD}, Cross-Sectional Studies, Exercise Tolerance, Muscle, Skeletal, Pathophysiology, Skeletal muscle, Training load},
}

@article{correia_long_2021,
	title = {Long Non-Coding {RNAs} in Cardiovascular Diseases: Potential Function as Biomarkers and Therapeutic Targets of Exercise Training},
	volume = {7},
	issn = {2311-553X},
	url = {https://www.mdpi.com/2311-553X/7/4/65},
	doi = {10.3390/ncrna7040065},
	abstract = {Despite advances in treatments and therapies, cardiovascular diseases ({CVDs}) remain one of the leading causes of death worldwide. The discovery that most of the human genome, although transcribed, does not encode proteins was crucial for focusing on the potential of long non-coding {RNAs} ({lncRNAs}) as essential regulators of cell function at the epigenetic, transcriptional, and post-transcriptional levels. This class of non-coding {RNAs} is related to the pathophysiology of the cardiovascular system. The different expression profiles of {lncRNAs}, in different contexts of {CVDs}, change a great potential in their use as a biomarker and targets of therapeutic intervention. Furthermore, regular physical exercise plays a protective role against {CVDs}; on the other hand, little is known about its underlying molecular mechanisms. In this review, we look at the accumulated knowledge on {lncRNAs} and their functions in the cardiovascular system, focusing on the cardiovascular pathology of arterial hypertension, coronary heart disease, acute myocardial infarction, and heart failure. We discuss the potential of these molecules as biomarkers for clinical use, their limitations, and how the manipulation of the expression profile of these transcripts through physical exercise can begin to be suggested as a strategy for the treatment of {CVDs}.},
	number = {4},
	journaltitle = {Non-Coding {RNA}},
	author = {Correia, Camila Caldas Martins and Rodrigues, Luis Felipe and de Avila Pelozin, Bruno Rocha and Oliveira, Edilamar Menezes and Fernandes, Tiago},
	date = {2021},
}

@article{wang_molecular_2011,
	title = {Molecular mechanisms of long noncoding {RNAs}},
	volume = {43},
	pages = {904--914},
	number = {6},
	journaltitle = {Molecular cell},
	author = {Wang, Kevin C. and Chang, Howard Y.},
	date = {2011},
	note = {{ISBN}: 1097-2765
Publisher: Elsevier},
}

@article{lopez-otin_hallmarks_2013,
	title = {The hallmarks of aging},
	volume = {153},
	pages = {1194--1217},
	number = {6},
	journaltitle = {Cell},
	author = {López-Otín, Carlos and Blasco, Maria A. and Partridge, Linda and Serrano, Manuel and Kroemer, Guido},
	date = {2013},
	note = {{ISBN}: 0092-8674
Publisher: Elsevier},
}

@article{nie_distinct_2022,
	title = {Distinct biological ages of organs and systems identified from a multi-omics study},
	volume = {38},
	number = {10},
	journaltitle = {Cell reports},
	author = {Nie, Chao and Li, Yan and Li, Rui and Yan, Yizhen and Zhang, Detao and Li, Tao and Li, Zhiming and Sun, Yuzhe and Zhen, Hefu and Ding, Jiahong},
	date = {2022},
	note = {{ISBN}: 2211-1247
Publisher: Elsevier},
}

@article{keshavarz_targeting_2023,
	title = {Targeting the “hallmarks of aging” to slow aging and treat age-related disease: fact or fiction?},
	volume = {28},
	pages = {242--255},
	number = {1},
	journaltitle = {Molecular Psychiatry},
	author = {Keshavarz, Maryam and Xie, Kan and Schaaf, Kristina and Bano, Daniele and Ehninger, Dan},
	date = {2023},
	note = {{ISBN}: 1359-4184
Publisher: Nature Publishing Group {UK} London},
}

@article{stegeman_transcriptional_2017,
	title = {Transcriptional Signatures of Aging},
	volume = {429},
	issn = {0022-2836},
	url = {https://www.sciencedirect.com/science/article/pii/S0022283617303200},
	doi = {https://doi.org/10.1016/j.jmb.2017.06.019},
	abstract = {Genome-wide studies of aging have identified subsets of genes that show age-related changes in expression. Although the types of genes that are age regulated vary among different tissues and organisms, some patterns emerge from these large data sets. First, aging is associated with a broad induction of stress response pathways, although the specific genes and pathways involved differ depending on cell type and species. In contrast, a wide variety of functional classes of genes are downregulated with age, often including tissue-specific genes. Although the upregulation of age-regulated genes is likely to be governed by stress-responsive transcription factors, questions remain as to why particular genes are susceptible to age-related transcriptional decline. Here, we discuss recent findings showing that splicing is misregulated with age. While defects in splicing could lead to changes in protein isoform levels, they could also impact gene expression through nonsense-mediated decay of intron-retained transcripts. The discovery that splicing is misregulated with age suggests that other aspects of gene expression, such as transcription elongation, termination, and polyadenylation, must also be considered as potential mechanisms for age-related changes in transcript levels. Moreover, the considerable variation between genome-wide aging expression studies indicates that there is a critical need to analyze the transcriptional signatures of aging in single-cell types rather than whole tissues. Since age-associated decreases in gene expression could contribute to a progressive decline in cellular function, understanding the mechanisms that determine the aging transcriptome provides a potential target to extend healthy cellular lifespan.},
	pages = {2427--2437},
	number = {16},
	journaltitle = {Journal of Molecular Biology},
	author = {Stegeman, R. and Weake, V. M.},
	date = {2017},
	keywords = {aging, splicing, transcription},
}

@article{wong_intron_2022,
	title = {Intron retention: importance, challenges, and opportunities},
	volume = {38},
	pages = {789--792},
	number = {8},
	journaltitle = {Trends in Genetics},
	author = {Wong, Justin J.-L. and Schmitz, Ulf},
	date = {2022},
	note = {{ISBN}: 0168-9525
Publisher: Elsevier},
}

@article{shah_towards_2022,
	title = {Towards resolution of the intron retention paradox in breast cancer},
	volume = {24},
	pages = {100},
	number = {1},
	journaltitle = {Breast Cancer Research},
	author = {Shah, Jaynish S. and Milevskiy, Michael {JG} and Petrova, Veronika and Au, Amy {YM} and Wong, Justin {JL} and Visvader, Jane E. and Schmitz, Ulf and Rasko, John {EJ}},
	date = {2022},
	note = {{ISBN}: 1465-542X
Publisher: Springer},
}

@article{hasler_alterations_2011,
	title = {Alterations of pre-{mRNA} splicing in human inflammatory bowel disease},
	volume = {90},
	pages = {603--611},
	number = {6},
	journaltitle = {European journal of cell biology},
	author = {Häsler, Robert and Kerick, Martin and Mah, Nancy and Hultschig, Claus and Richter, Gesa and Bretz, Frank and Sina, Christian and Lehrach, Hans and Nietfeld, Wilfried and Schreiber, Stefan},
	date = {2011},
	note = {{ISBN}: 0171-9335
Publisher: Elsevier},
}

@article{nelson_novel_2005,
	title = {A novel 5'{ATRX} mutation with splicing consequences in acquired alpha thalassemia-myelodysplastic syndrome},
	volume = {90},
	pages = {1463--1470},
	number = {11},
	journaltitle = {haematologica},
	author = {Nelson, Maria E. and Thurmes, Paul J. and Hoyer, James D. and Steensma, David P.},
	date = {2005},
	note = {{ISBN}: 1592-8721},
}

@article{de_melo_costa_splice-q_2021,
	title = {{SPLICE}-q: a Python tool for genome-wide quantification of splicing efficiency},
	volume = {22},
	pages = {1--14},
	journaltitle = {{BMC} bioinformatics},
	author = {de Melo Costa, Verônica R. and Pfeuffer, Julianus and Louloupi, Annita and Ørom, Ulf {AV} and Piro, Rosario M.},
	date = {2021},
	note = {Publisher: Springer},
}

@article{schwerk_regulation_2005,
	title = {Regulation of apoptosis by alternative pre-{mRNA} splicing},
	volume = {19},
	pages = {1--13},
	number = {1},
	journaltitle = {Molecular cell},
	author = {Schwerk, Christian and Schulze-Osthoff, Klaus},
	date = {2005},
	note = {{ISBN}: 1097-2765
Publisher: Elsevier},
}

@article{inoue_minor_2021,
	title = {Minor intron retention drives clonal hematopoietic disorders and diverse cancer predisposition},
	volume = {53},
	issn = {1546-1718},
	url = {https://doi.org/10.1038/s41588-021-00828-9},
	doi = {10.1038/s41588-021-00828-9},
	abstract = {Most eukaryotes harbor two distinct pre-{mRNA} splicing machineries: the major spliceosome, which removes {\textgreater}99\% of introns, and the minor spliceosome, which removes rare, evolutionarily conserved introns. Although hypothesized to serve important regulatory functions, physiologic roles of the minor spliceosome are not well understood. For example, the minor spliceosome component {ZRSR}2 is subject to recurrent, leukemia-associated mutations, yet functional connections among minor introns, hematopoiesis and cancers are unclear. Here, we identify that impaired minor intron excision via {ZRSR}2 loss enhances hematopoietic stem cell self-renewal. {CRISPR} screens mimicking nonsense-mediated decay of minor intron-containing {mRNA} species converged on {LZTR}1, a regulator of {RAS}-related {GTPases}. {LZTR}1 minor intron retention was also discovered in the {RASopathy} Noonan syndrome, due to intronic mutations disrupting splicing and diverse solid tumors. These data uncover minor intron recognition as a regulator of hematopoiesis, noncoding mutations within minor introns as potential cancer drivers and links among {ZRSR}2 mutations, {LZTR}1 regulation and leukemias.},
	pages = {707--718},
	number = {5},
	journaltitle = {Nature Genetics},
	shortjournal = {Nature Genetics},
	author = {Inoue, Daichi and Polaski, Jacob T. and Taylor, Justin and Castel, Pau and Chen, Sisi and Kobayashi, Susumu and Hogg, Simon J. and Hayashi, Yasutaka and Pineda, Jose Mario Bello and El Marabti, Ettaib and Erickson, Caroline and Knorr, Katherine and Fukumoto, Miki and Yamazaki, Hiromi and Tanaka, Atsushi and Fukui, Chie and Lu, Sydney X. and Durham, Benjamin H. and Liu, Bo and Wang, Eric and Mehta, Sanjoy and Zakheim, Daniel and Garippa, Ralph and Penson, Alex and Chew, Guo-Liang and {McCormick}, Frank and Bradley, Robert K. and Abdel-Wahab, Omar},
	date = {2021-05-01},
}

@article{dvinge_widespread_2015,
	title = {Widespread intron retention diversifies most cancer transcriptomes},
	volume = {7},
	pages = {1--13},
	journaltitle = {Genome medicine},
	author = {Dvinge, Heidi and Bradley, Robert K.},
	date = {2015},
	note = {Publisher: Springer},
}

@article{sznajder_intron_2018,
	title = {Intron retention induced by microsatellite expansions as a disease biomarker},
	volume = {115},
	pages = {4234--4239},
	number = {16},
	journaltitle = {Proceedings of the National Academy of Sciences},
	author = {Sznajder, Łukasz J. and Thomas, James D. and Carrell, Ellie M. and Reid, Tammy and {McFarland}, Karen N. and Cleary, John D. and Oliveira, Ruan and Nutter, Curtis A. and Bhatt, Kirti and Sobczak, Krzysztof},
	date = {2018},
	note = {{ISBN}: 0027-8424
Publisher: National Acad Sciences},
}

@article{mauger_targeted_2016,
	title = {Targeted intron retention and excision for rapid gene regulation in response to neuronal activity},
	volume = {92},
	pages = {1266--1278},
	number = {6},
	journaltitle = {Neuron},
	author = {Mauger, Oriane and Lemoine, Frédéric and Scheiffele, Peter},
	date = {2016},
	note = {{ISBN}: 0896-6273
Publisher: Elsevier},
}

@misc{garcia-ruiz_splicing_2023,
	location = {United States},
	title = {Splicing accuracy varies across human introns, tissues and age.},
	doi = {10.1101/2023.03.29.534370},
	abstract = {Alternative splicing impacts most multi-exonic human genes. Inaccuracies during this process may have an important role in ageing and disease. Here, we  investigated mis-splicing using {RNA}-sequencing data from {\textasciitilde}14K control samples and  42 human body sites, focusing on split reads partially mapping to known  transcripts in annotation. We show that mis-splicing occurs at different rates  across introns and tissues and that these splicing inaccuracies are primarily  affected by the abundance of core components of the spliceosome assembly and its  regulators. Using publicly available data on short-hairpin {RNA}-knockdowns of  numerous spliceosomal components and related regulators, we found support for the  importance of {RNA}-binding proteins in mis-splicing. We also demonstrated that age  is positively correlated with mis-splicing, and it affects genes implicated in  neurodegenerative diseases. This in-depth characterisation of mis-splicing can  have important implications for our understanding of the role of splicing  inaccuracies in human disease and the interpretation of long-read {RNA}-sequencing  data.},
	author = {García-Ruiz, S. and Zhang, D. and Gustavsson, E. K. and Rocamora-Perez, G. and Grant-Peters, M. and Fairbrother-Browne, A. and Reynolds, R. H. and Brenton, J. W. and Gil-Martínez, A. L. and Chen, Z. and Rio, D. C. and Botia, J. A. and Guelfi, S. and Collado-Torres, L. and Ryten, M.},
	date = {2023-03-30},
	pmid = {37034741},
	pmcid = {PMC10081249},
	note = {{ISSN}: 2692-8205
Journal Abbreviation: {bioRxiv}
Pages: 2023.03.29.534370
Publication Title: {bioRxiv} : the preprint server for biology},
}

@article{ge_functional_2014,
	title = {The functional consequences of intron retention: alternative splicing coupled to {NMD} as a regulator of gene expression},
	volume = {36},
	pages = {236--243},
	number = {3},
	journaltitle = {Bioessays},
	author = {Ge, Ying and Porse, Bo T.},
	date = {2014},
	note = {{ISBN}: 0265-9247
Publisher: Wiley Online Library},
}

@article{ong_increased_2020,
	title = {Increased intron retention is linked to Alzheimer’s disease},
	volume = {15},
	pages = {259--260},
	number = {2},
	journaltitle = {Neural regeneration research},
	author = {Ong, Chin-Tong and Adusumalli, Swarnaseetha},
	date = {2020},
	note = {{ISBN}: 1673-5374
Publisher: Medknow},
}

@article{zheng_intron_2020,
	title = {Intron retention as a mode for {RNA}-seq data analysis},
	volume = {11},
	pages = {586},
	journaltitle = {Frontiers in genetics},
	author = {Zheng, Jian-Tao and Lin, Cui-Xiang and Fang, Zhao-Yu and Li, Hong-Dong},
	date = {2020},
	note = {{ISBN}: 1664-8021
Publisher: Frontiers Media {SA}},
}

@article{baralle_age-related_2023,
	title = {Age-Related Alternative Splicing: Driver or Passenger in the Aging Process?},
	volume = {12},
	issn = {2073-4409},
	doi = {10.3390/cells12242819},
	abstract = {Alternative splicing changes are closely linked to aging, though it remains unclear if they are drivers or effects. As organisms age, splicing patterns  change, varying gene isoform levels and functions. These changes may contribute  to aging alterations rather than just reflect declining {RNA} quality control.  Three main splicing types-intron retention, cassette exons, and cryptic  exons-play key roles in age-related complexity. These events modify protein  domains and increase nonsense-mediated decay, shifting protein isoform levels and  functions. This may potentially drive aging or serve as a biomarker. Fluctuations  in splicing factor expression also occur with aging. Somatic mutations in  splicing genes can also promote aging and age-related disease. The interplay  between splicing and aging has major implications for aging biology, though  differentiating correlation and causation remains challenging. Declaring a  splicing factor or event as a driver requires comprehensive evaluation of the  associated molecular and physiological changes. A greater understanding of how  {RNA} splicing machinery and downstream targets are impacted by aging is essential  to conclusively establish the role of splicing in driving aging, representing a  promising area with key implications for understanding aging, developing novel  therapeutical options, and ultimately leading to an increase in the healthy human  lifespan.},
	number = {24},
	journaltitle = {Cells},
	shortjournal = {Cells},
	author = {Baralle, Marco and Romano, Maurizio},
	date = {2023-12-12},
	pmid = {38132139},
	pmcid = {PMC10742131},
	note = {Place: Switzerland},
	keywords = {Humans, senescence, aging, *Aging/genetics, *Alternative Splicing/genetics, age-associated splicing events, age-related diseases, alternative splicing, molecular aging, Nonsense Mediated {mRNA} Decay, Protein Isoforms/metabolism, {RNA} Splicing Factors/metabolism, {RNA}, Messenger/genetics, splice variants, splicing factors, splicing regulation, transcriptome changes},
}

@article{wong_intron_2016,
	title = {Intron retention in {mRNA}: No longer nonsense: Known and putative roles of intron retention in normal and disease biology.},
	volume = {38},
	rights = {© 2015 {WILEY} Periodicals, Inc.},
	issn = {1521-1878 0265-9247},
	doi = {10.1002/bies.201500117},
	abstract = {Until recently, retention of introns in mature {mRNAs} has been regarded as a consequence of mis-splicing. Intron-retaining transcripts are thought to be  non-functional because they are readily degraded by nonsense-mediated decay.  However, recent advances in next-generation sequencing technologies have enabled  the detection of numerous transcripts that retain introns. As we review herein,  intron-retaining {mRNAs} play an essential conserved role in normal physiology and  an emergent role in diverse diseases. Intron retention should no longer be  overlooked as a key mechanism that independently reduces gene expression in  normal biology. Exploring its contribution to the development and/or maintenance  of diseases is of increasing importance.},
	pages = {41--49},
	number = {1},
	journaltitle = {{BioEssays} : news and reviews in molecular, cellular and developmental biology},
	shortjournal = {Bioessays},
	author = {Wong, Justin J.-L. and Au, Amy Y. M. and Ritchie, William and Rasko, John E. J.},
	date = {2016-01},
	pmid = {26612485},
	note = {Place: United States},
	keywords = {Humans, Introns/*genetics, gene expression, alternative splicing, Alternative Splicing/*genetics, cancer, Gene Expression Regulation, Neoplastic, intron retention, {MicroRNAs}/genetics, {miRNAs}, Neoplasms/*genetics, non-coding {RNAs}, Nonsense Mediated {mRNA} Decay/genetics, nonsense-mediated decay, {RNA}, Messenger/*genetics, {RNA}, Untranslated/genetics},
}

@article{he_hypoxia-inducible_2020,
	title = {Hypoxia-inducible long noncoding {RNA} {NPSR}1-{AS}1 promotes the proliferation and glycolysis of hepatocellular carcinoma cells by regulating the {MAPK}/{ERK} pathway},
	volume = {533},
	pages = {886--892},
	number = {4},
	journaltitle = {Biochemical and Biophysical Research Communications},
	author = {He, Haibin and Chen, Tianxiang and Mo, Huanye and Chen, Shuangjiang and Liu, Qingguang and Guo, Cheng},
	date = {2020},
	note = {{ISBN}: 0006-291X
Publisher: Elsevier},
}

@article{zhang_comprehensive_2022,
	title = {Comprehensive Analysis of {NPSR}1‐{AS}1 as a Novel Diagnostic and Prognostic Biomarker Involved in Immune Infiltrates in Lung Adenocarcinoma},
	volume = {2022},
	pages = {2099327},
	number = {1},
	journaltitle = {Journal of Oncology},
	author = {Zhang, Hui and Yuan, Jin and Xiang, Yuehua and Liu, Yong},
	date = {2022},
	note = {{ISBN}: 1687-8469
Publisher: Wiley Online Library},
}

@article{yuan_circulating_2022,
	title = {Circulating Long Noncoding {RNAs} Positively Correlate with the Increased Risk, Elevated Severity and Unfavorable Prognosis in the Sepsis Patients},
	author = {Yuan, Jun and Cao, Limian and Bao, Junjie and Zha, Yutao and Chen, Shi and Fan, Wenjing and Fang, Ming and Gui, Yonghui and Liu, Nian and Shao, Min},
	date = {2022},
}

@article{yu_linc00702_2019,
	title = {{LINC}00702 suppresses proliferation and invasion in non-small cell lung cancer through regulating {miR}-510/{PTEN} axis},
	volume = {11},
	pages = {1471},
	number = {5},
	journaltitle = {Aging (Albany {NY})},
	author = {Yu, Wencheng and Li, Daowei and Ding, Xiaoyan and Sun, Yong and Liu, Yanli and Cong, Jinpeng and Yang, Jiong and Sun, Jian and Ning, Xuchao and Wang, Hongmei},
	date = {2019},
	note = {Publisher: Impact Journals, {LLC}},
}

@article{yu_linc00702_2020,
	title = {Linc00702 inhibits cell growth and metastasis through regulating {PTEN} in colorectal cancer.},
	volume = {24},
	number = {7},
	journaltitle = {European Review for Medical \& Pharmacological Sciences},
	author = {Yu, D. and Wang, X.-Y. and Jin, Z.-L.},
	date = {2020},
	note = {{ISBN}: 1128-3602},
}

@article{shah_lung_2024,
	title = {Lung Cancer Biomarker Identification from Differential Expression Analysis Using {RNA}-Seq Data for Multitargeted Drug Designing},
	author = {Shah, Syed Naseer Ahmad and Parveen, Rafat},
	date = {2024},
	note = {Publisher: {MDPI}},
}

@article{luo_development_2022,
	title = {Development of a novel five‐{lncRNA} prognostic signature for predicting overall survival in elderly patients with breast cancer},
	volume = {36},
	pages = {e24172},
	number = {1},
	journaltitle = {Journal of Clinical Laboratory Analysis},
	author = {Luo, Yang and Zhang, Yue and Wu, Yu-Xin and Li, Han-Bing and Shen, Di and Che, Yi-Qun},
	date = {2022},
	note = {{ISBN}: 0887-8013
Publisher: Wiley Online Library},
}

@article{qian_hypermethylation_2022,
	title = {Hypermethylation of tumor suppressor {lncRNA} {MEF}2C-{AS}1 frequently happened in patients at all stages of colorectal carcinogenesis},
	volume = {14},
	pages = {111},
	number = {1},
	journaltitle = {Clinical Epigenetics},
	author = {Qian, Sangni and Lin, Shujuan and Xu, Xin and Bai, Hao and Yeerken, Aibuta and Ying, Xiaojiang and Li, Zhenjun and Fei, Xinglin and Yang, Jinhua and Tang, Mengling},
	date = {2022},
	note = {{ISBN}: 1868-7075
Publisher: Springer},
}

@article{wang_novel_2021,
	title = {A novel identified long non-coding {RNA}, {lncRNA} {MEF}2C-{AS}1, inhibits cervical cancer via regulation of {miR}-592/{RSPO}1},
	volume = {8},
	pages = {687113},
	journaltitle = {Frontiers in molecular biosciences},
	author = {Wang, Xiaoping and Zhang, Changhong and Gong, Meixuan and Jiang, Chen},
	date = {2021},
	note = {{ISBN}: 2296-889X
Publisher: Frontiers Media {SA}},
}

@article{guo_mef2c-as1_2022,
	title = {{MEF}2C-{AS}1 regulates its nearby gene {MEF}2C to mediate cervical cancer cell malignant phenotypes in vitro},
	volume = {632},
	issn = {0006-291X},
	url = {https://www.sciencedirect.com/science/article/pii/S0006291X2201347X},
	doi = {https://doi.org/10.1016/j.bbrc.2022.09.091},
	abstract = {Cervical cancer ({CC}) is the second most common malignancy among women. {GEPIA} demonstrated that {MEF}2C-{AS}1 and its nearby gene {MEF}2C present downregulation in {CC} tissues. We attempted to clarify molecular mechanism between {MEF}2C-{AS}1 and {MEF}2C underlying {CC} progression. {RT}-{qPCR} was used to measure expression levels and subcellular distribution of {MEF}2C-{AS}1 and {MEF}2C in {CC} cell lines. Gain-of-function assays were conducted to reveal roles of {MEF}2C-{AS}1 and {MEF}2C in {CC} cell behaviors. Bioinformatics, {RNA} pull down, and {RIP} assays were performed to assess association of {MEF}2C-{AS}1 or {MEF}2C with {miR}-20 b-5p in {CC} cells. Rescue assays were done to assess regulatory function of the {MEF}2C-{AS}1-{miR}-20 b-5p-{MEF}2C axis in {CC} cellular processes. {MEF}2C-{AS}1 and its nearby gene {MEF}2C showed downregulation and had a positive expression correlation in {CC} tissues. {MEF}2C-{AS}1 and {MEF}2C presented downregulation in {CC} cells, and they majorly distributed in {CC} cell cytoplasm. {MEF}2C-{AS}1 and {MEF}2C upregulation repressed {CC} cell proliferative, migratory, and angiogenic abilities. {MEF}2C-{AS}1 competitively bound with {miR}-20 b-5p to upregulate {MEF}2C in {CC} cells. The impacts of {MEF}2C-{AS}1 elevation on {CC} cell proliferative, migratory, and angiogenic capabilities were countervailed by {miR}-20 b-5p overexpression. The impacts of {miR}-20 b-5p inhibitor on {CC} cell proliferative, migratory and angiogenic capabilities were countervailed by {MEF}2C depletion. To sum up, {MEF}2C-{AS}1 and its nearby gene {MEF}2C present downregulation and serve as tumor suppressors in {CC} cells. {MEF}2C-{AS}1 suppresses {CC} cell malignancy in vitro through sponging {miR}-20 b-5p to upregulate {MEF}2C, which may provide a potential new direction for seeking therapeutic plans of {CC}.},
	pages = {48--54},
	journaltitle = {Biochemical and Biophysical Research Communications},
	author = {Guo, Qi and Zhang, Lijia and Zhao, Lei and Pang, Xueying and Wang, Peng and Sun, Heng and Liu, Songjiang},
	date = {2022},
	keywords = {Cervical cancer, {MEF}2C, {MEF}2C-{AS}1, {miR}-20b-5p},
}

@article{luo_characterization_2018,
	title = {Characterization of long non-coding {RNAs} and {MEF}2C-{AS}1 identified as a novel biomarker in diffuse gastric cancer},
	volume = {11},
	issn = {1936-5233},
	url = {https://www.sciencedirect.com/science/article/pii/S1936523318300986},
	doi = {https://doi.org/10.1016/j.tranon.2018.06.007},
	abstract = {Previous studies proved that long noncoding {RNAs} ({lncRNAs}) play important role in human cancer. However, the knowledge of genome scale expression of {lncRNAs} and their potential biological function in gastric cancer is still lacking. Next generation {RNA} sequencing ({RNA}-seq) was performed on tumor tissues and matched adjacent normal tissues of six diffuse gastric cancer ({DGC}) patients. Then we performed a comprehensive analysis on {lncRNAs} and {mRNA}. Fifty-eight {lncRNAs} were upregulated and 54 {lncRNAs} were downregulated in diffuse gastric cancer tissue compared with adjacent tissue. The numbers of up- and downregulated {mRNAs} were 306 and 161, respectively. In addition, we inferred the function of {lncRNAs} by construction of a co-expression network for deregulated {mRNAs} and {lncRNAs}. Co-expressed genes of {MEF}2C-{AS}1 and {FENDRR} were enriched to {RAS} and {TGF}-beta signaling pathway. {MEF}2C-{AS}1 and {FENDRR} expression were re-evaluated by Real-time Quantitative {PCR} in 42 {DGC} patients' tumor and normal tissues, and other 46 {DGC} patents' and 21 healthy controls' plasma. Validation data showed {MEF}2C-{AS}1 and {FENDRR} were significantly downregulated in tumor tissues compared with normal tissues. And decreased {FENDRR} are associated with aggressive tumor characteristics including more advanced stage (P = .030), poor differentiation (P = .043) and lymphatic metastasis (P = .001). The expression level {MEF}2C-{AS}1 was significantly lower in {DGC} patients' plasma than that in healthy controls' plasma. In gastric cancer cell lines, knock-down of {MEF}2C-{AS}1 or {FENDRR} reduced the protein levels of {FAT}3, {NTN}1 and {LYVE}1 (the co-expressed genes), which were related with gastric cancer cell proliferation and invasion by previous studies. In addition, knock-down of {MEF}2C-{AS}1 or {FENDRR} promoted aggressive tumor behaviors in in-vitro assays. In this study, we provide a valuable resource of {lncRNAs} which might play important roles in the function of oncogenes or tumor suppressors affecting the development and progression of diffuse gastric cancer.},
	pages = {1080--1089},
	number = {5},
	journaltitle = {Translational Oncology},
	author = {Luo, Tianhang and Zhao, Jiangman and Lu, Zhengmao and Bi, Jianwei and Pang, Tao and Cui, Hangtian and Yang, Biao and Li, Wushuang and Wang, Yu and Wu, Shouxin and Xue, Xuchao},
	date = {2018},
}

@article{de_sanctis_non-coding_2021,
	title = {Non-Coding {RNAs} in the Transcriptional Network That Differentiates Skeletal Muscles of Sedentary from Long-Term Endurance- and Resistance-Trained Elderly.},
	volume = {22},
	issn = {1422-0067},
	doi = {10.3390/ijms22041539},
	abstract = {In a previous study, the whole transcriptome of the vastus lateralis muscle from sedentary elderly and from age-matched athletes with an exceptional record of  high-intensity, life-long exercise training was compared-the two groups  representing the two extremes on a physical activity scale. Exercise training  enabled the skeletal muscle to counteract age-related sarcopenia by inducing a  wide range of adaptations, sustained by the expression of protein-coding genes  involved in energy handling, proteostasis, cytoskeletal organization,  inflammation control, and cellular senescence. Building on the previous study, we  examined here the network of non-coding {RNAs} participating in the orchestration  of gene expression and identified differentially expressed micro- and  long-non-coding {RNAs} and some of their possible targets and roles. Unsupervised  hierarchical clustering analyses of all non-coding {RNAs} were able to discriminate  between sedentary and trained individuals, regardless of the exercise typology.  Validated targets of differentially expressed {miRNA} were grouped by {KEGG}  analysis, which pointed to functional areas involved in cell cycle, cytoskeletal  control, longevity, and many signaling pathways, including {AMP}-activated protein  kinase ({AMPK}) and mammalian target of rapamycin ({mTOR}), which had been shown to  be pivotal in the modulation of the effects of high-intensity, life-long exercise  training. The analysis of differentially expressed long-non-coding {RNAs}  identified transcriptional networks, involving {lncRNAs}, {miRNAs} and {mRNAs},  affecting processes in line with the beneficial role of exercise training.},
	number = {4},
	journaltitle = {International journal of molecular sciences},
	shortjournal = {Int J Mol Sci},
	author = {De Sanctis, Paola and Filardo, Giuseppe and Abruzzo, Provvidenza Maria and Astolfi, Annalisa and Bolotta, Alessandra and Indio, Valentina and Di Martino, Alessandro and Hofer, Christian and Kern, Helmut and Löfler, Stefan and Marcacci, Maurilio and Marini, Marina and Zampieri, Sandra and Zucchini, Cinzia},
	date = {2021-02-03},
	pmid = {33546468},
	pmcid = {PMC7913629},
	note = {Place: Switzerland},
	keywords = {Exercise, Humans, Aged, skeletal muscle, Transcriptome, Gene Expression Profiling, aging, *Gene Regulatory Networks, Models, Biological, Age Factors, gene expression, non-coding {RNAs}, *Endurance Training, *Sedentary Behavior, *Transcription, Genetic, Computational Biology/methods, exercise training, Geriatric Assessment, {MicroRNAs}, Muscle, Skeletal/*metabolism, {RNA}, Untranslated/*genetics},
}

@article{zhu_lnc_2019,
	title = {Lnc {RNA} {DUXAP} 9‐206 directly binds with Cbl‐b to augment {EGFR} signaling and promotes non‐small cell lung cancer progression},
	volume = {23},
	pages = {1852--1864},
	number = {3},
	journaltitle = {Journal of cellular and molecular medicine},
	author = {Zhu, Ting and An, Shu and Choy, Man-Ting and Zhou, Junhao and Wu, Shanshan and Liu, Shihua and Liu, Bangdong and Yao, Zhicheng and Zhu, Xun and Wu, Jueheng},
	date = {2019},
	note = {{ISBN}: 1582-1838
Publisher: Wiley Online Library},
}

@article{chen_overexpressed_2019,
	title = {Overexpressed pseudogenes, {DUXAP}8 and {DUXAP}9, promote growth of renal cell carcinoma and serve as unfavorable prognostic biomarkers.},
	volume = {11},
	issn = {1945-4589},
	doi = {10.18632/aging.102152},
	abstract = {{BACKGROUND}: Growing studies have reported that pseudogenes play key roles in multiple human cancers. However, expression and roles of pseudogenes in renal  cell carcinoma remains absent. {RESULTS}: 31 upregulated and 16 downregulated  pseudogenes were screened. Higher expression of {DUXAP}8 and {DUXAP}9 indicated  poorer prognosis of kidney cancer. 33 and 5 {miRNAs} were predicted to potentially  binding to {DUXAP}8 and {DUXAP}9, respectively. {miR}-29c-3p was identified as the most  potential binding {miRNAs} of {DUXAP}8 and {DUXAP}9 based on expression, survival and  correlation analyses. 254 target genes of {miR}-29c-3p were forecast. 47 hub genes  with node degree {\textgreater}= 10 were identified. Subsequent analysis for the top 10 hub  genes demonstrated that {COL}1A1 and {COL}1A2 may be two functional targets of {DUXAP}8  and {DUXAP}9. Expression of {DUXAP}8, {DUXAP}9, {COL}1A1 and {COL}1A2 were significantly  increased in cancer samples compared to normal controls while {miR}-29c-3p  expression was decreased. Luciferase reporter assay revealed that {miR}-29c-3p  could directly bind to {DUXAP}8, {DUXAP}9, {COL}1A1 and {COL}1A2. Functional experiments  showed that {DUXAP}8 and {DUXAP}9 enhanced but {miR}-29c-3p weakened growth of renal  cell carcinoma. {CONCLUSIONS}: In conclusion, upregulated {DUXAP}8 and {DUXAP}9 promote  growth of renal cell carcinoma and serve as two promising prognostic biomarkers.  {METHODS}: Dysregulated pseudogenes were obtained by {dreamBase} and {GEPIA}. The  binding {miRNAs} of pseudogene and targets of {miRNA} were predicted using {starBase}  and {miRNet}. Kaplan-Meier plotter was utilized to perform survival analysis, and  Enrichr database was introduced to conduct functional enrichment analysis. Hub  genes were identified through {STRING} and Cytoscape. {qRT}-{PCR}, luciferase reporter  assay, cell counting assay and colony formation assay were performed to validate  in silico analytic results.},
	pages = {5666--5688},
	number = {15},
	journaltitle = {Aging},
	shortjournal = {Aging (Albany {NY})},
	author = {Chen, Jing and Lou, Weiyang and Ding, Bisha and Wang, Xian},
	date = {2019-08-13},
	pmid = {31409759},
	pmcid = {PMC6710046},
	note = {Place: United States},
	keywords = {Humans, {MicroRNAs}/genetics, Carcinoma, Renal Cell/*genetics/*pathology, Cell Line, Tumor, Collagen Type I, alpha 1 Chain, Collagen Type I/genetics, {DUXAP}8, {DUXAP}9, Kaplan-Meier Estimate, kidney cancer, Kidney Neoplasms/*genetics/*pathology, Prognosis, pseudogene, Pseudogenes/*genetics, renal cell carcinoma ({RCC}), {RNA}, Long Noncoding/*genetics, Signal Transduction/genetics, Survival Analysis, Tumor Stem Cell Assay},
}

@article{zhu_overexpression_2018,
	title = {Overexpression of long non-coding {RNAs} {DUXAP}9 and {DUXAP}10 is associated with prognosis in patients with hepatocellular carcinoma after hepatectomy.},
	volume = {11},
	rights = {{IJCEP} Copyright © 2018.},
	issn = {1936-2625},
	abstract = {{AIM}: Hepatocellular carcinoma ({HCC}) is a common and aggressive malignant tumor with an especially high prevalence in Asian populations. This study aimed to  identify differentially expressed {lncRNAs} using expression microarray and to  explore the association between differential expression of {lncRNAs} and prognosis  of {HCC}. {METHODS}: We retrospectively reviewed 63 patients with primary {HCC} that  underwent a curative liver resection at the Department of General Surgery,  Jingmen First People's Hospital. The expression level of {lncRNAs} {DUXAP}9 and  {DUXAP}10 were detected by real-time {PCR}. Prognostic factors were evaluated using  Kaplan-Meier curves and Cox proportional hazards models. {RESULTS}: By microarray  profiling of {lncRNAs}, 256 were found to be differentially expressed, including  162 upregulated and 94 downregulated (P{\textless}0.05, fold change {\textgreater}2). Two candidate  {lncRNAs} were determined as targets in this study, including {DUXAP}9 (upregulated  by 6.35 fold) and {DUXAP}10 (upregulated by 4.53 fold). {DUXAP}9 and {DUXAP}10 were  downregulated in the normal liver cell lines Chang liver, {HL}7702, {THLE}-2, {THLE}-3,  {FL}62891, and {AML}12, which were significantly lower than {HCC} cell lines {SMMC}-7721,  Hep3B, {HuH}7, {MHCC}-97H, {HCC}-{LM}, and {SK}-Hep-1 (P{\textless}0.05). Overexpression of {lncRNAs}  {DUXAP}9 and {DUXAP}10 were associated with decreasing {OS} rates, respectively  (P=0.0263 and P=0.0285). Meanwhile, Overexpression of {DUXAP}9 and {DUXAP}10 was  associated with decreasing {PFS} rates, respectively (P=0.0174 and P=0.0041). After  adjusting for competing risk factors, we identified microvascular invasion  (P=0.014), tumor size (P=0.026), and {lncRNAs} {DUXAP}9 (P=0.001) and {DUXAP}10  (P=0.036) expression levels as independent prognostic factors associated with  prognosis of patients with {HCC}. {CONCLUSIONS}: We found that {lncRNAs} {DUXAP}9 and  {DUXAP}10 are expressed significantly higher in {HCC} tissues compared with  non-tumorous tissues. Overexpression of {DUXAP}9 and {DUXAP}10 were independent risk  factors associated with prognosis of patients with {HCC}.},
	pages = {1407--1414},
	number = {3},
	journaltitle = {International journal of clinical and experimental pathology},
	shortjournal = {Int J Clin Exp Pathol},
	author = {Zhu, Qian and Liu, Jian and Tang, Jie and Guo, De-Liang and Li, Yun and Duan, Rui},
	date = {2018},
	pmid = {31938237},
	pmcid = {PMC6958151},
	note = {Place: United States},
	keywords = {{DUXAP}9 and {DUXAP}10, {HCC}, prognosis},
}

@article{li_rsem_2011,
	title = {{RSEM}: accurate transcript quantification from {RNA}-Seq data with or without a reference genome},
	volume = {12},
	issn = {1471-2105},
	url = {https://doi.org/10.1186/1471-2105-12-323},
	doi = {10.1186/1471-2105-12-323},
	abstract = {{RNA}-Seq is revolutionizing the way transcript abundances are measured. A key challenge in transcript quantification from {RNA}-Seq data is the handling of reads that map to multiple genes or isoforms. This issue is particularly important for quantification with de novo transcriptome assemblies in the absence of sequenced genomes, as it is difficult to determine which transcripts are isoforms of the same gene. A second significant issue is the design of {RNA}-Seq experiments, in terms of the number of reads, read length, and whether reads come from one or both ends of {cDNA} fragments.},
	pages = {323},
	number = {1},
	journaltitle = {{BMC} Bioinformatics},
	shortjournal = {{BMC} Bioinformatics},
	author = {Li, Bo and Dewey, Colin N.},
	date = {2011-08-04},
}

@article{seifuddin_lncrnakb_2020,
	title = {{lncRNAKB}, a knowledgebase of tissue-specific functional annotation and trait association of long noncoding {RNA}},
	volume = {7},
	issn = {2052-4463},
	url = {https://doi.org/10.1038/s41597-020-00659-z},
	doi = {10.1038/s41597-020-00659-z},
	abstract = {Long non-coding {RNA} Knowledgebase ({lncRNAKB}) is an integrated resource for exploring {lncRNA} biology in the context of tissue-specificity and disease association. A systematic integration of annotations from six independent databases resulted in 77,199 human {lncRNA} (224,286 transcripts). The user-friendly knowledgebase covers a comprehensive breadth and depth of {lncRNA} annotation. {lncRNAKB} is a compendium of expression patterns, derived from analysis of {RNA}-seq data in thousands of samples across 31 solid human normal tissues ({GTEx}). Thousands of co-expression modules identified via network analysis and pathway enrichment to delineate {lncRNA} function are also accessible. Millions of expression quantitative trait loci (cis-{eQTL}) computed using whole genome sequence genotype data ({GTEx}) can be downloaded at {lncRNAKB} that also includes tissue-specificity, phylogenetic conservation and coding potential scores. Tissue-specific {lncRNA}-trait associations encompassing 323 {GWAS} ({UK} Biobank) are also provided. {LncRNAKB} is accessible at http://www.lncrnakb.org/, and the data are freely available through Open Science Framework (https://doi.org/10.17605/{OSF}.{IO}/{RU}4D2).},
	pages = {326},
	number = {1},
	journaltitle = {Scientific Data},
	shortjournal = {Scientific Data},
	author = {Seifuddin, Fayaz and Singh, Komudi and Suresh, Abhilash and Judy, Jennifer T. and Chen, Yun-Ching and Chaitankar, Vijender and Tunc, Ilker and Ruan, Xiangbo and Li, Ping and Chen, Yi and Cao, Haiming and Lee, Richard S. and Goes, Fernando S. and Zandi, Peter P. and Jafri, M. Saleet and Pirooznia, Mehdi},
	date = {2020-10-05},
}

@article{chapman_correlated_2022,
	title = {Correlated gene modules uncovered by high-precision single-cell transcriptomics.},
	volume = {119},
	issn = {1091-6490 0027-8424},
	doi = {10.1073/pnas.2206938119},
	abstract = {Correlations in gene expression are used to infer functional and regulatory relationships between genes. However, correlations are often calculated across  different cell types or perturbations, causing genes with unrelated functions to  be correlated. Here, we demonstrate that correlated modules can be better  captured by measuring correlations of steady-state gene expression fluctuations  in single cells. We report a high-precision single-cell {RNA}-seq method called  {MALBAC}-{DT} to measure the correlation between any pair of genes in a homogenous  cell population. Using this method, we were able to identify numerous cell-type  specific and functionally enriched correlated gene modules. We confirmed through  knockdown that a module enriched for p53 signaling predicted p53 regulatory  targets more accurately than a consensus of {ChIP}-seq studies and that  steady-state correlations were predictive of transcriptome-wide response patterns  to perturbations. This approach provides a powerful way to advance our functional  understanding of the genome.},
	pages = {e2206938119},
	number = {51},
	journaltitle = {Proceedings of the National Academy of Sciences of the United States of America},
	shortjournal = {Proc Natl Acad Sci U S A},
	author = {Chapman, Alec R. and Lee, David F. and Cai, Wenting and Ma, Wenping and Li, Xiang and Sun, Wenjie and Xie, Xiaoliang Sunney},
	date = {2022-12-20},
	pmid = {36508663},
	pmcid = {PMC9907105},
	note = {Place: United States},
	keywords = {Signal Transduction, transcriptomics, Transcriptome, Gene Expression Profiling, *Gene Regulatory Networks, *Tumor Suppressor Protein p53/genetics, correlated gene modules, {scRNA}-seq, single cell, Single-Cell Analysis/methods},
}

@article{durinck_mapping_2009,
	title = {Mapping identifiers for the integration of genomic datasets with the R/Bioconductor package {biomaRt}},
	volume = {4},
	issn = {1750-2799},
	url = {https://doi.org/10.1038/nprot.2009.97},
	doi = {10.1038/nprot.2009.97},
	abstract = {Genomic experiments produce multiple views of biological systems, among them are {DNA} sequence and copy number variation, and {mRNA} and protein abundance. Understanding these systems needs integrated bioinformatic analysis. Public databases such as Ensembl provide relationships and mappings between the relevant sets of probe and target molecules. However, the relationships can be biologically complex and the content of the databases is dynamic. We demonstrate how to use the computational environment R to integrate and jointly analyze experimental datasets, employing {BioMart} web services to provide the molecule mappings. We also discuss typical problems that are encountered in making gene-to-transcript–to-protein mappings. The approach provides a flexible, programmable and reproducible basis for state-of-the-art bioinformatic data integration.},
	pages = {1184--1191},
	number = {8},
	journaltitle = {Nature Protocols},
	shortjournal = {Nature Protocols},
	author = {Durinck, Steffen and Spellman, Paul T and Birney, Ewan and Huber, Wolfgang},
	date = {2009-08-01},
}

@article{bates_fitting_2015,
	title = {Fitting Linear Mixed-Effects Models Using lme4},
	volume = {67},
	url = {https://www.jstatsoft.org/index.php/jss/article/view/v067i01},
	doi = {10.18637/jss.v067.i01},
	abstract = {Maximum likelihood or restricted maximum likelihood ({REML}) estimates of the parameters in linear mixed-effects models can be determined using the lmer function in the lme4 package for R. As for most model-fitting functions in R, the model is described in an lmer call by a formula, in this case including both fixed- and random-effects terms. The formula and data together determine a numerical representation of the model from which the profiled deviance or the profiled {REML} criterion can be evaluated as a function of some of the model parameters. The appropriate criterion is optimized, using one of the constrained optimization functions in R, to provide the parameter estimates. We describe the structure of the model, the steps in evaluating the profiled deviance or {REML} criterion, and the structure of classes or types that represents such a model. Sufficient detail is included to allow specialization of these structures by users who wish to write functions to fit specialized linear mixed models, such as models incorporating pedigrees or smoothing splines, that are not easily expressible in the formula language used by lmer.},
	pages = {1 -- 48},
	number = {1},
	journaltitle = {Journal of Statistical Software},
	shortjournal = {J. Stat. Soft.},
	author = {Bates, Douglas and Mächler, Martin and Bolker, Ben and Walker, Steve},
	urldate = {2024-07-11},
	date = {2015-10-07},
	note = {Section: Articles},
}

@article{khan_increased_2020,
	title = {Increased biological relevance of transcriptome analyses in human skeletal muscle using a model-specific pipeline},
	volume = {21},
	issn = {1471-2105},
	url = {https://doi.org/10.1186/s12859-020-03866-y},
	doi = {10.1186/s12859-020-03866-y},
	abstract = {Human skeletal muscle responds to weight-bearing exercise with significant inter-individual differences. Investigation of transcriptome responses could improve our understanding of this variation. However, this requires bioinformatic pipelines to be established and evaluated in study-specific contexts. Skeletal muscle subjected to mechanical stress, such as through resistance training ({RT}), accumulates {RNA} due to increased ribosomal biogenesis. When a fixed amount of total-{RNA} is used for {RNA}-seq library preparations, {mRNA} counts are thus assessed in different amounts of tissue, potentially invalidating subsequent conclusions. The purpose of this study was to establish a bioinformatic pipeline specific for analysis of {RNA}-seq data from skeletal muscles, to explore the effects of different normalization strategies and to identify genes responding to {RT} in a volume-dependent manner (moderate vs. low volume). To this end, we analyzed {RNA}-seq data derived from a twelve-week {RT} intervention, wherein 25 participants performed both low- and moderate-volume leg {RT}, allocated to the two legs in a randomized manner. Bilateral muscle biopsies were sampled from m. vastus lateralis before and after the intervention, as well as before and after the fifth training session (Week 2).},
	pages = {548},
	number = {1},
	journaltitle = {{BMC} Bioinformatics},
	shortjournal = {{BMC} Bioinformatics},
	author = {Khan, Yusuf and Hammarström, Daniel and Rønnestad, Bent R. and Ellefsen, Stian and Ahmad, Rafi},
	date = {2020-11-30},
}

@article{wolfson_strength_1995,
	title = {Strength is a major factor in balance, gait, and the occurrence of falls.},
	volume = {50 Spec No},
	issn = {1079-5006},
	doi = {10.1093/gerona/50a.special_issue.64},
	abstract = {We studied the effects of lower extremity strength as well as gait and balance on the occurrence of falls in nursing home residents. Nursing home residents with a  history of falls had less than half of the knee and ankle strength of nonfalling  subjects residing in the same home. The differences were more prominent at the  ankle than the knee, and were most pronounced in the ankle dorsiflexors, where  they were one-tenth that of controls. Also of note was the fact that this same  group of fallers had slowed gait velocity (58\% of control) as well as an impaired  response to postural perturbation as determined on the Postural Stress Test (55\%  of control). In a recently completed study we measured strength as balance  ({EquiTest} balance platform) of community-dwelling subjects. The occurrence of  loss of balance during the sensory organization test was correlated with  diminished lower extremity (Pearson R = -.36, p = .001) as well as ankle dorsi  and plantar flexion moments (Pearson R = -.37, p = .001). Using a logistic  regression model, we demonstrated an independent effect of strength on the odds  ratio of an {SOT}-{LOB}; for each newtonmeter per kg increase in strength there was a  20\% decrease (95\% {CI}, .74-87) in the odds ratio. The data from both nursing home  and community-dwelling subjects indicate a strong relationship of lower extremity  strength to balance and gait. The nursing home studies demonstrated an  association between these functions and the occurrence of falls.({ABSTRACT}  {TRUNCATED} {AT} 250 {WORDS})},
	pages = {64--67},
	journaltitle = {The journals of gerontology. Series A, Biological sciences and medical sciences},
	shortjournal = {J Gerontol A Biol Sci Med Sci},
	author = {Wolfson, L. and Judge, J. and Whipple, R. and King, M.},
	date = {1995-11},
	pmid = {7493221},
	note = {Place: United States},
	keywords = {Humans, Aged, Muscle, Skeletal/*physiology, Aged, 80 and over, *Accidental Falls, Ankle/physiology, Biomechanical Phenomena, Foot/physiology, Gait/*physiology, Knee/physiology, Leg/physiology, Logistic Models, Muscle Contraction/physiology, Nursing Homes, Odds Ratio, Postural Balance/*physiology, Posture/physiology, Proprioception/physiology, Retrospective Studies, Walking/physiology},
}

@article{volpi_muscle_2004,
	title = {Muscle tissue changes with aging.},
	volume = {7},
	issn = {1363-1950 1473-6519},
	doi = {10.1097/01.mco.0000134362.76653.b2},
	abstract = {{PURPOSE} {OF} {REVIEW}: This review article focuses on the changes that occur in muscle with age, specifically the involuntary loss of muscle mass, strength and  function, termed sarcopenia. Particular emphasis is given to the metabolic  alterations that characterize sarcopenia, and to the potentially treatable causes  of this condition, including age-related endocrine and nutritional changes, and  inactivity. {RECENT} {FINDINGS}: Recent data reported include those regarding the  potential role of insulin resistance in the development of sarcopenia, the  potential role of androgens and growth hormone in the treatment of this  condition, the usefulness of exercise including both resistance and aerobic  training to improve muscle growth and function, and, finally, the possible use of  nutritional manipulations to improve muscle mass. {SUMMARY}: Sarcopenia is likely a  multifactorial condition that impairs physical function and predisposes to  disability. It may be prevented or treated with lifestyle interventions and  pharmacological treatment. Further long-term investigations are needed, however,  to ascertain what type and combinations of interventions are the most efficacious  in improving muscle mass and function in older people.},
	pages = {405--410},
	number = {4},
	journaltitle = {Current opinion in clinical nutrition and metabolic care},
	shortjournal = {Curr Opin Clin Nutr Metab Care},
	author = {Volpi, Elena and Nazemi, Reza and Fujita, Satoshi},
	date = {2004-07},
	pmid = {15192443},
	pmcid = {PMC2804956},
	note = {Place: England},
	keywords = {Humans, Aged, Exercise Therapy, Aging/pathology/*physiology, Growth Hormone/therapeutic use, Insulin Resistance/physiology, Muscle, Skeletal/metabolism/pathology/*physiology, Muscular Atrophy/etiology/*pathology/prevention \& control, Nutritional Status},
}

@article{noauthor_notitle_nodate,
}

@article{power_human_2013,
	title = {Human neuromuscular structure and function in old age: A brief review.},
	volume = {2},
	issn = {2095-2546 2213-2961},
	doi = {10.1016/j.jshs.2013.07.001},
	abstract = {Natural adult aging is associated with many functional impairments of the human neuromuscular system. One of the more observable alterations is the loss of  contractile muscle mass, termed sarcopenia. The loss of muscle mass occurs  primarily due to a progressive loss of viable motor units, and accompanying  atrophy of remaining muscle fibers. Not only does the loss of muscle mass  contribute to impaired function in old age, but alterations in fiber type and  myosin heavy chain isoform expression also contribute to weaker, slower, and less  powerful contracting muscles. This review will focus on motor unit loss  associated with natural adult aging, age-related fatigability, and the  age-related differences in strength across contractile muscle actions.},
	pages = {215--226},
	number = {4},
	journaltitle = {Journal of sport and health science},
	shortjournal = {J Sport Health Sci},
	author = {Power, Geoffrey A. and Dalton, Brian H. and Rice, Charles L.},
	date = {2013-12},
	pmid = {27011872},
	pmcid = {PMC4801513},
	note = {Place: China},
	keywords = {Aging, Sarcopenia, Muscle atrophy, Eccentric, Force, Motor unit, Power, Residual force enhancement, Velocity},
}

@article{doi:10.1177/2472630318780639,
	title = {Platforms for investigating {LncRNA} functions},
	volume = {23},
	url = {https://doi.org/10.1177/2472630318780639},
	doi = {10.1177/2472630318780639},
	abstract = {Prior to the sequencing of the human genome, it was presumed that most of the {DNA} coded for proteins. However, with the advent of next-generation sequencing, it has now been recognized that most complex eukaryotic genomes are in fact transcribed into noncoding {RNAs} ({ncRNAs}), including a family of transcripts referred to as long noncoding {RNAs} ({lncRNAs}). {LncRNAs} have been implicated in many biological processes ranging from housekeeping functions such as transcription to more specialized functions such as dosage compensation or genomic imprinting, among others. Interestingly, {lncRNAs} are not limited to a defined set of functions but can regulate varied activities such as messenger {RNA} degradation, translation, and protein kinetics or function as {RNA} decoys or scaffolds. Although still in its infancy, research into the biology of {lncRNAs} has demonstrated the importance of {lncRNAs} in development and disease. However, the specific mechanisms through which these {lncRNAs} act remain poorly defined. Focused research into a small number of these {lncRNAs} has provided important clues into the heterogeneous nature of this family of {ncRNAs}. Due to the complex diversity of {lncRNA} function, in this review, we provide an update on the platforms available for investigators to aid in the identification of {lncRNA} function.},
	pages = {493--506},
	number = {6},
	journaltitle = {{SLAS} {TECHNOLOGY}: Translating Life Sciences Innovation},
	author = {Richard, John Lalith Charles and Eichhorn, Pieter Johan Adam},
	date = {2018},
	note = {tex.eprint: https://doi.org/10.1177/2472630318780639},
}

@article{hammarstrom_ribosome_2022,
	title = {Ribosome accumulation during early phase resistance training in humans.},
	volume = {235},
	rights = {© 2022 The Authors. Acta Physiologica published by John Wiley \& Sons Ltd on behalf of Scandinavian Physiological Society.},
	issn = {1748-1716 1748-1708},
	doi = {10.1111/apha.13806},
	abstract = {{AIM}: To describe ribosome biogenesis during resistance training, its relation to training volume and muscle growth. {METHODS}: A training group (n = 11) performed  12 sessions (3-4 sessions per week) of unilateral knee extension with constant  and variable volume (6 and 3-9 sets per session respectively) allocated to either  leg. Ribosome abundance and biogenesis markers were assessed from vastus  lateralis biopsies obtained at baseline, 48 hours after sessions 1, 4, 5, 8, 9  and 12, and after eight days of de-training, and from a control group (n = 8).  Muscle thickness was measured before and after the intervention. {RESULTS}:  Training led to muscle growth (3.9\% over baseline values, 95\% {CrI}: [0.2, 7.5] vs.  control) with concomitant increases in total {RNA}, ribosomal {RNA}, upstream binding  factor ({UBF}) and ribosomal protein S6 with no differences between volume  conditions. Total {RNA} increased rapidly in response to the first four sessions  (8.6\% [5.6, 11.7] per session), followed by a plateau and peak values after  session 8 (49.5\% [34.5, 66.5] above baseline). Total {RNA} abundance was associated  with {UBF} protein levels (5.0\% [0.2, 10.2] per unit {UBF}), and the rate of increase  in total {RNA} levels predicted hypertrophy (0.3 mm [0.1, 0.4] per \%-point increase  in total {RNA} per session). After de-training, total {RNA} decreased (-19.3\% [-29.0,  -8.1]) without muscle mass changes indicating halted biosynthesis of ribosomes.  {CONCLUSION}: Ribosomes accumulate in the initial phase of resistance training with  abundances sensitive to training cessation and associated with {UBF} protein  levels. The average accumulation rate predicts muscle training-induced  hypertrophy.},
	pages = {e13806},
	number = {1},
	journaltitle = {Acta physiologica (Oxford, England)},
	shortjournal = {Acta Physiol (Oxf)},
	author = {Hammarström, Daniel and Øfsteng, Sjur J. and Jacobsen, Nicolai B. and Flobergseter, Krister B. and Rønnestad, Bent R. and Ellefsen, Stian},
	date = {2022-05},
	pmid = {35213791},
	pmcid = {PMC9540306},
	note = {Place: England},
	keywords = {*Resistance Training, Humans, resistance training, {RNA}/metabolism, Muscle, Skeletal/metabolism, Hypertrophy/metabolism, muscle hypertrophy, ribosome biogenesis, Ribosomes/metabolism},
}

@article{statello_gene_2021,
	title = {Gene regulation by long non-coding {RNAs} and its biological functions},
	volume = {22},
	issn = {1471-0080},
	url = {https://doi.org/10.1038/s41580-020-00315-9},
	doi = {10.1038/s41580-020-00315-9},
	abstract = {Evidence accumulated over the past decade shows that long non-coding {RNAs} ({lncRNAs}) are widely expressed and have key roles in gene regulation. Recent studies have begun to unravel how the biogenesis of {lncRNAs} is distinct from that of {mRNAs} and is linked with their specific subcellular localizations and functions. Depending on their localization and their specific interactions with {DNA}, {RNA} and proteins, {lncRNAs} can modulate chromatin function, regulate the assembly and function of membraneless nuclear bodies, alter the stability and translation of cytoplasmic {mRNAs} and interfere with signalling pathways. Many of these functions ultimately affect gene expression in diverse biological and physiopathological contexts, such as in neuronal disorders, immune responses and cancer. Tissue-specific and condition-specific expression patterns suggest that {lncRNAs} are potential biomarkers and provide a rationale to target them clinically. In this Review, we discuss the mechanisms of {lncRNA} biogenesis, localization and functions in transcriptional, post-transcriptional and other modes of gene regulation, and their potential therapeutic applications.},
	pages = {96--118},
	number = {2},
	journaltitle = {Nature Reviews Molecular Cell Biology},
	shortjournal = {Nature Reviews Molecular Cell Biology},
	author = {Statello, Luisa and Guo, Chun-Jie and Chen, Ling-Ling and Huarte, Maite},
	date = {2021-02-01},
}

@article{10.1093/nar/gky960,
	title = {{LncBook}: a curated knowledgebase of human long non-coding {RNAs}},
	volume = {47},
	issn = {0305-1048},
	url = {https://doi.org/10.1093/nar/gky960},
	doi = {10.1093/nar/gky960},
	abstract = {Long non-coding {RNAs} ({lncRNAs}) have significant functions in a wide range of important biological processes. Although the number of known human {lncRNAs} has dramatically increased, they are poorly annotated, posing great challenges for better understanding their functional significance and elucidating their complex functioning molecular mechanisms. Here, we present {LncBook} (http://bigd.big.ac.cn/lncbook), a curated knowledgebase of human {lncRNAs} that features a comprehensive collection of human {lncRNAs} and systematic curation of {lncRNAs} by multi-omics data integration, functional annotation and disease association. In the present version, {LncBook} houses a large number of 270 044 {lncRNAs} and includes 1867 featured {lncRNAs} with 3762 {lncRNA}–function associations. It also integrates an abundance of multi-omics data from expression, methylation, genome variation and {lncRNA}–{miRNA} interaction. Also, {LncBook} incorporates 3772 experimentally validated {lncRNA}-disease associations and further identifies a total of 97 998 {lncRNAs} that are putatively disease-associated. Collectively, {LncBook} is dedicated to the integration and curation of human {lncRNAs} as well as their associated data and thus bears great promise to serve as a valuable knowledgebase for worldwide research communities.},
	pages = {D128--D134},
	issue = {D1},
	journaltitle = {Nucleic Acids Research},
	author = {Ma, Lina and Cao, Jiabao and Liu, Lin and Du, Qiang and Li, Zhao and Zou, Dong and Bajic, Vladimir B and Zhang, Zhang},
	date = {2018-10},
	note = {tex.eprint: https://academic.oup.com/nar/article-pdf/47/D1/D128/27661126/gky960.pdf},
}

@article{uszczynska-ratajczak_towards_2018,
	title = {Towards a complete map of the human long non-coding {RNA} transcriptome},
	volume = {19},
	issn = {1471-0064},
	url = {https://doi.org/10.1038/s41576-018-0017-y},
	doi = {10.1038/s41576-018-0017-y},
	abstract = {Gene maps, or annotations, enable us to navigate the functional landscape of our genome. They are a resource upon which virtually all studies depend, from single-gene to genome-wide scales and from basic molecular biology to medical genetics. Yet present-day annotations suffer from trade-offs between quality and size, with serious but often unappreciated consequences for downstream studies. This is particularly true for long non-coding {RNAs} ({lncRNAs}), which are poorly characterized compared to protein-coding genes. Long-read sequencing technologies promise to improve current annotations, paving the way towards a complete annotation of {lncRNAs} expressed throughout a human lifetime.},
	pages = {535--548},
	number = {9},
	journaltitle = {Nature Reviews Genetics},
	shortjournal = {Nature Reviews Genetics},
	author = {Uszczynska-Ratajczak, Barbara and Lagarde, Julien and Frankish, Adam and Guigó, Roderic and Johnson, Rory},
	date = {2018-09-01},
}

@article{sweta_importance_2019,
	title = {Importance of Long Non-coding {RNAs} in the Development and Disease of Skeletal Muscle and Cardiovascular Lineages.},
	volume = {7},
	rights = {Copyright © 2019 Sweta, Dudnakova, Sudheer, Baker and Bhushan.},
	issn = {2296-634X},
	doi = {10.3389/fcell.2019.00228},
	abstract = {The early mammalian embryo is characterized by the presence of three germ layers-the outer ectoderm, middle mesoderm and inner endoderm. The mesoderm is  organized into paraxial, intermediate and lateral plate mesoderm. The  musculature, vasculature and heart of the adult body are the major derivatives of  mesoderm. Tracing back the developmental process to generate these specialized  tissues has sparked much interest in the field of regenerative medicine focusing  on generating specialized tissues to treat patients with degenerative diseases.  Several Long Non-Coding {RNAs} ({lncRNAs}) have been identified as regulators of  development, proliferation and differentiation of various tissues of mesodermal  origin. A better understanding of {lncRNAs} that can regulate the development of  these tissues will open potential avenues for their therapeutic utility and  enhance our knowledge about disease progression and development. In this review,  we aim to summarize the functions and mechanisms of {lncRNAs} regulating the early  mesoderm differentiation, development and homeostasis of skeletal muscle and  cardiovascular system with an emphasis on their therapeutic potential.},
	pages = {228},
	journaltitle = {Frontiers in cell and developmental biology},
	shortjournal = {Front Cell Dev Biol},
	author = {Sweta, Sweta and Dudnakova, Tatiana and Sudheer, Smita and Baker, Andrew H. and Bhushan, Raghu},
	date = {2019},
	pmid = {31681761},
	pmcid = {PMC6813187},
	note = {Place: Switzerland},
	keywords = {skeletal muscle, cardiovascular diseases, differentiation, endothelial cell, mesoderm, myogenesis, non-coding {RNA}, vascular smooth muscle cell ({VSMC})},
}

@article{bonilauri_long_2020,
	title = {Long Non-coding {RNAs} Are Differentially Expressed After Different Exercise Training Programs.},
	volume = {11},
	rights = {Copyright © 2020 Bonilauri and Dallagiovanna.},
	issn = {1664-042X},
	doi = {10.3389/fphys.2020.567614},
	abstract = {{BACKGROUND}: Molecular regulation related to the health benefits of different exercise modes remains unclear. Long non-coding {RNAs} ({lncRNAs}) have emerged as an  {RNA} class with regulatory functions in health and diseases. Here, we analyzed the  expression of {lncRNAs} after different exercise training programs and their  possible modes of action related to physical exercise adaptations. {METHODS}:  Public high-throughput {RNA}-seq data (skeletal muscle biopsies) were downloaded,  and bioinformatics analysis was performed. We primarily analyzed data reports of  12 weeks of resistance training ({RT}), high-intensity interval training ({HIIT}),  and combined ({CT}) exercise training. In addition, we analyzed data from 8 weeks  of endurance training ({ET}). Differential expression analysis of {lncRNAs} was  performed, and an adjusted P-value {\textless} 0.1 and log2 (fold change) ≥0.5 or ≤-0.5  were set as the cutoff values to identify differentially expressed {lncRNAs}  ({DELs}). {RESULTS}: We identified 204 {DELs} after 12 weeks of {HIIT}, 43 {DELs} after {RT},  and 15 {DELs} after {CT}. Moreover, 52 {lncRNAs} were differentially expressed after 8  weeks of {ET}. The {lncRNA} expression pattern after physical exercise was very  specific, with distinct expression profiles for the different training programs,  where few {lncRNAs} were common among the exercise types. {LncRNAs} may regulate  molecular responses to exercise, such as collagen fibril organization,  extracellular matrix organization, myoblast and plasma membrane fusion, skeletal  muscle contraction, synaptic transmission, {PI}3K and {TORC} regulation, autophagy,  and angiogenesis. {CONCLUSION}: For the first time, we show that {lncRNAs} are  differentially expressed in skeletal muscle after different physical exercise  programs, and these {lncRNAs} may act in various biological processes related to  physical activity adaptations.},
	pages = {567614},
	journaltitle = {Frontiers in physiology},
	shortjournal = {Front Physiol},
	author = {Bonilauri, Bernardo and Dallagiovanna, Bruno},
	date = {2020},
	pmid = {33071823},
	pmcid = {PMC7533564},
	note = {Place: Switzerland},
	keywords = {exercise, muscle, {RNA}-seq, {HIIT}, {lncRNAs}, training},
}

@article{statello_gene_2021-1,
	title = {Gene regulation by long non-coding {RNAs} and its biological functions.},
	volume = {22},
	issn = {1471-0080 1471-0072},
	doi = {10.1038/s41580-020-00315-9},
	abstract = {Evidence accumulated over the past decade shows that long non-coding {RNAs} ({lncRNAs}) are widely expressed and have key roles in gene regulation. Recent  studies have begun to unravel how the biogenesis of {lncRNAs} is distinct from that  of {mRNAs} and is linked with their specific subcellular localizations and  functions. Depending on their localization and their specific interactions with  {DNA}, {RNA} and proteins, {lncRNAs} can modulate chromatin function, regulate the  assembly and function of membraneless nuclear bodies, alter the stability and  translation of cytoplasmic {mRNAs} and interfere with signalling pathways. Many of  these functions ultimately affect gene expression in diverse biological and  physiopathological contexts, such as in neuronal disorders, immune responses and  cancer. Tissue-specific and condition-specific expression patterns suggest that  {lncRNAs} are potential biomarkers and provide a rationale to target them  clinically. In this Review, we discuss the mechanisms of {lncRNA} biogenesis,  localization and functions in transcriptional, post-transcriptional and other  modes of gene regulation, and their potential therapeutic applications.},
	pages = {96--118},
	number = {2},
	journaltitle = {Nature reviews. Molecular cell biology},
	shortjournal = {Nat Rev Mol Cell Biol},
	author = {Statello, Luisa and Guo, Chun-Jie and Chen, Ling-Ling and Huarte, Maite},
	date = {2021-02},
	pmid = {33353982},
	pmcid = {PMC7754182},
	note = {Place: England},
	keywords = {Humans, Signal Transduction, Animals, {RNA}, Long Noncoding/*genetics, *Gene Expression Regulation, Immune System Diseases/genetics/*pathology, Neoplasms/genetics/*pathology, Neurodevelopmental Disorders/genetics/*pathology},
}

@article{oo_long_2022,
	title = {Long non-coding {RNAs}: novel regulators of cellular physiology and function},
	volume = {474},
	issn = {1432-2013},
	url = {https://doi.org/10.1007/s00424-021-02641-z},
	doi = {10.1007/s00424-021-02641-z},
	abstract = {Long non-coding {RNAs} were once considered as “junk” {RNA} produced by aberrant {DNA} transcription. They are now understood to play central roles in diverse cellular processes from proliferation and migration to differentiation, senescence and {DNA} damage control. {LncRNAs} are classed as transcripts longer than 200 nucleotides that do not encode a peptide. They are relevant to many physiological and pathophysiological processes through their control of fundamental molecular functions. This review summarises the recent progress in {lncRNA} research and highlights the far-reaching physiological relevance of {lncRNAs}. The main areas of {lncRNA} research encompassing their characterisation, classification and mechanisms of action will be discussed. In particular, the regulation of gene expression and chromatin landscape through {lncRNA} control of proteins, {DNA} and other {RNAs} will be introduced. This will be exemplified with a selected number of {lncRNAs} that have been described in numerous physiological contexts and that should be largely representative of the tens-of-thousands of mammalian {lncRNAs}. To some extent, these {lncRNAs} have inspired the current thinking on the central dogmas of epigenetics, {RNA} and {DNA} mechanisms.},
	pages = {191--204},
	number = {2},
	journaltitle = {Pflügers Archiv - European Journal of Physiology},
	shortjournal = {Pflügers Archiv - European Journal of Physiology},
	author = {Oo, James A. and Brandes, Ralf P. and Leisegang, Matthias S.},
	date = {2022-02-01},
}

@article{de_sanctis_non-coding_2021-1,
	title = {Non-Coding {RNAs} in the Transcriptional Network That Differentiates Skeletal Muscles of Sedentary from Long-Term Endurance- and Resistance-Trained Elderly},
	volume = {22},
	issn = {1422-0067},
	doi = {10.3390/ijms22041539},
	abstract = {In a previous study, the whole transcriptome of the vastus lateralis muscle from sedentary elderly and from age-matched athletes with an exceptional record of high-intensity, life-long exercise training was compared—the two groups representing the two extremes on a physical activity scale. Exercise training enabled the skeletal muscle to counteract age-related sarcopenia by inducing a wide range of adaptations, sustained by the expression of protein-coding genes involved in energy handling, proteostasis, cytoskeletal organization, inflammation control, and cellular senescence. Building on the previous study, we examined here the network of non-coding {RNAs} participating in the orchestration of gene expression and identified differentially expressed micro- and long-non-coding {RNAs} and some of their possible targets and roles. Unsupervised hierarchical clustering analyses of all non-coding {RNAs} were able to discriminate between sedentary and trained individuals, regardless of the exercise typology. Validated targets of differentially expressed {miRNA} were grouped by {KEGG} analysis, which pointed to functional areas involved in cell cycle, cytoskeletal control, longevity, and many signaling pathways, including {AMP}-activated protein kinase ({AMPK}) and mammalian target of rapamycin ({mTOR}), which had been shown to be pivotal in the modulation of the effects of high-intensity, life-long exercise training. The analysis of differentially expressed long-non-coding {RNAs} identified transcriptional networks, involving {lncRNAs}, {miRNAs} and {mRNAs}, affecting processes in line with the beneficial role of exercise training.},
	number = {4},
	journaltitle = {International Journal of Molecular Sciences},
	author = {De Sanctis, Paola and Filardo, Giuseppe and Abruzzo, Provvidenza M. and Astolfi, Annalisa and Bolotta, Alessandra and Indio, Valentina and Di Martino, Alessandro and Hofer, Christian and Kern, Helmut and Löfler, Stefan and Marcacci, Maurilio and Marini, Marina and Zampieri, Sandra and Zucchini, Cinzia},
	date = {2021},
	keywords = {skeletal muscle, aging, gene expression, non-coding {RNAs}, exercise training},
}

@article{bridges_lnccation_2021,
	title = {{LNCcation}: {lncRNA} localization and function.},
	volume = {220},
	rights = {© 2021 Bridges et al.},
	issn = {1540-8140 0021-9525},
	doi = {10.1083/jcb.202009045},
	abstract = {Subcellular localization of {RNAs} has gained attention in recent years as a prevalent phenomenon that influences numerous cellular processes. This is also  evident for the large and relatively novel class of long noncoding {RNAs}  ({lncRNAs}). Because {lncRNAs} are defined as {RNA} transcripts {\textgreater}200 nucleotides that  do not encode protein, they are themselves the functional units, making their  subcellular localization critical to their function. The discovery of tens of  thousands of {lncRNAs} and the cumulative evidence involving them in almost every  cellular activity render assessment of their subcellular localization essential  to fully understanding their biology. In this review, we summarize current  knowledge of {lncRNA} subcellular localization, factors controlling their  localization, emerging themes, including the role of {lncRNA} isoforms and the  involvement of {lncRNAs} in phase separation bodies, and the implications of {lncRNA}  localization on their function and on cellular behavior. We also discuss gaps in  the current knowledge as well as opportunities that these provide for novel  avenues of investigation.},
	number = {2},
	journaltitle = {The Journal of cell biology},
	shortjournal = {J Cell Biol},
	author = {Bridges, Mary Catherine and Daulagala, Amanda C. and Kourtidis, Antonis},
	date = {2021-02-01},
	pmid = {33464299},
	pmcid = {PMC7816648},
	note = {Place: United States},
	keywords = {Humans, Animals, {RNA}, Long Noncoding/genetics/*metabolism, *{RNA} Transport/genetics, Cell Membrane/metabolism, Organelles/genetics},
}

@article{sirey_long_2019,
	title = {The long non-coding {RNA} Cerox1 is a post transcriptional regulator of mitochondrial complex I catalytic activity.},
	volume = {8},
	rights = {© 2019, Sirey et al.},
	issn = {2050-084X},
	doi = {10.7554/eLife.45051},
	abstract = {To generate energy efficiently, the cell is uniquely challenged to co-ordinate the abundance of electron transport chain protein subunits expressed from both  nuclear and mitochondrial genomes. How an effective stoichiometry of this many  constituent subunits is co-ordinated post-transcriptionally remains poorly  understood. Here we show that Cerox1, an unusually abundant cytoplasmic long  noncoding {RNA} ({lncRNA}), modulates the levels of mitochondrial complex I subunit  transcripts in a manner that requires binding to {microRNA}-488-3p. Increased  abundance of Cerox1 cooperatively elevates complex I subunit protein abundance  and enzymatic activity, decreases reactive oxygen species production, and  protects against the complex I inhibitor rotenone. Cerox1 function is conserved  across placental mammals: human and mouse orthologues effectively modulate  complex I enzymatic activity in mouse and human cells, respectively. Cerox1 is  the first {lncRNA} demonstrated, to our knowledge, to regulate mitochondrial  oxidative phosphorylation and, with {miR}-488-3p, represent novel targets for the  modulation of complex I activity.},
	journaltitle = {{eLife}},
	shortjournal = {Elife},
	author = {Sirey, Tamara M. and Roberts, Kenny and Haerty, Wilfried and Bedoya-Reina, Oscar and Rogatti-Granados, Sebastian and Tan, Jennifer Y. and Li, Nick and Heather, Lisa C. and Carter, Roderick N. and Cooper, Sarah and Finch, Andrew J. and Wills, Jimi and Morton, Nicholas M. and Marques, Ana Claudia and Ponting, Chris P.},
	date = {2019-05-02},
	pmid = {31045494},
	pmcid = {PMC6542586},
	note = {Place: England},
	keywords = {Humans, Animals, human, Gene Expression Profiling, Mice, mouse, *Gene Expression Regulation, biochemistry, Cell Line, chemical biology, Electron Transport Complex I/genetics/*metabolism, energy metabolism, genetics, genomics, long noncoding {RNA}, {MicroRNAs}/metabolism, {miRNA}, mitochondria, Mitochondria/*enzymology, post-transcriptional regulation, {RNA}, Long Noncoding/*metabolism},
}

@article{delas_lncrna_2017,
	title = {{lncRNA} requirements for mouse acute myeloid leukemia and normal differentiation.},
	volume = {6},
	issn = {2050-084X},
	doi = {10.7554/eLife.25607},
	abstract = {A substantial fraction of the genome is transcribed in a cell-type-specific manner, producing long non-coding {RNAs} ({lncRNAs}), rather than protein-coding  transcripts. Here, we systematically characterize transcriptional dynamics during  hematopoiesis and in hematological malignancies. Our analysis of annotated and de  novo assembled {lncRNAs} showed many are regulated during differentiation and  mis-regulated in disease. We assessed {lncRNA} function via an in vivo {RNAi} screen  in a model of acute myeloid leukemia. This identified several {lncRNAs} essential  for leukemia maintenance, and found that a number act by promoting leukemia stem  cell signatures. Leukemia blasts show a myeloid differentiation phenotype when  these {lncRNAs} were depleted, and our data indicates that this effect is mediated  via effects on the {MYC} oncogene. Bone marrow reconstitutions showed that a {lncRNA}  expressed across all progenitors was required for the myeloid lineage, whereas  the other leukemia-induced {lncRNAs} were dispensable in the normal setting.},
	journaltitle = {{eLife}},
	shortjournal = {Elife},
	author = {Delás, M. Joaquina and Sabin, Leah R. and Dolzhenko, Egor and Knott, Simon Rv and Munera Maravilla, Ester and Jackson, Benjamin T. and Wild, Sophia A. and Kovacevic, Tatjana and Stork, Eva Maria and Zhou, Meng and Erard, Nicolas and Lee, Emily and Kelley, David R. and Roth, Mareike and Barbosa, Inês Am and Zuber, Johannes and Rinn, John L. and Smith, Andrew D. and Hannon, Gregory J.},
	date = {2017-09-06},
	pmid = {28875933},
	pmcid = {PMC5619947},
	note = {Place: England},
	keywords = {Animals, Gene Expression Profiling, Mice, mouse, {lncRNA}, *Gene Expression Regulation, *Cell Differentiation, *Hematopoiesis, c-Myc, chromosomes, developmental biology, Disease Models, Animal, genes, hematopoiesis, leukemia, Leukemia, Myeloid, Acute/*pathology, {RNA}, Long Noncoding/*genetics/*metabolism, stem cells},
}

@article{kitagawa_cell_2013,
	title = {Cell cycle regulation by long non-coding {RNAs}.},
	volume = {70},
	issn = {1420-9071 1420-682X},
	doi = {10.1007/s00018-013-1423-0},
	abstract = {The mammalian cell cycle is precisely controlled by cyclin-dependent kinases ({CDKs}) and related pathways such as the {RB} and p53 pathways. Recent research on  long non-coding {RNAs} ({lncRNAs}) indicates that many {lncRNAs} are involved in the  regulation of critical cell cycle regulators such as the cyclins, {CDKs}, {CDK}  inhibitors, {pRB}, and p53. These {lncRNAs} act as epigenetic regulators,  transcription factor regulators, post-transcription regulators, and protein  scaffolds. These cell cycle-regulated {lncRNAs} mainly control cellular levels of  cell cycle regulators via various mechanisms, and may provide diversity and  reliability to the general cell cycle. Interestingly, several {lncRNAs} are induced  by {DNA} damage and participate in cell cycle arrest or induction of apoptosis as  {DNA} damage responses. Therefore, deregulations of these cell cycle regulatory  {lncRNAs} may be involved in tumorigenesis, and they are novel candidate molecular  targets for cancer therapy and diagnosis.},
	pages = {4785--4794},
	number = {24},
	journaltitle = {Cellular and molecular life sciences : {CMLS}},
	shortjournal = {Cell Mol Life Sci},
	author = {Kitagawa, Masatoshi and Kitagawa, Kyoko and Kotake, Yojiro and Niida, Hiroyuki and Ohhata, Tatsuya},
	date = {2013-12},
	pmid = {23880895},
	pmcid = {PMC3830198},
	note = {Place: Switzerland},
	keywords = {Humans, Signal Transduction, Animals, Models, Biological, {RNA}, Long Noncoding/*genetics, Cell Cycle Checkpoints/*genetics/physiology, Cyclin-Dependent Kinase Inhibitor Proteins/genetics/metabolism, Cyclin-Dependent Kinases/antagonists \& inhibitors/genetics/metabolism, Cyclins/genetics/metabolism, Epigenesis, Genetic, Retinoblastoma Protein/genetics/metabolism, Tumor Suppressor Protein p53/genetics/metabolism},
}

@article{liu_progressive_2009,
	title = {Progressive resistance strength training for improving physical function in older adults.},
	volume = {2009},
	issn = {1469-493X 1361-6137},
	doi = {10.1002/14651858.CD002759.pub2},
	abstract = {{BACKGROUND}: Muscle weakness in old age is associated with physical function decline. Progressive resistance strength training ({PRT}) exercises are designed to  increase strength. {OBJECTIVES}: To assess the effects of {PRT} on older people and  identify adverse events. {SEARCH} {STRATEGY}: We searched the Cochrane Bone, Joint  and Muscle Trauma Group Specialized Register (to March 2007), the Cochrane  Central Register of Controlled Trials (The Cochrane Library 2007, Issue 2),  {MEDLINE} (1966 to May 01, 2008), {EMBASE} (1980 to February 06 2007), {CINAHL} (1982  to July 01 2007) and two other electronic databases. We also searched reference  lists of articles, reviewed conference abstracts and contacted authors. {SELECTION}  {CRITERIA}: Randomised controlled trials reporting physical outcomes of {PRT} for  older people were included. {DATA} {COLLECTION} {AND} {ANALYSIS}: Two review authors  independently selected trials, assessed trial quality and extracted data. Data  were pooled where appropriate. {MAIN} {RESULTS}: One hundred and twenty one trials  with 6700 participants were included. In most trials, {PRT} was performed two to  three times per week and at a high intensity. {PRT} resulted in a small but  significant improvement in physical ability (33 trials, 2172 participants; {SMD}  0.14, 95\% {CI} 0.05 to 0.22). Functional limitation measures also showed  improvements: e.g. there was a modest improvement in gait speed (24 trials, 1179  participants, {MD} 0.08 m/s, 95\% {CI} 0.04 to 0.12); and a moderate to large effect  for getting out of a chair (11 trials, 384 participants, {SMD} -0.94, 95\% {CI} -1.49  to -0.38). {PRT} had a large positive effect on muscle strength (73 trials, 3059  participants, {SMD} 0.84, 95\% {CI} 0.67 to 1.00). Participants with osteoarthritis  reported a reduction in pain following {PRT}(6 trials, 503 participants, {SMD} -0.30,  95\% {CI} -0.48 to -0.13). There was no evidence from 10 other trials (587  participants) that {PRT} had an effect on bodily pain. Adverse events were poorly  recorded but adverse events related to musculoskeletal complaints, such as joint  pain and muscle soreness, were reported in many of the studies that prospectively  defined and monitored these events. Serious adverse events were rare, and no  serious events were reported to be directly related to the exercise programme.  {AUTHORS}' {CONCLUSIONS}: This review provides evidence that {PRT} is an effective  intervention for improving physical functioning in older people, including  improving strength and the performance of some simple and complex activities.  However, some caution is needed with transferring these exercises for use with  clinical populations because adverse events are not adequately reported.},
	pages = {CD002759},
	number = {3},
	journaltitle = {The Cochrane database of systematic reviews},
	shortjournal = {Cochrane Database Syst Rev},
	author = {Liu, Chiung-Ju and Latham, Nancy K.},
	date = {2009-07-08},
	pmid = {19588334},
	pmcid = {PMC4324332},
	note = {Place: England},
	keywords = {Humans, Aged, Randomized Controlled Trials as Topic, Activities of Daily Living, Muscle Weakness/*rehabilitation, Recovery of Function/physiology, Resistance Training/adverse effects/*methods},
}

@article{khan_distinct_2023,
	title = {Distinct regulatory functions and biological roles of {lncRNA} splice variants.},
	volume = {32},
	rights = {© 2023 The Author(s).},
	issn = {2162-2531},
	doi = {10.1016/j.omtn.2023.03.004},
	abstract = {Alternative splicing ({AS}) of {RNA} molecules is a key contributor to transcriptome diversity. In humans, 90\%-95\% of multi-exon genes produce alternatively spliced  {RNA} transcripts. Therefore, every single gene has the opportunity of producing  multiple splice variants, including long non-coding {RNA} ({lncRNA}) genes that  undergo {RNA} maturation steps such as conventional and alternative splicing.  Emerging evidence suggests significant roles for these {lncRNA} splice variants in  many aspects of cell biology. Differential changes in expression of specific  {lncRNA} splice variants have also been associated with many diseases including  cancer. This review covers the current knowledge on this emerging topic of  investigation. We provide exclusive insights on the {AS} landscape of {lncRNAs} and  also describe at the molecular level the functional relevance of {lncRNA} splice  variants, i.e., {RNA}-based differential functions, production of micropeptides,  and generation of circular {RNAs}. Finally, we discuss exciting perspectives for  this emerging field and outline the work required to further develop research  endeavors in this field.},
	pages = {127--143},
	journaltitle = {Molecular therapy. Nucleic acids},
	shortjournal = {Mol Ther Nucleic Acids},
	author = {Khan, Muhammad Riaz and Avino, Mariano and Wellinger, Raymund J. and Laurent, Benoit},
	date = {2023-06-13},
	pmid = {37025931},
	pmcid = {PMC10070373},
	note = {Place: United States},
	keywords = {alternative splicing, circular {RNA}, long non-coding {RNA}, micropeptide, {MT}: Non-coding {RNAs}, splice variant, therapeutics},
}

@article{gibb_functional_2011,
	title = {The functional role of long non-coding {RNA} in human carcinomas},
	volume = {10},
	issn = {1476-4598},
	url = {https://doi.org/10.1186/1476-4598-10-38},
	doi = {10.1186/1476-4598-10-38},
	abstract = {Long non-coding {RNAs} ({lncRNAs}) are emerging as new players in the cancer paradigm demonstrating potential roles in both oncogenic and tumor suppressive pathways. These novel genes are frequently aberrantly expressed in a variety of human cancers, however the biological functions of the vast majority remain unknown. Recently, evidence has begun to accumulate describing the molecular mechanisms by which these {RNA} species function, providing insight into the functional roles they may play in tumorigenesis. In this review, we highlight the emerging functional role of {lncRNAs} in human cancer.},
	pages = {38},
	number = {1},
	journaltitle = {Molecular Cancer},
	shortjournal = {Molecular Cancer},
	author = {Gibb, Ewan A. and Brown, Carolyn J. and Lam, Wan L.},
	date = {2011-04-13},
}

@article{yang_lncrnafunc_2022,
	title = {{lncRNAfunc}: a knowledgebase of {lncRNA} function in human cancer},
	volume = {50},
	issn = {0305-1048},
	url = {https://doi.org/10.1093/nar/gkab1035},
	doi = {10.1093/nar/gkab1035},
	abstract = {The long non-coding {RNAs} associating with other molecules can coordinate several physiological processes and their dysfunction can impact diverse human diseases. To date, systematic and intensive annotations on diverse interaction regulations of {lncRNAs} in human cancer were not available. Here, we built {lncRNAfunc}, a knowledgebase of {lncRNA} function in human cancer at https://ccsm.uth.edu/{lncRNAfunc}, aiming to provide a resource and reference for providing therapeutically targetable {lncRNAs} and intensive interaction regulations. To do this, we collected 15 900 {lncRNAs} across 33 cancer types from {TCGA}. For individual {lncRNAs}, we performed multiple interaction analyses of different biomolecules including {DNA}, {RNA}, and protein levels. Our intensive studies of {lncRNAs} provide diverse potential mechanisms of {lncRNAs} that regulate gene expression through binding enhancers and 3′-{UTRs} of genes, competing for {miRNA} binding sites with {mRNAs}, recruiting the transcription factors to gene promoters. Furthermore, we investigated {lncRNAs} that potentially affect the alternative splicing events through interacting with {RNA} binding Proteins. We also performed multiple functional annotations including cancer stage-associated {lncRNAs}, {RNA} A-to-I editing event-associated {lncRNAs}, and {lncRNA} expression quantitative trait loci. {lncRNAfunc} is a unique resource for cancer research communities to help better understand potential {lncRNA} regulations and therapeutic {lncRNA} targets.},
	pages = {D1295--D1306},
	issue = {D1},
	journaltitle = {Nucleic Acids Research},
	shortjournal = {Nucleic Acids Research},
	author = {Yang, Mengyuan and Lu, Huifen and Liu, Jiajia and Wu, Sijia and Kim, Pora and Zhou, Xiaobo},
	urldate = {2023-11-08},
	date = {2022-01-07},
}

@article{sabbir_ahmed_integrative_2021,
	title = {Integrative Analysis of {lncRNA}-{mRNA} Coexpression in Human Lung Epithelial Cells Exposed to Dimethyl Selenide-Derived Secondary Organic Aerosols.},
	volume = {34},
	issn = {1520-5010 0893-228X},
	doi = {10.1021/acs.chemrestox.0c00516},
	abstract = {Dimethyl selenide ({DMSe}) is one of the major volatile organoselenium compounds released into the atmosphere through plant metabolism and microbial methylation.  {DMSe} has been recently revealed as a precursor of secondary organic aerosol  ({SOA}), and its resultant {SOA} possesses strong oxidizing capability toward thiol  groups that can perturb several major biological pathways in human airway  epithelial cells and is linked to genotoxicity, {DNA} damage, and p53-mediated  stress responses. Mounting evidence has suggested that long noncoding {RNAs}  ({lncRNAs}) are involved in stress responses to internal and environmental stimuli.  However, the underlying molecular interactions remain to be elucidated. In this  study, we performed integrative analyses of {lncRNA}-{mRNA} coexpression in the  transformed human bronchial epithelial {BEAS}-2B cell line exposed to {DMSe}-derived  {SOA}. We identified a total of 971 differentially expressed {lncRNAs} in {BEAS}-2B  cells exposed to {SOA} derived from O(3) and {OH} oxidation of {DMSe}. Gene ontology  ({GO}) network analysis of cis-targeted genes showed significant enrichment of {DNA}  damage, apoptosis, and p53-mediated stress response pathways. trans-Acting  {lncRNAs}, including {PINCR}, {PICART}1, {DLGAP}1-{AS}2, and {LINC}01629, known to be  associated with human carcinogenesis, also showed altered expression in cell  treated with {DMSe}-{SOA}. Overall, this study highlights the regulatory role of  {lncRNAs} in altered gene expression induced by {DMSe}-{SOA} exposure.},
	pages = {892--900},
	number = {3},
	journaltitle = {Chemical research in toxicology},
	shortjournal = {Chem Res Toxicol},
	author = {Sabbir Ahmed, C. M. and Paul, Biplab Chandra and Cui, Yumeng and Frie, Alexander L. and Burr, Abigail and Kamath, Rohan and Chen, Jin Y. and Nordgren, Tara M. and Bahreini, Roya and Lin, Ying-Hsuan},
	date = {2021-03-15},
	pmid = {33656867},
	note = {Place: United States},
	keywords = {Humans, {RNA}-Seq, {RNA}, Messenger/*genetics, {RNA}, Long Noncoding/*genetics, Aerosols/pharmacology, Cells, Cultured, Epithelial Cells/*drug effects/metabolism, Lung/*drug effects/metabolism, Organoselenium Compounds/*pharmacology},
}

@article{molmen_vitamin_2021-1,
	title = {Vitamin D(3) supplementation does not enhance the effects of resistance training in older adults.},
	volume = {12},
	rights = {© 2021 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley \& Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting  Disorders.},
	issn = {2190-6009 2190-5991},
	doi = {10.1002/jcsm.12688},
	abstract = {{BACKGROUND}: Lifestyle therapy with resistance training is a potent measure to counteract age-related loss in muscle strength and mass. Unfortunately, many  individuals fail to respond in the expected manner. This phenomenon is  particularly common among older adults and those with chronic diseases (e.g.  chronic obstructive pulmonary disease, {COPD}) and may involve endocrine variables  such as vitamin D. At present, the effects of vitamin D supplementation on  responses to resistance training remain largely unexplored. {METHODS}: Ninety-five  male and female participants (healthy, n = 71; {COPD}, n = 24; age 68 ± 5 years)  were randomly assigned to receive either vitamin D(3) or placebo supplementation  for 28 weeks in a double-blinded manner (latitude 61°N, September-May).  Seventy-eight participants completed the {RCT}, which was initiated by 12 weeks of  supplementation-only (two weeks with 10 000 {IU}/day, followed by 2000 {IU}/day),  followed by 13 weeks of combined supplementation (2000 {IU}/day) and supervised  whole-body resistance training (twice weekly), interspersed with testing and  measurements. Outcome measures included multiple assessments of muscle strength  (n(variables)  = 7), endurance performance (n = 6), and muscle mass (n = 3, legs,  primary), as well as muscle quality (legs), muscle biology (m. vastus lateralis;  muscle fibre characteristics, transcriptome), and health-related variables (e.g.  visceral fat mass and blood lipid profile). For main outcome domains such as  muscle strength and muscle mass, weighted combined factors were calculated from  the range of singular assessments. {RESULTS}: Overall, 13 weeks of resistance  training increased muscle strength (13\% ± 8\%), muscle mass (9\% ± 8\%), and  endurance performance (one-legged, 23\% ± 15\%; whole-body, 8\% ± 7\%), assessed as  weighted combined factors, and were associated with changes in health variables  (e.g. visceral fat, -6\% ± 21\%; [{LDL}](serum) , -4\% ± 14\%) and muscle tissue  characteristics such as fibre type proportions (e.g. {IIX}, -3\% points), myonuclei  per fibre (30\% ± 65\%), total {RNA}/{rRNA} abundances (15\%/6-19\%), and transcriptome  profiles (e.g. 312 differentially expressed genes). Vitamin D(3) supplementation  did not affect training-associated changes for any of the main outcome domains,  despite robust increases in [25({OH})D](serum) (∆49\% vs. placebo). No conditional  effects were observed for {COPD} vs. healthy or pre-{RCT} [25({OH})D](serum) . In  secondary analyses, vitamin D(3) affected expression of gene sets involved in  vascular functions in muscle tissue and strength gains in participants with high  fat mass, which advocates further study. {CONCLUSIONS}: Vitamin D(3)  supplementation did not affect muscular responses to resistance training in older  adults with or without {COPD}.},
	pages = {599--628},
	number = {3},
	journaltitle = {Journal of cachexia, sarcopenia and muscle},
	shortjournal = {J Cachexia Sarcopenia Muscle},
	author = {Mølmen, Knut Sindre and Hammarström, Daniel and Pedersen, Karianne and Lian Lie, Anne Cecilie and Steile, Ragnvald B. and Nygaard, Håvard and Khan, Yusuf and Hamarsland, Håvard and Koll, Lise and Hanestadhaugen, Marita and Eriksen, Atle Lie and Grindaker, Eirik and Whist, Jon Elling and Buck, Daniel and Ahmad, Rafi and Strand, Tor A. and Rønnestad, Bent R. and Ellefsen, Stian},
	date = {2021-06},
	pmid = {33788419},
	pmcid = {PMC8200443},
	note = {Place: Germany},
	keywords = {*Resistance Training, Female, Humans, Middle Aged, Aged, Male, *Cholecalciferol/therapeutic use, Cholecalciferol, Dietary Supplements, Muscle plasticity, Strength training, Vitamin D, Vitamins},
}

@article{hammarstrom_benefits_2020,
	title = {Benefits of higher resistance-training volume are related to ribosome biogenesis.},
	volume = {598},
	rights = {© 2019 The Authors. The Journal of Physiology published by John Wiley \& Sons Ltd on behalf of The Physiological Society.},
	issn = {1469-7793 0022-3751},
	doi = {10.1113/JP278455},
	abstract = {{KEY} {POINTS}: For individuals showing suboptimal adaptations to resistance training, manipulation of training volume is a potential measure to facilitate  responses. This remains unexplored. Here, 34 untrained individuals performed  contralateral resistance training with moderate and low volume for 12 weeks.  Moderate volume led to larger increases in muscle cross-sectional area, strength  and type {II} fibre-type transitions. These changes coincided with greater  activation of signalling pathways controlling muscle growth and greater induction  of ribosome synthesis. Out of 34 participants, thirteen displayed clear benefit  of {MOD} on muscle hypertrophy and sixteen showed clear benefit of {MOD} on muscle  strength gains. This coincided with greater total {RNA} accumulation in the early  phase of the training period, suggesting that ribosomal biogenesis regulates the  dose-response relationship between training volume and muscle hypertrophy. These  results demonstrate that there is a dose-dependent relationship between training  volume and outcomes. On the individual level, benefits of higher training volume  were associated with increased ribosomal biogenesis. {ABSTRACT}:  Resistance-exercise volume is a determinant of training outcomes. However not all  individuals respond in a dose-dependent fashion. In this study, 34 healthy  individuals (males n = 16, 23.6 (4.1) years; females n = 18, 22.0 (1.3) years)  performed moderate- (3 sets per exercise, {MOD}) and low-volume (1 set, {LOW})  resistance training in a contralateral fashion for 12 weeks (2-3 sessions per  week). Muscle cross-sectional area ({CSA}) and strength were assessed at Weeks 0  and 12, along with biopsy sampling (m. vastus lateralis). Muscle biopsies were  also sampled before and 1 h after the fifth session (Week 2). {MOD} resulted in  larger increases in muscle {CSA} (5.2 (3.8)\% versus 3.7 (3.7)\%, P {\textless} 0.001) and  strength (3.4-7.7\% difference, all P {\textless} 0.05. This coincided with greater  reductions in type {IIX} fibres from Week 0 to Week 12 ({MOD}, -4.6 percentage  points; {LOW} -3.2 percentage points), greater phosphorylation of S6-kinase 1 (p85  S6K1(Thr412) , 19\%; p70 S6K1(Thr389) , 58\%) and ribosomal protein S6(Ser235/236)  (37\%), greater rested-state total {RNA} (8.8\%) and greater exercise-induced c-Myc  {mRNA} expression (25\%; Week 2, all P {\textless} 0.05). Thirteen and sixteen participants,  respectively, displayed clear benefits in response to {MOD} on muscle hypertrophy  and strength. Benefits were associated with greater accumulation of total {RNA} at  Week 2 in the {MOD} leg, with every 1\% difference increasing the odds of {MOD}  benefit by 7.0\% (P = 0.005) and 9.8\% (P = 0.002). In conclusion, {MOD} led to  greater functional and biological adaptations than {LOW}. Associations between  dose-dependent total {RNA} accumulation and increases in muscle mass and strength  point to ribosome biogenesis as a determinant of dose-dependent training  responses.},
	pages = {543--565},
	number = {3},
	journaltitle = {The Journal of physiology},
	shortjournal = {J Physiol},
	author = {Hammarström, Daniel and Øfsteng, Sjur and Koll, Lise and Hanestadhaugen, Marita and Hollan, Ivana and Apró, William and Whist, Jon Elling and Blomstrand, Eva and Rønnestad, Bent R. and Ellefsen, Stian},
	date = {2020-02},
	pmid = {31813190},
	note = {Place: England},
	keywords = {*Resistance Training, Exercise, Female, Humans, Male, Muscle Strength, Ribosomes, Muscle, Skeletal, ribosome biogenesis, resistance-training, training-volume},
}

@article{he_lncrnas_2017,
	title = {{LncRNAs}: key players and novel insights into diabetes mellitus},
	url = {https://www.oncotarget.com/article/19921/text/},
	abstract = {// Xiaoyun He 1, 2, * , Chunlin Ou 3, * , Yanhua Xiao 1 , Qing Han 1 , Hao Li 4 and Suxian Zhou 1 1 Department of Endocrinology, Affiliated Hospital of Guilin Medical University, Guilin 541001, China 2 Department of Endocrinology, Xiangya Hospital, Central South University, Changsha 410008, China 3 Cancer Research Institute, Central South University, Changsha 410078, China 4 Department of Neurology, Affiliated Hospital of Guilin Medical University, Guilin 541001, China * These authors contributed equally to this work and share co-first authors Correspondence to: Suxian Zhou, email: zoe\_doctor@163.com Keywords: {LncRNAs}, diabetes mellitus, pancreatic β cells, insulin resistance, epigenetic regulation Received: March 29, 2017      Accepted: July 19, 2017      Published: August 04, 2017 {ABSTRACT} Long non-coding {RNAs} ({LncRNAs}) are a class of endogenous {RNA} molecules, which have a transcribing length of over 200 nt, lack a complete functional open reading frame ({ORF}), and rarely encode a functional short peptide. Recent studies have revealed that disruption of {LncRNAs} levels correlates with several human diseases, including diabetes mellitus ({DM}), a complex multifactorial metabolic disorder affecting more than 400 million people worldwide. {LncRNAs} are emerging as pivotal regulators in various biological processes, in the progression of {DM} and its associated complications, involving pancreatic β-cell disorder, insulin resistance, and epigenetic regulation, etc . Further investigation into the mechanisms of action of {LncRNAs} in {DM} will be of great value in the thorough understanding of pathogenesis. However, prior to successful application of {LncRNAs}, further search for molecular biomarkers and drug targets to provide a new strategy for {DM} prevention, early diagnosis, and therapy is warranted.},
	journaltitle = {Oncotarget; Vol 8, No 41},
	author = {He, Xiaoyun and Ou, Chunlin and Xiao, Yanhua and Han, Qing and Li, Hao and Zhou, Suxian},
	urldate = {2017-01-01},
	date = {2017},
}

@article{bink_long_2019,
	title = {Long Non-Coding {RNA} in Vascular Disease and Aging},
	volume = {5},
	issn = {2311-553X},
	doi = {10.3390/ncrna5010026},
	abstract = {Cardiovascular diseases are the most prominent cause of death in Western society, especially in the elderly. With the increasing life expectancy, the number of patients with cardiovascular diseases will rise in the near future, leading to an increased healthcare burden. There is a need for new therapies to treat this growing number of patients. The discovery of long non-coding {RNAs} has led to a novel group of molecules that could be considered for their potential as therapeutic targets. This review presents an overview of long non-coding {RNAs} that are regulated in vascular disease and aging and which might therefore give insight into new pathways that could be targeted to diagnose, prevent, and/or treat vascular diseases.},
	number = {1},
	journaltitle = {Non-Coding {RNA}},
	author = {Bink, Diewertje I. and Lozano-Vidal, Noelia and Boon, Reinier A.},
	date = {2019},
	keywords = {aging, {lncRNA}, vascular disease},
}

@article{he_emerging_2019,
	title = {Emerging roles of {lncRNAs} in the post-transcriptional regulation in cancer},
	volume = {6},
	issn = {2352-3042},
	url = {https://www.sciencedirect.com/science/article/pii/S2352304219300017},
	doi = {10.1016/j.gendis.2019.01.003},
	abstract = {Accumulating evidence indicates that long non-coding {RNAs} ({lncRNAs}) can play a pivotal role in regulation of diverse cellular processes. In particular, {lncRNAs} can serve as master gene regulators at transcriptional and posttranscriptional levels, leading to tumorigenesis. In this review, we discuss latest developments in {lncRNA}-meditated gene expression at the post-transcriptional level, including gene splicing, {mRNA} stability, protein stability and nuclear trafficking.},
	pages = {6--15},
	number = {1},
	journaltitle = {Genes \& Diseases},
	shortjournal = {Genes \& Diseases},
	author = {He, Rong-Zhang and Luo, Di-Xian and Mo, Yin-Yuan},
	date = {2019-03-01},
	keywords = {Alternative splicing, {LncRNA}, Posttranscriptional regulation, Protein stability, {RNA} binding proteins, {RNA} stability},
}

@article{ali_beyond_2020,
	title = {Beyond the {RNA}-dependent function of {LncRNA} genes},
	volume = {9},
	issn = {2050-084X},
	url = {https://doi.org/10.7554/eLife.60583},
	doi = {10.7554/eLife.60583},
	abstract = {While long non-coding {RNA} ({lncRNA}) genes have attracted a lot of attention in the last decade, the focus regarding their mechanisms of action has been primarily on the {RNA} product of these genes. Recent work on several {lncRNAs} genes demonstrates that not only is the produced {RNA} species important, but also that transcription of the {lncRNA} locus alone can have regulatory functions. Like the functions of {lncRNA} transcripts, the mechanisms that underlie these genome-based functions are varied. Here we highlight some of these examples and provide an outlook on how the functional mechanisms of a {lncRNA} gene can be determined.},
	pages = {e60583},
	journaltitle = {{eLife}},
	author = {Ali, Tamer and Grote, Phillip},
	editor = {Stainier, Didier {YR}},
	date = {2020-10-23},
	note = {Publisher: {eLife} Sciences Publications, Ltd},
	keywords = {{lncRNA}, 3D genome, gene regulation},
}

@article{schaum_ageing_2020,
	title = {Ageing hallmarks exhibit organ-specific temporal signatures},
	volume = {583},
	issn = {1476-4687},
	url = {https://doi.org/10.1038/s41586-020-2499-y},
	doi = {10.1038/s41586-020-2499-y},
	abstract = {Ageing is the single greatest cause of disease and death worldwide, and understanding the associated processes could vastly improve quality of life. Although major categories of ageing damage have been identified—such as altered intercellular communication, loss of proteostasis and eroded mitochondrial function1—these deleterious processes interact with extraordinary complexity within and between organs, and a comprehensive, whole-organism analysis of ageing dynamics has been lacking. Here we performed bulk {RNA} sequencing of 17 organs and plasma proteomics at 10 ages across the lifespan of Mus musculus, and integrated these findings with data from the accompanying Tabula Muris Senis2—or ‘Mouse Ageing Cell Atlas’—which follows on from the original Tabula Muris3. We reveal linear and nonlinear shifts in gene expression during ageing, with the associated genes clustered in consistent trajectory groups with coherent biological functions—including extracellular matrix regulation, unfolded protein binding, mitochondrial function, and inflammatory and immune response. Notably, these gene sets show similar expression across tissues, differing only in the amplitude and the age of onset of expression. Widespread activation of immune cells is especially pronounced, and is first detectable in white adipose depots during middle age. Single-cell {RNA} sequencing confirms the accumulation of T cells and B cells in adipose tissue—including plasma cells that express immunoglobulin J—which also accrue concurrently across diverse organs. Finally, we show how gene expression shifts in distinct tissues are highly correlated with corresponding protein levels in plasma, thus potentially contributing to the ageing of the systemic circulation. Together, these data demonstrate a similar yet asynchronous inter- and intra-organ progression of ageing, providing a foundation from which to track systemic sources of declining health at old age.},
	pages = {596--602},
	number = {7817},
	journaltitle = {Nature},
	author = {Schaum, Nicholas and Lehallier, Benoit and Hahn, Oliver and Pálovics, Róbert and Hosseinzadeh, Shayan and Lee, Song E. and Sit, Rene and Lee, Davis P. and Losada, Patricia Morán and Zardeneta, Macy E. and Fehlmann, Tobias and Webber, James T. and {McGeever}, Aaron and Calcuttawala, Kruti and Zhang, Hui and Berdnik, Daniela and Mathur, Vidhu and Tan, Weilun and Zee, Alexander and Tan, Michelle and Almanzar, Nicole and Antony, Jane and Baghel, Ankit S. and Bakerman, Isaac and Bansal, Ishita and Barres, Ben A. and Beachy, Philip A. and Berdnik, Daniela and Bilen, Biter and Brownfield, Douglas and Cain, Corey and Chan, Charles K. F. and Chen, Michelle B. and Clarke, Michael F. and Conley, Stephanie D. and Darmanis, Spyros and Demers, Aaron and Demir, Kubilay and de Morree, Antoine and Divita, Tessa and du Bois, Haley and Ebadi, Hamid and Espinoza, F. Hernán and Fish, Matt and Gan, Qiang and George, Benson M. and Gillich, Astrid and Gòmez-Sjöberg, Rafael and Green, Foad and Genetiano, Geraldine and Gu, Xueying and Gulati, Gunsagar S. and Hahn, Oliver and Haney, Michael Seamus and Hang, Yan and Harris, Lincoln and He, Mu and Hosseinzadeh, Shayan and Huang, Albin and Huang, Kerwyn Casey and Iram, Tal and Isobe, Taichi and Ives, Feather and Jones, Robert and Kao, Kevin S. and Karkanias, Jim and Karnam, Guruswamy and Keller, Andreas and Kershner, Aaron M. and Khoury, Nathalie and Kim, Seung K. and Kiss, Bernhard M. and Kong, William and Krasnow, Mark A. and Kumar, Maya E. and Kuo, Christin S. and Y. Lam, Jonathan and Lee, Davis P. and Lee, Song E. and Lehallier, Benoit and Leventhal, Olivia and Li, Guang and Li, Qingyun and Liu, Ling and Lo, Annie and Lu, Wan-Jin and Lugo-Fagundo, Maria F. and Manjunath, Anoop and May, Andrew P. and Maynard, Ashley and {McGeever}, Aaron and {McKay}, Marina and {McNerney}, M. Windy and Merrill, Bryan and Metzger, Ross J. and Mignardi, Marco and Min, Dullei and Nabhan, Ahmad N. and Neff, Norma F. and Ng, Katharine M. and Nguyen, Patricia K. and Noh, Joseph and Nusse, Roel and Pálovics, Róbert and Patkar, Rasika and Peng, Weng Chuan and Penland, Lolita and Pisco, Angela Oliveira and Pollard, Katherine and Puccinelli, Robert and Qi, Zhen and Quake, Stephen R. and Rando, Thomas A. and Rulifson, Eric J. and Schaum, Nicholas and Segal, Joe M. and Sikandar, Shaheen S. and Sinha, Rahul and Sit, Rene V. and Sonnenburg, Justin and Staehli, Daniel and Szade, Krzysztof and Tan, Michelle and Tan, Weilun and Tato, Cristina and Tellez, Krissie and Dulgeroff, Laughing Bear Torrez and Travaglini, Kyle J. and Tropini, Carolina and Tsui, Margaret and Waldburger, Lucas and Wang, Bruce M. and van Weele, Linda J. and Weinberg, Kenneth and Weissman, Irving L. and Wosczyna, Michael N. and Wu, Sean M. and Wyss-Coray, Tony and Xiang, Jinyi and Xue, Soso and Yamauchi, Kevin A. and Yang, Andrew C. and Yerra, Lakshmi P. and Youngyunpipatkul, Justin and Yu, Brian and Zanini, Fabio and Zardeneta, Macy E. and Zee, Alexander and Zhao, Chunyu and Zhang, Fan and Zhang, Hui and Zhang, Martin Jinye and Zhou, Lu and Zou, James and Pisco, Angela Oliveira and Karkanias, Jim and Neff, Norma F. and Keller, Andreas and Darmanis, Spyros and Quake, Stephen R. and Wyss-Coray, Tony and The Tabula Muris, Consortium},
	date = {2020-07-01},
}

@article{sartorius_meanings_2006,
	title = {The meanings of health and its promotion.},
	volume = {47},
	issn = {1332-8166 0353-9504},
	pages = {662--664},
	number = {4},
	journaltitle = {Croatian medical journal},
	shortjournal = {Croat Med J},
	author = {Sartorius, Norman},
	date = {2006-08},
	pmid = {16909464},
	pmcid = {PMC2080455},
	note = {Place: Croatia},
	keywords = {Humans, *Health, *Health Promotion},
}

@article{hanssen_progressive_2022,
	title = {Progressive resistance training for children with cerebral palsy: A randomized controlled trial evaluating the effects on muscle strength and morphology.},
	volume = {13},
	rights = {Copyright © 2022 Hanssen, Peeters, De Beukelaer, Vannerom, Peeters, Molenaers, Van Campenhout, Deschepper, Van den Broeck and Desloovere.},
	issn = {1664-042X},
	doi = {10.3389/fphys.2022.911162},
	abstract = {Children with spastic cerebral palsy often present with muscle weakness, resulting from neural impairments and muscular alterations. While progressive  resistance training ({PRT}) improves muscle weakness, the effects on muscle  morphology remain inconclusive. This investigation evaluated the effects of a {PRT}  program on lower limb muscle strength, morphology and gross motor function.  Forty-nine children with spastic cerebral palsy were randomized by minimization.  The intervention group (nparticipants = 26, age: 8.3 ± 2.0 years, Gross Motor  Function Classification System [{GMFCS}] level I/{II}/{III}: 17/5/4, nlegs = 41)  received a 12-week {PRT} program, consisting of 3-4 sessions per week, with  exercises performed in 3 sets of 10 repetitions, aiming at 60\%-80\% of the  1-repetition maximum. Training sessions were performed under supervision with the  physiotherapist and at home. The control group (nparticipants = 22, age: 8.5 ±  2.1 year, {GMFCS} level I/{II}/{III}: 14/5/3, nlegs = 36) continued usual care  including regular physiotherapy and use of orthotics. We assessed pre- and  post-training knee extension, knee flexion and plantar flexion isometric  strength, rectus femoris, semitendinosus and medial gastrocnemius muscle  morphology, as well as functional strength, gross motor function and walking  capacity. Data processing was performed blinded. Linear mixed models were applied  to evaluate the difference in evolution over time between the control and  intervention group (interaction-effect) and within each group (time-effect). The  α-level was set at p = 0.01. Knee flexion strength and unilateral heel raises  showed a significant interaction-effect (p ≤ 0.008), with improvements in the  intervention group (p ≤ 0.001). Moreover, significant time-effects were seen for  knee extension and plantar flexion isometric strength, rectus femoris and medial  gastrocnemius {MV}, sit-to-stand and lateral step-up in the intervention group (p ≤  0.004). Echo-intensity, muscle lengths and gross motor function showed limited to  no changes. {PRT} improved strength and {MV} in the intervention group, whereby  strength parameters significantly or close to significantly differed from the  control group. Although, relative improvements in strength were larger than  improvements in {MV}, important effects were seen on the maintenance of muscle size  relative to skeletal growth. In conclusion, this study proved the effectiveness  of a home-based, physiotherapy supervised, {PRT} program to improve isometric and  functional muscle strength in children with {SCP} without negative effects on  muscle properties or any serious adverse events. Clinical Trial Registration:  {ClinicalTrials}.gov, identifier {NCT}03863197.},
	pages = {911162},
	journaltitle = {Frontiers in physiology},
	shortjournal = {Front Physiol},
	author = {Hanssen, Britta and Peeters, Nicky and De Beukelaer, Nathalie and Vannerom, Astrid and Peeters, Leen and Molenaers, Guy and Van Campenhout, Anja and Deschepper, Ellen and Van den Broeck, Christine and Desloovere, Kaat},
	date = {2022},
	pmid = {36267577},
	pmcid = {PMC9577365},
	note = {Place: Switzerland},
	keywords = {functional muscle strength, isometric muscle strength, lower extremity, muscle morphology, progressive resistance training, spastic cerebral palsy, ultrasonography},
}

@article{ahtiainen_inter-individual_2020,
	title = {Inter-individual variation in response to resistance training in cardiometabolic health indicators.},
	volume = {30},
	rights = {© 2020 The Authors. Scandinavian Journal of Medicine \& Science In Sports published by John Wiley \& Sons Ltd.},
	issn = {1600-0838 0905-7188},
	doi = {10.1111/sms.13650},
	abstract = {Resistance training ({RT}) may improve metabolic health; however, the extent of its effectiveness is constantly evaluated to assess improvements in the group means,  thus obscuring the heterogeneous individual effects. This study investigated  inter-individual variation in response to {RT} as reflected in metabolic health  indicators and how age, sex, nutrition, and pre-training phenotypes are  associated with such variabilities. {METHODS}: Previously collected data of men and  women (39-73 years, 135 trained, 73 non-trained controls) were pooled for  analysis. Measurements were taken twice before training to estimate individual  day-to-day variations and measurement errors (n = 208). The individual  responsiveness to the 21-week {RT} in cardiometabolic health indicators (ie,  systolic blood pressure, high-density lipoprotein cholesterol ({HDL}-C),  cholesterol and triglycerides) was determined. Body composition was estimated by  bioimpedance and dietary intake according to 4-day food diaries. {RESULTS}:  Metabolic responses to {RT} seemed to be highly individual, and both beneficial and  unfavorable changes were observed. Large inter-individual variations in training  response were not explained by a subject's age, sex, body composition, or  nutritional status, with the exception of improvements in {HDL}-C, which were  associated with simultaneous decreases in body fat in older women. The incidence  of metabolic syndrome diminished following {RT}. {CONCLUSION}: This study showed that  {RT} could improve some specific metabolic health indicators beyond normal  day-to-day variations, especially in blood lipid profile. Further studies are  needed to elucidate genetic and other mechanisms underlining the heterogeneity of  {RT} responses. This knowledge may be useful in providing individually tailored  exercise prescriptions as part of personalized preventative health care.},
	pages = {1040--1053},
	number = {6},
	journaltitle = {Scandinavian journal of medicine \& science in sports},
	shortjournal = {Scand J Med Sci Sports},
	author = {Ahtiainen, Juha P. and Sallinen, Janne and Häkkinen, Keijo and Sillanpää, Elina},
	date = {2020-06},
	pmid = {32150772},
	note = {Place: Denmark},
	keywords = {*Resistance Training, Female, Humans, Middle Aged, Adult, Aged, Body Composition, Male, Insulin/blood, Nutritional Status, *Blood Pressure, Blood Glucose/*metabolism, blood pressure, body composition, Cholesterol/*blood, glucose, insulin, lipid profile, Metabolic Syndrome/blood/epidemiology, Triglycerides/*blood},
}

@article{van_vossel_can_2023,
	title = {Can muscle typology explain the inter-individual variability in resistance training adaptations?},
	rights = {This article is protected by copyright. All rights reserved.},
	issn = {1469-7793 0022-3751},
	doi = {10.1113/JP284442},
	abstract = {Considerable inter-individual heterogeneity exists in the muscular adaptations to resistance training. It has been proposed that fast-twitch fibers are more  sensitive to hypertrophic stimuli and thus that variation in muscle fiber type  composition is a contributing factor to the magnitude of training response. This  study investigated if the inter-individual variability in resistance training  adaptations is determined by muscle typology and if the most appropriate weekly  training frequency depends on muscle typology. In strength-training novices, 11  slow ({ST}) and 10 fast typology ({FT}) individuals were selected by measuring muscle  carnosine with proton magnetic resonance spectroscopy. Participants trained both  upper arm and leg muscles to failure at 60\% 1RM for 10 weeks, whereby one arm and  leg trained 3x/week, the contralateral arm and leg 2x/week. Muscle volume  ({MRI}-based 3D segmentation), maximal dynamic strength (one-repetition maximum,  1RM) and fiber-type specific cross-sectional area (vastus lateralis biopsies)  were evaluated. The training response for total muscle volume (+3 to +14\%), fiber  size (-19 to +22\%) and strength (+17 to +47\%) showed considerable  inter-individual variability, but these could not be attributed to differences in  muscle typology. However, {ST} individuals performed a significantly higher  training volume to gain these similar adaptations as {FT} individuals. The limb  that trained 3x/week had generally more pronounced hypertrophy than the limb that  trained 2x/week, and there was no interaction with muscle typology. In  conclusion, muscle typology cannot explain the high variability in resistance  training adaptations when training is performed to failure at 60\% of 1RM. {KEY}  {POINTS}: This study investigated the influence of muscle typology ( = muscle fiber  type composition) on the variability in resistance training adaptations and on  its role in the individualization of resistance training frequency. We  demonstrate that an individual's muscle typology cannot explain the  inter-individual variability in resistance training induced increases in muscle  volume, maximal dynamic strength and fiber cross-sectional area when repetitions  are performed to failure. Importantly, slow typology individuals performed a  significantly higher training volume to obtain similar adaptations compared to  fast typology individuals. Muscle typology does not determine the most  appropriate resistance training frequency. However, regardless of muscle  typology, an additional weekly training (3x/week vs 2x/week) increases muscle  hypertrophy but not maximal dynamic strength. These findings expand on our  understanding of the underlying mechanisms for the large inter-individual  variability in resistance training adaptations. Abstract figure legend This study  investigated if muscle typology can explain the high variability in resistance  training adaptations. Slow and fast typology resistance training novices were  selected to participate in this study by the non-invasive measurement of muscle  carnosine with proton magnetic resonance spectroscopy. After the chronic training  period a high inter-individual variability was observed in changes in muscle  volume, maximal dynamic strength and fiber cross-sectional area. However, this  high inter-individual variability could not be explained by muscle typology for  any of the outcomes. Visual abstract created with {BioRender}. This article is  protected by copyright. All rights reserved.},
	journaltitle = {The Journal of physiology},
	shortjournal = {J Physiol},
	author = {Van Vossel, Kim and Hardeel, Julie and de Casteele, Freek Van and Van der Stede, Thibaux and Weyns, Anneleen and Boone, Jan and Blemker, Silvia and Lievens, Eline and Derave, Wim},
	date = {2023-04-11},
	pmid = {37038845},
	note = {Place: England},
	keywords = {resistance training, hypertrophy, blood flow, dynamic strength, fiber cross-sectional area, muscle typology, resistance training frequency, resistance training volume},
}

@article{lesinski_effects_2016,
	title = {Effects and dose-response relationships of resistance training on physical performance in youth athletes: a systematic review and meta-analysis.},
	volume = {50},
	rights = {Published by the {BMJ} Publishing Group Limited. For permission to use (where not already granted under a licence) please go to  http://www.bmj.com/company/products-services/rights-and-licensing/},
	issn = {1473-0480 0306-3674},
	doi = {10.1136/bjsports-2015-095497},
	abstract = {{OBJECTIVES}: To quantify age, sex, sport and training type-specific effects of resistance training on physical performance, and to characterise dose-response  relationships of resistance training parameters that could maximise gains in  physical performance in youth athletes. {DESIGN}: Systematic review and  meta-analysis of intervention studies. {DATA} {SOURCES}: Studies were identified by  systematic literature search in the databases {PubMed} and Web of Science  (1985-2015). Weighted mean standardised mean differences ({SMDwm}) were calculated  using random-effects models. {ELIGIBILITY} {CRITERIA} {FOR} {SELECTING} {STUDIES}: Only  studies with an active control group were included if these investigated the  effects of resistance training in youth athletes (6-18 years) and tested at least  one physical performance measure. {RESULTS}: 43 studies met the inclusion criteria.  Our analyses revealed moderate effects of resistance training on muscle strength  and vertical jump performance ({SMDwm} 0.8-1.09), and small effects on linear  sprint, agility and sport-specific performance ({SMDwm} 0.58-0.75). Effects were  moderated by sex and resistance training type. Independently computed  dose-response relationships for resistance training parameters revealed that a  training period of {\textgreater}23 weeks, 5 sets/exercise, 6-8 repetitions/set, a training  intensity of 80-89\% of 1 repetition maximum ({RM}), and 3-4 min rest between sets  were most effective to improve muscle strength ({SMDwm} 2.09-3.40).  {SUMMARY}/{CONCLUSIONS}: Resistance training is an effective method to enhance muscle  strength and jump performance in youth athletes, moderated by sex and resistance  training type. Dose-response relationships for key training parameters indicate  that youth coaches should primarily implement resistance training programmes with  fewer repetitions and higher intensities to improve physical performance measures  of youth athletes.},
	pages = {781--795},
	number = {13},
	journaltitle = {British journal of sports medicine},
	shortjournal = {Br J Sports Med},
	author = {Lesinski, Melanie and Prieske, Olaf and Granacher, Urs},
	date = {2016-07},
	pmid = {26851290},
	pmcid = {PMC4941165},
	note = {Place: England},
	keywords = {Female, Humans, Muscle Strength/*physiology, Resistance Training/*methods, Male, Adolescent, Athletes, Athletic Performance/*physiology, Child, Children, Physical fitness, Strength, Weight lifting},
}

@article{kekalainen_effects_2018,
	title = {Effects of a 9-month resistance training intervention on quality of life, sense of coherence, and depressive symptoms in older adults: randomized controlled  trial.},
	volume = {27},
	issn = {1573-2649 0962-9343},
	doi = {10.1007/s11136-017-1733-z},
	abstract = {{PURPOSE}: (1) To determine the effects of a 9-month resistance training intervention on quality of life, sense of coherence, and depressive symptoms in  older adults, and (2) to compare effects between different training frequencies.  {METHODS}: Men and women aged 65-75 (N = 106) were randomized to four groups  according to training frequency: training groups {RT}1 (n = 26), {RT}2 (n = 27), and  {RT}3 (n = 28) and non-training control group (n = 25). All training groups  attended supervised resistance training twice a week for 3 months. For the  following 6 months, they continued training with different frequencies (1, 2 or 3  times per week). Psychological functioning was measured by quality of life  ({WHOQOL}-Bref), sense of coherence (Antonovsky's {SOC}-13), and depressive symptoms  (Beck's Depression Inventory {II}). Measurements were conducted at baseline and 3  and 9 months after baseline. The effects of the intervention were analyzed using  generalized estimating equations ({GEE}). {RESULTS}: After 3 months, there was an  intervention effect on environmental quality of life (group × time p = .048).  Between 3 and 9 months, environmental quality of life decreased among {RT}1  compared to {RT}2 and {RT}3 (group × time p = .025). Between baseline and 9 months,  environmental quality of life increased in {RT}2 compared to all other groups  (group × time p = .011). Sense of coherence increased in {RT}2 compared to the  control group and {RT}3 (group × time p = .032). {CONCLUSION}: Resistance training is  beneficial for environmental quality of life and sense of coherence. Attending  resistance training twice a week seems to be the most advantageous for these  aspects of psychological functioning.},
	pages = {455--465},
	number = {2},
	journaltitle = {Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation},
	shortjournal = {Qual Life Res},
	author = {Kekäläinen, Tiia and Kokko, Katja and Sipilä, Sarianna and Walker, Simon},
	date = {2018-02},
	pmid = {29124498},
	pmcid = {PMC5846971},
	note = {Place: Netherlands},
	keywords = {Exercise, Female, Humans, Resistance Training/*methods, Aged, Male, Time Factors, Aging, Quality of life, Coping, Depression/*psychology, Mood, Quality of Life/*psychology, Sense of Coherence/*physiology, Well-being},
}

@article{cesana_long_2011,
	title = {A Long Noncoding {RNA} Controls Muscle Differentiation by Functioning as a Competing Endogenous {RNA}},
	volume = {147},
	issn = {0092-8674},
	url = {https://doi.org/10.1016/j.cell.2011.09.028},
	doi = {10.1016/j.cell.2011.09.028},
	pages = {358--369},
	number = {2},
	journaltitle = {Cell},
	author = {Cesana, Marcella and Cacchiarelli, Davide and Legnini, Ivano and Santini, Tiziana and Sthandier, Olga and Chinappi, Mauro and Tramontano, Anna and Bozzoni, Irene},
	urldate = {2024-09-10},
	date = {2011-10-14},
	note = {Publisher: Elsevier},
}

@article{hammarstrom_ribosome_2022-1,
	title = {Ribosome accumulation during early phase resistance training in humans},
	volume = {235},
	url = {https://onlinelibrary.wiley.com/doi/abs/10.1111/apha.13806},
	doi = {https://doi.org/10.1111/apha.13806},
	abstract = {Abstract Aim To describe ribosome biogenesis during resistance training, its relation to training volume and muscle growth. Methods A training group (n = 11) performed 12 sessions (3-4 sessions per week) of unilateral knee extension with constant and variable volume (6 and 3-9 sets per session respectively) allocated to either leg. Ribosome abundance and biogenesis markers were assessed from vastus lateralis biopsies obtained at baseline, 48 hours after sessions 1, 4, 5, 8, 9 and 12, and after eight days of de-training, and from a control group (n = 8). Muscle thickness was measured before and after the intervention. Results Training led to muscle growth (3.9\% over baseline values, 95\% {CrI}: [0.2, 7.5] vs. control) with concomitant increases in total {RNA}, ribosomal {RNA}, upstream binding factor ({UBF}) and ribosomal protein S6 with no differences between volume conditions. Total {RNA} increased rapidly in response to the first four sessions (8.6\% [5.6, 11.7] per session), followed by a plateau and peak values after session 8 (49.5\% [34.5, 66.5] above baseline). Total {RNA} abundance was associated with {UBF} protein levels (5.0\% [0.2, 10.2] per unit {UBF}), and the rate of increase in total {RNA} levels predicted hypertrophy (0.3 mm [0.1, 0.4] per \%-point increase in total {RNA} per session). After de-training, total {RNA} decreased (−19.3\% [−29.0, −8.1]) without muscle mass changes indicating halted biosynthesis of ribosomes. Conclusion Ribosomes accumulate in the initial phase of resistance training with abundances sensitive to training cessation and associated with {UBF} protein levels. The average accumulation rate predicts muscle training-induced hypertrophy.},
	pages = {e13806},
	number = {1},
	journaltitle = {Acta Physiologica},
	author = {Hammarström, Daniel and Øfsteng, Sjur J. and Jacobsen, Nicolai B. and Flobergseter, Krister B. and Rønnestad, Bent R. and Ellefsen, Stian},
	date = {2022},
	note = {\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/apha.13806},
	keywords = {resistance training, muscle hypertrophy, ribosome biogenesis},
}

@article{terzis_degree_2010,
	title = {The degree of p70 S6k and S6 phosphorylation in human skeletal muscle in response to resistance exercise depends on the training volume},
	volume = {110},
	pages = {835--843},
	journaltitle = {European journal of applied physiology},
	author = {Terzis, Gerasimos and Spengos, Konstantinos and Mascher, Henrik and Georgiadis, Giorgos and Manta, Panagiota and Blomstrand, Eva},
	date = {2010},
	note = {{ISBN}: 1439-6319
Publisher: Springer},
}

@article{ahtiainen_exercise_2015,
	title = {Exercise type and volume alter signaling pathways regulating skeletal muscle glucose uptake and protein synthesis},
	volume = {115},
	issn = {1439-6319},
	pages = {1835--1845},
	journaltitle = {European journal of applied physiology},
	shortjournal = {European journal of applied physiology},
	author = {Ahtiainen, Juha P and Walker, Simon and Silvennoinen, Mika and Kyröläinen, Heikki and Nindl, Bradley C and Häkkinen, Keijo and Nyman, Kai and Selänne, Harri and Hulmi, Juha J},
	date = {2015},
	note = {Publisher: Springer},
}

@article{burd_resistance_2010,
	title = {Resistance exercise volume affects myofibrillar protein synthesis and anabolic signalling molecule phosphorylation in young men},
	volume = {588},
	issn = {0022-3751},
	pages = {3119--3130},
	number = {16},
	journaltitle = {The Journal of physiology},
	shortjournal = {The Journal of physiology},
	author = {Burd, Nicholas A and Holwerda, Andrew M and Selby, Keegan C and West, Daniel {WD} and Staples, Aaron W and Cain, Nathan E and Cashaback, Joshua {GA} and Potvin, James R and Baker, Steven K and Phillips, Stuart M},
	date = {2010},
	note = {Publisher: Wiley Online Library},
}

@article{terzis_resistance_2008,
	title = {Resistance exercise-induced increase in muscle mass correlates with p70S6 kinase phosphorylation in human subjects},
	volume = {102},
	issn = {1439-6319},
	pages = {145--152},
	journaltitle = {European journal of applied physiology},
	shortjournal = {European journal of applied physiology},
	author = {Terzis, Gerasimos and Georgiadis, Giorgos and Stratakos, Grigoris and Vogiatzis, Ioannis and Kavouras, Stavros and Manta, Panagiota and Mascher, Henrik and Blomstrand, Eva},
	date = {2008},
	note = {Publisher: Springer},
}

@article{terzis_degree_2010-1,
	title = {The degree of p70 S6k and S6 phosphorylation in human skeletal muscle in response to resistance exercise depends on the training volume},
	volume = {110},
	issn = {1439-6319},
	pages = {835--843},
	journaltitle = {European journal of applied physiology},
	shortjournal = {European journal of applied physiology},
	author = {Terzis, Gerasimos and Spengos, Konstantinos and Mascher, Henrik and Georgiadis, Giorgos and Manta, Panagiota and Blomstrand, Eva},
	date = {2010},
	note = {Publisher: Springer},
}

@article{hung_long_2010,
	title = {Long noncoding {RNA} in genome regulation},
	volume = {7},
	issn = {1547-6286},
	url = {https://doi.org/10.4161/rna.7.5.13216},
	doi = {10.4161/rna.7.5.13216},
	pages = {582--585},
	number = {5},
	journaltitle = {{RNA} Biology},
	shortjournal = {{RNA} Biology},
	author = {Hung, Tiffany and Chang, Howard Y.},
	date = {2010-09-01},
	note = {Publisher: Taylor \& Francis},
}

@article{zyla_gene_2019,
	title = {Gene set enrichment for reproducible science: comparison of {CERNO} and eight other algorithms},
	volume = {35},
	issn = {1367-4803},
	url = {https://doi.org/10.1093/bioinformatics/btz447},
	doi = {10.1093/bioinformatics/btz447},
	abstract = {Analysis of gene set ({GS}) enrichment is an essential part of functional omics studies. Here, we complement the established evaluation metrics of {GS} enrichment algorithms with a novel approach to assess the practical reproducibility of scientific results obtained from {GS} enrichment tests when applied to related data from different studies.We evaluated eight established and one novel algorithm for reproducibility, sensitivity, prioritization, false positive rate and computational time. In addition to eight established algorithms, we also included Coincident Extreme Ranks in Numerical Observations ({CERNO}), a flexible and fast algorithm based on modified Fisher P-value integration. Using real-world datasets, we demonstrate that {CERNO} is robust to ranking metrics, as well as sample and {GS} size. {CERNO} had the highest reproducibility while remaining sensitive, specific and fast. In the overall ranking Pathway Analysis with Down-weighting of Overlapping Genes, {CERNO} and over-representation analysis performed best, while {CERNO} and {GeneSetTest} scored high in terms of reproducibility.tmod package implementing the {CERNO} algorithm is available from {CRAN} (cran.r-project.org/web/packages/tmod/index.html) and an online implementation can be found at http://tmod.online/. The datasets analyzed in this study are widely available in the {KEGGdzPathwaysGEO}, {KEGGandMetacoreDzPathwaysGEO} R package and {GEO} repository.Supplementary data are available at Bioinformatics online.},
	pages = {5146--5154},
	number = {24},
	journaltitle = {Bioinformatics},
	shortjournal = {Bioinformatics},
	author = {Zyla, Joanna and Marczyk, Michal and Domaszewska, Teresa and Kaufmann, Stefan H E and Polanska, Joanna and Weiner, 3rd, January},
	urldate = {2024-09-15},
	date = {2019-12-15},
}

@article{guo_competing_2015,
	title = {Competing endogenous {RNA} networks and gastric cancer.},
	volume = {21},
	issn = {2219-2840 1007-9327},
	doi = {10.3748/wjg.v21.i41.11680},
	abstract = {Recent studies have showed that {RNAs} regulate each other with {microRNA} ({miRNA}) response elements ({MREs}) and this mechanism is known as "competing endogenous {RNA}  ({ceRNA})" hypothesis. Long non-coding {RNAs} ({lncRNAs}) are supposed to play  important roles in cancer. Compelling evidence suggests that {lncRNAs} can interact  with {miRNAs} and regulate the expression of {miRNAs} as {ceRNAs}. Several {lncRNAs} such  as H19, {HOTAIR} and {MEG}3 have been found to be associated with {miRNAs} in gastric  cancer ({GC}), generating regulatory crosstalk across the transcriptome. These {MRE}  sharing elements implicated in the {ceRNA} networks ({ceRNETs}) are able to regulate  {mRNA} expression. The {ceRNA} regulatory networks including {mRNAs}, {miRNAs}, {lncRNAs}  and circular {RNAs} may play critical roles in tumorigenesis, and the perturbations  of {ceRNETs} may contribute to the pathogenesis of {GC}.},
	pages = {11680--11687},
	number = {41},
	journaltitle = {World journal of gastroenterology},
	shortjournal = {World J Gastroenterol},
	author = {Guo, Lei-Lei and Song, Chun-Hua and Wang, Peng and Dai, Li-Ping and Zhang, Jian-Ying and Wang, Kai-Juan},
	date = {2015-11-07},
	pmid = {26556995},
	pmcid = {PMC4631969},
	note = {Place: United States},
	keywords = {Humans, Animals, Gene Regulatory Networks, Gene Expression Regulation, Neoplastic, Competing endogenous {RNA}, Competitive endogenous {RNAs} networks, Databases, Genetic, Gastric cancer, Genetic Predisposition to Disease, {MicroRNA} response elements, {MicroRNAs}/*genetics/metabolism, Perturbation, Phenotype, Response Elements, {RNA}, Circular, {RNA}, Long Noncoding/*genetics/metabolism, {RNA}, Neoplasm/*genetics/metabolism, {RNA}/genetics/*metabolism, Stomach Neoplasms/*genetics/metabolism/pathology},
}

@article{fan_systematic_2018,
	title = {Systematic analysis of {lncRNA}–{miRNA}–{mRNA} competing endogenous {RNA} network identifies four-{lncRNA} signature as a prognostic biomarker for breast cancer},
	volume = {16},
	issn = {1479-5876},
	url = {https://doi.org/10.1186/s12967-018-1640-2},
	doi = {10.1186/s12967-018-1640-2},
	abstract = {Increasing evidence has underscored the role of long non-coding {RNAs} ({lncRNAs}) acting as competing endogenous {RNAs} ({ceRNAs}) in the development and progression of tumors. Nevertheless, {lncRNA} biomarkers in {lncRNA}-related {ceRNA} network that can predict the prognosis of breast cancer ({BC}) are still lacking. The aim of our study was to identify potential {lncRNA} signatures capable of predicting overall survival ({OS}) of {BC} patients.},
	pages = {264},
	number = {1},
	journaltitle = {Journal of Translational Medicine},
	shortjournal = {Journal of Translational Medicine},
	author = {Fan, Chun-Ni and Ma, Lei and Liu, Ning},
	date = {2018-09-27},
}

@article{liu_bioinformatics_2021,
	title = {Bioinformatics Analysis and Functional Verification of {ADAMTS}9-{AS}1/{AS}2 in Lung Adenocarcinoma},
	volume = {11},
	issn = {2234-943X},
	url = {https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.681777},
	abstract = {Long non-coding {RNAs} ({lncRNAs}), as competitive endogenous {RNAs} ({ceRNAs}), play a critical role in biological processes of cancer. However, the roles of specific {lncRNAs} in {ceRNA} network of lung adenocarcinoma ({LUAD}) remains largely unclear. Herein, we identified the roles of {lncRNA} {ADAMTS}9-{AS}1/{AS}2 ({ADAMTS}-{AS}1/{AS}2) in lung adenocarcinoma by bioinformatics analyses and functional verification. First, differentially expressed genes {ADAMTS}9-{AS}1, {ADAMTS}9-{AS}2 and {ADAMTS}9 were screened out from {GSE}130779. Then the expression correlation of these three genes was analyzed. The results showed that {ADAMTS}9-{AS}1, {ADAMTS}9-{AS}2 and {ADAMTS}9 were down-regulated in {LUAD}, and were positively correlated with each other. After that, {miRcode} was used to find {miR}-150 which binds to {ADAMTS}9-{AS}1/{ADAMTS}9-{AS}2/{ADAMTS}9. Next, co-expression analysis and functional enrichment analyses were performed to further analyze differentially expressed genes. The results showed that the differentially expressed genes were mainly enriched in Beta3 integrin cell surface interactions and epithelial-to-mesenchymal transition. Finally, the cell functions of {ADAMTS}9-{AS}1 and {ADAMTS}9-{AS}2 in A549 and {NCI}-H1299 cell lines were verified. In vitro cell studies confirmed that {ADAMTS}9-{AS}1 and {ADAMTS}9-{AS}2 play an inhibitory role in {LUAD} cells.},
	journaltitle = {Frontiers in Oncology},
	shortjournal = {Frontiers in Oncology},
	author = {Liu, Wei and Luo, Wenguang and Zhou, Peijie and Cheng, Yong and Qian, Liting},
	date = {2021},
}

@article{wan_data_2020,
	title = {Data Mining and Expression Analysis of Differential {lncRNA} {ADAMTS}9-{AS}1 in Prostate Cancer},
	volume = {10},
	issn = {1664-8021},
	url = {https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2019.01377},
	abstract = {Long noncoding {RNAs} ({lncRNAs}) play important roles in the regulation of gene expression by acting as competing endogenous {RNAs} ({ceRNAs}). However, the roles of {lncRNA}-associated {ceRNAs} in oncogenesis are not fully understood. The present study aims to determine whether a {ceRNA} network can serve as a prognostic marker in human prostate cancer ({PCa}). In order to identify a {ceRNA} network and the key {lncRNAs} in {PCa}, we constructed a differentially expressed {lncRNAs} ({DELs})–differentially expressed {miRNAs} ({DEMis})–differentially expressed {mRNAs} ({DEMs}) regulatory network based on the {ceRNA} theory using data from the Cancer Genome Atlas ({TCGA}). We found that the {DELs}–{DEMis}–{DEMs} network was composed of 27 {DELs} nodes, seven {DEMis} nodes, and three {DEMs} nodes. The 27 {DELs} were further analyzed with several public databases to provide meaningful information for understanding the functional roles of {lncRNAs} in regulatory networks in {PCa}. We selected {ADAMTS}9-{AS}1 to determine its role in {PCa} and found that {ADAMTS}9-{AS}1 significantly influences tumor cell growth and proliferation, suggesting that it plays a tumor suppressive role. In addition, {ADAMTS}9-{AS}1 functioned as {ceRNA}, effectively becoming a sponge for hsa-mir-96 and modulating the expression of {PRDM}16. These results suggest that {ceRNAs} could accelerate biomarker discovery and therapeutic strategies for {PCa}.},
	journaltitle = {Frontiers in Genetics},
	shortjournal = {Frontiers in Genetics},
	author = {Wan, Jiahui and Jiang, Shijun and Jiang, Ying and Ma, Wei and Wang, Xiuli and He, Zikang and Wang, Xiaojin and Cui, Rongjun},
	date = {2020},
}

@article{ronnestad_dissimilar_2007,
	title = {Dissimilar effects of one-and three-set strength training on strength and muscle mass gains in upper and lower body in untrained subjects},
	volume = {21},
	issn = {1064-8011},
	pages = {157--163},
	number = {1},
	journaltitle = {The Journal of Strength \& Conditioning Research},
	shortjournal = {The Journal of Strength \& Conditioning Research},
	author = {Rønnestad, Bent R and Egeland, Wilhelm and Kvamme, Nils H and Refsnes, Per E and Kadi, Fawzi and Raastad, Truls},
	date = {2007},
	note = {Publisher: {LWW}},
}

@article{simionescu-bankston_noncoding_2016,
	title = {Noncoding {RNAs} in the regulation of skeletal muscle biology in health and disease},
	volume = {94},
	issn = {1432-1440},
	url = {https://doi.org/10.1007/s00109-016-1443-y},
	doi = {10.1007/s00109-016-1443-y},
	abstract = {Skeletal muscle is composed of multinucleated myofibers that arise from the fusion of myoblasts during development. Skeletal muscle is essential for various body functions such as maintaining posture, locomotion, breathing, and metabolism. Skeletal muscle undergoes remarkable adaptations in response to environmental stimuli leading to atrophy or hypertrophy. Moreover, degeneration of skeletal muscle is a common feature in a number of muscular disorders including muscular dystrophy. Emerging evidence suggests that noncoding {RNAs}, such as {microRNAs} ({miRNAs}) and long noncoding {RNAs} ({lncRNAs}), are critical for skeletal muscle physiology. Several {miRNAs} and {lncRNAs} have now been found to control skeletal muscle development and regeneration. Noncoding {RNAs} also play an important role in the regulation of skeletal muscle mass in adults. Furthermore, aberrant expression of {miRNAs} and {lncRNAs} has been observed in several muscular disorders. In this article, we discuss the mechanisms of action of {miRNAs} and {lncRNAs} in skeletal muscle formation, growth, regeneration, and disease. We further highlight potential therapeutic strategies for utilizing noncoding {RNAs} to improve skeletal muscle function.},
	pages = {853--866},
	number = {8},
	journaltitle = {Journal of Molecular Medicine},
	shortjournal = {Journal of Molecular Medicine},
	author = {Simionescu-Bankston, Adriana and Kumar, Ashok},
	date = {2016-08-01},
}

@article{caretti_rna_2006,
	title = {The {RNA} Helicases p68/p72 and the Noncoding {RNA} {SRA} Are Coregulators of {MyoD} and Skeletal Muscle Differentiation},
	volume = {11},
	issn = {1534-5807},
	url = {https://doi.org/10.1016/j.devcel.2006.08.003},
	doi = {10.1016/j.devcel.2006.08.003},
	pages = {547--560},
	number = {4},
	journaltitle = {Developmental Cell},
	author = {Caretti, Giuseppina and Schiltz, R. Louis and Dilworth, F. Jeffrey and Di Padova, Monica and Zhao, Po and Ogryzko, Vasily and Fuller-Pace, Frances V. and Hoffman, Eric P. and Tapscott, Stephen J. and Sartorelli, Vittorio},
	urldate = {2024-09-20},
	date = {2006-10-01},
	note = {Publisher: Elsevier},
}

@article{kallen_imprinted_2013,
	title = {The imprinted H19 {lncRNA} antagonizes let-7 {microRNAs}},
	volume = {52},
	issn = {1097-2765},
	pages = {101--112},
	number = {1},
	journaltitle = {Molecular cell},
	shortjournal = {Molecular cell},
	author = {Kallen, Amanda N and Zhou, Xiao-Bo and Xu, Jie and Qiao, Chong and Ma, Jing and Yan, Lei and Lu, Lingeng and Liu, Chaochun and Yi, Jae-Sung and Zhang, Haifeng},
	date = {2013},
	note = {Publisher: Elsevier},
}

@article{legnini_feedforward_2014,
	title = {A Feedforward Regulatory Loop between {HuR} and the Long Noncoding {RNA} linc-{MD}1 Controls Early Phases of Myogenesis},
	volume = {53},
	issn = {1097-2765},
	url = {https://doi.org/10.1016/j.molcel.2013.12.012},
	doi = {10.1016/j.molcel.2013.12.012},
	pages = {506--514},
	number = {3},
	journaltitle = {Molecular Cell},
	author = {Legnini, Ivano and Morlando, Mariangela and Mangiavacchi, Arianna and Fatica, Alessandro and Bozzoni, Irene},
	urldate = {2024-09-20},
	date = {2014-02-06},
	note = {Publisher: Elsevier},
}

@article{han_malat1_2015,
	title = {Malat1 regulates serum response factor through {miR}‐133 as a competing endogenous {RNA} in myogenesis},
	volume = {29},
	issn = {0892-6638},
	pages = {3054--3064},
	number = {7},
	journaltitle = {The {FASEB} Journal},
	shortjournal = {The {FASEB} Journal},
	author = {Han, Xiaorui and Yang, Feng and Cao, Huiqing and Liang, Zicai},
	date = {2015},
	note = {Publisher: Wiley Online Library},
}

@article{gong_long_2015,
	title = {A long non-coding {RNA}, {LncMyoD}, regulates skeletal muscle differentiation by blocking {IMP}2-mediated {mRNA} translation},
	volume = {34},
	issn = {1534-5807},
	pages = {181--191},
	number = {2},
	journaltitle = {Developmental cell},
	shortjournal = {Developmental cell},
	author = {Gong, Chenguang and Li, Zhizhong and Ramanujan, Krishnan and Clay, Ieuan and Zhang, Yunyu and Lemire-Brachat, Sophie and Glass, David J},
	date = {2015},
	note = {Publisher: Elsevier},
}

@article{mueller_munc_2015,
	title = {{MUNC}, a long noncoding {RNA} that facilitates the function of {MyoD} in skeletal myogenesis},
	journaltitle = {Molecular and cellular biology},
	shortjournal = {Molecular and cellular biology},
	author = {Mueller, Adam C and Cichewicz, Magdalena A and Dey, Bijan K and Layer, Ryan and Reon, Brian J and Gagan, Jeffrey R and Dutta, Anindya},
	date = {2015},
	note = {Publisher: Am Soc Microbiol},
}

@article{wang_control_2013,
	title = {Control of myogenesis by rodent {SINE}-containing {lncRNAs}},
	volume = {27},
	issn = {0890-9369},
	pages = {793--804},
	number = {7},
	journaltitle = {Genes \& development},
	shortjournal = {Genes \& development},
	author = {Wang, Jiashi and Gong, Chenguang and Maquat, Lynne E},
	date = {2013},
	note = {Publisher: Cold Spring Harbor Lab},
}

@article{cesana_long_2011-1,
	title = {A long noncoding {RNA} controls muscle differentiation by functioning as a competing endogenous {RNA}.},
	volume = {147},
	rights = {Copyright © 2011 Elsevier Inc. All rights reserved.},
	issn = {1097-4172 0092-8674},
	doi = {10.1016/j.cell.2011.09.028},
	abstract = {Recently, a new regulatory circuitry has been identified in which {RNAs} can crosstalk with each other by competing for shared {microRNAs}. Such competing  endogenous {RNAs} ({ceRNAs}) regulate the distribution of {miRNA} molecules on their  targets and thereby impose an additional level of post-transcriptional  regulation. Here we identify a muscle-specific long noncoding {RNA}, linc-{MD}1,  which governs the time of muscle differentiation by acting as a {ceRNA} in mouse  and human myoblasts. Downregulation or overexpression of linc-{MD}1 correlate with  retardation or anticipation of the muscle differentiation program, respectively.  We show that linc-{MD}1 "sponges" {miR}-133 and {miR}-133 [corrected] to regulate the  expression of {MAML}1 and {MEF}2C, transcription factors that activate  muscle-specific gene expression. Finally, we demonstrate that linc-{MD}1 exerts the  same control over differentiation timing in human myoblasts, and that its levels  are strongly reduced in Duchenne muscle cells. We conclude that the {ceRNA} network  plays an important role in muscle differentiation.},
	pages = {358--369},
	number = {2},
	journaltitle = {Cell},
	shortjournal = {Cell},
	author = {Cesana, Marcella and Cacchiarelli, Davide and Legnini, Ivano and Santini, Tiziana and Sthandier, Olga and Chinappi, Mauro and Tramontano, Anna and Bozzoni, Irene},
	date = {2011-10-14},
	pmid = {22000014},
	pmcid = {PMC3234495},
	note = {Place: United States},
	keywords = {Humans, Animals, Mice, {RNA}, Untranslated/*metabolism, {MicroRNAs}/metabolism, *Gene Expression Regulation, Developmental, *Muscle Development, Base Sequence, {DNA}-Binding Proteins/genetics, {MADS} Domain Proteins/genetics, {MEF}2 Transcription Factors, Molecular Sequence Data, Muscle, Skeletal/*cytology/embryology/metabolism, Muscular Dystrophy, Duchenne/embryology/metabolism/pathology, Myoblasts/metabolism, Myogenic Regulatory Factors/genetics, Nuclear Proteins/genetics, {RNA} Processing, Post-Transcriptional, {RNA}, Long Noncoding, Transcription Factors/genetics},
}

@article{monteuuis_changing_2019,
	title = {The changing paradigm of intron retention: regulation, ramifications and recipes},
	volume = {47},
	issn = {0305-1048},
	url = {https://doi.org/10.1093/nar/gkz1068},
	doi = {10.1093/nar/gkz1068},
	abstract = {Intron retention ({IR}) is a form of alternative splicing that has long been neglected in mammalian systems although it has been studied for decades in non-mammalian species such as plants, fungi, insects and viruses. It was generally assumed that mis-splicing, leading to the retention of introns, would have no physiological consequence other than reducing gene expression by nonsense-mediated decay. Relatively recent landmark discoveries have highlighted the pivotal role that {IR} serves in normal and disease-related human biology. Significant technical hurdles have been overcome, thereby enabling the robust detection and quantification of {IR}. Still, relatively little is known about the cis- and trans-acting modulators controlling this phenomenon. The fate of an intron to be, or not to be, retained in the mature transcript is the direct result of the influence exerted by numerous intrinsic and extrinsic factors at multiple levels of regulation. These factors have altered current biological paradigms and provided unexpected insights into the transcriptional landscape. In this review, we discuss the regulators of {IR} and methods to identify them. Our focus is primarily on mammals, however, we broaden the scope to non-mammalian organisms in which {IR} has been shown to be biologically relevant.},
	pages = {11497--11513},
	number = {22},
	journaltitle = {Nucleic Acids Research},
	shortjournal = {Nucleic Acids Research},
	author = {Monteuuis, Geoffray and Wong, Justin J L and Bailey, Charles G and Schmitz, Ulf and Rasko, John E J},
	urldate = {2024-10-03},
	date = {2019-12-16},
}

@article{middleton_irfinder_2017,
	title = {{IRFinder}: assessing the impact of intron retention on mammalian gene expression.},
	volume = {18},
	issn = {1474-760X 1474-7596},
	doi = {10.1186/s13059-017-1184-4},
	abstract = {Intron retention ({IR}) occurs when an intron is transcribed into pre-{mRNA} and remains in the final {mRNA}. We have developed a program and database called  {IRFinder} to accurately detect {IR} from {mRNA} sequencing data. Analysis of 2573  samples showed that {IR} occurs in all tissues analyzed, affects over 80\% of all  coding genes and is associated with cell differentiation and the cell cycle.  Frequently retained introns are enriched for specific {RNA} binding protein sites  and are often retained in clusters in the same gene. {IR} is associated with lower  protein levels and intron-retaining transcripts that escape nonsense-mediated  decay are not actively translated.},
	pages = {51},
	number = {1},
	journaltitle = {Genome biology},
	shortjournal = {Genome Biol},
	author = {Middleton, Robert and Gao, Dadi and Thomas, Aubin and Singh, Babita and Au, Amy and Wong, Justin J.-L. and Bomane, Alexandra and Cosson, Bertrand and Eyras, Eduardo and Rasko, John E. J. and Ritchie, William},
	date = {2017-03-15},
	pmid = {28298237},
	pmcid = {PMC5353968},
	note = {Place: England},
	keywords = {Humans, Animals, Intron retention, Alternative Splicing, *Gene Expression Regulation, *Introns, *{RNA} Splicing, *Software, Binding Sites, Cell Cycle/genetics, Cell Differentiation/genetics, Computational Biology/*methods, Exons, Gene regulation, {mRNA} splicing, Nucleotide Motifs, {RNA}-Binding Proteins/metabolism},
}

@article{wong_orchestrated_2013,
	title = {Orchestrated Intron Retention Regulates Normal Granulocyte Differentiation},
	volume = {154},
	issn = {0092-8674},
	url = {https://doi.org/10.1016/j.cell.2013.06.052},
	doi = {10.1016/j.cell.2013.06.052},
	pages = {583--595},
	number = {3},
	journaltitle = {Cell},
	author = {Wong, Justin J.-L. and Ritchie, William and Ebner, Olivia A. and Selbach, Matthias and Wong, Jason W.H. and Huang, Yizhou and Gao, Dadi and Pinello, Natalia and Gonzalez, Maria and Baidya, Kinsha and Thoeng, Annora and Khoo, Teh-Liane and Bailey, Charles G. and Holst, Jeff and Rasko, John E.J.},
	urldate = {2024-10-02},
	date = {2013-08-01},
	note = {Publisher: Elsevier},
}

@article{braunschweig_widespread_2014,
	title = {Widespread intron retention in mammals functionally tunes transcriptomes.},
	volume = {24},
	rights = {© 2014 Braunschweig et al.; Published by Cold Spring Harbor Laboratory Press.},
	issn = {1549-5469 1088-9051},
	doi = {10.1101/gr.177790.114},
	abstract = {Alternative splicing ({AS}) of precursor {RNAs} is responsible for greatly expanding the regulatory and functional capacity of eukaryotic genomes. Of the different  classes of {AS}, intron retention ({IR}) is the least well understood. In plants and  unicellular eukaryotes, {IR} is the most common form of {AS}, whereas in animals, it  is thought to represent the least prevalent form. Using high-coverage poly(A)(+)  {RNA}-seq data, we observe that {IR} is surprisingly frequent in mammals, affecting  transcripts from as many as three-quarters of multiexonic genes. A highly  correlated set of cis features comprising an "{IR} code" reliably discriminates  retained from constitutively spliced introns. We show that {IR} acts widely to  reduce the levels of transcripts that are less or not required for the physiology  of the cell or tissue type in which they are detected. This "transcriptome  tuning" function of {IR} acts through both nonsense-mediated {mRNA} decay and nuclear  sequestration and turnover of {IR} transcripts. We further show that {IR} is linked  to a cross-talk mechanism involving localized stalling of {RNA} polymerase {II} (Pol  {II}) and reduced availability of spliceosomal components. Collectively, the  results implicate a global checkpoint-type mechanism whereby reduced recruitment  of splicing components coupled to Pol {II} pausing underlies widespread {IR}-mediated  suppression of inappropriately expressed transcripts.},
	pages = {1774--1786},
	number = {11},
	journaltitle = {Genome research},
	shortjournal = {Genome Res},
	author = {Braunschweig, Ulrich and Barbosa-Morais, Nuno L. and Pan, Qun and Nachman, Emil N. and Alipanahi, Babak and Gonatopoulos-Pournatzis, Thomas and Frey, Brendan and Irimia, Manuel and Blencowe, Benjamin J.},
	date = {2014-11},
	pmid = {25258385},
	pmcid = {PMC4216919},
	note = {Place: United States},
	keywords = {Humans, Animals, Introns/*genetics, Mice, Cell Line, Tumor, Cell Line, Cells, Cultured, Cell Differentiation/genetics, *Alternative Splicing, 3T3 Cells, Evolution, Molecular, {HeLa} Cells, K562 Cells, Mammals/classification/*genetics, Models, Genetic, Organ Specificity, Principal Component Analysis, Reverse Transcriptase Polymerase Chain Reaction, {RNA} Polymerase {II}/metabolism, {RNA} Precursors/genetics/metabolism, Species Specificity, Transcriptome/*genetics, Vertebrates/classification/genetics},
}

@article{benjamini_controlling_1995,
	title = {Controlling the false discovery rate: a practical and powerful approach to multiple testing},
	volume = {57},
	issn = {0035-9246},
	pages = {289--300},
	number = {1},
	journaltitle = {Journal of the Royal statistical society: series B (Methodological)},
	shortjournal = {Journal of the Royal statistical society: series B (Methodological)},
	author = {Benjamini, Yoav and Hochberg, Yosef},
	date = {1995},
	note = {Publisher: Wiley Online Library},
}

@article{pabis_concerted_2024,
	title = {A concerted increase in readthrough and intron retention drives transposon expression during aging and senescence},
	url = {http://dx.doi.org/10.7554/eLife.87811.2},
	doi = {10.7554/elife.87811.2},
	author = {Pabis, Kamil and Barardo, Diogo and Sirbu, Olga and Selvarajoo, Kumar and Gruber, Jan and Kennedy, Brian K.},
	date = {2024-01-18},
	note = {Publisher: {eLife} Sciences Publications, Ltd},
}

@article{schmitz_intron_2017,
	title = {Intron retention enhances gene regulatory complexity in vertebrates},
	volume = {18},
	issn = {1474-760X},
	url = {https://doi.org/10.1186/s13059-017-1339-3},
	doi = {10.1186/s13059-017-1339-3},
	abstract = {While intron retention ({IR}) is now widely accepted as an important mechanism of mammalian gene expression control, it remains the least studied form of alternative splicing. To delineate conserved features of {IR}, we performed an exhaustive phylogenetic analysis in a highly purified and functionally defined cell type comprising neutrophilic granulocytes from five vertebrate species spanning 430 million years of evolution.},
	pages = {216},
	number = {1},
	journaltitle = {Genome Biology},
	shortjournal = {Genome Biology},
	author = {Schmitz, Ulf and Pinello, Natalia and Jia, Fangzhi and Alasmari, Sultan and Ritchie, William and Keightley, Maria-Cristina and Shini, Shaniko and Lieschke, Graham J. and Wong, Justin J-L and Rasko, John E. J.},
	date = {2017-11-16},
}

@article{kodama_systematic_2024,
	title = {Systematic identification of exercise-induced anti-aging processes involving intron retention},
	url = {http://biorxiv.org/content/early/2024/04/28/2024.04.25.591048.abstract},
	doi = {10.1101/2024.04.25.591048},
	abstract = {Exercise is one of the most promising anti-aging interventions for maintaining skeletal muscle health in older adults. Nine “Aging Hallmarks”, proposed by López-Otín, offer insights into the aging process; however, the link between these hallmarks and exercise is not fully elucidated. In this study, we conducted a systematic multi-omics analysis of skeletal muscles, focusing on aging and exercise, based on gene signatures for aging hallmarks. It is posited that {mRNA} splicing activity, linked to genomic instability, constitutes a fundamental hallmark of aging, and it exhibits divergent expression patterns in response to aging and exercise. Additionally, we analysed splicing events and discovered that intron retention ({IR}) is significantly impacted by aging, exhibiting contrasting changes to those induced by resistance training in the older cohort. The isoforms characterised by {IR} are notably enriched in mitochondrial functions. Conclusively, our results underscore the significance of splicing mechanisms as a novel aspect of aging hallmarks in skeletal muscles and propose a new mechanism by which exercise exerts its anti-aging effects on skeletal muscles through intron retention.Key points {summarySkeletal} muscle aging involves significant structural and functional changes, including loss of muscle mass, decline in strength, and mitochondrial dysfunction, all influenced by genomic instability.Exercise has been identified as a key intervention that counters genomic instability and modulates {mRNA} splicing patterns, particularly through the regulation of Intron Retention, to mitigate aging effects in skeletal muscle.We reveal the novel role of {IR}, especially in principal isoforms, where it is linked to critical cellular processes like mitochondrial function, suggesting a targeted pathway through which exercise exerts its anti-aging effects.The findings provide new insights into the molecular mechanisms underlying the beneficial effects of exercise on aging skeletal muscle.This study lays the groundwork for future research on exercise-induced modulation of {mRNA} splicing as a therapeutic strategy for aging and potentially age-related diseases, pointing towards a significant shift in how we approach aging intervention strategies.Competing Interest {StatementThe} authors have declared no competing interest.},
	pages = {2024.04.25.591048},
	journaltitle = {{bioRxiv}},
	author = {Kodama, Hayata and Ijima, Hirotaka and Matsui, Yusuke},
	date = {2024-01-01},
}

@article{lopez-otin_hallmarks_2013-1,
	title = {The hallmarks of aging.},
	volume = {153},
	rights = {Copyright © 2013 Elsevier Inc. All rights reserved.},
	issn = {1097-4172 0092-8674},
	doi = {10.1016/j.cell.2013.05.039},
	abstract = {Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. This deterioration is  the primary risk factor for major human pathologies, including cancer, diabetes,  cardiovascular disorders, and neurodegenerative diseases. Aging research has  experienced an unprecedented advance over recent years, particularly with the  discovery that the rate of aging is controlled, at least to some extent, by  genetic pathways and biochemical processes conserved in evolution. This Review  enumerates nine tentative hallmarks that represent common denominators of aging  in different organisms, with special emphasis on mammalian aging. These hallmarks  are: genomic instability, telomere attrition, epigenetic alterations, loss of  proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular  senescence, stem cell exhaustion, and altered intercellular communication. A  major challenge is to dissect the interconnectedness between the candidate  hallmarks and their relative contributions to aging, with the final goal of  identifying pharmaceutical targets to improve human health during aging, with  minimal side effects.},
	pages = {1194--1217},
	number = {6},
	journaltitle = {Cell},
	shortjournal = {Cell},
	author = {López-Otín, Carlos and Blasco, Maria A. and Partridge, Linda and Serrano, Manuel and Kroemer, Guido},
	date = {2013-06-06},
	pmid = {23746838},
	pmcid = {PMC3836174},
	note = {Place: United States},
	keywords = {Humans, Animals, Epigenesis, Genetic, *Aging/genetics/metabolism/pathology, *Cellular Senescence, Genomic Instability, Telomere/genetics/metabolism},
}

@article{peterson_influence_2011,
	title = {Influence of resistance exercise on lean body mass in aging adults: a meta-analysis.},
	volume = {43},
	issn = {1530-0315 0195-9131},
	doi = {10.1249/MSS.0b013e3181eb6265},
	abstract = {{PURPOSE}: sarcopenia plays a principal role in the pathogenesis of frailty and functional impairment that occur with aging. There are few published accounts  that examine the overall benefit of resistance exercise ({RE}) for lean body mass  ({LBM}) while considering a continuum of dosage schemes and/or age ranges.  Therefore, the purpose of this meta-analysis was to determine the effects of {RE}  on {LBM} in older men and women while taking these factors into consideration.  {METHODS}: this study followed the Preferred Reporting Items for Systematic Reviews  and Meta-Analyses recommendations. Randomized controlled trials and randomized or  nonrandomized studies among adults ≥ 50 yr were included. Heterogeneity between  studies was assessed using the Cochran Q and the I statistics, and publication  bias was evaluated through physical inspection of funnel plots as well as formal  rank-correlation statistics. Mixed-effects meta-regression was incorporated to  assess the relationship between {RE} dosage and changes in {LBM}. {RESULTS}: data from  49 studies, representing a total of 1328 participants, were pooled using  random-effect models. Results demonstrated a positive effect for {LBM}, and there  was no evidence of publication bias. The Cochran Q statistic for heterogeneity  was 497.8, which was significant (P {\textless} 0.01). Likewise, I was equal to 84\%,  representing rejection of the null hypothesis of homogeneity. The weighted pooled  estimate of mean {LBM} change was 1.1 kg (95\% confidence interval = 0.9-1.2 kg).  Meta-regression revealed that higher-volume interventions were associated (β =  0.05, P {\textless} 0.01) with significantly greater increases in {LBM}, whereas older  individuals experienced less increase (β = -0.03, P = 0.01). {CONCLUSIONS}: {RE} is  effective for eliciting gains in {LBM} among aging adults, particularly with  higher-volume programs. Findings suggest that {RE} participation earlier in life  may provide superior effectiveness.},
	pages = {249--258},
	number = {2},
	journaltitle = {Medicine and science in sports and exercise},
	shortjournal = {Med Sci Sports Exerc},
	author = {Peterson, Mark D. and Sen, Ananda and Gordon, Paul M.},
	date = {2011-02},
	pmid = {20543750},
	pmcid = {PMC2995836},
	note = {Place: United States},
	keywords = {*Resistance Training, Female, Humans, Middle Aged, Aged, Male, Randomized Controlled Trials as Topic, Muscle, Skeletal/physiology, Muscle Strength/physiology, Aged, 80 and over, Body Composition/*physiology},
}

@article{kryger_resistance_2007,
	title = {Resistance training in the oldest old: consequences for muscle strength, fiber types, fiber size, and {MHC} isoforms.},
	volume = {17},
	issn = {0905-7188},
	doi = {10.1111/j.1600-0838.2006.00575.x},
	abstract = {Resistance training-related changes in muscle strength, muscle size, fiber type, and myosin heavy chain isoform composition in 11 elderly subjects (age range,  85-97 years) after 12 weeks of heavy resistance training (80\% of 1 {RM}) were  examined. Twelve subjects constituted a control group. Resistance training  increased isometric knee extensor strength 37\% (P{\textless}0.05) and isokinetic knee  strength 41-47\% (P{\textless}0.05). Lean-quadriceps cross-sectional area increased 9.8\%  (P{\textless}0.05). Muscle fiber hypertrophy occurred only in the type 2 fibers (22\%  (P{\textless}0.05)). Type 1 fiber-type area percentage decreased [4.0 \% (P{\textless}0.05)] whereas  fiber-type area percentage of type 2a fibers increased [5.9\% (P{\textless}0.05)]. The  relative amount of myosin heavy chain ({MHC}) I (P{\textless}0.05) decreased and the relative  amount of {MHC} {IIA} increased (P{\textless}0.05). No effects in the overall number of  capillaries per area was observed, but an increase in the number of capillary  contacts in the type 2 fiber pool was observed. Heavy resistance training does  have beneficial effects on muscle strength and muscle volume in very old frail  humans. Furthermore, an increase in fiber size of the fast muscle fibers and an  overall increase in the relative amount of fast {MHC} {IIA} can lead not only to a  stronger, but maybe more importantly, to a more powerful skeletal muscle.},
	pages = {422--430},
	number = {4},
	journaltitle = {Scandinavian journal of medicine \& science in sports},
	shortjournal = {Scand J Med Sci Sports},
	author = {Kryger, A. I. and Andersen, J. L.},
	date = {2007-08},
	pmid = {17490465},
	note = {Place: Denmark},
	keywords = {Female, Humans, Male, Aged, 80 and over, Denmark, Muscle Fibers, Skeletal/*physiology, Myosin Heavy Chains/*physiology, Protein Isoforms/*physiology, Weight Lifting/*physiology},
}

@article{lu_effects_2021,
	title = {Effects of different exercise training modes on muscle strength and physical performance in older people with sarcopenia: a systematic review and meta-analysis},
	volume = {21},
	issn = {1471-2318},
	pages = {708},
	number = {1},
	journaltitle = {{BMC} geriatrics},
	shortjournal = {{BMC} geriatrics},
	author = {Lu, Linqian and Mao, Lin and Feng, Yuwei and Ainsworth, Barbara E and Liu, Yu and Chen, Nan},
	date = {2021},
	note = {Publisher: Springer},
}

@article{ubaida-mohien_physical_2019,
	title = {Physical activity associated proteomics of skeletal muscle: being physically active in daily life may protect skeletal muscle from aging},
	volume = {10},
	issn = {1664-042X},
	pages = {312},
	journaltitle = {Frontiers in physiology},
	shortjournal = {Frontiers in physiology},
	author = {Ubaida-Mohien, Ceereena and Gonzalez-Freire, Marta and Lyashkov, Alexey and Moaddel, Ruin and Chia, Chee W and Simonsick, Eleanor M and Sen, Ranjan and Ferrucci, Luigi},
	date = {2019},
	note = {Publisher: Frontiers Media {SA}},
}

@article{latorre_splicing_2017,
	title = {Splicing regulatory factors, ageing and age-related disease},
	volume = {36},
	issn = {1568-1637},
	url = {https://www.sciencedirect.com/science/article/pii/S1568163717300624},
	doi = {10.1016/j.arr.2017.04.004},
	abstract = {Alternative splicing is a co-transcriptional process, which allows for the production of multiple transcripts from a single gene and is emerging as an important control point for gene expression. Alternatively expressed isoforms often have antagonistic function and differential temporal or spatial expression patterns, yielding enormous plasticity and adaptability to cells and increasing their ability to respond to environmental challenge. The regulation of alternative splicing is critical for numerous cellular functions in both pathological and physiological conditions, and deregulated alternative splicing is a key feature of common chronic diseases. Isoform choice is controlled by a battery of splicing regulatory proteins, which include the serine arginine rich ({SRSF}) proteins and the heterogeneous ribonucleoprotein ({hnRNP}) classes of genes. These important splicing regulators have been implicated in age-related disease, and in the ageing process itself. This review will outline the important contribution of splicing regulator proteins to ageing and age-related disease.},
	pages = {165--170},
	journaltitle = {Ageing Research Reviews},
	shortjournal = {Ageing Research Reviews},
	author = {Latorre, Eva and Harries, Lorna. W},
	date = {2017-07-01},
	keywords = {Cancer, Cardiovascular, Dementia, {hnRNPs}, Splicing, {SRSF}},
}

@article{holly_changes_2013,
	title = {Changes in splicing factor expression are associated with advancing age in man},
	volume = {134},
	issn = {0047-6374},
	pages = {356--366},
	number = {9},
	journaltitle = {Mechanisms of ageing and development},
	shortjournal = {Mechanisms of ageing and development},
	author = {Holly, Alice C and Melzer, David and Pilling, Luke C and Fellows, Alexander C and Tanaka, Toshiko and Ferrucci, Luigi and Harries, Lorna W},
	date = {2013},
	note = {Publisher: Elsevier},
}

@article{ubaida-mohien_discovery_2019,
	title = {Discovery proteomics in aging human skeletal muscle finds change in spliceosome, immunity, proteostasis and mitochondria},
	volume = {8},
	issn = {2050-084X},
	url = {https://doi.org/10.7554/eLife.49874},
	doi = {10.7554/eLife.49874},
	abstract = {A decline of skeletal muscle strength with aging is a primary cause of mobility loss and frailty in older persons, but the molecular mechanisms of such decline are not understood. Here, we performed quantitative proteomic analysis from skeletal muscle collected from 58 healthy persons aged 20 to 87 years. In muscle from older persons, ribosomal proteins and proteins related to energetic metabolism, including those related to the {TCA} cycle, mitochondria respiration, and glycolysis, were underrepresented, while proteins implicated in innate and adaptive immunity, proteostasis, and alternative splicing were overrepresented. Consistent with reports in animal models, older human muscle was characterized by deranged energetic metabolism, a pro-inflammatory environment and increased proteolysis. Changes in alternative splicing with aging were confirmed by {RNA}-seq analysis. We propose that changes in the splicing machinery enables muscle cells to respond to a rise in damage with aging.},
	pages = {e49874},
	journaltitle = {{eLife}},
	author = {Ubaida-Mohien, Ceereena and Lyashkov, Alexey and Gonzalez-Freire, Marta and Tharakan, Ravi and Shardell, Michelle and Moaddel, Ruin and Semba, Richard D and Chia, Chee W and Gorospe, Myriam and Sen, Ranjan and Ferrucci, Luigi},
	editor = {Kaeberlein, Matt and Rosen, Clifford J and Kaeberlein, Matt and Anderson, Rozalyn},
	date = {2019-10-23},
	note = {Publisher: {eLife} Sciences Publications, Ltd},
	keywords = {skeletal muscle, aging, mitochondria, proteomics, proteostasis, spliceosome},
}

@article{giresi_identification_2005,
	title = {Identification of a molecular signature of sarcopenia},
	volume = {21},
	issn = {1094-8341},
	pages = {253--263},
	number = {2},
	journaltitle = {Physiological genomics},
	shortjournal = {Physiological genomics},
	author = {Giresi, Paul G and Stevenson, Eric J and Theilhaber, Joachim and Koncarevic, Alan and Parkington, Jascha and Fielding, Roger A and Kandarian, Susan C},
	date = {2005},
	note = {Publisher: American Physiological Society},
}

@article{welle_gene_2003,
	title = {Gene expression profile of aging in human muscle},
	volume = {14},
	issn = {1094-8341},
	pages = {149--159},
	number = {2},
	journaltitle = {Physiological genomics},
	shortjournal = {Physiological genomics},
	author = {Welle, Stephen and Brooks, Andrew I and Delehanty, Joseph M and Needler, Nancy and Thornton, Charles A},
	date = {2003},
	note = {Publisher: American Physiological Society},
}

@article{ubaida-mohien_unbiased_2022,
	title = {Unbiased proteomics, histochemistry, and mitochondrial {DNA} copy number reveal better mitochondrial health in muscle of high-functioning octogenarians},
	volume = {11},
	issn = {2050-084X},
	url = {https://doi.org/10.7554/eLife.74335},
	doi = {10.7554/eLife.74335},
	abstract = {Background:. Master athletes ({MAs}) prove that preserving a high level of physical function up to very late in life is possible, but the mechanisms responsible for their high function remain unclear. Methods:. We performed muscle biopsies in 15 octogenarian world-class track and field {MAs} and 14 non-athlete age/sex-matched controls ({NA}) to provide insights into mechanisms for preserving function in advanced age. Muscle samples were assessed for respiratory compromised fibers, mitochondrial {DNA} ({mtDNA}) copy number, and proteomics by liquid-chromatography mass spectrometry. Results:. {MA} exhibited markedly better performance on clinical function tests and greater cross-sectional area of the vastus lateralis muscle. Proteomics analysis revealed marked differences, where most of the {\textasciitilde}800 differentially represented proteins in {MA} versus {NA} pertained to mitochondria structure/function such as electron transport capacity ({ETC}), cristae formation, mitochondrial biogenesis, and {mtDNA}-encoded proteins. In contrast, proteins from the spliceosome complex and nuclear pore were downregulated in {MA}. Consistent with proteomics data, {MA} had fewer respiratory compromised fibers, higher {mtDNA} copy number, and an increased protein ratio of the cristae-bound {ETC} subunits relative to the outer mitochondrial membrane protein voltage-dependent anion channel. There was a substantial overlap of proteins overrepresented in {MA} versus {NA} with proteins that decline with aging and that are higher in physically active than sedentary individuals. However, we also found 176 proteins related to mitochondria that are uniquely differentially expressed in {MA}. Conclusions:. We conclude that high function in advanced age is associated with preserving mitochondrial structure/function proteins, with underrepresentation of proteins involved in the spliceosome and nuclear pore complex. Whereas many of these differences in {MA} appear related to their physical activity habits, others may reflect unique biological (e.g., gene, environment) mechanisms that preserve muscle integrity and function with aging. Funding:. Funding for this study was provided by operating grants from the Canadian Institutes of Health Research ({MOP} 84408 to {TT} and {MOP} 125986 to {RTH}). This work was supported in part by the Intramural Research Program of the National Institute on Aging, {NIH}, Baltimore, {MD}, {USA}.},
	pages = {e74335},
	journaltitle = {{eLife}},
	author = {Ubaida-Mohien, Ceereena and Spendiff, Sally and Lyashkov, Alexey and Moaddel, Ruin and {MacMillan}, Norah J and Filion, Marie-Eve and Morais, Jose A and Taivassalo, Tanja and Ferrucci, Luigi and Hepple, Russell T},
	editor = {Grano, Maria and Isales, Carlos and Piasecki, Mathew and Degens, Hans},
	date = {2022-04-11},
	note = {Publisher: {eLife} Sciences Publications, Ltd},
	keywords = {exercise, skeletal muscle, mitochondria, proteomics, frailty, Master Athletes, physical activity},
}

@article{ferrucci_energysplicing_2022,
	title = {The energy–splicing resilience axis hypothesis of aging},
	volume = {2},
	issn = {2662-8465},
	url = {https://doi.org/10.1038/s43587-022-00189-w},
	doi = {10.1038/s43587-022-00189-w},
	abstract = {Aging can be conceptualized as the stochastic accumulation of damage and loss of resilience leading to organism demise. Resilience mechanisms that repair, recycle or replace damaged molecules and organelles are energy-demanding, therefore energy availability is essential to healthy aging. We propose that changes in mitochondrial and energy status regulate {RNA} splicing and that splicing is a resilience strategy that preserves energetic homeostasis with aging.},
	pages = {182--185},
	number = {3},
	journaltitle = {Nature Aging},
	shortjournal = {Nature Aging},
	author = {Ferrucci, Luigi and Wilson, David M. and Donegà, Stefano and Gorospe, Myriam},
	date = {2022-03-01},
}

@article{bhadra_alternative_2020,
	title = {Alternative splicing in aging and longevity},
	volume = {139},
	issn = {0340-6717},
	pages = {357--369},
	journaltitle = {Human genetics},
	shortjournal = {Human genetics},
	author = {Bhadra, Malini and Howell, Porsha and Dutta, Sneha and Heintz, Caroline and Mair, William B},
	date = {2020},
	note = {Publisher: Springer},
}

@article{saudemont_fitness_2017,
	title = {The fitness cost of mis-splicing is the main determinant of alternative splicing patterns},
	volume = {18},
	pages = {1--15},
	journaltitle = {Genome biology},
	shortjournal = {Genome biology},
	author = {Saudemont, Baptiste and Popa, Alexandra and Parmley, Joanna L and Rocher, Vincent and Blugeon, Corinne and Necsulea, Anamaria and Meyer, Eric and Duret, Laurent},
	date = {2017},
	note = {Publisher: Springer},
}

@article{veeneman_two-pass_2016,
	title = {Two-pass alignment improves novel splice junction quantification.},
	volume = {32},
	rights = {© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.},
	issn = {1367-4811 1367-4803},
	doi = {10.1093/bioinformatics/btv642},
	abstract = {{MOTIVATION}: Discovery of novel splicing from {RNA} sequence data remains a critical and exciting focus of transcriptomics, but reduced alignment power impedes  expression quantification of novel splice junctions. {RESULTS}: Here, we profile  performance characteristics of two-pass alignment, which separates splice  junction discovery from quantification. Per sample, across a variety of  transcriptome sequencing datasets, two-pass alignment improved quantification of  at least 94\% of simulated novel splice junctions, and provided as much as  1.7-fold deeper median read depth over those splice junctions. We further  demonstrate that two-pass alignment works by increasing alignment of reads to  splice junctions by short lengths, and that potential alignment errors are  readily identifiable by simple classification. Taken together, two-pass alignment  promises to advance quantification and discovery of novel splicing events.  {CONTACT}: arul@med.umich.edu, nesvi@med.umich.edu {AVAILABILITY} {AND} {IMPLEMENTATION}:  Two-pass alignment was implemented here as sequential alignment, genome indexing,  and re-alignment steps with {STAR}. Full parameters are provided in Supplementary  Table 2. {SUPPLEMENTARY} {INFORMATION}: Supplementary data are available at  Bioinformatics online.},
	pages = {43--49},
	number = {1},
	journaltitle = {Bioinformatics (Oxford, England)},
	shortjournal = {Bioinformatics},
	author = {Veeneman, Brendan A. and Shukla, Sudhanshu and Dhanasekaran, Saravana M. and Chinnaiyan, Arul M. and Nesvizhskii, Alexey I.},
	date = {2016-01-01},
	pmid = {26519505},
	pmcid = {PMC5006238},
	note = {Place: England},
	keywords = {Humans, Databases, Nucleic Acid, Cell Line, Tumor, Base Sequence, {RNA} Splice Sites/*genetics, {RNA} Splicing/*genetics, Sequence Alignment/*methods},
}

@article{wingett_fastq_2018,
	title = {{FastQ} Screen: A tool for multi-genome mapping and quality control.},
	volume = {7},
	issn = {2046-1402},
	doi = {10.12688/f1000research.15931.2},
	abstract = {{DNA} sequencing analysis typically involves mapping reads to just one reference genome. Mapping against multiple genomes is necessary, however, when the genome  of origin requires confirmation. Mapping against multiple genomes is also  advisable for detecting contamination or for identifying sample swaps which, if  left undetected, may lead to incorrect experimental conclusions. Consequently, we  present {FastQ} Screen, a tool to validate the origin of {DNA} samples by quantifying  the proportion of reads that map to a panel of reference genomes. {FastQ} Screen is  intended to be used routinely as a quality control measure and for analysing  samples in which the origin of the {DNA} is uncertain or has multiple sources.},
	pages = {1338},
	journaltitle = {F1000Research},
	shortjournal = {F1000Res},
	author = {Wingett, Steven W. and Andrews, Simon},
	date = {2018},
	pmid = {30254741},
	pmcid = {PMC6124377},
	note = {Place: England},
	keywords = {*Software, *High-Throughput Nucleotide Sequencing, Bioinformatics Contamination {FastQC} Illumina Metagenomics {NGS} {QC} Sequencing, Chromosome Mapping, Genome, Quality Control, Sequence Analysis, {DNA}},
}

@misc{noauthor_fastqc_2015,
	title = {{FastQC}},
	url = {https://qubeshub.org/resources/fastqc},
	date = {2015-06},
}

@article{mattick_long_2023,
	title = {Long non-coding {RNAs}: definitions, functions, challenges and recommendations},
	volume = {24},
	issn = {1471-0080},
	url = {https://doi.org/10.1038/s41580-022-00566-8},
	doi = {10.1038/s41580-022-00566-8},
	abstract = {Genes specifying long non-coding {RNAs} ({lncRNAs}) occupy a large fraction of the genomes of complex organisms. The term ‘{lncRNAs}’ encompasses {RNA} polymerase I (Pol I), Pol {II} and Pol {III} transcribed {RNAs}, and {RNAs} from processed introns. The various functions of {lncRNAs} and their many isoforms and interleaved relationships with other genes make {lncRNA} classification and annotation difficult. Most {lncRNAs} evolve more rapidly than protein-coding sequences, are cell type specific and regulate many aspects of cell differentiation and development and other physiological processes. Many {lncRNAs} associate with chromatin-modifying complexes, are transcribed from enhancers and nucleate phase separation of nuclear condensates and domains, indicating an intimate link between {lncRNA} expression and the spatial control of gene expression during development. {lncRNAs} also have important roles in the cytoplasm and beyond, including in the regulation of translation, metabolism and signalling. {lncRNAs} often have a modular structure and are rich in repeats, which are increasingly being shown to be relevant to their function. In this Consensus Statement, we address the definition and nomenclature of {lncRNAs} and their conservation, expression, phenotypic visibility, structure and functions. We also discuss research challenges and provide recommendations to advance the understanding of the roles of {lncRNAs} in development, cell biology and disease.},
	pages = {430--447},
	number = {6},
	journaltitle = {Nature Reviews Molecular Cell Biology},
	shortjournal = {Nature Reviews Molecular Cell Biology},
	author = {Mattick, John S. and Amaral, Paulo P. and Carninci, Piero and Carpenter, Susan and Chang, Howard Y. and Chen, Ling-Ling and Chen, Runsheng and Dean, Caroline and Dinger, Marcel E. and Fitzgerald, Katherine A. and Gingeras, Thomas R. and Guttman, Mitchell and Hirose, Tetsuro and Huarte, Maite and Johnson, Rory and Kanduri, Chandrasekhar and Kapranov, Philipp and Lawrence, Jeanne B. and Lee, Jeannie T. and Mendell, Joshua T. and Mercer, Timothy R. and Moore, Kathryn J. and Nakagawa, Shinichi and Rinn, John L. and Spector, David L. and Ulitsky, Igor and Wan, Yue and Wilusz, Jeremy E. and Wu, Mian},
	date = {2023-06-01},
}

@article{ahtiainen_heterogeneity_2016,
	title = {Heterogeneity in resistance training-induced muscle strength and mass responses in men and women of different ages.},
	volume = {38},
	issn = {1574-4647 0161-9152},
	doi = {10.1007/s11357-015-9870-1},
	abstract = {Physical activity recommendations for public health include typically muscle-strengthening activities for a minimum of 2 days a week. The range of  inter-individual variation in responses to resistance training ({RT}) aiming to  improve health and well-being requires to be investigated. The purpose of this  study was to quantify high and low responders for {RT}-induced changes in muscle  size and strength and to examine possible effects of age and sex on these  responses. Previously collected data of untrained healthy men and women (age 19  to 78 years, n = 287 with 72 controls) were pooled for the present study. Muscle  size and strength changed during {RT} are 4.8 ± 6.1 \% (range from -11 to 30 \%) and  21.1 ± 11.5 \% (range from -8 to 60 \%) compared to pre-{RT}, respectively. Age and  sex did not affect to the {RT} responses. Fourteen percent and 12 \% of the subjects  were defined as high responders ({\textgreater}1 standard deviation ({SD}) from the group mean)  for the {RT}-induced changes in muscle size and strength, respectively. When taking  into account the results of non-training controls (upper 95 \% {CI}), 29 and 7 \% of  the subjects were defined as low responders for the {RT}-induced changes in muscle  size and strength, respectively. The muscle size and strength responses varied  extensively between the subjects regardless of subject's age and sex. Whether  these changes are associated with, e.g., functional capacity and metabolic health  improvements due to {RT} requires further studies.},
	pages = {10},
	number = {1},
	journaltitle = {Age (Dordrecht, Netherlands)},
	shortjournal = {Age (Dordr)},
	author = {Ahtiainen, Juha P. and Walker, Simon and Peltonen, Heikki and Holviala, Jarkko and Sillanpää, Elina and Karavirta, Laura and Sallinen, Janne and Mikkola, Jussi and Valkeinen, Heli and Mero, Antti and Hulmi, Juha J. and Häkkinen, Keijo},
	date = {2016-02},
	pmid = {26767377},
	pmcid = {PMC5005877},
	note = {Place: Netherlands},
	keywords = {Female, Humans, Middle Aged, Adult, Muscle Strength/*physiology, Resistance Training/*methods, Young Adult, Aged, Male, Aging/*physiology, Time Factors, Aging, Muscle, Skeletal/*physiology, Retrospective Studies, Follow-Up Studies, Healthy Volunteers, Individual variation, Muscle hypertrophy, Responders},
}

@article{ekelund_dose-response_2019,
	title = {Dose-response associations between accelerometry measured physical activity and sedentary time and all cause mortality: systematic review and harmonised  meta-analysis.},
	volume = {366},
	rights = {Published by the {BMJ} Publishing Group Limited. For permission to use (where not already granted under a licence) please go to  http://group.bmj.com/group/rights-licensing/permissions.},
	issn = {1756-1833 0959-8138},
	doi = {10.1136/bmj.l4570},
	abstract = {{OBJECTIVE}: To examine the dose-response associations between accelerometer assessed total physical activity, different intensities of physical activity, and  sedentary time and all cause mortality. {DESIGN}: Systematic review and harmonised  meta-analysis. {DATA} {SOURCES}: {PubMed}, {PsycINFO}, Embase, Web of Science, Sport  Discus from inception to 31 July 2018. {ELIGIBILITY} {CRITERIA}: Prospective cohort  studies assessing physical activity and sedentary time by accelerometry and  associations with all cause mortality and reported effect estimates as hazard  ratios, odds ratios, or relative risks with 95\% confidence intervals. {DATA}  {EXTRACTION} {AND} {ANALYSIS}: Guidelines for meta-analyses and systematic reviews for  observational studies and {PRISMA} guidelines were followed. Two authors  independently screened the titles and abstracts. One author performed a full text  review and another extracted the data. Two authors independently assessed the  risk of bias. Individual level participant data were harmonised and analysed at  study level. Data on physical activity were categorised by quarters at study  level, and study specific associations with all cause mortality were analysed  using Cox proportional hazards regression analyses. Study specific results were  summarised using random effects meta-analysis. {MAIN} {OUTCOME} {MEASURE}: All cause  mortality. {RESULTS}: 39 studies were retrieved for full text review; 10 were  eligible for inclusion, three were excluded owing to harmonisation challenges  (eg, wrist placement of the accelerometer), and one study did not participate.  Two additional studies with unpublished mortality data were also included. Thus,  individual level data from eight studies (n=36 383; mean age 62.6 years; 72.8\%  women), with median follow-up of 5.8 years (range 3.0-14.5 years) and 2149 (5.9\%)  deaths were analysed. Any physical activity, regardless of intensity, was  associated with lower risk of mortality, with a non-linear dose-response. Hazards  ratios for mortality were 1.00 (referent) in the first quarter (least active),  0.48 (95\% confidence interval 0.43 to 0.54) in the second quarter, 0.34 (0.26 to  0.45) in the third quarter, and 0.27 (0.23 to 0.32) in the fourth quarter (most  active). Corresponding hazards ratios for light physical activity were 1.00, 0.60  (0.54 to 0.68), 0.44 (0.38 to 0.51), and 0.38 (0.28 to 0.51), and for  moderate-to-vigorous physical activity were 1.00, 0.64 (0.55 to 0.74), 0.55 (0.40  to 0.74), and 0.52 (0.43 to 0.61). For sedentary time, hazards ratios were 1.00  (referent; least sedentary), 1.28 (1.09 to 1.51), 1.71 (1.36 to 2.15), and 2.63  (1.94 to 3.56). {CONCLUSION}: Higher levels of total physical activity, at any  intensity, and less time spent sedentary, are associated with substantially  reduced risk for premature mortality, with evidence of a non-linear dose-response  pattern in middle aged and older adults. {SYSTEMATIC} {REVIEW} {REGISTRATION}: {PROSPERO}  {CRD}42018091808.},
	pages = {l4570},
	journaltitle = {{BMJ} (Clinical research ed.)},
	shortjournal = {{BMJ}},
	author = {Ekelund, Ulf and Tarp, Jakob and Steene-Johannessen, Jostein and Hansen, Bjørge H. and Jefferis, Barbara and Fagerland, Morten W. and Whincup, Peter and Diaz, Keith M. and Hooker, Steven P. and Chernofsky, Ariel and Larson, Martin G. and Spartano, Nicole and Vasan, Ramachandran S. and Dohrn, Ing-Mari and Hagströmer, Maria and Edwardson, Charlotte and Yates, Thomas and Shiroma, Eric and Anderssen, Sigmund A. and Lee, I.-Min},
	date = {2019-08-21},
	pmid = {31434697},
	pmcid = {PMC6699591},
	note = {Place: England},
	keywords = {Female, Humans, Middle Aged, Aged, Male, *Exercise, Risk Factors, *Sedentary Behavior, Accelerometry/*statistics \& numerical data, Mortality/*trends, Proportional Hazards Models, Prospective Studies},
}

@article{weidlich_addressing_2024,
	title = {Addressing muscle–tendon imbalances in adult male athletes with personalized exercise prescription based on tendon strain},
	volume = {124},
	issn = {1439-6327},
	url = {https://doi.org/10.1007/s00421-024-05525-z},
	doi = {10.1007/s00421-024-05525-z},
	abstract = {Imbalances of muscle strength and tendon stiffness can increase the operating strain of tendons and risk of injury. Here, we used a new approach to identify muscle–tendon imbalances and personalize exercise prescription based on tendon strain during maximum voluntary contractions (εmax) to mitigate musculotendinous imbalances in male adult volleyball athletes.},
	pages = {3201--3214},
	number = {11},
	journaltitle = {European Journal of Applied Physiology},
	shortjournal = {European Journal of Applied Physiology},
	author = {Weidlich, Kolja and Domroes, Theresa and Bohm, Sebastian and Arampatzis, Adamantios and Mersmann, Falk},
	date = {2024-11-01},
}

@article{smart_role_2022,
	title = {The role of resistance exercise training for improving cardiorespiratory fitness in healthy older adults: a systematic review and meta-analysis},
	volume = {51},
	issn = {1468-2834},
	url = {https://doi.org/10.1093/ageing/afac143},
	doi = {10.1093/ageing/afac143},
	abstract = {Declines in cardiorespiratory fitness ({CRF}) and muscle mass are both associated with advancing age and each of these declines is associated with worse health outcomes. Resistance exercise training ({RET}) has previously been shown to improve muscle mass and function in the older population. If {RET} is also able to improve {CRF}, as it has been shown to do in younger populations, it has the potential to improve multiple health outcomes in the expanding older population.This systematic review aimed to identify the role of {RET} for improving {CRF} in healthy older adults. A search across {CINAHL}, {MEDLINE}, {EMBASE} and {EMCARE} databases was conducted with meta-analysis performed on eligible papers to identify improvements in established {CRF} parameters ({VO}2 peak, aerobic threshold ({AT}), 6-minute walking distance test (6MWT) following {RET} intervention. Main eligibility criteria included older adults (aged over 60), healthy cohorts (disease-specific cohorts were excluded) and {RET} intervention.Thirty-seven eligible studies were identified. Meta-analysis revealed a significant improvement in {VO}2 peak ({MD} 1.89 ml/kg/min; 95\% confidence interval ({CI}) 1.21–2.57 ml/kg/min), {AT} ({MD} 1.27 ml/kg/min; 95\% {CI} 0.44–2.09 ml/kg/min) and 6MWT ({MD} 30.89; 95\% {CI} 26.7–35.08) in {RET} interventions less than 24 weeks. There was no difference in {VO}2 peak or 6MWT in interventions longer than 24 weeks.This systematic review adds to a growing body of evidence supporting the implementation of {RET} in the older population for improving whole-body health, particularly in time-limited timeframes.},
	pages = {afac143},
	number = {6},
	journaltitle = {Age and Ageing},
	shortjournal = {Age and Ageing},
	author = {Smart, Thomas F F and Doleman, Brett and Hatt, Jacob and Paul, Melanie and Toft, Suzanne and Lund, Jonathan N and Phillips, Bethan E},
	urldate = {2024-12-22},
	date = {2022-06-01},
}

@article{zhao_how_2020,
	title = {How to do quantile normalization correctly for gene expression data analyses},
	volume = {10},
	issn = {2045-2322},
	url = {https://doi.org/10.1038/s41598-020-72664-6},
	doi = {10.1038/s41598-020-72664-6},
	abstract = {Quantile normalization is an important normalization technique commonly used in high-dimensional data analysis. However, it is susceptible to class-effect proportion effects (the proportion of class-correlated variables in a dataset) and batch effects (the presence of potentially confounding technical variation) when applied blindly on whole data sets, resulting in higher false-positive and false-negative rates. We evaluate five strategies for performing quantile normalization, and demonstrate that good performance in terms of batch-effect correction and statistical feature selection can be readily achieved by first splitting data by sample class-labels before performing quantile normalization independently on each split (“Class-specific”). Via simulations with both real and simulated batch effects, we demonstrate that the “Class-specific” strategy (and others relying on similar principles) readily outperform whole-data quantile normalization, and is robust-preserving useful signals even during the combined analysis of separately-normalized datasets. Quantile normalization is a commonly used procedure. But when carelessly applied on whole datasets without first considering class-effect proportion and batch effects, can result in poor performance. If quantile normalization must be used, then we recommend using the “Class-specific” strategy.},
	pages = {15534},
	number = {1},
	journaltitle = {Scientific Reports},
	shortjournal = {Scientific Reports},
	author = {Zhao, Yaxing and Wong, Limsoon and Goh, Wilson Wen Bin},
	date = {2020-09-23},
}

@article{zhang_noisy_2009,
	title = {Noisy splicing, more than expression regulation, explains why some exons are subject to nonsense-mediated {mRNA} decay},
	volume = {7},
	issn = {1741-7007},
	url = {https://doi.org/10.1186/1741-7007-7-23},
	doi = {10.1186/1741-7007-7-23},
	abstract = {Nonsense-mediated decay is a mechanism that degrades {mRNAs} with a premature termination codon. That some exons have premature termination codons at fixation is paradoxical: why make a transcript if it is only to be destroyed? One model supposes that splicing is inherently noisy and spurious transcripts are common. The evolution of a premature termination codon in a regularly made unwanted transcript can be a means to prevent costly translation. Alternatively, nonsense-mediated decay can be regulated under certain conditions so the presence of a premature termination codon can be a means to up-regulate transcripts needed when nonsense-mediated decay is suppressed.},
	pages = {23},
	number = {1},
	journaltitle = {{BMC} Biology},
	shortjournal = {{BMC} Biology},
	author = {Zhang, Zhenguo and Xin, Dedong and Wang, Ping and Zhou, Li and Hu, Landian and Kong, Xiangyin and Hurst, Laurence D.},
	date = {2009-05-14},
}

@article{garatachea_exercise_2015,
	title = {Exercise attenuates the major hallmarks of aging},
	volume = {18},
	issn = {1549-1684},
	pages = {57--89},
	number = {1},
	journaltitle = {Rejuvenation research},
	shortjournal = {Rejuvenation research},
	author = {Garatachea, Nuria and Pareja-Galeano, Helios and Sanchis-Gomar, Fabian and Santos-Lozano, Alejandro and Fiuza-Luces, Carmen and Morán, María and Emanuele, Enzo and Joyner, Michael J and Lucia, Alejandro},
	date = {2015},
	note = {Publisher: Mary Ann Liebert, Inc. 140 Huguenot Street, 3rd Floor New Rochelle, {NY} 10801 {USA}},
}

@article{jung_intron_2015,
	title = {Intron retention is a widespread mechanism of tumor-suppressor inactivation},
	volume = {47},
	issn = {1546-1718},
	url = {https://doi.org/10.1038/ng.3414},
	doi = {10.1038/ng.3414},
	abstract = {Eunjung Lee, Peter Park, Dongwan Hong and colleagues report an analysis of cancer {RNA} sequencing data identifying approximately 900 somatic coding variants that cause disrupted splicing in cancer, leading to intron retention or exon skipping in many cases. Variants causing intron retention are enriched for loss-of-function mutations in tumor-suppressor genes.},
	pages = {1242--1248},
	number = {11},
	journaltitle = {Nature Genetics},
	shortjournal = {Nature Genetics},
	author = {Jung, Hyunchul and Lee, Donghoon and Lee, Jongkeun and Park, Donghyun and Kim, Yeon Jeong and Park, Woong-Yang and Hong, Dongwan and Park, Peter J and Lee, Eunjung},
	date = {2015-11-01},
}

@article{jacob_intron_2017,
	title = {Intron retention as a component of regulated gene expression programs},
	volume = {136},
	issn = {1432-1203},
	url = {https://doi.org/10.1007/s00439-017-1791-x},
	doi = {10.1007/s00439-017-1791-x},
	abstract = {Intron retention has long been an exemplar of regulated splicing with case studies of individual events serving as models that provided key mechanistic insights into the process of splicing control. In organisms such as plants and budding yeast, intron retention is well understood as a major mechanism of gene expression regulation. In contrast, in mammalian systems, the extent and functional significance of intron retention have, until recently, remained greatly underappreciated. Technical challenges to the global detection and quantitation of transcripts with retained introns have often led to intron retention being overlooked or dismissed as “noise”. Now, however, with the wealth of information available from high-throughput deep sequencing, combined with focused computational and statistical analyses, we are able to distinguish clear intron retention patterns in various physiological and pathological contexts. Several recent studies have demonstrated intron retention as a central component of gene expression programs during normal development as well as in response to stress and disease. Furthermore, these studies revealed various ways in which intron retention regulates protein isoform production, {RNA} stability and translation efficiency, and rapid induction of expression via post-transcriptional splicing of retained introns. In this review, we highlight critical findings from these transcriptomic studies and discuss commonalties in the patterns prevalent in intron retention networks at the functional and regulatory levels.},
	pages = {1043--1057},
	number = {9},
	journaltitle = {Human Genetics},
	shortjournal = {Human Genetics},
	author = {Jacob, Aishwarya G. and Smith, Christopher W. J.},
	date = {2017-09-01},
}

@online{lian_relief_2021,
	title = {{ReLiEf}: Resistance training for life– the efficacy of increasing resistance training volume for improving muscle functions, biology and health in young and elderly ({ReLiEf})},
	url = {https://www.inn.no/english/research/research-projects/relief/},
	author = {Lian, Kristian and Ellefsen, Stian},
	date = {2021},
}

@software{manual_orghsegdb_nodate,
	title = {org.Hs.eg.db: Genome wide annotation for Human},
	version = {3.19.1},
	author = {Manual, Carlson},
}

@article{dobin_star_2013,
	title = {{STAR}: ultrafast universal {RNA}-seq aligner.},
	volume = {29},
	issn = {1367-4811 1367-4803},
	doi = {10.1093/bioinformatics/bts635},
	abstract = {{MOTIVATION}: Accurate alignment of high-throughput {RNA}-seq data is a challenging and yet unsolved problem because of the non-contiguous transcript structure,  relatively short read lengths and constantly increasing throughput of the  sequencing technologies. Currently available {RNA}-seq aligners suffer from high  mapping error rates, low mapping speed, read length limitation and mapping  biases. {RESULTS}: To align our large ({\textgreater}80 billon reads) {ENCODE} Transcriptome  {RNA}-seq dataset, we developed the Spliced Transcripts Alignment to a Reference  ({STAR}) software based on a previously undescribed {RNA}-seq alignment algorithm  that uses sequential maximum mappable seed search in uncompressed suffix arrays  followed by seed clustering and stitching procedure. {STAR} outperforms other  aligners by a factor of {\textgreater}50 in mapping speed, aligning to the human genome 550  million 2 × 76 bp paired-end reads per hour on a modest 12-core server, while at  the same time improving alignment sensitivity and precision. In addition to  unbiased de novo detection of canonical junctions, {STAR} can discover  non-canonical splices and chimeric (fusion) transcripts, and is also capable of  mapping full-length {RNA} sequences. Using Roche 454 sequencing of reverse  transcription polymerase chain reaction amplicons, we experimentally validated  1960 novel intergenic splice junctions with an 80-90\% success rate, corroborating  the high precision of the {STAR} mapping strategy. {AVAILABILITY} {AND} {IMPLEMENTATION}:  {STAR} is implemented as a standalone C++ code. {STAR} is free open source software  distributed under {GPLv}3 license and can be downloaded from  http://code.google.com/p/rna-star/.},
	pages = {15--21},
	number = {1},
	journaltitle = {Bioinformatics (Oxford, England)},
	shortjournal = {Bioinformatics},
	author = {Dobin, Alexander and Davis, Carrie A. and Schlesinger, Felix and Drenkow, Jorg and Zaleski, Chris and Jha, Sonali and Batut, Philippe and Chaisson, Mark and Gingeras, Thomas R.},
	date = {2013-01-01},
	pmid = {23104886},
	pmcid = {PMC3530905},
	note = {Place: England},
	keywords = {Humans, Cluster Analysis, Gene Expression Profiling, Genome, Human, *Software, Sequence Alignment/*methods, Algorithms, {RNA} Splicing, Sequence Analysis, {RNA}/methods},
}

@article{garcia-ruiz_splicing_2025,
	title = {Splicing accuracy varies across human introns, tissues, age and disease},
	volume = {16},
	issn = {2041-1723},
	url = {https://doi.org/10.1038/s41467-024-55607-x},
	doi = {10.1038/s41467-024-55607-x},
	abstract = {Alternative splicing impacts most multi-exonic human genes. Inaccuracies during this process may have an important role in ageing and disease. Here, we investigate splicing accuracy using {RNA}-sequencing data from {\textgreater}14k control samples and 40 human body sites, focusing on split reads partially mapping to known transcripts in annotation. We show that splicing inaccuracies occur at different rates across introns and tissues and are affected by the abundance of core components of the spliceosome assembly and its regulators. We find that age is positively correlated with a global decline in splicing fidelity, mostly affecting genes implicated in neurodegenerative diseases. We find support for the latter by observing a genome-wide increase in splicing inaccuracies in samples affected with Alzheimer’s disease as compared to neurologically normal individuals. In this work, we provide an in-depth characterisation of splicing accuracy, with implications for our understanding of the role of inaccuracies in ageing and neurodegenerative disorders.},
	pages = {1068},
	number = {1},
	journaltitle = {Nature Communications},
	shortjournal = {Nature Communications},
	author = {García-Ruiz, S. and Zhang, D. and Gustavsson, E. K. and Rocamora-Perez, G. and Grant-Peters, M. and Fairbrother-Browne, A. and Reynolds, R. H. and Brenton, J. W. and Gil-Martínez, A. L. and Chen, Z. and Rio, D. C. and Botia, J. A. and Guelfi, S. and Collado-Torres, L. and Ryten, M.},
	date = {2025-01-27},
}

@article{hogenbirk_thickness_2022,
	title = {Thickness of Biceps and Quadriceps Femoris Muscle Measured Using Point-of-Care Ultrasound as a Representation of Total Skeletal Muscle Mass.},
	volume = {11},
	issn = {2077-0383},
	doi = {10.3390/jcm11226606},
	abstract = {Generalized loss of muscle mass is associated with increased morbidity and mortality in patients with cancer. The gold standard to measure muscle mass is by  using computed tomography ({CT}). However, the aim of this prospective  observational cohort study was to determine whether point-of-care ultrasound  ({POCUS}) could be an easy-to-use, bedside measurement alternative to evaluate  muscle status. Patients scheduled for major abdominal cancer surgery with a  recent preoperative {CT} scan available were included. {POCUS} was used to measure  the muscle thickness of mm. biceps brachii, mm. recti femoris, and mm. vasti  intermedius 1 day prior to surgery. The total skeletal muscle index ({SMI}) was  derived from patients’ abdominal {CT} scan at the third lumbar level. Muscle force  of the upper and lower extremities was measured using a handheld dynamometer. A  total of 165 patients were included (55\% male; 65 ± 12 years). All {POCUS}  measurements of muscle thickness had a statistically significant correlation with  {CT}-derived {SMI} (r ≥ 0.48; p {\textless} 0.001). The strongest correlation between {POCUS}  muscle measurements and {SMI} was observed when all {POCUS} muscle groups were added  together (r = 0.73; p {\textless} 0.001). Muscle strength had a stronger correlation with  {POCUS}-measured muscle thickness than with {CT}-derived {SMI}. To conclude, this study  indicated a strong correlation between combined muscle thickness measurements  performed by {POCUS}- and {CT}-derived {SMI} and measurements of muscle strength. These  results suggest that handheld ultrasound is a valid tool for the assessment of  skeletal muscle status.},
	number = {22},
	journaltitle = {Journal of clinical medicine},
	shortjournal = {J Clin Med},
	author = {Hogenbirk, Rianne N. M. and Viddeleer, Alain R. and Hentzen, Judith E. K. R. and van der Plas, Willemijn Y. and van der Schans, Cees P. and de Bock, Geertruida H. and Kruijff, Schelto and Klaase, Joost M.},
	date = {2022-11-08},
	pmid = {36431082},
	pmcid = {PMC9695176},
	note = {Place: Switzerland},
	keywords = {sarcopenia, muscle force, muscle status, {POCUS}, skeletal muscle index},
}

@article{wang_targeting_2022,
	title = {Targeting the splicing factor {NONO} inhibits {GBM} progression through {GPX}1 intron retention},
	volume = {12},
	issn = {1838-7640},
	url = {https://www.thno.org/v12p5451.htm},
	doi = {10.7150/thno.72248},
	pages = {5451--5469},
	number = {12},
	journaltitle = {Theranostics},
	shortjournal = {Theranostics},
	author = {Wang, Xu and Han, Mingzhi and Wang, Shuai and Sun, Yanfei and Zhao, Wenbo and Xue, Zhiyi and Liang, Xiangjun and Huang, Bin and Li, Gang and Chen, Anjing and Li, Xingang and Wang, Jian},
	date = {2022},
	note = {Publisher: Ivyspring International Publisher},
}

@article{naro_splicing_2024,
	title = {Splicing targeting drugs highlight intron retention as an actionable vulnerability in advanced prostate cancer.},
	volume = {43},
	rights = {© 2024. The Author(s).},
	issn = {1756-9966 0392-9078},
	doi = {10.1186/s13046-024-02986-0},
	abstract = {{BACKGROUND}: Advanced prostate cancer ({PC}) is characterized by insensitivity to androgen deprivation therapy and chemotherapy, resulting in poor outcome for most  patients. Thus, advanced {PC} urgently needs novel therapeutic strategies. Mounting  evidence points to splicing dysregulation as a hallmark of advanced {PC}. Moreover,  pharmacologic inhibition of the splicing process is emerging as a promising  option for this disease. {METHOD}: By using a representative androgen-insensitive  {PC} cell line (22Rv1), we have investigated the genome-wide transcriptomic effects  underlying the cytotoxic effects exerted by three splicing-targeting drugs:  Pladienolide B, indisulam and {THZ}531. Bioinformatic analyses were performed to  uncover the gene structural features underlying sensitivity to transcriptional  and splicing regulation by these treatments. Biological pathways altered by these  treatments were annotated by gene ontology analyses and validated by functional  experiments in cell models. {RESULTS}: Although eliciting similar cytotoxic effects  on advanced {PC} cells, Pladienolide B, indisulam and {THZ}531 modulate specific  transcriptional and splicing signatures. Drug sensitivity is associated with  distinct gene structural features, expression levels and cis-acting sequence  elements in the regulated exons and introns. Importantly, we identified  {PC}-relevant genes (i.e. {EZH}2, {MDM}4) whose drug-induced splicing alteration exerts  an impact on cell survival. Moreover, computational analyses uncovered a  widespread impact of splicing-targeting drugs on intron retention, with  enrichment in genes implicated in pre-{mRNA} 3'-end processing (i.e. {CSTF}3, {PCF}11).  Coherently, advanced {PC} cells displayed high sensitivity to a specific inhibitor  of the cleavage and polyadenylation complex, which enhances the effects of  chemotherapeutic drugs that are already in use for this cancer. {CONCLUSIONS}: Our  study uncovers intron retention as an actionable vulnerability for advanced {PC},  which may be exploited to improve therapeutic management of this currently  incurable disease.},
	pages = {58},
	number = {1},
	journaltitle = {Journal of experimental \& clinical cancer research : {CR}},
	shortjournal = {J Exp Clin Cancer Res},
	author = {Naro, Chiara and Antonioni, Ambra and Medici, Vanessa and Caggiano, Cinzia and Jolly, Ariane and de la Grange, Pierre and Bielli, Pamela and Paronetto, Maria Paola and Sette, Claudio},
	date = {2024-02-27},
	pmid = {38413979},
	pmcid = {PMC10898177},
	note = {Place: England},
	keywords = {Humans, Male, Transcriptomics, Alternative splicing, *Alternative Splicing, {RNA} Splicing, *Anilides, *Epoxy Compounds, *Macrolides, *Prostatic Neoplasms/drug therapy/genetics, *Pyrimidines, *Sulfonamides, 3’-end {mRNA} processing, Advanced prostate cancer, Androgen Antagonists, Androgens, Cell Cycle Proteins/genetics, Intron-retention, Introns, Proto-Oncogene Proteins/genetics, Splicing inhibitors},
}

@article{monteuuis_holding_2021,
	title = {Holding on to Junk Bonds: Intron Retention in Cancer and Therapy.},
	volume = {81},
	rights = {©2020 American Association for Cancer Research.},
	issn = {1538-7445 0008-5472},
	doi = {10.1158/0008-5472.CAN-20-1943},
	abstract = {Intron retention ({IR}) in cancer was for a long time overlooked by the scientific community, as it was previously considered to be an artifact of a dysfunctional  spliceosome. Technological advancements made in the last decade offer unique  opportunities to explore the role of {IR} as a widespread phenomenon that  contributes to the transcriptional diversity of many cancers. Numerous studies in  cancer have shed light on dysregulation of cellular mechanisms that lead to  aberrant and pathologic {IR}. {IR} is not merely a mechanism of gene regulation, but  rather it can mediate cancer pathogenesis and therapeutic resistance in various  human diseases. The burden of {IR} in cancer is governed by perturbations to  mechanisms known to regulate this phenomenon and include epigenetic variation,  mutations within the gene body, and splicing factor dysregulation. This review  summarizes possible causes for aberrant {IR} and discusses the role of {IR} in  therapy or as a consequence of disease treatment. As neoepitopes originating from  retained introns can be presented on the cancer cell surface, the development of  personalized cancer vaccines based on {IR}-derived neoepitopes should be  considered. Ultimately, a deeper comprehension about the origins and consequences  of aberrant {IR} may aid in the development of such personalized cancer vaccines.},
	pages = {779--789},
	number = {4},
	journaltitle = {Cancer research},
	shortjournal = {Cancer Res},
	author = {Monteuuis, Geoffray and Schmitz, Ulf and Petrova, Veronika and Kearney, Padraic S. and Rasko, John E. J.},
	date = {2021-02-15},
	pmid = {33046441},
	note = {Place: United States},
	keywords = {Humans, Animals, Introns/*genetics, Alternative Splicing/*genetics, Cancer Vaccines/genetics/therapeutic use, Epigenesis, Genetic/physiology, Neoplasms/*genetics/*therapy, Precision Medicine/methods/trends, Spliceosomes/genetics/metabolism},
}

@article{noble_cd19_2023,
	title = {{CD}19 Intron Retention Is Mechanism of {CAR}-T Treatment Resistance in Non-Hodgkin Lymphoma},
	volume = {142},
	issn = {0006-4971},
	url = {https://www.sciencedirect.com/science/article/pii/S000649712310108X},
	doi = {10.1182/blood-2023-185074},
	abstract = {Background: Chimeric antigen receptor T-cell ({CAR}-T) therapy has become a viable treatment option for patients (pts) with relapsed or refractory diffuse large B-cell lymphoma (R/R {DLBCL}). Transcriptomic markers for {CD}19 directed {CAR}-T failure have been characterized in pre-treatment B-cell acute lymphoblastic leukemia (B-{ALL}) but not in {DLBCL}. Here, we report the identification of {RNA} alternative splicing ({AS}) events associated with {CD}19 directed {CAR}-T response in pre-treatment {DLBCL} pts and of {RNA} binding proteins ({RNABP}) regulating these {AS} events. Methods: To identify putative {AS} markers for {CAR}-T treatment outcome, we performed differential {AS} on bulk {RNA}-seq samples of pre-treatment tumor biopsies in pts that had a durable response ({DR}), defined via remission up to 9 months post-treatment, and pts that had a non-durable response ({NDR}) with {rMATS}-turbo (Shen et al. {PNAS}. 2014). Intron retention ({IR}) events within {CD}19 were quantified with a secondary, more robust algorithm to ensure reproducibility and accuracy. Survival analyses were done using the survival and survminer libraries in R. Validation assays for the downstream effects {CD}19 {IR} were conducted in {EJ}1, Jeko-1, {OCI}-Ly3, {SU}-{DHL}-6, and Toledo cell lines. The surface protein expression of {CD}19 was assayed via flow cytometry ({FC}) followed by Quantibrite {PE} ({BD} Biosciences, San Jose, {CA}) quantification. Total {CD}19 protein expression was measured via western blot ({WB}) in the aforementioned cell lines. Analyses of {CD}19 {IR} was done via {RT}-{PCR} followed by electrophoresis, and bands were quantified with {iBright} Analysis Software (Thermo Fisher Scientific, Carlsbad, {CA}). The effect of {RNABP} was assessed via the creation of {CRISPR}/Cas9 knockout ({KO}) cell lines followed by {WB} of the target gene and quantification of {CD}19 surface protein expression by {FC}. Results: Introns 2 and 6 of {CD}19 are more highly expressed in {NDR} pts. A combined metric estimating the proportion of normal {CD}19 isoforms that do not express introns 2 or 6 (normal {CD}19) was created and {DR} pts expressed normal {CD}19 isoforms significantly higher than {NDR} pts (Figure 1). Normal {CD}19 isoforms classification performance was assessed via leave one out cross validation and achieved an overall accuracy of 67.6\%. Sensitivity (classifying {NDR}) was 61.1\% and specificity (classifying {DR}) was 81.3\%. The expression of normal {CD}19 relative to the median level within the cohort was significantly associated with progress free survival (Figure 2). The expression of {CD}19 intron 6 was negatively correlated with {CD}19 surface protein expression in {DLBCL} cell lines. Cell lines were sorted by cells that exhibited high {CD}19 surface expression (bright) and low expression (dim). Cell lines sorted into the dim category expressed higher levels of intron 6 than bright cells. The correlation of {RNABP} expression with {CD}19 intron 6 expression was done in this patient cohort and the {NCICCR}-{DLBCL} cohort. Six {RNABP} were significantly correlated in both cohorts (r 2 {\textgreater} 0.2 and p-value {\textless}0.01). {NOP}2, one of the {RNABP} that was positively correlated with intron 6 expression, was knocked out in Jeko-1 cell lines to validate the putative correlation with {CD}19 protein expression. The resulting knock out cells exhibited lower levels of intron 6 retention and higher {CD}19 protein expression by {FC} and {WB} than non-transformed cells. Conclusion: Pre-treatment tumors of R/R {DLBCL} patients who relapse before 9 months following {CD}19 directed {CAR}-T therapy have higher expression of {CD}19 isoforms that retain introns 2 and 6. The upregulated expression of the {CD}19 isoforms retaining these introns is correlated with {CD}19 surface protein expression and is a marker for sustained remission following {CAR}-T treatment. {NOP}2 is correlated with {CD}19 intron retention and surface protein expression and could be a target for modulating {CD}19 expression in conjunction with {CAR}-T treatment. Figure 1: The expression of normal {CD}19 isoforms in pre-treatment tumor samples of {DR} (red) and {NDR} patients (blue). Δ{PSI} denotes the difference in medians between the two groups. P-value yielded by a Wilcoxon test between the two groups is reported. Figure 2: Progress free survival ({PFS}) stratified by expression of normal {CD}19 isoforms. Red - above cohort median expression of normal {CD}19 isoforms. Blue - below cohort median expression of normal {CD}19 isoforms. P-value yielded via log-rank test.},
	pages = {3506},
	journaltitle = {65th {ASH} Annual Meeting Abstracts},
	shortjournal = {Blood},
	author = {Noble, Jerald and Locke, Frederick L. and Savid-Frontera, Constanza and Jain, Michael D. and Turner, Joel G. and Abraham Miranda, Julieta and Madanayake, Thushara W and Naderinezhad, Samira and Corallo, Salvatore and Menges, Meghan and Reid, Kayla and Robinson, Timothy J},
	date = {2023-11-02},
}

@article{sun_abnormalities_2023,
	title = {Abnormalities in intron retention characterize patients with systemic lupus erythematosus},
	volume = {13},
	issn = {2045-2322},
	url = {https://doi.org/10.1038/s41598-023-31890-4},
	doi = {10.1038/s41598-023-31890-4},
	abstract = {Regulation of intron retention ({IR}), a form of alternative splicing, is a newly recognized checkpoint in gene expression. Since there are numerous abnormalities in gene expression in the prototypic autoimmune disease systemic lupus erythematosus ({SLE}), we sought to determine whether {IR} was intact in patients with this disease. We, therefore, studied global gene expression and {IR} patterns of lymphocytes in {SLE} patients. We analyzed {RNA}-seq data from peripheral blood T cell samples from 14 patients suffering from systemic lupus erythematosus ({SLE}) and 4 healthy controls and a second, independent data set of {RNA}-seq data from B cells from16 {SLE} patients and 4 healthy controls. We identified intron retention levels from 26,372 well annotated genes as well as differential gene expression and tested for differences between cases and controls using unbiased hierarchical clustering and principal component analysis. We followed with gene-disease enrichment analysis and gene-ontology enrichment analysis. Finally, we then tested for significant differences in intron retention between cases and controls both globally and with respect to specific genes. Overall decreased {IR} was found in T cells from one cohort and B cells from another cohort of patients with {SLE} and was associated with increased expression of numerous genes, including those encoding spliceosome components. Different introns within the same gene displayed both up- and down-regulated retention profiles indicating a complex regulatory mechanism. These results indicate that decreased {IR} in immune cells is characteristic of patients with active {SLE} and may contribute to the abnormal expression of specific genes in this autoimmune disease.},
	pages = {5141},
	number = {1},
	journaltitle = {Scientific Reports},
	shortjournal = {Scientific Reports},
	author = {Sun, Xiaoqian and Liu, Zhichao and Li, Zongzhu and Zeng, Zhouhao and Peng, Weiqun and Zhu, Jun and Zhao, Joel and Zhu, Chenghao and Zeng, Chen and Stearrett, Nathaniel and Crandall, Keith A. and Bachali, Prathyusha and Grammer, Amrie C. and Lipsky, Peter E.},
	date = {2023-03-29},
}

@article{monteuuis_changing_2019-1,
	title = {The changing paradigm of intron retention: regulation, ramifications and recipes},
	volume = {47},
	issn = {0305-1048},
	url = {https://doi.org/10.1093/nar/gkz1068},
	doi = {10.1093/nar/gkz1068},
	abstract = {Intron retention ({IR}) is a form of alternative splicing that has long been neglected in mammalian systems although it has been studied for decades in non-mammalian species such as plants, fungi, insects and viruses. It was generally assumed that mis-splicing, leading to the retention of introns, would have no physiological consequence other than reducing gene expression by nonsense-mediated decay. Relatively recent landmark discoveries have highlighted the pivotal role that {IR} serves in normal and disease-related human biology. Significant technical hurdles have been overcome, thereby enabling the robust detection and quantification of {IR}. Still, relatively little is known about the cis- and trans-acting modulators controlling this phenomenon. The fate of an intron to be, or not to be, retained in the mature transcript is the direct result of the influence exerted by numerous intrinsic and extrinsic factors at multiple levels of regulation. These factors have altered current biological paradigms and provided unexpected insights into the transcriptional landscape. In this review, we discuss the regulators of {IR} and methods to identify them. Our focus is primarily on mammals, however, we broaden the scope to non-mammalian organisms in which {IR} has been shown to be biologically relevant.},
	pages = {11497--11513},
	number = {22},
	journaltitle = {Nucleic Acids Research},
	shortjournal = {Nucleic Acids Research},
	author = {Monteuuis, Geoffray and Wong, Justin J L and Bailey, Charles G and Schmitz, Ulf and Rasko, John E J},
	urldate = {2025-04-11},
	date = {2019-12-16},
}

@article{ewels_multiqc_2016,
	title = {{MultiQC}: summarize analysis results for multiple tools and samples in a single report},
	volume = {32},
	issn = {1367-4803},
	url = {https://doi.org/10.1093/bioinformatics/btw354},
	doi = {10.1093/bioinformatics/btw354},
	abstract = {Motivation: Fast and accurate quality control is essential for studies involving next-generation sequencing data. Whilst numerous tools exist to quantify {QC} metrics, there is no common approach to flexibly integrate these across tools and large sample sets. Assessing analysis results across an entire project can be time consuming and error prone; batch effects and outlier samples can easily be missed in the early stages of analysis.Results: We present {MultiQC}, a tool to create a single report visualising output from multiple tools across many samples, enabling global trends and biases to be quickly identified. {MultiQC} can plot data from many common bioinformatics tools and is built to allow easy extension and customization.Availability and implementation: {MultiQC} is available with an {GNU} {GPLv}3 license on {GitHub}, the Python Package Index and Bioconda. Documentation and example reports are available at http://multiqc.{infoContact}:  phil.ewels@scilifelab.se},
	pages = {3047--3048},
	number = {19},
	journaltitle = {Bioinformatics},
	shortjournal = {Bioinformatics},
	author = {Ewels, Philip and Magnusson, Måns and Lundin, Sverker and Käller, Max},
	urldate = {2025-05-10},
	date = {2016-10-01},
}

@article{fox_effect_2003,
	title = {Effect Displays in R for Generalised Linear Models},
	volume = {8},
	url = {https://www.jstatsoft.org/index.php/jss/article/view/v008i15},
	doi = {10.18637/jss.v008.i15},
	abstract = {This paper describes the implementation in R of a method for tabular or graphical display of terms in a complex generalised linear model. By complex, I mean a model that contains terms related by marginality or hierarchy, such as polynomial terms, or main effects and interactions. I call these tables or graphs effect displays. Effect displays are constructed by identifying high-order terms in a generalised linear model. Fitted values under the model are computed for each such term. The lower-order \&quot;relatives\&quot; of a high-order term (e.g., main effects marginal to an interaction) are absorbed into the term, allowing the predictors appearing in the high-order term to range over their values. The values of other predictors are fixed at typical values: for example, a covariate could be fixed at its mean or median, a factor at its proportional distribution in the data, or to equal proportions in its several levels. Variations of effect displays are also described, including representation of terms higher-order to any appearing in the model.},
	pages = {1 -- 27},
	number = {15},
	journaltitle = {Journal of Statistical Software},
	shortjournal = {J. Stat. Soft.},
	author = {Fox, John},
	urldate = {2025-05-11},
	date = {2003-07-22},
	note = {Section: Articles},
}

@article{lee_intron_2023,
	title = {Intron retention decreases {METTL}3 expression by inhibiting {mRNA} export to the cytoplasm.},
	volume = {56},
	issn = {1976-670X 1976-6696},
	doi = {10.5483/BMBRep.2023-0069},
	abstract = {Methyltransferase-like 3 ({METTL}3), a key component of the m6A methyltransferase complex, regulates the splicing, nuclear transport, stability, and translation of  its target genes. However, the mechanism underlying the regulation of {METTL}3  expression by alternative splicing ({AS}) remains unknown. We analyzed the  expression pattern of {METTL}3 after {AS} in human tissues and confirmed the  expression of an isoform retaining introns 8 and 9 ({METTL}3-{IR}). We confirmed the  different intracellular localizations of {METTL}3-{IR} and {METTL}3 proteins using  immunofluorescence microscopy. Furthermore, the endogenous expression of  {METTL}3-{IR} at the protein level was different from that at the {mRNA} level. We  found that 3'-{UTR} generation by intron retention ({IR}) inhibited the export of  {METTL}3-{IR} {mRNA} to the cytoplasm, which in turn suppressed protein expression. To  the best of our knowledge, this is the first study to confirm the regulation of  {METTL}3 gene expression by {AS}, providing evidence that the suppression of {METTL}3  protein expression by {IR} is an integral part of the mechanism by which 3'-{UTR}  generation regulates protein expression via inhibition of {RNA} export to the  cytoplasm. [{BMB} Reports 2023; 56(9): 514-519].},
	pages = {514--519},
	number = {9},
	journaltitle = {{BMB} reports},
	shortjournal = {{BMB} Rep},
	author = {Lee, Sangsoo and Jung, Haesoo and Choi, Sunkyung and Cho, Namjoon and Kim, Eun-Mi and Kim, Kee Kwang},
	date = {2023-09},
	pmid = {37357537},
	pmcid = {PMC10547966},
	note = {Place: Korea (South)},
	keywords = {Humans, {RNA}, Messenger/genetics/metabolism, *Methyltransferases/genetics/metabolism, Active Transport, Cell Nucleus, Cytoplasm/genetics/metabolism, Introns/genetics},
}

@article{chang_intron_2024,
	title = {Intron Retention of {DDX}39A Driven by {SNRPD}2 is a Crucial Splicing Axis for Oncogenic {MYC}/Spliceosome Program in Hepatocellular Carcinoma.},
	volume = {11},
	rights = {© 2024 The Author(s). Advanced Science published by Wiley‐{VCH} {GmbH}.},
	issn = {2198-3844},
	doi = {10.1002/advs.202403387},
	abstract = {{RNA} splicing is a dynamic molecular process in response to environmental stimuli and is strictly regulated by the spliceosome. Sm proteins, constituents of the  spliceosome, are key components that mediate splicing reactions; however, their  potential role in hepatocellular carcinoma ({HCC}) is poorly understood. In the  study, {SNRPD}2 ({PD}2) is found to be the most highly upregulated Sm protein in {HCC}  and to act as an oncogene. {PD}2 modulates {DDX}39A intron retention together with  {HNRNPL} to sustain the {DDX}39A short variant (39A\_S) expression. Mechanistically,  39A\_S can mediate {MYC} {mRNA} nuclear export to maintain high {MYC} protein  expression, while {MYC} in turn potentiates {PD}2 transcription. Importantly,  digitoxin can directly interact with {PD}2 and has a notable cancer-suppressive  effect on {HCC}. The study reveals a novel mechanism by which {DDX}39A senses  oncogenic {MYC} signaling and undergoes splicing via {PD}2 to form a positive  feedback loop in {HCC}, which can be targeted by digitoxin.},
	pages = {e2403387},
	number = {35},
	journaltitle = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
	shortjournal = {Adv Sci (Weinh)},
	author = {Chang, Cunjie and Li, Lina and Su, Ling and Yang, Fan and Zha, Quanxiu and Sun, Mengqing and Tao, Lin and Wang, Menglan and Song, Kangli and Jiang, Liangyu and Gao, Haojin and Liang, Yexin and Xu, Chao and Yong, Caiyu and Wang, Minmin and Huang, Jiacheng and Liu, Jing and Jin, Weiwei and Lv, Wenyuan and Dong, Heng and Li, Qian and Bu, Fangtian and Yan, Shuanghong and Qi, Haoxiang and Zhao, Shujuan and Zhu, Yingshuang and Wang, Yu and Shi, Junping and Qiao, Yiting and Xu, Jian and Chabot, Benoit and Chen, Jianxiang},
	date = {2024-09},
	pmid = {39018261},
	pmcid = {PMC11425265},
	note = {Place: Germany},
	keywords = {Humans, Male, Animals, Mice, Cell Line, Tumor, *Carcinoma, Hepatocellular/genetics/metabolism, *{DEAD}-box {RNA} Helicases/genetics/metabolism, *Introns/genetics, *Liver Neoplasms/genetics/metabolism, *{RNA} Splicing/genetics, *Spliceosomes/genetics/metabolism, digitoxin, Gene Expression Regulation, Neoplastic/genetics, Mice, Inbred {BALB} C, Mice, Nude, {MYC} signaling, Proto-Oncogene Proteins c-myc/genetics/metabolism, Ribonucleoproteins, Small Nuclear/genetics/metabolism, {RNA} splicing, Sm proteins},
}

@article{yue_histone_2024,
	title = {Histone H3K9 Lactylation Confers Temozolomide Resistance in Glioblastoma via {LUC}7L2-Mediated {MLH}1 Intron Retention.},
	volume = {11},
	rights = {© 2024 The Authors. Advanced Science published by Wiley‐{VCH} {GmbH}.},
	issn = {2198-3844},
	doi = {10.1002/advs.202309290},
	abstract = {Temozolomide ({TMZ}) resistance remains the major obstacle in the treatment of glioblastoma ({GBM}). Lactylation is a novel post-translational modification that  is involved in various tumors. However, whether lactylation plays a role in {GBM}  {TMZ} resistance remains unclear. Here it is found that histone H3K9 lactylation  (H3K9la) confers {TMZ} resistance in {GBM} via {LUC}7L2-mediated intron 7 retention of  {MLH}1. Mechanistically, lactylation is upregulated in recurrent {GBM} tissues and  {TMZ}-resistant cells, and is mainly concentrated in histone H3K9. Combined  multi-omics analysis, including {CUT}\&Tag, {SLAM}-seq, and {RNA}-seq, reveals that H3K9  lactylation is significantly enriched in the {LUC}7L2 promoter and activates {LUC}7L2  transcription to promote its expression. {LUC}7L2 mediates intron 7 retention of  {MLH}1 to reduce {MLH}1 expression, and thereby inhibit mismatch repair ({MMR}),  ultimately leading to {GBM} {TMZ} resistance. Of note, it is identified that a  clinical anti-epileptic drug, stiripentol, which can cross the blood-brain  barrier and inhibit lactate dehydrogenase A/B ({LDHA}/B) activity, acts as a  lactylation inhibitor and renders {GBM} cells more sensitive to {TMZ} in vitro and in  vivo. These findings not only shed light on the mechanism of lactylation in {GBM}  {TMZ} resistance but also provide a potential combined therapeutic strategy for  clinical {GBM} treatment.},
	pages = {e2309290},
	number = {19},
	journaltitle = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
	shortjournal = {Adv Sci (Weinh)},
	author = {Yue, Qu and Wang, Zhao and Shen, Yixiong and Lan, Yufei and Zhong, Xiangyang and Luo, Xin and Yang, Tao and Zhang, Manqing and Zuo, Boming and Zeng, Tianci and Lu, Jiankun and Wang, Yuankai and Liu, Boyang and Guo, Hongbo},
	date = {2024-05},
	pmid = {38477507},
	pmcid = {PMC11109612},
	note = {Place: Germany},
	keywords = {Female, Humans, Animals, Mice, intron retention, Cell Line, Tumor, Disease Models, Animal, *Introns/genetics, Mice, Nude, *Drug Resistance, Neoplasm/genetics/drug effects, *Glioblastoma/genetics/drug therapy/metabolism, *Histones/metabolism/genetics, *{MutL} Protein Homolog 1/genetics/metabolism, *Temozolomide/pharmacology, Antineoplastic Agents, Alkylating/pharmacology/therapeutic use, Brain Neoplasms/genetics/drug therapy/metabolism, glioblastoma, lactylation, {LUC}7L2, temozolomide resistance},
}

@article{lim_resistance_2019,
	title = {Resistance Exercise-induced Changes in Muscle Phenotype Are Load Dependent.},
	volume = {51},
	issn = {1530-0315 0195-9131},
	doi = {10.1249/MSS.0000000000002088},
	abstract = {{INTRODUCTION}: Lower-load ({LL}), higher-repetition resistance exercise training ({RET}) can increase muscle mass in a similar degree as higher-load ({HL}),  lower-repetition {RET}. However, little is known about how {LL} and {HL} {RET} modulate  other aspects of the {RET} phenotype such as satellite cells, myonuclei, and  mitochondrial proteins. We aimed to investigate changes in muscle mass, muscle  strength, satellite cell activity, myonuclear addition, and mitochondrial protein  content after prolonged {RET} with {LL} and {HL} {RET}. {METHODS}: We recruited 21 young  men and randomly assigned them to perform 10 wk {RET} (leg press, leg extension,  and leg curl) three times per week with the following conditions: 80FAIL (80\%  one-repetition maximum [1RM] performed to volitional fatigue), 30WM (30\%1RM with  volume matched to 80FAIL), and 30FAIL (30\%1RM to volitional fatigue). Skeletal  muscle biopsies were taken from the vastus lateralis pre- and post-{RET}  intervention. {RESULTS}: After 10 wk of {RET}, only 30FAIL and 80FAIL showed an  increase in peak torque and type I fiber cross-sectional area (P {\textless} 0.05).  Moreover, only 30FAIL resulted in a significant decrease in the myonuclear domain  of type {II} muscle fibers and an increase in mitochondrial proteins related to  autophagy, fission, and fusion (all P {\textless} 0.05). {CONCLUSION}: We discovered that {LL}  {RET} was effective at increasing the content of several mitochondrial proteins.  Similar to previous research, we found that changes in muscle mass and strength  were independent of load when repetitions were performed to volitional fatigue.},
	pages = {2578--2585},
	number = {12},
	journaltitle = {Medicine and science in sports and exercise},
	shortjournal = {Med Sci Sports Exerc},
	author = {Lim, Changhyun and Kim, Hyo Jeong and Morton, Robert W. and Harris, Roger and Phillips, Stuart M. and Jeong, Tae Seok and Kim, Chang Keun},
	date = {2019-12},
	pmid = {31306302},
	note = {Place: United States},
	keywords = {Humans, Muscle Strength/*physiology, Resistance Training/*methods, Male, Phenotype, Cell Nucleus/physiology, Mitochondria, Muscle/metabolism, Muscle Fatigue/physiology, Muscle Fibers, Fast-Twitch/physiology, Muscle Fibers, Slow-Twitch/physiology, Muscle Proteins/metabolism, Muscle, Skeletal/*cytology/*physiology, Satellite Cells, Skeletal Muscle/metabolism, Weight Lifting/physiology},
}

@article{dokht_abdiyan_effect_2023,
	title = {Effect of resistance exercise on cardiac perturbations and systolic performance: A cross-over randomized trial comparing volumes and techniques.},
	volume = {41},
	issn = {1466-447X 0264-0414},
	doi = {10.1080/02640414.2023.2260636},
	abstract = {This study investigated the magnitude and time-course of resistance exercise ({RE}) technique induced transient cardiac perturbations. Twenty-four participants were  assigned to one of four arms: sets to failure or non-failure with 8-10 repetition  maximum ({RM}), and sets to failure or non-failure with 15RM. Echocardiographic and  blood pressure ({BP}) data were recorded at baseline and 30 min, 6 h and 24 h  post-exercise. In all groups end-systolic circumferential wall stress ({cESS}), and  ratio of transmitral inflow velocities (E/A) were significantly decreased while  posterior wall thickness ({PWT}), global circumferential strain ({GCS}), {GCS} strain  rate ({GCSR}), global longitudinal strain rate ({GLSR}), and stroke volume ({SV}) were  significantly increased for up to 6 h of follow-up. In the 15RM groups, left  ventricular ({LV}) mass and interventricular septal thickness ({IVST}) were  significantly increased, and left atrial ({LA}) area was significantly decreased  (p {\textless} 0.05) compared to the 8-10 {RM} groups. In the 15RM groups, {RE} decreased  global longitudinal strain ({GLS}) and increased ejection fraction ({EF}) (p{\textless}0.01).  After {RE}, transient cardiac perturbations, the reduction in {LA} compliance, and  the improvement in {LV} myofibril geometry were volume dependent and influenced  more by sets to failure technique. {RE} increased {GCS} and reduced the afterload,  thus helping to preserve {SV} and {EF}.},
	pages = {1196--1206},
	number = {12},
	journaltitle = {Journal of sports sciences},
	shortjournal = {J Sports Sci},
	author = {Dokht Abdiyan, Rasoul and Sadeghpour, Anita and Alizadehasl, Azin and Ahmadi, Azizeh and Saed, Daryoush and Ravasi, Ali Asghar and Akbarnejad, Ali and Maleki, Majid and Shariati, Akram and Shahed, Atabak and Aziminia, Mahdiye},
	date = {2023-06},
	pmid = {37729561},
	note = {Place: England},
	keywords = {afterload, athlete, heart, left ventricular hypertrophy, Resistance exercises, strain},
}

@article{balducci_volume-dependent_2015,
	title = {Volume-dependent effect of supervised exercise training on fatty liver and visceral adiposity index in subjects with type 2 diabetes The Italian Diabetes  Exercise Study ({IDES}).},
	volume = {109},
	rights = {Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.},
	issn = {1872-8227 0168-8227},
	doi = {10.1016/j.diabres.2015.05.033},
	abstract = {{AIMS}: This study evaluated the effect of supervised exercise training on liver enzymes and two surrogate measures of non-alcoholic fatty liver disease ({NAFLD})  in subjects with type 2 diabetes. {METHODS}: Sedentary patients from 22 outpatient  diabetes clinics were randomized by center, age and treatment to twice-a-week  supervised aerobic and resistance training plus structured exercise counseling  (exercise group, {EXE}; n=303) versus counseling alone (control group, {CON}; n=303)  for 12 months. {EXE} participants were further randomized to low-to-moderate  (n=142) or moderate-to-high (n=161) intensity training of equal energy cost.  Baseline and end-of-study levels of liver enzymes, fatty liver index ({FLI}) and  visceral adiposity index ({VAI}) were obtained. {RESULTS}: Enzyme levels did not  change, whereas {FLI} and {VAI} decreased significantly in {EXE}, but not {CON}  participants. Physical activity ({PA}) volume was an independent predictor of both  {FLI} and {VAI} reductions, the extent of which increased from the 1st to the 4th  quintile of {PA} volume and baseline to end-of-study changes in fitness parameters.  Differences in the effect of {LI} versus {HI} training were negligible. {CONCLUSIONS}:  Data from this large cohort of subjects with type 2 diabetes indicate that {FLI}  and {VAI} decrease with supervised training in a volume-dependent manner.},
	pages = {355--363},
	number = {2},
	journaltitle = {Diabetes research and clinical practice},
	shortjournal = {Diabetes Res Clin Pract},
	author = {Balducci, Stefano and Cardelli, Patrizia and Pugliese, Luca and D'Errico, Valeria and Haxhi, Jonida and Alessi, Elena and Iacobini, Carla and Menini, Stefano and Bollanti, Lucilla and Conti, Francesco G. and Nicolucci, Antonio and Pugliese, Giuseppe},
	date = {2015-08},
	pmid = {26047682},
	note = {Place: Ireland},
	keywords = {Female, Humans, Middle Aged, Resistance Training/*methods, Male, Exercise Therapy/*methods, Exercise/*psychology, *Adiposity, Diabetes Mellitus, Type 2/*complications/psychology, Exercise volume, {FLI}, Incidence, Italy/epidemiology, Liver enzymes, Non-alcoholic Fatty Liver Disease/epidemiology/etiology/*therapy, Supervised exercise, {VAI}},
}

@article{lai_dose-response_2023,
	title = {Dose-response effects of resistance training on physical function in frail older Chinese adults: A randomized controlled trial.},
	volume = {14},
	rights = {© 2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals {LLC}.},
	issn = {2190-6009 2190-5991},
	doi = {10.1002/jcsm.13359},
	abstract = {{BACKGROUND}: Effective exercise for the frail elderly has been found to contribute to healthy aging; the corresponding relationship between intensity and volume of  exercise and health effects remains unclear. The present study aimed to  investigate the dose-response effects of resistance training on muscle strength  and physical fitness in frail older adults. {METHODS}: In this randomized  controlled trial, participants were randomized into seven groups: moderate-volume  low-intensity, moderate-volume moderate-intensity, moderate-volume  high-intensity, high-volume low-intensity, high-volume moderate-intensity,  high-volume high-intensity and routine care, receiving 12 weeks of resistance  training of different intensities and volumes of exercise. The outcomes were  muscle strength (assessed by ergonomics force gauges) and physical fitness  function (assessed by the 6-min walking test [6MWT], the 30-s sit-to-stand test  [30sSTST] and the 8-foot up-and-go test [8-{FUGT}]) before and at 6 and 12 weeks of  intervention. {RESULTS}: A total of 161 participants completed the exercise  intervention. There were no significant differences in age, sex, height, body  weight and body mass index among the seven groups. The exercise volume of  resistance training showed linear relationships with muscle strength of the lower  limbs, 30sSTST and 6MWT results and a non-linear relationship with 8-{FUGT}.  Resistance training intensity was found to have a linear relationship with muscle  strength of the lower limbs and 6MWT and non-linear relationships with 30sSTST  and 8-{FUGT}. The mixed linear model analysis revealed that the lower limb muscle  strength differed significantly before and during the intervention (W = 8571.5,  P(adj)  {\textless} 0.001), before and after the intervention (W = 6968, P(adj)  = 0.001)  and during and after the intervention (W = 2834.5, P(adj)  {\textless} 0.001); that the  6MWT performance differed during and after the intervention (W = 3184, P(adj)  {\textless} 0.001); and that the 30sSTST was different between before and during the  intervention (W = 2350.5, P(adj)  = 0.012) and between during and after the  intervention (W = 2290.5, P(adj)  = 0.045). {CONCLUSIONS}: Resistance training was  found to be associated with muscle strength and physical fitness in frail older  adults in a dose-dependent manner. High-intensity resistance training could be  more effective for improving the muscle strength of frail older adults, and the  improvement of 6MWT performance was even higher. High-volume resistance training  significantly improved muscle strength, with even greater improvement in the  30sSTST and 6MWT performances. Both the intensity and volume of exercise were  found to greatly value physical function in frail older adults.  Low-moderate-intensity resistance training and low-moderate-volume resistance  training also had some advantages in terms of safety, efficacy and acceptance in  elderly with frailty.},
	pages = {2824--2834},
	number = {6},
	journaltitle = {Journal of cachexia, sarcopenia and muscle},
	shortjournal = {J Cachexia Sarcopenia Muscle},
	author = {Lai, Xiaoxing and Zhu, Hongwei and Wu, Zhao and Chen, Baoyu and Jiang, Qian and Du, Hongdi and Huo, Xiaopeng},
	date = {2023-12},
	pmid = {37875291},
	pmcid = {PMC10751415},
	note = {Place: Germany},
	keywords = {Humans, Middle Aged, *Resistance Training/methods, physical fitness, resistance training, *Frail Elderly, Aged, Exercise/physiology, muscle strength, frailty, China, dose-response, older adults, Physical Fitness/physiology, volume and intensity},
}

@article{ritchie_limma_2015,
	title = {limma powers differential expression analyses for {RNA}-sequencing and microarray studies.},
	volume = {43},
	rights = {© The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.},
	issn = {1362-4962 0305-1048},
	doi = {10.1093/nar/gkv007},
	abstract = {limma is an R/Bioconductor software package that provides an integrated solution for analysing data from gene expression experiments. It contains rich features  for handling complex experimental designs and for information borrowing to  overcome the problem of small sample sizes. Over the past decade, limma has been  a popular choice for gene discovery through differential expression analyses of  microarray and high-throughput {PCR} data. The package contains particularly strong  facilities for reading, normalizing and exploring such data. Recently, the  capabilities of limma have been significantly expanded in two important  directions. First, the package can now perform both differential expression and  differential splicing analyses of {RNA} sequencing ({RNA}-seq) data. All the  downstream analysis tools previously restricted to microarray data are now  available for {RNA}-seq as well. These capabilities allow users to analyse both  {RNA}-seq and microarray data with very similar pipelines. Second, the package is  now able to go past the traditional gene-wise expression analyses in a variety of  ways, analysing expression profiles in terms of co-regulated sets of genes or in  terms of higher-order expression signatures. This provides enhanced possibilities  for biological interpretation of gene expression differences. This article  reviews the philosophy and design of the limma package, summarizing both new and  historical features, with an emphasis on recent enhancements and features that  have not been previously described.},
	pages = {e47},
	number = {7},
	journaltitle = {Nucleic acids research},
	shortjournal = {Nucleic Acids Res},
	author = {Ritchie, Matthew E. and Phipson, Belinda and Wu, Di and Hu, Yifang and Law, Charity W. and Shi, Wei and Smyth, Gordon K.},
	date = {2015-04-20},
	pmid = {25605792},
	pmcid = {PMC4402510},
	note = {Place: England},
	keywords = {*Sequence Analysis, {RNA}, *Gene Expression Regulation, *Software, *Oligonucleotide Array Sequence Analysis},
}

@article{love_moderated_2014,
	title = {Moderated estimation of fold change and dispersion for {RNA}-seq data with {DESeq}2},
	volume = {15},
	issn = {1474-760X},
	url = {https://doi.org/10.1186/s13059-014-0550-8},
	doi = {10.1186/s13059-014-0550-8},
	abstract = {In comparative high-throughput sequencing assays, a fundamental task is the analysis of count data, such as read counts per gene in {RNA}-seq, for evidence of systematic changes across experimental conditions. Small replicate numbers, discreteness, large dynamic range and the presence of outliers require a suitable statistical approach. We present {DESeq}2, a method for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates. This enables a more quantitative analysis focused on the strength rather than the mere presence of differential expression. The {DESeq}2 package is available at http://www.bioconductor.org/packages/release/bioc/html/{DESeq}2.html.},
	pages = {550},
	number = {12},
	journaltitle = {Genome Biology},
	shortjournal = {Genome Biology},
	author = {Love, Michael I. and Huber, Wolfgang and Anders, Simon},
	date = {2014-12-05},
}

@article{anders_differential_2010,
	title = {Differential expression analysis for sequence count data},
	volume = {11},
	issn = {1474-760X},
	url = {https://doi.org/10.1186/gb-2010-11-10-r106},
	doi = {10.1186/gb-2010-11-10-r106},
	abstract = {High-throughput sequencing assays such as {RNA}-Seq, {ChIP}-Seq or barcode counting provide quantitative readouts in the form of count data. To infer differential signal in such data correctly and with good statistical power, estimation of data variability throughout the dynamic range and a suitable error model are required. We propose a method based on the negative binomial distribution, with variance and mean linked by local regression and present an implementation, {DESeq}, as an R/Bioconductor package.},
	pages = {R106},
	number = {10},
	journaltitle = {Genome Biology},
	shortjournal = {Genome Biology},
	author = {Anders, Simon and Huber, Wolfgang},
	date = {2010-10-27},
}

@article{robinson_edger_2010,
	title = {{edgeR}: a Bioconductor package for differential expression analysis of digital gene expression data.},
	volume = {26},
	issn = {1367-4811 1367-4803},
	doi = {10.1093/bioinformatics/btp616},
	abstract = {{SUMMARY}: It is expected that emerging digital gene expression ({DGE}) technologies will overtake microarray technologies in the near future for many functional  genomics applications. One of the fundamental data analysis tasks, especially for  gene expression studies, involves determining whether there is evidence that  counts for a transcript or exon are significantly different across experimental  conditions. {edgeR} is a Bioconductor software package for examining differential  expression of replicated count data. An overdispersed Poisson model is used to  account for both biological and technical variability. Empirical Bayes methods  are used to moderate the degree of overdispersion across transcripts, improving  the reliability of inference. The methodology can be used even with the most  minimal levels of replication, provided at least one phenotype or experimental  condition is replicated. The software may have other applications beyond  sequencing data, such as proteome peptide count data. {AVAILABILITY}: The package  is freely available under the {LGPL} licence from the Bioconductor web site  (http://bioconductor.org).},
	pages = {139--140},
	number = {1},
	journaltitle = {Bioinformatics (Oxford, England)},
	shortjournal = {Bioinformatics},
	author = {Robinson, Mark D. and {McCarthy}, Davis J. and Smyth, Gordon K.},
	date = {2010-01-01},
	pmid = {19910308},
	pmcid = {PMC2796818},
	note = {Place: England},
	keywords = {*Software, *Algorithms, *Programming Languages, *Signal Processing, Computer-Assisted, Gene Expression Profiling/*methods, Oligonucleotide Array Sequence Analysis/*methods},
}

@article{vestal_lmerseq_2022,
	title = {{lmerSeq}: an R package for analyzing transformed {RNA}-Seq data with linear mixed effects models},
	volume = {23},
	issn = {1471-2105},
	url = {https://doi.org/10.1186/s12859-022-05019-9},
	doi = {10.1186/s12859-022-05019-9},
	abstract = {Studies that utilize {RNA} Sequencing ({RNA}-Seq) in conjunction with designs that introduce dependence between observations (e.g. longitudinal sampling) require specialized analysis tools to accommodate this additional complexity. This R package contains a set of utilities to fit linear mixed effects models to transformed {RNA}-Seq counts that properly account for this dependence when performing statistical analyses.},
	pages = {489},
	number = {1},
	journaltitle = {{BMC} Bioinformatics},
	shortjournal = {{BMC} Bioinformatics},
	author = {Vestal, Brian E. and Wynn, Elizabeth and Moore, Camille M.},
	date = {2022-11-16},
}

@article{lewis_glmmseq_2022,
	title = {{glmmSeq}: General Linear Mixed Models for Gene-Level Differential Expression},
	journaltitle = {https://myles-lewis.github.io/{glmmSeq}/},
	author = {Lewis, Myles and Goldmann, Katriona and Elisabetta, Sciacca},
	date = {2022},
}

@article{hoffman_dream_2021,
	title = {Dream: powerful differential expression analysis for repeated measures designs},
	volume = {37},
	issn = {1367-4803},
	url = {https://doi.org/10.1093/bioinformatics/btaa687},
	doi = {10.1093/bioinformatics/btaa687},
	abstract = {Large-scale transcriptome studies with multiple samples per individual are widely used to study disease biology. Yet, current methods for differential expression are inadequate for cross-individual testing for these repeated measures designs. Most problematic, we observe across multiple datasets that current methods can give reproducible false-positive findings that are driven by genetic regulation of gene expression, yet are unrelated to the trait of interest. Here, we introduce a statistical software package, dream, that increases power, controls the false positive rate, enables multiple types of hypothesis tests, and integrates with standard workflows. In 12 analyses in 6 independent datasets, dream yields biological insight not found with existing software while addressing the issue of reproducible false-positive findings.Dream is available within the {variancePartition} Bioconductor package at http://bioconductor.org/packages/{variancePartition}.gabriel.hoffman@mssm.{eduSupplementary} data are available at Bioinformatics online.},
	pages = {192--201},
	number = {2},
	journaltitle = {Bioinformatics},
	shortjournal = {Bioinformatics},
	author = {Hoffman, Gabriel E and Roussos, Panos},
	urldate = {2025-07-01},
	date = {2021-04-19},
}

@article{nguyen_rmrnaseq_2020,
	title = {{rmRNAseq}: differential expression analysis for repeated-measures {RNA}-seq data},
	volume = {36},
	issn = {1367-4803},
	url = {https://doi.org/10.1093/bioinformatics/btaa525},
	doi = {10.1093/bioinformatics/btaa525},
	abstract = {With the reduction in price of next-generation sequencing technologies, gene expression profiling using {RNA}-seq has increased the scope of sequencing experiments to include more complex designs, such as designs involving repeated measures. In such designs, {RNA} samples are extracted from each experimental unit at multiple time points. The read counts that result from {RNA} sequencing of the samples extracted from the same experimental unit tend to be temporally correlated. Although there are many methods for {RNA}-seq differential expression analysis, existing methods do not properly account for within-unit correlations that arise in repeated-measures designs.We address this shortcoming by using normalized log-transformed counts and associated precision weights in a general linear model pipeline with continuous autoregressive structure to account for the correlation among observations within each experimental unit. We then utilize parametric bootstrap to conduct differential expression inference. Simulation studies show the advantages of our method over alternatives that do not account for the correlation among observations within experimental units.We provide an R package {rmRNAseq} implementing our proposed method (function {TC}\_CAR1) at https://cran.r-project.org/web/packages/{rmRNAseq}/index.html. Reproducible R codes for data analysis and simulation are available at https://github.com/ntyet/{rmRNAseq}/tree/master/simulation.},
	pages = {4432--4439},
	number = {16},
	journaltitle = {Bioinformatics},
	shortjournal = {Bioinformatics},
	author = {Nguyen, Yet and Nettleton, Dan},
	urldate = {2025-07-01},
	date = {2020-08-15},
}

@article{khan_normalization_2022,
	title = {Normalization of gene expression data revisited: the three viewpoints of the transcriptome in human skeletal muscle undergoing load-induced hypertrophy and  why they matter.},
	volume = {23},
	rights = {© 2022. The Author(s).},
	issn = {1471-2105},
	doi = {10.1186/s12859-022-04791-y},
	abstract = {{BACKGROUND}: The biological relevance and accuracy of gene expression data depend on the adequacy of data normalization. This is both due to its role in resolving  and accounting for technical variation and errors, and its defining role in  shaping the viewpoint of biological interpretations. Still, the choice of the  normalization method is often not explicitly motivated although this choice may  be particularly decisive for conclusions in studies involving pronounced cellular  plasticity. In this study, we highlight the consequences of using three  fundamentally different modes of normalization for interpreting {RNA}-seq data from  human skeletal muscle undergoing exercise-training-induced growth. Briefly, 25  participants conducted 12 weeks of high-load resistance training. Muscle biopsy  specimens were sampled from m. vastus lateralis before, after two weeks of  training (week 2) and after the intervention (week 12), and were subsequently  analyzed using {RNA}-seq. Transcript counts were modeled as (1) per-library-size,  (2) per-total-{RNA}, and (3) per-sample-size (per-mg-tissue). {RESULT}: Initially,  the three modes of transcript modeling led to the identification of three unique  sets of stable genes, which displayed differential expression profiles.  Specifically, genes showing stable expression across samples in the  per-library-size dataset displayed training-associated increases in per-total-{RNA}  and per-sample-size datasets. These gene sets were then used for normalization of  the entire dataset, providing transcript abundance estimates corresponding to  each of the three biological viewpoints (i.e., per-library-size, per-total-{RNA},  and per-sample-size). The different normalization modes led to different  conclusions, measured as training-associated changes in transcript expression.  Briefly, for 27\% and 20\% of the transcripts, training was associated with changes  in expression in per-total-{RNA} and per-sample-size scenarios, but not in the  per-library-size scenario. At week 2, this led to opposite conclusions for 4\% of  the transcripts between per-library-size and per-sample-size datasets (↑ vs. ↓,  respectively). {CONCLUSION}: Scientists should be explicit with their choice of  normalization strategies and should interpret the results of gene expression  analyses with caution. This is particularly important for data sets involving a  limited number of genes or involving growing or differentiating cellular models,  where the risk of biased conclusions is pronounced.},
	pages = {241},
	number = {1},
	journaltitle = {{BMC} bioinformatics},
	shortjournal = {{BMC} Bioinformatics},
	author = {Khan, Yusuf and Hammarström, Daniel and Ellefsen, Stian and Ahmad, Rafi},
	date = {2022-06-18},
	pmid = {35717158},
	pmcid = {PMC9206305},
	note = {Place: England},
	keywords = {Humans, Resistance training, Hypertrophy, Muscle, Skeletal, Skeletal muscle, *Transcriptome, {RNA}-seq, *{RNA}, Gene Library, Normalization},
}

@article{vestal_mcmseq_2020,
	title = {{MCMSeq}: Bayesian hierarchical modeling of clustered and repeated measures {RNA} sequencing experiments.},
	volume = {21},
	issn = {1471-2105},
	doi = {10.1186/s12859-020-03715-y},
	abstract = {{BACKGROUND}: As the barriers to incorporating {RNA} sequencing ({RNA}-Seq) into biomedical studies continue to decrease, the complexity and size of {RNA}-Seq  experiments are rapidly growing. Paired, longitudinal, and other correlated  designs are becoming commonplace, and these studies offer immense potential for  understanding how transcriptional changes within an individual over time differ  depending on treatment or environmental conditions. While several methods have  been proposed for dealing with repeated measures within {RNA}-Seq analyses, they  are either restricted to handling only paired measurements, can only test for  differences between two groups, and/or have issues with maintaining nominal false  positive and false discovery rates. In this work, we propose a Bayesian  hierarchical negative binomial generalized linear mixed model framework that can  flexibly model {RNA}-Seq counts from studies with arbitrarily many repeated  observations, can include covariates, and also maintains nominal false positive  and false discovery rates in its posterior inference. {RESULTS}: In simulation  studies, we showed that our proposed method ({MCMSeq}) best combines high  statistical power (i.e. sensitivity or recall) with maintenance of nominal false  positive and false discovery rates compared the other available strategies,  especially at the smaller sample sizes investigated. This behavior was then  replicated in an application to real {RNA}-Seq data where {MCMSeq} was able to find  previously reported genes associated with tuberculosis infection in a cohort with  longitudinal measurements. {CONCLUSIONS}: Failing to account for repeated  measurements when analyzing {RNA}-Seq experiments can result in significantly  inflated false positive and false discovery rates. Of the methods we  investigated, whether they model {RNA}-Seq counts directly or worked on transformed  values, the Bayesian hierarchical model implemented in the mcmseq R package  (available at https://github.com/stop-pre16/mcmseq ) best combined sensitivity  and nominal error rate control.},
	pages = {375},
	number = {1},
	journaltitle = {{BMC} bioinformatics},
	shortjournal = {{BMC} Bioinformatics},
	author = {Vestal, Brian E. and Moore, Camille M. and Wynn, Elizabeth and Saba, Laura and Fingerlin, Tasha and Kechris, Katerina},
	date = {2020-08-28},
	pmid = {32859148},
	pmcid = {PMC7455910},
	note = {Place: England},
	keywords = {Humans, {RNA}-Seq, *User-Computer Interface, Bayes Theorem, Correlated data, Longitudinal data, Markov chain Monte Carlo, Monte Carlo Method, {RNA}/*chemistry/genetics/metabolism, Sequence Analysis, {RNA}/*methods, Tuberculosis/genetics/pathology},
}

@article{bian_pairedfb_2019,
	title = {{PairedFB}: a full hierarchical Bayesian model for paired {RNA}-seq data with heterogeneous treatment effects},
	volume = {35},
	issn = {1367-4803},
	url = {https://doi.org/10.1093/bioinformatics/bty731},
	doi = {10.1093/bioinformatics/bty731},
	abstract = {Several methods have been proposed for the paired {RNA}-seq analysis. However, many of them do not consider the heterogeneity in treatment effect among pairs that can naturally arise in real data. In addition, it has been reported in literature that the false discovery rate ({FDR}) control of some popular methods has been problematic. In this paper, we present a full hierarchical Bayesian model for the paired {RNA}-seq count data that accounts for variation of treatment effects among pairs and controls the {FDR} through the posterior expected {FDR}.Our simulation studies show that most competing methods can have highly inflated {FDR} for small to moderate sample sizes while {PairedFB} is able to control {FDR} close to the nominal levels. Furthermore, {PairedFB} has overall better performance in ranking true differentially expressed genes ({DEGs}) on the top than others, especially when the sample size gets bigger or when the heterogeneity level of treatment effects is high. In addition, {PairedFB} can be applied to identify the biologically significant {DEGs} with controlled {FDR}. The real data analysis also indicates {PairedFB} tends to find more biologically relevant genes even when the sample size is small. {PairedFB} is also shown to be robust with respect to the model misspecification in terms of its relative performance compared to others.Software to implement this method ({PairedFB}) can be downloaded at: https://sites.google.com/a/udel.edu/qiujing/publication.Supplementary data are available at Bioinformatics online.},
	pages = {787--797},
	number = {5},
	journaltitle = {Bioinformatics},
	shortjournal = {Bioinformatics},
	author = {Bian, Yuanyuan and He, Chong and Hou, Jie and Cheng, Jianlin and Qiu, Jing},
	urldate = {2025-08-02},
	date = {2019-03-01},
}

@article{van_de_wiel_shrinkbayes_2014,
	title = {{ShrinkBayes}: a versatile R-package for analysis of count-based sequencing data in complex study designs.},
	volume = {15},
	issn = {1471-2105},
	doi = {10.1186/1471-2105-15-116},
	abstract = {{BACKGROUND}: Complex designs are common in (observational) clinical studies. Sequencing data for such studies are produced more and more often, implying  challenges for the analysis, such as excess of zeros, presence of random effects  and multi-parameter inference. Moreover, when sample sizes are small, inference  is likely to be too liberal when, in a Bayesian setting, applying a  non-appropriate prior or to lack power when not carefully borrowing information  across features. {RESULTS}: We show on {microRNA} sequencing data from a clinical  cancer study how our software {ShrinkBayes} tackles the aforementioned challenges.  In addition, we illustrate its comparatively good performance on multi-parameter  inference for groups using a data-based simulation. Finally, in the small sample  size setting, we demonstrate its high power and improved {FDR} estimation by use of  Gaussian mixture priors that include a point mass. {CONCLUSION}: {ShrinkBayes} is a  versatile software package for the analysis of count-based sequencing data, which  is particularly useful for studies with small sample sizes or complex designs.},
	pages = {116},
	journaltitle = {{BMC} bioinformatics},
	shortjournal = {{BMC} Bioinformatics},
	author = {van de Wiel, Mark A. and Neerincx, Maarten and Buffart, Tineke E. and Sie, Daoud and Verheul, Henk M. W.},
	date = {2014-04-26},
	pmid = {24766777},
	pmcid = {PMC4098777},
	note = {Place: England},
	keywords = {Humans, *Software, Bayes Theorem, Sequence Analysis, {RNA}/*methods, Colonic Neoplasms/genetics, {MicroRNAs}/chemistry, Sample Size},
}

@article{wynn_comparison_2022,
	title = {A comparison of methods for multiple degree of freedom testing in repeated measures {RNA}-sequencing experiments.},
	volume = {22},
	rights = {© 2022. The Author(s).},
	issn = {1471-2288},
	doi = {10.1186/s12874-022-01615-8},
	abstract = {{BACKGROUND}: As the cost of {RNA}-sequencing decreases, complex study designs, including paired, longitudinal, and other correlated designs, become increasingly  feasible. These studies often include multiple hypotheses and thus multiple  degree of freedom tests, or tests that evaluate multiple hypotheses jointly, are  often useful for filtering the gene list to a set of interesting features for  further exploration while controlling the false discovery rate. Though there are  several methods which have been proposed for analyzing correlated {RNA}-sequencing  data, there has been little research evaluating and comparing the performance of  multiple degree of freedom tests across methods. {METHODS}: We evaluated 11  different methods for modelling correlated {RNA}-sequencing data by performing a  simulation study to compare the false discovery rate, power, and model  convergence rate across several hypothesis tests and sample size scenarios. We  also applied each method to a real longitudinal {RNA}-sequencing dataset. {RESULTS}:  Linear mixed modelling using transformed data had the best false discovery rate  control while maintaining relatively high power. However, this method had high  model non-convergence, particularly at small sample sizes. No method had high  power at the lowest sample size. We found a mix of conservative and  anti-conservative behavior across the other methods, which was influenced by the  sample size and the hypothesis being evaluated. The patterns observed in the  simulation study were largely replicated in the analysis of a longitudinal study  including data from intensive care unit patients experiencing cardiogenic or  septic shock. {CONCLUSIONS}: Multiple degree of freedom testing is a valuable tool  in longitudinal and other correlated {RNA}-sequencing experiments. Of the methods  that we investigated, linear mixed modelling had the best overall combination of  power and false discovery rate control. Other methods may also be appropriate in  some scenarios.},
	pages = {153},
	number = {1},
	journaltitle = {{BMC} medical research methodology},
	shortjournal = {{BMC} Med Res Methodol},
	author = {Wynn, Elizabeth A. and Vestal, Brian E. and Fingerlin, Tasha E. and Moore, Camille M.},
	date = {2022-05-28},
	pmid = {35643435},
	pmcid = {PMC9148455},
	note = {Place: England},
	keywords = {Humans, Longitudinal Studies, {RNA}-seq, Sequence Analysis, {RNA}/methods, Correlated data, Sample Size, *Research Design, *{RNA}/genetics, Multiple {DF} testing},
}

@article{cruz-jentoft_sarcopenia_2019,
	title = {Sarcopenia},
	volume = {393},
	issn = {0140-6736},
	url = {https://www.sciencedirect.com/science/article/pii/S0140673619311389},
	doi = {10.1016/S0140-6736(19)31138-9},
	abstract = {Summary
Sarcopenia is a progressive and generalised skeletal muscle disorder involving the accelerated loss of muscle mass and function that is associated with increased adverse outcomes including falls, functional decline, frailty, and mortality. It occurs commonly as an age-related process in older people, influenced not only by contemporaneous risk factors, but also by genetic and lifestyle factors operating across the life course. It can also occur in mid-life in association with a range of conditions. Sarcopenia has become the focus of intense research aiming to translate current knowledge about its pathophysiology into improved diagnosis and treatment, with particular interest in the development of biomarkers, nutritional interventions, and drugs to augment the beneficial effects of resistance exercise. Designing effective preventive strategies that people can apply during their lifetime is of primary concern. Diagnosis, treatment, and prevention of sarcopenia is likely to become part of routine clinical practice.},
	pages = {2636--2646},
	number = {10191},
	journaltitle = {The Lancet},
	shortjournal = {The Lancet},
	author = {Cruz-Jentoft, Alfonso J and Sayer, Avan A},
	date = {2019-06-29},
}

@article{sayer_sarcopenia_2024,
	title = {Sarcopenia},
	volume = {10},
	issn = {2056-676X},
	url = {https://doi.org/10.1038/s41572-024-00550-w},
	doi = {10.1038/s41572-024-00550-w},
	abstract = {Sarcopenia is the accelerated loss of skeletal muscle mass and function commonly, but not exclusively, associated with advancing age. It is observed across many species including humans in whom it can lead to decline in physical function and mobility as well as to increased risk of adverse outcomes including falls, fractures and premature mortality. Although prevalence estimates vary because sarcopenia has been defined in different ways, even using a conservative approach, the prevalence is between 5\% and 10\% in the general population. A life course framework has been proposed for understanding not only the occurrence of sarcopenia in later life but also influences operating at earlier life stages with potentially important implications for preventive strategies. Harnessing progress in understanding the hallmarks of ageing has been key to understanding sarcopenia pathophysiology. Considerable convergence in approaches to diagnosis of sarcopenia has occurred over the last 10 years, with a growing emphasis on the central importance of muscle strength. Resistance exercise is currently the mainstay of treatment; however, it is not suitable for all. Hence, adjunctive and alternative treatments to improve quality of life are needed. An internationally agreed approach to definition and diagnosis will enable a step change in the field and is likely to be available in the near future through the Global Leadership Initiative in Sarcopenia.},
	pages = {68},
	number = {1},
	journaltitle = {Nature Reviews Disease Primers},
	shortjournal = {Nature Reviews Disease Primers},
	author = {Sayer, Avan A. and Cooper, Rachel and Arai, Hidenori and Cawthon, Peggy M. and Ntsama Essomba, Marie-Josiane and Fielding, Roger A. and Grounds, Miranda D. and Witham, Miles D. and Cruz-Jentoft, Alfonso J.},
	date = {2024-09-19},
}

@article{sayer_sarcopenia_2024-1,
	title = {Sarcopenia},
	volume = {10},
	issn = {2056-676X},
	url = {https://doi.org/10.1038/s41572-024-00550-w},
	doi = {10.1038/s41572-024-00550-w},
	abstract = {Sarcopenia is the accelerated loss of skeletal muscle mass and function commonly, but not exclusively, associated with advancing age. It is observed across many species including humans in whom it can lead to decline in physical function and mobility as well as to increased risk of adverse outcomes including falls, fractures and premature mortality. Although prevalence estimates vary because sarcopenia has been defined in different ways, even using a conservative approach, the prevalence is between 5\% and 10\% in the general population. A life course framework has been proposed for understanding not only the occurrence of sarcopenia in later life but also influences operating at earlier life stages with potentially important implications for preventive strategies. Harnessing progress in understanding the hallmarks of ageing has been key to understanding sarcopenia pathophysiology. Considerable convergence in approaches to diagnosis of sarcopenia has occurred over the last 10 years, with a growing emphasis on the central importance of muscle strength. Resistance exercise is currently the mainstay of treatment; however, it is not suitable for all. Hence, adjunctive and alternative treatments to improve quality of life are needed. An internationally agreed approach to definition and diagnosis will enable a step change in the field and is likely to be available in the near future through the Global Leadership Initiative in Sarcopenia.},
	pages = {68},
	number = {1},
	journaltitle = {Nature Reviews Disease Primers},
	shortjournal = {Nature Reviews Disease Primers},
	author = {Sayer, Avan A. and Cooper, Rachel and Arai, Hidenori and Cawthon, Peggy M. and Ntsama Essomba, Marie-Josiane and Fielding, Roger A. and Grounds, Miranda D. and Witham, Miles D. and Cruz-Jentoft, Alfonso J.},
	date = {2024-09-19},
}

@article{bates_fitting_2015-1,
	title = {Fitting Linear Mixed-Effects Models Using lme4},
	volume = {67},
	url = {https://www.jstatsoft.org/index.php/jss/article/view/v067i01},
	doi = {10.18637/jss.v067.i01},
	abstract = {Maximum likelihood or restricted maximum likelihood ({REML}) estimates of the parameters in linear mixed-effects models can be determined using the lmer function in the lme4 package for R. As for most model-fitting functions in R, the model is described in an lmer call by a formula, in this case including both fixed- and random-effects terms. The formula and data together determine a numerical representation of the model from which the profiled deviance or the profiled {REML} criterion can be evaluated as a function of some of the model parameters. The appropriate criterion is optimized, using one of the constrained optimization functions in R, to provide the parameter estimates. We describe the structure of the model, the steps in evaluating the profiled deviance or {REML} criterion, and the structure of classes or types that represents such a model. Sufficient detail is included to allow specialization of these structures by users who wish to write functions to fit specialized linear mixed models, such as models incorporating pedigrees or smoothing splines, that are not easily expressible in the formula language used by lmer.},
	pages = {1 -- 48},
	number = {1},
	journaltitle = {Journal of Statistical Software},
	shortjournal = {J. Stat. Soft.},
	author = {Bates, Douglas and Mächler, Martin and Bolker, Ben and Walker, Steve},
	urldate = {2025-08-28},
	date = {2015-10-07},
	note = {Section: Articles},
}

@article{brooks_glmmtmb_nodate,
	title = {{glmmTMB} Balances Speed and Flexibility Among Packages for Zero-inflated Generalized Linear Mixed Modeling.},
	volume = {9},
	doi = {doi: 10.32614/RJ-2017-066},
	pages = {378--400},
	number = {2},
	journaltitle = {The R journal},
	author = {Brooks, Mollie and Kristensen, Kasper and van Benjamin, Koen and Magnusson, Ani and Berg, Casper and Nielsen, Anders and Skaug, Hans and Maechler, Martin and Bolker, Benjamin},
}

@misc{brooks2017a,
  title = {{{glmmTMB}}: {{Generalized Linear Mixed Models}} Using {{Template Model Builder}}},
  shorttitle = {{{glmmTMB}}},
  author = {Brooks, Mollie and Bolker, Ben and Kristensen, Kasper and Maechler, Martin and Magnusson, Arni and Skaug, Hans and Nielsen, Anders and Berg, Casper and Van Bentham, Koen},
  year = 2017,
  month = feb,
  pages = {1.1.13},
  publisher = {Comprehensive R Archive Network},
  doi = {10.32614/CRAN.package.glmmTMB},
  urldate = {2025-11-14},
  abstract = {Fit linear and generalized linear mixed models with various extensions, including zero-inflation. The models are fitted using maximum likelihood estimation via 'TMB' (Template Model Builder). Random effects are assumed to be Gaussian on the scale of the linear predictor and are integrated out using the Laplace approximation. Gradients are calculated using automatic differentiation.},
  langid = {english}
}



@article{kuznetsova_lmertest_2017,
	title = {{lmerTest} Package: Tests in Linear Mixed Effects Models},
	volume = {82},
	url = {https://www.jstatsoft.org/index.php/jss/article/view/v082i13},
	doi = {10.18637/jss.v082.i13},
	abstract = {One of the frequent questions by users of the mixed model function lmer of the lme4 package has been: How can I get p values for the F and t tests for objects returned by lmer? The {lmerTest} package extends the '{lmerMod}' class of the lme4 package, by overloading the anova and summary functions by providing p values for tests for fixed effects. We have implemented the Satterthwaite's method for approximating degrees of freedom for the t and F tests. We have also implemented the construction of Type I - {III} {ANOVA} tables. Furthermore, one may also obtain the summary as well as the anova table using the Kenward-Roger approximation for denominator degrees of freedom (based on the {KRmodcomp} function from the pbkrtest package). Some other convenient mixed model analysis tools such as a step method, that performs backward elimination of nonsignificant effects  -  both random and fixed, calculation of population means and multiple comparison tests together with plot facilities are provided by the package as well.},
	pages = {1 -- 26},
	number = {13},
	journaltitle = {Journal of Statistical Software},
	shortjournal = {J. Stat. Soft.},
	author = {Kuznetsova, Alexandra and Brockhoff, Per B. and Christensen, Rune H. B.},
	urldate = {2025-08-28},
	date = {2017-12-06},
	note = {Section: Articles},
}

@software{lenth_emmeans_2025,
	title = {emmeans:  Estimated Marginal Means, aka Least-Squares Means},
	version = {1.11.1},
	author = {Lenth, Russell},
	date = {2025},
}

@article{ludecke_performance_2021,
	title = {performance: An R package for assessment, comparison and testing of statistical models},
	volume = {6},
	number = {60},
	journaltitle = {Journal of open source software},
	author = {Lüdecke, Daniel and Ben-Shachar, Mattan S. and Patil, Indrajeet and Waggoner, Philip and Makowski, Dominique},
	date = {2021},
}

@article{arel-bundock_how_2024,
	title = {How to Interpret Statistical Models Using marginaleffects for R and Python},
	volume = {111},
	url = {https://www.jstatsoft.org/index.php/jss/article/view/v111i09},
	doi = {10.18637/jss.v111.i09},
	abstract = {\&lt;p\&gt;The parameters of a statistical model can sometimes be difficult to interpret substantively, especially when that model includes nonlinear components, interactions, or transformations. Analysts who fit such complex models often seek to transform raw parameter estimates into quantities that are easier for domain experts and stakeholders to understand. This article presents a simple conceptual framework to describe a vast array of such quantities of interest, which are reported under imprecise and inconsistent terminology across disciplines: predictions, marginal predictions, marginal means, marginal effects, conditional effects, slopes, contrasts, risk ratios, etc. We introduce marginaleffects, a package for R and Python which offers a simple and powerful interface to compute all of those quantities, and to conduct (non-)linear hypothesis and equivalence tests on them. marginaleffects is lightweight; extensible; it works well in combination with other R and Python packages; and it supports over 100 classes of models, including linear, generalized linear, generalized additive, mixed effects, Bayesian, and several machine learning models.\&lt;/p\&gt;},
	pages = {1 -- 32},
	number = {9},
	journaltitle = {Journal of Statistical Software},
	shortjournal = {J. Stat. Soft.},
	author = {Arel-Bundock, Vincent and Greifer, Noah and Heiss, Andrew},
	urldate = {2025-08-28},
	date = {2024-11-30},
	note = {Section: Articles},
}

@article{shetty_peripheral_2024,
	title = {Peripheral blood transcriptomic profiling of molecular mechanisms commonly regulated by binge drinking and placebo effects.},
	volume = {14},
	rights = {© 2024. This is a U.S. Government work and not under copyright protection in the {US}; foreign copyright protection may apply.},
	issn = {2045-2322},
	doi = {10.1038/s41598-024-56900-x},
	abstract = {Molecular responses to alcohol consumption are dynamic, context-dependent, and arise from a complex interplay of biological and external factors. While many  have studied genetic risk associated with drinking patterns, comprehensive  studies identifying dynamic responses to pharmacologic and psychological/placebo  effects underlying binge drinking are lacking. We investigated transcriptome-wide  response to binge, medium, and placebo alcohol consumption by 17 healthy heavy  social drinkers enrolled in a controlled, in-house, longitudinal study of up to  12 days. Using {RNA}-seq, we identified 251 and 13 differentially expressed genes  ({DEGs}) in response to binge drinking and placebo, respectively. Eleven  protein-coding {DEGs} had very large effect sizes in response to binge drinking  (Cohen's d {\textgreater} 1). Furthermore, binge dose significantly impacted the  Cytokine-cytokine receptor interaction pathway ({KEGG}: hsa04060) across all  experimental sequences. Placebo also impacted hsa04060, but only when  administered following regular alcohol drinking sessions. Similarly, medium-dose  and placebo commonly impacted {KEGG} pathways of Systemic lupus erythematosus,  Neutrophil extracellular trap formation, and Alcoholism based on the sequence of  drinking sessions. These findings together indicate the "dose-extending effects"  of placebo at a molecular level. Furthermore, besides supporting alcohol  dose-specific molecular changes, results suggest that the placebo effects may  induce molecular responses within the same pathways regulated by alcohol.},
	pages = {10733},
	number = {1},
	journaltitle = {Scientific reports},
	shortjournal = {Sci Rep},
	author = {Shetty, Amol Carl and Sivinski, John and Cornell, Jessica and {McCracken}, Carrie and Sadzewicz, Lisa and Mahurkar, Anup and Wang, Xing-Qun and Colloca, Luana and Lin, Weihong and Pilli, Nageswara and Kane, Maureen A. and Seneviratne, Chamindi},
	date = {2024-05-10},
	pmid = {38730024},
	pmcid = {PMC11087488},
	note = {Place: England},
	keywords = {*Binge Drinking/blood/genetics, *Gene Expression Profiling, *Placebo Effect, *Transcriptome, Adult, Ethanol, Female, Gene Expression Regulation/drug effects, Humans, Longitudinal Studies, Male, Young Adult},
}


@article{pillon2022,
  title = {Distinctive Exercise-Induced Inflammatory Response and Exerkine Induction in Skeletal Muscle of People with Type 2 Diabetes},
  author = {Pillon, Nicolas J. and Smith, Jonathon A. B. and Alm, Petter S. and Chibalin, Alexander V. and Alhusen, Julia and Arner, Erik and Carninci, Piero and Fritz, Tomas and Otten, Julia and Olsson, Tommy and {van Doorslaer de ten Ryen}, Sophie and Deldicque, Louise and Caidahl, Kenneth and {Wallberg-Henriksson}, Harriet and Krook, Anna and Zierath, Juleen R.},
  year = 2022,
  month = sep,
  journal = {Science Advances},
  volume = {8},
  number = {36},
  pages = {eabo3192},
  issn = {2375-2548},
  doi = {10.1126/sciadv.abo3192},
  urldate = {2022-11-25},
  abstract = {Mechanistic insights into the molecular events by which exercise enhances the skeletal muscle phenotype are lacking, particularly in the context of type 2 diabetes. Here, we unravel a fundamental role for exercise-responsive cytokines (               exerkines               ) on skeletal muscle development and growth in individuals with normal glucose tolerance or type 2 diabetes. Acute exercise triggered an inflammatory response in skeletal muscle, concomitant with an infiltration of immune cells. These exercise effects were potentiated in type 2 diabetes. In response to contraction or hypoxia, cytokines were mainly produced by endothelial cells and macrophages. The chemokine CXCL12 was induced by hypoxia in endothelial cells, as well as by conditioned medium from contracted myotubes in macrophages. We found that CXCL12 was associated with skeletal muscle remodeling after exercise and differentiation of cultured muscle. Collectively, acute aerobic exercise mounts a noncanonical inflammatory response, with an atypical production of exerkines, which is potentiated in type 2 diabetes.                        ,              Exercise triggers a noncanonical inflammatory response in people with type 2 diabetes, with an atypical production of exerkines.},
  langid = {english},
  file = {C:\Users\706194\Zotero\storage\6MZJGLDI\Pillon et al. - 2022 - Distinctive exercise-induced inflammatory response.pdf}
}

@article{robinson2010,
  title = {A Scaling Normalization Method for Differential Expression Analysis of {{RNA-seq}} Data},
  author = {Robinson, Mark D. and Oshlack, Alicia},
  year = 2010,
  month = mar,
  journal = {Genome Biology},
  volume = {11},
  number = {3},
  pages = {R25},
  issn = {1474-760X},
  doi = {10.1186/gb-2010-11-3-r25},
  abstract = {The fine detail provided by sequencing-based transcriptome surveys suggests that RNA-seq is likely to become the platform of choice for interrogating steady state RNA. In order to discover biologically important changes in expression, we show that normalization continues to be an essential step in the analysis. We outline a simple and effective method for performing normalization and show dramatically improved results for inferring differential expression in simulated and publicly available data sets.},
  file = {C:\Users\706194\Zotero\storage\6C6B7LB7\Robinson-2010-A scaling normalization method f.pdf}
}

@book{pinheiro2000,
  title = {Mixed-Effects Models in {{S}} and {{S-PLUS}}},
  author = {Pinheiro, Jos{\'e} C. and Bates, Douglas M.},
  year = 2000,
  series = {Statistics and Computing},
  publisher = {Springer},
  address = {New York},
  isbn = {0387989579 (alk. paper)},
  lccn = {QA76.73.S15 P56 2000},
  file = {C:\Users\706194\Zotero\storage\TQ73TRX9\Pinheiro-2000-Mixed-effects models in S and S-.pdf}
}


@article{cui2016,
  title = {What If We Ignore the Random Effects When Analyzing {{RNA-seq}} Data in a Multifactor Experiment},
  author = {Cui, S. and Ji, T. and Li, J. and Cheng, J. and Qiu, J.},
  year = 2016,
  month = apr,
  journal = {Stat Appl Genet Mol Biol},
  edition = {2016/03/02},
  volume = {15},
  number = {2},
  eprint = {26926865},
  eprinttype = {pubmed},
  pages = {87--105},
  issn = {1544-6115 (Electronic) 1544-6115 (Linking)},
  doi = {10.1515/sagmb-2015-0011},
  urldate = {2020-02-14},
  abstract = {Identifying differentially expressed (DE) genes between different conditions is one of the main goals of RNA-seq data analysis. Although a large amount of RNA-seq data were produced for two-group comparison with small sample sizes at early stage, more and more RNA-seq data are being produced in the setting of complex experimental designs such as split-plot designs and repeated measure designs. Data arising from such experiments are traditionally analyzed by mixed-effects models. Therefore an appropriate statistical approach for analyzing RNA-seq data from such designs should be generalized linear mixed models (GLMM) or similar approaches that allow for random effects. However, common practices for analyzing such data in literature either treat random effects as fixed or completely ignore the experimental design and focus on two-group comparison using partial data. In this paper, we examine the effect of ignoring the random effects when analyzing RNA-seq data. We accomplish this goal by comparing the standard GLMM model to the methods that ignore the random effects through simulation studies and real data analysis. Our studies show that, ignoring random effects in a multi-factor experiment can lead to the increase of the false positives among the top selected genes or lower power when the nominal FDR level is controlled.},
  keywords = {Biometry,Gene Expression Profiling/statistics & numerical data,High-Throughput Nucleotide Sequencing/methods/*statistics & numerical data,Linear Models,Models Statistical,Sequence Analysis RNA/methods/*statistics & numerical data},
  file = {C:\Users\706194\Zotero\storage\MAQCV6TQ\Cui-2016-What if we ignore the random effects.pdf}
}

@article{sun2017,
  title = {Differential Expression Analysis for {{RNAseq}} Using {{Poisson}} Mixed Models},
  author = {Sun, Shiquan and Hood, Michelle and Scott, Laura and Peng, Qinke and Mukherjee, Sayan and Tung, Jenny and Zhou, Xiang},
  year = 2017,
  month = jun,
  journal = {Nucleic Acids Research},
  volume = {45},
  number = {11},
  pages = {e106},
  issn = {1362-4962},
  doi = {10.1093/nar/gkx204},
  abstract = {Identifying differentially expressed (DE) genes from RNA sequencing (RNAseq) studies is among the most common analyses in genomics. However, RNAseq DE analysis presents several statistical and computational challenges, including over-dispersed read counts and, in some settings, sample non-independence. Previous count-based methods rely on simple hierarchical Poisson models (e.g. negative binomial) to model independent over-dispersion, but do not account for sample non-independence due to relatedness, population structure and/or hidden confounders. Here, we present a Poisson mixed model with two random effects terms that account for both independent over-dispersion and sample non-independence. We also develop a scalable sampling-based inference algorithm using a latent variable representation of the Poisson distribution. With simulations, we show that our method properly controls for type I error and is generally more powerful than other widely used approaches, except in small samples (n {$<$}15) with other unfavorable properties (e.g. small effect sizes). We also apply our method to three real datasets that contain related individuals, population stratification or hidden confounders. Our results show that our method increases power in all three data compared to other approaches, though the power gain is smallest in the smallest sample (n = 6). Our method is implemented in MACAU, freely available at www.xzlab.org/software.html.},
  langid = {english},
  pmcid = {PMC5499851},
  pmid = {28369632},
  keywords = {Algorithms,Bayes Theorem,Computer Simulation,Gene Expression Profiling,Humans,Linear Models,Markov Chains,Models Genetic,Monte Carlo Method,Poisson Distribution,Sequence Analysis RNA,Software},
  file = {C:\Users\706194\Zotero\storage\EB35I4AT\Sun et al. - 2017 - Differential expression analysis for RNAseq using Poisson mixed models.pdf}
}

@article{harrison2014,
  title = {Using Observation-Level Random Effects to Model Overdispersion in Count Data in Ecology and Evolution},
  author = {Harrison, Xavier A.},
  year = 2014,
  journal = {PeerJ},
  volume = {2},
  pages = {e616},
  issn = {2167-8359},
  doi = {10.7717/peerj.616},
  abstract = {Overdispersion is common in models of count data in ecology and evolutionary biology, and can occur due to missing covariates, non-independent (aggregated) data, or an excess frequency of zeroes (zero-inflation). Accounting for overdispersion in such models is vital, as failing to do so can lead to biased parameter estimates, and false conclusions regarding hypotheses of interest. Observation-level random effects (OLRE), where each data point receives a unique level of a random effect that models the extra-Poisson variation present in the data, are commonly employed to cope with overdispersion in count data. However studies investigating the efficacy of observation-level random effects as a means to deal with overdispersion are scarce. Here I use simulations to show that in cases where overdispersion is caused by random extra-Poisson noise, or aggregation in the count data, observation-level random effects yield more accurate parameter estimates compared to when overdispersion is simply ignored. Conversely, OLRE fail to reduce bias in zero-inflated data, and in some cases increase bias at high levels of overdispersion. There was a positive relationship between the magnitude of overdispersion and the degree of bias in parameter estimates. Critically, the simulations reveal that failing to account for overdispersion in mixed models can erroneously inflate measures of explained variance (r (2)), which may lead to researchers overestimating the predictive power of variables of interest. This work suggests use of observation-level random effects provides a simple and robust means to account for overdispersion in count data, but also that their ability to minimise bias is not uniform across all types of overdispersion and must be applied judiciously.},
  langid = {english},
  pmcid = {PMC4194460},
  pmid = {25320683},
  keywords = {Explained variance,Generalized linear mixed models,Observation-level random effect,Poisson-lognormal models,Quasi-Poisson,r-squared},
  file = {C:\Users\706194\Zotero\storage\5CGWWPQV\Harrison - 2014 - Using observation-level random effects to model overdispersion in count data in ecology and evolutio.pdf}
}

@article{mccarthy2012,
  title = {Differential Expression Analysis of Multifactor {{RNA-Seq}} Experiments with Respect to Biological Variation},
  author = {McCarthy, Davis J. and Chen, Yunshun and Smyth, Gordon K.},
  year = 2012,
  journal = {Nucleic Acids Research},
  volume = {40},
  number = {10},
  pages = {4288--4297},
  issn = {0305-1048},
  doi = {10.1093/nar/gks042},
  urldate = {2020-05-16},
  abstract = {A flexible statistical framework is developed for the analysis of read counts from RNA-Seq gene expression studies. It provides the ability to analyse complex experiments involving multiple treatment conditions and blocking variables while still taking full account of biological variation. Biological variation between RNA samples is estimated separately from the technical variation associated with sequencing technologies. Novel empirical Bayes methods allow each gene to have its own specific variability, even when there are relatively few biological replicates from which to estimate such variability. The pipeline is implemented in the edgeR package of the Bioconductor project. A case study analysis of carcinoma data demonstrates the ability of generalized linear model methods (GLMs) to detect differential expression in a paired design, and even to detect tumour-specific expression changes. The case study demonstrates the need to allow for gene-specific variability, rather than assuming a common dispersion across genes or a fixed relationship between abundance and variability. Genewise dispersions de-prioritize genes with inconsistent results and allow the main analysis to focus on changes that are consistent between biological replicates. Parallel computational approaches are developed to make non-linear model fitting faster and more reliable, making the application of GLMs to genomic data more convenient and practical. Simulations demonstrate the ability of adjusted profile likelihood estimators to return accurate estimators of biological variability in complex situations. When variation is gene-specific, empirical Bayes estimators provide an advantageous compromise between the extremes of assuming common dispersion or separate genewise dispersion. The methods developed here can also be applied to count data arising from DNA-Seq applications, including ChIP-Seq for epigenetic marks and DNA methylation analyses.},
  file = {C:\Users\706194\Zotero\storage\X4KPN6KM\McCarthy-2012-Differential expression analysis.pdf}
}

@article{zyla2019,
  title = {Gene Set Enrichment for Reproducible Science: Comparison of {{CERNO}} and Eight Other Algorithms},
  author = {Zyla, J. and Marczyk, M. and Domaszewska, T. and Kaufmann, S. H. E. and Polanska, J. and Weiner, J.},
  year = 2019,
  month = dec,
  journal = {Bioinformatics},
  edition = {2019/06/06},
  volume = {35},
  number = {24},
  pages = {5146--5154},
  issn = {1367-4803 (Print) 1367-4803},
  doi = {10.1093/bioinformatics/btz447},
  abstract = {MOTIVATION: Analysis of gene set (GS) enrichment is an essential part of functional omics studies. Here, we complement the established evaluation metrics of GS enrichment algorithms with a novel approach to assess the practical reproducibility of scientific results obtained from GS enrichment tests when applied to related data from different studies. RESULTS: We evaluated eight established and one novel algorithm for reproducibility, sensitivity, prioritization, false positive rate and computational time. In addition to eight established algorithms, we also included Coincident Extreme Ranks in Numerical Observations (CERNO), a flexible and fast algorithm based on modified Fisher P-value integration. Using real-world datasets, we demonstrate that CERNO is robust to ranking metrics, as well as sample and GS size. CERNO had the highest reproducibility while remaining sensitive, specific and fast. In the overall ranking Pathway Analysis with Down-weighting of Overlapping Genes, CERNO and over-representation analysis performed best, while CERNO and GeneSetTest scored high in terms of reproducibility. AVAILABILITY AND IMPLEMENTATION: tmod package implementing the CERNO algorithm is available from CRAN (cran.r-project.org/web/packages/tmod/index.html) and an online implementation can be found at http://tmod.online/. The datasets analyzed in this study are widely available in the KEGGdzPathwaysGEO, KEGGandMetacoreDzPathwaysGEO R package and GEO repository. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.},
  langid = {english},
  file = {C:\Users\706194\Zotero\storage\3B98Q5D3\Zyla-2019-Gene set enrichment for reproducible.pdf}
}

@article{conesa2016,
  title = {A Survey of Best Practices for {{RNA-seq}} Data Analysis},
  author = {Conesa, Ana and Madrigal, Pedro and Tarazona, Sonia and {Gomez-Cabrero}, David and Cervera, Alejandra and McPherson, Andrew and Szcze{\'s}niak, Micha{\l} Wojciech and Gaffney, Daniel J. and Elo, Laura L. and Zhang, Xuegong and Mortazavi, Ali},
  year = 2016,
  journal = {Genome biology},
  volume = {17},
  pages = {13--13},
  issn = {1474-760X 1474-7596},
  doi = {10.1186/s13059-016-0881-8},
  abstract = {RNA-sequencing (RNA-seq) has a wide variety of applications, but no single analysis pipeline can be used in all cases. We review all of the major steps in RNA-seq data analysis, including experimental design, quality control, read alignment, quantification of gene and transcript levels, visualization, differential gene expression, alternative splicing, functional analysis, gene fusion detection and eQTL mapping. We highlight the challenges associated with each step. We discuss the analysis of small RNAs and the integration of RNA-seq with other functional genomics techniques. Finally, we discuss the outlook for novel technologies that are changing the state of the art in transcriptomics.},
  langid = {english},
  keywords = {*Genomics,Alternative Splicing/genetics,Base Sequence,Gene Expression Profiling,Gene Fusion/genetics,High-Throughput Nucleotide Sequencing/*methods,RNA/*genetics,Sequence Analysis RNA/*methods,Software},
  file = {C:\Users\706194\Zotero\storage\ZPSBSWRH\Conesa-2016-A survey of best practices for RNA.pdf}
}

@book{efron2010,
  title = {Large-{{Scale Inference}}: {{Empirical Bayes Methods}} for {{Estimation}}, {{Testing}}, and {{Prediction}}},
  shorttitle = {Large-{{Scale Inference}}},
  author = {Efron, Bradley},
  year = 2010,
  month = aug,
  edition = {1},
  publisher = {Cambridge University Press},
  doi = {10.1017/CBO9780511761362},
  urldate = {2025-11-17},
  abstract = {We live in a new age for statistical inference, where modern scientific technology such as microarrays and fMRI machines routinely produce thousands and sometimes millions of parallel data sets, each with its own estimation or testing problem. Doing thousands of problems at once is more than repeated application of classical methods. Taking an empirical Bayes approach, Bradley Efron, inventor of the bootstrap, shows how information accrues across problems in a way that combines Bayesian and frequentist ideas. Estimation, testing and prediction blend in this framework, producing opportunities for new methodologies of increased power. New difficulties also arise, easily leading to flawed inferences. This book takes a careful look at both the promise and pitfalls of large-scale statistical inference, with particular attention to false discovery rates, the most successful of the new statistical techniques. Emphasis is on the inferential ideas underlying technical developments, illustrated using a large number of real examples.},
  copyright = {https://www.cambridge.org/core/terms},
  isbn = {978-0-521-19249-1 978-0-511-76136-2 978-1-107-61967-8},
  file = {C:\Users\706194\Zotero\storage\WKP3J9BI\Efron - 2010 - Large-Scale Inference Empirical Bayes Methods for Estimation, Testing, and Prediction.pdf}
}

@article{chen2020,
  title = {Bioinformatics {{Methods}} for {{Mass Spectrometry-Based Proteomics Data Analysis}}},
  author = {Chen, Chen and Hou, Jie and Tanner, John J. and Cheng, Jianlin},
  year = 2020,
  month = apr,
  journal = {International Journal of Molecular Sciences},
  volume = {21},
  number = {8},
  pages = {2873},
  issn = {1422-0067},
  doi = {10.3390/ijms21082873},
  urldate = {2025-11-21},
  abstract = {Recent advances in mass spectrometry (MS)-based proteomics have enabled tremendous progress in the understanding of cellular mechanisms, disease progression, and the relationship between genotype and phenotype. Though many popular bioinformatics methods in proteomics are derived from other omics studies, novel analysis strategies are required to deal with the unique characteristics of proteomics data. In this review, we discuss the current developments in the bioinformatics methods used in proteomics and how they facilitate the mechanistic understanding of biological processes. We first introduce bioinformatics software and tools designed for mass spectrometry-based protein identification and quantification, and then we review the different statistical and machine learning methods that have been developed to perform comprehensive analysis in proteomics studies. We conclude with a discussion of how quantitative protein data can be used to reconstruct protein interactions and signaling networks.},
  langid = {english},
  file = {C:\Users\706194\Zotero\storage\GYGNDPR5\Chen et al. - 2020 - Bioinformatics Methods for Mass Spectrometry-Based Proteomics Data Analysis.pdf}
}

@Manual{DHARMa,
    title = {DHARMa: Residual Diagnostics for Hierarchical (Multi-Level / Mixed)
Regression Models},
    author = {Florian Hartig},
    year = {2024},
    note = {R package version 0.4.7},
    url = {https://CRAN.R-project.org/package=DHARMa},
    doi = {10.32614/CRAN.package.DHARMa},
  }

@article{xu2024,
  title = {Using {{clusterProfiler}} to Characterize Multiomics Data},
  author = {Xu, Shuangbin and Hu, Erqiang and Cai, Yantong and Xie, Zijing and Luo, Xiao and Zhan, Li and Tang, Wenli and Wang, Qianwen and Liu, Bingdong and Wang, Rui and Xie, Wenqin and Wu, Tianzhi and Xie, Liwei and Yu, Guangchuang},
  year = 2024,
  month = nov,
  journal = {Nature Protocols},
  volume = {19},
  number = {11},
  pages = {3292--3320},
  issn = {1754-2189, 1750-2799},
  doi = {10.1038/s41596-024-01020-z},
  urldate = {2025-11-28},
  langid = {english}
}

@article{dungan2022,
  title = {Senolytic Treatment Rescues Blunted Muscle Hypertrophy in Old Mice},
  author = {Dungan, Cory M. and Figueiredo, Vandre C. and Wen, Yuan and VonLehmden, Georgia L. and Zdunek, Christopher J. and Thomas, Nicholas T. and Mobley, C. Brooks and Murach, Kevin A. and Brightwell, Camille R. and Long, Douglas E. and Fry, Christopher S. and Kern, Philip A. and McCarthy, John J. and Peterson, Charlotte A.},
  year = 2022,
  month = aug,
  journal = {GeroScience},
  volume = {44},
  number = {4},
  pages = {1925--1940},
  issn = {2509-2715, 2509-2723},
  doi = {10.1007/s11357-022-00542-2},
  urldate = {2025-12-05},
  abstract = {Abstract                            With aging, skeletal muscle plasticity is attenuated in response to exercise. Here, we report that senescent cells, identified using senescence-associated {$\beta$}-galactosidase (SA {$\beta$}-Gal) activity and p21 immunohistochemistry, are very infrequent in resting muscle, but emerge approximately 2~weeks after a bout of resistance exercise in humans. We hypothesized that these cells contribute to blunted hypertrophic potential in old age. Using synergist ablation-induced mechanical overload (MOV) of the plantaris muscle to model resistance training in adult (5--6-month) and old (23--24-month) male C57BL/6~J mice, we found increased senescent cells in both age groups during hypertrophy. Consistent with the human data, there were negligible senescent cells in plantaris muscle from adult and old sham controls, but old mice had significantly more senescent cells 7 and 14~days following MOV relative to young. Old mice had blunted whole-muscle hypertrophy when compared to adult mice, along with smaller muscle fibers, specifically glycolytic type 2x\,+\,2b fibers. To ablate senescent cells using a hit-and-run approach, old mice were treated with vehicle or a senolytic cocktail consisting of 5~mg/kg dasatinib and 50~mg/kg quercetin (D\,+\,Q) on days 7 and 10 during 14~days of MOV; control mice underwent sham surgery with or without senolytic treatment. Old mice given D\,+\,Q had larger muscles and muscle fibers after 14~days of MOV, fewer senescent cells when compared to vehicle-treated old mice, and changes in the expression of genes (i.e.,               Igf1               ,               Ddit4               ,               Mmp14               ) that are associated with hypertrophic growth. Our data collectively show that senescent cells emerge in human and mouse skeletal muscle following a hypertrophic stimulus and that D\,+\,Q improves muscle growth in old mice.},
  langid = {english},
  file = {C:\Users\706194\Zotero\storage\A5HBRU2A\Dungan et al. - 2022 - Senolytic treatment rescues blunted muscle hypertrophy in old mice.pdf}
}

@article{smyth2004,
  title = {Linear {{Models}} and {{Empirical Bayes Methods}} for {{Assessing Differential Expression}} in {{Microarray Experiments}}},
  author = {Smyth, Gordon K},
  year = 2004,
  month = jan,
  journal = {Statistical Applications in Genetics and Molecular Biology},
  volume = {3},
  number = {1},
  pages = {1--25},
  issn = {1544-6115},
  doi = {10.2202/1544-6115.1027},
  urldate = {2025-11-17},
  abstract = {The problem of identifying differentially expressed genes in designed microarray experiments is considered. Lonnstedt and Speed (2002) derived an expression for the posterior odds of differential expression in a replicated two-color experiment using a simple hierarchical parametric model. The purpose of this paper is to develop the hierarchical model of Lonnstedt and Speed (2002) into a practical approach for general microarray experiments with arbitrary numbers of treatments and RNA samples. The model is reset in the context of general linear models with arbitrary coefficients and contrasts of interest. The approach applies equally well to both single channel and two color microarray experiments. Consistent, closed form estimators are derived for the hyperparameters in the model. The estimators proposed have robust behavior even for small numbers of arrays and allow for incomplete data arising from spot filtering or spot quality weights. The posterior odds statistic is reformulated in terms of a moderated t-statistic in which posterior residual standard deviations are used in place of ordinary standard deviations. The empirical Bayes approach is equivalent to shrinkage of the estimated sample variances towards a pooled estimate, resulting in far more stable inference when the number of arrays is small. The use of moderated t-statistics has the advantage over the posterior odds that the number of hyperparameters which need to estimated is reduced; in particular, knowledge of the non-null prior for the fold changes are not required. The moderated t-statistic is shown to follow a t-distribution with augmented degrees of freedom. The moderated t inferential approach extends to accommodate tests of composite null hypotheses through the use of moderated F-statistics. The performance of the methods is demonstrated in a simulation study. Results are presented for two publicly available data sets.},
  file = {C:\Users\706194\Zotero\storage\TQL62J4G\Smyth - 2004 - Linear Models and Empirical Bayes Methods for Assessing Differential Expression in Microarray Experi.pdf}
}

@article{chen2025,
  title = {{{edgeR}} v4: Powerful Differential Analysis of Sequencing Data with Expanded Functionality and Improved Support for Small Counts and Larger Datasets},
  shorttitle = {{{edgeR}} V4},
  author = {Chen, Yunshun and Chen, Lizhong and Lun, Aaron~T L and Baldoni, Pedro~L and Smyth, Gordon~K},
  year = 2025,
  month = jan,
  journal = {Nucleic Acids Research},
  volume = {53},
  number = {2},
  pages = {gkaf018},
  issn = {0305-1048, 1362-4962},
  doi = {10.1093/nar/gkaf018},
  urldate = {2025-04-04},
  abstract = {Abstract             edgeR is an R/Bioconductor software package for differential analyses of sequencing data in the form of read counts for genes or genomic features. Over the past 15~years, edgeR has been a popular choice for statistical analysis of data from sequencing technologies such as RNA-seq or ChIP-seq. edgeR pioneered the use of the negative binomial distribution to model read count data with replicates and the use of generalized linear models to analyze complex experimental designs. edgeR implements empirical Bayes moderation methods to allow reliable inference when the number of replicates is small. This article announces edgeR version 4, which includes new developments across a range of application areas. Infrastructure improvements include support for fractional counts, implementation of model fitting in C and a new statistical treatment of the quasi-likelihood pipeline that improves accuracy for small counts. The revised package has new functionality for differential methylation analysis, differential transcript expression, differential transcript and exon usage, testing relative to a fold-change threshold and pathway analysis. This article reviews the statistical framework and computational implementation of edgeR, briefly summarizing all the existing features and functionalities but with special attention to new features and those that have not been described previously.},
  copyright = {https://creativecommons.org/licenses/by/4.0/},
  langid = {english},
  file = {C:\Users\706194\Zotero\storage\8L9MVQHY\Chen et al. - 2025 - edgeR v4 powerful differential analysis of sequencing data with expanded functionality and improved.pdf}
}

@article{stephens2016,
  title = {False Discovery Rates: A New Deal},
  shorttitle = {False Discovery Rates},
  author = {Stephens, Matthew},
  year = 2016,
  month = oct,
  journal = {Biostatistics},
  pages = {kxw041},
  issn = {1465-4644, 1468-4357},
  doi = {10.1093/biostatistics/kxw041},
  urldate = {2025-12-08},
  langid = {english}
}

@article{sen2025,
  title = {Down-Regulation of Human-Specific {{lncRNA TMEM9B-AS1}} in Skeletal Muscle of People with Type 2 Diabetes Affects Ribosomal Biogenesis},
  author = {Sen, Ilke and Smith, Jonathon A. B. and Caria, Elena and Orlov, Iurii and Savikj, Mladen and Brady, Aidan J. and Lian, Kristian and Ellefsen, Stian and Zierath, Juleen R. and Krook, Anna},
  year = 2025,
  month = jul,
  journal = {Science Advances},
  volume = {11},
  number = {28},
  pages = {eads4371},
  issn = {2375-2548},
  doi = {10.1126/sciadv.ads4371},
  urldate = {2025-12-08},
  abstract = {Long noncoding RNAs (lncRNAs) are important regulators of skeletal muscle physiology, with altered expression noted in several human diseases including type 2 diabetes. We report that TMEM9B-AS1, a previously uncharacterized lncRNA, is down-regulated in skeletal muscle of men with type 2 diabetes and skeletal muscle from individuals with sarcopenia. Silencing of TMEM9B-AS1 in primary human myotubes attenuated protein synthesis, concomitant with reduced phosphorylation of ribosomal protein S6. Moreover, we show that TMEM9B-AS1 plays a pivotal role in regulation of ribosomal biogenesis by facilitating messenger RNA stabilization of the transcription factor MYC through direct physical interaction with the RNA binding protein, insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1). Disrupted ribosomal biogenesis resulting from TMEM9B-AS1 silencing leads to decreased expression of muscle contractile and structural proteins important for maintenance of skeletal muscle mass and function. Collectively, our data reveal a role of TMEM9B-AS1 in skeletal muscle loss associated with metabolic disorders.           ,              TMEM9B-AS1, down-regulated in type 2 diabetes, regulates ribosomal biogenesis in muscle by promoting IGF2BP1-MYC mRNA interaction.},
  langid = {english}
}

@article{li2022,
  title = {Exaggerated False Positives by Popular Differential Expression Methods When Analyzing Human Population Samples},
  author = {Li, Yumei and Ge, Xinzhou and Peng, Fanglue and Li, Wei and Li, Jingyi Jessica},
  year = 2022,
  month = mar,
  journal = {Genome Biology},
  volume = {23},
  number = {1},
  pages = {79},
  issn = {1474-760X},
  doi = {10.1186/s13059-022-02648-4},
  abstract = {When identifying differentially expressed genes between two conditions using human population RNA-seq samples, we found a phenomenon by permutation analysis: two popular bioinformatics methods, DESeq2 and edgeR, have unexpectedly high false discovery rates. Expanding the analysis to limma-voom, NOISeq, dearseq, and Wilcoxon rank-sum test, we found that FDR control is often failed except for the Wilcoxon rank-sum test. Particularly, the actual FDRs of DESeq2 and edgeR sometimes exceed 20\% when the target FDR is 5\%. Based on these results, for population-level RNA-seq studies with large sample sizes, we recommend the Wilcoxon rank-sum test.},
  langid = {english},
  pmcid = {PMC8922736},
  pmid = {35292087},
  keywords = {Computational Biology,Gene Expression Profiling,Humans,RNA-Seq,Sample Size,Sequence Analysis RNA},
  file = {C:\Users\706194\Zotero\storage\JVIIL966\Li et al. - 2022 - Exaggerated false positives by popular differential expression methods when analyzing human populati.pdf}
}

@article{zyla2017,
  title = {Ranking Metrics in Gene Set Enrichment Analysis: Do They Matter?},
  author = {Zyla, Joanna and Marczyk, Michal and Weiner, January and Polanska, Joanna},
  year = 2017,
  month = may,
  journal = {BMC bioinformatics},
  volume = {18},
  number = {1},
  pages = {256},
  issn = {1471-2105},
  doi = {10.1186/s12859-017-1674-0},
  langid = {english},
  keywords = {Algorithms},
  file = {C:\Users\706194\Zotero\storage\F4IRWFE4\Zyla-2017-Ranking metrics in gene set enrichme.pdf}
}

