Exercise and nutrition to improve cancer Treatment-Related outcomes (ENICTO).

Chemotherapy treatment-related side-effects are common and increase the risk of suboptimal outcomes. Exercise interventions during cancer treatment improve self-reported physical functioning, fatigue, anxiety, and depression, but it is unclear whether these interventions improve important clinical outcomes, such as chemotherapy relative dose intensity (RDI). The National Cancer Institute funded the Exercise and Nutrition to Improve Cancer Treatment-Related Outcomes (ENICTO) Consortium, to address this knowledge gap. This paper describes the mechanisms hypothesized to underpin intervention effects on clinically-relevant treatment outcomes, briefly outlines each project's distinct research aims, summarizes the scope and organizational structure of ENICTO, and provides an overview of the integrated common data elements used to pursue research questions collectively. In addition, the paper includes a description of consortium-wide activities and broader research community opportunities for collaborative research. Findings from the ENICTO Consortium have the potential to accelerate a paradigm shift in oncology care such that cancer patients could receive exercise and nutrition programming as the standard of care in tandem with chemotherapy to improve RDI for a curative outcome.

Accurate prediction of three-dimensional humanoid avatars for anthropometric modeling.

OBJECTIVE: To evaluate the hypothesis that anthropometric dimensions derived from a person's manifold-regression predicted three-dimensional (3D) humanoid avatar are accurate when compared to their actual circumference, volume, and surface area measurements acquired with a ground-truth 3D optical imaging method. Avatars predicted using this approach, if accurate with respect to anthropometric dimensions, can serve multiple purposes including patient body composition analysis and metabolic disease risk stratification in clinical settings. METHODS: Manifold regression 3D avatar prediction equations were developed on a sample of 570 adults who completed 3D optical scans, dual-energy X-ray absorptiometry (DXA), and bioimpedance analysis (BIA) evaluations. A new prospective sample of 84 adults had ground-truth measurements of 6 body circumferences, 7 volumes, and 7 surface areas with a 20-camera 3D reference scanner. 3D humanoid avatars were generated on these participants with manifold regression including age, weight, height, DXA %fat, and BIA impedances as potential predictor variables. Ground-truth and predicted avatar anthropometric dimensions were quantified with the same software. RESULTS: Following exploratory studies, one manifold prediction model was moved forward for presentation that included age, weight, height, and %fat as covariates. Predicted and ground-truth avatars had similar visual appearances; correlations between predicted and ground-truth anthropometric estimates were all high (R2s, 0.75-0.99; all p < 0.001) with non-significant mean differences except for arm circumferences (%Δ ~ 5%; p < 0.05). Concordance correlation coefficients ranged from 0.80-0.99 and small but significant bias (p < 0.05-0.01) was present with Bland-Altman plots in 13 of 20 total anthropometric measurements. The mean waist to hip circumference ratio predicted by manifold regression was non-significantly different from ground-truth scanner measurements. CONCLUSIONS: 3D avatars predicted from demographic, physical, and other accessible characteristics can produce body representations with accurate anthropometric dimensions without a 3D scanner. Combining manifold regression algorithms into established body composition methods such as DXA, BIA, and other accessible methods provides new research and clinical opportunities.

Analysis of the Types of Retracted COVID-19 Articles Published in PubMed-Listed Journals.

OBJECTIVES: Periodically, medical publications are retracted. The reasons vary from minor situations, such as author attributions, which do not undermine the validity of the data or the analysis in the article, to serious reasons, such as fraud. Understanding the reasons for retraction can provide important information for clinicians, educators, researchers, journals, and editorial boards. METHODS: The PubMed database was searched using the term "COVID-19" (coronavirus disease 2019) and the term limitation "retracted publication." The characteristics of the journals with retracted articles, the types of article, and the reasons for retraction were analyzed. RESULTS: This search recovered 196 articles that had been retracted. These retractions were published in 179 different journals; 14 journals had >1 retracted article. The mean impact factor of these journals was 8.4, with a range of 0.32-168.9. The most frequent reasons for retractions were duplicate publication, concerns about data validity and analysis, concerns about peer review, author request, and the lack of permission or ethical violation. There were significant differences between the types of article and the reasons for retraction but no consistent pattern. A more detailed analysis of two particular retractions demonstrates the complexity and the effort required to make decisions about article retractions. CONCLUSIONS: The retraction of published articles presents a significant challenge to journals, editorial boards, peer reviewers, and authors. This process has the potential to provide important benefits; it also has the potential to undermine confidence in both research and the editorial process.

Accurate Prediction of Three-Dimensional Humanoid Avatars for Anthropometric Modeling.

Objective: To evaluate the hypothesis that anthropometric dimensions derived from a person's manifold-regression predicted three-dimensional (3D) humanoid avatar are accurate when compared to their actual circumference, volume, and surface area measurements acquired with a ground-truth 3D optical imaging method. Avatars predicted using this approach, if accurate with respect to anthropometric dimensions, can serve multiple purposes including patient metabolic disease risk stratification in clinical settings. Methods: Manifold regression 3D avatar prediction equations were developed on a sample of 570 adults who completed 3D optical scans, dual-energy X-ray absorptiometry (DXA), and bioimpedance analysis (BIA) evaluations. A new prospective sample of 84 adults had ground-truth measurements of 6 body circumferences, 7 volumes, and 7 surface areas with a 20-camera 3D reference scanner. 3D humanoid avatars were generated on these participants with manifold regression including age, weight, height, DXA %fat, and BIA impedances as potential predictor variables. Ground-truth and predicted avatar anthropometric dimensions were quantified with the same software. Results: Following exploratory studies, one manifold prediction model was moved forward for presentation that included age, weight, height, and %fat as covariates. Predicted and ground-truth avatars had similar visual appearances; correlations between predicted and ground-truth anthropometric estimates were all high (R2s, 0.75-0.99; all p < 0.001) with non-significant mean differences except for arm circumferences (%D ~ 5%; p < 0.05). Concordance correlation coefficients ranged from 0.80-0.99 and small but significant bias (p < 0.05 - 0.01) was present with Bland-Altman plots in 13 of 20 total anthropometric measurements. The mean waist to hip circumference ratio predicted by manifold regression was non-significantly different from ground-truth scanner measurements. Conclusions: 3D avatars predicted from demographic, physical, and other accessible characteristics can produce body representations with accurate anthropometric dimensions without a 3D scanner. Combining manifold regression algorithms into established body composition methods such as DXA, BIA, and other accessible methods provides new research and clinical opportunities.

Effect of resistance training on physical function during chemotherapy in colon cancer.

BACKGROUND: The decline of physical function during chemotherapy predicts poor quality of life and premature death. It is unknown if resistance training prevents physical function decline during chemotherapy in colon cancer survivors. METHODS: This multicenter trial randomly assigned 181 colon cancer survivors receiving postoperative chemotherapy to home-based resistance training or usual care control. Physical function outcomes included the short physical performance battery, isometric handgrip strength, and the physical function subscale of the Medical Outcomes Short-Form 36-item questionnaire. Mixed models for repeated measures quantified estimated treatment differences. RESULTS: At baseline, participants had a mean (SD) age of 55.2 (12.8) years; 67 (37%) were 60 years or older, and 29 (16%) had a composite short physical performance battery score of no more than 9. Compared with usual care control, resistance training did not improve the composite short physical performance battery score (estimated treatment difference = -0.01, 95% confidence interval [CI] = -0.32 to 0.31; P = .98) or the short physical performance battery scores for balance (estimated treatment difference = 0.01, 95% CI = -0.10 to 0.11; P = .93), gait speed (estimated treatment difference = 0.08, 95% CI = -0.06 to 0.22; P = .28), and sit-to-stand (estimated treatment difference = -0.08, 95% CI = -0.29 to 0.13; P = .46). Compared with usual care control, resistance training did not improve isometric handgrip strength (estimated treatment difference = 1.50 kg, 95% CI = -1.06 to 4.05; P = .25) or self-reported physical function (estimated treatment difference = -3.55, 95% CI = -10.03 to 2.94); P = .28). The baseline short physical performance battery balance score (r = 0.21, 95% CI = 0.07 to 0.35) and handgrip strength (r = 0.23, 95% CI = 0.09 to 0.36) correlated with chemotherapy relative dose intensity. CONCLUSION: Among colon cancer survivors with relatively high physical functioning, random assignment to home-based resistance training did not prevent physical function decline during chemotherapy. CLINICAL TRIAL REGISTRATION: NCT03291951.

Effects of exercise or metformin on myokine concentrations in patients with breast and colorectal cancer: A phase II multi-centre factorial randomized trial.

BACKGROUND: Physical activity and metformin pharmacotherapy are associated with improved clinical outcomes in breast and colorectal cancer survivors. Myokines are cytokines secreted from skeletal muscle that may mediate these associations. METHODS: This hypothesis-generating analysis used biospecimens collected from a multi-centre 2 × 2 factorial randomized design of 116 patients with stage I-III breast and colorectal cancer who were randomized to 12 weeks of (1) aerobic exercise (moderate intensity titrated to 220 min/week); (2) metformin (850 mg daily for 2 weeks and then titrated to 850 mg twice per day); (3) aerobic exercise and metformin; or (4) control. Fourteen myokines were quantified using a multiplex panel. Myokine concentrations were log-transformed, and main effects analyses were conducted using linear mixed-effects regression models. The type I error rate was controlled with the Holm sequential testing procedure. RESULTS: Randomization to exercise increased leukaemia inhibitory factor (1.26 pg/mL, 95% confidence interval [CI]: 0.69, 1.84; adjusted P = 0.001) and interleukin-15 (2.23 pg/mL, 95% CI: 0.87, 3.60; adjusted P = 0.013) compared with randomization to no exercise. Randomization to metformin decreased apelin (-2.69 pg/mL, 95% CI: -4.31, -1.07; adjusted P = 0.014) and interleukin-15 (-1.74 pg/mL, 95% CI: -2.79, -0.69; adjusted P = 0.013) compared with randomization to no metformin. Metformin decreased myostatin, irisin, oncostatin M, fibroblast growth factor 21 and osteocrin; however, these changes were not statistically significant after correction for multiple comparisons. CONCLUSIONS: This pilot study demonstrates that randomization to exercise and metformin elicit unique effects on myokine concentrations in cancer patients. This hypothesis-generating observation warrants further basic, translational and clinical investigation and replication.

An analysis of retracted COVID-19 articles published by one medical publisher with multiple journals.

Background: The retraction of medical articles periodically occurs in most medical journals and can involve multiple article types. These retractions are beneficial if they remove flawed or fraudulent information from the medical literature. However, retractions may also decrease confidence in the medical literature and require significant amounts of time by editors. Methods: One publisher (Hindawi) announced that it will retract over 1200 articles. Given this, the PubMed database was searched to identify retracted publications on or related to COVID-19, and articles retracted by journals sponsored by the publisher Hindawi were then identified. Results: These journals retracted 25 articles and, in most cases, did not provide an exact explanation about the particular problem(s) resulting in the retraction. The time to retraction was 468.7 ± 109.8 days (median = 446 days). These articles had 9.3 ± 9.9 citations. Conclusion: Analysis of the titles and abstracts of the articles suggests that their removal from the medical literature would have limited effects on the near-term management decisions during the COVID-19 pandemic. Nevertheless, retraction of medical articles creates uncertainty in medical care and science and in the public regarding the validity of medical research and related publications and the level of professionalism of the individuals submitting these articles.

Influence of Food Security Status and Diet Quality on Maternal Gestational Weight Gain.

BACKGROUND: Recommended gestational weight gain (GWG) is crucial for health of women and their offspring. Food security status is hypothesized to influence diet quality and GWG. Therefore, we examined the relationship between diet quality and GWG by food security status. METHODS: Participants (n = 679) were enrolled in the Initial Vanguard Study of the National Children's Study. GWG was calculated as third trimester weight minus prepregnancy weight. Food security status and diet quality (Healthy Eating Index [HEI]-2015) were assessed using the Household Food Security Survey and a Diet History Questionnaire, respectively. General linear models evaluated the relationship between GWG and HEI-2015 by food security status. RESULTS: A greater proportion of women experienced food security (81.3%) compared with food insecurity (18.7%). In women with food security, GWG was negatively associated with HEI-2015 in women having overweight (r = -0.421, P = .003) and positively associated with HEI-2015 in women with inadequate GWG (r = 0.224, P = .019). Conversely, no significant relationships were found between GWG and HEI-2015 in women with food insecurity. DISCUSSION: Improved diet quality potentially lowers GWG in women with food security. However, in vulnerable populations, including women with food insecurity, improvements in diet quality may not effectively enhance GWG.

Postoperative chemotherapy relative dose intensity and overall survival in patients with colon cancer.

PURPOSE: Quantifying the association of chemotherapy relative dose intensity (RDI) with overall survival may enable supportive care interventions that improve chemotherapy RDI to estimate their magnitude of potential clinical benefit. METHODS: This cohort study included 533 patients with stage II-III colon cancer who initiated a planned regimen of 12 cycles of 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy. The primary exposure was chemotherapy RDI. The primary outcome was overall survival. Restricted cubic splines estimated hazard ratios (HR). RESULTS: Chemotherapy regimen RDI was associated with overall survival in an L-shaped pattern (linear P = 0.006; nonlinear P = 0.057); the risk of death was flat above 85% but increased linearly below 85%. For example, a decrease in RDI from 85 to 75% was associated with an increased risk of death [HR: 1.20 (95% CI: 1.08, 1.52)], whereas an increase in RDI from 85 to 95% was not associated with the risk of death [HR: 1.06 (95% CI: 0.82, 1.38)]. CONCLUSION: If chemotherapy RDI is considered a potential surrogate of overall survival, supportive care interventions that improve chemotherapy RDI might confer a potential clinical benefit in this population.

Impact of lifestyle and clinical factors on the prognosis of tennis elbow.

Tennis elbow (lateral epicondylitis) typically responds well to conservative treatment, and few patients require surgical intervention. This study aimed to investigate the influence of lifestyle and clinical factors on the prognosis of tennis elbow. This prospective, multicenter, nested case-control study included patients diagnosed with lateral epicondylitis after excluding other conditions. Patients who required surgery because of inadequate improvement after 6 months of conservative treatment were defined as the case group; the remaining patients constituted the control group. Propensity score matching was performed to eliminate baseline differences. Univariate and multivariate analyses were performed using logistic regression. This study included 265 patients (53 in the case group, 212 in the control group). Multivariate analysis revealed that smoking, alcohol consumption, and frequent physical exercise were independent risk factors for surgical intervention, whereas combined treatment with oral nonsteroidal anti-inflammatory drugs (NSAIDs) and local corticosteroid injections was a protective factor against surgery. Subgroup analysis showed that heavy drinkers had a 3.74-fold higher risk of requiring surgical treatment within 1 year than occasional drinkers. Smoking and alcohol consumption were associated with non-operative treatment failure in patients with lateral epicondylitis. Combining oral NSAIDs and corticosteroid injections is a favorable conservative treatment option.

Enzymatically modified isoquercitrin and its protective effects against photoaging: In-vitro and clinical studies.

This research examines the anti-aging potential of the flavonoid derivative of isoquercitrin known as enzymatically modified isoquercitrin (EMIQ). Initial HPLC analyses showed that EMIQ used in the study contained 1-12 glucosides and 10.7% pentahydroxyflavonoids, promising potent antioxidant properties. In subsequent in-vitro studies with UVA-exposed human dermal fibroblasts (HDFa), EMIQ demonstrated protective properties by reducing collagen damage. It modulated both the TGFß/Smad pathway and the MMP1 pathway, contributing to collagen preservation. This protective effect was further confirmed using the T-Skin™ model, a reconstructed full-thickness human skin model, which illustrated that EMIQ could defend the physiological structures of both the epidermis and dermis against UV radiation. A 28-day clinical trial with 30 volunteers aged 31-55 years highlighted EMIQ's effectiveness. Participants using EMIQ-containing Essence displayed reduced facial trans-epidermal water loss and skin roughness, alongside improved skin elasticity. This study emphasizes EMIQ's potential as an anti-photoaging ingredient in cosmetics, warranting further research. The findings pave the way for developing innovative skincare products addressing photoaging effects.

Effect of home-based resistance training on chemotherapy relative dose intensity and tolerability in colon cancer: The FORCE randomized control trial.

BACKGROUND: Many patients with colon cancer cannot fully adhere to postoperative chemotherapy due to dose-limiting toxicities, resulting in lower relative dose intensity (RDI) and potentially compromising overall survival. This study examined whether home-based resistance training (RT) during adjuvant chemotherapy improves RDI and patient-reported toxicities versus usual care (UC) in colon cancer patients. METHODS: Multicenter, randomized control trial (RCT) conducted at community and academic practices. Enrollment of patients receiving postoperative chemotherapy for colon cancer occurred between February 23, 2018, and September 29, 2021; final follow-up was March 21, 2022. Participants were randomized to RT (n = 90) or UC (n = 91) for the duration of chemotherapy. Participants in the RT group engaged in twice weekly home-based progressive RT. At the end of the study, UC was given an online exercise program. RESULTS: Among 181 randomized patients (mean age, 55.2 [SD, 12.8] years, 95 [52.5%] were men), there were no differences in the mean RDI among those in RT (79% [SD, 19%]) and those in UC (82% [SD, 19%]); (mean difference -0.04 [95% confidence interval (CI), -0.09 to 0.02]). Assignment to RT did not significantly reduce the number of moderate/severe symptoms per week across follow-up (relative rate: 0.94 [95% CI, 0.72-1.22]). Additionally, time since randomization did not significantly modify the effect of RT on the overall number of symptoms (p = .06). CONCLUSIONS: Among patients with colon cancer, these results do not support home-based RT as an adjunct to chemotherapy specifically to improve planned treatment intensity.

Proportion of caloric restriction-induced weight loss as skeletal muscle.

OBJECTIVE: This study's objective was to develop models predicting the relative reduction in skeletal muscle (SM) mass during periods of voluntary calorie restriction (CR) and to validate model predictions in longitudinally monitored samples. METHODS: The model development group included healthy nonexercising adults (n = 897) who had whole-body SM mass measured with magnetic resonance imaging. Model predictions of relative SM changes with CR were evaluated in two longitudinal studies, one 12 to 14 weeks in duration (n = 74) and the other 12 months in duration (n = 26). RESULTS: A series of SM prediction models were developed in a sample of 415 males and 482 females. Model-predicted changes in SM mass relative to changes in body weight (i.e., ΔSM/Δbody weight) with a representative model were (mean ± SE) 0.26 ± 0.013 in males and 0.14 ± 0.007 in females (sex difference, p < 0.001). The actual mean proportions of weight loss as SM in the longitudinal studies were 0.23 ± 0.02/0.20 ± 0.06 in males and 0.10 ± 0.02/0.17 ± 0.03 in females, similar to model-predicted values. CONCLUSIONS: Nonelderly males and females with overweight and obesity experience respective reductions in SM mass with voluntary CR in the absence of a structured exercise program of about 2 to 2.5 kg and 1 to 1.5 kg per 10-kg weight loss, respectively. These estimates are predicted to be influenced by interactions between age and body mass index in males, a hypothesis that needs future testing.

The dose-response effect of aerobic exercise on inflammation in colon cancer survivors.

Background: Physical activity after surgical resection for colon cancer is associated with significantly longer disease-free survival. Inflammation is hypothesized to mediate the association between physical activity and disease-free survival in colon cancer. Methods: In this exploratory analysis of a randomized dose-response trial, 39 colon cancer survivors who completed standard therapy were stratified by cancer stage and randomized in a 1:1:1 ratio to one of three treatment groups for 24 weeks of usual-care control, 150 min/wk of moderate-intensity aerobic exercise (low-dose), or 300 min/wk of moderate-intensity aerobic exercise (high-dose). Inflammation outcomes included high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL6), and soluble tumor necrosis factor-alpha receptor 2 (sTNFαR2). Mixed models for repeated measures were used to test the hypothesis that exercise was associated with dose-response reductions in inflammation; exploratory analyses examined treatment effects by cancer stage. Results: In the overall population, aerobic exercise was not associated with dose-response reductions in hs-CRP, IL6, or sTNFαR2. Cancer stage modified the association between randomized group and hs-CRP (P=0.022) and IL6 (P<0.001) but not sTNFαR2 (P=0.39). In stage I-II disease, compared to control, exercise was not associated with inflammation outcomes. In stage III disease, compared to control, low-dose exercise reduced hs-CRP: -35.4% (95% CI: -70.1, -0.7) and IL6: -29.6% (95% CI: -58.4, -0.8) but not sTNFαR2: 2.7% (95% CI: sTNFαR2: -15.7, 21.1); high-dose exercise was not associated with inflammation outcomes in stage III disease. Conclusion: This exploratory analysis offers preliminary data to support the hypothesis that inflammation may mediate the association between physical activity and disease-free survival in colon cancer. Clinical trial registration: clinicaltrials.gov, identifier NCT02250053.

Epigenetic Dysregulation and Its Correlation with the Steroidogenic Machinery Impacting Breast Pathogenesis: Data Mining and Molecular Insights into Therapeutics.

Breast cancer (BC) is a heterogeneous condition and comprises molecularly distinct subtypes. An imbalance in the levels of epigenetic histone deacetylases (HDACs), modulating estrogen accumulation, especially 17ß-estradiol (E2), promotes breast tumorigenesis. In the present study, analyses of The Cancer Genome Atlas (TCGA) pan-cancer normalized RNA-Seq datasets revealed the dysregulation of 16 epigenetic enzymes (among a total of 18 members) in luminal BC subtypes, in comparison to their non-cancerous counterparts. Explicitly, genomic profiling of these epigenetic enzymes displayed increases in HDAC1, 2, 8, 10, 11, and Sirtuins (SIRTs) 6 and 7, and decreases in HDAC4-7, -9, and SIRT1-4 levels, respectively, in TCGA breast tumors. Kaplan-Meier plot analyses showed that these HDACs, with the exception of HDAC2 and SIRT2, were not correlated with the overall survival of BC patients. Additionally, disruption of the epigenetic signaling in TCGA BC subtypes, as assessed using both heatmaps and boxplots, was associated with the genomic expression of factors that are instrumental for cholesterol trafficking/utilization for accelerating estrogen/E2 levels, in which steroidogenic acute regulatory protein (STAR) mediates the rate-limiting step in steroid biosynthesis. TCGA breast samples showed diverse expression patterns of a variety of key steroidogenic markers and hormone receptors, including LIPE, CYP27A1, STAR, STARD3, CYP11A1, CYP19A1, ER, PGR, and ERBB2. Moreover, regulation of STAR-governed steroidogenic machinery was found to be influenced by various transcription factors, i.e., CREB1, CREM, SF1, NR4A1, CEBPB, SREBF1, SREBF2, SP1, FOS, JUN, NR0B1, and YY1. Along these lines, ingenuity pathway analysis (IPA) recognized a number of new targets and downstream effectors influencing BCs. Of note, genomic, epigenomic, transcriptional, and hormonal anomalies observed in human primary breast tumors were qualitatively similar in pertinent BC cell lines. These findings identify the functional correlation between dysregulated epigenetic enzymes and estrogen/E2 accumulation in human breast tumors, providing the molecular insights into more targeted therapeutic approaches involving the inhibition of HDACs for combating this life-threatening disease.

Article retraction rates in selected MeSH term categories in PubMed published between 2010 and 2020.

BACKGROUND: Academic article retractions occur across all disciplines, though few studies have examined the association between research topics and retraction rates. OBJECTIVES: We assessed and compared the rate of retraction across several important clinical research topics. METHODS: Information about the number of publications, the number of retractions, the retraction rate, and the time to retraction was collected for articles identified by 15 Medical Subject Headings (MeSH) terms. These articles were published between 1 January 2010 and 31 December 2020. The searches took place between 18 September 2021 and 24 October 2021. The MeSH terms were selected based on our clinical experience with the expectation that there will be multiple publications during the timeframe to use for the searches. Additional topics were selected based on the frequency of controversy in the public media and were identified by the Altmetric Top 100 report. RESULTS: The mean number of publications for all categories was 181,975 ± 332,245; the median number of publications was 67,991 [Q1, Q3; 31951.5, 138,981.5]. The mean number of retractions was 100.3 ± 251.3, and the median number of retractions was 22 [Q1, Q3; 6.5, 53]. The mean time to retraction ranged from 114 days to 1,409.5 days; the median was 857.3 days [Q1, Q3; 684.7, 1098.6], depending on the topic. The various MeSH term categories used in this study had significant differences in retraction rate and time to retraction. The "Neoplasms" category had the highest total number of retractions (993) and one of the highest retraction rates (75.4 per 100,000 publications). DISCUSSION: All PubMed categories analyzed in this study had retracted articles. The median time to retraction was 857 days. The long delays in some categories could contribute to potentially misleading information which might have adverse effects on clinical decisions in patient care and on research design. CONCLUSION: Rate of retraction varies across research topics and further studies are needed to explore this relationship.

• Article retractions occurred in all subsets of articles classified by the 15 PubMed MeSH terms used in this study.• The time to retraction and the rate of retraction differed significantly across research topics classified by these MeSH terms. This suggests that research content and visibility affect retraction rates.• As an example, the "Neoplasms" category had the highest total number of retractions (993) and one of the highest retraction rates (75.4 per 100,000 publications).• Readers, editors, and authors need to understand that retractions do occur following publication in the medical literature. These retractions potentially have important consequences and require attention from all individuals involved in the multiple steps needed to create high-quality medical and scientific information.

The Personalized Nutrition Study (POINTS): evaluation of a genetically informed weight loss approach, a Randomized Clinical Trial.

Weight loss (WL) differences between isocaloric high-carbohydrate and high-fat diets are generally small; however, individual WL varies within diet groups. Genotype patterns may modify diet effects, with carbohydrate-responsive genotypes losing more weight on high-carbohydrate diets (and vice versa for fat-responsive genotypes). We investigated whether 12-week WL (kg, primary outcome) differs between genotype-concordant and genotype-discordant diets. In this 12-week single-center WL trial, 145 participants with overweight/obesity were identified a priori as fat-responders or carbohydrate-responders based on their combined genotypes at ten genetic variants and randomized to a high-fat (n = 73) or high-carbohydrate diet (n = 72), yielding 4 groups: (1) fat-responders receiving high-fat diet, (2) fat-responders receiving high-carbohydrate diet, (3) carbohydrate-responders receiving high-fat diet, (4) carbohydrate-responders receiving high-carbohydrate diet. Dietitians delivered the WL intervention via 12 weekly diet-specific small group sessions. Outcome assessors were blind to diet assignment and genotype patterns. We included 122 participants (54.4 [SD:13.2] years, BMI 34.9 [SD:5.1] kg/m2, 84% women) in the analyses. Twelve-week WL did not differ between the genotype-concordant (-5.3 kg [SD:1.0]) and genotype-discordant diets (-4.8 kg [SD:1.1]; adjusted difference: -0.6 kg [95% CI: -2.1,0.9], p = 0.50). With the current ability to genotype participants as fat- or carbohydrate-responders, evidence does not support greater WL on genotype-concordant diets. ClinicalTrials identifier: NCT04145466.

Weight-independent effects of Roux-en-Y gastric bypass surgery on remission of nonalcoholic fatty liver disease in mice.

OBJECTIVE: Obesity is a driver of non-alcoholic fatty liver disease (NAFLD), and interventions that decrease body weight, such as bariatric surgery and/or calorie restriction (CR), may serve as effective therapies. This study compared the effects of Roux-en-Y gastric bypass surgery (RYGB) and CR on hepatic function in mice with obesity and NAFLD. METHODS: C57BL/6J mice were fed a high-fat diet to promote obesity. At 16 weeks of age, mice were randomized to sham surgery (sham), RYGB, or CR weight matched to RYGB (WM). Body weight/composition, food intake, and energy expenditure (EE) were measured throughout treatment. Liver histopathology was evaluated from H&E-stained sections. Hepatic enzymes and glycogen content were determined by ELISA. Transcriptional signatures were revealed via RNA sequencing. RESULTS: RYGB reduced hepatic lipid content and adiposity while increasing EE and lean body mass relative to WM. Hepatic glycogen and bile acid content were increased after RYGB relative to sham and WM. RYGB activated enterohepatic signaling and genes regulating hepatic lipid homeostasis. CONCLUSIONS: RYGB improved whole-body composition and hepatic lipid homeostasis to a greater extent than CR in mice. RYGB was associated with discrete remodeling of the hepatic transcriptome, suggesting that surgery may be mechanistically additive to CR.

Factors Influencing Nutritional Intake and Interests in Educational Content of Athletes and Sport Professionals Toward the Development of a Clinician-Supported Mobile App to Combat Relative Energy Deficiency in Sport: Formative Research and a Description of App Functions.

BACKGROUND: Relative energy deficiency in sport (RED-S) as a consequence of athlete malnutrition remains a prominent issue. However, it remains underrecognized, in part due to the perceived outward health of athletes. The Eat2Win app was designed to combat RED-S and athlete malnutrition by providing education, behavior modification, and direct communication with expert sports dietitians to athletes and sport professionals (professionals who work with athletes, eg, sport coaches and athletic trainers). OBJECTIVE: The purpose of this formative research was to gain critical insight on motivators and barriers to optimal nutritional intake from both the athletes' and sport professionals' perspectives. Additionally, since these 2 groups represent the primary end users of an app aimed at improving athlete nutrition and reducing the risk of RED-S, a secondary objective was to gain insight on the preferences and perceptions of app-based educational content and functionality. METHODS: An electronic survey was developed by an interdisciplinary team of experts. Survey questions were established based upon prevailing literature, professional dietetic field experience, and app design considerations to obtain respondent knowledge on key sports nutrition topics along with motivations and barriers to meal choices. Additionally, the survey included questions about the development of an integrative, clinician-support app aimed at addressing RED-S. These questions included preferences for educational content, modes of in-app information, and communication delivery for the target population (app end users: athletes and sport professionals). The survey was distributed through Research Electronic Data Capture (REDCap) to athletes and sport professionals using targeted email, social media, and community engagement campaigns. The electronic survey was available from May 4 to August 2, 2022. RESULTS: Survey respondents (n=1352) included athletes and professionals who work with athletes from a variety of settings, like high school, collegiate, professional, and club sports. Respondents reported high interest in 8 core sports nutrition topics. The preferred modes of information and communication delivery were visual formats (eg, videos and infographics) and in-app alerts (eg, direct messaging and meal reminders). Only athlete respondents were asked about motivators and barriers that influence meal choices. "Health" and "sports performance" were the highest scoring motivators, while the highest scoring barriers were "cost of food," "easy access to unhealthy food," and "time to cook or prepare food." Notably, survey respondents provided positive feedback and interest using a novel function of the app: real-time meal feedback through food photography. CONCLUSIONS: The Eat2Win app is designed to combat RED-S and athlete malnutrition. Results from this study provide critical information on end-user opinions and preferences and will be used to further develop the Eat2Win app. Future research will aim to determine whether the Eat2Win app can prevent RED-S and the risk of athlete malnutrition to improve both health and performance.