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At least 19 recordsLinked to original sources
PubMed2026

Impact of Annual School Fitness Reports on Students' Cardiorespiratory Fitness: A Cluster-Randomized Controlled Trial of Parental Reporting.

BACKGROUND: School-based physical fitness testing is an important population health monitoring tool and has the potential to improve student fitness performance. However, few studies exist on the impact of reporting student fitness to parents. METHODS: Using data from the Fit Study (2014-2017) from 12 California public schools, we used mixed-effects models to compare changes in cardiorespiratory fitness (estimated peak oxygen consumption, calculated from the 1-mile run) and strength (curl-ups and push-ups) over 1 and 2 years between students randomized to having their parents receive an annual fitness report (intervention, n = 1638 students) and control (n = 2070) in grades 5 to 8 (ages 10-15 y). The student sample was 47.9% female, 55.9% Hispanic, and 24.1% Asian. RESULTS: After 1 year, intervention students did not demonstrate differential change compared with control students in estimated peak oxygen consumption (between-group change: -0.03 mL/kg/min; 95% CI, -.367 to 0.302), curl-ups (between-group change: 1.2 curl-ups; 95% CI, -0.306 to 2.660), or push-ups (between-group change: 0.1 push-ups; 95% CI, -0.672 to 0.787). Similarly, no differences were seen after 2 years. CONCLUSION: Sending a 2-page, once-a-year school-based fitness report home to parents-in the absence of environmental changes and/or behavioral coaching and support-does not impact student fitness performance after either 1 or 2 years of reporting.

fitness reporting↗
PubMed1977

Fitness effects of EMS-induced mutations on the X chromosome of Drosophila melanogaster. I. Viability effects and heterozygous fitness effects.

Drosophila melanogaster X chromosomes were mutagenized by feeding males sucrose solutions containing ethyl methanesulfonate (EMS); the concentrations of EMS in the food were 2.5 mM, 5.0 mM, and 10.0 mM. Chromosomes were exposed to the mutagen up to three times by treating males in succeeding generations. After treatment, the effective exposures were 2.5, 5.0, 7.5, 10.0, 15.0, and 30.0 mM EMS. X chromosomes treated in this manner were tested for effects on fitness in both hemizygous and heterozygous conditions, and for effects on viability in hemizygous and homozygous conditions. In addition, untreated X chromosomes were available for study. The viability and heterozygous fitness effects are presented in this paper, and the hemizygous fitness effects are discussed in the accompanying one (MITCHELL and SIMMONS 1977). Hemizygous and homozygous viability effects were measured by segregation tests in vial cultures. For hemizygous males, viability was reduced 0.5 percent per mM EMS treatment; for homozygous females, it was reduced 0.7% per mM treatment. The decline in viability appeared to be a linear function of EMS dose. The viabilities of males and females were strongly correlated. Heterozygous fitness effects were measured by monitoring changes in the frequencies of treated and untreated X chromosomes in discrete generation populations which, through the use of an X-Y translocation, maintained them only in heterozygous condition. Flies that were heterozygous for a treated chromosome were found to be 0.4% less fit per mM EMS than flies heterozygous for an untreated one.

Animals↗
PubMed1979

The effect of a four-month physical fitness program on a young and an old group matched for physical fitness.

A young (X = 36.8 years) and an old (X = 52.9 years) group (n = 12) matched for physical fitness performed a graded exercise test at the beginning and after a 4-month physical fitness program consisting of calisthenics, jogging, and recreational activities. The purpose of the study was to determine if there were any differences in response to physical training in the two age groups of similar fitness. Sixteen physiological and four biochemical variables were measured. There was no significant difference in VO2 max between the young and old groups. Also, there were no significant differences between groups for serum total lipids, cholesterol, triglycerides, or glucose levels. The effects of the training program were similar for both the young and old groups.

Adult↗
PubMed1978

Genetic and evolutionary fitness.

The advantages and disadvantages of evolutionary fitness (probability that a single mutant line will not become extinct) and genetic fitness (mean fecundity) are compared. For deterministic processes the two are equivalent, but for stochastic branching processes they may be totally unrelated except that an absolute genetic fitness of unity or less implies an evolutionary fitness of zero. To know the variance as well as the mean family size does not in general uniquely determine the evolutionary fitness. Except where genetic fitness is close to unity, the impact of selection is shown to be rapid for the binomial, Poisson, negative binomial, and truncated negative binomial distributions. Evolutionary fitness, though somewhat cumbersome, has greater relevance to evolution, genetic counseling, and voluntary population control; but genetic fitness which is much easier to handle is the more appropriate measure where a large number of mutants is involved. Some empirical data on the transmission of various types of characters from parent to child are analyzed to allow comparison of genetic fitness, Crow's index, and a Malthusian parameter, with evolutionary fitness. There is a fair, but far from perfect, agreement among them. Multiple correlation of evolutionary fitness with mean and variance of family size taken jointly suggests a much more satisfactory approximation. It thus appears that, at the least, the population geneticist cannot afford to ignore the variance (which is not adequately represented in Crow's index). These relationships, based on two sets of data only may be accidental and should be invoked with caution. It seems more than likely that other aspects of the distribution of family size (eg, even higher moments) may contain relevant information in certain cases.

Biological Evolution↗
PubMed2026

Competing subclones and fitness diversity shape tumor evolution across cancer types.

MOTIVATION: Intratumor heterogeneity arises from ongoing somatic evolution and complicates cancer diagnosis, prognosis, and treatment. Reconstructing evolutionary dynamics typically requires spatiotemporal samples, which are often unavailable in clinical settings. Computational approaches that can infer tumor evolutionary history from single-timepoint bulk sequencing data remain limited. RESULTS: We present estimating evolutionary events through single-timepoint sequencing (TEATIME), a novel computational framework that models tumors as mixtures of two competing cell populations: an ancestral clone with baseline fitness and a derived subclone with elevated fitness. Using cross-sectional bulk sequencing data, TEATIME estimates mutation rates, timing of subclone emergence, relative fitness, and number of generations of growth. To quantify intratumor fitness asymmetries, we introduce a novel metric-fitness diversity-which captures the imbalance between competing cell populations and serves as a measure of functional intratumor heterogeneity. Applying TEATIME to 33 tumor types from The Cancer Genome Atlas, we revealed divergent as well as convergent evolutionary patterns. Notably, we found that immune-hot microenvironments constraint subclonal expansion and limit fitness diversity. Moreover, we detected temporal dependencies in mutation acquisition, where early driver mutations in ancestral clones epistatically shape the fitness landscape, predisposing specific subclones to selective advantages. These findings underscore the importance of intratumor competition and tumor-microenvironment interactions in shaping evolutionary trajectories, driving intratumor heterogeneity. Lastly, we demonstrate that TEATIME-derived evolutionary parameters and fitness diversity offer novel prognostic insights across multiple cancer types. AVAILABILITY AND IMPLEMENTATION: R implementation of TEATIME is available on GitHub (https://github.com/liliulab/TEATIME) and Zenodo (https://zenodo.org/records/17422174).

Neoplasms↗
PubMed1979

Strength and fitness and subsequent back injuries in firefighters.

This prospective investigation was done to evaluate five strength and fitness measurements and the subsequent occurrence of back injuries in 1652 firefighters for the years 1971 to 1974. The prospective measurements included flexibility, isometric lifting strength, bicycle ergometer exercise measurements of two-minute recovery heart rate, diastolic blood pressure at a heart rate of 160 beats per minute and watts of effort required to sustain heart rate at 160. Three fitness and conditioning groups were established by multivariate ranking and regression techniques (259 high, 266 low, and 1127 middle) and the subsequent back injuries were tabulated for the three groups. The results showed a graded and statistically significant protective effect for added levels of fitness and conditioning (least fit, 7.1% injured; middle fit, 3.2% jured; and most fit, 0.8% injured). It was concluded that physical fitness and conditioning of firefighters are preventive of back injuries and that further investigations are warranted to study other injuries and physical fitness in this physically active occupational group.

Adult↗
PubMed2026

Synonymous mutations in essential genes infrequently produce fitness effects in human cell lines.

The assumption that synonymous mutations are fitness-neutral is central to many foundational results in the fields of genetics, genomics, evolutionary biology, and medicine. However, recent results suggest synonymous mutations have pervasive and strong fitness effects. These vigorously debated studies in non-human model systems have even suggested that the proportion of synonymous mutations and their fitness effect sizes are similar to non-synonymous mutations. To probe the fitness effect of synonymous mutations, we utilized recent advances in base editing to test 8558 potential synonymous mutations in 128 highly essential genes in human cell lines. Importantly, our library design excluded splice-proximal sites, ensuring a direct test of codon-level synonymous effects independent of splicing disruption. We find that synonymous mutations rarely have fitness effects on growth, occurring around 37.9-fold (95% CI: 22.16-81.48-fold) less frequently than missense mutations. In this experimental context, these findings demonstrate that synonymous mutations impact cellular fitness far less frequently than missense mutations. These results deviate from earlier reports of widespread synonymous fitness effects in yeast, yet they align with recent prime editing data observed in other human cell lines.

Humans↗
PubMed2026

Associations Between Health-Related Physical Fitness and Accelerometry-Based Energy Expenditure in Physiotherapy Workers.

BACKGROUND AND PURPOSE: Although it has been assumed that higher physical activity (PA) levels will contribute to better physical fitness (PF) performance, the interplay between these two has yet to be investigated. Moreover, the majority of studies have been presented in children and adolescents, and older adults, while little is known about the correlation in the adult working population of physiotherapists. Therefore, the main purpose of the study was to examine associations between objectively measured PA and health-related PF. METHODS: We recruited 50 physiotherapists (72.6% women) from several public and private settings in the city of Zagreb. The SenseWearArmbandPro3 (SWA), a triaxial accelerometer placed on the nondominant hand for 7 consecutive days, was used to capture total energy expenditure (TEE) and active EE (AEE). Cardiorespiratory fitness included the Harvard step test, and muscular fitness was composed of sit-ups in 60&#xa0;sec and the Handgrip strength. Flexibility was evaluated using the Toe-touch test. RESULTS: TEE and AEE were moderately and positively correlated with the Harvard step test (r&#xa0;=&#xa0;0.65 and 0.62, p&#xa0;<&#xa0;0.001), sit-ups (r&#xa0;=&#xa0;0.70 and 0.59, p&#xa0;<&#xa0;0.001), and the Handgrip strength test (r&#xa0;=&#xa0;0.74 and 0.64, p&#xa0;<&#xa0;0.001). No significant correlation with the Toe-touch test was observed (r&#xa0;=&#xa0;-0.25 and -0.19, p&#xa0;>&#xa0;0.05). When models were adjusted for age, weaker, but significant positive correlations remained. DISCUSSION: The findings suggest that both cardiorespiratory and muscular fitness are positively associated with PA, whereas no statistically significant association with flexibility was detected. Thus, it is not surprising that we obtained moderate to almost strong correlations between TEE and AEE with cardiorespiratory and muscular fitness. CONCLUSIONS: In physiotherapists, TEE and AEE yield moderate correlations with health-related PF, especially for cardiorespiratory and muscular fitness.

Humans↗
PubMed2026

Repeated emergence and fitness heterogeneity of KPC-33 in ST11 Klebsiella pneumoniae under ceftazidime-avibactam pressure.

Ceftazidime-avibactam (CZA) is an important therapeutic option for infections caused by Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae. However, CZA exposure also selects for emergent KPC variants. Their in vivo evolutionary patterns, fitness consequences, and underlying molecular mechanisms remain unclear. We performed a longitudinal multiomics analysis of 35 clonally related ST11 KPC-producing K. pneumoniae isolates collected from eight hospitalized patients during clinical follow-up, most of whom had received CZA therapy. Whole-genome sequencing, antimicrobial susceptibility testing, in vitro competition assays, enzyme kinetic analysis, and transcriptomic sequencing were used to systematically characterize the within-host evolutionary dynamics of KPC variants and the fitness heterogeneity of KPC-33. Multiple KPC variants were identified during longitudinal follow-up, among which KPC-33 was the most frequently detected. Among the seven patients who received CZA treatment, KPC-33 was detected in longitudinal isolates from four patients. It was also identified in patient P3, who had not received CZA, whereas other variants were only sporadically identified. Biochemical analysis showed that KPC-33 exhibited an altered kinetic profile relative to KPC-2, characterized by reduced catalytic turnover and altered substrate affinity. KPC-33 did not exhibit a uniform and pronounced fitness defect but instead showed marked strain-dependent heterogeneity. Strains with higher competitive fitness generally showed only limited transcriptional changes, whereas those with lower fitness were accompanied by broader transcriptional remodeling. In this longitudinal cohort, KPC-33 was repeatedly detected, predominantly under CZA-associated selective conditions. Its fitness consequences were clearly strain background dependent and may be associated with the extent of transcriptional remodeling. These findings provide new evidence for understanding the in vivo evolution of CZA resistance.

KPC-33↗
PubMed2025

The modern expansion of Dscam1 isoform diversity in Drosophila is linked to fitness and immunity.

Drosophila melanogaster Down Syndrome cell adhesion molecule 1 (Dscam1) gene encodes 38,016 diverse cell surface receptor proteins via alternative splicing, which have both nervous and immune functions. However, it remains elusive why organisms have evolved such an astonishing diversity of isoforms. Here, we show that fitness and immunity properties have driven the modern evolution of Dscam1 isoform diversity. We assess multiple aspects of fly fitness in deletion mutants harboring exon 4, 6, or 9 clusters, respectively, reducing ectodomain isoform diversity stepwise from 18,612 to 396. All fitness-related traits generally improved as the potential number of isoforms increased; however, the magnitude of the changes varied remarkably in a variable cluster-specific manner. Correlation analysis revealed that fitness-related traits were much more sensitive to reductions in Dscam1 diversity compared to canonical neuronal self/non-self discrimination. We conclude that the role of Dscam1 isoforms in canonical neuronal self-avoidance and self/non-self discrimination is mediated by a small fraction of all isoforms (<1/10), whereas a separate role essential for other developmental contexts and resistances, likely in fitness and immunity, requires almost full isoform diversity. Thus, fitness and immunity properties, rather than canonical neuronal functions, are the dominant drivers during the modern diversification of the Dscam1 isoform. Our findings suggest that Dscam1 diversity is closely linked to adaptation and species diversification in arthropods.

Animals↗
PubMed1979

A survey of aerobic fitness levels in a Canadian military population.

Aerobic fitness was assessed for 3171 men aged 17-55 years and for 610 women aged 17-29 years serving in almost every segment of the Canadian Forces (CF). Maximal oxygen uptake (Vo2 max) was predicted from heart rate measured during submaximal exercise. The survey showed that recruit training markedly improved Vo2 max for both men and women but that, after graduates were assigned to their trades and classifications and fitness training was no longer compulsory, fitness returned to pre-training levels. The relationship between daily activity and aerobic fitness was further demonstrated by comparing land, air, and sea elements in the CF. The active life of the young infantry soldiers is reflected in their relatively high Vo2 max. The available evidence indicates that, unless their duties involve compulsory fitness training (recruits) or hard physical work (infantry soldiers), the military in Canada have aerobic fitness levels which are not markedly higher than their civilian counterparts.

Adolescent↗
PubMed2026

Exploring an Intermediate Colorectal Cancer Screening Test Based on Stool Proteomics and Machine Learning for Optimizing the Selection of Patients for Colonoscopy Identified From FIT.

The fecal immunochemical test (FIT) for detecting fecal occult blood, used alone or in combination with other stool biomarkers, has been demonstrated to be effective in the context of colorectal cancer (CRC) screening programs. However, FIT yields a significant proportion of false positives leading to unnecessary colonoscopies. In this study, we have investigated whether leftover FIT stool samples could be repurposed for proteomics analysis as a triage step for patients before recommending colonoscopy. High-throughput mass spectrometry analyses on a set of 141 FIT-positive samples (50 controls with no lesion, 45 with advanced adenomas and 46 with CRC) in combination with machine learning tools were used. Results showed that with a specificity &#x2265;90%, a large proportion of the false FIT positives could be identified thus providing an efficient strategy for reducing unnecessary colonoscopies. Furthermore, CRC cases were also precisely predicted to be true positives, thus providing an approach for prioritizing patients for colonoscopy. In conclusion, this study demonstrates the feasibility of using proteomics for analysis of leftover FIT stool samples as an intermediate step to triage patients selected for colonoscopy in CRC screening programs.

Humans↗
PubMed2024

Estimation of SARS-CoV-2 fitness gains from genomic surveillance data without prior lineage classification.

The emergence of SARS-CoV-2 variants with increased fitness has had a strong impact on the epidemiology of COVID-19, with the higher effective reproduction number of the viral variants leading to new epidemic waves. Tracking such variants and their genetic signatures, using data collected through genomic surveillance, is therefore crucial for forecasting likely surges in incidence. Current methods of estimating fitness advantages of variants rely on tracking the changing proportion of a particular lineage over time, but describing successful lineages in a rapidly evolving viral population is a difficult task. We propose a method of estimating fitness gains directly from nucleotide information generated by genomic surveillance, without a priori assigning isolates to lineages from phylogenies, based solely on the abundance of single nucleotide polymorphisms (SNPs). The method is based on mapping changes in the genetic population structure over time. Changes in the abundance of SNPs associated with periods of increasing fitness allow for the unbiased discovery of new variants, thereby obviating a deliberate lineage assignment and phylogenetic inference. We conclude that the method provides a fast and reliable way to estimate fitness advantages of variants without the need for a priori assigning isolates to lineages.

COVID-19↗
PubMed2026

Epistasis and the changing fitness landscapes of SARS-CoV-2.

Since its emergence in late 2019, millions of SARS-CoV-2 genomes have been generated as part of global efforts to monitor the evolution and spread of the virus. This unprecedented volume of data provides a unique opportunity to study viral evolution at unparalleled resolution. In particular, individual genomic sites can be observed to have mutated independently thousands of times. These mutation counts have been used to estimate site-specific mutation rates and fitness effects for most mutations across the viral genome. Here, we use these data to investigate how the landscape of mutational fitness costs has changed over the course of the pandemic. SARS-CoV-2 evolution over the past 6 years has been characterized by the emergence of distinct variants separated by long branches corresponding to evolutionary saltations involving up to 50 mutations. We compare inferred fitness landscapes of the Spike protein across these variants and find that shifts in the estimated effects of non-synonymous mutations are linked to genetic differences between them. Sites with altered fitness costs are enriched near positions where the genetic backgrounds differ. To explain the observed changes, we introduce a model with pairwise epistatic interactions between mutations and residues that differ between variants. This model is able to explain about half of the variance in the shifts of fitness effects and suggests that each mismatch between variants substantially alters mutation effects at typically 1 to 3 additional positions.

SARS-CoV-2↗
PubMed2026

Marginal fit and five-year outcomes of posterior monolithic zirconia restorations: A randomized paired and observational clinical study.

OBJECTIVES: The aim of this study was to evaluate the marginal fit and five-year clinical performance of posterior 5 mol% yttria-partially stabilized zirconia restorations. A randomized paired comparison with lithium disilicate crowns was performed for marginal fit. METHODS: A total of 65 posterior restorations were placed in 38 patients, including 32 zirconia crowns, 17 lithium disilicate crowns, and 16 zirconia partial coverage restorations. In the randomized paired comparison, 17 patients received one lithium disilicate crown and one zirconia crown. Additional zirconia crowns (n=15) and zirconia partial coverage restorations (n=16) were included in a prospective observational cohort. The primary outcome was marginal fit within the randomized cohort. Marginal and internal fit were assessed using the replica technique. Marginal and internal gap values were compared using the Wilcoxon signed-rank test; clinical outcomes were analyzed descriptively, and Kaplan-Meier estimates were calculated for survival and complication-free survival. Clinical performance was assessed using CDA criteria, periodontal parameters, complication recording, and patient-reported outcomes. Clinical examinations were performed at baseline and at 12, 24, 36, 48, and 60 months. RESULTS: Mean marginal gap values at the crown margin were 46 &#xb1;33 &#xb5;m for lithium disilicate crowns and 50 &#xb1;32 &#xb5;m for zirconia crowns (p>0.05). No restoration required replacement, resulting in 100% restoration survival after a median follow-up of 60 months (range: 57-64 months). Most complications were biological or functional, including endodontic, periodontal, occlusal, and proximal-contact-related events. One zirconia partial coverage restoration exhibited a small ceramic fracture managed by polishing. The Kaplan-Meier probability of complication-free survival was 76.4% for zirconia crowns, 66.7% for lithium disilicate crowns, and 87.5% for zirconia partial coverage restorations. CONCLUSIONS: In the randomized paired comparison, 5 mol% yttria-partially stabilized zirconia crowns showed marginal gap values similar to lithium disilicate crowns. All restorations remained in situ during the observation period. Lower complication-free survival was mainly related to biological and functional events and should be interpreted separately from restoration survival. CLINICAL SIGNIFICANCE: Clinical evidence for posterior 5 mol% yttria-partially stabilized zirconia restorations remains limited. This study provides mid-term clinical data on crowns and partial coverage restorations. In the randomized full-crown comparison, marginal fit was similar to that of lithium disilicate crowns, supporting the clinical consideration of monolithic zirconia restorations for posterior teeth.

Humans↗
PubMed2025

Bayesian inference of fitness landscapes via tree-structured branching processes.

MOTIVATION: The complex dynamics of cancer evolution, driven by mutation and selection, underlies the molecular heterogeneity observed in tumors. The evolutionary histories of tumors of different patients can be encoded as mutation trees and reconstructed in high resolution from single-cell sequencing data, offering crucial insights for studying fitness effects of and epistasis among mutations. Existing models, however, either fail to separate mutation and selection or neglect the evolutionary histories encoded by the tumor phylogenetic trees. RESULTS: We introduce FiTree, a tree-structured multi-type branching process model with epistatic fitness parameterization and a Bayesian inference scheme to learn fitness landscapes from single-cell tumor mutation trees. Through simulations, we demonstrate that FiTree outperforms state-of-the-art methods in inferring the fitness landscape underlying tumor evolution. Applying FiTree to a single-cell acute myeloid leukemia dataset, we identify epistatic fitness effects consistent with known biological findings and quantify uncertainty in predicting future mutational events. The new model unifies probabilistic graphical models of cancer progression with population genetics, offering a principled framework for understanding tumor evolution and informing therapeutic strategies. AVAILABILITY AND IMPLEMENTATION: The Python package FiTree and the analysis workflows are available at https://github.com/cbg-ethz/FiTree.

Bayes Theorem↗