Diverse papillomaviruses identified from Antarctic fur seals, leopard seals and Weddell seals from the Antarctic.

Papillomaviruses (family Papillomaviridae) are non-enveloped, circular, double-stranded DNA viruses known to infect squamous and mucosal epithelial cells. In the family Papillomaviridae there are 53 genera and 133 viral species whose members infect a variety of mammalian, avian, reptilian, and fish species. Within the Antarctic context, papillomaviruses (PVs) have been identified in Adélie penguins (Pygoscelis adeliae, 2 PVs), Weddell seals (Leptonychotes weddellii, 7 PVs), and emerald notothen (Trematomus bernacchii, 1 PV) in McMurdo Sound and Ross Island in eastern Antarctica. Here we identified 13 diverse PVs from buccal swabs of Antarctic fur seals (Arctocephalus gazella, 2 PVs) and leopard seal (Hydrurga leptonyx, 3 PVs) in western Antarctica (Antarctic Peninsula), and vaginal and nasal swabs of Weddell seals (8 PVs) in McMurdo Sound. These PV genomes group into four genera representing 11 new papillomavirus types, of which five are from two Antarctic fur seals and a leopard seal and six from Weddell seals.

The Canadian Women's Heart Health Alliance ATLAS on the Epidemiology, Diagnosis, and Management of Cardiovascular Disease in Women - Chapter 8: Knowledge Gaps and Status of Existing Research Programs in Canada.

Despite significant progress in medical research and public health efforts, gaps in knowledge of women's heart health remain across epidemiology, presentation, management, outcomes, education, research, and publications. Historically, heart disease was viewed primarily as a condition in men and male individuals, leading to limited understanding of the unique risks and symptoms that women experience. These knowledge gaps are particularly problematic because globally heart disease is the leading cause of death for women. Until recently, sex and gender have not been addressed in cardiovascular research, including in preclinical and clinical research. Recruitment was often limited to male participants and individuals identifying as men, and data analysis according to sex or gender was not conducted, leading to a lack of data on how treatments and interventions might affect female patients and individuals who identify as women differently. This lack of data has led to suboptimal treatment and limitations in our understanding of the underlying mechanisms of heart disease in women, and is directly related to limited awareness and knowledge gaps in professional training and public education. Women are often unaware of their risk factors for heart disease or symptoms they might experience, leading to delays in diagnosis and treatments. Additionally, health care providers might not receive adequate training to diagnose and treat heart disease in women, leading to misdiagnosis or undertreatment. Addressing these knowledge gaps requires a multipronged approach, including education and policy change, built on evidence-based research. In this chapter we review the current state of existing cardiovascular research in Canada with a specific focus on women.

En dépit des avancées importantes de la recherche médicale et des efforts en santé publique, il reste des lacunes dans les connaissances sur la santé cardiaque des femmes sur les plans de l'épidémiologie, du tableau clinique, de la prise en charge, des résultats, de l'éducation, de la recherche et des publications. Du point de vue historique, la cardiopathie a d'abord été perçue comme une maladie qui touchait les hommes et les individus de sexe masculin. De ce fait, la compréhension des risques particuliers et des symptômes qu'éprouvent les femmes est limitée. Ces lacunes dans les connaissances posent particulièrement problème puisqu'à l'échelle mondiale la cardiopathie est la cause principale de décès chez les femmes. Jusqu'à récemment, la recherche en cardiologie, notamment la recherche préclinique et clinique, ne portait pas sur le sexe et le genre. Le recrutement souvent limité aux participants masculins et aux individus dont l'identité de genre correspond au sexe masculin et l'absence d'analyses de données en fonction du sexe ou du genre ont eu pour conséquence un manque de données sur la façon dont les traitements et les interventions nuisent aux patientes féminines et aux individus dont l'identité de genre correspond au sexe féminin, et ce, de façon différente. Cette absence de données a mené à un traitement sous-optimal et à des limites de notre compréhension des mécanismes sous-jacents de la cardiopathie chez les femmes, et est directement reliée à nos connaissances limitées, et à nos lacunes en formation professionnelle et en éducation du public. Le fait que les femmes ne connaissent souvent pas leurs facteurs de risque de maladies du cœur ou les symptômes qu'elles peuvent éprouver entraîne des retards de diagnostic et de traitements. De plus, le fait que les prestataires de soins de santé ne reçoivent pas la formation adéquate pour poser le diagnostic et traiter la cardiopathie chez les femmes les mène à poser un mauvais diagnostic ou à ne pas traiter suffisamment. Pour pallier ces lacunes de connaissances, il faut une approche à plusieurs volets, qui porte notamment sur l'éducation et les changements dans les politiques, et qui repose sur la recherche fondée sur des données probantes. Dans ce chapitre, nous passons en revue l'état actuel de la recherche existante sur les maladies cardiovasculaires au Canada, plus particulièrement chez les femmes.

The Canadian Women's Heart Health Alliance ATLAS on the Epidemiology, Diagnosis, and Management of Cardiovascular Disease in Women - Chapter 9: Summary of Current Status, Challenges, Opportunities, and Recommendations.

This final chapter of the Canadian Women's Heart Health Alliance "ATLAS on the Epidemiology, Diagnosis, and Management of Cardiovascular Disease in Women" presents ATLAS highlights from the perspective of current status, challenges, and opportunities in cardiovascular care for women. We conclude with 12 specific recommendations for actionable next steps to further the existing progress that has been made in addressing these knowledge gaps by tackling the remaining outstanding disparities in women's cardiovascular care, with the goal to improve outcomes for women in Canada.

Dans ce chapitre final de l'ATLAS sur l'épidémiologie, le diagnostic et la prise en charge de la maladie cardiovasculaire chez les femmes de l'Alliance canadienne de santé cardiaque pour les femmes, nous présentons les points saillants de l'ATLAS au sujet de l'état actuel des soins cardiovasculaires offerts aux femmes, ainsi que des défis et des occasions dans ce domaine. Nous concluons par 12 recommandations concrètes sur les prochaines étapes à entreprendre pour donner suite aux progrès déjà réalisés afin de combler les lacunes dans les connaissances, en s'attaquant aux disparités qui subsistent dans les soins cardiovasculaires prodigués aux femmes, dans le but d'améliorer les résultats de santé des femmes au Canada.

Determinants of Impaired Peak Oxygen Uptake in Breast Cancer Survivors: JACC: CardioOncology Primer.

•Exercise intolerance is common among breast cancer survivors.•Exercise intolerance in breast cancer survivors is related to cardiac, vascular, and skeletal muscle impairments.•Holistic rehabilitation or pharmacological therapies are needed to address these impairments.

Reference Values for Water-Specific T1 of the Liver at 3 T: T2*-Compensation and the Confounding Effects of Fat.

BACKGROUND: T1 mapping of the liver is confounded by the presence of fat. Multiparametric T1 mapping combines fat-water separation with T1-weighting to enable imaging of water-specific T1 (T1Water ), proton density fat fraction (PDFF), and T2* values. However, normative T1Water values in the liver and its dependence on age/sex is unknown. PURPOSE: Determine normative values for T1Water in the liver with comparison to MOLLI and evaluate a T2*-compensation approach to reduce T1 variability. STUDY TYPE: Prospective observational; phantoms. POPULATIONS: One hundred twenty-four controls (56 male, 18-75 years), 50 patients at-risk for liver disease (18 male, 30-76 years). FIELD STRENGTH/SEQUENCE: 2.89 T; Saturation-recovery chemical-shift encoded T1 Mapping (SR-CSE); MOLLI. ASSESSMENT: SR-CSE provided T1Water measurements, PDFF and T2* values in the liver across three slices in 6 seconds. These were compared with MOLLI T1 values. A new T2*-compensation approach to reduce T1 variability was evaluated test/re-test reproducibility. STATISTICAL TESTS: Linear regression, ANCOVA, t-test, Bland and Altman, intraclass correlation coefficient (ICC). P < 0.05 was considered statistically significant. RESULTS: Liver T1 values were significantly higher in healthy females (F) than males (M) for both SR-CSE (F-973 ± 78 msec, M-930 ± 72 msec) and MOLLI (F-802 ± 55 msec, M-759 ± 69 msec). T1 values were negatively correlated with age, with similar sex- and age-dependencies observed in T2*. The T2*-compensation model reduced the variability of T1 values by half and removed sex- and age-differences (SR-CSE: F-946 ± 36 msec, M-941 ± 43 msec; MOLLI: F-775 ± 35 msec, M-770 ± 35 msec). At-risk participants had elevated PDFF and T1 values, which became more distinct from the healthy cohort after T2*-compensation. MOLLI systematically underestimated liver T1 values by ~170 msec with an additional positive T1-bias from fat content (~11 msec/1% in PDFF). Reproducibility ICC values were ≥0.96 for all parameters. DATA CONCLUSION: Liver T1Water values were lower in males and decreased with age, as observed for SR-CSE and MOLLI acquisitions. MOLLI underestimated liver T1 with an additional large positive fat-modulated T1 bias. T2*-compensation removed sex- and age-dependence in liver T1, reduced the range of healthy values and increased T1 group differences between healthy and at-risk groups. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

Plastid-localized xanthorhodopsin increases diatom biomass and ecosystem productivity in iron-limited surface oceans.

Microbial rhodopsins are photoreceptor proteins that convert light into biological signals or energy. Proteins of the xanthorhodopsin family are common in eukaryotic photosynthetic plankton including diatoms. However, their biological role in these organisms remains elusive. Here we report on a xanthorhodopsin variant (FcR1) isolated from the polar diatom Fragilariopsis cylindrus. Applying a combination of biophysical, biochemical and reverse genetics approaches, we demonstrate that FcR1 is a plastid-localized proton pump which binds the chromophore retinal and is activated by green light. Enhanced growth of a Thalassiora pseudonana gain-of-function mutant expressing FcR1 under iron limitation shows that the xanthorhodopsin proton pump supports growth when chlorophyll-based photosynthesis is iron-limited. The abundance of xanthorhodopsin transcripts in natural diatom communities of the surface oceans is anticorrelated with the availability of dissolved iron. Thus, we propose that these proton pumps convey a fitness advantage in regions where phytoplankton growth is limited by the availability of dissolved iron.

Cardio-oncology and Cancer Rehabilitation: Is an Integrated Approach Possible?

With significant improvements in the understanding of cancer biology, improved detection, and the use of novel adjuvant therapies, each year more Canadians are surviving a cancer diagnosis. Despite their effectiveness these therapies often result in short- and long-term deleterious effects to major organ systems, particularly cardiovascular. Cardio-oncology is an emerging field of study with the aim to improve cardiovascular health across the oncology disease spectrum. International guidelines distinguish "cardio-oncology" rehabilitation from "cancer" rehabilitation, but how this is navigated is currently unknown. How such care should be assessed and integrated acutely or in the longer term remains unknown. Accordingly, the aim of this article is to consider the cancer patient's needs beyond the scope of cardio-oncology rehabilitation to holistically integrate cancer rehabilitation across the disease trajectory.

Time-Restricted Eating: A Novel Dietary Strategy for Cardiac Rehabilitation.

Cardiac rehabilitation (CR) is a multimodal program considered to be the standard of care for secondary prevention of cardiovascular disease (CVD). The primary goals of CR are managing CVD risk factors and improving quality of life. Exercise is the cornerstone, but nutrition education delivered by registered dietitians (RDs) is a core component of CR. Yet patient constraints to adherence to dietary change and limited availability of RDs represent major barriers to the success of completion of nutrition intervention during CR. Therefore, nutritional strategies that reduce CVD risk factors, barriers to adherence, and have capacity for broad dissemination are warranted within CR programs. In this review, we propose time-restricted eating (TRE) as a nutrition strategy to improve the outcomes of CR by drawing on parallels to CVD in other populations and describe the available preliminary data on the efficacy of TRE for CVD. TRE is a dietary strategy that involves alternating periods of fasting and consumption of calories each day. We outline the feasibility, safety, and beneficial cardiometabolic impact of TRE from TRE research in other populations. We also discuss the potential for synergistic benefits of exercise when combined with TRE. Although there is currently limited research on TRE within CR programs, we highlight CR as a unique clinical setting where TRE could play a role in secondary prevention of CVD. Overall, we outline the potential of TRE as a promising nutrition strategy to enhance the benefits of CR.

Evolution of anelloviruses from a circovirus-like ancestor through gradual augmentation of the jelly-roll capsid protein.

Anelloviruses are highly prevalent in diverse mammals, including humans, but so far have not been linked to any disease and are considered to be part of the 'healthy virome'. These viruses have small circular single-stranded DNA (ssDNA) genomes and encode several proteins with no detectable sequence similarity to proteins of other known viruses. Thus, anelloviruses are the only family of eukaryotic ssDNA viruses currently not included in the realm Monodnaviria. To gain insights into the provenance of these enigmatic viruses, we sequenced more than 250 complete genomes of anelloviruses from nasal and vaginal swab samples of Weddell seal (Leptonychotes weddellii) from Antarctica and a fecal sample of grizzly bear (Ursus arctos horribilis) from the USA and performed a comprehensive family-wide analysis of the signature anellovirus protein ORF1. Using state-of-the-art remote sequence similarity detection approaches and structural modeling with AlphaFold2, we show that ORF1 orthologs from all Anelloviridae genera adopt a jelly-roll fold typical of viral capsid proteins (CPs), establishing an evolutionary link to other eukaryotic ssDNA viruses, specifically, circoviruses. However, unlike CPs of other ssDNA viruses, ORF1 encoded by anelloviruses from different genera display remarkable variation in size, due to insertions into the jelly-roll domain. In particular, the insertion between ß-strands H and I forms a projection domain predicted to face away from the capsid surface and function at the interface of virus-host interactions. Consistent with this prediction and supported by recent experimental evidence, the outermost region of the projection domain is a mutational hotspot, where rapid evolution was likely precipitated by the host immune system. Collectively, our findings further expand the known diversity of anelloviruses and explain how anellovirus ORF1 proteins likely diverged from canonical jelly-roll CPs through gradual augmentation of the projection domain. We suggest assigning Anelloviridae to a new phylum, 'Commensaviricota', and including it into the kingdom Shotokuvirae (realm Monodnaviria), alongside Cressdnaviricota and Cossaviricota.

Phase angle is associated with muscle health and cardiorespiratory fitness in older breast cancer survivors.

BACKGROUND & AIM: Phase angle (PhA) obtained from bioelectrical impedance analysis (BIA) is an indicator of cellular integrity and relates to several chronic conditions. The purpose of this secondary analysis was to evaluate the association of PhA with health-related physical fitness, namely, cardiorespiratory fitness, skeletal muscle volume, and myosteatosis (i.e. muscle health) in older breast cancer survivors. METHODS: Twenty-two women ≥60 years with a body mass index (BMI) ≥25 kg/m2 and who completed chemotherapy for early-stage breast cancer were included. BIA, cardiopulmonary exercise tests and magnetic resonance imaging scans were completed before and after eight weeks of time-restricted eating. RESULTS: At baseline, PhA was associated with cardiorespiratory fitness (R2 = 0.54, p < 0.01) and skeletal muscle volume (R2 = 0.83, p < 0.01) and myosteatosis (R2 = 0.25, p = 0.02). Results were similar at follow-up. CONCLUSION: Findings from this pilot study suggest that higher values of PhA are associated with better health-related physical fitness among older breast cancer survivors.

Time-Restricted Eating in Breast Cancer Survivors: Effects on Body Composition and Nutritional Status.

In this secondary analysis of an 8-wk single-arm feasibility study of weekday time-restricted eating (TRE), we explored the effects of TRE on body composition. Women (n = 22; ≥60 yr) who had completed chemotherapy for early-stage breast cancer and had a body mass index ≥25 kg/m2 were enrolled. Bioelectrical impedance analysis was performed before and after 8 wk of TRE, and nutritional status was evaluated by bioelectrical impedance vector analysis (BIVA). Body weight (p = 0.01) and total fat mass (p = 0.04) decreased with TRE. Phase angle was low (defined as ≤5.6°) in 86% of participants at baseline and did not change. Four participants who initially presented with obesity (>95% ellipse, BIVA) had favorable body composition modifications after TRE. Our study highlighted a less favorable body composition profile, poorer cell integrity and overhydration in these patients. BIVA was a useful method to assess body composition and hydration. A short TRE intervention was associated with decreased estimated fat mass and a favorable change in nutritional status in those with obesity.

Implementation of weekday time-restricted eating to improve metabolic health in breast cancer survivors with overweight/obesity.

OBJECTIVE: This study aimed to evaluate the implementation of telephone-based delivery of weekday-only time-restricted eating (TRE), its preliminary efficacy for metabolic outcomes, and concurrent lifestyle changes. METHODS: Twenty-two breast cancer survivors aged 60+ years with overweight/obesity completed an 8-week feasibility study of 12 to 8 p.m. weekday-only ad libitum TRE. The intervention was delivered by one registered dietitian call, twice-daily automated text messages asking about eating start and stop times, and three support phone calls. Magnetic resonance imaging, venipuncture, and 3 days of diet records and accelerometry were performed at baseline and after intervention. RESULTS: Participants had a mean age of 66 (SD 5) years with BMI of 31.8 (4.8) kg/m2 . Intervention implementation was successful, including excellent adherence (98%), participant acceptability, and a low symptom profile and cost ($63/participant). There were no significant changes in individual components of metabolic syndrome, lipid profile, or hemoglobin A1c , despite clinically relevant changes occurring within individual participants. Magnetic resonance imaging-derived hepatic steatosis and thigh myosteatosis did not change. Dietary intake changes included reduced energy (-22%) and protein (-0.2 g/kg). Physical activity and sleep did not change. CONCLUSIONS: Eight weeks of telephone-delivered weekday TRE is a feasible, acceptable, low-symptom, and low-cost intervention. Future studies may consider a longer intervention length for more consistent metabolic improvements and counseling to enhance protein intake.

Rationale and design of IMPACT-women: a randomised controlled trial of the effect of time-restricted eating, healthy eating and reduced sedentary behaviour on metabolic health during chemotherapy for early-stage breast cancer.

Metabolic dysfunction and excess accumulation of adipose tissue are detrimental side effects from breast cancer treatment. Diet and physical activity are important treatments for metabolic abnormalities, yet patient compliance can be challenging during chemotherapy treatment. Time-restricted eating (TRE) is a feasible dietary pattern where eating is restricted to 8 h/d with water-only fasting for the remaining 16 h. The purpose of this study is to evaluate the effect of a multimodal intervention consisting of TRE, healthy eating, and reduced sedentary time during chemotherapy treatment for early-stage (I-III) breast cancer on accumulation of visceral fat (primary outcome), other fat deposition locations, metabolic syndrome and cardiovascular disease risk (secondary outcomes) compared with usual care. The study will be a two-site, two-arm, parallel-group superiority randomised control trial enrolling 130 women scheduled for chemotherapy for early-stage breast cancer. The intervention will be delivered by telephone, including 30-60-minute calls with a registered dietitian who will provide instructions on TRE, education and counselling on healthy eating, and goal setting for reducing sedentary time. The comparison group will receive usual cancer and supportive care including a single group-based nutrition class and healthy eating and physical activity guidelines. MRI, blood draws and assessment of blood pressure will be performed at baseline, after chemotherapy (primary end point), and 2-year follow-up. If our intervention is successful in attenuating the effect of chemotherapy on visceral fat accumulation and cardiometabolic dysfunction, it has the potential to reduce risk of cardiometabolic disease and related mortality among breast cancer survivors.

Determinants of oxygen utilization in breast cancer: Similarities between heart failure with preserved ejection fraction.

Reduced exercise tolerance and fatigue are hallmark features in both breast cancer (BC) and heart failure with preserved ejection fraction (HFpEF) and are associated with decreased physical function and quality of life. This brief review focuses on the mechanisms of exercise intolerance in women with BC across the survivorship continuum and highlights how these disturbances within the oxygen transport cascade are similar to that of HFpEF patients. Specifically, the role that impaired cardiac, peripheral vascular and skeletal muscle function play in limiting peak oxygen uptake are discussed. We propose that women with BC are at increased risk of developing HFpEF potentially due to the adverse effects of chemotherapy and concurrent adverse lifestyle behaviors on cardiovascular and skeletal muscle function.

Prevalence of Breast Cancer Survivors Among Canadian Women.

BACKGROUND: The 49% decrease in breast cancer mortality since 1986 has increased the number of breast cancer survivors requiring survivorship care. The purpose of this analysis was to estimate the 2022 prevalence of breast cancer survivors diagnosed within the past 15 years among Canadian women. METHODS: We extracted the projected female breast cancer cases from 2007 to 2021 and rates of net survival (competing noncancer causes of death removed) from the Canadian Cancer Society's statistical reports. Overall survival was extracted from published Ontario data. Using known survival rates for 1, 5, 10, and 15 years, we interpolated remaining years and applied the corresponding net and overall survival rates to the projected cases for each year from 2007 to 2021 to determine survivors in 2022. Prevalence for predefined age groups was also calculated. As an example of excess healthcare costs attributable to breast cancer, we calculated the excess costs of heart failure hospitalizations. RESULTS: From 2007 to 2021, there were 370,756 breast cancer cases. Using net survival, 318,429 (85.9%) of these patients were projected to survive breast cancer by 2022, a prevalence of 2.1% of Canadian women. Using overall survival, prevalence was 1.8%. Prevalence increased with age group, from 0.01% of those aged 20 to 24 years to 12.7% of those aged ≥90 years, and from 1.0% among the working and/or child-raising (age 20-64 years) to 5.4% among elderly populations (age ≥65 years). Among these survivors, 24.9% of projected heart failure hospitalizations would be in excess of those among matched control subjects, with projected excess costs of $16.5 million CAD. Given the excess healthcare costs, potential for reduced contributions to the workforce, and reduced quality of life associated with long-term impairments and risk of excess non-breast cancer death, enhanced breast cancer survivorship care is warranted. CONCLUSIONS: With an overall prevalence of 2% among Canadian women, breast cancer survivors represent an increasing segment of the working-age and elderly populations.

Cardiometabolic health impacts of time-restricted eating: implications for type 2 diabetes, cancer and cardiovascular diseases.

PURPOSE OF REVIEW: Time-restricted eating (TRE) entails consuming energy intake within a 4- to 10-h window, with the remaining time spent fasting. Although studies have reported health benefits from TRE, little is known about the impact of TRE on common chronic diseases such as type 2 diabetes, cancer and cardiovascular disease. This review summarizes and critically evaluates the most recent TRE research findings relevant to managing and treating these chronic diseases. RECENT FINDINGS: Most recent TRE studies have been in populations with overweight/obesity or metabolic syndrome; two have been in populations with diabetes, three in cancer survivors and none in populations with cardiovascular disease. Collectively, these studies showed that participants could adhere to TRE and TRE is well tolerated. These studies also showed preliminary efficacy for improved glucose regulation and insulin sensitivity, a reduction in body fat and blood pressure, reduced cardiovascular risk scores and increased quality of life. More research is required to define the most effective TRE protocol (i.e. length and timing of eating window, intervention duration). SUMMARY: TRE has demonstrated benefits on cardiovascular, metabolic and clinical outcomes relevant to the underlying pathophysiology, but there are limited data on TRE implemented specifically within populations with diabetes, cancer or cardiovascular disease.

Iron mobilization during lactation reduces oxygen stores in a diving mammal.

The profound impacts that maternal provisioning of finite energy resources has on offspring survival have been extensively studied across mammals. This study shows that in addition to calories, high hemoprotein concentrations in diving mammals necessitates exceptional female-to-pup iron transfer. Numerous indices of iron mobilization (ferritin, serum iron, total-iron-binding-capacity, transferrin saturation) were significantly elevated during lactation in adult female Weddell seals (Leptonychotes weddellii), but not in skip-breeders. Iron was mobilized from endogenous stores for incorporation into the Weddell seal's milk at concentrations up to 100× higher than terrestrial mammals. Such high rates of iron offload to offspring drew from the female's own heme stores and led to compromised physiologic dive capacities (hemoglobin, myoglobin, and total body oxygen stores) after weaning their pups, which was further reflected in shorter dive durations. We demonstrate that lactational iron transfer shapes physiologic dive thresholds, identifying a cost of reproduction to a marine mammal.

Longitudinal Changes in Skeletal Muscle Metabolism, Oxygen Uptake, and Myosteatosis During Cardiotoxic Treatment for Early-Stage Breast Cancer.

BACKGROUND: While cardiotoxic chemotherapy is known to negatively impact cardiac function and hemoglobin levels, the impact on skeletal muscle has been understudied among patients. The purpose was to longitudinally characterize myosteatosis (muscle fat), skeletal muscle metabolism, and oxygen (O2) consumption during cardiotoxic chemotherapy for breast cancer. PATIENTS AND METHODS: Thirty-four patients with stage I-III breast cancer were enrolled before trastuzumab-containing and/or anthracycline-containing chemotherapy. We used magnetic resonance imaging to non-invasively quantify thigh myosteatosis (fat-water imaging), and lower leg metabolism (31P spectroscopy), O2 consumption (custom techniques), and peak power output during single-leg plantarflexion exercise at pre-, mid-, end-chemotherapy, and 1-year. We also measured pulmonary VO2peak and maximal leg press strength. RESULTS: During chemotherapy, VO2peak and leg press strength decreased while peak plantarflexion power output was maintained. At mid-chemotherapy, hemoglobin decreased (16%) and lower leg blood flow increased (37%) to maintain lower leg O2 delivery; exercise Pi:PCr and myosteatosis increased. Between mid- and end-chemotherapy, lower leg O2 extraction (28%) and O2 consumption (21%) increased, while plantarflexion exercise efficiency (watts/O2 consumed) decreased. At one year, VO2peak and leg press strength returned to pre-chemotherapy levels, but lower leg exercise O2 extraction, consumption and Pi:PCr, and myosteatosis remained elevated. CONCLUSION: Lower leg skeletal muscle blood flow and O2 extraction adapt to compensate for chemotherapy-related hemoglobin reduction for small muscle mass exercise but are insufficient to maintain large muscle mass exercise (pulmonary VO2peak, leg press strength). The excess O2 required to perform work, increased Pi:PCr ratio and myosteatosis together suggest suppressed fat oxidation during chemotherapy.