European Journal of Applied Physiology

Mental fatigue is induced by prolonged engagement in cognitively demanding tasks and impairs endurance performance. The neuropsychophysiological mechanisms underlying this decreased performance remain unclear, with suggestion that mental fatigue may disrupt motor command and consequently muscle activation. We aimed to test this hypothesis in a repeated cross-over design study in which 18 participants completed two experimental sessions involving a time-to-exhaustion cycling test at 80% of peak power output. Each cycling task was preceded by 1h of a prolonged Stroop task (Stroop session) or a neutral control task (Control session). Perception of effort and surface electromyography from ten lower-limb muscles of the right leg were recorded at regular intervals during cycling. Mental fatigue was higher in the Stroop compared to the Control session (p = .002). Endurance cycling time was 111 {+/-} 160 s shorter in the Stroop than in the Control session (p = .009). No significant differences in electromyography parameters were observed between Stroop and Control sessions, for any muscle (p > .05). Perception of effort was higher in the Stroop session from the onset of the cycling task (p = .006), and the rate of increase in perception of effort was significantly higher in the Stroop than Control session (p = .031). Our findings do not support the hypothesis that mental fatigue alters motor control or increases central motor command, as no changes in muscle activation were detected. Conversely, our results reinforce the notion that prolonged cognitive engagement impairs endurance performance primarily through an increased perception of effort. Future research should consider combining surface electromyography with more sensitive neurophysiological techniques to investigate potential subtle changes in motor drive during dynamic, whole-body tasks under mental fatigue. Impact statementOur study confirms that mental fatigue induced by prolonged cognitive exertion impairs cycling endurance performance. By combining measurements of perceptual responses and multi-muscle surface EMG during the endurance task, we observed that the decreased endurance performance is related to an increased perceived effort in the presence of mental fatigue, not related to alterations in motor command.

ObjectiveTandem cycling requires a coordinated effort between the pilot and the stoker. Previous research suggests that randomly paired tandem cyclists produce lower power output than when cycling solo. This study examined how a cyclists individual ability and their position on the tandem (pilot or stoker) affects pair performance, when partners are either closely matched or differ substantially in solo cycling capacity, as this might be relevant for training and selection. MethodsTwenty-three trained cyclists completed three 10-minute time trials: solo, equal-capacity tandem ([≤]25 W difference in solo performance), and unequal-capacity tandem ([≥]40 W difference). Mean power output, heart rate, cadence, and rating of perceived exertion (RPE) were recorded. Positions (pilot or stoker) were counterbalanced. Linear mixed-effects models assessed effects of capacity and position. ResultsRelative to solo cycling, equal-capacity tandem pairs revealed lower power output (-3.9%), lower heart rate (-2.3%), and lower RPE (-11.5%). Unequal-capacity tandems differed from solo only in heart rate (-2.7%). Stokers produced lower power relative to solo (-5.3%) and relative to pilots (-3.7%) and reported lower RPE relative to solo (-13.9%), while pilots matched their solo power at a lower heart rate (-2.9%). Cadence did not differ across conditions. Total tandem power averaged 95.6% of combined solo power, and differences in partner capacity did not significantly affect combined power output. ConclusionThis study provides the first known experimental data on how partner matching affects individual and combined power output in tandem cycling. Equal- and unequal-capacity tandem pairs showed similar performance. Lower power and RPE among stokers suggest reduced engagement or a redistribution of effort between riders. These findings highlight that effective tandem performance depends on physiological capacity and rider position on the tandem, but not on the difference in capacity between partners.

This study investigates closed kinematic chain biomechanics in cycling with a focus on knee joint loading. Data from 16 cyclists collected on a standardized ergometer were analyzed in OpenSim using inverse dynamics, static optimization, and joint reaction analysis. To keep the pipeline consistent across all subjects, the report summarizes right-knee outputs over a steady-state interval between 120 and 124 s. Peak knee joint moments ranged from 15.79 to 44.85 Nm (mean 30.49 {+/-} 7.66 Nm), while peak resultant knee reaction forces ranged from 1187.61 to 3309.04 N (mean 2317.19 {+/-} 728.19 N). Static optimization showed strong contributions from the rectus femoris and vastus lateralis during power production, with additional stabilization from the biceps femoris long head and gastrocnemius medialis. Mean peak muscle activation was highest for the rectus femoris (0.72 {+/-} 0.19), followed by the biceps femoris long head (0.66 {+/-} 0.20). Mean peak muscle force was highest for the vastus lateralis (1078.1 {+/-} 305.8 N) and rectus femoris (994.1 {+/-} 379.2 N). The results confirm substantial inter-subject variability in knee loading and support the use of personalized training or rehabilitation strategies when cycling is used for performance development or joint recovery.

Muscle mass significantly influences skeletal muscle behaviour, potentially explaining why traditional massless Hill-type models struggle to predict the forces generated by larger muscles during dynamic, submaximal contractions. However, the applicability of mass-enhanced Hill-type models in human locomotion remains unexplored. Here, we compared the predicted force from a 1D mass-enhanced Hill-type muscle model with a traditional 1D massless Hill-type muscle model across a range of experimentally measured human movements. Kinematic and electromyographic data were collected from twenty participants performing locomotor tasks and supplemented with existing cycling data. Muscle size was geometrically scaled by factors from 0.1 to 10, which causes lengths to be scaled proportionally, cross-sectional area and peak isometric force F0 with the square, and mass with the cube of the factor. Muscle tissue mass (inertia) and cadence increased the differences between mass-enhanced and massless predictions of force and power. At high cadence and the largest scale, the normalized root mean square difference between force traces reached 7% of F0, (averaged across muscles). However, differences between models were minimal (<1%) at human-sized scale 1. Real muscle additionally deforms in 3D, we still do not know the extent to which this extra dimensionality affects muscle forces for these human movements.

The transition to higher education is characterized by increased academic demands and psychosocial stress, which may negatively affect cognitive functioning and student well-being. Executive functions (working memory, inhibitory control, and cognitive flexibility) are critical for academic adaptation and can be enhanced through structured interventions. Physical exercise, mind-body practices, and cognitive training have demonstrated potential benefits for executive functioning and stress reduction; however, few randomized controlled trials have directly compared interventions with different physical and cognitive demands in university students, particularly in Latin America. In addition, most studies have relied on self-report measures and physiological stress biomarkers such as salivary cortisol. This protocol describes a three-arm, parallel-group randomized controlled trial designed to evaluate the effects of a 12-week intervention on executive functions and stress in first-year university students. The study will recruit 120 first-year health-science students aged 18-25 years. Participants will be randomly assigned (1:1:1), using block randomization stratified by sex, to one of three interventions delivered twice weekly (24 sessions of 60 minutes): (1) moderate-to-vigorous motor-cognitive dual-task exercise (DT); (2) low-to-moderate intensity Tai Chi (TC); or (3) supervised digital cognitive stimulation (CS) using structured graphomotor tasks. Primary outcomes include executive functions assessed through standardized neuropsychological measures. Secondary outcomes include stress will be evaluated using the Academic Stress Inventory, Depression Anxiety Stress Scales and salivary cortisol collected in the morning using passive drool and analyzed by competitive ELISA.Other outcomes include physical activity levels, anthropometric and body composition measures, and handgrip strength. Data will be analyzed following an intention-to-treat approach using repeated-measures models, with multiple imputation for missing data. The study has received institutional ethics and biosafety approval. Trial registration: ClinicalTrials.gov Identifier: NCT07443904.

The association between higher levels of physical activity and lower cancer risk and mortality is well established. However, a causal link is yet to be proven. Recent studies showed a decrease in the proliferation rates of cultured human cancer cells when the human serum employed to stimulate them was conditioned by acute exercise. Here, we tested the hypothesis that serum mediates some of the putative benefits of exercise on cancer through alterations to the growth pattern and susceptibility to chemotherapy agents of cancer cells. To this end, human non-small cell lung cancer (NSCLC) cells were exposed to serum from two cohorts that differed significantly on their levels of physical activity and, accordingly, cardiorespiratory fitness, but were otherwise identical (master athletes and non-exercisers), collected before and after an acute exercise intervention. Serum levels of glucose, lipids, albumin, C-reactive protein and cytokines were determined and the impact of the serum responses to acute and lifelong exercise on the above-mentioned parameters were analyzed. We found that acute exercise decreased the cells proliferation rate, yet shortened the cells lag phase after detachment, whereas lifelong exercise had the opposite effects. Significantly, we showed, for the first time, that lifelong exercise increased susceptibility to a chemotherapy agent (cisplatin), which may contribute to the decreased cancer mortality rates found among those who exercise regularly. Similar to the cellular effects, changes to serum cytokine levels - several of them linked to the senescence-associated secretory phenotype - depended on whether serum was conditioned by acute or by chronic exercise. Key pointsChronic exercise increased the in vitro susceptibility of lung cancer cells to cisplatin. Acute and chronic exercise modulated the in vitro tumorigenic potential of lung cancer cells. Effects were mediated by serological changes produced by exercise. Acute and chronic exercise had distinct impacts on serological cytokine levels.

BackgroundTranscranial Magnetic Stimulation (TMS) studies identify the Resting Motor Threshold (RMT) to calibrate stimulation intensity. However, this procedure is time-consuming and subject to variability. We developed an automated procedure to improve the efficiency and standardization of RMT determination. New methodWe developed an algorithm that measures MEP amplitudes and automatically adjusts stimulation intensity to determine the RMT. Experiment 1 compared this automated method with the manual procedure in terms of reliability and equivalence. Experiment 2 developed a "Fast" automated process, assessing it against both the manual and initial automated procedures. ResultsAcross both experiments the automated approach demonstrated excellent test-retest reliability and strong agreement with the manual method (Intraclass Correlation Coefficients [&ge;]0.95), giving estimates of RMT statistically equivalent to those of manual measurements within {+/-}3% MSO, with the majority of comparisons within {+/-}2% MSO. Experiment 2 optimized the procedure, allowing empirical determination of the RMT in an average of <3 minutes with only 33-34 pulses. Comparison with existing methods RMT-Finder provides a reliable and time-efficient alternative to manual approaches. To the best of our knowledge RMT-Finder presents the first closed-loop feedback approach to identify the RMT without manual intervention. This procedure can improve standardization and reproducibility in TMS studies. ConclusionsAutomating RMT assessment allows rapid and highly reproducible assessment of this standard TMS measurement, making it viable for inclusion in routine clinical applications that require standardized procedures.

Objective: To investigate the effects of breaking up prolonged sedentary behavior (SB) on daily movement behavior and energy balance in adults with overweight/obesity. Methods: Thirty participants (16F/14M; 34.2+-7.3y; 29.5+-3.2kg/m2) were randomized to either BREAK (nine hourly 5-min brisk walking bouts) or a duration-matched intervention, ONE (45-min brisk walking), both performed 5 days/week for 6 weeks. Pre- and post-intervention, daily SB and physical activity (PA; accelerometry), body composition (doubly labeled water [DLW]), total daily energy expenditure (TDEE; DLW), appetite, and fasting leptin were measured. Linear-mixed effects models tested time effects and time-by-group interactions. Results: Only BREAK reduced prolonged SB (-8%; interaction: p=0.043). Both groups shifted SB-PA composition toward greater moderate-to-vigorous PA with proportional reductions in SB and light PA (time: all p<0.012), which were associated with increases in TDEE (+0.67 MJ/d; time: p=0.040). Body and fat mass increased in ONE only (interaction: p=0.061 and p=0.055). No differences were noted in energy intake, appetite, or leptin levels. Conclusions: Spreading short PA bouts throughout the day increases MVPA and TDEE to the same extent as a traditional continuous PA bout. Future studies should investigate whether minor differences in body composition are driven by distinct behavioral/physiological compensations influenced by the daily pattern of PA/SB.

ObjectiveTo develop and internally validate a field-side triage model to support early specialist referral decisions in young athletes with acute lower extremity sports injuries, where diagnostic resources are often limited. DesignRetrospective cohort study. SettingSingle-center sports medicine clinic. ParticipantsAthletes aged [&le;]22 years presenting with acute lower extremity sports injuries between January 2017 and November 2025. Independent VariablesAge, sex, functional severity, injury site, and injury mechanism assessed at initial presentation. ResultsA total of 2,129 athletes were included, with 276 (13.0%) undergoing surgery. Independent predictors were older age, female sex, greater functional severity, knee involvement, and high-energy deceleration mechanisms. The full model showed good performance (AUC 0.890; Brier score 0.073; calibration slope 1.00), and the simplified model also demonstrated high discrimination (AUC 0.883). Risk stratification showed increasing surgical rates across low-, intermediate-, and high-risk groups. Decision curve analysis demonstrated greater net benefit than treat-all and treat-none strategies across clinically relevant thresholds. ConclusionsA field-side prediction model based on readily obtainable clinical variables demonstrated good performance for identifying young athletes at risk of requiring surgical intervention and may support early specialist referral decisions in resource-limited settings. Clinical RelevanceThis model provides a practical tool for early risk stratification using simple clinical information, supporting timely and appropriate referral decisions in field-side and initial clinical settings.

ObjectiveTo investigate the effects of different gait patterns on knee joint biomechanics and dynamic stability during stair ascent. MethodsFourteen healthy males were recruited to ascend stairs using two distinct gait patterns: the "single-step" (leading with the same leg) and "cross-step" (alternating legs) strategies. Kinematic and kinetic data were collected synchronously using a Qualisys infrared motion capture system and a Kistler 3D force plate. Dynamic stability was quantified using the Margin of Stability (MOS), and knee joint biomechanics were evaluated using Patellofemoral Joint Stress (PFJS) and other relevant metrics. ResultsThroughout the gait cycle, there was no significant difference in the Medio-Lateral (ML) MOS between the single-step and cross-step patterns (P=0.318). However, in the Anterior-Posterior (AP) direction, the MOS for both patterns remained negative and decreased over time, with the cross-step pattern exhibiting significantly lower AP MOS values than the single-step pattern (P=0.002). At the moment of left foot-off, significant differences were observed in the right knee joint angle, right knee joint moment, net joint moment, effective quadriceps muscle lever arm, Quadriceps Force (QF), the angle between the quadriceps tendon and patellar ligament, Patellofemoral Joint Force (PFJF), patellofemoral joint stress, and patellofemoral contact area (all P<0.001). ConclusionsDuring stair ascent, the cross-step pattern reduces body stability, thereby increasing the risk of backward falls. Furthermore, this pattern increases patellofemoral joint stress, subjecting the knee to greater loading. Therefore, it is recommended to enhance lower limb muscle strength through targeted training to reduce fall risk. Additionally, adopting a more cautious gait strategy (such as the single-step pattern) can help minimize patellofemoral joint loading and mitigate the risk of patellofemoral pain.

OBJECTIVE To guide treatment of adults with rotator cuff tendinopathy (RoCuTe) by evaluating the relative efficacy of treatments, benchmarked against minimal intervention, for the co-primary outcomes of pain, function and quality-of-life (QoL) across short, medium, and long-term follow-up. DESIGN Systematic review with Bayesian predictive and network meta-analyses for synthesising complex interventions, guided by stakeholder involvement. FUNDING Private Physiotherapy Education Foundation (UK) Silver Jubilee Award. DATA SOURCES PubMed, Embase, Web of Science, CINAHL, and SPORTDiscus, searched to 22/8/2025. ELIGIBILITY CRITERIA FOR SELECTING STUDIES High-quality (PEDro score equal or above 7) randomised controlled trials comparing any intervention with another active or minimal intervention for patients clinically diagnosed with RoCuTe of either traumatic or insidious presentation; and reporting outcomes for pain, function and/or QoL. METHODS Title and abstract screening, full-text screening, and quality assessments were completed by two reviewers. Data extraction used the Elicit AI tool and was manually checked. Interventions were classified by treatment focus. Guided by patient and public involvement, pooled results from active interventions at short (1 to 12 weeks included), mid (>12 weeks to <12 months) and long-term (12 months included or more) were calculated for the primary analysis using Bayesian predictive meta-analysis models of within group change scores. Outcomes were benchmarked against an empirically derived minimal-intervention comparator (wait-and-see or sham). As a secondary analysis, network meta-analyses were conducted to synthesise relative effects and provide comparative rankings of active interventions. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool, and certainty of evidence evaluated using GRADE. RESULTS We retained and analysed 140 high-quality studies that included 10,260 patients, 55.9% female, with a mean age of 48 (SD 8) years. Minimal interventions were associated with small short-term improvements, modest medium-term improvements and some regression in the long-term; in pain (0 to 100 scale: short=2.6; mid=23.3; long=21.1), function (standardised mean change (SMC): short=0.13; mid=0.87; long=0.76), and QoL (SMC: short=0.05; mid=0.33). At all timepoints, all active interventions with sufficient data were superior to minimal intervention for pain (0 to 100 scale: short = 18.1 to 37.9 [14 categories]; mid = 25.8 to 34.8 [8 categories]; long = 30.8 to 45.0 [6 categories]), function (SMC: short = 1.1 to 2.4 [14 categories]; mid = 1.1 to 2.0 [11 categories]; long = 1.0 to 1.8 [10 categories]), and QoL (short = 0.8 to 1.7 [7 categories]; mid = 0.9 to 1.8 [6 categories]). Certainty varied widely. Accordingly, three recommendation groups were defined based on the availability of comparative evidence and presence of higher-certainty findings. The strongest recommendation group included strengthening, range-of-motion exercises, complex interventions and movement pattern retraining. CONCLUSIONS A range of active treatments were superior to minimal intervention at each time point, so a wait-and-see approach should not be used, even in in the short-term. The most credible evidence was for interventions with a focus on strengthening, range-of-motion exercises, movement pattern retraining, and complex interventions. Clinicians should prioritise active management and deploy personalised clinical reasoning to tailor treatment to patient preferences and the available resources. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42024584126

Heat-related illnesses pose a significant public health challenge in Europe, resulting in increased mortality. Although cold water immersion (CWI) is the most effective treatment for heat stroke, its clinical use is limited. A better understanding of temperature changes in the peripheral body regions can lead to more effective CWI application. Nevertheless, most muscle temperature measurement techniques are invasive. This study evaluated magnetic resonance spectroscopy (MRS) for non-invasive assessment of intramuscular temperature during cold stress and rewarming. Nine healthy volunteers (7 men, 2 women) participated in three 3T MRI sessions: baseline (PRE), immediately after 15 minutes of CWI at 10 degrees to the iliac crest (POST-CWI), and following 100-Watt cycling (POST-cycling). Each scan session included T1w and localized spectroscopy acquisitions in the right thigh. Absolute temperature was estimated from the proton resonance frequency shift between water and creatine peaks. The measurements were split into three groups of voxels, defined as follows: close to the top (TL), bottom (BL), or central (DL) thigh positions. Measurement depth showed a location main effect (p<0.001, p^2=0.40), with DL (35.4[5.9] mm) significantly deeper than TL (22.5[4.2] mm) and BL (25.3[5.1] mm), remaining constant across phases. Temperature decreased significantly from PRE to POST-CWI across all locations (TL: p<0.001, d=2.74; BL: p<0.001, d=1.84; DL: p<0.005, d=1.14). Post-cycling temperature increased at all sites compared to POST-CWI (DL: p=0.040, d=1.06; TL: p<0.001, d=1.7; BL: p<0.001, d=1.80), though TL remained lower than PRE (p<0.017, d=1.48). During POST-CWI, DL showed a significantly higher temperature than TL (p<0.001, d=2.13) and BL (p<0.001, d=2.06). These findings demonstrate that MRS-based temperature mapping provides unique anatomical and thermal characterization of muscle during thermoregulatory stress. While results are promising for understanding CWI mechanisms, validation in larger cohorts is necessary to establish clinical reliability and reproducibility for heat illness management.

Background: Individuals with coronary artery disease (CAD) are at higher risk of cognitive decline and dementia, in which gray matter cerebral blood flow (CBF) plays a critical role. This study investigated the effects of High Intensity Interval Training (HIIT) and HIIT plus resistance training (RT) on CBF and other health outcomes in individuals with CAD. Methods: This trial included 105 participants with CAD (age 62.1 (SD 6.6) years, 21% women) randomly assigned to HIIT+RT (n=37), HIIT (n=35) or usual care (n=33). The primary outcome was the change in global CBF from baseline to 12-week follow-up. Secondary outcomes included: region-specific CBF (hippocampus, precuneus, and anterior/posterior cingulate cortex), cognitive function (general cognition, episodic memory, processing speed, working memory and executive function/attentional control), peak oxygen uptake (VO2peak), muscular fitness (30s sit-to-stand) and body composition [weight, body mass index (BMI), and fat and muscle mass). Data were analyzed using available-case intention-to-treat constrained (baseline-adjusted) linear mixed models. Predefined subgroup analyses were conducted for age, sex, education, and baseline level of the outcome studied. Results: No significant between-group differences were observed in CBF changes in the whole sample. However, participants with lower CBF at baseline showed greater CBF increases in the HIIT group compared to both usual care (+7.1 ml/100g/min, P=0.02) and HIIT+RT (+5.53 ml/100g/min, P=0.04). No effects were observed on regional CBF or cognition. Both exercise groups improved VO2peak compared to usual care (HIIT+RT: +2.6; HIIT: +2.5 mL/kg/min, both P<0.001). Only HIIT+RT increased muscular fitness (vs usual care: +3.3; vs HIIT: +3.1 repetitions, both P<0.001), and only HIIT decreased BMI (vs usual care: -0.47; vs HIIT+RT: -0.44 kg/m2, both P<0.03). No life-threatening events or deaths occurred during 1995 training sessions in the exercise groups, nor in the usual care group. Conclusion: Twelve weeks of HIIT+RT or HIIT did not increase CBF in the whole sample with CAD, but HIIT effectively increased CBF in those who had poorer CBF at baseline. While no cognitive benefits were observed, we found exercise-specific improvements in other clinically relevant outcomes, such as VO2peak, muscular fitness, and BMI.

In "Experiment-free exoskeleton assistance via learning in simulation", Luo et al. [1] present an ambitious framework for developing exoskeleton controllers through reinforcement learning exclusively in computer simulation. The authors report that a control policy trained on a small dataset from one subject was directly transferred to physical hardware, reducing human metabolic cost during walking, running, and stair climbing by more than any prior device. If confirmed, this would represent a major breakthrough for the field of wearable robotics and their clinical applications. However, a close examination of the published materials casts doubt on these claims. The reported experimental results violate physiological limits on the relationship between mechanical power and muscle energy use during gait2,3,4. The algorithmic claims are surprising and cannot be verified; in contrast with established replicability standards in machine learning5,6, executable code has not been made available. We conclude that the goals of this study have not yet been verifiably achieved and make recommendations for avoiding publication errors of this type in the future.

BackgroundCardiovascular disease (CVD) prevention is limited by the major challenge of low long-term adherence to effective lifestyle regimens. Arterial stiffness (measured by carotid-femoral pulse wave velocity, cfPWV) and maximal cardiorespiratory fitness (measured by VO2max), are modifiable risk factors for CVD but require sustained lifestyle change. Wearable technology provides continuous measurement and offers a scalable platform to deliver health interventions. A combination of continuous monitoring with a wearable device and an artificial intelligence (AI) -based coach personalized for individual data and preferences could be a powerful, low-barrier tool for achieving sustainable cardiovascular health benefits by directly addressing the adherence challenge. ObjectiveWe will study the comparative effectiveness of a wearable and an interactive app-based AI coaching intervention promoting moderate exercise on improving gold-standard cfPWV and VO2max. This will be compared to a supervised high-intensity interval training (HIIT) group (benchmark with known benefits for VO2max) and a control group using only Oura Ring (passive monitoring). We will also conduct a detailed Process Evaluation (structured interviews) to study the feasibility and experience of interacting with the AI coach. MethodsThis randomized controlled trial recruited 165 eligible sedentary participants aged 30-65 years. Co-primary outcomes cfPWV and VO2max were measured at baseline and will be repeated after 12 weeks. Participants were equally randomized into three groups: an AI-based coaching group (steady-state exercise), a HIIT group (supervised exercise) and a control group (usual low activity). The AI-based coaching group receives personalized guidance using large language model (LLM) technology. All participants wear Oura Ring and are blinded to cardiovascular health metrics provided by the ring. ResultsThe recruitment for the study began in October 2024 and will end when 165 men and women have been recruited. Data collection for the study is scheduled to conclude early 2026. Data collection is ongoing. ConclusionsThis study will evaluate if a highly scalable, AI-based coaching intervention can achieve comparable gains in CV structural health (cfPWV) and functional capacity VO2max relative to a resource-intensive supervised HIIT benchmark. The findings will provide essential evidence on the use of digital health tools to promote sustainable exercise adherence. ClinicalTrials.gov registration identifierNCT06644014 (Registered: 2024-10-15)

Objective: To examine the joint associations of cardiorespiratory fitness (CRF) and polygenic risk with incident breast cancer and whether higher CRF attenuates excess breast cancer risk associated with high polygenic risk in postmenopausal women. Methods: This prospective cohort study included postmenopausal women from the UK Biobank. CRF was estimated using a submaximal cycle ergometer test, and genetic susceptibility was assessed using a breast cancer polygenic risk score (PRS). Associations of CRF and PRS with incident breast cancer were examined using Cox proportional hazards models with age as the underlying time scale. Analyses were conducted overall and stratified by age (40-59 and [&ge;]60 years) and body mass index (BMI) (<25 and [&ge;]25 kg/m2). Multiplicative and additive interactions were evaluated, with additive interaction assessed using the relative excess risk due to interaction (RERI). Results: During a median follow-up of 10.7 years, 500 incident breast cancer cases were identified among 13,907 postmenopausal women. Higher CRF was associated with a lower breast cancer risk in a dose-response manner. Although multiplicative interaction was not significant, higher CRF attenuated excess risk associated with high polygenic risk on the additive scale (RERI -0.84, 95% CI -1.56 to -0.12). This attenuation was particularly evident among women aged [&ge;]60 years and those with BMI [&ge;]25 kg/m2. Conclusion: Higher CRF was associated with a lower breast cancer risk and attenuated excess breast cancer risk associated with high polygenic risk, particularly among postmenopausal women at elevated baseline risk, supporting a potential role for improving CRF in genetically informed breast cancer prevention.

IntroductionMusculoskeletal conditions have high, and increasing, incidence and prevalence. Although there are many clinical guidelines available for common conditions, most are poor quality and sparsely adopted into practice. We aim to improve patient outcomes by developing robust Best Practice Guidelines (BPG) to get research findings into practice for a range of common musculoskeletal conditions. Methods and analysisMixed methods with systematic review of high-quality studies and qualitative elicitation of both patients perspectives and expert clinical reasoning through in-depth interviews will form the basis for the BPGs. A segregated convergent synthesis, informed throughout by stakeholder engagement, will guide the format and structure of the BPGs. Ethics, outputs and disseminationEthical approval for the qualitative studies and implementation events will be obtained from university and health service research ethics committees. Educational packages for each BPG condition will be hosted online and be available for students, clinicians, and education providers. Dissemination will follow traditional routes including publications and presentations; alongside innovative approaches such as collaboration with higher education institutions, online hosting, adoption by professional bodies, and a social media campaign. Implementation will occur adaptively in multiple national contexts to reflect local requirements and resources, deploying participatory and implementation methods that are contextually and culturally appropriate. KEY MESSAGESO_LIWhat is already known on this topic - Clinical guidelines for the management of musculoskeletal conditions are common, but have limitations regarding quality, applicability, editorial independence, and patient perspective. They are rarely adopted into clinical practice. C_LIO_LIWhat this study adds - We have developed a robust (supported by Patient and Participant Involvement) mixed-methods approach that integrates the three components of evidence-based medicine: synthesis of high-quality evidence, patients perspectives/values, and expert clinical reasoning. We have also developed an education, dissemination, and implementation approach to facilitate international adoption of these guidelines. C_LIO_LIHow this study might affect research, practice or policy - The guideline development methods will integrate the three pillars of evidence-based practice and ensure they are robust and clinically applicable. Creation of educational material combined with an implementation and dissemination plan will support adoption into clinical practice of different countries and cultures, designed to lead to improved patient outcomes. C_LI

AO_SCPLOWBSTRACTC_SCPLOWDecoding imagined speech from electroencephalography (EEG) recordings is potentially useful for brain-computer interfaces. Previous studies have focused on decoding semantic information from EEG, leaving the decoding of emotion - an important component of human communication - largely unexplored. Here, we report two experiments involving participants tasked with overt (n = 14) or imagined (n = 21) emotional vocalisation in five different categories: anger, happiness, neutral, sadness, and pleasure. Throughout, we recorded 64-channel EEG; we computed time-frequency features and used a logistic-regression classifier to evaluate emotion decoding accuracy. In five participants, we also recorded facial surface electromyography (sEMG) during imagined vocalisation, and studied the contamination of EEG by sEMG. Our results show that emotion can be decoded from single-trial EEG recordings of both overt (78.1%, chance = 20%) and imagined vocalisation (36.4%). The high-gamma band (50 to 100 Hz) and lateral EEG channels (T7, T8, and proximal) were important for decoding. sEMG analysis indicated that involuntary facial muscle activity contributed to these spectral and spatial patterns during imagined vocalisation, especially during happy vocalisations. We conclude that involuntary facial muscle activity is associated with certain emotion categories (i.e., happiness), and drives above-chance decoding of emotion from single-trial EEG recordings of imagined vocalisation.

Dance is a core form of human-environment interaction and a powerful medium for emotional expression, yet dancers are routinely exposed to environmental affective cues that may shape their movement. We tested whether a negative emotional context induced immediately before improvisation alters dance biomechanics. Twenty professional dancers performed two 3-min improvised dances. Between dances, they viewed either Neutral or Negatively valenced pictures from the International Affective Picture System (IAPS; 2 min 40 s, 5 s per image). Eye tracking verified attention to the visual stream. Mood was assessed at four time points (PT1-PT4) using the Brazilian Mood Scale (BRAMS), and full-body, three-dimensional kinematics were captured at 300 Hz using a 9-camera optoelectronic system (Qualisys) and processed to measure global movement amplitude and expansion. Negative IAPS exposure increased tension, depression, fatigue, and decreased vigor from PT2 to PT3. Biomechanically, the Negative Stimulus dancers showed a significant reduction in global movement amplitude after negative IAPS exposure, with reduced movement amplitude of the body extremities. In contrast, global movement expansion remained unchanged; that is, the extremities were not positioned closer or farther from the pelvis. Neutral images produced no mood change and no measurable modulation of movement amplitude or expansion. Together, these results support the hypothesis that improvised dance carries biomechanical signatures of the dancers current affective state, beyond the intended expressive content, and provide an automated motion-capture workflow for studying emotion-movement coupling in spontaneous dance. HighlightsNegative visual context shifted dancers mood toward negative affect Negative images reduced movement amplitude in improvised dance Movement expansion remained stable despite mood induction Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/711707v1_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@aeaacdorg.highwire.dtl.DTLVardef@14f9bf5org.highwire.dtl.DTLVardef@18805fcorg.highwire.dtl.DTLVardef@1411256_HPS_FORMAT_FIGEXP M_FIG C_FIG

Right ventricular failure (RVF) is a serious disease with a high mortality but no effective pharmacologic treatments. We reported RVF was reversed by chronic treatment with an 1A-adrenergic receptor (1A-AR) agonist. Recent studies suggest mitochondrial dysfunction contributes to RVF. Therefore, we investigated if reversal of RVF by chronic 1A-AR agonist treatment involved improved mitochondrial function. A mouse model of RVF caused by pulmonary artery constriction (PAC) for 2 wk was chronically treated for a further 2 wk. with a low dose of the 1A-AR agonist A61603 (10 ng/kg/day) or vehicle (no drug control). RV dysfunction was assessed from the fractional shortening of the RV outflow tract (RVOT FS). RVOT FS for sham controls (46.5 {+/-} 1.3 %, n = 9) was reduced 4 wk after PAC (27.6 {+/-} 1.5 %, n = 13, P < 0.0001), but was higher after PAC plus 2 wk A61603 treatment (34.5 {+/-} 0.6 %, n = 14, P < 0.001). RV myocardial respiration rate (O2 consumption) for sham controls (776 {+/-} 51 pM/s/mg, n = 9) was reduced 4 wk after PAC (493 {+/-} 28 pM/s/mg, n = 15, P <0.0001), but was higher after PAC plus 2 wk A61603 treatment (634 {+/-} 30 pM/s/mg, n = 11, P <0.05). RV myocardial ATP level for sham controls (3.3 {+/-} 0.1 mM, n = 10) was reduced 4 wk after PAC (1.9 {+/-} 0.1 mM, n = 6, P < 0.0001), but was higher after PAC plus 2 wk A61603 treatment (2.6 {+/-} 0.13 mM, n = 7, P < 0.01). In conclusion, reversal of RVF after chronic A61603 treatment involved reversal of mitochondrial dysfunction. Consistent with our previous studies, this study suggests that the 1A-AR is a therapeutic target to treat RVF. HighlightsRV failure is reported to involve mitochondrial dysfunction which might impair RV contraction by decreasing cardiomyocyte ATP level. Using the pulmonary artery constriction model of RV failure, we found that chronic treatment with an 1A-adrenergic receptor agonist increased RV myocardial respiration rate, increased RV myocardial ATP level, and increased RV function. These findings suggest that the 1A-adrenergic receptor is a therapeutic target for treating RV failure, and that the mechanism involves improved RV cardiomyocyte bioenergetic status.