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Identification of biomarkers to drive treatment using cell-free DNA allows dynamic and safe assessment of tumor biology representing an important advance adding to tissue-based genotyping. Caution must be exercised interpreting commercial matching information as validation is often lacking, and true matching is feasible in a minority of patients.See related article by Vidula et al., p. 3404.
To define dominant molecular and cellular features associated with PD-1/PD-L1 blockade resistance in metastatic urothelial cancer.

We pursued an unbiased approach using bulk RNA sequencing data from two clinical trials to discover (IMvigor 210) and validate (CheckMate 275) pretreatment molecular features associated with resistance to PD-1/PD-L1 blockade in metastatic urothelial cancer. We then generated single-cell RNA sequencing (scRNA-seq) data from muscle-invasive bladder cancer specimens to dissect the cellular composition underlying the identified gene signatures.

We identified an adaptive immune response gene signature associated with response and a protumorigenic inflammation gene signature associated with resistance to PD-1/PD-L1 blockade. The adaptive immune responseprotumorigenic inflammation signature expression ratio, coined the 2IR score, best correlated with clinical outcomes, and was externally validated. Mapping these bulk gene signatures onto scRNA-seq data uncovered their underlying ceorigenic inflammation in individual tumor microenvironments is associated with PD-1/PD-L1 resistance in urothelial cancer with the latter linked to a proinflammatory cellular state of myeloid phagocytic cells detectable in tumor and blood.Concussion is a frequent injury in many sports and is also common in para athletes. However, there is a paucity of concussion research related to para sport, and prior International Concussion in Sport (CIS) consensus papers have not substantively addressed this population. To remedy this and to improve concussion care provided to para athletes, the concussion in para sport (CIPS) multidisciplinary expert group was created. This group analysed and discussed in-depth para athlete-specific issues within the established key clinical domains of the current (2017) consensus statement on CIS. Due to the onset of the COVID-19 pandemic, the group held all meetings by video conferencing. PF06882961 The existing Sport Concussion Assessment Tool 5 (SCAT5) for the immediate on-field and office-based off-field assessment of concussion was evaluated as part of this process, to identify any para athlete-specific concerns. Regular preparticipation and periodic health examinations are essential to determine a baseline reference point foebral Palsy Football, also should be carefully considered to reduce the occurrence of concussion in para athletes.
To describe the incidence rate, severity, burden and aetiology of medical attention and time-loss injuries across five consecutive seasons at a professional ballet company.

Medical attention injuries, time-loss injuries and dance exposure hours of 123 professional ballet dancers (women n=66, age 28.0±8.3 years; men n=57, age 27.9±8.5 years) were prospectively recorded between the 2015/2016 and 2019/2020 seasons.

The incidence rate (per 1000 hours) of medical attention injury was 3.9 (95% CI 3.3 to 4.4) for women and 3.1 (95% CI 2.6 to 3.5) for men. The incidence rate (per 1000 hours) of time-loss injury was 1.2 (95% CI 1.0 to 1.5) for women and 1.1 (95% CI 0.9 to 1.3) for men. First Soloists and Principals experienced between 2.0-2.2 additional medical attention injuries per 1000 hours and 0.9-1.1 additional time-loss injuries per 1000 hours compared with Apprentices (p≤0.025). Further, intraseason differences were observed in medical attention, but not time-loss, injury incidence rates with the highest incidence rates in early (August and September) and late (June) season months. Thirty-five per cent of time-loss injuries resulted in over 28 days of modified dance training. A greater percentage of time-loss injuries were classified as overuse (women 50%; men 51%) compared with traumatic (women 40%; men 41%).

This is the first study to report the incidence rate of medical attention and time-loss injuries in professional ballet dancers. Incidence rates differed across company ranks and months, which may inform targeted injury prevention strategies.
This is the first study to report the incidence rate of medical attention and time-loss injuries in professional ballet dancers. Incidence rates differed across company ranks and months, which may inform targeted injury prevention strategies.Gender refers to the socially constructed roles, behaviours, expressions and identities of girls, women, boys, men and gender diverse people. Gender-related factors are seldom assessed as determinants of health outcomes, despite their powerful contribution. The Gender Outcomes INternational Group to Further Well-being Development (GOING-FWD) project developed a standard five-step methodology applicable to retrospectively identify gender-related factors and assess their relationship to outcomes across selected cohorts of non-communicable chronic diseases from Austria, Canada, Spain, Sweden. Step 1 (identification of gender-related variables) Based on the gender framework of the Women Health Research Network (ie, identity, role, relations and institutionalised gender), and available literature for a certain disease, an optimal 'wish-list' of gender-related variables was created and discussed by experts. Step 2 (definition of outcomes) Data dictionaries were screened for clinical and patient-relevant outcomes, using the International Consortium for Health Outcome Measurement framework. Step 3 (building of feasible final list) a cross-validation between variables per database and the 'wish-list' was performed. Step 4 (retrospective data harmonisation) The harmonisation potential of variables was evaluated. Step 5 (definition of data structure and analysis) The following analytic strategies were identified (1) local analysis of data not transferable followed by a meta-analysis combining study-level estimates; (2) centrally performed federated analysis of data, with the individual-level participant data remaining on local servers; (3) synthesising the data locally and performing a pooled analysis on the synthetic data and (4) central analysis of pooled transferable data. The application of the GOING-FWD multistep approach can help guide investigators to analyse gender and its impact on outcomes in previously collected data.
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