Search

Purpose: The anti-NECTIN4 antibody-drug conjugate enfortumab vedotin (EV) is approved for patients with metastatic urothelial cancer (mUC). However, durable benefit is only achieved in a small, yet uncharacterized patient subset. NECTIN4 is located on chromosome 1q23.3, and 1q23.3 gains represent frequent copy number variations (CNVs) in urothelial cancer. Here, we aimed to evaluate NECTIN4 amplifications as a genomic biomarker to predict EV response in patients with mUC., Materials and Methods: We established a NECTIN4 -specific fluorescence in situ hybridization (FISH) assay to assess the predictive value of NECTIN4 CNVs in a multicenter EV-treated mUC patient cohort (mUC-EV, n = 108). CNVs were correlated with membranous NECTIN4 protein expression, EV treatment responses, and outcomes. We also assessed the prognostic value of NECTIN4 CNVs measured in metastatic biopsies of non-EV-treated mUC (mUC-non-EV, n = 103). Furthermore, we queried The Cancer Genome Atlas (TCGA) data sets (10,712 patients across 32 cancer types) for NECTIN4 CNVs., Results: NECTIN4 amplifications are frequent genomic events in muscle-invasive bladder cancer (TCGA bladder cancer data set: approximately 17%) and mUC (approximately 26% in our mUC cohorts). In mUC-EV, NECTIN4 amplification represents a stable genomic alteration during metastatic progression and associates with enhanced membranous NECTIN4 protein expression. Ninety-six percent (27 of 28) of patients with NECTIN4 amplifications demonstrated objective responses to EV compared with 32% (24 of 74) in the nonamplified subgroup ( P < .001). In multivariable Cox analysis adjusted for age, sex, and Bellmunt risk factors, NECTIN4 amplifications led to a 92% risk reduction for death (hazard ratio, 0.08 [95% CI, 0.02 to 0.34]; P < .001). In the mUC-non-EV, NECTIN4 amplifications were not associated with outcomes. TCGA Pan-Cancer analysis demonstrated that NECTIN4 amplifications occur frequently in other cancers, for example, in 5%-10% of breast and lung cancers., Conclusion: NECTIN4 amplifications are genomic predictors of EV responses and long-term survival in patients with mUC.

Considering the importance of body composition and lower-body strength and power for basketball players' on-court performance, as well as a lack of sports science research focused on female athletes, the purpose of the present investigation was to record the anthropometric and countermovement vertical jump (CMJ) characteristics of top-tier U16 and U18 female basketball players and examine between-group differences in the aforementioned tests. Thirty-two athletes who were a part of the national basketball academy volunteered to participate in the present investigation. Following the body composition assessment conducted via a segmental multifrequency bioimpedance analyzer, athletes performed three CMJs while standing on a force plate system sampling at 1000 Hz. Independent t -test and Mann-Whitney U -test were used to examine between-group differences. The findings reveal significant differences in body composition and lower-body neuromuscular performance characteristics between female basketball players ages 16 and 18. Although no differences were observed in muscle and body fat percentages, the U18 group had significantly greater height, overall body mass (both muscle and fat mass), as well as greater segmental fat-free mass (trunk, both legs and arms), intracellular and extracellular water, and body mass index when compared to their U16 counterparts. On the other hand, the U18 group demonstrated longer eccentric, concentric, and braking phase duration, as well as overall contraction time when compared to the U16 players. In addition, the U18 athletes exhibited higher eccentric mean force and power, concentric impulse, peak power, and mean and peak force., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Cabarkapa, Cabarkapa, Nagy, Szabo, Balogh, Safar and Ratgeber.)

Background: The shortage of pathologists in Germany, coupled with an aging workforce, requires innovative approaches to attract medical students to the field. Medical education must address different learning styles to ensure that all students are successful., Methods: The pilot project "Practical Pathology" aims to enhance students' understanding of pathology by providing hands-on experience in macroscopic gross analysis through the use of tumor dummies built from scratch., Results: An evaluation survey, completed by 63 participating students provided positive feedback on the course methodology, its relevance to understanding the pathology workflow, and its improvement over traditional teaching methods. The majority of students recognized the importance of hands-on training in medical education. Students with previous work experience rated the impact of the course on knowledge acquisition even more positively., Conclusion: The course improved students' understanding of pathological processes and potential sources of clinical-pathological misunderstanding. An increase in motivation for a potential career in the field of pathology was observed in a minority of students, although this exceeded the percentage of pathologists in the total medical workforce., (© 2024. The Author(s).)

Short sprints are predominantly assessed using timing gates and analyzed through parameters of the mono-exponential equation, including estimated maximal sprinting speed (MSS) and relative acceleration (TAU), derived maximum acceleration (MAC), and relative propulsive maximal power (PMAX), further referred to as the No Correction model. However, the frequently recommended flying start technique introduces a bias during parameter estimation. To correct this, two additional models (Estimated TC and Estimated FD) were proposed. To estimate model precision and sensitivity to detect the change, 31 basketball players executed multiple 30 m sprints. Athlete performance was simultaneously measured by a laser gun and timing gates positioned at 5, 10, 20, and 30 m. Short sprint parameters were estimated using a laser gun, representing the criterion measure, and five different timing gate models, representing the practical measures. Only the MSS parameter demonstrated a high agreement between the laser gun and timing gate models, using the percent mean absolute difference (%MAD) estimator (%MAD < 10%). The MSS parameter also showed the highest sensitivity, using the minimum detectable change estimator (%MDC95), with an estimated %MDC95 < 17%. Interestingly, sensitivity was the highest for the No Correction model (%MDC95 < 7%). All other parameters and models demonstrated an unsatisfying level of sensitivity. Thus, sports practitioners should be cautious when using timing gates to estimate maximum acceleration indices and changes in their respective levels.

Inflammatory fibroid polyps (IFP) are rare and benign mesenchymal tumours of the gastrointestinal tract. They are submucosal spindle cell lesions with an eosinophilic-rich inflammatory infiltrate and mutations in the platelet-derived growth factor receptor alpha (PDGFRA) gene. In this report, we present the case of a 74-year-old female with a solid tumour of the kidney, which presented as a bland proliferation of spindle cells with thin-walled blood vessels and an inflammatory infiltrate with eosinophilic granulocytes. Immunohistochemistry revealed a positivity for vimentin and a weak staining for CD99 and CD34 in the spindle cells. Because of the morphological similarity to IFPs of the gastrointestinal tract, a molecular pathology analysis was performed. This identified an oncogenic mutation in exon 18 of the PDGFRA gene, which is characteristic for inflammatory fibroid polyps of the gastrointestinal tract. To the best of our knowledge, this is the first case of an IFP in the urogenital tract., (© 2023. The Author(s).)

Endurance training-induced changes in left ventricular diastolic function and right ventricular parameters have been investigated extensively in adolescent athletes. Our aim was to examine the parameters for adolescent athletes (n=121, 15.1±1.6 years) compared to adult athletes and age-matched non-athletes. We explored the effects of influencing factors on the echocardiographic parameters. Significantly higher E/A (p<0.05) and e' values (p<0.001) were detected in adolescent athletes compared to age-matched non-athletes' and also adult athletes' parameters. Significantly lower structural and functional right ventricular parameters (p<0.05) were detected in adult athletes. In adolescent athletes significantly higher right ventricular diameters, tricuspid S wave, right ventricular end-diastolic and end-systolic area values (p<0.05) were found compared to the matching parameters of non-athletes. We found significantly higher corrected tricuspid annular plane systolic excursion values (p<0.001) in athletes compared to the non-athletes. Based on multivariate analysis lean body mass, body surface area, age and cumulative training time were proved as strong predictive factors of both left ventricular diastolic and right ventricular parameters. Supernormal left ventricular diastolic function and significantly higher right ventricular parameters are indicative of cardiac adaptation. Well-defined cut-off values should be applied to discriminate pathological conditions in the relation of the influencing factors., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Unlike many insects where photoperiod per se induces diapause, reproductive arrest in Drosophila melanogaster adult females is observed at colder temperatures and can be enhanced by shorter photoperiods. Traditional experimental protocols raise flies at 25 °C from the larval stage and then the adults are placed at 12 °C for between 12 and 28 days. After 12 days diapause levels are usually higher than at 28 days, suggesting that the flies are in a cold induced quiescence, rather than a true diapause. By raising flies at more realistic lower temperatures, we observe quite dramatic and counter-intuitive effects on diapause, whose levels nevertheless correlate with various indices of cryoprotectant metabolites as well as resistance to chill shock. We also observe that photoperiodic effects are minimised when very small temperature oscillations associated with the light-dark incubator cycles are neutralised. Our results suggest that the reported photoperiodic component of fly diapause, at least in these strains, is mostly due to thermoperiodic rather than photoperiodic stimuli. In addition, the metabolite and chill shock analyses reveal that even by 12 days, flies are entering a state that is resistant to environmental stresses., (Copyright © 2018 Elsevier Ltd. All rights reserved.)