The assessment of neuromuscular fatigue during 120 min of simulated soccer exercise

Purpose This investigation examined the development of neuromuscular fatigue during a simulated soccer match incorporating a period of extra time (ET) and the reliability of these responses on repeated test occasions. Methods Ten male amateur football players completed a 120 min soccer match simulation (SMS). Before, at half time (HT), full time (FT), and following a period of ET, twitch responses to supramaximal femoral nerve and transcranial magnetic stimulation (TMS) were obtained from the knee-extensors to measure neuromuscular fatigue. Within 7 days of the first SMS, a second 120 min SMS was performed by eight of the original ten participants to assess the reliability of the fatigue response. Results At HT, FT, and ET, reductions in maximal voluntary force (MVC; −11, −20 and −27%, respectively, P ≤ 0.01), potentiated twitch force (−15, −23 and −23%, respectively, P < 0.05), voluntary activation (FT, −15 and ET, −18%, P ≤ 0.01), and voluntary activation measured with TMS (−11, −15 and −17%, respectively, P ≤ 0.01) were evident. The fatigue response was robust across both trials; the change in MVC at each time point demonstrated a good level of reliability (CV range 6–11%; ICC2,1 0.83–0.94), whilst the responses identified with motor nerve stimulation showed a moderate level of reliability (CV range 5–18%; ICC2,1 0.63–0.89) and the data obtained with motor cortex stimulation showed an excellent level of reliability (CV range 3–6%; ICC2,1 0.90–0.98). Conclusion Simulated soccer exercise induces a significant level of fatigue, which is consistent on repeat tests, and involves both central and peripheral mechanisms

Tide and wind coupling in a semienclosed bay driven by coastal upwelling

The Ría de Vigo is a semi-enclosed bay in which tidal residual currents are associated with coastal upwelling events. Both upwelling and downwelling favourable winds generate a bidirectional exchange flow with the shelf – a two-layer circulation with surface waters leaving (entering) the ria and a compensating inflow (outflow) through the bottom layer under upwelling (downwelling) conditions. This vertical circulation changes the vertical density structure inside the ria. In the ria, the tide is mainly semidiurnal (M2, S2 and K2), with some energy in the diurnal band (K1). Our velocity observations show that the vertical structure of the tidal currents in the ria do not exhibit a classic barotropic profile with a bottom boundary layer beneath uniform “free-stream” flow as the tidal bottom boundary layer is affected by stratification. This links tidal circulation to the wind-driven residual circulation, since the latter also greatly helps to control the stratification. We quantify this effect by fitting tidal ellipses to observed velocities through the water column. In addition to this indirect coupling through stratification, there is a direct interaction in which velocities in the upper and bottom layers are best correlated with winds while the mid-water velocities are best correlated with tides. These wind-tide interactions are expected to play a key role in the resuspension and transport of nutrients and phytoplankton in the Ria.CTM2012-3515

Tidal and wind influences on circulation in the southern mouth of the Ría de Vigo (NW Iberian Peninsula)

Tidal and wind influences on the velocity field in the Ría de Vigo were assessed using atmospheric data from two meteorological stations located at Bouzas port and on an oceanic buoy off Silleiro Cape along with oceanic data from an ADCP moored in the Ría for a 72-day period. A two-layer circulation pattern was observed. Near-surface and near-bottom currents are primarily influenced by wind (especially remote winds), separated by an intermediate layer dominated by tidal variability. At subtidal frequencies, residual currents are well correlated with wind variability. Remote wind forcing exhibited a markedly high correlation with surface layer currents, indicating the major role played by wind in the long-term upwelling-modulated circulation of the Ría

Identification and validation of a machine learning model of complete response to radiation in rectal cancer reveals immune infiltrate and TGFβ as key predictors

Background: It is uncertain which biological features underpin the response of rectal cancer (RC) to radiotherapy. No biomarker is currently in clinical use to select patients for treatment modifications. Methods: We identified two cohorts of patients (total N = 249) with RC treated with neoadjuvant radiotherapy (45Gy/25) plus fluoropyrimidine. This discovery set included 57 cases with pathological complete response (pCR) to chemoradiotherapy (23%). Pre-treatment cancer biopsies were assessed using transcriptome-wide mRNA expression and targeted DNA sequencing for copy number and driver mutations. Biological candidate and machine learning (ML) approaches were used to identify predictors of pCR to radiotherapy independent of tumour stage. Findings were assessed in 107 cases from an independent validation set (GSE87211). Findings: Three gene expression sets showed significant independent associations with pCR: Fibroblast-TGFβ Response Signature (F-TBRS) with radioresistance; and cytotoxic lymphocyte (CL) expression signature and consensus molecular subtype CMS1 with radiosensitivity. These associations were replicated in the validation cohort. In parallel, a gradient boosting machine model comprising the expression of 33 genes generated in the discovery cohort showed high performance in GSE87211 with 90% sensitivity, 86% specificity. Biological and ML signatures indicated similar mechanisms underlying radiation response, and showed better AUC and p-values than published transcriptomic signatures of radiation response in RC. Interpretation: RCs responding completely to chemoradiotherapy (CRT) have biological characteristics of immune response and absence of immune inhibitory TGFβ signalling. These tumours may be identified with a potential biomarker based on a 33 gene expression signature. This could help select patients likely to respond to treatment with a primary radiotherapy approach as for anal cancer. Conversely, those with predicted radioresistance may be candidates for clinical trials evaluating addition of immune-oncology agents and stromal TGFβ signalling inhibition. Funding: The Stratification in Colorectal Cancer Consortium (S:CORT) was funded by the Medical Research Council and Cancer Research UK (MR/M016587/1)

Sediment mobilization and seawater warming affect ecophysiology of the clam polititapes rhomboides

Poster.-- Poster.-- VIII International Symposium on Marine Science, Las Palmas de Gran Canaria, 6-8 July 2022High-energy hydrodynamic events associated to currents and waves may disturb bivalve mollusks´ ecophysiology, especially those buried in the the sea bed due to sediment mobilization. Evidences of massive mortality for the clam Polititapes rhomboides (banded carpet shell clam) in Galicia (NW Spain) have been associated to warm water temperatures and high wave magnitudes above climatic averages and the presence of rickettsias (intracellular prokaryotic colonies) in gills (Villalba et al. 1999; Darriba et al. 2019; Villacieros-Robineau et al. 2021)Project PID2019-106008RB-C21 financed by MCIN/AEI/10.13039/501100011033N

Combined bictegravir, emtricitabine and tenofovir alafenamide for treating people with HIV: a plain language summary of the BICSTaR study up to 1 year

What is this summary about?: This is a summary of an article about an ongoing study called the BICSTaR study. The BICSTaR study includes people with HIV (human immunodeficiency virus) who are taking a medicine called bictegravir/emtricitabine/tenofovir alafenamide (shortened to B/F/TAF). B/F/TAF is a single tablet that contains 3 different drugs for the treatment of HIV. The drugs work together to reduce the levels of HIV so that the virus can no longer be detected by a blood test. People taking part in the study are adults with HIV living in Europe, Canada, Israel, Japan, South Korea, Singapore and Taiwan. People take 1 tablet of B/F/TAF once a day. They are either taking B/F/TAF as their first treatment for HIV, or they have switched to B/F/TAF from another HIV treatment. Researchers looked at how well B/F/TAF worked and how safe it was in people who took B/F/TAF for a year. What are the key takeaways?: Researchers found that B/F/TAF worked well in almost all people in the study by reducing levels of HIV in the blood. The virus could not be found in the blood of more than 9 out of 10 (94%) people who were taking B/F/TAF as their first HIV medicine and more than 9 out of 10 people (97%) who had taken another HIV medicine before starting B/F/TAF. This is known as having an ‘undetectable viral load’ and is a major goal for HIV treatment success. Researchers did not find any evidence of HIV developing resistance to B/F/TAF, which might stop B/F/TAF from working properly. Around 1 out of 10 people (13%) had side effects (any unwanted sign or symptom that people have when taking a medicine that researchers think might be caused by the medicine) that might have been caused by B/F/TAF. Most of these side effects were not classified as serious. Less than 1 out of 100 (0.1%) people had serious side effects that might have been caused by B/F/TAF. Only 6 out of 100 people stopped taking B/F/TAF due to side effects caused by B/F/TAF. As a result, more than 9 out of 10 people (95%) took B/F/TAF for at least 1 year. What were the main conclusions reported by the researchers?: B/F/TAF worked well in people with HIV in this study. Most people (around 9 out of 10) did not have any side effects

Twelve-month effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide in people with HIV: Real-world insights from BICSTaR cohorts

Background: Real-world evidence is an essential component of evidence-based medicine. The aim of the BICSTaR (BICtegravir Single Tablet Regimen) study is to assess effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in antiretroviral treatment-naïve (TN) and treatment-experienced (TE) people with HIV. Methods: BICSTaR is a prospective, observational cohort study. Participants (≥18 years) are being followed for 24 months. A pooled analysis is presented at 12 months, with the primary endpoint of effectiveness (HIV-1 RNA <50 copies/mL) and secondary endpoints of safety and tolerability (as per protocol). An exploration of patient-reported outcome measures using standardized questionnaires is included. Results: Between June 2018 and May 2021, 1552 people with HIV were enrolled across 12 countries. The analysed population comprised 1509 individuals (279 TN, 1230 TE); most were white (76%), male (84%) and had one or more comorbid conditions (68%). Median age was 47 years. After 12 months of B/F/TAF treatment, HIV-1 RNA was <50 copies/mL in 94% (221/236) of TN participants and 97% (977/1008) of TE participants. Median CD4 cell count increased by 214 cells/μL (p < 0.001) in TN participants and 13 cells/μL (p = 0.014) in TE participants; median CD4/CD8 ratios increased by 0.30 and 0.03, respectively (both p < 0.001). Persistence was high at 12 months (TN, 97%; TE, 95%). No resistance to B/F/TAF emerged. Study drug-related adverse events occurred in 13% of participants through 12 months, leading to B/F/TAF discontinuation in 6%. Conclusions: The findings of this study provide robust real-world evidence to support the broad use of B/F/TAF in both TN and TE people with HIV

Tumour purity assessment with deep learning in colorectal cancer and impact on molecular analysis

Tumour content plays a pivotal role in directing the bioinformatic analysis of molecular profiles such as copy number variation (CNV). In clinical application, tumour purity estimation (TPE) is achieved either through visual pathological review [conventional pathology (CP)] or the deconvolution of molecular data. While CP provides a direct measurement, it demonstrates modest reproducibility and lacks standardisation. Conversely, deconvolution methods offer an indirect assessment with uncertain accuracy, underscoring the necessity for innovative approaches. SoftCTM is an open-source, multiorgan deep-learning (DL) model for the detection of tumour and non-tumour cells in H&E-stained slides, developed within the Overlapped Cell on Tissue Dataset for Histopathology (OCELOT) Challenge 2023. Here, using three large multicentre colorectal cancer (CRC) cohorts (N = 1,097 patients) with digital pathology and multi-omic data, we compare the utility and accuracy of TPE with SoftCTM versus CP and bioinformatic deconvolution methods (RNA expression, DNA methylation) for downstream molecular analysis, including CNV profiling. SoftCTM showed technical repeatability when applied twice on the same slide (r = 1.0) and excellent correlations in paired H&E slides (r > 0.9). TPEs profiled by SoftCTM correlated highly with RNA expression (r = 0.59) and DNA methylation (r = 0.40), while TPEs by CP showed a lower correlation with RNA expression (r = 0.41) and DNA methylation (r = 0.29). We show that CP and deconvolution methods respectively underestimate and overestimate tumour content compared to SoftCTM, resulting in 6–13% differing CNV calls. In summary, TPE with SoftCTM enables reproducibility, automation, and standardisation at single-cell resolution. SoftCTM estimates (M = 58.9%, SD ±16.3%) reconcile the overestimation by molecular data extrapolation (RNA expression: M = 79.2%, SD ±10.5, DNA methylation: M = 62.7%, SD ±11.8%) and underestimation by CP (M = 35.9%, SD ±13.1%), providing a more reliable middle ground. A fully integrated computational pathology solution could therefore be used to improve downstream molecular analyses for research and clinics. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland