To assess the time course of changes in physical performance in response to match-play tennis under heat stress.
Two matches consisting of 20 min of effective playing time (2×10 min segments) were ...played in COOL (∼102 min; ∼22°C and 70% relative humidity (RH)) and HOT (∼119 min; ∼36°C and 35% RH) environments. Repeated-sprint ability (3×15 m, 15 s rest), 15 m sprint time with a direction change (180°), vertical jump height (squat and countermovement jumps) and leg stiffness (multirebound jumps) were assessed in 12 competitive male players prematch, midmatch and postmatch, and 24 and 48 h after match completion.
During the repeated-sprint ability test, initial (+2.3% and +3.1%) and cumulated sprint (+1.5% and +2.8%) times increased from prematch to midmatch and postmatch, respectively (p<0.001), while the sprint decrement score did not change. Match-play tennis induced a slowing (average of both conditions: +1.1% and +1.3% at midmatch and postmatch time points; p=0.05) of 15 m sprint time with direction change. Compared with prematch, leg stiffness (-6.4% and -6.5%; p<0.001) and squat jump height (-1.5% and -2.4%; p=0.05), but not countermovement jump height (-0.7% and -1.3%; p>0.05), decreased midmatch and postmatch, respectively, regardless of the condition. Complete recovery in all physical performance markers occurred within 24 h.
In tennis, match-related fatigue is characterised by impaired repeated-sprint ability, explosive power and leg stiffness at midmatch and postmatch, with values restored to prematch baseline 24 h into recovery. In addition, physical performance responses (match and recovery kinetics) are identical when competing in cool and hot environments.
We present a simulation-assisted methodology for the design of point or distributed fiber dosimeters exploiting the linear dependence of the infrared radiation-induced attenuation of a single-mode ...phosphosilicate optical fiber. We demonstrate by comparing Monte Carlo simulations and experiments at different irradiation facilities (X-rays, γ-rays, protons and atmospheric neutrons) that the sensitivity coefficient of this fiber is independent on the nature of particles and on dose rate, at least up to total ionizing doses in the order of 500 Gy. Our simulations allow us to simulate the dose deposited in the fiber core (and then the Radiation Induced Attenuation (RIA) levels) for the different classes of particles (photons, electrons, neutrons, protons and heavy ions) and for different energy ranges. From this data, and knowing the environments of targeted applications for the fiber optic dosimeters, we can discuss the different designs and achievable performance using this fiber. Examples are discussed with space applications, atmospheric balloon experiments and fusion-devoted facilities.
Non-small cell lung carcinoma patients are frequently treated with cisplatin (CDDP), most often yielding temporary clinical responses. Here, we show that PARP1 is highly expressed and constitutively ...hyperactivated in a majority of human CDDP-resistant cancer cells of distinct histologic origin. Cells manifesting elevated intracellular levels of poly(ADP-ribosyl)ated proteins (PAR(high)) responded to pharmacologic PARP inhibitors as well as to PARP1-targeting siRNAs by initiating a DNA damage response that translated into cell death following the activation of the intrinsic pathway of apoptosis. Moreover, PARP1-overexpressing tumor cells and xenografts displayed elevated levels of PAR, which predicted the response to PARP inhibitors in vitro and in vivo more accurately than PARP1 expression itself. Thus, a majority of CDDP-resistant cancer cells appear to develop a dependency to PARP1, becoming susceptible to PARP inhibitor-induced apoptosis.
Single-cell CRISPR-based transcriptome screens are potent genetic tools for concomitantly assessing the expression profiles of cells targeted by a set of guides RNA (gRNA), and inferring target gene ...functions from the observed perturbations. However, due to various limitations, this approach lacks sensitivity in detecting weak perturbations and is essentially reliable when studying master regulators such as transcription factors. To overcome the challenge of detecting subtle gRNA induced transcriptomic perturbations and classifying the most responsive cells, we developed a new supervised autoencoder neural network method. Our Sparse supervised autoencoder (SSAE) neural network provides selection of both relevant features (genes) and actual perturbed cells. We applied this method on an in-house single-cell CRISPR-interference-based (CRISPRi) transcriptome screening (CROP-Seq) focusing on a subset of long non-coding RNAs (lncRNAs) regulated by hypoxia, a condition that promote tumor aggressiveness and drug resistance, in the context of lung adenocarcinoma (LUAD). The CROP-seq library of validated gRNA against a subset of lncRNAs and, as positive controls, HIF1A and HIF2A, the 2 main transcription factors of the hypoxic response, was transduced in A549 LUAD cells cultured in normoxia or exposed to hypoxic conditions during 3, 6 or 24 h. We first validated the SSAE approach on HIF1A and HIF2 by confirming the specific effect of their knock-down during the temporal switch of the hypoxic response. Next, the SSAE method was able to detect stable short hypoxia-dependent transcriptomic signatures induced by the knock-down of some lncRNAs candidates, outperforming previously published machine learning approaches. This proof of concept demonstrates the relevance of the SSAE approach for deciphering weak perturbations in single-cell transcriptomic data readout as part of CRISPR-based screening.
The gain degradations of an Er‐doped fiber amplifier (EDFA) during the exposure of its active Er‐doped fiber to 40 keV X‐rays (≈2.7 mrad(SiO2) s−1 up to 300 krad) at three different temperatures: ...−40, 25, and 120 °C, are characterized. The spectral dependence of the fiber radiation‐induced attenuation (RIA) is monitored in situ in the 900–1600 nm spectral range, highlighting a combined temperature and radiation effect on the near‐infrared RIA levels and kinetics. At the system level, the kinetics of EDFA gain degradation are only slightly affected by varying the irradiation temperature for the tested backward pumping EDFA configuration. On the theoretical side, a homemade computer code based on the particle swarm optimization and the rate equations to model the radiation behavior of EDFA is used, considering only the RIA impact on its gain. Despite a good agreement between experimental and simulation results below the dose of 70 krad corresponding to current space missions, the comparison between the modeled and measured gain degradation kinetics at higher doses shows that a more precise modeling of the temperature impact on the absorption properties of the erbium ions is necessary to better reproduce the EDFA radiation behavior for future space missions.
The X‐rays radiation responses of an Er‐doped fiber amplifier (EDFA) at three different temperatures to the one of the same EDFA theoretically optimized via homemade simulation code based on the particle swarm optimization are compared. Despite a good agreement until 70 krad accumulated dose, the simulations need a more precise modeling of the temperature impact for higher doses.
Prediction of neurological outcome after cardiac arrest is a major challenge. The aim of this study was to assess whether quantitative whole-brain white matter fractional anisotropy (WWM-FA) measured ...by diffusion tensor imaging between day 7 and day 28 after cardiac arrest can predict long-term neurological outcome.
This prospective, observational, cohort study (part of the MRI-COMA study) was done in 14 centres in France, Italy, and Belgium. We enrolled patients aged 18 years or older who had been unconscious for at least 7 days after cardiac arrest into the derivation cohort. The following year, we recruited the validation cohort on the same basis. We also recruited a minimum of five healthy volunteers at each centre for the normalisation procedure. WWM-FA values were compared with standard criteria for unfavourable outcome, conventional MRI sequences (fluid-attenuated inversion recovery and diffusion-weighted imaging), and proton magnetic resonance spectroscopy. The primary outcome was the best achieved Glasgow-Pittsburgh Cerebral Performance Categories (CPC) at 6 months, dichotomised as favourable (CPC 1–2) and unfavourable outcome (CPC 3–5). Prognostication performance was assessed by the area under the receiver operating characteristic (ROC) curves and compared between groups. This study was registered with ClinicalTrials.gov, number NCT00577954.
Between Oct 1, 2006, and June 30, 2014, 185 patients were enrolled in the derivation cohort, of whom 150 had an interpretable multimodal MRI and were included in the analysis. 33 (22%) patients had a favourable neurological outcome at 6 months. Prognostic accuracy, as quantified by the area under the ROC curve, was significantly higher with the normalised WWM-FA value (area under the ROC curve 0·95, 95% CI 0·91–0·98) than with the standard criteria for unfavourable outcome or other MRI sequences. In a subsequent validation cohort of 50 patients (enrolled between April 1, 2015, and March 31, 2016), a normalised WWM-FA value lower than 0·91, set from the derivation cohort, had a negative predictive value of 71·4% (95% CI 41·9–91·6) and a positive predictive value of 100% (90·0–100), with 89·7% sensitivity (75·8–97·1) and 100% specificity (69·1–100) for the prediction of unfavourable outcome.
In patients who are unconscious 7 days after cardiac arrest, the normalised WWM-FA value, measured by diffusion tensor imaging, could be used to accurately predict neurological outcome at 6 months. This evidence requires confirmation from future large-scale trials with a strict protocol of withdrawal or limitation-of-care decisions and time window for MRI.
French Ministry of Health, French National Agency for Research, Italian Ministry of Health, and Regione Lombardia.
Athletes engaged in repeated-sprint training in the heat can be at an increased risk of gastrointestinal ischemia and damage in response to a redistribution of blood to working skeletal muscles and ...the skin. This study investigated the effects of repeated sprinting in hot and cool conditions on markers of gastrointestinal damage.
Twenty-five, well-trained, nonheat acclimated male team-sport athletes completed a five-session, repeated-sprint training regimen over 7 days in either HOT (40 °C and 40% relative humidity RH) or COOL (20 °C and 40% RH) conditions. Participants underwent a 20-min warm-up and four sets of 5 × 6-s maximal cycling sprints, with 24-s rest and 5-min recovery between sets. Venous blood was collected pre-, post-, and 1 hr postexercise and analyzed for intestinal fatty acid binding protein, lipopolysaccharide binding protein, soluble CD14, and heat-shock protein.
Intestinal fatty acid binding protein concentrations were significantly increased (p < .004) postexercise (593 and 454 pg/ml) and 1 hr postexercise (466 and 410 pg/ml) on both Days 1 and 5 in HOT. Soluble CD14 increased by 398 and 308 ng/ml postexercise (p = .041), and lipopolysaccharide binding protein increased by 1,694 ng/ml postexercise on Day 1 in HOT (p < .05) and by 1,520 ng/ml on Day 5 in COOL (p = .026). Core and skin temperature, rating of perceived exertion, and thermal sensation were higher (p < .05) in HOT on Days 1 and 5 during sprinting.
Repeated sprinting in the heat induced greater thermal strain and mild changes in gastrointestinal damage, likely attributable to the combination of environmental conditions and maximal-intensity exercise.
A prevalence of around 26% of human papillomavirus (HPV) in head and neck squamous cell carcinoma (HNSCC) has been previously reported. HPV induced oncogenesis mainly involving E6 and E7 viral ...oncoproteins. In some cases, HPV viral DNA has been detected to integrate with the host genome and possibly contributes to carcinogenesis by affecting the gene expression. We retrospectively assessed HPV integration sites and signatures in 80 HPV positive patients with HNSCC, by using a double capture‐HPV method followed by next‐generation Sequencing. We detected HPV16 in 90% of the analyzed cohort and confirmed five previously described mechanistic signatures of HPV integration episomal (EPI), integrated in a truncated form revealing two HPV‐chromosomal junctions colinear (2J‐COL) or nonlinear (2J‐NL), multiple hybrid junctions clustering in a single chromosomal region (MJ‐CL) or scattered over different chromosomal regions (MJ‐SC) of the human genome. Our results suggested that HPV remained episomal in 38.8% of the cases or was integrated/mixed in the remaining 61.2% of patients with HNSCC. We showed a lack of association of HPV genomic signatures to tumour and patient characteristics, as well as patient survival. Similar to other HPV associated cancers, low HPV copy number was associated with worse prognosis. We identified 267 HPV‐human junctions scattered on most chromosomes. Remarkably, we observed four recurrent integration regions: PDL1/PDL2/PLGRKT (8.2%), MYC/PVT1 (6.1%), MACROD2 (4.1%) and KLF5/KLF12 regions (4.1%). We detected the overexpression of PDL1 and MYC upon integration by gene expression analysis. In conclusion, we identified recurrent targeting of several cancer genes such as PDL1 and MYC upon HPV integration, suggesting a role of altered gene expression by HPV integration during HNSCC carcinogenesis.
Five previously described mechanistic signatures of human papillomavirus (HPV) integration episomal, integrated in a truncated form revealing two HPV‐chromosomal junctions colinear (2J‐COL) or nonlinear (2J‐NL), multiple hybrid junctions clustering in a single chromosomal region (MJ‐CL) or scattered over different chromosomal regions (MJ‐SC) of the human genome are confirmed in our head and neck squamous cell carcinoma cohort. Two hundred sixty‐seven HPV‐human junctions scattered on most chromosomes are reported.
Highlights • The treatment of advanced, refractory thymic epithelial tumors is challenging. • A phase II trial with sunitinib demonstrated its activity in selected patients. • Off-label sunitinib ...produced an overall response rate of 22% and a PFS of 3.7 months
Purpose
To determine performances of 2-deoxy-2-(18F)fluoro-
d
-glucose (18F-FDG) positron emission tomography (PET) to detect the development of permanent thyroid dysfunction (PTD), and to evaluate ...the prognostic value of early increased thyroid uptake in stage IV melanoma patients treated with anti-programmed death 1 (anti-PD-1) antibodies.
Methods
Twenty-nine patients were retrospectively enrolled. PTD was defined as symptomatic thyroid disorder requiring long-term specific treatment. On the first PET performed during follow-up, maximal standardized uptake value of the thyroid (SUVmax-Th) and SUVmax-Th/SUVmax-blood-pool ratio (Th/B) were measured. Areas under ROC curves (AUC) of these parameters for the diagnostic of PTD were compared. Cutoff values were defined to maximize the Youden’s index. Survival analyses were performed according to the Kaplan–Meier method and compared using the log-rank method between patients with and without enhanced thyroid uptake according to cutoff values defined with the Hothorn and Lausen method.
Results
Four patients presented PTD. Median SUVmax-Th and Th/B were, respectively, 2.11 and 1.00. The median follow-up period was 21.7 months. AUC were 1.0 (CI
95%
0.88–1.0) for both parameters. Optimal cutoff values were, respectively, SUVmax-Th > 4.1 and Th/B > 2.0, both conferring sensitivities of 100% (CI
95%
40–100%) and specificities of 100% (CI
95%
86–100%). The median progression-free survival and overall survival were 11.3 months and 33.5 months, respectively. Using optimized cutoffs, there was no statistically significant difference of survival.
Conclusion
SUVmax-Th > 4.1 and Th/B > 2.0 provided perfect diagnostic performances to detect patients that developed PTD. No significant survival difference was found between patients with and without increased thyroid uptake.
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