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Electrocatalytic generation of H2 is challenging in neutral pH water, where high catalytic currents for the hydrogen evolution reaction (HER) are particularly sensitive to the proton source and solution characteristics. A tris(hydroxymethyl)aminomethane (TRIS) solution at pH 7 with a [2Fe-2S]-metallopolymer electrocatalyst gave catalytic current densities around two orders of magnitude greater than either a more conventional sodium phosphate solution or a potassium chloride (KCl) electrolyte solution. For a planar polycrystalline Pt disk electrode, a TRIS solution at pH 7 increased the catalytic current densities for H2 generation by 50 mA/cm2 at current densities over 100 mA/cm2 compared to a sodium phosphate solution. As a special feature of this study, TRIS is acting not only as the primary source of protons and the buffer of the pH, but the protonated TRIS ([TRIS-H]+) is also the sole cation of the electrolyte. A species that is simultaneously the proton source, buffer, and sole electrolyte is termed a protic buffer electrolyte (PBE). The structure-activity relationships of the TRIS PBE that increase the HER rate of the metallopolymer and platinum catalysts are discussed. These results suggest that appropriately designed PBEs can improve HER rates of any homogeneous or heterogeneous electrocatalyst system. General guidelines for selecting a PBE to improve the catalytic current density of HER systems are offered.Fatty acids (FAs) are central cellular metabolites that contribute to lipid synthesis, and can be stored or harvested for metabolic energy. Dysregulation in FA processing and storage causes toxic FA accumulation or altered membrane compositions and contributes to metabolic and neurological disorders. Saturated lipids are particularly detrimental to cells, but how lipid saturation levels are maintained remains poorly understood. Here, we identify the cerebellar ataxia spinocerebellar ataxia, autosomal recessive 20 (SCAR20)-associated protein Snx14, an endoplasmic reticulum (ER)-lipid droplet (LD) tethering protein, as a factor required to maintain the lipid saturation balance of cell membranes. We show that following saturated FA (SFA) treatment, the ER integrity of SNX14KO cells is compromised, and both SNX14KO cells and SCAR20 disease patient-derived cells are hypersensitive to SFA-mediated lipotoxic cell death. Using APEX2-based proximity labeling, we reveal the protein composition of Snx14-associated ER-LD contacts and define a functional interaction between Snx14 and Δ-9 FA desaturase SCD1. Lipidomic profiling reveals that SNX14KO cells increase membrane lipid saturation following exposure to palmitate, phenocopying cells with perturbed SCD1 activity. In line with this, SNX14KO cells manifest delayed FA processing and lipotoxicity, which can be rescued by SCD1 overexpression. Altogether, these mechanistic insights reveal a role for Snx14 in FA and ER homeostasis, defects in which may underlie the neuropathology of SCAR20.The drift-diffusion model (DDM) is a model of sequential sampling with diffusion signals, where the decision maker accumulates evidence until the process hits either an upper or lower stopping boundary and then stops and chooses the alternative that corresponds to that boundary. In perceptual tasks, the drift of the process is related to which choice is objectively correct, whereas in consumption tasks, the drift is related to the relative appeal of the alternatives. The simplest version of the DDM assumes that the stopping boundaries are constant over time. More recently, a number of papers have used nonconstant boundaries to better fit the data. This paper provides a statistical test for DDMs with general, nonconstant boundaries. As a by-product, we show that the drift and the boundary are uniquely identified. We use our condition to nonparametrically estimate the drift and the boundary and construct a test statistic based on finite samples.The celebrated Hong-Ou-Mandel effect is the paradigm of two-particle quantum interference. It has its roots in the symmetry of identical quantum particles, as dictated by the Pauli principle. Two identical bosons impinging on a beam splitter (of transmittance 1/2) cannot be detected in coincidence at both output ports, as confirmed in numerous experiments with light or even matter. Here, we establish that partial time reversal transforms the beam splitter linear coupling into amplification. We infer from this duality the existence of an unsuspected two-boson interferometric effect in a quantum amplifier (of gain 2) and identify the underlying mechanism as time-like indistinguishability. This fundamental mechanism is generic to any bosonic Bogoliubov transformation, so we anticipate wide implications in quantum physics.Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, employs two key host proteins to gain entry and replicate within cells, angiotensin-converting enzyme 2 (ACE2) and the cell surface transmembrane protease serine 2 (TMPRSS2). TMPRSS2 was first characterized as an androgen-regulated gene in the prostate. Supporting a role for sex hormones, males relative to females are disproportionately affected by COVID-19 in terms of mortality and morbidity. Several studies, including one employing a large epidemiological cohort, suggested that blocking androgen signaling is protective against COVID-19. Here, we demonstrate that androgens regulate the expression of ACE2, TMPRSS2, and androgen receptor (AR) in subsets of lung epithelial cells. AR levels are markedly elevated in males relative to females greater than 70 y of age. In males greater than 70 y old, smoking was associated with elevated levels of AR and ACE2 in lung epithelial cells. Transcriptional repression of the AR enhanceosome with AR or bromodomain and extraterminal domain (BET) antagonists inhibited SARS-CoV-2 infection in vitro. Taken together, these studies support further investigation of transcriptional inhibition of critical host factors in the treatment or prevention of COVID-19.

Postoperative atrial fibrillation (POAF) is a recognised complication in approximately 10% of major lung resections. In order to best target preoperative treatment, this study aimed at determining the association of incidence of POAF in patients undergoing lung resection to surgical and anatomical factors, such as surgical approach, extent of resection and laterality.

Evaluation of Post-operative Atrial Fibrillation in Thoracic surgery (EPAFT) a multicentre, population-based, retrospective, cross-sectional, observational study including 1367 patients undergoing lung resections between April 2016 and March 2017. The primary outcome was the presence of POAF following resection. POAF was defined as at least one episode of symptomatic or asymptomatic AF confirmed by ECG within 7 days from the thoracic procedure or prior to discharge from the hospital.

POAF was observed in 7.4% of patients 3.1% in minor resection (video-assisted thoracoscopic surgery (VATS) 2.5%; thoracotomy 3.8%), 9.0% in simple lobectomy (xis should be targeted at these groups.

Among patients undergoing lung resection, POAF was significantly associated with age, increasing invasiveness of approach and increasing extent of resection. In addition, POAF carried a significant long-term mortality rate and burden of cerebrovascular accident. Appropriate prophylaxis should be targeted at these groups.

The relation between body mass index (BMI) and coronary artery disease (CAD) extension remains controversial. A new score was developed to estimate body fat percentage (BFP) known as Relative Fat Mass (RFM) Index. This study aimed to evaluate the value of RFM Index in predicting the severity of the CAD, compared with other anthropometric measurements.

A total of 325 patients with chronic CAD were investigated. RFM, BFP, BMI and other anthropometric characteristics of patients were measured before angiography. CAD severity was determined by SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery trial (SYNTAX) Score. The association between SYNTAX Score and variables was evaluated using linear regression models. In order to compare the model performance, R-squared (R

), Akaike's information criterion, Bayesian information criterion and root mean square error were used.

Univariate linear regression outcome variable, SYNTAX was used to determine whether there was any relationship between variables. Independent variables were included in the multivariable linear logistic regression models. The analysis showed that in model 1, RFM (β coefficient 2.31 (0.90 to 3.71), p=0.001)), diabetes mellitus (β coefficient 3.72 (1.67 to 3.76), p=0.004)), haemoglobin (β coefficient -2.12 (-3.70 to -0.53), p=0.03) and age (β coefficient 1.83 (0.29 to 3.37), p=0.02)) were statistically significant. The adjusted R

values in model 1 were higher than model 2 (BFP) and model 3 (BMI) (0.155, 0.137 and 0.130, respectively), and χ

values of RFM were higher than BFP and BMI (10.5, 3.4 and 1.0, respectively).

RFM Index is a more reliable and compatible marker of obesity in showing the severity of CAD compared to BMI.

RFM Index is a more reliable and compatible marker of obesity in showing the severity of CAD compared to BMI.

Socioeconomic deprivation is associated with health inequality. Previous studies have described associations between primary care prescribing rates and deprivation for individual drugs or drug classes. We explore the correlation between socioeconomic deprivation and the rate of prescribing of individual pharmaceutical drugs, and drug classes, in primary care in England, to identify prescribing inequalities that would require further investigation.

In this cross-sectional study, national primary care prescribing data, by primary care practice, were retrieved for the calendar year 2019 in England. Socioeconomic deprivation was quantified using the Index of Multiple Deprivation (IMD) score. Correlations were calculated using Spearman's rank correlation coefficient (ρ), adjusting for practice list size and demographics, with a Bonferroni-corrected p value threshold of 5×10

.

We included 1.05 billion prescription items dispensed from 6896 England practices. 142/206 (69%) drug classes and 505/774 (65%) drugsof inequality.

In

-rearranged non-small cell lung cancer (NSCLC), impacts of concomitant genetic alterations on targeted therapies with ALK-tyrosine kinase inhibitors (ALK-TKI) are not yet well understood. Here, we investigated genetic alterations related to ALK-TKI resistance using clinico-genomic data and explored effective therapies to overcome the resistance in preclinical models through the identification of underlying molecular mechanisms.

We used integrated clinical and next-generation sequencing data generated in a nationwide lung cancer genome screening project (LC-SCRUM-Japan).

-rearranged NSCLC cell lines expressing wild-type or mutant

were used to evaluate cellular apoptosis induced by ALK-TKIs.

In 90 patients with

-rearranged NSCLC who were treated with a selective ALK-TKI, alectinib,

comutated patients showed significantly worse progression-free survival (PFS) than

wild-type patients [median PFS, 11.7 months (95% confidence interval, CI, 6.3-not reached, NR) vs. NR (23.6-NR);

= 0.0008; HR, 0.