bluuebunny/crossref_metadata_2025 huggingface dataset:
S100A4 is activated by RhoA and catalyses the polymerization of non‐muscle myosin, adhesion complex assembly and contraction in airway smooth muscle
Authors: Zhang Wenwu , Gunst Susan J.
Published: August 2020

Key points

S100A4 is expressed in many tissues, including smooth muscle (SM), but its physiologic function is unknown. S100A4 regulates the motility of metastatic cancer cells by binding to non‐muscle (NM) myosin II.

Contractile stimulation causes the polymerization of NM myosin in airway SM, which is necessary for tension development. NM myosin regulates the assembly of adhesion junction signalling complexes (adhesomes) that catalyse actin polymerization.

In airway SM, ACh (acetylcholine) stimulated the binding of S100A4 to the NM myosin heavy chain, which was catalysed by RhoA GTPase via the RhoA‐binding protein, rhotekin. The binding of S100A4 to NM myosin was required for NM myosin polymerization, adhesome assembly and actin polymerization.

S100A4 plays a critical function in the regulation of airway SM contraction by catalysing NM myosin filament assembly. The interaction of S100A4 with NM myosin may also play an important role in the physiologic function of other tissues.

S100A4 binds to the heavy chain of non‐muscle (NM) myosin II and can regulate the motility of crawling cells. S100A4 is widely expressed in many tissues including smooth muscle (SM), although its role in the regulation of their physiologic function is not known. We hypothesized that S100A4 contributes to the regulation of contraction in airway SM by regulating a pool of NM myosin II at the cell cortex. NM myosin II undergoes polymerization in airway SM and regulates contraction by catalysing the assembly of integrin‐associated adhesome complexes that activate pathways that catalyse actin polymerization. ACh stimulated the interaction of S100A4 with NM myosin II in airway SM at the cell cortex and catalysed NM myosin filament assembly. RhoA GTPase regulated the activation of S100A4 via rhotekin, which facilitated the formation of a complex between RhoA, S100A4 and NM myosin II. The depletion of S100A4, RhoA or rhotekin from airway SM tissues using short hairpin RNA or small interfering RNA prevented NM myosin II polymerization as well as the recruitment of vinculin and paxillin to adhesome signalling complexes in response to ACh, and inhibited actin polymerization and tension development. S100A4 depletion did not affect ACh‐stimulated SM myosin regulatory light chain phosphorylation. The results show that S100A4 plays a critical role in tension development in airway SM tissue by catalysing NM myosin filament assembly, and that the interaction of S100A4 with NM myosin in response to contractile stimulation is activated by RhoA GTPase. These results may be broadly relevant to the physiologic function of S100A4 in other cell and tissue types.
Estimation of Radiological Consequences at a Proposed Nuclear Power Plant Site Using Atmospheric Dispersion Code
Authors: Gyamfi Kwame , Birikorang Sylvester Attakorah , Ampomah-Amoako Emmanuel , Fletcher John Justice
Published: August 2020

Atmospheric dispersion modeling and radiation dose calculation have been performed for a generic 1000 MW water-water energy reactor (VVER-1000) assuming a hypothetical loss of coolant accident (LOCA). Atmospheric dispersion code, International Radiological Assessment System (InterRAS), was employed to estimate the radiological consequences of a severe accident at a proposed nuclear power plant (NPP) site. The total effective dose equivalent (TEDE) and the ground deposition were calculated for various atmospheric stability classes, A to F, with the site-specific averaged meteorological conditions. From the analysis, 3.7×10−1 Sv was estimated as the maximum TEDE corresponding to a downwind distance of 0.1 km within the dominating atmospheric stability class (class A) of the proposed site. The intervention distance for evacuation (50 mSv) and sheltering (10 mSv) were estimated for different stability classes at different distances. The intervention area for evacuation ended at 0.5 km and that for sheltering at 1.5 km. The results from the study show that designated area for public occupancy will not be affected since the estimated doses were below the annual regulatory limits of 1 mSv.
Automating Model Generation for Image-Based Cardiac Flow Simulation
Authors: Kong Fanwei , Shadden Shawn C.
Published: August 2020

Computational fluid dynamics (CFD) modeling of left ventricle (LV) flow combined with patient medical imaging data has shown great potential in obtaining patient-specific hemodynamics information for functional assessment of the heart. A typical model construction pipeline usually starts with segmentation of the LV by manual delineation followed by mesh generation and registration techniques using separate software tools. However, such approaches usually require significant time and human efforts in the model generation process, limiting large-scale analysis. In this study, we propose an approach toward fully automating the model generation process for CFD simulation of LV flow to significantly reduce LV CFD model generation time. Our modeling framework leverages a novel combination of techniques including deep-learning based segmentation, geometry processing, and image registration to reliably reconstruct CFD-suitable LV models with little-to-no user intervention.1 We utilized an ensemble of two-dimensional (2D) convolutional neural networks (CNNs) for automatic segmentation of cardiac structures from three-dimensional (3D) patient images and our segmentation approach outperformed recent state-of-the-art segmentation techniques when evaluated on benchmark data containing both magnetic resonance (MR) and computed tomography(CT) cardiac scans. We demonstrate that through a combination of segmentation and geometry processing, we were able to robustly create CFD-suitable LV meshes from segmentations for 78 out of 80 test cases. Although the focus on this study is on image-to-mesh generation, we demonstrate the feasibility of this framework in supporting LV hemodynamics modeling by performing CFD simulations from two representative time-resolved patient-specific image datasets.
Guest Editorial: Interpack 2019
Authors: Narumanchi Sreekant , Choi Sukwon , Karajgikar Saket , Sun Haiding , Zhang Guangsheng
Published: August 2020

n/a
Thermoviscoplasticity in Body-Centered Cubic Metals: A Two-Temperature Model With Grain Boundary Evolution
Authors: Kar Gurudas , Roy Debasish , Reddy J. N.
Published: August 2020

In this work, we develop a thermo-viscoplasticity model for body-centered cubic (BCC) metals based on a two-temperature theory of nonequilibrium thermodynamics. Modeling the plastic deformation here involves two subsystems, viz., a configurational subsystem related to grain growth, dislocation motion, and a kinetic vibrational subsystem describing the vibration of atoms. Due to a separation of the time scales, the two subsystems are described by two different temperatures. In this study, we introduce a grain boundary density, in addition to the mobile and forest dislocation densities, as an internal variable. The focus in this paper is on how large plastic deformation is affected by the evolving grain boundaries. In order to check the predictive quality of the model, numerical simulations are conducted and validated against available experimental evidence wherever possible.
XPS of the surface chemical environment of CsMAFAPbBrI trication-mixed halide perovskite film
Authors: Rodriguez-Pereira Jhonatan , Tirado Juan , Gualdrón-Reyes Andrés F. , Jaramillo Franklin , Ospina Rogelio
Published: August 2020

Perovskite-based materials have been considered as the most promising materials in several solar-driven processes, especially photovoltaics. Some features such as high sunlight harvesting and improved carrier transport have been highlighted to have an impact on the efficiency of the above topics, but limited studies have pointed out their surface composition, which mainly influence the above abilities. As a starting point to recognize the surface environment and chemical states of these materials, x-ray photoelectron spectroscopy measurements were performed. Trication-mixed halide perovskite films based on Cs0.08MA0.18FA0.78PbBr0.42I2.58 were prepared by a one step process and deposited on an indium tin oxide substrate by spin-coating. Survey spectra, Pb 4f, I 3d, Br 3d, Cs 3d, C 1s, N 1s, Pb 4d, and Pb 5d core levels, and valence band spectra were measured for the semiconductor sample. Results exhibit symmetrical peaks, indicating that a homogenous solid solution was achieved. Main chemical states of this kind of perovskites such as Cs-Br and Pb-I species are also shown. We deduced that the later signals are associated with the [PbI6]4− octahedra existing in the perovskite lattice, while the former one is related to Cs+ bounded to [PbBr6]4− units on the perovskite surface. Interestingly, the NR4+ signal was also identified, associated with the presence of methylammonium and formamidinium cations.
Neural rate difference model can account for lateralization of high-frequency stimuli
Authors: Klug Jonas , Schmors Lisa , Ashida Go , Dietz Mathias
Published: August 2020

Lateralization of complex high-frequency sounds is conveyed by interaural level differences (ILDs) and interaural time differences (ITDs) in the envelope. In this work, the authors constructed an auditory model and simulate data from three previous behavioral studies obtained with, in total, over 1000 different amplitude-modulated stimuli. The authors combine a well-established auditory periphery model with a functional count-comparison model for binaural excitatory–inhibitory (EI) interaction. After parameter optimization of the EI-model stage, the hemispheric rate-difference between pairs of EI-model neurons relates linearly with the extent of laterality in human listeners. If a certain ILD and a certain envelope ITD each cause a similar extent of laterality, they also produce a similar rate difference in the same model neurons. After parameter optimization, the model accounts for 95.7% of the variance in the largest dataset, in which amplitude modulation depth, rate of modulation, modulation exponent, ILD, and envelope ITD were varied. The model also accounts for 83% of the variances in each of the other two datasets using the same EI model parameters.
Atmospheric dynamics drive most interannual U.S. droughts over the last millennium
Authors: Erb M. P. , Emile-Geay J. , Hakim G. J. , Steiger N. , Steig E. J.
Published: August 2020

U.S. drought is analyzed over the past millennium, showing that ENSO has some influence but much variability remains unexplained.
High-throughput 3D screening for differentiation of hPSC-derived cell therapy candidates
Authors: Muckom Riya , Bao Xiaoping , Tran Eric , Chen Evelyn , Murugappan Abirami , Dordick Jonathan S. , Clark Douglas S. , Schaffer David V.
Published: August 2020

A high-throughput 3D hPSC differentiation screening strategy reveals basic and translational insight for CNS cell therapies.
Development of a potent Zika virus vaccine using self-amplifying messenger RNA
Authors: Luisi Kate , Morabito Kaitlyn M. , Burgomaster Katherine E. , Sharma Mayuri , Kong Wing-Pui , Foreman Bryant M. , Patel Sonal , Fisher Brian , Aleshnick Maya A. , Laliberte Jason , Wallace Madison , Ruckwardt Tracy J. , Gordon David N. , Linton Christine , Ruggiero Nicole , Cohen Jessica L. , Johnson Russell , Aggarwal Kunal , Ko Sung-Youl , Yang Eun Sung , Pelc Rebecca S. , Dowd Kimberly A. , O’Hagan Derek , Ulmer Jeffrey , Mossman Sally , Sambor Anna , Lepine Edith , Mascola John R. , Pierson Theodore C. , Graham Barney S. , Yu Dong
Published: August 2020

A Zika self-amplifying mRNA vaccine delivered by a flexible bedside mixing formulation induces protective immunity in NHPs.
Target switch of centipede toxins for antagonistic switch
Authors: Yang Shilong , Wang Yunfei , Wang Lu , Kamau Peter , Zhang Hao , Luo Anna , Lu Xiancui , Lai Ren
Published: August 2020

Centipedes use toxins against conspecific centipedes or heterospecific prey species.
Supplemental Material: Methanogen microfossils and methanogenesis in Permian lake deposits
Authors: Sun Funing , Hu Wenxuan , al. et
Published: August 2020

Geological background, samples and methods, Figures S1–S7, and Tables S1–S3.
Supplemental Material: Quantifying shortening across the central Appalachian fold-thrust belt, Virginia and West Virginia, USA: Reconciling grain-, outcrop-, and map-scale shortening
Authors: Lammie D. , al. et
Published: August 2020

Plate 1. (A and B) Balanced (A) and restored (B) cross section A-A' extending from the eastern Great Valley westward to the Burning Spring anticline (Fig. 1). Total deformed length (274 km) and undeformed restored length (346 km) are measured from a pin line east of the extent of documented map-scale shortening on the Appalachian Plateau, resulting in 78 km (23%) total shortening. (C) As shown, shortening in Upper Devonian through Permian rocks assumes 10% layer-parallel shortening (LPS) in the Appalachian Plateau and across the Appalachian front (to thick vertical bar) and 25% LPS in the Valley and Ridge (region between thick vertical bars). Shortening in the Great Valley requires 35% LPS, compared to the >50% LPS measured in that region (Wright and Platt, 1982). Cross sections drawn with no vertical exaggeration; Circled numbers—duplex numbers; Fm–Formation; Gp—Group. Plate 2. Geologic cross section divided into 16 sequentially numbered intervals (circled numbers above the cross section) spanning from the western limb of the Burning Springs anticline eastward to the Great Valley. Locations of each of the 40 samples used to constrain grain-scale layer-parallel shortening (LPS) are shown as small white dots projected into the line of section; calculated LPS (as a percentage) are shown above each sample. Mean LPS values for each interval are summarized in Table 2. (A) Cross section constructed to minimize the amount of unit thickness variation in the Reedsville-Martinsburg Formations. Balancing this section requires 10% outcrop-scale shortening between the Elkins Valley anticline and the boundary between the Valley and Ridge and Great Valley. (B) Cross section constructed to minimize contributions from outcrop-scale shortening. Balancing this section requires 5% outcrop-scale shortening between the Elkins Valley anticline and the boundary between the Valley and Ridge and Great Valley. Cross sections drawn with no vertical exaggeration; circled numbers—duplex numbers; Fm—Formation; Gp—Group.
Temporal trends and geographical disparities in comprehensive stroke centre capabilities in Japan from 2010 to 2018
Authors: Kurogi Ai , Nishimura Ataru , Nishimura Kunihiro , Kada Akiko , Onozuka Daisuke , Hagihara Akihito , Ogasawara Kuniaki , Shiokawa Yoshiaki , Kitazono Takanari , Arimura Koichi , Iihara Koji
Published: August 2020

Objectives

Comprehensive stroke centre (CSC) capabilities are associated with reduced in-hospital mortality due to acute stroke. However, it remains unclear whether there are improving trends in the CSC capabilities or how hospital-related factors determine quality improvement. This study examined whether CSC capabilities changed in Japan between 2010 and 2018 and and whether any changes were influenced by hospital characteristics.

Design

A hospital-based cross-sectional study.

Setting

We sent out questionnaires to the training institutions of the Japan Neurosurgical Society and Japan Stroke Society in 2010, 2014 and 2018.

Participants

749 hospitals in 2010, 532 hospitals in 2014 and 786 hospitals in 2018 participated in the J-ASPECT study, a nationwide survey of acute stroke care capacity for proper designation of a comprehensive stroke centre in Japan.

Main outcome measures

CSC capabilities were assessed using the validated scoring system (CSC score: 1–25 points) in 2010, 2014 and 2018 survey. The effect of hospital characteristics was examined using multiple logistic regression analysis.

Results

Among the 323 hospitals that responded to all surveys, the implementation of 13 recommended items increased. The CSC score (median and IQR) was 16 (13–19), 18 (14–20) and 19 (15–21) for 2010, 2014 and 2018, respectively (p<0.001). There was a ≥20% increase in six items (eg, endovascular physicians, stroke unit and interventional coverage 24/7), and a ≤20% decrease in community education. A lower baseline CSC score (OR: 0.82, 95% CI 0.75 to 0.9), the number of beds≥500 (OR: 3.9, 95% CI 1.2 to 13.0) and the number of stroke physicians (7–9) (OR: 2.6, 95% CI 1.1 to 6.3) were associated with improved CSC capabilities, independent of geographical location.

Conclusions

There was a significant improvement in CSC capabilities between 2010 and 2018, which was mainly related to the availability of endovascular treatment and multidisciplinary care. Our findings may be useful to determine which hospitals should be targeted to improve CSC capabilities in a defined area.
Mangomoments - preconditions and impact on patients and families, healthcare professionals and organisations: a multi-method study in Flemish hospitals
Authors: Vanhaecht Kris , Van Bael Elly , Coeckelberghs Ellen , Van der Auwera Charlotte , Claessens Fien , Bruyneel Luk , De Ridder Dirk , Panella Massimiliano , Bisognano Maureen , Delgado Pedro L , Seys Deborah
Published: August 2020

Objective

Understanding how small unexpected acts or gestures by healthcare professionals, known as Mangomoments, are translated into practice, what their preconditions are and what their impact is on patients and families, healthcare professionals and organisations.

Design

A multi-method design was used based on four phases: (1) A (media)campaign to collect Mangomoment stories (n=1045), of which 94% (n=983) were defined as Mangomoments; (2) Semi-structured interviews (n=120); (3) Focus group interviews (n=3); and (4) A consensus meeting.

Setting

Respondents from a hospital and primary care setting.

Participants

Patients, family, healthcare professionals, managers, researchers and a policymaker participated.

Results

Mangomoments are mainly classified in the dimensions ‘Respect for values, preferences and needs’ and ‘Emotional support’. Differences in importance of the dimensions were found between healthcare professionals, oncological patients and family and non-oncological patients and family. The results of the interviews, focus groups and consensus meeting were visualised by the Mangomoment model. It identifies several preconditions on the level of patients, healthcare professionals and leadership. For each of these preconditions a catalyst was identified to increase the prevalence of Mangomoments. In general, Mangomoments improved the patient and family experience and facilitated adherence to therapy and led to a positive perception on the healing process. Positive effects for professionals include personal accomplishment and anti-burnout, joy in work and a positive team atmosphere. This led to positive resonance by a relationship of trust between the patient and the healthcare professionals, feelings of tolerance during negative experiences and open communication and a safe climate. Overall, patients and healthcare workers concluded that Mangomoments led to loyalty to the healthcare organisation.

Conclusion

Mangomoments do not only have a positive impact on patient and family but also on the healthcare professional. Leadership should shape several preconditions and catalysts which can lead to positive resonance and loyalty of patients and professionals.
Surgical intervention for paediatric infusion-related extravasation injury: a systematic review
Authors: Little Max , Dupré Sophie , Wormald Justin Conrad Rosen , Gardiner Matthew , Gale Chris , Jain Abhilash
Published: August 2020

Objectives

This systematic review aims to assess the quality of literature supporting surgical interventions for paediatric extravasation injury and to determine whether there is sufficient evidence to support invasive techniques in children.

Methods

We performed a systematic review by searching Ovid MEDLINE and EMBASE as well as AMED, CINAHL, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and clinicaltrials.gov from inception to February 2019. Studies other than case reports were eligible for inclusion if the population was younger than 18 years old, if there was a surgical intervention aimed at treating extravasation injury and if they reported on outcomes. Study quality was graded according to the National Institutes of Health study quality assessment tools.

Results

26 studies involving 728 children were included—one before-and-after study and 25 case series. Extravasation injuries were mainly confined to skin and subcutaneous tissues but severe complications were also encountered, including amputation (one toe and one below elbow). Of the surgical treatments described, the technique of multiple puncture wounds and instillation of saline and/or hyaluronidase was the most commonly used. However, there were no studies in which its effectiveness was tested against another treatment or a control and details of functional and aesthetic outcomes were generally lacking.

Conclusion

Surgical management is commonly reported in the literature in cases where there is significant soft tissue injury but as there are no comparative studies, it is unclear whether this is optimal. Further observational and experimental research evaluating extravasation injuries, including a centralised extravasation register using a universal grading scheme and core outcome set with adequate follow-up, are required to provide evidence to guide clinician decision-making.
Caring and living with Prader-Willi syndrome in Italy: integrating children, adults and parents’ experiences through a multicentre narrative medicine research
Authors: Ragusa Letizia , Crinò Antonio , Grugni Graziano , Reale Luigi , Fiorencis Alessandra , Licenziati Maria Rosaria , Faienza Maria Felicia , Wasniewska Malgorzata , Delvecchio Maurizio , Franzese Adriana , Rutigliano Irene , Fusilli Paola , Corica Domenico , Campana Giuseppina , Greco Donatella , Chiarito Mariangela , Sacco Michele , Toscano Silvia , Marini Maria Giulia
Published: August 2020

Objectives

Prader-Willi syndrome (PWS) significantly impacts health-related quality of life; however, its relational and existential aspects remain unknown in Italian clinical and social debate. The project aimed to investigate the impact of PWS on illness experience through narrative medicine (NM) to understand the daily life, needs and resources of patients with PWS and their caregivers, and to furnish insights for clinical practice.

Design and setting

The project involved 10 medical centres of the Italian Network for Rare Diseases and PWS family associations and targeted underage and adult patients with PWS and their caregivers. Written interviews, composed by a sociodemographic survey and a narrative, were collected through the project’s website. Three dedicated illness plots employed evocative and open words to facilitate individual expression and to encourage reflection. Narratives were analysed through NVivo software. Researchers discussed the results with the project’s steering committee.

Participants

Twenty-one children and adolescents and 34 adults with PWS joined the project, as well as 138 caregivers. A PWS diagnosis or the caregiving of a patient with PWS older than 5 years represented the eligibility criteria, as well as the willingness to share their illness experience by writing and the ability to communicate in Italian.

Results

The analysis of narratives led to understanding the PWS social and relational issues concerning diagnosis and current management, PWS daily experiences and social contexts, PWS implications in the working sphere and participants’ future perspectives. Narratives demonstrated that PWS management affects relationships and work-life balance and that social stigma remains present.

Conclusion

The project represented the first effort to investigate the impact of PWS on illness experience in Italy through NM while considering the perspectives of patients with PWS and their caregivers. The findings indicated that a multiprofessional approach is fundamental to ensure adequate treatment and provided elements for its improvement.
Quantifying alcohol audio-visual content in UK broadcasts of the 2018 Formula 1 Championship: a content analysis and population exposure
Authors: Barker Alexander , Opazo-Breton Magdalena , Thomson Emily , Britton John , Grant-Braham Bruce , Murray Rachael L
Published: August 2020

Objectives

Exposure to alcohol imagery is associated with subsequent alcohol use among young people, and UK broadcasting regulations protect young people from advertising alcohol content in UK television. However, alcohol promotion during sporting events, a significant potential medium of advertising to children, is exempt. We report an analysis and estimate the UK population exposure to, alcohol content, including branding, in UK broadcasts of the 2018 Formula 1 (F1) Championship.

Setting

UK.

Participants

None. Content analysis of broadcast footage of 21 2018 F1 Championship races on Channel 4, using 1-minute interval coding of any alcohol content, actual or implied use, other related content or branding. Census data and viewing figures were used to estimate gross and per capita alcohol impressions.

Results

Alcohol content occurred in all races, in 1613 (56%) 1-minute intervals of race footage and 44 (9%) of intervals across 28% of advertisement breaks. The most prominent content was branding, occurring in 51% of race intervals and 7% of advertisement break intervals, appearing predominantly on billboard advertisements around the track, with the Heineken and Johnnie Walker brands being particularly prominent. The 21 races delivered an estimated 3.9 billion alcohol gross impressions (95% CI 3.6 to 4.3) to the UK population, including 154 million (95% CI 124 to 184) to children, and 3.6 billion alcohol gross impressions of alcohol branding, including 141 million impressions to children. Branding was also shown in race footage from countries where alcohol promotion is prohibited.

Conclusions

Alcohol content was highly prevalent in the 2018 F1 Championship broadcasts, delivering millions of alcohol impressions to young viewers. This exposure is likely to represent a significant driver of alcohol consumption among young people.
Implementing a pharmacogenetic-driven algorithm to guide dual antiplatelet therapy (DAPT) in Caribbean Hispanics: protocol for a non-randomised clinical trial
Authors: Hernandez-Suarez Dagmar F , Melin Kyle , Marin-Maldonado Frances , Nunez Hector J , Gonzalez Ariel F , Gonzalez-Sepulveda Lorena , Rivas-Tumanyan Sona , Naik Hetanshi , Ruaño Gualberto , Scott Stuart A , Duconge Jorge
Published: August 2020

Introduction

Minority populations in the USA are disproportionately affected by cardiovascular conditions. Reduced responsiveness to clopidogrel among carriers ofCYP2C19variants has been reported in patients with either coronary artery disease (CAD) or acute coronary syndrome (ACS) after the percutaneous coronary intervention (PCI). Previous studies have evaluatedCYP2C19genotyping-guided antiplatelet therapy in selected populations; however, this has yet to be tested among Hispanics. Given the paucity of clinical research onCYP2C19and antiplatelet clinical outcomes in Hispanics, our study will test the safety and efficacy of a genetic-driven treatment algorithm to guide dual antiplatelet therapy (DAPT) in Caribbean Hispanics.

Methods and analysis

This is a multicentre, prospective, non-randomised clinical trial that proposes an assessment of pharmacogenomic-guided DAPT in post-PCI Caribbean Hispanic patients with ACS or CAD. We will recruit 250 patients to be compared with a matched non-concurrent cohort of 250 clopidogrel-treated patients (standard-of-care). Major adverse cardiovascular events (MACEs) such as all-cause death, myocardial infarction (MI), stroke, coronary revascularisation, stent thrombosis and bleedings over 6 months will be the study endpoints. Among the recruited, high-risk patients will be escalated to ticagrelor and low-risk patients will remain on clopidogrel. The primary objective is to determine whether genetic-guided therapy is superior to standard of care. The secondary objective will determine if clopidogrel treatment in low-risk patients is not associated with a higher rate of MACEs compared with escalated antiplatelet therapy in high-risk patients. Patients will be enrolled up to the group’s completion.

Ethics and dissemination

Approval was obtained from the Institutional Review Board of the University of Puerto Rico Medical Sciences Campus (protocol # A4070417). The study will be carried out in compliance with the Declaration of Helsinki and International Conference on Harmonization Good Clinical Practice Guidelines. Findings will be published in a peer-reviewed journal and controlled access to experimental data will be available.

Trial registration number

NCT03419325; Pre-results.
Lower socioeconomic status predicts higher mortality and morbidity in patients with heart failure
Authors: Schrage Benedikt , Lund Lars H , Benson Lina , Stolfo Davide , Ohlsson Anna , Westerling Ragnar , Westermann Dirk , Strömberg Anna , Dahlström Ulf , Braunschweig Frieder , Ferreira João Pedro , Savarese Gianluigi
Published: August 2020

Objective

It is not fully understood whether and how socioeconomic status (SES) has a prognostic impact in patients with heart failure (HF). We assessed SES and its association with patient characteristics and outcomes in a contemporary and well-characterised HF cohort.

Methods

Socioeconomic risk factors (SERF) were defined in the Swedish HF Registry based on income (low vs high according to the annual median value), education level (no degree/compulsory school vs university/secondary school) and living arrangement (living alone vs cohabitating).

Results

Of 44 631 patients, 21% had no, 33% one, 30% two and 16% three SERF. Patient characteristics strongly and independently associated with lower SES were female sex and no specialist referral. Additional independent associations were older age, more severe HF, heavier comorbidity burden, use of diuretics and less use of HF devices. Lower SES was associated with higher risk of HF hospitalisation/mortality, and overall cardiovascular and non-cardiovascular events. These associations persisted after extensive adjustment for patient characteristics, treatments and care. The magnitude of the association increased linearly with the increasing number of coexistent SERF: HR (95% CI) 1.09 (1.05 to 1.13) for one, 1.16 (1.12 to 1.20) for two and 1.22 (1.18 to 1.28) for three SERF (p<0.01).

Conclusions

In a contemporary and well-characterised HF cohort and after comprehensive adjustment for confounders, lower SES was linked with multiple factors such as less use of HF devices and age, but most strongly with female sex and lack of specialist referral; and associated with greater risk of morbidity/mortality.
Genetic associations of T cell cancer immune response-related genes with T cell phenotypes and clinical outcomes of early-stage lung cancer
Authors: Wang Qinchuan , Gu Jianchun , Wang Linbo , Chang David W , Ye Yuanqing , Huang Maosheng , Roth Jack A , Wu Xifeng
Published: August 2020

Background

Recent advances in T cell-related immunotherapy have brought remarkable progress in the treatment of non-small cell lung cancer (NSCLC). However, whether and how genetic variations of T cell cancer immune response genes can influence clinical outcomes of NSCLC patients remain obscure.

Methods

In this multiphase study, we assessed 2450 single-nucleotide polymorphisms (SNPs) from 280 T cell cancer immune response-related genes in 941 early-stage NSCLC patients (discovery n=536; validation n=405) to analyze the variants’ associations with outcomes and to observe the effects on T cell phenotypes.

Results

We found 14 SNPs in 10 genes were associated with NSCLC outcomes (p<0.05) in both phases. Among them,TRB:rs1964986 was the most significant variant associated with recurrence risk after meta-analysis (HR 1.84, 95% CI 1.35 to 2.52, p=1.15E-04), whileIDO1:rs10108662 was the most significant SNP associated with death risk (HR 1.87, 95% CI 1.40 to 2.51, p=2.17E-05). Analysis of unfavorable genotypes indicated cumulative effects on death and recurrence risks. Seven treatment-specific variants were found to predict opposite outcomes in surgery-only and surgery-plus-chemotherapy subgroups. Expression quantitative trait loci analysis indicated that six SNPs significantly correlated with their corresponding gene expression. T cells from high-risk subjects displayed reduced degranulation (p=0.02) and decreased cytotoxicity against cancer cells (p<0.01). Gene expression profile indicated increased IDO1 expression and decreased IL2, PRF and GZMB expression in high-risk subjects.

Conclusions

Genetic variations in T cell cancer immune response pathways can impact outcomes and may be served as predictors for treatment efficacy in early-stage NSCLC patients. The correlation between immune genotypes and T cell antitumor immunity suggests a biological link between host immune genetics and NSCLC prognosis.
Tragic choices in intensive care during the COVID-19 pandemic: on fairness, consistency and community
Authors: Newdick Chris , Sheehan Mark , Dunn Michael
Published: August 2020

Tragic choices arise during the COVID-19 pandemic when the limited resources made available in acute medical settings cannot be accessed by all patients who need them. In these circumstances, healthcare rationing is unavoidable. It is important in any healthcare rationing process that the interests of the community are recognised, and that decision-making upholds these interests through a fair and consistent process of decision-making. Responding to recent calls (1) to safeguard individuals’ legal rights in decision-making in intensive care, and (2) for new authoritative national guidance for decision-making, this paper seeks to clarify what consistency and fairness demand in healthcare rationing during the COVID-19 pandemic, from both a legal and ethical standpoint. The paper begins with a brief review of UK law concerning healthcare resource allocation, considering how community interests and individual rights have been marshalled in judicial deliberation about the use of limited health resources within the National Health Service (NHS). It is then argued that an important distinction needs to be drawn between procedural and outcome consistency, and that a procedurally consistent decision-making process ought to be favoured. Congruent with the position that UK courts have adopted for resource allocation decision-making in the NHS more generally, specific requirements for a procedural framework and substantive triage criteria to be applied within that framework during the COVID-19 pandemic are considered in detail.
AAC Redstar hard red spring wheat
Authors: Burt A.J. , Humphreys D.G. , Mitchell Fetch J. , Green D. , Fetch T.G. , McCallum B.D. , Menzies J. , Aboukhaddour R. , Henriquez M.A. , Kumar S.
Published: August 2020

AAC Redstar is an early maturing, high-yielding hard red spring wheat (Triticum aestivum L.) cultivar that is well adapted to the northern Canadian Prairies and eligible for grades of Canada Western Red Spring (CWRS) wheat. Over 3 yr (2016–2018) of testing in the Parkland Wheat Cooperative registration trials, AAC Redstar was 11% higher yielding than AC Splendor, 6% higher than Parata, and 4% higher than Glenn and Carberry. AAC Redstar matured 3 d earlier than Glenn, 2 d earlier than Carberry, and had similar maturity to Parata. AAC Redstar was shorter than all checks except Carberry and had better lodging resistance compared with all the check cultivars in the registration trial. The test weight and thousand-kernel weight of AAC Redstar were similar to Carberry. The grain protein concentration of AAC Redstar was 0.2% lower than Carberry. AAC Redstar was rated moderately resistant to Fusarium head blight, leaf rust, stripe rust, and common bunt. AAC Redstar had resistant reactions to loose smut and stem rust. AAC Redstar was registered under the CWRS market class.
Investigating the impact of the partonic structure on the description of hadronic collisions at high energies
Authors: Broilo M. , Gonçalves V. P. , Silva P. V. R. G.
Published: August 2020

The impact of the partonic structure on the description of the hadronic cross-sections is investigated considering a multichannel eikonal model based on the Good–Walker approach. The total, elastic and single diffractive cross-sections are estimated considering different parametrizations for the parton distribution functions and the predictions are compared with the experimental data for proton–proton [Formula: see text] and antiproton–proton [Formula: see text] collisions. We show that the description of the high-energy behavior of the hadronic cross-sections is sensitive to the partonic structure.
A Novel Bipolar Photon-Controlled Generalized Memristor Based on Avalanche Photodiode
Authors: Hao Jianxiu , Jin Xiangliang , Peng Bo
Published: August 2020

A novel bipolar photon-controlled generalized memristor model with an avalanche photodiode (APD) passive quenching circuit is presented in this paper. The SPICE model of the circuit is established and its fingerprints are analyzed by the pinched hysteresis loops with different bipolar periodic stimuli. The dynamical characteristics of the proposed circuit model are investigated both theoretically and simulatively. The results verified by Cadence Spectre circuit simulator demonstrate that the proposed circuit model is a simple bipolar photon-controlled generalized memristor. Compared with the previously published memristor models, the biggest innovation of this paper is to propose a bipolar generalized memristor model instead of the traditional model, which can easily form the pinched hysteresis loop. Another highlight is that the generalized memristor model in this paper is controlled by photons while conventional memristors are charge-controlled/flux-controlled. Furthermore, the circuit level models are more stable, more reliable and more resistant to interference than the device level models. The topological structure of the proposed circuit model in this paper is much more simpler.
Facile One-Step Preparation and Efficient Photocatalytic Hydrogen Production of Composite MoS2/g-C3N4 Sensitized by Erythrosin B
Authors: Yin Mingcai , Li Yixian , Liang Kaiyue , Sun Jiangfan , Fan Yaoting , Li Zhongjun
Published: August 2020

MoS2/g-C3N4 (g-C3N4 [Formula: see text] graphitic carbon nitride) composite is considered as a promising photocatalyst for hydrogen production, while the preparation method still needs to be improved. Herein for the first time, nanosized MoS3 and melamine were used as starting materials and a facile one-pot calcination method was successfully applied for the synthesis of MoS2/g-C3N4. The physical and photophysical properties of the as-prepared MoS2/g-C3N4 were characterized by XRD, IR, SEM, TEM and XPS techniques. Sensitized by Erythrosin B (EB), the photocatalytic hydrogen production performance of MoS2/g-C3N4 was investigated and the amount of MoS2 was optimized. An excellent H2 production activity of 1091.2[Formula: see text][Formula: see text] was achieved for 43% MoS2/g-C3N4, which is about 330 times that of pure g-C3N4 (3.3[Formula: see text][Formula: see text]. In addition, its performance was compared with those of three other MoS2/g-C3N4 samples prepared by conventional methods and a possible mechanism of H2 production was proposed based on the photoluminescence and photoelectrochemical results.
A revised age-model for the Eocene deep-marine siliciclastic systems, Aínsa Basin, Spanish Pyrenees
Authors: Cantalejo Blanca , Pickering Kevin T. , McNiocaill Conall , Bown Paul , Johansen Kyrre , Grant Melissa
Published: August 2020

Using new palaeomagnetic and biostratigraphic data, we revise the age-model for the middle Eocene, deep-marine Aínsa Basin (Spanish Pyrenees), a tectonically active basin formed at a convergent-plate margin. This new age model provides a framework for evaluating the depositional history and sediment accumulation rates. New integrated magneto- and biostratigraphy data identify two normal and two reverse chrons of the geomagnetic polarity timescale (C21r, C21n, C20r, C20n) and place these Upper Hecho Group deposits in the middle Eocene (Lutetian). Nannofossil analysis identifies a biostratigraphic range from Subzone NP14b in the Gerbe System to Subzone NP15b at the top of the Aínsa System using key, age-diagnostic marker species such as
Blackites inflatus
,
Blackites piriformis
and
Coccolithus gigas
. We also present new nannofossil biostratigraphy from the Lower Hecho Group. This new Aínsa Basin chronostratigraphy enables inter-basinal correlations between the proximal fluvio-deltaic Tremp-Graus Basin and the more distal Jaca Basin, thereby providing a better understanding of the basin evolution.

Supplementary materials
:
Field photographs of the sampled sections, magnetostratigraphic results, biostratigraphy results, alternative age model scenario and discussion on previous age model are available at
https://doi.org/10.6084/m9.figshare.c.5083076
Towards a Harmonized Accelerated Stress Test Protocol for Fuel Starvation Induced Cell Reversal Events in PEM Fuel Cells: The Effect of Pulse Duration
Authors: Marić Robert , Gebauer Christian , Nesselberger Markus , Hasché Frédéric , Strasser Peter
Published: August 2020

Global fuel starvation is an undesired event during fuel cell operation that results in serious degradations at the anode catalyst layer caused by the concomitant reversal of the cell potentials. Several groups have therefore intensified their research efforts towards the implementation of suitable diagnostic tools and accelerated stress test (AST) protocols that mimic cell reversal events. However, the current number of different test protocols requires consolidation and harmonization to define durability targets towards cell reversal tolerance and to benchmark newly developed materials. To create a basis for harmonization, this study examines the difference between pulsed and quasi-continuous AST protocols at the catalyst-coated membrane level. Utilizing a single-cell setup combined with an on-line mass spectrometer, a 2.5-fold increase in the carbon corrosion rates were found for short-pulsed compared to long-lasting cell reversal events. The enhanced corrosion was associated with a 2.2-fold higher loss of electrochemically active surface area and a 15% higher reduction in anode catalyst layer thickness. By contrast, the overall cell performance decreased additionally by 40–50 mV for samples under long-lasting cell reversal events. The decay is mainly driven by an increased ohmic resistance, presumably originating from a more pronounced surface oxide formation on the carbon support.
Operando Observations of Reversible α-BiF3 Conversion in Liquid Electrolyte by Synchrotron Radiation Diffraction and 7Li Nuclear Magnetic Resonance
Authors: Kawasaki Mitsuo , Kiuchi Hisao , Shimoda Keiji , Kano Gentaro , Fujimoto Hiroyuki , Ogumi Zempachi , Abe Takeshi
Published: August 2020

The electrochemically-driven conversion reaction of BiF3 with Li+ ions is of interest for potential application as a positive electrode system in conversion type rechargeable batteries. Here, we use synchrotron radiation diffraction and 7Li nuclear magnetic resonance (NMR) for complementary operando observations of reversible or quasi-reversible conversion reactions of α-BiF3 nanocomposite electrode at room temperature. The nanocomposite electrode was fabricated by ball milling and subsequent heat treatments. A pronounced XRD peak broadening indicated a disordered fine crystalline state in the electrode. The operando synchrotron radiation diffraction measurements revealed a quasi-reversible smooth crystallographic transformation between α-BiF3 and metallic Bi. The operando
7Li NMR measurement quantitatively showed reversible conversion reactions. The series of in-situ
7Li NMR spectra contained sharp signals from Li+ ions in the electrolyte and a broad signal associated with a solid phase of LiF. These signals followed a stoichiometric relationship that conformed to a three-electron BiF3 conversion pathway.
Review—Silicon Nitride and Silicon Nitride-Rich Thin Film Technologies: State-of-the-Art Processing Technologies, Properties, and Applications
Authors: Kaloyeros Alain E. , Pan Youlin , Goff Jonathan , Arkles Barry
Published: August 2020

Accelerating interest in silicon nitride thin film material system continues in both academic and industrial communities due to its highly desirable physical, chemical, and electrical properties and the potential to enable new device technologies. As considered here, the silicon nitride material system encompasses both non-hydrogenated (SiNx) and hydrogenated (SiNx:H) silicon nitride, as well as silicon nitride-rich films, defined as SiNx with C inclusion, in both non-hydrogenated (SiNx(C)) and hydrogenated (SiNx:H(C)) forms. Due to the extremely high level of interest in these materials, this article is intended as a follow-up to the authors’ earlier publication [A. E. Kaloyeros, F. A. Jové, J. Goff, B. Arkles, Silicon nitride and silicon nitride-rich thin film technologies: trends in deposition techniques and related applications, ECS J. Solid State Sci. Technol., 6, 691 (2017)] that summarized silicon nitride research and development (R&D) trends through the end of 2016. In this survey, emphasis is placed on cutting-edge achievements and innovations from 2017 through 2019 in Si and N source chemistries, vapor phase growth processes, film properties, and emerging applications, particularly in heterodevice areas including sensors, biointerfaces and photonics.
Vascular mechanisms and molecular targets in hypertensive pregnancy and preeclampsia
Authors: Qu Hongmei , Khalil Raouf A.
Published: August 2020

Preeclampsia is a major complication of pregnancy manifested as hypertension and often intrauterine growth restriction, but the underlying pathophysiological mechanisms are unclear. Predisposing genetic and environmental factors cause placental maladaptations leading to defective placentation, apoptosis of invasive cytotrophoblasts, inadequate expansive remodeling of the spiral arteries, reduced uteroplacental perfusion pressure, and placental ischemia. Placental ischemia promotes the release of bioactive factors into the maternal circulation, causing an imbalance between antiangiogenic soluble fms-like tyrosine kinase-1 and soluble endoglin and proangiogenic vascular endothelial growth factor, placental growth factor, and transforming growth factor-β. Placental ischemia also stimulates the release of proinflammatory cytokines, hypoxia-inducible factor, reactive oxygen species, and angiotensin type 1 receptor agonistic autoantibodies. These circulating factors target the vascular endothelium, causing generalized endotheliosis in systemic, renal, cerebral, and hepatic vessels, leading to decreases in endothelium-derived vasodilators such as nitric oxide, prostacyclin, and hyperpolarization factor and increases in vasoconstrictors such as endothelin-1 and thromboxane A2. The bioactive factors also target vascular smooth muscle and enhance the mechanisms of vascular contraction, including cytosolic Ca2+, protein kinase C, and Rho-kinase. The bioactive factors could also target matrix metalloproteinases and the extracellular matrix, causing inadequate vascular remodeling, increased arterial stiffening, and further increases in vascular resistance and hypertension. As therapeutic options are limited, understanding the underlying vascular mechanisms and molecular targets should help design new tools for the detection and management of hypertension in pregnancy and preeclampsia.