bluuebunny/crossref_metadata_2025_split huggingface dataset:
F0F1 ATP synthase regulates extracellular calcium influx in human neutrophils by interacting with Cav2.3 and modulates neutrophil accumulation in the lipopolysaccharide-challenged lung
Authors: Zhu Baoyi , Feng Zhengfu , Guo Yan , Zhang Tian , Mai Ai , Kang Zhanfang , Weijen Ting , Wang Dai , Yin Dazhong , Zhu Dongxing , Gao Jun 
Published: February 2021

Abstract
Background
Neutrophils form the first line of innate host defense against invading microorganisms. We previously showed that F0F1 ATP synthase (F-ATPase), which is widely known as mitochondrial respiratory chain complex V, is expressed in the plasma membrane of human neutrophils and is involved in regulating cell migration. Whether F-ATPase performs cellular functions through other pathways remains unknown.

Methods
Blue native polyacrylamide gel electrophoresis followed by nano-ESI-LC MS/MS identification and bioinformatic analysis were used to identify protein complexes containing F-ATPase. Then, the identified protein complexes containing F-ATPase were verified by immunoblotting, immunofluorescence colocalization, immunoprecipitation, real-time RT-PCR and agarose gel electrophoresis. Immunoblotting, flow cytometry and a LPS-induced mouse lung injury model were used to assess the effects of the F-ATPase-containing protein complex in vitro and in vivo.

Results
We found that the voltage-gated calcium channel (VGCC) α2δ-1 subunit is a binding partner of cell surface F-ATPase in human neutrophils. Further investigation found that the physical connection between the two proteins may exist between the F1 part (α and β subunits) of F-ATPase and the α2 part of VGCC α2δ-1. Real-time RT-PCR and PCR analyses showed that Cav2.3 (R-type) is the primary type of VGCC expressed in human neutrophils. Research on the F-ATPase/Cav2.3 functional complex indicated that it can regulate extracellular Ca2+ influx, thereby modulating ERK1/2 phosphorylation and reactive oxygen species production, which are typical features of neutrophil activation. In addition, the inhibition of F-ATPase can reduce neutrophil accumulation in the lungs of mice that were intratracheally instilled with lipopolysaccharide, suggesting that the inhibition of F-ATPase may prevent neutrophilic inflammation-induced tissue damage.

Conclusions
In this study, we identified a mechanism by which neutrophil activity is modulated, with simultaneous regulation of neutrophil-mediated pulmonary damage. These results show that surface F-ATPase of neutrophils is a potential innate immune therapeutic target.

Graphical abstract
Association of ultra-processed food consumption with cardiovascular mortality in the US population: long-term results from a large prospective multicenter study
Authors: Zhong Guo-Chao , Gu Hai-Tao , Peng Yang , Wang Kang , Wu You-Qi-Le , Hu Tian-Yang , Jing Feng-Chuang , Hao Fa-Bao 
Published: February 2021

AbstractBackgroundUltra-processed foods have now become dominant in the global food system. Whether their consumption is associated with cardiovascular mortality remains controversial. Moreover, data on ultra-processed foods and cardiovascular outcomes are scarce in the US population. We aimed to examine the association of ultra-processed food consumption with cardiovascular mortality in a US population.MethodsA population-based cohort of 91,891 participants was identified from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Dietary data were collected through a validated 137-item food frequency questionnaire. Ultra-processed foods were defined by the NOVA classification. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for cardiovascular mortality. Restricted cubic spline regression was used to test nonlinearity. Subgroup analyses were conducted to identify the potential effect modifiers.ResultsAfter an average follow-up of 13.5 years (1,236,049.2 person-years), 5490 cardiovascular deaths were documented, including 3985 heart disease deaths and 1126 cerebrovascular deaths. In the fully adjusted model, participants in the highest vs. the lowest quintiles of ultra-processed food consumption had higher risks of death from cardiovascular disease (HRquintile 5 vs. 1, 1.50; 95% CI, 1.36–1.64) and heart disease (HRquintile 5 vs. 1, 1.68; 95% CI, 1.50–1.87) but not cerebrovascular disease (HRquintile 5 vs. 1, 0.94; 95% CI, 0.76–1.17). A nonlinear dose–response pattern was observed for overall cardiovascular and heart disease mortality (allPnonlinearity < 0.05), with a threshold effect observed at ultra-processed food consumption of 2.4 servings/day and 2.3 servings/day, respectively; below the thresholds, no significant associations were observed for these two outcomes. Subgroup analyses showed that the increased risks of mortality from ultra-processed foods were significantly higher in women than in men (allPinteraction < 0.05).ConclusionsHigh consumption of ultra-processed foods is associated with increased risks of overall cardiovascular and heart disease mortality. These harmful associations may be more pronounced in women. Our findings need to be confirmed in other populations and settings.
Brain lateralization in children with upper-limb reduction deficiency
Authors: Zuniga Jorge M. , Pierce James E. , Copeland Christopher , Cortes-Reyes Claudia , Salazar David , Wang YingYing , Arun K. M. , Huppert Theodore 
Published: February 2021

AbstractBackgroundThe purpose of the current study was to determine the influence of upper-limb prostheses on brain activity and gross dexterity in children with congenital unilateral upper-limb reduction deficiencies (ULD) compared to typically developing children (TD).MethodsFive children with ULD (3 boys, 2 girls, 8.76 ± 3.37 years of age) and five age- and sex-matched TD children (3 boys, 2 girls, 8.96 ± 3.23 years of age) performed a gross manual dexterity task (Box and Block Test) while measuring brain activity (functional near-infrared spectroscopy; fNIRS).ResultsThere were no significant differences (p = 0.948) in gross dexterity performance between the ULD group with prosthesis (7.23 ± 3.37 blocks per minute) and TD group with the prosthetic simulator (7.63 ± 5.61 blocks per minute). However, there was a significant (p = 0.001) difference in Laterality Index (LI) between the ULD group with prosthesis (LI = − 0.2888 ± 0.0205) and TD group with simulator (LI = 0.0504 ± 0.0296) showing in a significant ipsilateral control for the ULD group. Thus, the major finding of the present investigation was that children with ULD, unlike the control group, showed significant activation in the ipsilateral motor cortex on the non-preferred side using a prosthesis during a gross manual dexterity task.ConclusionsThis ipsilateral response may be a compensation strategy in which the existing cortical representations of the non-affected (preferred) side are been used by the affected (non-preferred) side to operate the prosthesis. This study is the first to report altered lateralization in children with ULD while using a prosthesis.Trial registrationThe clinical trial (ClinicalTrial.gov ID: NCT04110730 and unique protocol ID: IRB # 614-16-FB) was registered on October 1, 2019 (https://clinicaltrials.gov/ct2/show/NCT04110730) and posted on October 1, 2019. The study start date was January 10, 2020. The first participant was enrolled on January 14, 2020, and the trial is scheduled to be completed by August 23, 2023. The trial was updated January 18, 2020 and is currently recruiting
Data analytics and clinical feature ranking of medical records of patients with sepsis
Authors: Chicco Davide , Oneto Luca 
Published: February 2021

AbstractBackgroundSepsis is a life-threatening clinical condition that happens when the patient’s body has an excessive reaction to an infection, and should be treated in one hour. Due to the urgency of sepsis, doctors and physicians often do not have enough time to perform laboratory tests and analyses to help them forecast the consequences of the sepsis episode. In this context, machine learning can provide a fast computational prediction of sepsis severity, patient survival, and sequential organ failure by just analyzing the electronic health records of the patients. Also, machine learning can be employed to understand which features in the medical records are more predictive of sepsis severity, of patient survival, and of sequential organ failure in a fast and non-invasive way.Dataset and methodsIn this study, we analyzed a dataset of electronic health records of 364 patients collected between 2014 and 2016. The medical record of each patient has 29 clinical features, and includes a binary value for survival, a binary value for septic shock, and a numerical value for the sequential organ failure assessment (SOFA) score. We disjointly utilized each of these three factors as an independent target, and employed several machine learning methods to predict it (binary classifiers for survival and septic shock, and regression analysis for the SOFA score). Afterwards, we used a data mining approach to identify the most important dataset features in relation to each of the three targets separately, and compared these results with the results achieved through a standard biostatistics approach.Results and conclusionsOur results showed that machine learning can be employed efficiently to predict septic shock, SOFA score, and survival of patients diagnoses with sepsis, from their electronic health records data. And regarding clinical feature ranking, our results showed that Random Forests feature selection identified several unexpected symptoms and clinical components as relevant for septic shock, SOFA score, and survival. These discoveries can help doctors and physicians in understanding and predicting septic shock. We made the analyzed dataset and our developed software code publicly available online.
High dispersal capacity of Culicoides obsoletus (Diptera: Ceratopogonidae), vector of bluetongue and Schmallenberg viruses, revealed by landscape genetic analyses
Authors: Mignotte Antoine , Garros Claire , Dellicour Simon , Jacquot Maude , Gilbert Marius , Gardès Laetitia , Balenghien Thomas , Duhayon Maxime , Rakotoarivony Ignace , de Wavrechin Maïa , Huber Karine 
Published: February 2021

Abstract
Background
In the last two decades, recurrent epizootics of bluetongue virus and Schmallenberg virus have been reported in the western Palearctic region. These viruses affect domestic cattle, sheep, goats and wild ruminants and are transmitted by native hematophagous midges of the genus Culicoides (Diptera: Ceratopogonidae). Culicoides dispersal is known to be stratified, i.e. due to a combination of dispersal processes occurring actively at short distances and passively or semi-actively at long distances, allowing individuals to jump hundreds of kilometers.

Methods
Here, we aim to identify the environmental factors that promote or limit gene flow of Culicoides obsoletus, an abundant and widespread vector species in Europe, using an innovative framework integrating spatial, population genetics and statistical approaches. A total of 348 individuals were sampled in 46 sites in France and were genotyped using 13 newly designed microsatellite markers.

Results
We found low genetic differentiation and a weak population structure for C. obsoletus across the country. Using three complementary inter-individual genetic distances, we did not detect any significant isolation by distance, but did detect significant anisotropic isolation by distance on a north-south axis. We employed a multiple regression on distance matrices approach to investigate the correlation between genetic and environmental distances. Among all the environmental factors that were tested, only cattle density seems to have an impact on C. obsoletus gene flow.

Conclusions
The high dispersal capacity of C. obsoletus over land found in the present study calls for a re-evaluation of the impact of Culicoides on virus dispersal, and highlights the urgent need to better integrate molecular, spatial and statistical information to guide vector-borne disease control.

Graphical Abstract
Reliability of the Clinical Frailty Scale in very elderly ICU patients: a prospective European study
Authors:   the VIP2 Study Group, Flaatten Hans , Guidet Bertrand , Andersen Finn H. , Artigas Antonio , Cecconi Maurizio , Boumendil Ariane , Elhadi Muhammed , Fjølner Jesper , Joannidis Michael , Jung Christian , Leaver Susannah , Marsh Brian , Moreno Rui , Oeyen Sandra , Nalapko Yuriy , Schefold Joerg C. , Szczeklik Wojciech , Walther Sten , Watson Ximena , Zafeiridis Tilemachos , de Lange Dylan W. 
Published: February 2021

Abstract
Purpose
Frailty is a valuable predictor for outcome in elderly ICU patients, and has been suggested to be used in various decision-making processes prior to and during an ICU admission. There are many instruments developed to assess frailty, but few of them can be used in emergency situations. In this setting the clinical frailty scale (CFS) is frequently used. The present study is a sub-study within a larger outcome study of elderly ICU patients in Europe (the VIP-2 study) in order to document the reliability of the CFS.

Materials and methods
From the VIP-2 study, 129 ICUs in 20 countries participated in this sub-study. The patients were acute admissions ≥ 80 years of age and frailty was assessed at admission by two independent observers using the CFS. Information was obtained from the patient, if not feasible, from the family/caregivers or from hospital files. The profession of the rater and source of data were recorded along with the score. Interrater variability was calculated using linear weighted kappa analysis.

Results
1923 pairs of assessors were included and background data of patients were similar to the whole cohort (n = 3920). We found a very high inter-rater agreement (weighted kappa 0.86), also in subgroup analyses. The agreement when comparing information from family or hospital records was better than using only direct patient information, and pairs of raters from same profession performed better than from different professions.

Conclusions
Overall, we documented a high reliability using CFS in this setting. This frailty score could be used more frequently in elderly ICU patients in order to create a more holistic and realistic impression of the patient´s condition prior to ICU admission.
Substance use and substance use disorder, in relation to COVID-19: protocol for a scoping review
Authors: Kumar Navin , Janmohamed Kamila , Nyhan Kate , Martins Silvia S. , Cerda Magdalena , Hasin Deborah , Scott Jenny , Pates Richard , Ghandour Lilian , Wazaify Mayyada , Khoshnood Kaveh 
Published: February 2021

Abstract
Background
The COVID-19 pandemic is creating severe issues for healthcare and broad social structures, exposing societal vulnerabilities. Among the populations affected by COVID-19 are people engaged in substance use, such as people who smoke; vape (e-cigarette use); use opioids, cannabis, alcohol, or psychoactive prescription drugs; or have a substance use disorder (SUD). Monitoring substance use and SUD during the pandemic is essential, as people who engage in substance use or present with SUD are at greater risk for COVID-19, and the economic and social changes resulting from the pandemic may aggravate SUD. There have been several reviews focused on COVID-19 in relation to substance use and SUD. Reviews generally did not consider on a large range of substance use variants or SUDs. We plan a scoping review that seeks to fill gaps in our current understanding of substance use and SUD, in the COVID-19 era.

Methods
A scoping review focused on substance use and SUD, in relation to COVID-19, will be conducted. We will search (from January 2020 onwards) Cumulative Index to Nursing and Allied Health Literature, Africa-Wide Information, Web of Science Core Collection, Embase, Global Health, WHO Global Literature on Coronavirus Disease Database, WHO Global Index Medicus, PsycINFO, PubMed, Middle Eastern Central Asian Studies, CINAHL Complete, and Sociological Abstracts. Grey literature will be identified using Disaster Lit, Google Scholar, HSRProj, governmental websites, and clinical trials registries (e.g., ClinicalTrial.gov, World Health Organization, International Clinical Trials Registry Platform and International Standard Randomized Con-trolled Trial Number registry). Study selection will conform to Joanna Briggs Institute Reviewers’ Manual 2015 Methodology for JBI Scoping Reviews. Only English language, original studies investigating substance use and SUD, in relation to COVID-19 in all populations and settings, will be considered for inclusion. Two reviewers will independently screen all citations, full-text articles, and abstract data. A narrative summary of findings will be conducted. Data analysis will involve quantitative (e.g., frequencies) and qualitative (e.g., content and thematic analysis) methods.

Discussion
Original research is urgently needed to mitigate the risks of COVID-19 on substance use and SUD. The planned scoping review will help to address this gap.

Systematic review registration
Open Science Framework (osf/io/tzgm5).
MiR-146a-5p targeting SMAD4 and TRAF6 inhibits adipogenensis through TGF-β and AKT/mTORC1 signal pathways in porcine intramuscular preadipocytes
Authors: Zhang Que , Cai Rui , Tang Guorong , Zhang Wanrong , Pang Weijun 
Published: February 2021

AbstractBackgroundIntramuscular fat (IMF) content is a vital parameter for assessing pork quality. Increasing evidence has shown that microRNAs (miRNAs) play an important role in regulating porcine IMF deposition. Here, a novel miRNA implicated in porcine IMF adipogenesis was found, and its effect and regulatory mechanism were further explored with respect to intramuscular preadipocyte proliferation and differentiation.ResultsBy porcine adipose tissue miRNA sequencing analysis, we found that miR-146a-5p is a potential regulator of porcine IMF adipogenesis. Further studies showed that miR-146a-5p mimics inhibited porcine intramuscular preadipocyte proliferation and differentiation, while the miR-146a-5p inhibitor promoted cell proliferation and adipogenic differentiation. Mechanistically, miR-146a-5p suppressed cell proliferation by directly targeting SMAD family member 4 (SMAD4) to attenuate TGF-β signaling. Moreover, miR-146a-5p inhibited the differentiation of intramuscular preadipocytes by targeting TNF receptor-associated factor 6 (TRAF6) to weaken the AKT/mTORC1 signaling downstream of theTRAF6pathway.ConclusionsMiR-146a-5p targetsSMAD4andTRAF6to inhibit porcine intramuscular adipogenesis by attenuating TGF-β and AKT/mTORC1 signaling, respectively. These findings provide a novel miRNA biomarker for regulating intramuscular adipogenesis to promote pork quality.
COVID-19 case fatality risk by age and gender in a high testing setting in Latin America: Chile, March–August 2020
Authors: Undurraga Eduardo A. , Chowell Gerardo , Mizumoto Kenji 
Published: February 2021

AbstractBackgroundEarly severity estimates of coronavirus disease 2019 (COVID-19) are critically needed to assess the potential impact of the ongoing pandemic in different demographic groups. Here we estimate the real-time delay-adjusted case fatality rate across nine age groups by gender in Chile, the country with the highest testing rate for COVID-19 in Latin America.MethodsWe used a publicly available real-time daily series of age-stratified COVID-19 cases and deaths reported by the Ministry of Health in Chile from the beginning of the epidemic in March through August 31, 2020. We used a robust likelihood function and a delay distribution to estimate real-time delay-adjusted case-fatality risk and estimate model parameters using a Monte Carlo Markov Chain in a Bayesian framework.ResultsAs of August 31, 2020, our estimates of the time-delay adjusted case fatality rate (CFR) for men and women are 4.16% [95% Credible Interval (CrI): 4.09–4.24%] and 3.26% (95% CrI: 3.19–3.34%), respectively, while the overall estimate is 3.72% (95% CrI: 3.67–3.78%). Seniors aged 80 years and over have an adjusted CFR of 56.82% (95% CrI: 55.25–58.34%) for men and 41.10% (95% CrI: 40.02–42.26%) for women. Results showed a peak in estimated CFR during the June peak of the epidemic. The peak possibly reflects insufficient laboratory capacity, as illustrated by high test positivity rates (33% positive 7-day average nationally in June), which may have resulted in lower reporting rates.ConclusionsSeverity estimates from COVID-19 in Chile suggest that male seniors, especially among those aged ≥ 70 years, are being disproportionately affected by the pandemic, a finding consistent with other regions. The ongoing pandemic is imposing a high death toll in South America, and Chile has one of the highest reported mortality rates globally thus far. These real-time estimates may help inform public health officials' decisions in the region and underscore the need to implement more effective measures to ameliorate fatality.
Pre-clinical characterisation of E2814, a high-affinity antibody targeting the microtubule-binding repeat domain of tau for passive immunotherapy in Alzheimer’s disease
Authors: Roberts Malcolm , Sevastou Ioanna , Imaizumi Yoichi , Mistry Kavita , Talma Sonia , Dey Madhurima , Gartlon Jane , Ochiai Hiroshi , Zhou Zhi , Akasofu Shigeru , Tokuhara Naoki , Ogo Makoto , Aoyama Muneo , Aoyagi Hirofumi , Strand Kate , Sajedi Ezat , Agarwala Kishan Lal , Spidel Jared , Albone Earl , Horie Kanta , Staddon James M. , de Silva Rohan 
Published: February 2021

AbstractTau deposition in the brain is a pathological hallmark of many neurodegenerative disorders, including Alzheimer’s disease (AD). During the course of these tauopathies, tau spreads throughout the brain via synaptically-connected pathways. Such propagation of pathology is thought to be mediated by tau species (“seeds”) containing the microtubule binding region (MTBR) composed of either three repeat (3R) or four repeat (4R) isoforms. The tau MTBR also forms the core of the neuropathological filaments identified in AD brain and other tauopathies. Multiple approaches are being taken to limit tau pathology, including immunotherapy with anti-tau antibodies. Given its key structural role within fibrils, specifically targetting the MTBR with a therapeutic antibody to inhibit tau seeding and aggregation may be a promising strategy to provide disease-modifying treatment for AD and other tauopathies. Therefore, a monoclonal antibody generating campaign was initiated with focus on the MTBR. Herein we describe the pre-clinical generation and characterisation of E2814, a humanised, high affinity, IgG1 antibody recognising the tau MTBR. E2814 and its murine precursor, 7G6, as revealed by epitope mapping, are antibodies bi-epitopic for 4R and mono-epitopic for 3R tau isoforms because they bind to sequence motif HVPGG. Functionally, both antibodies inhibited tau aggregation in vitro. They also immunodepleted a variety of MTBR-containing tau protein species. In an in vivo model of tau seeding and transmission, attenuation of deposition of sarkosyl-insoluble tau in brain could also be observed in response to antibody treatment. In AD brain, E2814 bound different types of tau filaments as shown by immunogold labelling and recognised pathological tau structures by immunohistochemical staining. Tau fragments containing HVPGG epitopes were also found to be elevated in AD brain compared to PSP or control. Taken together, the data reported here have led to E2814 being proposed for clinical development.