bluuebunny/crossref_metadata_2025_split huggingface dataset:
Liver Transplant Center Size and the Impact on Clinical Outcomes and Resource Utilization
Authors: Alqahtani Saleh A. , Stepanova Maria , Kabbara Khaled W. , Younossi Issah , Mishra Alita , Younossi Zobair 
Published: August 2021

Background.
Prior studies suggest that transplant center volume is associated with liver transplantation (LT) outcomes. We compared patient characteristics and waitlist outcomes among transplant centers in the United States with different volumes.

Methods.
Data for adult waitlisted candidates and LT recipients in the United States between 2008 and 2017 were extracted from the Scientific Registry of Transplant Recipients database. Transplant centers were categorized by transplants/year into tertiles: low-volume centers (LVCs; <20 transplantations/y); medium-volume centers (MVCs; 20–55 transplantations/y); and high-volume centers (HVCs; >55 transplantations/y). Patient characteristics, waitlist outcomes, and factors associated with posttransplantation mortality were compared.

Results.
From 141 centers, 112 110 patients were waitlisted for LT: 6% at LVCs, 26% at MVCs, and 68% at HVCs. Patients listed at LVCs were less likely to have private insurance but had higher Medicaid and Veterans Affairs healthcare rates. Patients at LVCs were less likely to receive LT (47% versus 53% in MVC versus 61% in HVC), had higher transfer rates to other centers, and were more likely to be removed from the waitlist. In competing risk survival analysis, adjusted for center location, MELD score, and clinicodemographic factors, patients listed at an HVC were more likely to receive LT (adjusted hazard ratio:1.30; 95% confidence interval = 1.27-1.33; P < 0.001). Among LT recipients (n = 62 131), receiving a transplant at an LVC was associated with higher post-LT mortality (adjusted hazard ratio: 1.16; 95% confidence interval = 1.05-1.28; P = 0.003).

Conclusions.
Patients at LVCs were less likely to receive a LT and had a higher risk of post-LT death.
Modeling spatiotemporal Aedes aegypti risk in French Guiana using meteorological and remote sensing data
Authors: Bailly Sarah , Machault Vanessa , Beneteau Samuel , Palany Philippe , Girod Romain , Lacaux Jean-Pierre , Quenel Philippe , Flamand Claude 
Published: August 2021

AbstractAlthough the development of vaccines for the prevention of arboviral diseases has been a priority in recent years, prevention strategies continue to depend on vector control. Risk maps at scales appropriate for these strategies can provide valuable information to assess entomological risk levels and guide actions. We used a spatio-temporal modeling approach to predict, at the local scale, the risk of homes potentially harboring Aedes aegypti larvae. The model used integrated larvae risk data collected in the field from September 2011 to February 2013, environmental data obtained from very high spatial resolution Pleiades imagery, and daily meteorological data, collected in the city of Matoury in French Guiana. Various environmental and meteorological conditions were identified as risk or protective factors for the presence of immature stages of Aedes aegypti in homes on a given date and used to produce dynamic maps with high spatial and temporal resolution. Aedes vector risk was modeled between 50 and 200 m, around houses, on a time scale of 3 to 5 days. The resulting model was extrapolated to other municipalities with the same characteristics of urbanization during the 2019-2020 dengue epidemic in French Guiana. This work represents a major opportunity to monitor the evolution of vector risk and constitutes information that could be particularly useful for public health authorities in charge of vector control.
Green spaces, especially forest, linked to lower SARS-CoV-2 infection rates: A one-year nationwide study
Authors: Jiang Bin , Yang Yuwen , Chen Long , Liu Xueming , Wu Xueying , Chen Bin , Webster Chris , Sullivan William C. , Wang JingJing , Lu Yi 
Published: August 2021

AbstractThis study examined the associations between green spaces and one-years’ worth of SARS-CoV- 2 infection rates across all 3,108 counties in the contiguous United States after controlling for multiple categories of confounding factors. We found green spaces at the county level have a significant negative association with infection rates. Among all types of green spaces, forest yields the most consistent and strongest negative association. Sensitivity analyses confirmed the negative association of forest across five urbanicity levels, and the strength of the association increases as disease incidence increases across five time periods. Although forest located in moderately urbanized counties yields the strongest association, the negative pattern of significant associations holds across all five urbanicity levels. A population-weighted analysis revealed that proximity to forest within a moderate walking distance (≤ 1.0–1.4 km) may provide the greatest protection against the risk of infection.
Durability and Cross-Reactivity of Immune Responses Induced by an AS03-Adjuvanted Plant-Based Recombinant Virus-Like Particle Vaccine for COVID-19
Authors: Gobeil Philipe , Pillet Stéphane , Boulay Iohann , Charland Nathalie , Lorin Aurélien , Cheng Matthew P. , Vinh Donald C. , Boutet Philippe , Van Der Most Robbert , Roman François , Angeles Ceregido Maria , Landry Nathalie , D’Aoust Marc-André , Ward Brian J. 
Published: August 2021

AbstractAs the SARS-COV-2 pandemic evolves, what is expected of vaccines extends beyond efficacy to include consideration of both durability and variant cross-reactivity. This report expands on previously reported immunogenicity results from a Phase 1 trial of an AS03-adjuvanted, plant-based coronavirus-like particle (CoVLP) displaying the spike (S) glycoprotein of the ancestral SARS-CoV-2 virus in healthy adults 18-49 years of age (NCT04450004). When humoral and cellular responses against the ancestral strain were evaluated 6 months post-second dose (D201), 100% of vaccinated individuals retained binding antibodies, and ∼95% retained neutralizing antibodies; interferon gamma (IFN-γ) and interleukin 4 (IL-4) responses directed against the ancestral S protein were also still detectable in ∼94% and ∼92% of vaccinees respectively. Variant-specific, cross-reactive neutralizing antibody (NAb) levels were assessed at D42 and D201 using both live wild-type and pseudovirion assays (Alpha, Beta, Gamma) or the wild-type assay alone (Delta, Omicron). In the wild-type assay, broad cross-reactivity was detected against all variants at D42 (100% Alpha and Delta, 94% Beta and Gamma, 74% Omicron). At D201, cross-reactive antibodies were detectable in almost all participants against Alpha, Gamma and Delta variants (94%) and the Beta variant (83%) and in a smaller proportion against Omicron (44%). Results were similar in the pseudovirion assay (D42, 100% cross-reactivity to Alpha and Gamma variants, 95% to Beta variant, D201, 94% for Alpha, Beta and Gamma variants). These data suggest that two doses of 3.75 µg CoVLP+AS03 elicit a durable and cross-reactive response that persists for at least 6 months post-vaccination.
Genetic variants associated with cross-disorder and disorder-specific risk for psychiatric disorders are enriched at epigenetically active sites in peripheral lymphoid cells
Authors: Lynall Mary-Ellen , Soskic Blagoje , Hayhurst James , Schwartzentruber Jeremy , Levey Daniel F. , Pathak Gita A. , Polimanti Renato , Gelernter Joel , Stein Murray B. , Trynka Gosia , Clatworthy Menna R. , Bullmore Ed 
Published: August 2021

AbstractMultiple psychiatric disorders have been associated with abnormalities in both the innate and adaptive immune systems. The role of these abnormalities in pathogenesis, and whether they are driven by psychiatric risk variants, remains unclear. We tested for enrichment of GWAS variants associated with multiple psychiatric disorders (cross-disorder or trans-diagnostic risk), or 5 specific disorders (cis-diagnostic risk), in regulatory elements in immune cells. We used three independent epigenetic datasets representing multiple organ systems and immune cell subsets. Trans-diagnostic and cis-diagnostic risk variants (for schizophrenia and depression) were enriched at epigenetically active sites in brain tissues and in lymphoid cells (T, B and NK cells), especially stimulated CD4+ T cells. There was no evidence for enrichment of either trans-risk or cis-risk variants for schizophrenia or depression in myeloid cells. This suggests a model where stimuli (e.g. infection) activate T cells to unmask the effects of psychiatric risk variants, contributing to the pathogenesis of mental health disorders.
Defective X-gating caused byde novogain-of-function mutations inKCNK3underlies a developmental disorder with sleep apnea
Authors: Sörmann Janina , Schewe Marcus , Proks Peter , Jouen-Tachoire Thibault , Rao Shanlin , Riel Elena B. , Agre Katherine E. , Begtrup Amber , Dean John , Descartes Maria , Fischer Jan , Gardham Alice , Lahner Carrie , Mark Paul R. , Muppidi Srikanth , Pichurin Pavel N. , Porrmann Joseph , Schallner Jens , Smith Kirstin , Straub Volker , Vasudevan Pradeep , Willaert Rebecca , Carpenter Elisabeth P. , Rödström Karin E.J. , Hahn Michael G. , Müller Thomas , Baukrowitz Thomas , Hurles Matthew E. , Wright Caroline F. , Tucker Stephen J. 
Published: August 2021

AbstractSleep apnea is a common disorder that represents a global public health burden.KCNK3encodes TASK-1, a K+channel implicated in the control of breathing, but its link with sleep apnea remains poorly understood. Here we describe a novel developmental disorder with sleep apnea caused by rarede novogain-of-function mutations inKCNK3. The mutations cluster around the ‘X-gate’, a gating motif which controls channel opening, and produce overactive channels that no longer respond to inhibition by G-protein coupled receptor pathways, but which can be inhibited by several clinically relevant drugs. These findings demonstrate a clear role for TASK-1 in sleep apnea and identify possible therapeutic strategies.
Safety and Immunogenicity of CpG 1018 and Aluminium Hydroxide-Adjuvanted SARS-CoV-2 S-2P Protein Vaccine MVC-COV1901: A Large-Scale Double-Blind, Randomised, Placebo-Controlled Phase 2 Trial
Authors: Szu-Min Hsieh , Liu Ming-Che , Chen Yen-Hsu , Lee Wen-Sen , Hwang Shinn-Jang , Cheng Shu-Hsing , Ko Wen-Chien , Hwang Kao-Pin , Wang Ning-Chi , Lee Yu-Lin , Lin Yi-Ling , Shih Shin-Ru , Huang Chung-Guei , Liao Chun-Che , Liang Jian-Jong , Chang Chih-Shin , Chen Charles , Lien Chia En , Tai I-Chen , Lin Tzou-Yien 
Published: August 2021

SummaryBackgroundWe have assessed the safety and immunogenicity of the COVID-19 vaccine MVC-COV1901, a recombinant protein vaccine containing prefusion-stabilized spike protein S-2P adjuvanted with CpG 1018 and aluminium hydroxide.MethodsThis is a phase 2, prospective, randomised, double-blind, placebo-controlled, and multi-centre study to evaluate the safety, tolerability, and immunogenicity of the SARS-CoV-2 vaccine candidate MVC-COV1901. The study comprised 3,844 participants of ≥ 20 years who were generally healthy or with stable pre-existing medical conditions. The study participants were randomly assigned in a 6:1 ratio to receive either MVC-COV1901 containing 15 μg of S-2P protein or placebo containing saline. Participants received two doses of MVC-COV1901 or placebo, administered 28 days apart via intramuscular injection. The primary outcomes were to evaluate the safety, tolerability, and immunogenicity of MVC-COV1901 from Day 1 (the day of first vaccination) to Day 57 (28 days after the second dose). Immunogenicity of MVC-COV1901 was assessed through geometric mean titres (GMT) and seroconversion rates (SCR) of neutralising antibody and antigen-specific immunoglobulin. This clinical trial is registered at ClinicalTrials.gov: NCT04695652.FindingsFrom the start of this phase 2 trial to the time of interim analysis, no vaccine-related Serious Adverse Events (SAEs) were recorded. The most common solicited adverse events across all study participants were pain at the injection site (64%), and malaise/fatigue (35%). Fever was rarely reported (<1%). For all participants in the MVC-COV1901 group, at 28 days after the second dose against wild type SARS-CoV-2 virus, the GMT was 662·3 (408 IU/mL), the GMT ratio was 163·2, and the seroconversion rate was 99·8%.InterpretationMVC-COV1901 shows good safety profiles and promising immunogenicity responses. The current data supports MVC-COV1901 to enter phase 3 efficacy trials and could enable regulatory considerations for Emergency Use Authorisation (EUA).FundingMedigen Vaccine Biologics Corporation and Taiwan Centres for Disease Control.
Analysis of Whole Genome Sequencing in a Cohort of Individuals with PHACE Syndrome Suggests Dysregulation of RAS/PI3K Signaling
Authors: Partan Elizabeth S. , Blei Francine , Chamlin Sarah L. , Davies Olivia M. T. , Drolet Beth A. , Frieden Ilona J. , Karakikes Ioannis , Lin Chien-Wei , Mancini Anthony J. , Metry Denise , Oro Anthony , Stefanko Nicole S. , Sundaram Laksshman , Tutaj Monika , Urban Alexander E. , Wang Kevin C. , Zhu Xiaowei , Sobreira Nara , Siegel Dawn H. 
Published: August 2021

ABSTRACTThe acronym PHACE stands for the co-occurrence of posterior brain fossa malformations, hemangiomas, arterial anomalies, cardiac defects, and eye abnormalities. The majority of patients have a segmental hemangioma and at least one developmental structural anomaly. The etiology and pathogenesis are unknown. Here we discuss the candidate causative genes identified in a de novo analysis of whole genome sequencing of germline samples from 98 unrelated trios in which the probands had PHACE, all sequenced as part of the Gabriella Miller Kids First Pediatric Research Program. A g:Profiler pathway analysis of the genes with rare, de novo variants suggested dysregulation of the RAS/MAPK and PI3K/AKT pathways that regulate cell growth, migration, and angiogenesis. These findings, along with the developmental anomalies and the vascular birthmark, support including PHACE within the RASopathy family of syndromes.
Occupational risk of SARS-CoV-2 infection and reinfection during the second pandemic surge: a cohort study
Authors: Leidi Antonio , Berner Amandine , Dumont Roxane , Dubos Richard , Koegler Flora , Piumatti Giovanni , Vuilleumier Nicolas , Kaiser Laurent , Balavoine Jean-François , Trono Didier , Pittet Didier , Chappuis François , Kherad Omar , Courvoisier Delphine , Azman Andrew S , Zaballa María-Eugenia , Guessous Idris , Stringhini Silvia ,   SEROCoV-WORK+ study group
Published: August 2021

AbstractObjectivesThis cohort study including essential workers, assessed the□risk and incidence of SARS-CoV-2□infection during the second surge of COVID-19 according to baseline serostatus and occupational sector.MethodsEssential workers were selected from a seroprevalence survey cohort in Geneva, Switzerland and were linked to a state centralized registry compiling SARS-CoV-2 infections. Primary outcome was the number of virologically-confirmed infections from serological assessment (between May and September 2020) to January 25, 2021, according to baseline antibody status and stratified by three pre-defined occupational groups (occupations requiring sustained physical proximity, involving brief regular contact or others). Secondary outcomes included the incidence of infection.Results10457 essential workers were included (occupations requiring sustained physical proximity accounted for 3057 individuals, those involving regular brief contact, 3645, and 3755 workers were classified under “Other essential occupations”). After a follow-up period of over 27 weeks, 5 (0.6%) seropositive and 830 (8.5%) seronegative individuals had a positive SARS-CoV-2 test, with an incidence rate of 0.2 (95% CI 0.1 to 0.6) and 3.2 (95% CI 2.9 to 3.4) cases per person-week, respectively. Incidences were similar across occupational groups. Seropositive essential workers had a 93% reduction in the hazard (HR of 0.07, 95% CI 0.03 to 0.17) of having a positive test during follow-up with no significant between-occupational group difference.ConclusionsA ten-fold reduction in the hazard of being virologically tested positive was observed among anti-SARS-CoV-2 seropositive essential workers regardless of their sector of occupation, confirming the seroprotective effect of a previous SARS-CoV2 exposure at least six months after infection.Key messagesWhat is already known about this subject?Risk of SARS-CoV-2 reinfection is low in the general population and among healthcare workers.What are the new findings?A ten-fold reduction of risk of being virologically tested positive reinfection is observed among anti-SARS-CoV-2 seropositive essential workers of different activity sectors, regardless of their occupation-related risk of exposure.How might this impact on policy or clinical practice in the foreseeable future?Vaccination could be delayed in individuals with previous history of SARS-CoV-2 infection with serologic confirmation, regardless of their occupational exposure. These observations need to be confirmed for new SARS-CoV-2 variants.
Awake Prone Position in Hypoxemic Patients with Coronavirus Disease 19 (COVI-PRONE): A Study protocol and Statistical Analysis Plan for Randomized Clinical Trial
Authors: Duhailib Zainab Al , Arabi Yaseen M , Culgin Sarah , Weatherald Jason , Parhar Ken Kuljit S. , Nelson Kate , Tamim Hani , Alhazzani Waleed ,   the COVI-PRONE Trial investigators
Published: August 2021

AbstractBackgroundCoronavirus disease 2019 (COVID-19), may progress to respiratory failure requiring invasive mechanical ventilation. Due to ventilator shortage and healthcare systems strain, affordable interventions such as awake prone positioning has been used to improve oxygenation, however, the effect of this intervention on patient-important outcomes is uncertain. The COVI-PRONE trial aims to determine if awake prone positioning in hypoxemic COVID-19 patients reduces the need for invasive mechanical ventilation.Study designA pragmatic, multicenter, international, parallel-group, and stratified randomized controlled trial, aiming to enrol 400 hospitalized adults with COVID-19.ParticipantsThe target population is hospitalized adults with confirmed or suspected COVID-19, hypoxemia that requires ≥40% oxygen or ≥ 5 L/min by nasal cannula, and abnormal chest x-ray. We will exclude patients with any of the following: immediate need for intubation; altered mental status; contraindication to prone positioning; hemodynamic instability; body mass index > 40 kg/m2; third trimester pregnancy; do not intubate status; previous enrolment or intubation within the same hospital admission; and prone positioning for more than one day prior to randomization.Study intervention and controlFollowing informed a priori or deferred consent, eligible patients will be centrally randomized to either the intervention arm (prone positioning) or standard of care (no prone positioning). Patients randomized to the prone position will be required to either self-prone or assist-prone for a total of eight to ten hours per day until they meet pre-specified stopping criteria.Study outcomesThe primary outcome is invasive mechanical ventilation at 30-days of randomization. Other outcomes include mortality at 60 days, invasive and non-invasive mechanical ventilation free days at 30 days, hospital length of stay at 60 days, days alive and outside of the hospital at 60 days, complications of proning, and serious adverse events.
Association of VEGF and KDR polymorphisms with the development of schizophrenia
Authors: Saoud Hana , Aflouk Youssef , Ben Afia Amira , Gaha Lotfi , Bel Hadj Jrad Besma 
Published: August 2021

AbstractAimSeveral approaches indicate different blood flow disturbances in schizophrenia (Scz). Vascular endothelial growth factor (VEGF) is widely recognized as one of the key molecules implicated in the angiogenesis process through mainly its receptor KDR. The current work was designed to investigate the potential association between three polymorphisms (rs699947; rs833061 and rs3025039) in VEGF gene and two SNPs (rs2305948 and rs1870377) within KDR gene and predisposition to Scz among the Tunisian population.MethodsWe carried-out a case-control study composed of 200 schizophrenic patients and 200 healthy subjects using RFLP-PCR.ResultsOf all analyzed polymorphisms, only rs3025039, rs833061 and rs1870377 showed a significant risk for Scz. Following the stratified analysis, rs833061 was more prevalent among undifferentiated form. Yet, rs1870377 was especially correlated with paranoid subtype. We found also that rs699947 and rs833061 had an impact on patients’ symptomatology. Haplotype analysis unveiled a strong LD between rs833061 and rs3025039 only for undifferentiated patients. Moreover, the -2578/-460/+936 CTT haplotype, with only one mutated allele +936T, conferred a high risk to Scz and, in particular, to undifferentiated and paranoid forms. Among the last-mentioned subgroup, we noticed another overrepresented haplotype (ATT). Furthermore, the +1192/+1719 GT haplotype carrying the minor allele +1719T displayed increased frequencies in schizophrenics as well as in paranoid patients.ConclusionOur results show that all SNPs associated with the development or the severity of schizophrenia, were subsequently correlated with a decrease in the VEGF levels or influence VEGFR-2 binding affinity. Nevertheless, these data need to be strengthened by further independent analyses.
The Impact of Climate Change on the Prevalence of Mental Illness Symptoms
Authors: Monsour Molly , Clarke-Rubright Emily , Lieberman-Cribbin Wil , Timmins Christopher , Taioli Emanuela , Schwartz Rebecca M. , Corley Samantha S. , Laucis Anna M. , Morey Rajendra A. 
Published: August 2021

ABSTRACTBackgroundThe repercussions of climate change threaten the population with an increased prevalence of extreme climate events. We explored the impact of climate change induced sea level rise (SLR) and tropical cyclone (TC) exposure on mental illness symptom prevalence.MethodsUsing three datasets, TC exposure scores were calculated for each subject to determine how exposure affects posttraumatic stress disorder (PTSD), anxiety, and major depressive disorder (MDD) symptom prevalence. Inundation mapping of various SLR and storm surge (SS) scenarios were performed for the susceptible region of Miami-Dade and Broward counties to determine the population impact of flooding.ResultsWe found an elevated risk of mental illness symptoms from exposure to more high-intensity TCs and identified demographic variables that may contribute to this risk. Furthermore, inundation mapping demonstrated severe and widespread impact of SLR and SS on the mental health of communities.LimitationsThis study did not include data directly measuring comorbidity, resilience, preparedness, or ability to adapt to climate change. Also, multiple imputation using chained equations may have been imperfect. Finally, when conducting inundation mapping, static mapping may overestimate flooding severity.ConclusionThe impacts of climate change have been frequently studied in terms of physical health, natural disaster prevalence, and economic impacts, but rarely on mental health burden. However, it is vital that national, state, and local governments develop and deploy plans to address mental health needs along with expenditures for protecting infrastructure, the economy, and physical health from the combined effects of SLR and climate change-induced natural disasters.