bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiac Inflammation after COVID-19 mRNA Vaccines: A Global Pharmacovigilance Analysis
Authors: Chouchana Laurent , Blet Alice , Al-Khalaf Mohammad , Kafil Tahir S. , Nair Girish , Robblee James , Drici Milou-Daniel , Valnet-Rabier Marie-Blanche , Micallef Joëlle , Salvo Francesco , Treluyer Jean-Marc , Liu Peter P. 
Published: August 2021

ABSTRACTBackgroundTo counter the COVID-19 pandemic, mRNA vaccines, namely tozinameran and elasomeran, have been authorized in several countries. These next generation vaccines have shown high efficacy against COVID-19 and demonstrated a favorable safety profile. As widespread vaccinations efforts are taking place, incidents of myocarditis and pericarditis cases following vaccination have been reported. This safety signal has been recently confirmed by the European Medicine Agency and the U.S. Food and Drug Administration.This study aimed to investigate and analyze this safety signal using a dual pharmacovigilance database analysis.MethodsThis is as an observational study of reports of inflammatory heart reactions associated with mRNA COVID-19 vaccines reported in the World Health Organization’s global individual case safety report database (up to June 30th2021), and in the U.S. Vaccine Adverse Event Reporting System (VAERS, up to May 21st2021). Cases were described, and disproportionality analyses using reporting odds-ratios (ROR) and their 95% confidence interval (95%CI) were performed to assess relative risk of reporting according to patient sex and age.ResultsAt a global scale, the inflammatory heart reactions most frequently reported were myocarditis (1241, 55%) and pericarditis (851, 37%), the majority requiring hospitalization (n=796 (64%)). Overall, patients were young (median age 33 [21-54] years). The main age group was 18-29 years old (704, 31%), and mostly males (1555, 68%). Pericarditis onset was delayed compared to myocarditis with a median time to onset of 8 [3-21] vs. 3 [2-6] days, respectively (p=0.001). Regarding myocarditis, an important disproportionate reporting in males (ROR, 9.4 [8.3-10.6]) as well as in adolescents (ROR, 22.3 [19.2-25.9]) and 18-29 years old (ROR, 6.6 [5.9-7.5]) compared to older patients were observed.ConclusionsThe inflammatory heart reactions, namely myocarditis and pericarditis, have been reported world-wide shortly following COVID-19 mRNA vaccination. An important disproportionate reporting among adolescents and young adults, particularly in males, was observed especially for myocarditis. Guidelines must take this specific risk into account and to optimize vaccination protocols according to sex and age. While the substantial benefits of COVID-19 vaccination still prevail over risks, clinicians and the public should be aware of these reactions and seek appropriate medical attention.
Patient-centered care, advance care planning, and treatment preferences among home medical care patients in Japan: The ZEVIOUS study
Authors: Hayashi Shinu , Shirahige Yutaka , Tsugihashi Yukio , Iida Hidekazu , Hirose Misaki , Yasunaka Masakazu , Kurita Noriaki ,   the ZEVIOUS group
Published: August 2021

AbstractBackgroundIt remains unclear how both the quality of patient-centered care and the patient’s illness affect advance care planning (ACP) in primary care settings. Identifying the facilitators and barriers to ACP in primary care settings has become a growing scientific and clinical challenge.ObjectiveTo examine the association between the quality of primary care and ACP preparedness among patients. Additionally, to investigate whether ACP preparedness and the patient’s illness are associated with the expression of future treatment preferences.DesignMulticenter cross-sectional study.ParticipantsAdult Japanese patients receiving home medical care.Main MeasuresA survey was run to assess consideration of ACP by patients and expression of future treatment preferences. The quality of primary care, which reflects patient centeredness, was assessed with the Japanese version of the Primary Care Assessment Tool– Short Form. Information on the clinical conditions that required home medical care was collected from physicians.Key ResultsOf 194 patients using 29 home medical services, 62 patients (32%) showed signs of ACP preparedness, and 153 patients (78%) expressed their treatment preferences. In a multivariable-adjusted generalized estimating equation, primary care quality was associated with ACP preparedness (per 10-point increase, adjusted OR: 1.96, 95% CI: 1.51–2.56). However, we found insufficient evidence to support that ACP preparedness was associated with a lower incidence of non-expression of treatment preferences (adjusted OR: 1.02, 95% CI 0.49–2.12). In contrast, having cancer was associated with a lower incidence of non-expression of treatment preferences (adjusted OR: 0.12, 95% CI: 0.01–0.995).ConclusionsAt a minimum, patient centeredness in home medical care facilitates must ensure the initiation of ACP preparedness. To understand the association between ACP preparedness and expression of treatment preferences, further efforts are warranted to clarify the quality and content of ACP preparedness simultaneously with the patient’s illness.
Early Reduction of SARS-CoV-2 Replication in Bronchial Epithelium by Kinin B2 Receptor Antagonism
Authors: Jakwerth Constanze A. , Feuerherd Martin , Guerth Ferdinand M. , Oelsner Madlen , Schellhammer Linda , Giglberger Johanna , Pechtold Lisa , Jerin Claudia , Kugler Luisa , Mogler Carolin , Haller Bernhard , Erb Anna , Wollenberg Barbara , Spinner Christoph D. , Buch Thorsten , Protzer Ulrike , Schmidt-Weber Carsten B. , Zissler Ulrich M. , Chaker Adam M. 
Published: August 2021

ABSTRACTBackgroundSARS-CoV2 has evolved to enter the host via the ACE2 receptor which is part of the Kinin-kallirein pathway. This complex pathway is only poorly understood in context of immune regulation but critical to control infection. This study examines SARS-CoV2 infection and epithelial mechanisms of the kinin-kallikrein system at the kinin B2 receptor level in SARS-CoV-2 infection that is of direct translational relevance.MethodsFrom acute SARS-CoV-2-positive patients and -negative controls, transcriptomes of nasal brushings were analyzed. Primary airway epithelial cells (NHBEs) were infected with SARS-CoV-2 and treated with the approved B2R antagonist icatibant. SARS-CoV-2 RNA RT-qPCR, cytotoxicity assays, plaque assays and transcriptome analyses were performed. The treatment effect was further studied in a murine airway inflammation model in vivo.ResultsHere, we report a broad and strong upregulation of kallikreins and the kinin B2 receptor (B2R) in the nasal mucosa of acutely symptomatic SARS-CoV-2-positive patients. A B2R antagonist impeded SARS-CoV-2 replication and spread in NHBEs, as determined in plaque assays on Vero E6 cells. B2R antagonism reduced the expression of SARS-CoV-2 entry receptor ACE2 in vitro and in a murine airway inflammation model in vivo. In addition, it suppressed gene expression broadly, particularly genes involved in G-protein-coupled-receptor signaling and ion transport.ConclusionsIn summary, this study provides evidence that treatment with B2R antagonists protects airway epithelial cells from SARS-CoV-2 by inhibiting its replication and spread, through the reduction of ACE2 levels and the interference with several cellular signaling processes. Future clinical studies need to shed light on the airway protection potential of approved B2R antagonists, like icatibant, in the treatment of early-stage COVID-19.
Gut microbiome activity predicts risk of type 2 diabetes and metformin control in a large human cohort
Authors: Shen Nan , Dimitrova Nevenka , Ho Cleo H. , Torres Pedro J. , Camacho Francine R , Cai Ying , Vuyisich Momchilo , Tanton Damon , Banavar Guruduth 
Published: August 2021

AbstractRecognizing and treating the early stages of type 2 diabetes (T2D) is the most cost effective way to decrease prevalence, before heart disease, renal disease, blindness, and limb amputation become inevitable. In this study, we employ high resolution gut microbiome metatranscriptomic analysis of stool samples from 53,970 individuals to identify predictive biomarkers of type 2 diabetes progression and potential for diagnosis and treatment response. The richness of the metatranscriptomic data enabled us to develop a T2D risk model to delineate individuals with glycemic dysregulation from those within normal glucose levels, with ROC-AUC of 0.83+/-0.04. This risk score can predict the probability of having insulin dysregulation before detecting high glycated hemoglobin (HbA1c), the standard-of-care marker for prediabetes and diabetes. Additionally, a machine learning model was able to distinguish novel metatranscriptomic features that segregate patients who receive metformin and are able to control their HbA1c from those who do not. These discoveries set the stage for developing multiple therapeutic avenues for prevention and treatment of T2D.
Triaging and Referring In Adjacent General and Emergency Departments (the TRIAGE trial): a cluster randomised controlled trial
Authors: Morreel Stefan , Philips Hilde , De Graeve Diana , Monsieurs Koenraad G , Kampen Jarl K , Meysman Jasmine , Lefevre Eva , Verhoeven Veronique 
Published: August 2021

AbstractObjectivesTo determine the effectiveness and safety of a tool diverting low urgency patients eligible for primary care from an emergency department (ED) to the adjacent general practitioner cooperative (GPC).MethodsUnblinded, randomised controlled trial with weekends serving as clusters (three intervention clusters for each control). The intervention was nurse-led triage using a new tool assigning patients to either ED or GPC. During intervention weekends, patients were encouraged to follow this assignment while it was not communicated to the patients during control weekends (they remained at the ED). The primary outcome was the proportion of patients assigned to and handled by the GPC during intervention weekends. The trial was randomised for the secondary outcome: the proportion of patients assigned to the GPC during intervention and control weekends. Additional outcomes were association of these outcomes with possible confounders (study tool parameters, nurse, and patient characteristics), proportion of patients referred back to the ED by the GPC, hospitalisations, and performance of the study tool to detect primary care eligible patients (with the opinion of the treating physician as the gold standard).ResultsIn the intervention group, 838/6374 patients (13.3%, 95% CI 12.5 to 14.2) were assigned to the GPC (secondary outcome), in the control group 431/1744 (24.7%, 95% CI 22.7 to 26.8). In the intervention group, 599/6374 patients (9.5%, 95% CI 8.8 to 10.3) experienced the primary outcome which was influenced by the chosen MTS presentational flowchart, patient’s age, and the nurse. 24/599 patients (4.0%, 95% CI 2.7 to 5.9) patients were referred back to the ED of which three were hospitalised. Positive and negative predictive values of the studied tool during intervention weekends were 0.96 (95%CI 0.94 to 0.97) and 0.60 (95% CI 0.58 to 0.62). Out of the patients assigned to the GPC, 2.4% (95% CI 1.7 to 3.4) were hospitalised.ConclusionsED nurses using a new tool safely diverted 9.5% of the included patients to primary care.ClinicalTrials.gov IdentifierNCT03793972FundingResearch Foundation – Flanders (FWO)
Comparison of Demographic and Diagnostic Markers in New Onset Pediatric Type 1 and Type 2 Diabetes
Authors: Nieto Teresa , Castillo Beatriz , Nieto Jacobo , Redondo Maria J. 
Published: August 2021

AbstractPurposeType 1 diabetes (T1D) is the most common type of diabetes in children, but the frequency of type 2 diabetes (T2D) is increasing rapidly. Classification of diabetes is based on a constellation of features that are typical of each type. We aimed to compare demographic, clinical and laboratory characteristics at diabetes diagnosis in pediatric T1D and T2D.MethodsWe studied children who attended a large academic hospital in Houston, Texas (USA) with a new diagnosis of T2D (n=753) or T1D (n=758). We compared age, sex, race/ethnicity, presence of obesity, glucose, hemoglobin A1c, islet autoantibody positivity, C-peptide, and presence of diabetic ketoacidosis (DKA) at diabetes diagnosis.ResultsAt diagnosis of diabetes, children with T2D, compared with those with T1D, were older (13.6 vs 9.7% years old), more likely females (63.2% vs 47.8%), of racial/ethnic minority (91.1%% versus 42.3%) and obese (90.9% vs 19.4%), and were less likely to have DKA (7.8% vs 35.0%) and diabetes autoantibodies (5.5% vs 95.4%). Children with T2D also had significantly less marked elevation of glucose and hemoglobin A1c, and lower C-peptide levels (all comparisons, p<0.0001). In multiple logistic regression analysis, older age, racial/ethnic minority, obesity, higher C-peptide and negative islet autoantibodies were independently associated with T2D (all, p<0.05) while sex, glucose, hemoglobin A1c and DKA were not (model p<0.0001).ConclusionsThere are important demographic, clinical and laboratory differences between T1D and T2D in children. However, none of the characteristics was unique to either diabetes type, which poses challenges to diabetes classification at diagnosis.
Public opinion on global distribution of COVID-19 vaccines: evidence from two nationally representative surveys in Germany and the United States
Authors: Klumpp Matthias , Monfared Ida G. , Vollmer Sebastian 
Published: August 2021

AbstractBackgroundDespite ongoing calls for more equity in the global distribution of COVID-19 vaccines, there remains a great disparity between high- and low- or middle-income countries. Based on the principles of distributive justice, we assessed the public opinion on this issue in the United States and Germany as examples for high-income countries with a high potential for redistribution.MethodsWe conducted representative surveys among the adult population in the United States (N=1,000) and Germany (N=1,003) in June 2021 using two instances of an analytic hierarchy process (AHP) to elicit how the public weighs different principles and criteria according to which the vaccines should be allocated as well as discrete choice experiments to split a limited supply of vaccine doses between a hypothetical high-income and low-income country.FindingsIn the first AHP, respondents in the United States and Germany gave weight to “medical urgency” by 37·4% (37·2-37·5) and 49·4% (49·2-49·5), “equal access for all” 32·7% (32·6-32·8) and 25·4% (25·2-25·5), “production contribution” 13·7% (13·6-13·8) and 13·3% (13·2-13·4), and “free market rules” 16·3% (16·2-16·4) and 12·0% (11·9-12·1), respectively. In the discrete choice experiment responds in the United States split available vaccine doses such that the low-income country on average received 53·9 percent (95% CI: 52·6-55·1). For Germany this number was 57·5 percent (95% CI: 56·3-58·7). The low-income country had three times as many inhabitants as the high-income country. When facing the dilemma where a vulnerable family member was waiting for a vaccine as opposed to when there was no clear self-interest, 20·7% (18·2-23·3) of respondents in the United States and 18·2% (15·8-20·6) in Germany reduced the amount they allocated to the low-income countryInterpretationsThe public in the United States and Germany favours utilitarian and egalitarian distribution principles of vaccines for COVID-19 over the currently prevailing libertarian or meritocratic principles. This implies that political approaches and decision favouring higher levels of redistribution would be supported by the public opinion in these two countries.FundingGerman Research Foundation DFG RTG 1723.
Serological survey of SARS-CoV-2 incidence conducted at a rural West Virginia hospital
Authors: Horspool Alexander M. , Russ Brynnan P. , Wolf M. Allison , Kang Jason , Blackwood Catherine B. , Hall Jesse M. , Wong Ting Y. , DeJong Megan A. , Bitzer Graham , Bevere Justin R. , Eggleston Robert , Stewart Anita , Costello Lisa , Welch Shelley , Kieffer Theodore , Hodder Sally , Damron F. Heath 
Published: August 2021

ABSTRACTThe SARS-CoV-2 pandemic has affected all types of global communities. Differences in urban and rural environments have led to varying levels of transmission within these subsets of the population. To fully understand the prevalence and impact of SARS-CoV-2 it is critical to survey both types of community. This study establishes the prevalence of SARS-CoV-2 in a rural community: Montgomery, West Virginia. Approximately 10% of participants exhibited serological or PCR-based results indicating exposure to SARS-CoV-2 within 6 months of the sampling date. Quantitative analysis of IgG levels against SARS-CoV-2 receptor binding domain (RBD) was used to stratify individuals based on antibody response to SARS-CoV-2. A significant negative correlation between date of exposure and degree of anti-SARS-CoV-2 RBD IgG (R2 = 0.9006) was discovered in addition to a correlation between neutralizing anti-SARS-CoV-2 antibodies (R2 = 0.8880) and days post exposure. Participants were confirmed to have normal immunogenic profiles by determining serum reactivity B. pertussis antigens commonly used in standardized vaccines. No significant associations were determined between anti-SARS-CoV-2 RBD IgG and age or biological sex. Reporting of viral-like illness symptoms was similar in SARS-CoV-2 exposed participants greater than 30 years old (100% reporting symptoms 30-60 years old, 75% reporting symptoms >60 years old) in contrast to participants under 30 years old (25% reporting symptoms). Overall, this axnalysis of a rural population provides important information about the SARS-CoV-2 pandemic in small rural communities. The study also underscores the fact that prior infection with SARS-CoV-2 results in antibody responses that wane over time which highlights the need for vaccine mediated protection in the absence of lasting protection.
COVID-19 Infection, Admission and Death Amongst People with Rare Autoimmune Rheumatic Disease in England. Results from the RECORDER Project
Authors: Rutter Megan , Lanyon Peter C. , Grainge Matthew J. , Hubbard Richard , Peach Emily , Bythell Mary , Stilwell Peter , Aston Jeanette , Stevens Sarah , Pearce Fiona A. 
Published: August 2021

AbstractObjectivesTo calculate the rates of COVID-19 infection and COVID-19-related death among people with rare autoimmune rheumatic diseases (RAIRD) during the first wave of the COVID-19 pandemic in England compared to the general population.MethodsWe used Hospital Episode Statistics to identify all people alive 01 March 2020 with ICD-10 codes for RAIRD from the whole population of England. We used linked national health records (demographic, death certificate, admissions and PCR testing data) to calculate rates of COVID-19 infection and death up to 31 July 2020. Our primary definition of COVID-19-related death was mention of COVID-19 on the death certificate. General population data from Public Health England and the Office for National Statistics were used for comparison. We also describe COVID-19-related hospital admissions and all-cause deaths.ResultsWe identified a cohort of 168,680 people with RAIRD, of whom 1874 (1.11%) had a positive COVID-19 PCR test. The age-standardised infection rate was 1.54 (95% CI 1.50-1.59) times higher than in the general population. 713 (0.42%) people with RAIRD died with COVID-19 on their death certificate and the age-sex-standardised mortality rate for COVID-19-related death was 2.41 (2.30 – 2.53) times higher than in the general population. There was no evidence of an increase in deaths from other causes in the RAIRD population.ConclusionsDuring the first wave of COVID-19 in England, people with RAIRD had a 54% increased risk of COVID-19 infection and more than twice the risk of COVID-19-related death compared to the general population. These increases were seen despite shielding policies.Key MessagesPeople with RAIRD were at increased risk of COVID-19 infection during the first wave.Compared to the general population, they had over twice the risk of COVID-19-related death.These increased risks were seen despite shielding policies in place in England.
Expression Atlas of Avian Neural Crest Proteins: Neurulation to Migration
Authors: Monroy Brigette Y. , Adamson Carly J. , Camacho-Avila Alexis , Guerzon Christian N. , Echeverria Camilo V. , Rogers Crystal D. 
Published: August 2021

ABSTRACTNeural crest (NC) cells are a dynamic population of embryonic stem cells that create various adult tissues in vertebrate species including craniofacial bone and cartilage and the peripheral and enteric nervous systems. NC development is a conserved and complex process that is controlled by a tightly regulated gene regulatory network (GRN) of morphogens, transcription factors, and cell adhesion proteins. While multiple studies have characterized the expression of several GRN factors in single species, a comprehensive protein analysis that directly compares expression across development is lacking. To address this, we used three closely related avian models, Gallus gallus (chicken), Coturnix japonica (Japanese quail), and Pavo cristatus (Indian peafowl), to compare the localization and timing of four GRN transcription factors, PAX7, SOX9, SNAI2, and SOX10 from the onset of neurulation to migration. While the spatial expression of these factors is largely conserved, we find that quail NC cells express SOX9, SNAI2, and SOX10 proteins at the equivalent of earlier developmental stages than chick and peafowl. In addition, quail NC cells migrate farther and more rapidly than the larger organisms. These data suggest that despite a conservation of NC GRN players, differences in the timing of NC development between species remain a significant frontier to be explored with functional studies.Graphical abstractComparative analysis of neural crest (NC) protein spatiotemporal localization in quail, chick, and peafowl embryos.Avian embryos were incubated for different lengths of time to achieve the same developmental stage marked by somite number (somite stage, SS) as described by Hamburger and Hamilton (HH) in 1951. (A) Quail, (B) chick, and (C) peafowl embryos were collected for immunohistochemistry (IHC) to define and quantify the timeline of NC protein expression. We specifically focused on the expression of PAX7, SNAI2, SOX9, and SOX10 proteins. We determined that neural crest development as marked by common NC-specific proteins differs between species. Rather than similar, but scaled development, each organism has its own NC developmental timeline. Quail embryos develop much more rapidly than their counterparts, chick and peafowl. Further, chick and peafowl amino acid sequences are more similar to each other than they are to quail.
Evidence of multiple genome duplication events inMytilusevolution
Authors: Corrochano-Fraile Ana , Davie Andrew , Carboni Stefano , Bekaert Michaël 
Published: August 2021

ABSTRACTMolluscs remain one significantly under-represented taxa amongst available genomic resources, despite being the second-largest animal phylum and the recent advances in genomes sequencing technologies and genome assembly techniques. With the present work, we want to contribute to the growing efforts by filling this gap, presenting a new high-quality reference genome forMytilus edulisand investigating the evolutionary history within the Mytilidae family, in relation to other species in the class Bivalvia.Here we present, for the first time, the discovery of multiple whole genome duplication events in the Mytilidae family and, more generally, in the class Bivalvia. In addition, the calculation of evolution rates for three species of the Mytilinae subfamily sheds new light onto the taxa evolution and highlights key orthologs of interest for the study ofMytilusspecies divergences.The reference genome presented here will enable the correct identification of molecular markers for evolutionary, population genetics, and conservation studies. Mytilidae have the capability to become a model shellfish for climate change adaptation using genome-enabled systems biology and multi-disciplinary studies of interactions between abiotic stressors, pathogen attacks, and aquaculture practises.