bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sequencing of 19,219 exomes identifies a low-frequency variant inFKBP5promoter predisposing to high myopia in a Han Chinese population
Authors: Su Jianzhong , Yuan Jian , Xu Liangde , Xing Shilai , Sun Mengru , Yao Yinghao , Ma Yunlong , Chen Fukun , Jiang Longda , Li Kai , Yu Xiangyi , Xue Zhengbo , Zhang Yaru , Fan Dandan , Zhang Ji , Liu Hui , Liu Xinting , Zhang Guosi , Wang Hong , Zhou Meng , Lyu Fan , An Gang , Yu Xiaoguang ,   Myopia Associated Genetics and Intervention Consortium, Xue Yuanchao , Yang Jian , Qu Jia 
Published: September 2022

SUMMARYHigh myopia (HM) is one of the leading causes of visual impairment and blindness worldwide. Here, we report a whole-exome sequencing (WES) study in 9,613 HM cases and 9,606 controls of Han Chinese ancestry to pinpoint HM-associated risk variants. Single-variant association analysis identified three novel genetic loci associated with HM, including an East Asian ancestry-specific low-frequency variant (rs533280354) inFKBP5. Multi-ancestry meta-analysis with WES data of 2,696 HM cases and 7,186 controls of European ancestry from the UK Biobank discerned a novel European ancestry-specific rare variant inFOLH1. Functional experiments revealed a mechanism whereby a single G to A transition at rs533280354 disrupted the binding of transcription activator KLF15 to the promoter ofFKBP5, resulting in decreased transcription ofFKBP5. Furthermore, burden tests showed a significant excess of rare protein-truncating variants among HM cases involved in retinal blood vessel morphogenesis and neurotransmitter transport.
Using genome-wide association results to identify drug repurposing candidates
Authors: Bell Nathaniel , Uffelmann Emil , van Walree Eva , de Leeuw Christiaan , Posthuma Danielle 
Published: September 2022

AbstractDrug repurposing may provide a solution to the substantial challenges facingde novodrug development. Given that 66% of FDA-approved drugs in 2021 were supported by human genetic evidence, drug repurposing methods based on genome wide association studies (GWAS), such as drug gene-set analysis, may prove an efficient way to identify new treatments. However, to our knowledge, drug gene-set analysis has not been tested in non-psychiatric phenotypes, and previous implementations may have contained statistical biases when testing groups of drugs. Here, 1201 drugs were tested for association with hypercholesterolemia, type 2 diabetes, coronary artery disease, asthma, schizophrenia, bipolar disorder, Alzheimer’s disease, and Parkinson’s disease. We show that drug gene-set analysis can identify clinically relevant drugs (e.g., simvastatin for hypercholesterolemia [p= 2.82E-06]; mitiglinide for type 2 diabetes [p= 2.66E-07]) and drug groups (e.g., C10A for coronary artery disease [p =2.31E-05]; insulin secretagogues for type 2 diabetes [p= 1.09E-11]) for non-psychiatric phenotypes. Additionally, we demonstrate that when the overlap of genes between drug-gene sets is considered we find no groups containing approved drugs for the psychiatric phenotypes tested. However, several drug groups were identified for psychiatric phenotypes that may contain possible repurposing candidates, such as ATC codes J02A (p= 2.99E-09) and N07B (p= 0.0001) for schizophrenia. Our results demonstrate that clinically relevant drugs and groups of drugs can be identified using drug gene-set analysis for a number of phenotypes. These findings have implications for quickly identifying novel treatments based on the genetic mechanisms underlying diseases.
Racial/ethnic disparities in cardiovascular disease mortality attributable to long-term PM2.5exposure in the United States from 2001 to 2016
Authors: Ma Yiqun , Zang Emma , Opara Ijeoma , Lu Yuan , Krumholz Harlan M. , Chen Kai 
Published: September 2022

AbstractBackgroundThe average concentration of fine particulate matter (PM2.5) has decreased in the U.S. in recent years. However, the health benefits of this improvement among different racial/ethnic groups are not known. This study aimed to estimate the associations between long-term exposure to ambient PM2.5and cause-specific cardiovascular disease (CVD) mortality rate and assess the PM2.5-attributable CVD deaths in non-Hispanic White, non-Hispanic Black, and Hispanic people across all counties in the contiguous U.S. from 2001 to 2016.MethodsUsing nationwide CVD mortality data for all ages obtained from National Center for Health Statistics, this study applied interactive fixed effects models to estimate the associations between 12-month moving average of PM2.5concentrations and monthly age-adjusted CVD mortality rates by race/ethnicity, controlling for both measured and unmeasured spatiotemporal confounders. Mortality from major types of CVD (ischemic heart disease [IHD], myocardial infarction [MI], stroke, hypertensive disease, and hypertensive heart disease) was also studied. We then calculated the burden of PM2.5-attributable CVD deaths in different race/ethnicity groups and examined the magnitude of racial/ethnic disparity and its changes over time.ResultsA total of 13,289,147 CVD deaths were included in the study. Each 1-µg/m3increase in 12-month moving average of PM2.5concentration was associated with increases of 7.16 (95% confidence interval [CI]: 3.81, 10.51) CVD deaths per 1,000,000 Black people per month, significantly higher than the estimates for non-Hispanic White people (Pvalue: 0.002). The higher vulnerability in non-Hispanic Black people was also observed for mortality from IHD, MI, and stroke. Long-term PM2.5exposure contributed to approximately 75.47 (95% CI: 40.14, 110.80) CVD deaths per 1,000,000 non-Hispanic Black people annually, over 3 times higher than the estimated rate in non-Hispanic White people (16.89, 95% CI:13.17, 20.62). From 2001 to 2016, the difference in attributable CVD mortality rate between Black and White people reduced by 44.04% (from 75.80 to 42.42 per 1,000,000 people), but the burden in Black people was still over 3 times higher compared to White people.ConclusionsNon-Hispanic Black people have the highest PM2.5-attributable CVD mortality burden. Although the racial/ethnic disparity in this burden was narrowed over time, the gap between racial/ethnic minorities and non-Hispanic White people remains substantial.
An Early and Preliminary Assessment of the Clinical Severity of the Emerging SARS-CoV-2 Omicron Variants in Maharashtra, India
Authors: Karyakarte Rajesh , Das Rashmita , Taji Nyabom , Yanamandra Sushma , Shende Smriti , Joshi Suvarna , Karekar Bhagyashree , Bawale Reshma , Tiwari Rahul , Jadhav Madhuri , Sakalkar Shivani , Chaudhari Geetanjali , Rane Srushti , Agarasen Jeanne , Pillai Praveena , Dudhate Sonali , Chandankhede Priyanka , Labhshetwar Rutika , Gadiyal Yogita , Rajmane Mansi , Mukade Savita , Kulkarni Preeti 
Published: September 2022

ABSTRACTBackgroundThe SARS-CoV-2 Omicron variants BA.2.74, BA.2.75 and BA.2.76 have appeared recently in India and have already spread to over 40 countries. They have acquired additional mutations in their spike protein compared to BA.2, branching away on the SARS-CoV-2 phylogenetic tree. These added mutations, over and above those of the parental BA.2 variant, have raised concerns about the impact on viral pathogenicity, transmissibility, and immune evasion properties of the new variants.Material and MethodsA total of 990 RT-PCR positive SARS-CoV-2 samples, with a cycle threshold value (Ct) less than 25, were processed for SARS-CoV-2 whole genome sequencing between 3rd June 2022 to 7th August 2022. All corresponding demographic and clinical data were recorded and analyzed using Microsoft® Excel.ResultsOut of 990 samples sequenced, BA.2.75 (23.03%) was the predominant Omicron sublineage, followed by BA.2.38 (21.01%), BA.5 (9.70%), BA.2 (9.09%), BA.2.74 (8.89%) and BA.2.76 (5.56%). A total of 228 cases of BA.2.74, BA.2.75 and BA.2.76 were contacted by telephone, of which 215 (94.30%) were symptomatic with mild symptoms, and 13 (5.70%) had no symptoms. Fever (82.02%) was the most common symptom, followed by cough (49.12%), cold (35.97%), fatigue (27.19%), headache (21.05%) and myalgia (20.61%). Of the 228 cases, 195 (85.53%) cases recovered at home, and 33 (14.47%) required institutional quarantine. Recovery with conservative treatment was observed in 92.98% of cases, while 4.83% required additional oxygen therapy. Only 03 (1.32%) cases had poor outcomes resulting in death, and the remaining 225 (98.68%) had a good outcome. Among the 228 cases, 219 (96.05%) cases were vaccinated with COVID-19 vaccine; of these 72.60% had received both doses, 26.03% had also received the precautionary booster dose, while 1.37% were incompletely vaccinated with a single dose of vaccine.ConclusionThe current study indicates that the three BA.2 sublineages are causing mild disease in India. However, BA.2.75 has key mutations that are notable for accelerated growth and transmission and require close and effective monitoring.
SARS-CoV-2 seroprevalence on the north coast of Peru: A cross-sectional study after the first wave
Authors: Moyano Luz M. , Toledo Angie K. , Chirinos Jenny , Vilchez Barreto Percy Mc Quen , Cavalcanti Sofia , Gamboa Ricardo , Ypanaque Jhon , Meza Mauro , Noriega Sheila , Herrera Victor , Bazan Edgar , Requena Alexandra , Silva Henry , Burgos Harold , León-Jimenez Franco ,   Group of Neuroepidemiology and Science of Life of Peru
Published: September 2022

AbstractBackgroundThe devastating repercussions of COVID-19 were felt in developing nations like Peru. However, few studies have been conducted in these countries. To make good decisions about public health, it is important to understand how the disease is spread in our area.Methodology/Principal findingsAn observational, cross-sectional study was performed between November 11th and November 30th, 2020. In Puerto Pizarro, one out of every four homes was invited to participate in a systematic randomized sampling. Individuals were screened for the qualitative detection of anti-SARS-CoV-2 nucleocapsid (N) protein antibodies and anti-SARS-CoV-2 spike RBD with a rapid chromatographic immunoassay. An adult of legal age was selected, and an additional molecular test (RT-PCR) was taken to look for active COVID-19 cases.Conclusions/SignificanceThis study shows an adjusted seroprevalence of 24.72% posterior to the first wave of COVID-19 in Tumbes. When adjusted by participant characteristics, women had higher adjusted seroprevalence compared to men (213/356 vs 143/356 [28.01 % vs 21.18 %], p=0.005). More than 20% of IgG seropositive cases belong to the age group under 16 years old. Asymptomatic individuals with recent infections were 66.3% (IgM and IgM/IgG) across all age groups. No association between positive seroprevalence and water supply, water resources, or sanitation services was found. The information is relevant to the Ministry of Health’s establishment of a regional program of COVID-19 control and strategic interventions, targeting vulnerable groups and improving vaccination campaigns.Author summaryCOVID-19 had devastating effects on developing countries such as Peru. It’s crucial to understand the disease’s underlying distribution in our region to create useful dynamics that engage the population in prevention measures. We performed an observational, cross-sectional study between November 11th and November 30th, 2020, in Puerto Pizarro. One out of every four houses was invited to participate, and individuals were screened for the qualitative detection of anti-SARS-CoV-2 antibodies (IgG and IgM) with a rapid test. This study shows an adjusted seroprevalence of 24.72% posterior to the first wave of COVID-19 in Tumbes. Women had a higher adjusted seroprevalence compared to men (213/356 vs 143/356 [28.01 % vs 21.18 %], p=0.005). More than 20% of IgG seropositive cases belong to the age group under 16 years old. Asymptomatic individuals with recent infections were 66.3% (IgM and IgM/IgG) across all age groups. Community participation in epidemiological surveillance strategies is crucial to establish a future follow-up cohort and evaluate the medium-term sequelae of this disease.
Psychological factors associated with reporting side effects following COVID-19 vaccination: a prospective cohort study (CoVAccS – wave 3)
Authors: Smith Louise E. , Sim Julius , Sherman Susan M. , Amlôt Richard , Cutts Megan , Dasch Hannah , Sevdalis Nick , Rubin G James 
Published: September 2022

AbstractObjectiveTo investigate symptom reporting following the first and second COVID-19 vaccine doses, attribution of symptoms to the vaccine, and factors associated with symptom reporting.MethodsProspective cohort study (T1: 13-15 January 2021, T2: 4-15 October 2021). Participants were aged 18 years or older, living in the UK. Personal, clinical, and psychological factors were investigated at T1. Symptoms were reported at T2. We used logistic regression analyses to investigate associations.ResultsAfter the first COVID-19 vaccine dose, 74.1% (95% CI 71.4% to 76.7%, n=762/1028) of participants reported at least one injection-site symptom, while 65.0% (95% CI 62.0% to 67.9%, n=669/1029) reported at least one other (non-injection-site) symptom. Symptom reporting was associated with being a woman and younger. After the second dose, 52.9% (95% CI 49.8% to 56.0%, n=532/1005) of participants reported at least one injection-site symptom and 43.7% (95% CI 40.7% to 46.8%, n=440/1006) reported at least one other (non-injection-site) symptom. Symptom reporting was associated with having reported symptoms after the first dose, having an illness that put one at higher risk of COVID-19 (non-injection-site symptoms only), and not believing that one had enough information about COVID-19 to make an informed decision about vaccination (injection-site symptoms only).ConclusionsWomen and younger people were more likely to report symptoms from vaccination. People who had reported symptoms from previous doses were also more likely to report symptoms subsequently, although symptom reporting following the second vaccine was lower than following the first vaccine. Few psychological factors were associated with symptom reporting.HighlightsWe measured symptom reporting and attributions from the COVID-19 vaccines.A prospective cohort study was used (T1: January 2021, T2: October 2021).Women and younger people were more likely to report side effects.Side effects reporting after the first and second dose was strongly associated.
Single and 2-dose vaccinations with MVA-BN® induce durable B cell memory responses in healthy volunteers that are comparable to older generation replicating smallpox vaccines
Authors: Ilchmann Heiko , Samy Nathaly , Reichhardt Daniela , Schmidt Darja , Powell Jacqueline D , Meyer Thomas PH , Silbernagl Günter , Nichols Rick , Weidenthaler Heinz , De Moerlooze Laurence , Chen Liddy , Chaplin Paul 
Published: September 2022

AbstractWhile the MVA-BN vaccine has been proven protective against smallpox and monkeypox, the long-term immunological persistence or booster effect has not been described. In this set of clinical studies, participants who had never been immunized against smallpox were randomized to receive, 4 weeks apart: 2 placebo vaccinations (PBO group, N =181); 1 MVA-BN vaccination followed by placebo(1×MVA group, N =181); or 2 MVA-BN vaccinations (2×MVA group, N = 183). In addition, participants with a history of smallpox vaccination received 1 MVA-BN booster (HSPX+ group, N = 200). The 1×MVA and 2×MVA groups responded with increases in neutralizing antibody (nAb) GMTs at Week 2 (5.1 and 4.8, respectively) that further increased at Week 4 (7.2 and 7.5). Two weeks after the second primary vaccination in the 2×MVA group (at Week 6), nAb GMT peaked (45.6) before stabilizing 2 weeks thereafter (at Week 8) (34.0). In the HSPX+ group, a rapid anamnestic response was observed with a peak nAb GMT at Week 2 (175.1) that was much larger than the peak responses in either of the primary vaccination (1× or 2×MVA) dose groups of smallpox vaccine-naïve subjects. Persistence of nAbs relative to baseline was observed at 6 months in all groups (highest in HSPX+), with a return to near baseline nAb levels 2 years later. Subsets of ∼75 participants each, who received primary vaccinations in the 1×MVA and 2×MVA groups, were administered an MVA-BN booster 2 years later. Both booster dose (BD) groups exhibited rapid anamnestic responses with nAb GMTs that peaked 2 weeks post-booster (80.7 and 125.3). These post-booster titers in the 1×MVA and 2×MVA groups were higher than those observed at any timepoint following primary vaccination, were comparable to HSPX+ subjects who had been administered a booster, and remained elevated at 6 months post-booster (25.6 and 49.3). The observed anamnestic responses, in the absence of sustained detectable nAbs, support the presence of durable immunological memory following MVA-BN immunization. No safety concerns were identified, and the most common adverse event following the 2-year MVA-BN booster was injection site erythema in 82.2% of participants.Clinical Trial Registry NumbersNCT00316524 and NCT00686582HighlightsMVA-BN booster-induced anamnestic responses support durable immune memoryOne or two primary MVA-BN vaccinations induce similar durable B cell memory responsesAnamnestic responses were observed in those immunized with MVA-BN 2 years earlierNo safety concerns were revealed following a 2-year MVA-BN booster
Improved Robustness of SARS-CoV-2 Whole-Genome Sequencing from Wastewater with a Nonselective Virus Concentration Method
Authors: Segelhurst Emily , Bard Jonathan E. , Pillsbury Annemarie N. , Alam Md Mahbubul , Lamb Natalie A. , Zhu Chonglin , Pohlman Alyssa , Boccolucci Amanda , Emerson Jamaal , Marzullo Brandon J. , Yergeau Donald A. , Nowak Norma J. , Bradley Ian M. , Surtees Jennifer A. , Ye Yinyin 
Published: September 2022

ABSTRACTThe sequencing of human virus genomes from wastewater samples is an efficient method for tracking viral transmission and evolution at the community level. However, this requires the recovery of viral nucleic acids of high quality. We developed a reusable tangential-flow filtration system to concentrate and purify viruses from wastewater for whole-genome sequencing. A pilot study was conducted with 94 wastewater samples from four local sewersheds, from which viral nucleic acids were extracted, and the whole genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was sequenced using the ARTIC V4.0 primers. Our method yielded a high probability (0.9) of recovering complete or near-complete SARS-CoV-2 genomes (>90% coverage at 10× depth) from wastewater when the COVID-19 incidence rate exceeded 33 cases per 100 000 people. The relative abundances of sequenced SARS-CoV-2 variants followed the trends observed from patient-derived samples. We also identified SARS-CoV-2 lineages in wastewater that were underrepresented or not present in the clinical whole-genome sequencing data. The developed tangential-flow filtration system can be easily adopted for the sequencing of other viruses in wastewater, particularly those at low concentrations.SYNOPSISThe tangential-flow filtration method extracts viral nucleic acids of high enough quality from wastewater for robust and successful whole-genome sequencing.GRAPHIC FOR TABLE OF CONTENTS (TOC)
Statistical Evaluation of the Test Threshold for the Alzheimer’s Disease EEG Coherence Marker
Authors: Radinski Crystal , Perez Grace 
Published: September 2022

AbstractA progressive reduction in synaptic connections between neurons is one neurophysiological indicator of brain ageing and was linked to the severity of dementia. In our study, we hypothesized that if synaptic disconnection as the neuropathology of Alzheimer’s disease (AD) is responsible for the brain’s inability to integrate diverse regions into efficient networks, then electroencephalographic data may be utilized to identify Alzheimer’s dementia. The study explored EEG coherence, reflecting connectivity between regions, as a potential AD indicator and identified four promising EEG coherence markers. As the pattern of degeneration follows the temporal-parietal-frontal axis, the temporal gamma marker was chosen for further evaluation. We utilize conventional analysis, producing paired results such as sensitivity and specificity and the receiver operating characteristic (ROC) curve to evaluate the accuracy of the temporal gamma marker. The optimal cut-off point of 0.950 was confirmed by both methods and provided 95% correct classification indicating an almost perfect differentiation between control and impaired cognitive status. This evaluation will be used in a blinded diagnostic test accuracy study to determine the TG_marker validity in detecting AD and excluding pseudo-dementias.
Neural mechanisms of psychedelic visual imagery
Authors: Stoliker Devon , Preller Katrin H. , Novelli Leonardo , Anticevic Alan , Egan Gary F. , Vollenweider Franz X. , Razi Adeel 
Published: September 2022

AbstractVisual alterations under classic psychedelics can include rich phenomenological accounts of eyes-closed imagery. Preclinical evidence suggests agonism of the 5-HT2A receptor may reduce synaptic gain to produce psychedelic-induced imagery. However, this has not been investigated in humans. To infer the directed connectivity changes to visual sensory connectivity underlying psychedelic visual imagery in healthy adults, a double-blind, randomised, placebo-controlled, cross-over study was performed, and dynamic causal modelling was applied to the resting state eyes-closed functional MRI scans of 24 subjects after administration of 0.2mg/kg of the serotonergic psychedelic drug, psilocybin (magic mushrooms), or placebo. The effective connectivity model included the early visual area, fusiform gyrus, intraparietal sulcus, and inferior frontal gyrus. We observed a pattern of increased self-inhibition of both early visual and higher visual-association regions under psilocybin that was consistent with preclinical findings. We also observed a pattern of reduced inhibition from visual-association regions to earlier visual areas that indicated top-down connectivity is enhanced during visual imagery. The results were associated with behavioural measures taken immediately after the scans, suggesting psilocybin-induced decreased sensitivity to neural inputs is associated with the perception of eyes-closed visual imagery. The findings inform our basic and clinical understanding of visual perception. They reveal neural mechanisms that, by affecting balance, may increase the impact of top-down feedback connectivity on perception, which could contribute to the visual imagery seen with eyes-closed during psychedelic experiences.
The Asgard archaeal ESCRT-III system forms helical filaments and remodels eukaryotic membranes, shedding light on the emergence of eukaryogenesis
Authors: Melnikov Nataly , Junglas Benedikt , Halbi Gal , Nachmias Dikla , Zerbib Erez , Upcher Alexander , Zalk Ran , Sachse Carsten , Bernheim-Groswasser Ann , Elia Natalie 
Published: September 2022

ABSTRACTThe ESCRT machinery mediates membrane remodeling in numerous processes in cells including cell division and nuclear membrane reformation. The identification of ESCRT homologs in Asgard archaea, currently considered the closest ancestor of eukaryotes, implies a role for ESCRTs in the membrane remodeling processes that occurred during eukaryogenesis. Yet, the function of these distant ESCRT homologs is mostly unresolved. Here we show that Asgard ESCRT-III proteins of the Lokiarcheota self-assemble into helical filaments, a hallmark of the ESCRT system. We determined the cryo-EM structure of the filaments at 3.6 Å resolution and found that they share features of bacterial and eukaryotic ESCRT-III assemblies. Markedly, Asgard ESCRT-III filaments bound and deformed eukaryotic-like membrane vesicles. Oligonucleotides facilitated the assembly of ESCRT-III filaments and tuned the extent of membrane remodeling. The ability of Asgard archaeal ESCRTs to remodel eukaryotic-like membranes, which are fundamentally different from archaeal membranes, and the structural properties of these proteins places them at the junction between prokaryotes and eukaryotes, substantiating a role for ESCRTs in eukaryogenesis.GRAPHICAL ABSTRACT