bluuebunny/crossref_metadata_2025_split huggingface dataset:
UV-Induced Neuronal Degeneration in the Rat Cerebral Cortex
Authors: Nakata Mariko , Shimoda Masayuki , Yamamoto Shinya 
Published: January 2021

Abstract
Irradiation with ultraviolet (UV) light on the cortical surface can induce a focal brain lesion (UV lesion) in rodents. In the present study, we investigated the process of establishing a UV lesion. Rats underwent UV irradiation (365-nm wavelength, 2.0 mWh) over the dura, and time-dependent changes in the cortical tissue were analyzed histologically. We found that the majority of neurons in the lesion started to degenerate within 24 h and the rest disappeared within 5 days after irradiation. UV-induced neuronal degeneration progressed in a layer-dependent manner. Moreover, UV-induced terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positivity and heme oxygenase-1 (HO-1) immunoreactivity were also detected. These findings suggest that UV irradiation in the brain can induce gradual neural degeneration and oxidative stress. Importantly, UV vulnerability may vary among cortical layers. UV-induced cell death may be due to apoptosis; however, there remains a possibility that UV-irradiated cells were degenerated via processes other than apoptosis. The UV lesion technique will not only assist in investigating brain function at a targeted site but may also serve as a pathophysiological model of focal brain injury and/or neurodegenerative disorders.
Comparison of gefitinib-induced skin adverse reactions (SAR) in C57BL/6 and FVB/N mice
Authors: Zhang Yali , Wang Yalei , Chen Ziwei , Cheng Shuo , Ding Chengcheng , Zhang Jiani , Peng Tiantian , Chen Weihang , Zhang Dingyang , Tan Yan , Wang Xu , Dong Ruijuan , Jiang Miao , Hua Qian 
Published: January 2021

Abstract
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) such as gefitinib, erlotinib, and afatinib, are widely used in clinical practice and remarkably effective in treatment of advanced non-small cell lung cancer. However, there are some adverse effects while taking EGFR-TKIs, among which skin adverse reactions (SAR) are the most common events. At present, the poor outcome of SAR and insufficient research on SAR models need to be addressed. In this study we focused on the SAR models to lay a foundation for mechanism researches. Gefitinib, one of the EGFR-TKIs, was used as SAR inducing agents. We chose C57BL/6 and FVB/N mice as experimental model and they were divided into four groups. The weight and skin moisture of mice were detected every 7 days, itching behavior and abnormal eyelids were tested at 35th day after gavage, and survival rate was also recorded. The weight of unit area hair, length of whiskers and inflammatory cells were evaluated after mice sacrificed. C57BL/6 animals treated with gefitinib showed significant differences in survival rate, weight of unit area hair, skin moisture changes, skin dryness, itching behavior, whisker irregular growth, abnormal eyelids, and inflammatory cells; FVB/N animals treated with gefitinib only showed significant differences in survival rate, whisker irregular growth and abnormal eyelids, compared with the control group, respectively. In this study, we compared the similarities and differences of gefitinib-induced SAR between C57BL/6 and FVB/N mice, which illustrated different patients probably showing different symptoms clinically and provided experimental basis for researching mechanism of EGFR-TKIs induced SAR.
What does 16S rRNA gene-targeted next generation sequencing contribute to the study of infective endocarditis in valve tissue?
Authors: Santibáñez Paula , Portillo Aránzazu , Santibáñez Sonia , García-Álvarez Lara , de Toro María , A. Oteo José 
Published: January 2021

AbstractInfective endocarditis (IE) is a severe and life-threatening disease. Identification of infectious etiology is essential for establishing the appropriate antimicrobial treatment and decreasing mortality. The aim of this study was to explore potential utility of metagenomics for improving microbiological diagnosis of IE. In this work, next-generation sequencing (NGS) of V3-V4 region of the 16S rRNA gene was performed in 27 heart-valve tissues (18 natives, 5 intravascular devices, and 4 prosthetics) of patients diagnosed by IE. Initial microbiological diagnosis, blood culture (BC) and/or PCR, was compared with NGS-based diagnosis. Metagenomics matched with conventional techniques diagnosis in 24/27 cases (88.9%). The same bacterial family was assigned to 24 cases, the same genus to 23 cases, and the same specie for 13 cases. In 22 of them, the etiological agent was represented by percentages >99% of the reads and in two by ∼70%. Staphylococcus aureus was detected in a previously undiagnosed patient, making the microbiological diagnosis possible in one more sample than with previously used techniques. The remaining two patients showed no coincidence between traditional and NGS microbiological diagnoses. Minority records verified mixed infections in four cases and suggested confections in two cases, supported by clinical data. In conclusion: 16S rRNA gene-targeted NGS allowed to diagnose one case of IE without microbiological entity based on traditional techniques. However, the application of metagenomics to the study of IE in resected heart valves provides no benefits in comparison with BC and/or PCR. More studies are needed before implementation of NGS for the diagnosis of IE.
Trans-ethnic eQTL meta-analysis of human brain reveals regulatory architecture and candidate causal variants for brain-related traits
Authors: Zeng Biao , Bendl Jaroslav , Kosoy Roman , Fullard John F. , Hoffman Gabriel E. , Roussos Panos 
Published: January 2021

AbstractWhile large-scale genome-wide association studies (GWAS) have identified hundreds of loci associated with neuropsychiatric and neurodegenerative traits, identifying the variants, genes and molecular mechanisms underlying these traits remains challenging. Integrating GWAS results with expression quantitative trait loci (eQTLs) and identifying shared genetic architecture has been widely adopted to nominate genes and candidate causal variants. However, this integrative approach is often limited by the sample size, the statistical power of the eQTL dataset, and the strong linkage disequilibrium between variants. Here we developed the multivariate multiple QTL (mmQTL) approach and applied it to perform a large-scale trans-ethnic eQTL meta-analysis to increase power and fine-mapping resolution. Importantly, this method also increases power to identify conditional eQTL’s that are enriched for cell type specific regulatory effects. Analysis of 3,188 RNA-seq samples from 2,029 donors, including 444 non-European individuals, yields an effective sample size of 2,974, which is substantially larger than previous brain eQTL efforts. Joint statistical fine-mapping of eQTL and GWAS identified 301 variant-trait pairs for 23 brain-related traits driven by 189 unique candidate causal variants for 179 unique genes. This integrative analysis identifies novel disease genes and elucidates potential regulatory mechanisms for genes underlying schizophrenia, bipolar disorder and Alzheimer’s disease.
Ranking videolaryngoscopes and direct laryngoscopes by orotracheal intubation performance in children: protocol of a systematic review and network meta-analysis of randomized clinical trials at patient level
Authors: C Carvalho Clístenes , LPA Regueira Stéphanie , Souza Ana Beatriz S , Medeiros Lucas MLF , Manoel Marielle BS 
Published: January 2021

ABSTRACTBackgroundVideolaryngoscopy was shown to improve glottic visualization in children as compared to direct laryngoscopy, but at the expenses of delayed time for intubation. As little evidence is available regarding the relative performance of different laryngoscopes at present, we designed this systematic review and network meta-analysis to rank the different videolaryngoscopes (VLs) and direct laryngoscopes (DLs) for orotracheal intubation in children.MethodsWe will conduct a search in PubMed, LILACS, Scielo, Embase, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL; 2021, Issue 1) on 27/01/2021. We will include randomized clinical trials fully reported with patients aged ≤ 18 years, making comparisons between different types of laryngoscopes (any of both VLs and DLs) for failed first intubation attempt, intubation time, number of attempts at intubation or number of unsuccessful intubations, failed intubation, glottic view score, or adverse responses to endotracheal intubation. Pooled effects will be estimated by both fixed and random-effects models and presented according to qualitative and quantitative heterogeneity assessment. Sensitivity analyses will be performed as well as a priori subgroup, meta-regression and multiple meta-regression analyses. Additionally, network meta-analyses will be applied to rank the different VLs and DLs. We will also assess the risk of selective publication by funnel plot asymmetry.DiscussionThis systematic review and network meta-analysis aim to understand which laryngoscopes perform better than others for orotracheal intubation.Systematic review registrationThe current protocol was submitted to PROSPERO on 25/01/2021.
Point-of-Care CRISPR-Cas-Assisted SARS-CoV-2 Detection in an Automated and Mobile Droplet Magnetofluidic Device
Authors: Chen Fan-En , Lee Pei-Wei , Park Joon Soo , Trick Alexander Y. , Chen Liben , Shah Kushagra , Hsieh Kuangwen , Wang Tza-Huei 
Published: January 2021

AbstractIn the fight against COVID-19, there remains unmet needs in developing point-of-care (POC) diagnostic testing tools that can rapidly and sensitively detect the causative SARS-CoV-2 virus to control disease transmission and improve patient management. Although recent CRISPR-Cas-assisted SARS-CoV-2 detection assays (such as DETECTR and SHERLOCK) are viewed as transformative solutions for POC diagnostic testing, their lack of simple sample processing and full integration within an automated and portable device hamper their potential for POC use. We report herein POC-CRISPR – a new single-step CRISPR-Cas-assisted assay that is coupled to droplet magnetofluidics (DM) – that leverages simple magnetic concentration and transport of nucleic acid-binding magnetic beads to accomplish sample preparation and assay automation. By further adapting the assay into a fully integrated thermoplastic cartridge within a palm-sized mobile device, POC-CRISPR was able to detect 1 genome equivalent (GE)/µL SARS-CoV-2 RNA from a sample volume of 100 µL in 30 min. Moreover, when evaluated with unprocessed clinical nasopharyngeal (NP) swab eluates, POC-CRISPR identified SARS-CoV-2 positive samples in as short as 20 min and achieved full concordance with standard RT-qPCR.
Modeling the asymptomatic prevalence of SARS-CoV-2 epidemic in Italy and the ISTAT survey
Authors: Traini Marco Claudio , Caponi Carla , Ferrari Riccardo , De Socio Giuseppe Vittorio 
Published: January 2021

objectivesAugust 3rd, 2020, the Italian National Institute of Statistics (ISTAT) presented preliminary results of seroprevalence survey on the percentage of individuals affected by Covid-19. The survey aims to define (within the entire population of Italy) the portion of individuals that developed an antibody response against SARS-CoV-2. For the first time one has an estimate of the asymptomatic infected population and the possibility to acknowledge its potential rôle in the infection spread in Italy, one of the most affected areas in Europe. The information obtained allow a particularly sensitive validation of epidemiological models which include the asymptomatic class.methodsThe present study is devoted to the construction of a model able to simulate, in a systematic way, the asymptomatic group whose relevance in the, SARS-CoV-2 epidemic, has been recently investigated and discussed. The investigation involves the description of the first epidemic outbreak in Italy as well as the predictive analysis of the ongoing second wave. In particular the possible correction to the data of the serological tests because of their sensitivity and specificity.resultsThe model: taken as an example of the models presently used, satisfactory reproduces the data of the ISTAT survey showing a relevant predictive power and relegating in a secondary position models which do not include, in the simulation, the presence of asymptomatic groups. The corrections due to the serological test sensitivity (in particular those ones depending on the symptoms onset) make the comparison between data and models less accurate.conclusionsThe predictions of the model confirm a relevant presence of asymptomatic individuals also during the second pandemic wave in Italy. The ratio of reported to unreported cases is predicted to be roughly 1:4. A more detailed knowledge of the results of the survey could allow to correct, in a relevant way, the data by means of the experimental evidences on the antibodies sensibility. The model analyses of the vaccination strategies, confirms the relevance of a massive administration with the beginning of the year to arrive at the end of the infection within August 2021.
Neighbourhood-level risk factors of COVID-19 incidence and mortality
Authors: van Ingen Trevor , Akingbola Samantha , Brown Kevin A. , Daneman Nick , Buchan Sarah A. , Smith Brendan T. 
Published: January 2021

AbstractBackgroundRacialized and low income communities face disproportionally high rates of coronavirus 2019 (COVID-19) infection and death. However, data on inequities in COVID-19 across granular categories of socio-demographic characteristics is more sparse.MethodsNeighbourhood-level counts of COVID-19 cases and deaths in Ontario, Canada recorded as of July 28th, 2020 were extracted from provincial and local reportable infectious disease surveillance systems. Associations between COVID-19 incidence and mortality and 18 neighbourhood-level measures of immigration, race, housing and socio-economic characteristics were estimated with Poisson generalized linear mixed models. Housing characteristic variables were subsequently added to models to explore if housing may have a confounding influence on the relationships between immigration, race, and socio-economic status and COVID-19 incidence.ResultsThere were large inequities in COVID-19 incidence and mortality across the socio-demographic variables examined. Neighbourhoods having a higher proportion immigrants, racialized populations, large households and low socio-economic status were associated with COVID-19 risk. Adjusting for housing characteristics, especially unsuitably crowded housing, attenuated COVID-19 risks. However persistent risk remained for neighbourhoods having high proportions of immigrants, racialized populations, and proportion of Black, Latin American, and South Asian residents.ConclusionsSocio-demographic factors account for some of the neighbourhood-level differences in COVID-19 across Ontario. Housing characteristics account for a portion, but not all, of the excess burden of COVID-19 experienced by immigrant, racialized, low income and low education populations.
Assessing antimicrobial resistance, utilization and stewardship in Yemen: An exploratory mixed-methods study
Authors: Orubu ESF , Najwa A , Ching C , Bu Jawdeh S , Anderson J , Sheikh R , Hariri F , Basaleem H , Zaman MH 
Published: January 2021

AbstractAntimicrobial resistance (AMR), largely driven by irrational use of antimicrobials, is a global, multi-faceted problem calling for a complete understanding of all contributory factors for effective containment. In conflict settings, war-wounds and malnutrition can combine with existing social determinants to increase demand for antibiotics, compounding irrational use. In this study, we focus on Yemen, a low-income country with active conflict for the last five years, and analyze the current status of awareness and stewardship efforts regarding AMR. We performed a survey of prescribers/physicians and pharmacists to describe perceptions of AMR prevalence, antibiotic use practices and stewardship in Yemen, supported by a non-systematic scoping literature review and a key informant interview. Participants (96%, n=57) reported a perceived high AMR prevalence rate. Prescribers (74%, 20/27) reported pressure to prescribe broad-spectrum antibiotics. In the majority of cases (81%, 22/27), Antimicrobial Sensitivity Tests (AST) were not performed to inform antibiotic choice. The main barrier to AST was cost. Most pharmacists (67%, 18/27) sold antibiotics without prescriptions. Amoxicillin (including amoxicillin-clavulanate) was the most-commonly prescribed (63%, 17/27) or dispensed (82%, 22/27) antibiotic. AST was rated the least important solution to AMR in Yemen. While there was awareness of a high AMR rate, stewardship is poor in Yemen. We note that barriers to the use of AST could be addressed through the deployment of low-cost AST kits. Compulsory continuing education emphasizing the use of AST to guide prescribing and patients’ awareness programs could help avoid irrational use.
Evidence for SARS-CoV-2 Spike Protein in the Urine of COVID-19 patients
Authors: George Santosh , Pal Anasuya Chattopadhyay , Gagnon Jacqueline , Timalsina Sushma , Singh Pallavi , Vydyam Pratap , Munshi Muhammad , Chiu Joy E. , Renard Isaline , Harden Christina A. , Ott Isabel M. , Watkins Anne E. , Vogels Chantal B.F. , Lu Peiwen , Tokuyama Maria , Venkataraman Arvind , Casanovas-Massana Arnau , Wyllie Anne L. , Rao Veena , Campbell Melissa , Farhadian Shelli F. , Grubaugh Nathan D. , Dela Cruz Charles S. , Ko Albert I. ,   ‘Yale IMPACT study’ team, Perez Amalia Berna , Akaho Elikplim H. , Moledina Dennis G , Testani Jeffrey , John Audrey R , Ledizet Michel , Mamoun Choukri Ben 
Published: January 2021

ABSTRACTSARS-CoV-2 infection has so far affected over 42 million people worldwide, causing over 1.1 million deaths. With the large majority of SARS-CoV-2 infected individuals being asymptomatic, major concerns have been raised about possible long-term consequences of the infection. We developed an antigen capture assay to detect SARS-CoV-2 spike protein in urine samples from COVID-19 patients whose diagnosis was confirmed by PCR from nasopharyngeal swabs (NP-PCR+). The study used a collection of 233 urine samples from 132 participants from Yale New Haven Hospital and the Children’s Hospital of Philadelphia obtained during the pandemic (106 NP-PCR+ and 26 NP-PCR-) as well as a collection of 20 urine samples from 20 individuals collected before the pandemic. Our analysis identified 23 out of 91 (25%) NP-PCR+ adult participants with SARS-CoV-2 spike S1 protein in urine (Ur-S+). Interestingly, although all NP-PCR+ children were Ur-S-, 1 NP-PCR-child was found to be positive for spike protein in urine. Of the 23 Ur-S+ adults, only 1 individual showed detectable viral RNA in urine. Our analysis further showed that 24% and 21% of NP-PCR+ adults have high levels of albumin and cystatin C in urine, respectively. Among individuals with albuminuria (>0.3 mg/mg of creatinine) statistical correlation could be found between albumin and spike protein in urine. Together, our data showe that 1 of 4 of SARS-CoV-2 infected individuals develop renal abnormalities such as albuminuria. Awareness about the long-term impact of these findings is warranted.
Mitigation policies and vaccination in the COVID-19 pandemic: a modelling study
Authors: Valiati Naiara C.M. , Villela Daniel A.M. 
Published: January 2021

SummaryThe perspective of vaccination to protect human population from infection of SARS-CoV-2 virus has great potential to control the pandemic. Nevertheless, vaccine planning requires phased introduction with age groups, health workers, and vulnerable people. We developed a mathematical model capable of capturing the dynamics of the SARS-CoV-2 dissemination aligned with social distancing, isolation measures, and vaccination. The city of Rio de Janeiro provides a case study to analyze possible scenarios including non–pharmaceutical interventions and vaccination in the epidemic scenario. Our results shows that a combination of different policies such as case isolation and social distancing are more effective for mitigating the epidemics. Furthermore, these policies will still be necessary in a phased vaccination program. Therefore, health surveillance activities should be maintained along with vaccination planning in scheduled groups until a large vaccinated coverage is reached.
Disease-specific ACMG/AMP guidelines improve sequence variant interpretation for hearing loss
Authors: Patel Mayher J , DiStefano Marina T , Oza Andrea M , Hughes Madeline Y , Wilcox Emma H , Hemphill Sarah E , Cushman Brandon J , Grant Andrew R , Siegert Rebecca K , Shen Jun , Chapin Alex , Boczek Nicole J , Schimmenti Lisa A , Nara Kiyomitsu , Kenna Margaret , Azaiez Hela , Booth Kevin T , Griffith Andrew , Avraham Karen B , Kremer Hannie , Rehm Heidi L , Amr Sami S , Abou Tayoun Ahmad N ,   ClinGen Hearing Loss Clinical Domain Working Group
Published: January 2021

AbstractPurposeThe ClinGen Variant Curation Expert Panels (VCEPS) provide disease-specific rules for accurate variant interpretation. Using hearing loss-specific American College of Medical Genetics/Association for Molecular Pathology (HL-specific ACMG/AMP) guidelines, the ClinGen Hearing Loss VCEP (HL VCEP) illustrates the utility of expert specifications in resolving conflicting variant interpretations.MethodsA total of 157 variants across nine hearing loss genes were curated and submitted to ClinVar by the HL VCEP. The curation process consisted of collecting published and unpublished data for each variant by biocurators, followed by bi-monthly meetings of an expert curation subgroup that reviewed all evidence and applied the HL-specific ACMG/AMP guidelines to reach a final classification.ResultsBefore expert curation, 75% (117/157) of variants had single or multiple VUS submissions (17/157) or had conflicting interpretations in ClinVar (100/157). After applying the HL-specific ACMG/AMP guidelines, 24% (4/17) of VUS variants and 69% (69/100) of discordant variants were resolved into Benign (B), Likely Benign (LB), Likely Pathogenic (LP), or Pathogenic (P). Overall, 70% (109/157) variants had unambiguous classifications (B, LB, LP, P). We quantify the contribution of the HL-specified ACMG/AMP codes to variant interpretation.ConclusionExpert specification and application of the HL-specific ACMG/AMP guidelines effectively resolved discordant interpretations in ClinVar. This study supports the utility of ClinGen VCEPs in helping the community move towards more consistent variant interpretations, which will improve the care of patients with genetic disorders.
SARS-CoV-2 antigen rapid diagnostic test enhanced with silver amplification technology
Authors: Miyakawa Kei , Funabashi Rikako , Yamaoka Yutaro , Jeremiah Sundararaj Stanleyraj , Katada Junichi , Wada Atsuhiko , Takei Toshiki , Shimizu Kohei , Ozawa Hiroki , Kawakami Chiharu , Usuku Shuzo , Tanaka Nobuko , Yamazaki Etsuko , Shimizu Hideaki , Okabe Nobuhiko , Hasegawa Hideki , Ryo Akihide 
Published: January 2021

AbstractRapid diagnosis of COVID-19 is essential for instituting measures to prevent viral spread. SARS-CoV-2 antigen rapid diagnostic test (Ag-RDT) based on lateral flow immunochromatography assay (LFIA) principle can visually indicate the presence of SARS-CoV-2 antigens as a band. Ag-RDT is clinically promising as a point-of-care testing because it can give results in a short time without the need for special equipment. Although various antigen capture LFIAs are now available for rapid diagnosis for SARS-CoV-2 infection, they face the problems of low sensitivity. We have previously developed highly specific monoclonal antibodies (mAb) against SARS-CoV-2 nucleocapsid protein (NP) and in this study, we have employed these mAbs to develop a new LFIA that can detect SARS-CoV-2 NP in nasopharyngeal swab samples with higher sensitivity by combining them with silver amplification technology. We also compared the performance of our Ag-RDT against the commercially available Ag-RDTs using clinical samples to find that our newly developed LFIA performed best among tested, highlighting the superiority of silver amplification technology.