bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stakeholders’ views on an institutional dashboard with metrics for responsible research
Authors: Haven Tamarinde , Holst Martin , Strech Daniel 
Published: September 2021

AbstractBackgroundConcerns about research waste have fueled debate about incentivizing individual researchers and research institutions to conduct responsible research. Instead of looking at impact factors or grants, research institutions should be assessed based on indicators that pertain to responsible research. In this study, we showed stakeholders a proof-of-principle dashboard with quantitative metrics that visualized responsible research performance on a German University Medical Center (UMC) level. Our research question was: What are stakeholders’ views on a dashboard that displays the adoption of responsible research practices on a UMC-level?MethodsWe recruited different stakeholders to participate in an online interview. Stakeholders included UMC leadership, support staff, funders, and experts in responsible research. We asked interviewees to reflect on the strengths and weaknesses of this institutional dashboard approach and enquired their perceptions of the metrics it included. The interviews were recorded and transcribed. We applied content analysis to understand what stakeholders considered the Strengths, Weaknesses, Opportunities, and Threats of the dashboard and its metrics.ResultsWe interviewed 28 international stakeholders (60% German). Overall, interviewees thought the dashboard was helpful in seeing where an institution stands and appreciated the fact that the metrics were based on concrete behaviors. Main weaknesses included the lack of a narrative explaining the choice of the metrics covered. Interviewees considered the dashboard a good opportunity to initiate change and hoped the dashboard could be supplemented with other indicators in the future. They feared that making the dashboard public might risk incorrect interpretation of the metrics and put UMCs in a bad light.DiscussionWhile the feedback was given specifically to our proof-of-principle dashboard, our findings indicate that discussion with stakeholders is needed to develop an overarching framework governing responsible research on an institutional level, and to involve research-performing organizations.
Detailed Quantification of Glomerular Structural Lesions Associates with Clinical Outcomes and Transcriptomic Profiles in Nephrotic Syndrome
Authors: Hodgin Jeffrey B. , Mariani Laura H. , Zee Jarcy , Liu Q , Smith Abigail R. , Eddy Sean , Hartman John , Hamidi Habib , Gaut Joseph P. , Palmer Matthew B. , Nast Cynthia C. , Chang Anthony , Hewitt Stephen , Gillespie Brenda W. , Kretzler Matthias , Holzman Lawrence B. , Barisoni Laura ,   for the Nephrotic Syndrome Study Network (NEPTUNE)
Published: September 2021

ABSTRACTThe current classification system for focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) does not fully capture the complex structural changes in kidney biopsies, nor the clinical and molecular heterogeneity of these diseases. The Nephrotic Syndrome Study Network (NEPTUNE) Digital Pathology Scoring System (NDPSS) was applied to 221 NEPTUNE FSGS/MCD digital kidney biopsies for glomerular scoring using 37 descriptors. The descriptor-based glomerular profiles were used to cluster patients with similar morphologic characteristics. Glomerular descriptors and patient clusters were assessed for association with time to proteinuria remission and disease progression by using adjusted Cox models, and eGFR measures over time by using linear mixed models. Messenger RNA from glomerular tissue was used to assess differentially expressed genes (DEG) between clusters and identify genes associated with individual descriptors driving cluster membership. Three clusters were identified: X (N=56), Y (N=68), and Z (N=97). Clusters Y and Z had higher probabilities of proteinuria remission (HR [95% CI]= 1.95 [0.99, 3.85] and 3.29 [1.52, 7.13], respectively), lower hazards of disease progression 0.22 [0.08, 0.57] and 0.11 [0.03, 0.45], respectively), and greater loss of eGFR over time compared with X. Cluster X had 1920 DEGs compared to Y+Z, which reflected activation of pathways of immune response and inflammation. Six individual descriptors driving the clusters individually correlated with clinical outcomes and gene expression. The NDPSS allows for characterization of FSGS/MCD patients into clinically and biologically relevant categories and uncovers histologic parameters associated with clinical outcomes and molecular signatures not included in current classification systems.TRANSLATIONAL STATEMENTFSGS and MCD are heterogeneous diseases that manifest with a variety of structural changes often not captured by conventional classification systems. This study shows that a detailed morphologic analysis and quantification of these changes allows for better representation of the structural abnormalities within each patient and for grouping patients with similar morphologic profiles into categories that are clinically and biologically relevant.
Deep Learning Segmentation of Glomeruli on Kidney Donor Frozen Sections
Authors: Davis Richard C. , Li Xiang , Xu Yuemei , Wang Zehan , Souma Nao , Sotolongo Gina , Bell Jonathan , Ellis Matthew , Howell David , Shen Xiling , Lafata Kyle , Barisoni Laura 
Published: September 2021

ABSTRACTPurposeRecent advances in computational image analysis offer the opportunity to develop automatic quantification of histologic parameters as aid tools for practicing pathologists. This work aims to develop deep learning (DL) models to quantify non-sclerotic and sclerotic glomeruli on frozen sections from donor kidney biopsies.ApproachA total of 258 whole slide images (WSI) from cadaveric donor kidney biopsies performed at our institution (n=123) and at external institutions (n=135) were used in this study. WSIs from our institution were divided at the patient level into training and validation datasets (Ratio: 0.8:0.2) and external WSIs were used as an independent testing dataset. Non-sclerotic (n=22767) and sclerotic (n=1366) glomeruli were manually annotated by study pathologists on all WSIs. A 9-layer convolutional neural network based on the common U-Net architecture was developed and tested for the segmentation of non-sclerotic and sclerotic glomeruli. DL-derived, manual segmentation and reported glomerular count (standard of care) were compared.ResultsThe average Dice Similarity Coefficient testing was 0.90 and 0.83. and the F1, Recall, and Precision scores were 0.93, 0.96, and 0.90, and 0.87, 0.93, and 0.81, for non-sclerotic and sclerotic glomeruli, respectively. DL-derived and manual segmentation derived glomerular counts were comparable, but statistically different from reported glomerular count.ConclusionsDL segmentation is a feasible and robust approach for automatic quantification of glomeruli. This work represents the first step toward new protocols for the evaluation of donor kidney biopsies.
Genome-wide Meta-analysis of Alcohol Use Disorder in East Asians
Authors: Zhou Hang , Kalayasiri Rasmon , Sun Yan , Nuñez Yaira Z. , Deng Hong-Wen , Chen Xiang-Ding , Justice Amy C. , Kranzler Henry R. , Chang Suhua , Lu Lin , Shi Jie , Sanichwankul Kittipong , Mutirangura Apiwat , Malison Robert T. , Gelernter Joel 
Published: September 2021

AbstractBACKGROUNDAlcohol use disorder (AUD) is a leading cause of death and disability worldwide. Genome-wide association studies (GWAS) have identified ∼30 AUD risk genes in European populations, but many fewer in East Asians.METHODSWe conducted GWAS and genome-wide meta-analysis of AUD in 13,551 subjects with East Asian ancestry, using published summary data and newly genotyped data from four cohorts: 1) electronic health record (EHR)-diagnosed AUD in the Million Veteran Program (MVP)sample; 2) DSM-IV diagnosed alcohol dependence (AD) in a Han Chinese-GSA (array) cohort;3) AD in a Han Chinese-Cyto (array) cohort; and 4) two AD datasets in a Thai cohort. The MVP and Thai samples included newly genotyped subjects from ongoing recruitment. In total, 2,254 cases and 11,297 controls were analyzed. An AUD polygenic risk score was analyzed in an independent sample with 4,464 East Asians (Kaiser Permanente data from dbGaP). Phenotypes from survey data and ICD-9-CM diagnoses were tested for association with the AUD PRS.RESULTSTwo risk loci were detected: the well-known functional variant rs1229984 in ADH1B and rs3782886 in BRAP (near the ALDH2 gene locus) are the lead variants. AUD PRS was significantly associated with days per week of alcohol consumption (beta = 0.43, se = 0.067, p = 2.47×10−10) and nominally associated with pack years of smoking (beta = 0.09, se = 0.05, p = 4.52×10−2) and ever vs. never smoking (beta = 0.06, se = 0.02, p = 1.14×10−2).CONCLUSIONSThis is the largest GWAS of AUD in East Asians to date. Building on previous findings, we were able to analyze pleiotropy, but did not identify any new risk regions, underscoring the importance of recruiting additional East Asian subjects for alcohol GWAS.
Decreased door-to-balloon time in patients with ST-segment elevation myocardial infarction during the early COVID-19 pandemic in South Korea – an observational study
Authors: Ryu Sukhyun , Kim Dasom , Jung Lae Young , Kim Baekjin , Lee Chang-Seop 
Published: September 2021

AbstractBackgroundThe coronavirus disease 2019 (COVID-19) resulted in a marked decrease in the number of patient visits for acute myocardial infarction (AMI) and delayed patient response and intervention in several countries. This study evaluated the effect of the COVID-19 pandemic on the number of patients, patient response time (pain-to-door), and intervention time (door-to-balloon) for patients with ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI).MethodsPatients with STEMI or NSTEMI visiting a hospital in South Korea who underwent primary coronary intervention during the COVID-19 pandemic (January 29, 2020, to December 31, 2020) were compared with those in the equivalent period in 2018 to 2019. Patient response and intervention times were compared for the COVID-19 pandemic window (2020) and the equivalent period in 2018 to 2019.ResultsWe observed no decrease in the number of patients with STEMI (P=0.50) and NSTEMI (P=0.94) during the COVID-19 pandemic compared to that in the previous years. Patient response times (STEMI: P=0.34; NSTEMI: P=0.89) during the overall COVID-19 pandemic period did not differ significantly. However, we identified a significant decrease in time to intervention among patients with STEMI (14%; p<0.01) during the early COVID-19 pandemic.ConclusionsWe found that the number of patient with STEMI and NSTEMI was consistent during the COVID-19 pandemic and that no time delays in patient response and intervention occurred. However, the door-to-balloon time among patients with STEMI significantly reduced during the early COVID-19 pandemic, which could be attributed to reduced emergency care utilization during the early pandemic.
COVID-19 Acceleration and Vaccine Status in France - Summer 2021
Authors: Baunez Christelle , Degoulet Mickael , Luchini Stéphane , Pintus Patrick A. , Teschl Miriam 
Published: September 2021

AbstractObjectivesThis note provides an assessment of COVID-19 acceleration among groups with different vaccine status in France.MethodsWe assess viral acceleration using a novel indicator introduced in Baunez et al. (2021). The acceleration index relates the percentage change of tests that have been performed on a given day to the percentage change in the associated positive cases that same day. We compare viral acceleration among vaccinated and unvaccinated individuals in France over the period May 31st - August 29, 2021.ResultsOnce the state of the epidemic within each groups is accounted for, it turns out that viralaccelerationhas since mid-July converged to similar levels among vaccinated and unvaccinated individuals in France, even though viralspeedis larger for the latter group compared to the former.ConclusionOur results call for an increasing testing effort forbothvaccinated and unvaccinated individuals, in view of the fact that viral circulation is currently accelerating at similar levels for both groups in France.
Alterations in CD39/CD73 Axis of T cells associated with COVID-19 severity
Authors: Dorneles Gilson P , Teixeira Paula C , da Silva Igor M , Schipper Lucas L , Santana Filho Paulo C , Rodrigues Júnior Luiz Carlos , Bonorino Cristina , Peres Alessandra , Gonçalves Fonseca Simone , Monteiro Marta Chagas , Boeck Carina Rodrigues , Eller Sarah , Oliveira Tiago F , Wendland Eliana M , Romão Pedro R T 
Published: September 2021

AbstractPurinergic signaling modulates immune function and is involved in the immunopathogenesis of several viral infections. This study aimed to investigate alterations in purinergic pathways in COVID-19 patients. Lower plasma ATP and adenosine levels were identified in mild and severe COVID-19 patients associated with proinflammatory cytokine profiles compared to healthy controls. Mild COVID-19 patients presented lower frequencies of CD4+CD25+CD39+ (activated/memory Treg) and CD4+CD25+CD39+CD73+ T cells, and increased frequencies of high differentiated (CD27-CD28-) CD8+T cells compared to health controls. Severe COVID-19 patients also showed higher frequencies of CD4+CD39+, CD4+CD25-CD39+ (memory T effector cell), high differentiated CD8+ T cells (CD27-CD28-) and diminished frequencies of CD4+CD73+, CD4+CD25+CD39+ mTreg, CD4+CD25+CD39+CD73+, CD8+CD73+ and low-differentiated CD8+ T cells (CD27+CD28+) in the blood in relation to mild COVID-19 patients and controls. Moreover, severe COVID-19 patients presented higher expression of PD-1 on low-differentiated CD8+ T cells. Both severe and mild COVID-19 patients presented higher frequencies of CD4+Annexin-V+ and CD8+Annexin-V+ T cells, showing increased T cell apoptosis. Plasma samples collected from severe COVID-19 patients were able to decrease the expression of CD73 on CD4+ and CD8+ T cells of a healthy donor. Interestingly, the in vitro incubation of PBMC from severe COVID-19 patients with adenosine reduced the NF-kB activation in T cells and monocytes. Together, these data add new knowledge regarding the immunopathology of COVID-19 through purinergic regulation, especially concerning adenosine deficiency.Brief CommentaryBackgroundHost factors modulates the type and the strength of the immune response during the viral infection, as well as the disease outcomes. However, to date, the role of purinergic signaling in SARS-CoV-2 infection remains unclear. We sought to evaluate alterations in extracellular adenine nucleotides and CD39/CD73 axis in T cells and their relationship with acute COVID-19 immunopathogenesis.Translational SignificanceCOVID-19 patients present lower extracellular ATP and adenosine levels associated with altered CD39 and CD73 expression in CD4+ and CD8+ T cells. Purinergic signaling correlated with alterations in the differentiation status of CD8+ T cells, lymphocyte mitochondrial membrane polarization and T cell apoptosis. Our demonstration of the lower NF-κB activation in T cells and monocytes afterin vitroadenosine treatment may indicate the regulatory effect of adenosine in the inflammation and cytokine storm of COVID-19. This study adds new knowledge regarding the immunopathology of COVID-19 through purinergic regulation.
Genomic analysis of SARS-CoV-2 breakthrough infections from Varanasi, India
Authors: Zaveri Lamuk , Singh Royana , Basu Priyoneel , Banu Sofia , Mukherjee Payel , Vishwakarma Shani , Sahni Chetan , Kaur Manpreet , Singh Nitish Kumar , Yadav Abhay Kumar , Yadav Ajay Kumar , Ashish  , Mishra Shivani , Tiwari Shivam , Mishra Surendra Pratap , Vodapalli Amareshwar , Bollu Himasri , Das Debashruti , Singh Prajjval Pratap , Chaubey Gyaneshwer , Sowpati Divya Tej , Tallapaka Karthik Bharadwaj 
Published: September 2021

AbstractStudies worldwide have shown that the available vaccines are highly effective against SARS-CoV-2. However, there are growing laboratory reports that the newer variants of concerns (VOCs e.g. Alpha, Beta, Delta etc) may evade vaccine induced defense. In addition to that, there are few ground reports on health workers having breakthrough infections. In order to understand VOC driven breakthrough infection we investigated 14 individuals who tested positive for SARS-CoV-2 after being administered a single or double dose of Covishield (ChAdOx1, Serum Institute of India) from the city of Varanasi, which is located in the Indian state of Uttar Pradesh. Genomic analysis revealed that 78.6% (11/14) of the patients were infected with the B.1.617.2 (Delta) variant. Notably, the frequency (37%) of this variant in the region was significantly lower (p<0.01), suggesting that the vaccinated people were asymmetrically infected with the Delta variant. Most of the patients tested displayed mild symptoms, indicating that even a single dose of the vaccine can help in reducing the severity of the disease. However, more comprehensive epidemiological studies are required to understand the effectiveness of vaccines against the newer VOCs.
Comparative analysis of genome-encoded viral sequences reveals the evolutionary history of flavivirids (family Flaviviridae)
Authors: Bamford Connor G. G. , de Souza William M. , Parry Rhys , Gifford Robert J. 
Published: September 2021

ABSTRACTThe flavivirids (family Flaviviridae) are a group of positive-strand RNA viruses that pose serious risks to human and animal health on a global scale. Here we use flavivirid-derived DNA sequences, identified in animal genomes, to reconstruct the long-term evolutionary history of family Flaviviridae. We demonstrate that flavivirids are >100 million years old and show that this timing can be combined with dates inferred from co-phyletic analysis to produce a cohesive overview of their evolution, distribution and diversity wherein the main flavivirid subgroups originate in early animals and broadly co-diverge with major animal phyla. In addition, we reveal evidence that the ‘classical flaviviruses’ of vertebrates, most of which are transmitted via blood-feeding arthropod vectors, originally evolved in hematophagous arachnids and later acquired the capacity to be transmitted by insects. Our findings imply that the biological properties of flavivirids have been acquired gradually over the course of animal evolution. Thus, broad-scale comparative analysis will likely reveal fundamental insights into their biology. We therefore published our results via an open, extensible, database (Flavivirid-GLUE), which we constructed to facilitate the wider utilisation of genomic data and evolution-related domain knowledge in flavivirid research.
Exosome-transmitted miR-769-5p confers cisplatin resistance and tumorigenesis in gastric cancer by targeting CASP9 and promoting the ubiquitination degradation of p53
Authors: Jing Xinming , Xie Mengyan , Ding Kun , Xu Tingting , Fang Yuan , Ma Pei , Shu Yongqian 
Published: September 2021

AbstractCisplatin resistance is the main cause of poor clinical prognosis in patients with gastric cancer (GC). Yet, the exact mechanism of cisplatin resistance remains unclear. Recent studies have suggested that exocrine miRNAs found in the tumor microenvironment participates in tumor metastasis and drug resistance. In this study, we discovered that cisplatin-resistant GC cells communicate with the tumor microenvironment by secreting microvesicles. The biologically active miR-769-5p can be integrated into exosomes and delivered to sensitive cells, thereby spreading cisplatin resistance. Mi769-5p was upregulated in GC tissues and enriched in the serum exosomes of cisplatin-resistant patients. Mechanistically, miR-769-5p promotes cisplatin resistance by targeting CASP9 so as to inhibit the downstream caspase pathway and promote the degradation of the apoptosis-related protein p53 through the ubiquitin-proteasome pathway. Targeting miR-769 with its antagonist to treat cisplatin-resistant GC cells can restore the cisplatin response, confirming that exosomal miR-769-5p can be a key regulator of cisplatin resistance in GC. Therefore, exosomal miR-769-5p derived from drug-resistant cells can be used as a potential therapeutic predictor of anti-tumor chemotherapy to enhance the effect of anti-cancer chemotherapy, which provides a new treatment option for GC.
A Data-Driven Framework for Identifying Intensive Care Unit Admissions Colonized with Multidrug-Resistant Organisms
Authors: Çağlayan Çağlar , Barnes Sean , Pineles Lisa L. , Klein Eili Y. , Harris Anthony D. 
Published: September 2021

AbstractThe rising prevalence of multi-drug resistant organisms (MDROs), such as Methicillin-resistantStaphylococcus aureus(MRSA), Vancomycin-resistantEnterococci(VRE), and Carbapenem-resistantEnterobacteriaceae(CRE), is an increasing concern in healthcare settings. Leveraging electronic healthcare record data, we developed a data-driven framework to predict MRSA, VRE, and CRE colonization upon intensive care unit admission (ICU), and identify the associated socio-demographic and clinical factors using logistic regression (LR), random forest (RF), and XGBoost algorithms. We performed threshold optimization for converting predicted probabilities into binary predictions and identified the cut-off maximizing the sum of sensitivity and specificity. We achieved the following sensitivity and specificity values with the best performing models: 80% and 66% for VRE with LR, 73% and 77% for CRE with XGBoost, 76% and 59% for MRSA with RF, and 82% and 83% for MDRO (i.e., VRE or CRE or MRSA) with RF. Further, we identified several predictors of MDRO colonization, including long-term care facility exposure, current diagnosis of skin/subcutaneous tissue or infectious/parasitic disease, and recent isolation precaution procedures before ICU admission. Our data-driven modeling framework can be used as a clinical decision support tool for timely predictions, identification of high-risk patients, and selective and timely use of infection control measures in ICUs.