bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence for secondary thrombotic microangiopathy in COVID-19
Authors: Sweeney Joseph M. , Barouqa Mohammad , Krause Gregory J. , Gonzalez-Lugo Jesus D. , Rahman Shafia , Gil Morayma Reyes 
Published: October 2020

ABSTRACTThe causes of coagulopathy associated with COVID-19 disease are poorly understood. We aimed to investigate the relationship between markers of endothelial activation, intravascular hemolysis, coagulation, and organ damage in COVID-19 patients and study their association with disease severity and mortality. We conducted a retrospective study of 181 hospitalized COVID-19 patients randomly selected with equal distribution of survivors and non-survivors. Patients who died had significantly lower ADAMTS13 activity, significantly higher LDH, schistocytes and von Willebrand Factor levels compared to patients discharged alive. Only 30% of patients with an initial ADAMTS13 activity <43% survived vs. 60% with ADAMTS13 ≥43% who survived. In conclusion, COVID-19 may manifest as a TMA-like illness in a subset of hospitalized patients. Presence of schistocytes on admission may warrant a work-up for TMA. These findings indicate the need for future investigation to study the relationship between endothelial and coagulation activation and the efficacy of TMA treatments in COVID-19.
SARS-CoV-2 antibodies in the Southern Region of New Zealand, 2020
Authors: Craigie Alyson , McGregor Reuben , Whitcombe Alana , Carlton Lauren , Harte David , Sutherland Michelle , Parry Matthew , Smit Erasmus , McAuliffe Gary , Ussher James , Moreland Nicole , Jack Susan , Upton Arlo 
Published: October 2020

AbstractBackgroundDuring New Zealand’s first outbreak in early 2020 the Southern Region had the highest per capita SARS-CoV-2 infection rate. PCR testing was initially limited by a narrow case definition and limited laboratory capacity, so cases may have been missed.ObjectivesTo evaluate the Abbott® SARS-CoV-2 IgG nucleocapsid assay, alongside spike-based assays, and to determine the frequency of antibodies among PCR-confirmed and probable cases, contacts, and higher risk individuals in the Southern Region of NZ.Study designPre-pandemic sera (n=300) were used to establish assay specificity and sera from PCR-confirmed SARS-CoV-2 patients (n=78) to establish sensitivity. For prevalence analysis, all samples (n=1214) were tested on the Abbott assay, and all PCR-confirmed cases (n=78), probable cases (n=9), and higher risk individuals with grey-zone (n=14) or positive results (n=11) were tested on four additional SARS-CoV-2 serological assays.ResultsThe median time from infection onset to serum collection for PCR-confirmed cases was 14 weeks (range 11-17 weeks). The Abbott assay demonstrated a specificity of 99.7% (95% CI, 98.2%-99.99%) and a sensitivity of 76.9% (95% CI, 66.0%-85.7%). Spike-based assays demonstrated superior sensitivity ranging 89.7-94.9%. Nine previously undiagnosed sero-positive individuals were identified, and all had epidemiological risk factors.ConclusionsSpike-based assays demonstrated higher sensitivity than the Abbott IgG assay, likely due to temporal differences in antibody persistence. No unexpected SARS-CoV-2 infections were found in the Southern region of NZ, supporting the elimination status of the country at the time this study was conducted.
Trends in knowledge of HIV status and efficiency of HIV testing services in Sub-Saharan Africa (2000-2020): a modelling study of survey and HIV testing program data
Authors: Giguère Katia , Eaton Jeffrey W. , Marsh Kimberly , Johnson Leigh F. , Johnson Cheryl C. , Ehui Eboi , Jahn Andreas , Wanyeki Ian , Mbofana Francisco , Bakiono Fidèle , Mahy Mary , Maheu-Giroux Mathieu 
Published: October 2020

AbstractBackgroundKnowledge of HIV status (KOS) among people living with HIV (PLHIV) is essential for an effective national HIV response. This study estimates progress and gaps in reaching the UNAIDS 2020 target of 90% KOS, and the efficiency of HIV testing services (HTS) in sub-Saharan Africa (SSA), where two thirds of all PLHIV live.MethodsWe used data from 183 population-based surveys (N=2.7 million participants) and national HTS programs (N=315 country-years) from 40 countries as inputs into a mathematical model to examine trends in KOS among PLHIV, median time from HIV infection to diagnosis, HIV testing positivity, and proportion of new diagnoses among all positive tests, adjusting for retesting.FindingsAcross SSA, KOS steadily increased from 6% (95% credible interval [95%CrI]: 5% to 7%) in 2000 to 84% (95%CrI: 82% to 86%) in 2020. Twelve countries and one region, Southern Africa, reached the 90% target. In 2020, KOS was lower among men (79%) than women (87%) across SSA. PLHIV aged 15-24 years were the least likely to know their status (65%), but the largest gap in terms of absolute numbers was among men aged 35-49 years, with over 700,000 left undiagnosed. As KOS increased from 2000 to 2020, the median time to diagnosis decreased from 10 to 3 years, HIV testing positivity declined from 9% to 3%, and the proportion of first-time diagnoses among all positive tests dropped from 89% to 42%.InterpretationOn the path towards the next UNAIDS target of 95% diagnostic coverage by 2030, and in a context of declining positivity and yield of first-time diagnoses, we need to focus on addressing disparities in KOS. Increasing KOS and treatment coverage among older men could be critical to reduce HIV incidence among women in SSA, and by extension, reducing mother-to-child transmission.
Covid-19 in children: is there any correlation with renal function and severity of the disease?
Authors: Rachmadi Dedi , Widiasta Ahmedz , Sukandar Hadyana , Sekarwana Nanan , Hilmanto Dany 
Published: October 2020

AbstractBackgroundKidney manifestations are life-threatening conditions, such as end-stage renal disease (ESRD), especially when attributed to viral infections. The severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2), is an emerging health problem worldwide, potentially affecting all organs, including the kidney. Most reports on kidney manifestations were conducted mostly on the adult and elderly population, and limited on children. Therefore, this study aims to analyse the correlation between kidney manifestations with the renal function of pediatric patients suffering from COVID-19.MethodsAn observational analytic study was conducted in Hasan Sadikin General Hospital, Bandung, Indonesia, from March to August 2020. The demographic data, clinical signs, laboratory results, and notable kidney function were analysed, while the disease was classified as severe and nonsevere based on its clinical appearance. The Mann-Whitney test for nonparametric was used to analyze the collected data. Results. In this study, 16 COVID-19 children were selected as the research subjects, the median eGFR value in the severe group was lower (49.59 ml / minute / 1.73m2) compared to the nonsevere (113 ml / minute / 1.73m2), however, not statistically significant (p = 0.521). Significant high CRP and low thrombocyte levels were found in severe SARS-CoV-2 infection (p<0.05). Conclusion. A severe SARS-CoV-2 infection tends to affect the kidney, which is manifested as decreased glomerular filtration rate (GFR).
NGSremix: A software tool for estimating pairwise relatedness between admixed individuals from next-generation sequencing data
Authors: Nøhr Anne Krogh , Hanghøj Kristian , Erill Genis Garcia , Moltke Ida , Albrechtsen Anders 
Published: October 2020

AbstractEstimation of relatedness between pairs of individuals is important in many genetic research areas. When estimating relatedness, it is important to account for admixture if this is present. However, the methods that can account for admixture are all based on genotype data as input, which is a problem for low depth next-generation sequencing (NGS) data from which genotypes are called with high uncertainty. Here we present a software tool, NGSremix, for maximum likelihood estimation of relatedness between pairs of admixed individuals from low depth NGS data, which takes the uncertainty of the genotypes into account via geno-type likelihoods. Using both simulated and real NGS data for admixed individuals with an average depth of 4x or below we show that our method works well and clearly outperforms all the commonly used state-of-the-art relatedness estimation methods PLINK, KING, relateAdmix, and ngsRelate that all perform quite poorly. Hence, NGSremix is a useful new tool for estimating relatedness in admixed populations from low-depth NGS data. NGSremix is implemented in C/C++ in a multi-threaded software and is freely available on Githubhttps://github.com/KHanghoj/NGSremix.
Tocilizumab in nonventilated patients hospitalized with Covid-19 pneumonia
Authors: Salama Carlos , Han Jian , Yau Linda , Reiss William G. , Kramer Benjamin , Neidhart Jeffrey D. , Criner Gerard J. , Kaplan-Lewis Emma , Baden Rachel , Pandit Lavannya , Cameron Miriam L. , Garcia-Diaz Julia , Chávez Victoria , Mekebeb-Reuter Martha , Menezes Ferdinando Lima , Shah Reena , González-Lara Maria F. , Assman Beverly , Freedman Jamie , Mohan Shalini V. 
Published: October 2020

AbstractBackgroundCoronavirus disease 2019 (Covid-19) pneumonia is often associated with hyperinflammation. Safety and efficacy of the anti–interleukin-6 receptor antibody tocilizumab was evaluated in patients hospitalized with Covid-19 pneumonia.MethodsNonventilated patients hospitalized with Covid-19 pneumonia were randomized (2:1) to tocilizumab (8 mg/kg intravenous) or placebo plus standard care. Sites enrolling high-risk and minority populations were emphasized. The primary endpoint was cumulative proportion of patients requiring mechanical ventilation or who had died by Day 28.ResultsOf 389 randomized patients, 249 patients received tocilizumab and 128 received placebo in the modified intent-to-treat population (Hispanic/Latino, 56.0%; Black/African American, 14.9%; American Indian/Alaska Native, 12.7%; White, 12.7%; other/unknown, 3.7%). The cumulative proportion (95% confidence interval [CI]) of patients requiring mechanical ventilation or who had died by Day 28 was 12.0% (8.52% to 16.86%) and 19.3 % (13.34% to 27.36%) for the tocilizumab and placebo arms, respectively (log-rank P=0.0360; hazard ratio, 0.56 [95% CI, 0.33 to 0.97]). Median time to clinical failure up to Day 28 favored tocilizumab over placebo (hazard ratio 0.55 [95% CI, 0.33 to 0.93]). All-cause mortality by Day 28 was 10.4% with tocilizumab and 8.6% with placebo (weighted difference, 2.0% [95% CI, – 5.2% to 7.8%). In the safety population, serious adverse events occurred in 15.2% of tocilizumab patients (38/250 patients) and 19.7% of placebo patients (25/127).ConclusionsThis trial demonstrated the efficacy and safety of tocilizumab over placebo in reducing the likelihood of progression to requiring mechanical ventilation or death in nonventilated patients hospitalized with Covid-19 pneumonia.Trial registrationClinicalTrials.govNCT04372186
Prevalence of Depressive Disorders and Associated Demographic Factors Among Refugees Amidst COVID-19 in Nakivale Refugee Camp in Southwestern Uganda
Authors: Kabunga Amir , Anyayo Lucas Goodgame 
Published: October 2020

AbstractIntroductionThe COVID-19 pandemic and health measures to prevent it have unprecedented effects on the mental health of the refugees. However, the situation of refugees in developing countries is unclear. Thus, this study estimated the prevalence of and associated demographic factors during COVID-19 pandemic.The methodologyemployed a cross-sectional survey carried out in June 2020 in which 146 adult refugees from Nakivale settlement camp were randomly selected to fill out a questionnaires-demographics and PHQ9.Resultsrevealed that the majority of respondents were female (53%) and 47% had a depressive disorder. There was no statistical relationship between demographics (gender, age and marital status) and depressive disorders.In Conclusionfindings indicate that depressive disorders are prevalent among refugees in Nakivale settlement and it is important to identify refugees affected mentally and given proper treatment.
Automated Feature Extraction from Large Cardiac Electrophysiological Data Sets
Authors: Jurkiewicz John , Kroboth Stacie , Zlochiver Viviana , Hinow Peter 
Published: October 2020

AbstractRationaleA new multi-electrode array-based application for the long-term recording of action potentials from electrogenic cells makes possible exciting cardiac electrophysiology studies in health and disease. With hundreds of simultaneous electrode recordings being acquired over a period of days, the main challenge becomes achieving reliable signal identification and quantification.ObjectiveWe set out to develop an algorithm capable of automatically extracting regions of high-quality action potentials from terabyte size experimental results and to map the trains of action potentials into a low-dimensional feature space for analysis.Methods and ResultsOur automatic segmentation algorithm finds regions of acceptable action potentials in large data sets of electrophysiological readings. We use spectral methods and support vector machines to classify our readings and to extract relevant features. We are able to show that action potentials from the same cell site can be recorded over days without detrimental effects to the cell membrane. The variability between measurements 24 h apart is comparable to the natural variability of the features at a single time point.ConclusionsOur work contributes towards a non-invasive approach for cardiomyocyte functional maturation, as well as developmental, pathological and pharmacological studies. As the human-derived cardiac model tissue has the genetic makeup of its donor, a powerful tool for individual drug toxicity screening emerges.
Rice Calcium/Calmodulin-Dependent Protein Kinase Directly Phosphorylates a Mitogen-Activated Protein Kinase Kinase to Regulate Abscisic Acid Responses
Authors: Chen Min , Ni Lan , Chen Jing , Sun Manman , Qin Caihua , Zhang Gang , Zhang Aying , Jiang Mingyi 
Published: October 2020

ABSTRACTCa2+/calmodulin (CaM)-dependent protein kinase (CCaMK) is an important positive regulator of abscisic acid (ABA) and abiotic stress signaling in plants and is believed to act upstream of mitogen-activated protein kinase (MAPK) in ABA signaling. However, it is unclear how CCaMK activates MAPK in ABA signaling. Here, we show that OsDMI3, a rice (Oryza sativa) CCaMK, directly interacts with and phosphorylates OsMKK1, a MAPK kinase (MKK) in rice, in vitro and in vivo. OsDMI3 was found to directly phosphorylate Thr-25 in the N-terminus of OsMKK1, and this Thr-25 phosphorylation is OsDMI3-specific in ABA signaling. The activation of OsMKK1 and its downstream kinase OsMPK1 is dependent on Thr-25 phosphorylation of OsMKK1 in ABA signaling. Moreover, ABA treatment also induces the phosphorylation in the activation loop of OsMKK1, and the two phosphorylations in the N-terminus and in the activation loop are independent. Further analyses revealed that OsDMI3-mediated phosphorylation of OsMKK1 positively regulates ABA responses in seed germination, root growth, and tolerance to both water stress and oxidative stress. Our results indicate that OsMKK1 is a direct target of OsDMI3, and OsDMI3-mediated phosphorylation of OsMKK1 plays an important role in the activation of MAPK cascade and ABA signaling.One-sentence summaryOsMKK1 is a direct target of OsDMI3, and OsDMI3-mediated phosphorylation of OsMKK1 plays an important role in the activation of MAPK cascade and ABA signaling.The author responsible for distribution of materials integral to the findings presented in this article in accordance with the policy described in the Instructions for Authors (www.plantcell.org) is: Mingyi Jiang (myjiang@njau.edu.cn)
Cancer immunotherapy by NC410, a LAIR-2 Fc protein blocking LAIR-collagen interaction
Authors: Ramos M. Inês Pascoal , Tian Linjie , de Ruiter Emma J. , Song Chang , Paucarmayta Ana , Singh Akashdip , Elshof Eline , Vijver Saskia V. , Shaik Jahangheer , Bosiacki Jason , Cusumano Zachary , Liu Linda , Langermann Sol , Willems Stefan , Flies Dallas , Meyaard Linde 
Published: October 2020

AbstractCollagens are a primary component of the extracellular matrix and are functional ligands for the inhibitory immune receptor leukocyte associated immunoglobulin-like receptor-1 (LAIR-1). Leukocyte associated immunoglobulin-like receptor-2 (LAIR-2) is a secreted protein that can act as a decoy receptor by binding collagen with higher affinity than LAIR-1. We propose that collagens promote immune evasion by interacting with LAIR-1 and that LAIR-2 could release LAIR-1 mediated immune suppression. Analysis of public datasets shows high LAIR-2 expression being associated with a favorable outcome in certain tumors. We designed a dimeric LAIR-2 with a functional IgG1 Fc tail, NC410, and showed that NC410 reduces tumor growth and increases T cell expansion and effector function in humanized tumor models. Immunohistochemical analysis of human tumors shows that NC410 binds to collagen-rich areas where LAIR-1+immune cells are localized. Our findings show that NC410 might be a powerful new strategy for cancer immunotherapy for immune-excluded tumors.
Variations of intracellular density during the cell cycle arise from tip-growth regulation in fission yeast
Authors: Odermatt Pascal D. , Miettinen Teemu P. , Kang Joon Ho , Bostan Emrah , Manalis Scott , Huang Kerwyn Casey , Chang Fred 
Published: October 2020

AbstractIntracellular density impacts the physical nature of the cytoplasm and can globally affect cellular processes, yet density regulation remains poorly understood. Here, using a new quantitative phase imaging method, we determined that dry-mass density varies during the cell cycle in fission yeast. Density decreased during G2, increased in mitosis and cytokinesis, and rapidly dropped at cell birth. These density variations were explained by a constant rate of biomass synthesis, coupled to slowdown of volume growth during cell division and rapid expansion post-cytokinesis. Arrest at specific cell-cycle stages led to continued increases or decreases in density. Spatially heterogeneous patterns of density suggested links between density regulation and tip growth, and septum bending away from higher-density daughters linked density to intracellular osmotic pressure. Our results demonstrate that systematic density variations during the cell cycle are predominantly due to modulation of volume expansion, and reveal functional consequences of density gradients and cell-cycle arrests.
Databiology Lab CORONAHACK: Collection of Public COVID-19 Data
Authors: Pérez Juan Caballero , Contreras José Manuel Caballero , de Blas Pérez Carlos , Alvarez Felipe Leza 
Published: October 2020

AbstractCOVID-19 has had an unprecedented global impact in health and economy affecting millions of persons world-wide. To support and enable a collaborative response from the global research communities, we created a data collection for different public sources for anonymized patient clinical data, imaging datasets, molecular data as nucleotide and protein sequences for the SARS-CoV-2 virus, reports of count of cases and deaths per city/country, and other economic indicators in Databiology Lab (https://www.lab.databiology.net/) where researchers could access these data assets and use the hundreds of available open source bioinformatic applications to analyze them. These data assets are regularly updated and was used in a successful virtual 3-day hackathon organized by Databiology Ltd and Mindstream-AI where hundreds of attendees to work collaboratively to analyze these data collections.
Identification of specific biomarkers and pathways in the synovial tissues of patients with osteoarthritis in comparison to rheumatoid arthritis
Authors: Gu Hanming , Yuan Gongsheng 
Published: October 2020

AbstractOsteoarthritis and rheumatoid arthritis are two common arthritis with different pathogenesis. Here, we explore the difference of genes and biological pathways in human synovial fibroblasts by using a bioinformatics method to clarify their potential pathogenesis. The GSE7669 dataset was originally produced by using an Affymetrix Human Genome U95 platform. We used the KEGG and GO analysis to identify the functional categories and pathways. Our results suggested that biological adhesion and cell adhesion are the main signaling pathways in osteoarthritis in comparison to rheumatoid arthritis. Furthermore, Albumin, MAPK3, PTPRC, COL1A1, and CXCL12 may be key genes in osteoarthritis. Therefore, our study provides potential targets for the specific and accurate therapy of osteoarthritis.
Histone H2A ubiquitination resulting from Brap loss of function connects multiple aging hallmarks and accelerates neurodegeneration
Authors: Guo Y. , Chomiak A. A. , Hong Y. , Lowe C. C. , Chan W-C. , Andrade J. , Pan H. , Zhou X. , Berezovski E. , Monuki E. S. , Feng Y. 
Published: October 2020

SUMMARYAging is an intricate process that is characterized by multiple hallmarks including stem cell exhaustion, genome instability, epigenome alteration, impaired proteostasis, and cellular senescence. While each of these traits is detrimental at the cellular level, it remains unclear how they are interconnected to cause systemic organ deterioration. Here we show that abrogating Brap, a BRCA1 associated protein important for neurogenesis, results in cellular senescence with persistent DNA double-strand breaks and elevation of histone H2A mono- and poly-ubiquitination (H2Aub). The high H2Aub initiates histone proteolysis, leading to both epigenetic alteration and proteasome overflow. These defects induce neuroinflammation, impair proteostasis, accelerate neurodegeneration, and substantially shorten lifespan in mice carrying Brap deletions in the brain. We further show H2Aub is also increased in human brain tissues of Alzheimer’s disease. These data together suggest that chromatin aberrations mediated by H2Aub act as a nexus of multiple aging hallmarks and promote tissue-wide degeneration.
Theta-gamma coupling depends on breathing rate
Authors: Hammer Maximilian , Schwale Chrysovalandis , Brankačk Jurij , Draguhn Andreas , Tort Adriano BL 
Published: October 2020

AbstractTemporal coupling between theta and gamma oscillations is a hallmark activity pattern of several cortical networks and becomes especially prominent during REM sleep. In a parallel approach, nasal breathing has been recently shown to generate phase-entrained network oscillations which also modulate gamma. Both slow rhythms (theta and respiration-entrained oscillations) have been suggested to aid large-scale integration but they differ in frequency, display low coherence, and modulate different gamma sub-bands. Respiration and theta are therefore believed to be largely independent. In the present work, however, we report an unexpected but robust relation between theta-gamma coupling and respiration in mice. Interestingly, this relation takes place not through the phase of individual respiration cycles, but through respiration rate: the strength of theta-gamma coupling exhibits an inverted V-shaped dependence on breathing rate, leading to maximal coupling at breathing frequencies of 4-6 Hz. Noteworthy, when subdividing sleep epochs into phasic and tonic REM patterns, we find that breathing differentially relates to theta-gamma coupling in each state, providing new evidence for their physiological distinctiveness. Altogether, our results reveal that breathing correlates with brain activity not only through phase-entrainment but also through rate-dependent relations with theta-gamma coupling. Thus, the link between respiration and other patterns of cortical network activity is more complex than previously assumed.