bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of COVID-19 infection during pregnancy and neonatal prognosis: what is the evidence?
Authors: Sousa Álvaro Francisco Lopes , de Carvalho Herica Emilia Félix , de Oliveira Layze Braz , Schneider Guilherme , Camargo Emerson Lucas Silva , Watanabe Evandro , de Andrade Denise , Fernandes Ana Fátima Carvalho , Mendes Isabel Amélia Costa , Fronteira Inês 
Published: April 2020

BackgroundLittle is known about how COVID-19 infection affects pregnant women, as well as about the possibility of vertical transmission or complications in childbirth. This study’s aims to assess the current evidence presented in the literature regarding the potential risks of COVID-19 infection among pregnant women and consequent fetal transmission.Methodsa systematic literature review assessing papers published in the most comprehensive databases in the field of health, intended to answer the question: “What are the effects of COVID-19 infection during pregnancy and what is the neonatal prognosis?”Results42 papers published in 2020 were eligible. Were included 19 case reports (45%), 15 cross-sectional descriptive studies (35%), 6 cross-sectional analytical studies (14%), one case-control study (3%) and one cohort study (3%), presenting low levels of evidence. A total of 650 pregnant women and 511 infants were assessed. More than half of pregnant women having cesarean deliveries (324/64%). Only 410 (80%) infants were tested for SARS-CoV-2, of which 8 (2%) were positive, however, based on what was assessed that there is no evidence of vertical transmission so far, as there are gaps concerning the care taken during and after delivery, and biological sample proper for testing the SARS-CoV-2.Conclusionshealth professionals cannot rule out a possible worsening of the clinical picture of the pregnant woman infected with SARS-CoV-2 because she is asymptomatic or does not have comorbidities related to gestation. Pregnant women and health professionals should be cautious and vigilant, as soon as their pregnancy is confirmed, with or without confirmed infection, as this review checks for infected pregnant women in all trimesters of pregnancy.
The role of corticosteroids in the management of critically ill patients with coronavirus disease 2019 (COVID-19): A meta-analysis
Authors: Gangopadhyay Kalyan Kumar , Mukherjee Jagat J , Sinha Binayak , Ghosal Samit 
Published: April 2020

AbstractObjectiveThere are no controlled studies on the role of systemic corticosteroids (CS) in patients with coronavirus disease 2019 (COVID-19). In the absence of high-quality evidence, understandably the recommendations from various organizations are cautious. Several randomized controlled trials are underway but shall take time to conclude. We therefore undertook a meta-analysis to ascertain the role of CS in the management of critically ill patients with COVID-19.Data SourcesElectronic databases, including Pubmed, Cochrane library and Embase, were searched, using the keywords of interest and the PICO search technique, from inception to 12th April 2020.Study SelectionStudies highlighting the use of CS in coronavirus infection with severe acute respiratory syndrome (SARS), Middle East Respiratory Syndrome (MERS) and COVID-19 were selected based on pre-determined inclusion criteria.Data extractionData was extracted into an excel sheet and transferred to comprehensive meta-analysis software version 3, Biostat Inc., Englewood, NJ, USA, for analysis.Data synthesisFive studies with SARS-CoV-2 infection were included in the meta-analysis. The rate ratio (RR) for mortality in patients with SARS-CoV-2 infection was 1.26 (95% CI: 0.96-1.65, I2: 74.46), indicating lack of benefit of CS therapy on mortality in critically ill patients with COVID-19. The RR for mortality on analysis of the three studies that particularly reported on patients with significant pulmonary compromise secondary to SARS-CoV-2 infection was neutral (RR: 0.91, 95% CI: 0.63-1.33, I2: 63.38).ConclusionsThe use of CS in critically ill patients with COVID-19 did not improve or worsen mortality. Pending further information from controlled studies, CS can be used in critically ill patients with COVID-19 with ‘critical illness related corticosteroid insufficiency’ and moderate to severe ARDS without the risk of increased mortality.
Estimating the impact of COVID-19 control measures using a Bayesian model of physical distancing
Authors: Anderson Sean C. , Edwards Andrew M. , Yerlanov Madi , Mulberry Nicola , Stockdale Jessica E. , Iyaniwura Sarafa A. , Falcao Rebeca C. , Otterstatter Michael C. , Irvine Michael A. , Janjua Naveed Z. , Coombs Daniel , Colijn Caroline 
Published: April 2020

AbstractExtensive physical distancing measures are currently the primary intervention against coronavirus disease 2019 (COVID-19) worldwide. It is therefore urgent to estimate the impact such measures are having. We introduce a Bayesian epidemiological model in which a proportion of individuals are willing and able to participate in distancing measures, with the timing of these measures informed by survey data on attitudes to distancing and COVID-19. We fit our model to reported COVID-19 cases in British Columbia, Canada, using an observation model that accounts for both underestimation and the delay between symptom onset and reporting. We estimate the impact that physical distancing (also known as social distancing) has had on the contact rate and examine the projected impact of relaxing distancing measures. We find that distancing has had a strong impact, consistent with declines in reported cases and in hospitalization and intensive care unit numbers. We estimate that approximately 0.78 (0.66–0.89 90% CI) of contacts have been removed for individuals in British Columbia practising physical distancing and that this fraction is above the threshold of 0.45 at which prevalence is expected to grow. However, relaxing distancing measures beyond this threshold re-starts rapid exponential growth. Because the extent of underestimation is unknown, the data are consistent with a wide range in the prevalence of COVID-19 in the population; changes to testing criteria over time introduce additional uncertainty. Our projections indicate that intermittent distancing measures—if sufficiently strong and robustly followed— could control COVID-19 transmission, but that if distancing measures are relaxed too much, the epidemic curve would grow to high prevalence.
Single cell transcriptomic analysis of diffuse large B cells in cerebrospinal fluid of central nervous system lymphoma
Authors: Ruan Haoyu , Wang Zhe , Zhai Yue , Xu Ying , Pi Linyu , Zheng Jihong , Zhou Yihang , Zhang Cong , Huang RuoFan , Chen Kun , Li Xiangyu , Ma Weizhe , Wu Zhiyuan , Shen Jie , Deng Xuan , Zhang Chao , Guan Ming 
Published: April 2020

AbstractDiffuse large B-cell lymphoma (DLBCL) is the predominant type of central nervous system lymphoma (CNSL) including primary CNSL and secondary CNSL. Diffuse large B cells in cerebrospinal fluid (CSF-DLBCs) have offered great promise for the diagnostics and therapeutics of CNSL leptomeningeal involvement. To explore the distinct phenotypic states of CSF-DLBCs, we analyzed the transcriptomes of 902 CSF-DLBCs from six CNSL-DLBCL patients using single-cell RNA sequencing technology. We defined CSF-DLBCs based on abundant expression of B-cell markers, as well as the enrichment of cell proliferation and energy metabolism pathways. CSF-DLBCs within individual patients exhibited monoclonality with similar variable region of light chains (VL) expression. It is noteworthy that we observed some CSF-DLBCs have double classes of VL (lambda and kappa) transcripts. We identified substantial heterogeneity in CSF-DLBCs, and found significantly greater among-patient heterogeneity compared to among-cell heterogeneity within a given patient. The transcriptional heterogeneity across CSF-DLBCs is manifested in cell cycle state and cancer-testis antigens expression. Our results will provide insight into the mechanism research and new diagnostic direction of CNSL-DLBCL leptomeningeal involvement.
Dissemination routes of the carbapenem resistance plasmid pOXA-48 in a hospital setting
Authors: León-Sampedro Ricardo , DelaFuente Javier , Díaz-Agero Cristina , Crellen Thomas , Musicha Patrick , Rodriguez-Beltran Jerónimo , de la Vega Carmen , Hernández-García Marta ,   R-GNOSIS WP5 Study Group, Lopez-Fresneña Nieves , Ruiz-Garbajosa Patricia , Canton Rafael , Cooper Ben S , Millan Alvaro San 
Published: April 2020

Introductory paragraphInfections caused by carbapenemase-producing enterobacteria (CPE) are a major concern in clinical settings worldwide. Two fundamentally different processes shape the epidemiology of CPE in hospitals: the dissemination of CPE clones from patient to patient (between-patient transfer), and the transfer of carbapenemase-encoding plasmids between enterobacteria in the gut microbiota of individual patients (within-patient transfer). The relative contribution of each process to the overall dissemination of carbapenem resistance in hospitals remains poorly understood. Here, we used mechanistic models combining epidemiological data from more than 9,000 patients with whole genome sequence information from 250 enterobacteria clones to characterise the dissemination routes of the carbapenemase-encoding plasmid pOXA-48 in a hospital setting over a two-year period. Our results revealed frequent between-patient transmission of high-risk pOXA-48-carrying clones, mostly ofKlebsiella pneumoniaeand sporadicallyEscherichia coli.The results also identified pOXA-48 dissemination hotspots within the hospital, such as specific wards and individual rooms within wards. Using high-resolution plasmid sequence analysis, we uncovered the pervasive within-patient transfer of pOXA-48, suggesting that horizontal plasmid transfer occurs in the gut of virtually every colonised patient. The complex and multifaceted epidemiological scenario exposed by this study provides new insights for the development of intervention strategies to control the in-hospital spread of CPE.
Interleukin-6 blockade for severe COVID-19
Authors: Roumier Mathilde , Paule Romain , Groh Matthieu , Vallée Alexandre , Ackermann Félix ,   for the Foch COVID-19 Study Group
Published: April 2020

AbstractIn the context of COVID-19 pandemic and growing tensions worldwide regarding healthcare facilities, there is an urgent need for effective treatments likely to reduce the crunch of ICU beds. Following the assumption by Mehta and colleagues who exhorted physicians to screen patients with severe COVID-19 for hyperinflammation and investigate immunomodulatory drugs in this setting, we relate our short-term - yet promising - experience regarding IL6 blockade with tocilizumab in 30 selected patients of less than 80 years of age, >5 days of prior disease duration, severe (i.e. requiring strictly over 6L/min of oxygen therapy) rapidly deteriorating (i.e. increase by more than 3L/min of oxygen flow within the previous 12 hours) COVID-19-related pneumonia. By comparison with a control group of patients (matched for age, gender and disease severity using the inverse probability of treatment weighted methodology) that did not receive tocilizumab. We demonstrate that, in highly selected patients, IL6 blockade could curb the “cytokine storm”, prevent ICU admission and the requirement for mechanical ventilation. Notwithstanding the shortcomings of this retrospective small sample-size study, we believe that these preliminary findings support the fostering of research efforts in the fight against COVID-19-induced inflammation, especially before patients require admission to the ICU.
Antigenicity, stability, and reproducibility of Zika reporter virus particles for long-term applications
Authors: Whitbeck J. Charles , Thomas Anu , Kadash-Edmondson Kathryn , Escuer Ariadna Grinyo i , Cheng Celine , Liao Grant C. , Holtsberg Frederick W. , Aman M. Javad , Simmons Graham , Davidson Edgar , Doranz Benjamin J. 
Published: April 2020

ABSTRACTThe development of vaccines against flaviviruses, including Zika virus (ZIKV) and dengue virus (DENV), continues to be a major challenge, hindered by the lack of efficient and reliable methods for screening neutralizing activity of sera or antibodies. To address this need, we previously developed a plasmid-based, replication-incompetent DENV reporter virus particle (RVP) production system as an efficient and safe alternative to the Plaque Reduction Neutralization Test (PRNT). As part of the response to the 2015-2016 ZIKV outbreak, we recently developed pseudo-infectious ZIKV RVPs by modifying our DENV RVP system. The use of ZIKV RVPs as critical reagents in human clinical trials requires their further validation using stability and reproducibility metrics for large-scale applications. In the current study, we validated ZIKV RVPs using infectivity, neutralization, and enhancement assays with monoclonal antibodies (MAbs) and human ZIKV-positive patient serum. ZIKV RVPs are antigenically identical to live virus based on binding ELISA and neutralization results and are nonreplicating based on the results of plaque formation assays. We demonstrate reproducible neutralization titer data (NT50values) across different RVP production lots, volumes, time frames, and laboratories. We also show RVP stability across experimentally relevant time intervals and temperatures. Our results demonstrate that ZIKV RVPs provide a safe, rapid, and reproducible reagent for large-scale, long-term studies of neutralizing antibodies and sera, which can facilitate large-scale screening and epidemiological studies to help expedite ZIKV vaccine development.AUTHOR SUMMARYZIKV is a mosquito-borne virus that can cause severe birth defects and other disorders. Large outbreaks of ZIKV occurred in 2015 and 2016 and there are still no drugs or vaccines available to protect against ZIKV infection. Vaccine development has been hindered by the lack of safe and efficient methods to screen ZIKV neutralizing properties of patient sera or antibodies, especially in the context of large clinical trials. To address this unmet need, we developed and validated the use of ZIKV reporter virus particles (RVPs), a safe, high-throughput and quantitative alternative to using live virus for neutralization studies. We show that ZIKV RVPs are stable, show lot-to-lot consistency and provide reproducible neutralization data that is suitable for large-scale studies are needed for development of a ZIKV vaccine, epidemiologic surveillance, and high-throughput screening.
Tendon and Motor Phenotypes in theCrtap-/-Mouse Model of Recessive Osteogenesis Imperfecta
Authors: Grol Matthew W. , Haelterman Nele A. , Lim Joohyun , Munivez Elda M. , Archer Marilyn , Hudson David M. , Tufa Sara F. , Keene Douglas R. , Lei Kevin , Park Dongsu , Eyre David R. , Lee Brendan H. 
Published: April 2020

ABSTRACTOsteogenesis imperfecta (OI) is characterized by short stature, skeletal deformities, low bone mass with bone fragility, and motor deficits. A subset of OI patients also present with joint hypermobility; however, the role of tendon/ligament dysfunction in OI pathogenesis is largely unknown. Using theCrtap-/-mouse model of severe, recessive OI, we found that mutant Achilles tendons and patellar ligaments were thinner with increased collagen cross-links and reduced collagen fibril size at 1- and 4-months compared to wildtype. Patellar ligaments fromCrtap-/-mice also had fewer progenitors with a concomitant increase in immature cells. RNA-seq analysis of Achilles tendons and patellar ligaments from 1-monthCrtap-/-mice revealed dysregulation in matrix gene expression concomitant with predicted alterations in TGF-β, inflammatory, and metabolic signaling. Finally, a series of behavioral tests revealed severe motor impairments and reduced grip strength in 4-monthCrtap-/-mice – a phenotype that correlates with the tendon/ligament pathology.
A New Resource for Genomics and Precision Health Information and Publications on the Investigation and Control of COVID-19 and other Coronaviruses
Authors: Yu Wei , Gwinn Marta , Khoury Muin J. 
Published: April 2020

AbstractSummaryWe developed a new online database that contains the most updated published scientific literature, online news and reports, CDC and National Institutes of Health (NIH) resources. The tool captures emerging discoveries and applications of genomics, molecular, and other precision medicine and precision public health tools in the investigation and control of coronavirus diseases, including COVID-19, MERS-CoV, and SARS.AvailabilityCoronavirus Disease Portal (CDP) can be freely accessed viahttps://phgkb.cdc.gov/PHGKB/coVInfoStartPage.action.Contactwyu@cdc.gov
VisEgg: A robust phenotyping tool to assess rainbow trout egg features and viability
Authors: Cardona Emilie , Bugeon Jérôme , Segret Emilien , Bobe Julien 
Published: April 2020

AbstractAssessing female fish reproductive success requires a thorough evaluation of egg characteristics, including egg number, size and variability as well as egg developmental potential through the monitoring of embryo survival after fertilization. While embryonic success relies, at least in part, on paternal contribution, some parameters are strictly related to egg characteristics, one of the main ones being the viability of the egg when released into the water at spawning. It is however not necessarily possible, at least in salmonid fish that lay non-transparent eggs, to separate the different causes of egg/embryo failure.In this context, our aim was i) to develop a simple and rapid system to capture images of rainbow trout eggs combined with computerized processing of these images to perform a fully automatic individual characterization of egg features including number and size ii) to estimate unfertilized egg viability through the monitoring of the percentage of eggs that will not survive to water hydration.To evaluate the VisEgg system, unfertilized eggs (approximatively 400 eggs per batch) originating from 105 different females were hydrated in water. After 24h, a picture of the eggs was obtained using a dedicated shooting system consisting of a light source and a digital single-lens reflex (SLR) camera. An image processing algorithm was developed to allow the automatic detection and separation of the eggs and to perform automatic measurements of egg number and individual egg size. The presence of white egg was used as an indirect measure of egg integrity, the “whitening” being the result of water entry into the egg through the vitelline membrane. These white eggs were therefore considered as non-viable, as a result of their lack of physical integrity.Fertilization assays were performed in parallel using a subsample of the same egg batch. Embryonic development was monitored and hatching rate was calculated. A significant correlation between white egg percentage after hydration and hatching rate was observed (Spearman coefficient =-0.557, p<0.001), in consistency with the fact that non-viable egg will not allow successful embryonic development. In contrast, the percentage of eggs that do not successfully hatched includes egg/embryo failures of different nature including egg viability, their capacity to be fertilized and to develop into an embryo. Using VisEgg, we were able to quantify the lack of viability of the eggs separately from the different other events that may occur during fertilization and incubation. VisEgg is a convenient and reliable tool to obtain individuals measures on trout eggs. It can be used to assess not only egg size and egg number but also unfertilized egg viability before fertilization.
Mitochondrial survivin reduces oxidative phosphorylation in cancer cells by inhibiting mitophagy
Authors: Townley Amelia R. , Wheatley Sally P. 
Published: April 2020

AbstractSurvivin is a cancer-associated protein that is pivotal for cellular life and death: it is an essential mitotic protein and an inhibitor of apoptosis. In cancer cells, a small pool of survivin localises to the mitochondria, the function of which remains to be elucidated. Here, we report that mitochondrial survivin inhibits the selective form of autophagy, called “mitophagy”, causing an accumulation of respiratory defective mitochondria. Mechanistically the data reveal that survivin prevents recruitment of the E3-ubiquitin ligase Parkin to mitochondria and their subsequent recognition by the autophagosome. The data also demonstrate that, as a consequence of this blockade, cells expressing high levels of survivin have an increased dependency on anaerobic glycolysis. As these effects were found exclusively in cancer cells they suggest that the primary act of mitochondrial survivin is to force cells to implement the “Warburg Effect” by inhibiting mitochondrial turnover.
TargetDB: A target information aggregation tool and tractability predictor
Authors: De Cesco Stephane P. , Davis John B. , Brennan Paul E. 
Published: April 2020

ABSTRACTWhen trying to identify new potential therapeutic targets, access to data and knowledge is increasingly important. In a field where new resources and data sources become available every day, it is crucial to be able to take a step back and look at the wider picture in order to identify potential drug targets. While this task is routinely performed by bespoke researchers, it is often time-consuming and lacks uniformity when one wants to compare multiple targets at the same time. Therefore we developed TargetDB, a tool that aggregates public information available on given target(s) (Links to disease, safety, 3D structures, ligandability, novelty,…) and assembles it in an easy to read output ready for the researcher to analyze. In this manuscript, we will present the methodology used to develop TargetDB as well as test cases.
Structural basis for human TRPC5 channel inhibition by two distinct inhibitors
Authors: Song Kangcheng , Wei Miao , Guo Wenjun , Kang Yunlu , Wu Jing-Xiang , Chen Lei 
Published: April 2020

AbstractTRPC5 channel is a non-selective cation channel that participates diverse physiological processes. Human TRPC5 inhibitors show promise in the treatment of anxiety disorder, depression and kidney disease. Despite the high relevance of TRPC5 to human health, its inhibitor binding pockets have not been fully characterized due to the lack of structural information, which greatly hinders structure-based drug discovery. Here we show cryo-EM structures of human TRPC5 in complex with two distinct inhibitors, namely clemizole and HC-070, to the resolution of 2.7 Å. Based on the high-quality cryo-EM maps, we uncover the different binding pockets and detailed binding modes for these two inhibitors. Clemizole binds inside the voltage sensor-like domain of each subunit, while HC-070 binds close to the ion channel pore and is wedged between adjacent subunits. Both of them exert the inhibitory function by stabilizing the ion channel in a closed state. These structures provide templates for further design and optimization of inhibitors targeting human TRPC5.
A Structure-Based Mechanism for DNA Entry into the Cohesin Ring
Authors: Higashi Torahiko L. , Eickhoff Patrik , Simoes Joana S. , Locke Julia , Nans Andrea , Flynn Helen R. , Snijders Ambrosius P. , Papageorgiou George , O’Reilly Nicola , Chen Zhuo A. , O’Reilly Francis J. , Rappsilber Juri , Costa Alessandro , Uhlmann Frank 
Published: April 2020

SUMMARYDespite key roles in sister chromatid cohesion and chromosome organization, the mechanism by which cohesin rings are loaded onto DNA is still unknown. Here, we combine biophysical approaches and cryo-EM to visualize a cohesin loading intermediate in which DNA is locked between two gates that lead into the cohesin ring. Building on this structural framework, we design biochemical experiments to establish the order of events during cohesin loading. In an initial step, DNA traverses an N-terminal kleisin gate that is first opened upon ATP binding and then closed as the cohesin loader locks the DNA against a shut ATPase gate. ATP hydrolysis leads to ATPase gate opening to complete DNA entry. Whether DNA loading is successful, or rather results in loop extrusion, might be dictated by a conserved kleisin N-terminal tail that guides the DNA through the kleisin gate. Our results establish the molecular basis for cohesin loading onto DNA.