bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of clinical course and outcomes of critically ill patients with SARS-CoV2 infection managed in traditional ICU and “Flex” ICU during the surge of the pandemic in the Bronx
Authors: Gutierrez Victor Perez , Carlos Alex , Nino Jessica , Osella Julieta , Dimitrov Vihren , Kasubhai Moiz , Menon Vidya 
Published: March 2021

ABSTRACTBACKGROUNDAs part of the response to increase critical care capacity during the unprecedented surge of COVID-19 infections, NYC Health + Hospital systems identified and resourced areas in the hospital that could deliver critical care as “Flex” ICUs to complement the traditional ICUs to manage the rapid influx of critically ill patients.OBJECTIVEComparison of clinical features and outcomes of mechanically ventilated COVID-19 patients admitted to the traditional and “Flex” ICUs during the surge of the pandemicMETHODSRetrospective comparative cohort study of patients with confirmed SARS-CoV-2 infection on mechanical ventilation admitted to traditional ICU and ‘Flex’ ICU. Univariate and multivariate analysis to detect factors associated with death from COVID-19 patients in mechanical ventilation were performed with the Cox proportional hazards regression modelRESULTSOut of the 312 patients on mechanical ventilation, 111 were admitted to the traditional ICU and 201 to the ‘Flex’ ICU. The mortality rate was higher in the ‘Flex’ ICU compared with the traditional ICU, but the adjusted risk model was not significantly associated with increased mortalityCONCLUSION“Flex” ICUs played a crucial role in the management of critically ill patients during the pandemic. Mortality risk of patients in the “Flex” ICUs were comparable to traditional ICUs in the adjusted analysis. While there is enough evidence for Intensivist managed ICUs to have better outcomes, our study demonstrates the feasibility of non-intensivist led Flex” ICUs during a crisis.
Characterization of patients that can continue conservative treatment for adenomyosis
Authors: Miyagawa Chiho , Murakami Kosuke , Tobiume Takako , Nonogaki Takafumi , Matsumura Noriomi 
Published: March 2021

AbstractIntroductionHistorically, hysterectomy has been the radical treatment for adenomyosis. However, some patients do not wish to hysterectomy. Nevertheless, patients often required hysterectomy during the course of conservative treatment, but the factors involved remain unknown. The purpose of this study was to determine which patients can continue conservative treatment for adenomyosis.Materials and MethodsWe selected women diagnosed with adenomyosis and provided with conservative treatment at the Kindai University Hospital and Osaka Red Cross Hospital. Age at diagnosis, parity, uterine size, subtype of adenomyosis, type of conservative treatment, and timing of hysterectomy for cases with difficulty continuing conservative treatment were examined retrospectively.ResultsA total of 885 patients were diagnosed with adenomyosis, and 124 started conservative treatment. Conservative treatment was continued in 96 patients (77.4%) and hysterectomy was required in 28 patients (22.6%). The cumulative hysterectomy rate was 32.4%, and all women had hysterectomy within 63 months. In the decision tree analysis, 82% (23/28) of women aged 46 years or younger were able to continue conservative treatment when parity was zero or one. If parity was two and over, 95% (20/21) of those aged 39 years and older had hysterectomy.ConclusionsPatients that continue conservative treatment for approximately 5 years are more likely to have successful preservation of the uterus. Multipara and higher age of diagnosis are factors that contribute to hysterectomy after conservative treatment. Parity and age at diagnosis may be stratifying factor in future clinical trials on hormone therapy.
Digital Health-Enabled Community-Centered Care (D-CCC): A Scalable Model to Empower Future Community Health Workers utilizing Human-in-the-Loop AI
Authors: Rodrigues Sarah M. , Kanduri Anil , Nyamathi Adeline M. , Dutt Nikil , Khargonekar Pramod P. , Rahmani Amir M. 
Published: March 2021

AbstractDigital Health-Enabled Community-Centered Care (D-CCC) represents a pioneering vision for the future of community-centered care. Utilizing an artificial intelligence-enabled closed-loop digital health platform designed for, and with, community health workers, D-CCC enables timely and individualized delivery of interventions by community health workers to the communities they serve. D-CCC has the potential to transform the current landscape of manual, episodic and restricted community health worker-delivered care and services into an expanded, digitally interconnected and collaborative community-centered health and social care ecosystem which centers around a digitally empowered community health workforce of the future.
Multi-Omic Profiling of Plasma Identify Biomarkers and Pathogenesis of COVID-19 in Children
Authors: Wang Chong , Li Xufang , Ning Wanshan , Gong Sitang , Yang Fengxia , Fang Chunxiao , Gong Yu , Wu Di , Huang Muhan , Gou Yujie , Fu Shanshan , Ren Yujie , Yang Ruyi , Qiu Yang , Xue Yu , Xu Yi , Zhou Xi 
Published: March 2021

AbstractAlthough children usually develop less severe disease responding to COVID-19 than adults, little is known about the pathogenesis of COVID-19 in children. Herein, we conducted the plasma proteomic and metabolomic profiling of a cohort of COVID-19 pediatric patients with mild symptoms. Our data show that numerous proteins and metabolites involved in immune as well as anti-inflammatory processes were up-regulated on a larger scale in children than in adults. By developing a machine learning-based pipeline, we prioritized two sets of biomarker combinations, and identified 5 proteins and 5 metabolites as potential children-specific COVID-19 biomarkers. Further study showed that these identified metabolites not only inhibited the expression of pro-inflammatory factors, but also suppressed coronaviral replication, implying that these factors played key roles in protecting pediatric patients from both viral infection and infection-induced inflammation. Together, our study uncovered a protective mechanism responding to COVID-19 in children, and sheds light on potential therapies.TeaserAnti-inflammatory metabolites were highly elevated in the plasma of COVID-19 pediatric patients with mild symptoms.
Prevalence of vitamin D is not associated with the COVID-19 epidemic in Europe. A critical update of the existing evidence
Authors: Bakaloudi Dimitra Rafailia , Chourdakis Michail 
Published: March 2021

ABSTRACTBackgroundCOVID-19 has emerged as a global pandemic, affecting nearly 104 million people worldwide as of February 4th 2021. In previous published studies, the association between the mean Vit D status of each country and COVID-19 infection rate, and mortality among the adult population in European countries was examined. The aim of this study was to re-examine the relationship between the Vit D status of each country and COVID-19 infection, recovery, and mortality using updated data and a different methodological approach.MethodsInformation only form the last decade on Vit D concentration/deficiency for each country was retrieved through literature search on PubMed® database. As of February, 4th 2021, COVID-19 infections and mortalities per one million population as well as total recoveries were extracted from the Worldometer website. The association between vitamin D deficiency and COVID-19 infection, recovery, and mortality were explored using correlation coefficients and scatterplots.FindingsThe prevalence of vitamin D deficiency among European countries ranged from 6.0 (Finland) to 75.5% (Turkey), with several countries facing more than 50% of vitamin D deficiency among their population. Non-significant correlations were observed between the number of COVID-19 infections (r=0.190; p=0.374), recoveries (rs=0.317, p=0.131), and mortalities (r=0.129; p=0.549) per one million population, with the prevalence of vitamin D deficiency.InterpretationPrevalence of vitamin D deficiency was not significantly associated with either number of infections, recoveries or mortality rate of COVID-19 among European countries. Thus, it is an important parameter to be considered when implementing preventive measures to face COVID-19.FundingNone
Comparing the Evidential Strength for Psychotropic Drugs: A Bayesian Meta-Analysis
Authors: Pittelkow Merle-Marie , de Vries Ymkje Anna , Monden Rei , Bastiaansen Jojanneke A. , van Ravenzwaaij Don 
Published: March 2021

AbstractObjectiveApproval and prescription of drugs should be informed by the strength of evidence for efficacy. While there is no formal policy towards different standards for drug approval, the typical strength of evidence might differ for different psychotropic drug groups. Using a Bayesian framework, we examine (1) whether psychotropic drugs are supported by substantial evidence (at the time of Food and Drug Administration [FDA] approval), and (2) whether there are systematic differences across drug groups.MethodsData from short-term, placebo-controlled phase II/III clinical trials for 15 antipsychotics, 16 antidepressants for depression, nine antidepressants for anxiety, and 20 drugs for ADHD were extracted from FDA reviews evaluating efficacy prior to marketing approval. Bayesian model-averaged meta-analysis was performed and strength of evidence was quantified with the Bayes factor (BFBMA).ResultsWe observed substantial variation in strength of evidence and trialling between approved psychotropic drugs: Median evidential strength was extremely strong for ADHD medication (BFBMA= 1820.4), but considerably lower and more frequently classified as weak or moderate for antidepressants for both depression (BFBMA= 94.2) and anxiety (BFBMA= 49.8). Differences might be accounted for by varying median effect sizes (schizophrenia:ESBMA= 0.45, depression:ESBMA= 0.30, anxiety:ESBMA= 0.37, ADHD:ESBMA= 0.72), sample sizes (schizophrenia:N= 324, depression:N= 218, anxiety:N= 254, ADHD:N= 189.5), and numbers of trials (schizophrenia:Nr= 3, depression:Nr= 5.5, anxiety:Nr= 3, ADHD:Nr= 2).LimitationsThe analysis only included pre-marketing studies.ConclusionEvidential strength varied across drug groups: Although most psychotropic drugs were supported by strong evidence at the time of approval, some drugs only had moderate or even ambiguous evidence. These results show the need for more systematic quantification and classification of statistical evidence for psychotropic drugs, and for transparent and clear communication of evidential strength toward clinical decision makers.Registrationhttps://osf.io/5jn2d
Pharmacological targeting of a PWWP domain demonstrates cooperative control of NSD2 localization
Authors: Dilworth David , Hanley Ronan P. , de Freitas Renato Ferreira , Allali-Hassani Abdellah , Zhou Mengqi , Mehta Naimee , Marunde Matthew R. , Ackloo Suzanne , Marcon Edyta , Li Fengling , Chau Irene , Bolotokova Albina , Qin Su , Lei Ming , Liu Yanli , Szewczyk Magdalena M , Dong Aiping , Kazemzadeh Sina , Abramyan Tigran , Popova Irina K , Hall Nathan W , Meiners Matthew J , Cheek Marcus A , Gibson Elisa , Kireev Dmitri , Greenblatt Jack F. , Keogh Michael-C. , Min Jinrong , Brown Peter J. , Vedadi Masoud , Arrowsmith Cheryl H. , Barsyte-Lovejoy Dalia , James Lindsey I , Schapira Matthieu 
Published: March 2021

AbstractNSD2 is the primary enzyme responsible for the dimethylation of lysine 36 of histone 3 (H3K36me2), a mark associated with active gene transcription and intergenic DNA methylation. In addition to a methyltransferase domain, NSD2 harbors two PWWP and five PHD domains believed to serve as chromatin reading modules, but their exact function in the regulation of NSD2 activity remains underexplored. Here we report a first-in-class chemical probe targeting the N-terminal PWWP (PWWP1) domain of NSD2.UNC6934binds potently (Kdof 91 ± 8 nM) to PWWP1, antagonizes its interaction with nucleosomal H3K36me2, and selectively engages endogenous NSD2 in cells. Crystal structures show thatUNC6934occupies the canonical H3K36me2-binding pocket of PWWP1 which is juxtaposed to the DNA-binding surface. In cells,UNC6934induces accumulation of endogenous NSD2 in the nucleolus, phenocopying the localization defects of NSD2 protein isoforms lacking PWWP1 as a result of translocations prevalent in multiple myeloma. Mutation of other NSD2 chromatin reader domains also increases NSD2 nucleolar localization, and enhances the effect ofUNC6934. Finally we identified two C-terminal nucleolar localization sequences in NSD2 that appear to drive nucleolar accumulation when one or more chromatin reader domains are disabled. These data support a model in which NSD2 chromatin engagement is achieved in a cooperative manner and subcellular localization is controlled by multiple competitive structural determinants. This chemical probe and the accompanying negative control,UNC7145, will be useful tools in defining NSD2 biology.
Multiplexed VaxArray Immunoassay for Rapid Antigen Quantification in Measles and Rubella Vaccine Manufacturing
Authors: Gillis Jacob H. , Thomas Keely N. , Manoharan Senthilkumar , Panchakshari Mallikarjuna , Taylor Amber W. , Miller David F. , Byrne-Nash Rose T. , Riley Christine , Rowlen Kathy L. , Dawson Erica 
Published: March 2021

ABSTRACTMeasles-containing vaccines (MCV), specifically vaccines against measles and rubella (MR), are extremely effective and critical for the eradication of measles and rubella diseases. In developed countries, vaccination rates are high and vaccines are readily available, but continued high prevalence of both diseases in developing countries and surges in measles deaths in recent years have highlighted the need to expand vaccination efforts. To meet demand for additional vaccines at a globally affordable price, it is highly desirable to streamline vaccine production thereby reducing cost and speeding up time to delivery. MR vaccine characterization currently relies on the 50% cell culture infectious dose (CCID50) assay, an endpoint assay with low reproducibility that requires 10-14 days to complete. For streamlining bioprocess analysis and improving measurement precision relative to CCID50, we developed the VaxArray Measles and Rubella assay kit, which is based on a multiplexed microarray immunoassay with a 5-hour time to result. Here we demonstrate vaccine-relevant sensitivity ranging from 345 – 800 IFU/mL up to 100,000 IFU/mL and specificity that allows simultaneous analysis in bivalent vaccine samples. The assay is sensitive to antigen stability and has minimal interference from common vaccine additives. The assay exhibits high reproducibility and repeatability, with 15% CV, much lower than the typical 0.3 log10error (~65%) observed for the CCID50assay. The intact protein concentration measured by VaxArray is reasonably correlated to, but not equivalent to, CCID50infectivity measurements for harvest samples. However, the measured protein concentration exhibits equivalency to CCID50for more purified samples, including concentrated virus pools and monovalent bulks, making the assay a useful new tool for same-day analysis of vaccine samples for bioprocess development, optimization, and monitoring.
Protein-bound sialic acid in saliva contributes directly to salivary anti-influenza virus activity
Authors: Kobayashi Kaori , Shono Chika , Mori Takuya , Kitazawa Hidefumi , Ota Noriyasu , Kurebayashi Yuki , Suzuki Takashi 
Published: March 2021

ABSTRACTThe oral cavity is an entrance for respiratory viruses, such as influenza. Recently, saliva has been shown to exert both antimicrobial and antiviral activities. Thus, saliva may be a biological factor that contributes to the prevention of influenza infection. However, the actual salivary anti-influenza A virus (IAV) activity in individuals and its determinant factors are unknown. By assessing individual variations in salivary anti-IAV activity in 92 people using an established new high-throughput system in this study, we found that the anti-IAV activity varied widely between individuals and showed a significant positive correlation with protein-bound sialic acid (BSA) level (ρ=0.473;p< 0.001). Furthermore, the anti-IAV activity of saliva with enzymatically reduced BSA content was significantly lower. These results indicate that BSA is a direct regulator of salivary anti-IAV activity and is a determinant of individual differences. Additionally, after comparing the anti-IAV activity across the groups by age, anti-IAV activity in young people (aged 5–19 years) were lower than in adults aged 20–59 years and elderly people aged 60–79 years. Our study suggests that BSA levels in saliva may be important in preventing influenza infection.
Exploration of polyyne biosynthetic gene cluster diversity in bacteria leads to the discovery of thePseudomonaspolyyne protegencin
Authors: Mullins Alex J. , Webster Gordon , Kim Hak Joong , Zhao Jinlian , Petrova Yoana D. , Ramming Christina E. , Jenner Matthew , Murray James A. H. , Connor Thomas R. , Hertweck Christian , Challis Gregory L. , Mahenthiralingam Eshwar 
Published: March 2021

AbstractNatural products that possess alkyne or polyyne moieties have been isolated from a variety of biological sources. In bacteria their biosynthesis has been defined, however, the distribution of polyyne biosynthetic gene clusters (BGCs), and their evolutionary relationship to alkyne biosynthesis, have not been addressed. We explored the distribution of alkyne biosynthesis gene cassettes throughout bacteria, revealing evidence of multiple horizontal gene transfer events. Investigating the evolutionary connection between alkyne and polyyne biosynthesis identified a monophyletic clade possessing a conserved seven-gene cassette for polyyne biosynthesis. Mapping the diversity of these conserved genes revealed a phylogenetic clade representing a polyyne BGC inPseudomonas, pgn, and subsequent pathway mutagenesis and analytical chemistry characterised the associated metabolite, protegencin. In addition to unifying and expanding our knowledge of polyyne diversity, our results show that alkyne and polyyne biosynthetic gene clusters are promiscuous within bacteria. Systematic mapping of conserved biosynthetic genes across bacterial genomic diversity has proven to be a successful method for discovering natural products.
Critical Assessment of Metaproteome Investigation (CAMPI): A Multi-Lab Comparison of Established Workflows
Authors: Van Den Bossche Tim , Kunath Benoit J. , Schallert Kay , Schäpe Stephanie S. , Abraham Paul E. , Armengaud Jean , Arntzen Magnus Ø. , Bassignani Ariane , Benndorf Dirk , Fuchs Stephan , Giannone Richard J. , Griffin Timothy J. , Hagen Live H. , Halder Rashi , Henry Céline , Hettich Robert L. , Heyer Robert , Jagtap Pratik , Jehmlich Nico , Jensen Marlene , Juste Catherine , Kleiner Manuel , Langella Olivier , Lehmann Theresa , Leith Emma , May Patrick , Mesuere Bart , Miotello Guylaine , Peters Samantha L. , Pible Olivier , Queiros Pedro T. , Reichl Udo , Renard Bernhard Y. , Schiebenhoefer Henning , Sczyrba Alexander , Tanca Alessandro , Trappe Kathrin , Trezzi Jean-Pierre , Uzzau Sergio , Verschaffelt Pieter , von Bergen Martin , Wilmes Paul , Wolf Maximilian , Martens Lennart , Muth Thilo 
Published: March 2021

AbstractMetaproteomics has matured into a powerful tool to assess functional interactions in microbial communities. While many metaproteomic workflows are available, the impact of method choice on results remains unclear.Here, we carried out the first community-driven, multi-laboratory comparison in metaproteomics: the critical assessment of metaproteome investigation study (CAMPI). Based on well-established workflows, we evaluated the effect of sample preparation, mass spectrometry, and bioinformatic analysis using two samples: a simplified, laboratory-assembled human intestinal model and a human fecal sample.We observed that variability at the peptide level was predominantly due to sample processing workflows, with a smaller contribution of bioinformatic pipelines. These peptide-level differences largely disappeared at the protein group level. While differences were observed for predicted community composition, similar functional profiles were obtained across workflows.CAMPI demonstrates the robustness of present-day metaproteomics research, serves as a template for multi-laboratory studies in metaproteomics, and provides publicly available data sets for benchmarking future developments.
Dysbiotic oral and gut viromes in untreated and treated rheumatoid arthritis patients
Authors: Guo Ruochun , Li Shenghui , Zhang Yu , Zhang Yue , Wang Guangyang , Ma Yufang , Yan Qiulong 
Published: March 2021

AbstractBackgroundRheumatoid arthritis (RA) has been considered to be influenced by bacteria from the oral cavity and gut for many years. Despite potential impact of viruses in RA was mentioned in some studies, specific roles of oral and gut viromes in RA is still unclear.ResultsIn this study, we observed the viral community variation in the oral and gut samples, performed a comparative analysis of oral and gut viromes in health controls, untreated and treated RA patients, and constructed interaction networks among viruses, bacteria, and RA-associated clinical indexes to address the potential associations between viral community and RA. The results showed that the viromes could be isolated from dental plaque, saliva, and feces samples, among which the saliva having the highest with in-sample diversity. Meanwhile, remarkable variations of viral diversity and composition in the oral (i.e., dental plaque and saliva) virome could be observed in RA patients and healthy controls yet in untreated and treated RA patients, with a relatively low variability in the gut virome. Distraction of viruses-bacteria interaction network was discovered in three sites of RA patients. In addition, some RA-associated oral taxa, includingLactococcus phage vOTU70, Bacteroides vulgatus, Lactococcus lactis, Escherichia coli, Neisseria elongate, were correlated to the RA-related clinical indexes.ConclusionWhole-virome analysis illustrated the potential role of oral and gut viral communities in the development of RA.
A specialized bone marrow microenvironment for fetal haematopoiesis
Authors: Liu Yang , Chen Qi , Jeong Hyun-Woo , Watson Emma C. , Xu Cong , Stehling Martin , Zhou Bin , Adams Ralf H. 
Published: March 2021

AbstractLocal signals provided by cells in specialized niche microenvironments regulate stem cell behaviour in many different organs and species. In adult mammalian bone marrow (BM), leptin receptor-positive (LepR+) reticular cells express secreted factors that control the function of haematopoietic stem and progenitor cells (HSPCs). During fetal development, the developing skeletal system is colonized by c-Kit+ haematopoietic cellsde novoafter a transient phase of liver haematopoiesis. The cellular and molecular mechanisms regulatingde novohaematopoietic cell colonization and expansion remain largely unknown. Here, we report that fetal and adult BM exhibit fundamental differences both in terms of cellular composition and molecular interactions by single cell RNA sequencing (scRNA-seq) analysis. While LepR+ reticular cells are almost completely absent in fetal femur, arterial endothelial cells (AECs) are a source of signals controlling the initial HSPC expansion during BM development. Long-term haematopoietic stem cells (HSCs) and other c-Kit+ HSPCs are reduced when Wnt ligand secretion by AECs is genetically blocked. We identify Wnt2 as an AEC-derived signal that directly activates β-catenin dependent proliferation of fetal HSPCs. Treatment of HSPCsex vivowith Wnt2 promotes their proliferation and improves engraftmentin vivoafter transplantation. Our work reveals a fundamental switch in the cellular organization and molecular regulation of BM niches in the embryonic and adult organism.