bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multicenter point-prevalence evaluation of the utilization and safety of drug therapies for COVID-19
Authors: Rhodes Nathaniel J. , Dairem Atheer , Moore William J. , Shah Anooj , Postelnick Michael J. , Badowski Melissa E. , Michienzi Sarah M. , Borkowski Jaime L. , Polisetty Radhika S. , Fong Karen , Spivak Emily S. , Beardsley James R. , Hale Cory M. , Pallotta Andrea M. , Srinivas Pavithra , Schulz Lucas T. 
Published: June 2020

AbstractBackgroundThere are currently no FDA-approved medications for the treatment of COVID-19. At the onset of the pandemic, off-label medication use was supported by limited or no clinical data. We sought to characterize experimental COVID-19 therapies and identify safety signals during this period.MethodsWe conducted a non-interventional, multicenter, point prevalence study of patients hospitalized with suspected/confirmed COVID-19. Clinical and treatment characteristics within a 24-hour window were evaluated in a random sample of up to 30 patients per site. The primary objective was to describe COVID-19 targeted therapies. The secondary objective was to describe adverse drug reactions (ADRs).ResultsA total of 352 patients from 15 US hospitals were included. Most patients were treated at academic medical centers (53.4%) or community hospitals (42.6%). Sixty-seven patients (19%) were receiving drug therapy in addition to supportive care. Drug therapies included hydroxychloroquine (69%), remdesivir (10%), and interleukin-6 inhibitors (9%). Five patients (7.5%) were receiving combination therapy. Patients with a history of asthma (14.9% vs. 7%, p = 0.037) and those enrolled in clinical trials (26.9% vs.3.2%, p< 0.001) were more likely to receive therapy. Among those receiving COVID-19 therapy, eight patients (12%) experienced an ADR, and ADRs were more commonly recognized in patients enrolled in clinical trials (62.5% vs 22%, OR = 5.9, p = 0.028).ConclusionsWhile we observed high rates of supportive care for patients with COVID-19, we also found that ADRs were common among patients receiving drug therapy including in clinical trials. Comprehensive systems are needed to identify and mitigate ADRs associated with experimental COVID-19 therapies.
Dissection of the Spindle Assembly Checkpoint by Proximity Proteomics
Authors: Garcia Yenni A. , Velasquez Erick F. , Gao Lucy W. , Cheung Keith , Clutario Kevin M. , Williams-Hamilton Taylor , Gholkar Ankur A. , Whitelegge Julian P. , Torres Jorge Z. 
Published: June 2020

SUMMARYThe spindle assembly checkpoint (SAC) is critical for sensing defective microtubule-kinetochore attachments and tension across the kinetochore and functions to arrest cells in prometaphase to allow time to repair any errors prior to proceeding into anaphase. The SAC has a central role in ensuring the fidelity of chromosome segregation and its dysregulation has been linked to the development of human diseases like cancer. The establishment and maintenance of the SAC relies on multiple protein complexes that are intricately regulated in a spatial and temporal manner through posttranslational modifications like phosphorylation. Over the past few decades the SAC has been highly investigated and much has been learned about its protein constituents and the pathways and factors that regulate its activity. However, the spatio-temporal proximity associations of the core SAC components have not been explored in a systematic manner. Here, we have taken a BioID2 proximity-labeling proteomic approach to define the proximity protein environment for each of the five core SAC proteins BUB1, BUB3, BUBR1, MAD1L1, and MAD2L1 under conditions where the SAC is active in prometaphase. These five protein association maps were integrated to generate the SAC proximity protein network that contains multiple layers of information related to core SAC protein complexes, protein-protein interactions, and proximity associations. Our analysis validated many of the known SAC complexes and protein-protein interactions. Additionally, it uncovered new protein associations that lend insight into the functioning of the SAC and highlighted future areas that should be investigated to generate a comprehensive understanding of the SAC.
When Gaze-Pattern Similarity May Interfere With Future Memory
Authors: Selle Nathalie klein , Gamer Matthias , Pertzov Yoni 
Published: June 2020

AbstractHuman brains have a remarkable ability to separate streams of visual input into distinct memory-traces. It is unclear, however, how this ability relates to the way these inputs are explored via unique gaze-patterns. Moreover, it is yet unknown how motivation to forget or remember influences the gaze similarity and memory relationship. In two experiments, we therefore used a modified directed-forgetting paradigm and either showed blurred versions of the encoded scenes (Experiment 1) or pink noise images (Experiment 2) during attempted memory control. Both experiments demonstrated that higher levels of across-stimulus gaze similarity relate to worse future memory. Although thisacross-stimulus interference effectwas unaffected by motivation, it depended on the perceptual overlap between stimuli and was more pronounced for different scene comparisons, than scene-pink noise comparisons. Intriguingly, these findings echo the pattern similarity effects from the neuroimaging literature and pinpoint a mechanism that could aid the regulation of unwanted memories.
Genetic screen to saturate guard cell signaling network reveals a role of GDP-L-fucose metabolism in stomatal closure
Authors: Waszczak Cezary , Vahisalu Triin , Yarmolinsky Dmitry , Sierla Maija , Zamora Olena , Gavarrón Marina Leal , Palorinne Julia , Carter Ross , Pandey Ashutosh K. , Nuhkat Maris , Carmody Melanie , Puukko Tuomas , Sipari Nina , Lamminmäki Airi , Durner Jörg , Ernst Dieter , Winkler J. Barbro , Paulin Lars , Auvinen Petri , Fleming Andrew J. , Salojärvi Jarkko , Kollist Hannes , Kangasjärvi Jaakko 
Published: June 2020

ABSTRACTGuard cells regulate plant gas exchange by controlling the aperture of stomatal pores. The process of stomatal closure involves a multi-input signaling network that governs the activity of ion channels, which in turn regulate guard cell turgor pressure and volume. Here we describe a forward genetic screen to identify novel components involved in stomatal movements. Through an ozone-sensitivity approach combined with whole-rosette gas exchange analysis, 130 mutants of established stomatal regulators and 76 novel mutants impaired in stomatal closure were identified. One of the novel mutants was mapped to MURUS1 (MUR1), the first enzyme inde novoGDP-L-fucose biosynthesis. Defects in synthesis or import of GDP-L-Fuc into the Golgi apparatus resulted in impaired stomatal closure to multiple stimuli. Stomatal phenotypes observed inmur1were independent from the canonical guard cell signaling and instead could be related to altered mechanical properties of guard cell walls. Impaired fucosylation of xyloglucan, N-linked glycans and arabinogalactan proteins did not explain the aberrant function ofmur1stomata, however our data suggest that the stomatal phenotypes observed inmur1can at least partially be attributed to defective dimerization of rhamnogalactouronan-II. In addition to providing the genetic framework for future studies on guard cell signaling, our work emphasizes the impact of fucose metabolism on stomatal movement.
The household resistome – frequency of beta-lactamases, class 1 integron and antibiotic resistant bacteria in the domestic environment
Authors: Schages Laura , Lucassen Ralf , Wichern Florian , Kalscheuer Rainer , Bockmühl Dirk 
Published: June 2020

AbstractThe widespread of antibiotic resistance (ABR) among bacteria has become a global health concern for humans, animals and the environment. In this respect, beta-lactams and colistin are of particular interest due to the emergence of multidrug-resistant gram-negative bacteria. Households provide a habitat for bacteria originating from humans, animals, foods, contaminated clothes or other sources in which detergents and biocides are frequently used. Thus, bacteria carrying antibiotic resistance genes (ARGs) might be introduced into private households and may consequently be also released from households to the environment via domestic wastewater. Since data on ABR in the domestic environment is limited, this study aimed to determine the abundance and correlation of beta-lactamase, mobile colistin resistance and class 1 integron genes and to characterize phenotypic resistant strains in private households in Germany. Additionally, the persistence of ABR bacteria to laundering and automated dishwashing was assessed. Shower drains, washing machines and dishwashers were sampled and analyzed using quantitative real-time PCR. Resistant strains were isolated, followed by identification and antibiotic susceptibility testing using VITEK 2. The results show a significantly higher occurrence of ARGs in shower drains compared to washing machines and dishwashers. Several beta-lactamase genes co-occurred and resistance of bacterial isolates correlated positively with genotypic resistance. Laundering and automated dishwashing reduced ABR bacteria significantly and the efficacy increased with increasing duration and temperature. Overall, the domestic environment seems to represent a potential reservoir of beta-lactamase genes and beta-lactam resistant bacteria with shower drains as the dominant source of ABR.ImportanceThe abundance of ABR bacteria and ARGs is steadily increasing and has been comprehensively analyzed in natural environments, animals, foods or wastewater treatment plants. Despite of their connection to these environments, private households seem to be neglected. Therefore, the present study investigated shower drains, washing machines and dishwashers as possible sites of ARGs and ABR bacteria. The analysis of the domestic environment as a potential reservoir of resistant bacteria is crucial to determine whether households contribute to the spread of ABR or are a habitat where resistant bacteria from the environment, humans, food or water accumulate.
Molecular epidemiology and clone transmission of carbapenem-resistantAcinetobacter baumanniiin ICU rooms
Authors: Zhang Xiufeng , Li Fangping , Hou Zhuangwei , Awan Furqan , Jiang Hongye , Li Xiaohua , Zeng Zhenling , Lv Weibiao 
Published: June 2020

AbstractCarbapenem-resistantAcinetobacter baumannii(CRAB) is a major cause of nosocomial infections and hospital outbreaks worldwide, remaining a critical clinical concern. Here we characterized and investigated the phylogenetic relationships of 105 CRAB isolates on intensive care unit surfaces from one hospital in China collected over six years. All strains carriedblaOXA-23,blaOXA-66genes for carbapenem resistance, also had high resistance gene, virulence factor and insertion sequences burdens. Whole-genome sequencing revealed all strains belonged to ST2, the global clone CC2. The phylogenetic analysis based on the core genome showed all isolates was dominated by a single lineage of three clusters and eight different clones. Two clones were popular during the collection time. Using chi-square test to identify the epidemiologically meaningful groupings, we found the significant difference in community structure only present in strains from separation time. The haplotype and median-joining network analysis revealed genetic differences among clusters and changes occurred overtime in the dominating cluster. Our results highlighted substantial multidrug-resistant CRAB burden in hospital ICU environment, demonstrated potential clone outbreak in hospital.
Human mobility and poverty as key drivers of COVID-19 transmission and control
Authors: Yechezkel Matan , Weiss Amit , Rejwan Idan , Shahmoon Edan , Ben-Gal Shachaf , Yamin Dan 
Published: June 2020

AbstractBackgroundApplying heavy nationwide restrictions is a powerful method to curtail COVID-19 transmission but poses a significant humanitarian and economic crisis. Thus, it is essential to improve our understanding of COVID-19 transmission and develop more focused and effective strategies. As human mobility drives transmission, data from cell phone devices can be utilized to achieve these goals.MethodsWe analyzed aggregated and anonymized mobility data from the cell-phone devices of>3 million users between February 1, 2020, to May 16, 2020 – in which several movement restrictions were applied and lifted in Israel. We integrated these mobility patterns into age-, risk- and region-structured transmission model. Calibrated to coronavirus incidence in 250 regions covering Israel, we evaluated the efficacy and effectiveness in decreasing mortality of applying localized and temporal lockdowns (stay-at-home order).ResultsPoorer regions exhibited lower and slower compliance with the restrictions. Our transmission model further indicated that individuals from poverty areas were associated with high transmission rates. Model projections suggested that, counterintuitively, school closure has an adverse effect and increases COVID-19 mortality in the long run, while interventions focusing on the elderly are the most efficient. We also found that applying localized and temporal lockdowns during regional outbreaks reduce mortality compared to nationwide lockdowns. These trends were consistent across vast ranges of epidemiological parameters, possible seasonal forcing, and even when we assumed that vaccination would be commercially available in 1-3 years.ConclusionsMore resources should be devoted to helping impoverished regions. Utilizing cellphone data despite being anonymized and aggregated can help policymakers worldwide identify hotspots and apply designated strategies against future COVID-19 outbreaks.
Characteristics and risk factors for COVID-19 diagnosis and adverse outcomes in Mexico: an analysis of 89,756 laboratory–confirmed COVID-19 cases
Authors: Giannouchos Theodoros V , Sussman Roberto A , Mier Odriozola José Manuel , Poulas Konstantinos , Farsalinos Konstantinos 
Published: June 2020

AbstractBackgroundThere is insufficient information about risk factors for COVID-19 diagnosis and adverse outcomes from low and middle-income countries (LMICs).ObjectivesWe estimated the association between patients’ characteristics and COVID-19 diagnosis, hospitalization and adverse outcome in Mexico.MethodsThis retrospective case series used a publicly available nation-level dataset released on May 31, 2020 by the Mexican Ministry of Health, with patients classified as suspected cases of viral respiratory disease. Patients with COVID-19 were laboratory-confirmed. Their profile was stratified by COVID-19 diagnosis or not. Differences among COVID-19 patients based on two separate clinical endpoints, hospitalization and adverse outcome, were examined. Multivariate logistic regressions examined the associations between patient characteristics and hospitalization and adverse outcome.ResultsOverall, 236,439 patients were included, with 89,756 (38.0%) being diagnosed with COVID-19. COVID-19 patients were disproportionately older, males and with increased prevalence of one or more comorbidities, particularly diabetes, obesity, and hypertension. Age, male gender, diabetes, obesity and having one or more comorbidities were independently associated with laboratory-confirmed COVID-19. Current smokers were 23% less likely to be diagnosed with COVID-19 compared to non-smokers. Of all COVID-19 patients, 34.8% were hospitalized and 13.0% experienced an adverse outcome. Male gender, older age, having one or more comorbidities, and chronic renal disease, diabetes, obesity, COPD, immunosuppression and hypertension were associated with hospitalization and adverse outcome. Current smoking was not associated with adverse outcome.ConclusionThis largest ever case series of COVID-19 patients identified risk factors for COVID-19 diagnosis, hospitalization and adverse outcome. The findings could provide insight for the priorities the need to be set, especially by LMICs, to tackle the pandemic.
Estimating the effect of lipids on IGF axis and subsequent breast cancer risk
Authors: Tan Vanessa Y , Bull Caroline J , Biernacka Kalina M , Teumer Alexander , Corbin Laura , Dudding Tom , Sanderson Eleanor , Qi Qibin , Kaplan Robert C , Rotter Jerome I , Friedrich Nele , Völker Uwe , Mayerle Julia , Perks Claire M , Holly Jeff MP , Timpson Nicholas J 
Published: June 2020

AbstractCirculating lipids have been associated with breast cancer (BCa). This association may, in part, be due to an effect of lipids on insulin-like growth factors (IGFs), which have been reliably associated with BCa. In two-sample Mendelian randomization (MR) analyses, we found that low density lipoprotein (LDL-C) was associated with IGFBP-3 (beta:0.08 SD; 95%CI:0.02,0.15; p = 0.01, per SD increase in LDL-C) and IGFBP-3 was associated with postmenopausal BCa (OR:1.09; 95%CI:1.00,1.19; p = 0.05, per SD increase in IGFBP-3). We also found that triglycerides were associated with IGF-I (beta:-0.13SD; 95%CI:-0.22,-0.03, per SD increase in triglycerides) and that IGF-I was associated with overall BCa (OR:1.10;95%CI:1.02,1.18, per SD increase in IGF-I). Taken together, these results suggest that IGFBP-3 may be a potential causal step between LDL-C and postmenopausal BCa and IGF-I a potential causal for triglycerides. Our two-step MR results build on evidence linking circulating lipids and IGFs with BCa, however, multivariable MR analyses are currently unable to support this relationship due to weak instruments.
First environmental surveillance for the presence of SARS-CoV-2 RNA in wastewater and river water in Japan
Authors: Haramoto Eiji , Malla Bikash , Thakali Ocean , Kitajima Masaaki 
Published: June 2020

ABSTRACTWastewater-based epidemiology is a powerful tool to understand the actual incidence of coronavirus disease 2019 (COVID-19) in a community because severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, can be shed in the feces of infected individuals regardless of their symptoms. The present study aimed to assess the presence of SARS-CoV-2 RNA in wastewater and river water in Yamanashi Prefecture, Japan, using four quantitative and two nested PCR assays. Influent and secondary-treated (before chlorination) wastewater samples and river water samples were collected five times from a wastewater treatment plant and three times from a river, respectively, between March 17 and May 7, 2020. The wastewater and river water samples (200–5,000 mL) were processed by using two different methods: the electronegative membrane-vortex (EMV) method and the membrane adsorption-direct RNA extraction method. Based on the observed concentrations of indigenous pepper mild mottle virus RNA, the EMV method was found superior to the membrane adsorption-direct RNA extraction method. SARS-CoV-2 RNA was successfully detected in one of five secondary-treated wastewater samples with a concentration of 2.4 × 103 copies/L by N_Sarbeco qPCR assay following the EMV method, whereas all the influent samples were tested negative for SARS-CoV-2 RNA. This result could be attributed to higher limit of detection for influent (4.0 × 103–8.2 × 104 copies/L) with a lower filtration volume (200 mL) compared to that for secondary-treated wastewater (1.4 × 102–2.5 × 103 copies/L) with a higher filtration volume of 5,000 mL. None of the river water samples tested positive for SARS-CoV-2 RNA. Comparison with the reported COVID-19 cases in Yamanashi Prefecture showed that SARS-CoV-2 RNA was detected in the secondary-treated wastewater sample when the cases peaked in the community. This is the first study reporting the detection of SARS-CoV-2 RNA in wastewater in Japan.
‘Drawing on Wisdom to Cope with Adversity:’ A Systematic Review Protocol of Older Adults’ Mental and Psychosocial Health During Acute Respiratory Disease Propagated-Type Epidemics and Pandemics (COVID-19, SARS-CoV, MERS, and Influenza)
Authors: Aravena Jose M. , Aceituno Cristopher , Nyhan Kate , Shi Kewei , Vermund Sten , Levy Becca R. 
Published: June 2020

AbstractBackgroundMental health has become one of the fundamental priorities during the COVID-19 pandemic. Situations like physical distancing as well as being constantly tagged as the most vulnerable group could expose older adults to mental and psychosocial burdens. Nonetheless, there is little clarity about the impact of the COVID-19 pandemic or similar pandemics in the past on the mental illness, wellbeing, and psychosocial health of the older population compared to other age groups.ObjectivesTo describe the patterns of older adults’ mental and psychosocial health related to acute respiratory disease propagated-type epidemics and pandemics and to evaluate the differences with how other age groups respond.Eligibility criteriaquantitative and qualitative studies evaluating mental illness, wellbeing, or psychosocial health outcomes associated with respiratory propagated epidemics and pandemics exposure or periods (COVID-19, SARS-CoV, MERS, and Influenza) in people 65 years or older.Data sourceOriginal articles published until June 1st, 2020, in any language searched in the electronic healthcare and social sciences database: MEDLINE, Embase, CINAHL, PsycINFO, Scopus, WHO Global literature on coronavirus disease database, China National Knowledge Infrastructure (中国 知网 –CNKI). Furthermore, EPPI Centre’s COVID-19 living systematic map and the publicly available publication list of the COVID-19 living systematic review will be incorporated for preprints and recent COVID-19 publications.Data extractionTwo independent reviewers will extract predefined parameters. The risk of bias will be assessed.Data synthesisData synthesis will be performed according to study type and design, type of epidemic and pandemic, types of outcomes (mental health and psychosocial outcomes), and participant characteristics (e.g., sex, race, age, socioeconomic status, food security, presence of dependency in daily life activities independent/dependent older adults). Comparison between sex, race, and other age groups will be performed qualitatively, and quantitatively if enough data is available. The risk of bias and study heterogeneity will be reported for quantitative studies.ConclusionThis study will provide information to take actions to address potential mental health difficulties during the COVID-19 pandemic in older adults and to understand responses on this age group. Furthermore, it will be useful to identify potential groups that are more vulnerable or resilient to the mental-health challenges of the current worldwide pandemic.