bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hasty Reduction of COVID-19 Lockdown Measures Leads to the Second Wave of Infection
Authors: Hazem Yara , Natarajan Suchitra , Berikaa Essam R. 
Published: May 2020

AbstractThe outbreak of COVID-19 has an undeniable global impact, both socially and economically. March 11th, 2020, COVID-19 was declared as a pandemic worldwide. Many governments, worldwide, have imposed strict lockdown measures to minimize the spread of COVID-19. However, these measures cannot last forever; therefore, many countries are already considering relaxing the lockdown measures. This study, quantitatively, investigated the impact of this relaxation in the United States, Germany, the United Kingdom, Italy, Spain, and Canada. A modified version of the SIR model is used to model the reduction in lockdown based on the already available data. The results showed an inevitable second wave of COVID-19 infection following loosening the current measures. The study tries to reveal the predicted number of infected cases for different reopening dates. Additionally, the predicted number of infected cases for different reopening dates is reported.
MRI-guided histology of TDP-43 knock-in mice implicates parvalbumin interneuron loss, impaired neurogenesis and aberrant neurodevelopment in ALS-FTD
Authors: Lin Ziqiang , Kim Eugene , Ahmed Mohi , Han Gang , Simmons Camilla , Redhead Yushi , Bartlett Jack , Altamira Luis Emiliano Pena , Callaghan Isobel , White Matthew A. , Singh Nisha , Sawiak Stephen , Spires-Jones Tara , Vernon Anthony C. , Coleman Michael P. , Green Jeremy , Henstridge Christopher , Davies Jeff S. , Cash Diana , Sreedharan Jemeen 
Published: May 2020

AbstractAmyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are overlapping neurodegenerative diseases that are increasingly understood to have long prodromal periods. Investigation of these early stages promises to yield valuable biomarkers of disease and will be key to understanding mechanisms underlying the genesis of ALS-FTD. Here, we usein vivomagnetic resonance imaging (MRI), histology and computed tomography to identify structural and cellular readouts of early stage disease in the TDP-43Q331Kknock-in mouse model of ALS-FTD. Adult mutant mice demonstrated parenchymal volume reductions affecting the frontal lobe and entorhinal cortex in a manner reminiscent of ALS-FTD. Subcortical, cerebellar and brain stem regions were also affected in line with observations in presymptomatic carriers of mutations inC9orf72, the commonest genetic cause of both ALS and FTD. Volume loss, as measured by MRI, was also observed in the dentate gyrus (DG) of the hippocampus, along with ventricular enlargement. Guided by these imaging findings, detailedpost-mortembrain tissue analysis revealed reduced parvalbumin-positive (PV+) interneurons as a potential cellular correlate of MRI changes in mutant mice. By contrast, microglia were in a disease activated state even in the absence of brain volume loss. A reduction in immature neurons was found in the DG, indicative of impaired adult neurogenesis, while a paucity of PV+ interneurons in juvenile mutant mice (P14) suggests that TDP-43Q331Kdisrupts neurodevelopment. Computerised tomography imaging also showed altered skull morphology in mutants, further suggesting a role for TDP-43Q331Kin development. Finally, analysis of human post-mortem prefrontal cortices confirmed a paucity of PV+ interneurons in the prefrontal cortex in cases with both sporadic ALS and ALS linked toC9orf72mutations. This study suggests an important role for PV+ interneurons in regional brain vulnerability associated with ALS-FTD, and identifies novel MRI and histological biomarkers that will be of value in assessing the efficacy of putative therapeutics in TDP-43Q331Kknock-in mice.
Performance evaluation of the point-of-care SAMBA II SARS-CoV-2 Test for detection of SARS-CoV-2
Authors: Assennato Sonny M , Ritchie Allyson V , Nadala Cesar , Goel Neha , Zhang Hongyi , Datir Rawlings , Gupta Ravindra K , Curran Martin D , Lee Helen H 
Published: May 2020

AbstractNucleic acid amplification for the detection of SARS-CoV-2 RNA in respiratory samples is the standard method for diagnosis. These tests are centralised and therefore turnaround times can be 2-5 days. Point-of-care testing with rapid turnaround times would allow more effective triage in settings where patient management and infection control decisions need to be made rapidly.Inclusivity and specificity of the SAMBA II SARS-CoV-2 assay was determined by in silico analyses of the primers and probes. Analytical and clinical sensitivity and specificity of the SAMBA II SARS-CoV-2 Test was evaluated for analytical sensitivity and specificity. Clinical performance was evaluated in residual clinical samples compared to the Public Health England reference tests.The limit of detection of the SAMBA II SARS-CoV-2 Test is 250 cp/mL and is specific for detection of 2 regions of the SARS-CoV-2 genome. The clinical sensitivity was evaluated in 172 clinical samples provided by the Clinical Microbiology and Public Health Laboratory, Addenbrooke’s Hospital, Cambridge (CMPHL), which showed a sensitivity of 98.9% (95% CI 94.03-99.97%), specificity of 100% (95% CI 95.55-100%), PPV of 100% and NPV of 98.78% (92.02-99.82%) compared to testing by CMPHLSAMBA detected 3 positive samples that were initially negative by PHE Test. The data shows that the SAMBA II SARS-CoV-2 Test performs equivalently to the centralised testing methods with a much quicker turnaround time. Point of care testing, such as SAMBA, should enable rapid patient management and effective implementation of infection control measures.
Patient trajectories and risk factors for severe outcomes among persons hospitalized for COVID-19 in the Maryland/DC region
Authors: Garibaldi Brian T. , Fiksel Jacob , Muschelli John , Robinson Matthew , Rouhizadeh Masoud , Nagy Paul , Gray Josh H. , Malapati Harsha , Ghobadi-Krueger Mariam , Niessen Timothy M. , Kim Bo Soo , Hill Peter M. , Shafeeq Ahmed M. , Dobkin Eric D. , Blanding Renee , Abele Jennifer , Woods Bonnie , Harkness Kenneth , Thiemann David R. , Bowring Mary G. , Shah Aalok B. , Wang Mei-Cheng , Bandeen-Roche Karen , Rosen Antony , Zeger Scott L. , Gupta Amita 
Published: May 2020

AbstractBackgroundRisk factors for poor outcomes from COVID-19 are emerging among US cohorts, but patient trajectories during hospitalization ranging from mild-moderate, severe, and death and the factors associated with these outcomes have been underexplored.MethodsWe performed a cohort analysis of consecutive COVID-19 hospital admissions at 5 Johns Hopkins hospitals in the Baltimore/DC area between March 4 and April 24, 2020. Disease severity and outcomes were classified using the WHO COVID-19 disease severity ordinal scale. Cox proportional-hazards regressions were performed to assess relationships between demographics, clinical features and progression to severe disease or death.Results832 COVID-19 patients were hospitalized; 633 (76.1%) were discharged, 113 (13.6%) died, and 85 (10.2%) remained hospitalized. Among those discharged, 518 (82%) had mild/moderate and 116 (18%) had severe illness. Mortality was statistically significantly associated with increasing age per 10 years (adjusted hazard ratio (aHR) 1.54; 95%CI 1.28-1.84), nursing home residence (aHR 2.13, 95%CI 1.41-3.23), Charlson comorbidity index (1.13; 95% CI 1.02-1.26), respiratory rate (aHR 1.13; 95%CI 1.09-1.17), D-dimer greater than 1mg/dL (aHR 2.79; 95% 1.53-5.09), and detectable troponin (aHR 2.79; 95%CI 1.53-5.09). In patients under 60, only male sex (aHR 1.7;95%CI 1.11-2.58), increasing body mass index (BMI) (aHR1.25 1.14-1.37), Charlson score (aHR 1.27; 1.1-1.46) and respiratory rate (aHR 1.16; 95%CI 1.13-1.2) were associated with severe illness or death.ConclusionsA combination of demographic and clinical features on admission is strongly associated with progression to severe disease or death in a US cohort of COVID-19 patients. Younger patients have distinct risk factors for poor outcomes.
The H3.3 chaperone Hira complex orchestrates oocyte developmental competence
Authors: Smith Rowena , Jiang Zongliang , Susor Andrej , Ming Hao , Tait Janet , Conti Marco , Lin Chih-Jen 
Published: May 2020

AbstractReproductive success relies on a healthy oocyte competent for fertilisation and capable of sustaining early embryo development. By the end of oogenesis, the oocyte is characterised by a transcriptionally silenced state, but the significance of this state and how it is achieved remains poorly understood. Histone H3.3, one of the H3 variants, has unique functions in chromatin structure and gene expression that are cell cycle-independent. We report here a comprehensive characterisation of the roles of the subunits of the Hira complex (i.e. Hira, Cabin1 and Ubn1), which is primarily responsible for H3.3 deposition during mouse oocyte development. Loss-of-function of any component of the Hira complex led to early embryogenesis failure. Transcriptome and nascent RNA analyses revealed that mutant oocytes fail to silence global transcription. Hira complex mutants are unable to establish the H3K4me3 and H3K9me3 repressive marks, resulting in aberrant chromatin accessibility. Among the misregulated genes in mutant oocytes is Zscan4, a 2-cell specific gene that is involved in zygote genome activation. Overexpression of Zscan4 recapitulates the phenotypes of Hira mutants, illustrating that temporal and spatial expression of Zscan4 is fine-tuned at the oocyte-to-embryo transition. Thus, the H3.3 chaperone Hira complex has a maternal effect function in oocyte developmental competence and early embryogenesis by modulating chromatin condensation and transcriptional quiescence.
Fecal filtrate transfer protects against necrotizing enterocolitis in preterm pigs
Authors: Brunse Anders , Deng Ling , Pan Xiaoyu , Hui Yan , Kot Witold , Nguyen Duc Ninh , Secher Jan Bojsen-Møller , Nielsen Dennis Sandris , Thymann Thomas 
Published: May 2020

ABSTRACTBackground and aimsNecrotizing enterocolitis (NEC) is an acute and life-threatening gastrointestinal disorder afflicting preterm infants, which is currently unpreventable. Fecal microbiota transplantation (FMT) is a promising preventative therapy, but potential side effects raise concern. Removal of bacteria from donor fecal water may reduce side effects while maintaining wanted effects. We aimed to assess preclinical efficacy and safety of bacteria-free fecal filtrate transfer (FFT).MethodsUsing fecal material from healthy suckling piglets, we administered rectal FMT or cognate FFT by either rectal or oro-gastric administration to formula-fed preterm, cesarean piglets, and compared gut pathology and related safety parameters with saline controls. We then analyzed mucosa and luminal bacterial and viral composition using 16S rRNA gene amplicon and metavirome sequencing, respectively. Finally, we used isolated ileal mucosa, coupled with RNA-Seq, to gauge the host response to the different treatments.ResultsOro-gastric FFT eliminated NEC, which was confirmed by microscopy, whereas FMT did not perform better than control. Moreover, FFT but not FMT reduced intestinal permeability, whereas FMT animals had reduced body weight increase and intestinal growth. Oro-gastric FFT increased viral diversity and reduced Proteobacteria abundance in ileal mucosa relative to control. Global gene expression of host mucosa responded to FMT but not FFT with increased and decreased bacterial and viral defense mechanisms, respectively.ConclusionsAs preterm infants are extremely vulnerable, rational therapies need incontestable safety profiles. Here we show in a clinically relevant animal model that FFT, as opposed to FMT, efficiently prevents NEC without any recognizable side effects. If translatable to preterm infants, this could lead to a change of practice and in turn a reduction in NEC burden.
Curiosity is associated with enhanced tonic firing in dorsal anterior cingulate cortex
Authors: Wang Maya Zhe , Hayden Benjamin Yost 
Published: May 2020

ABSTRACTDisparity between current and desired information, known as information gap, is an important driver of information-seeking and curiosity. To gain insight into its neural basis, we recorded responses of single neurons in dorsal anterior cingulate cortex (dACC) while rhesus macaques performed a task that induces and quantifies demand for information. We find that enhanced firing rates in dACC before the start of a trial predict a stronger bias towards information-seeking choices. Following choices of uninformative options, firing rates are tonically enhanced until information is delivered. The level of enhancement observed is correlated on a trial-by-trial basis with the value assigned to the prospective information. Finally, variation in this tone is positively correlated with receptiveness to new information, as inferred by preference changes on subsequent trials. These patterns are not observed in a complementary dataset collected in orbitofrontal cortex (OFC), suggesting these effects reflect at least somewhat anatomically localized processing.
Giantin is required for intracellular N-terminal processing of type I procollagen
Authors: Stevenson Nicola L. , Dylan J. M. Bergen , Hammond Chrissy L. , Stephens David J. 
Published: May 2020

AbstractKnockout of the golgin giantin leads to skeletal and craniofacial defects driven by poorly studied changes in glycosylation and extracellular matrix deposition. Here, we sought to determine how giantin impacts the production of healthy bone tissue by focussing on the main protein component of the osteoid, type I collagen. Giantin mutant zebrafish accumulate multiple spontaneous fractures in their caudal fin, suggesting their bones may be more brittle. Inducing new experimental fractures revealed defects in the mineralisation of newly deposited collagen as well as diminished procollagen reporter expression in mutant fish. Analysis of giantin knockout cells expressing a GFP-tagged procollagen showed that procollagen trafficking is independent of giantin. However, our data show that intracellular N-propeptide processing of pro-α1(I) is defective in the absence of giantin. These data demonstrate a conserved role for giantin in collagen biosynthesis and extracellular matrix assembly. Our work also provides evidence of a giantin-dependent pathway for intracellular procollagen processing.
Prioritizing COVID-19 tests based on participatory surveillance and spatial scanning
Authors: Leal-Neto OB , Santos FAS , Lee JY , Albuquerque JO , Souza WV 
Published: May 2020

AbstractObjectivesThis study aimed to identify, describe and analyze priority areas for COVID-19 testing combining participatory surveillance and traditional surveillance.DesignIt was carried out a descriptive transversal study in the city of Caruaru, Pernambuco state, Brazil, within the period of 20/02/2020 to 05/05/2020. Data included all official reports for influenza-like illness notified by the municipality health department and the self-reports collected through the participatory surveillance platform Brasil Sem Corona.MethodsWe used linear regression and loess regression to verify a correlation between Participatory Surveillance (PS) and Traditional Surveillance (TS). Also a spatial scanning approach was deployed in order to identify risk clusters for COVID-19.ResultsIn Caruaru, the PS had 861 active users, presenting an average of 1.2 reports per user per week. The platform Brasil Sem Corona started on March 20th and since then, has been officially used by the Caruaru health authority to improve the quality of information from the traditional surveillance system. Regarding the respiratory syndrome cases from TS, 1,588 individuals were positive for this clinical outcome. The spatial scanning analysis detected 18 clusters and 6 of them presented statistical significance (p-value < 0.1). Clusters 3 and 4 presented an overlapping area that was chosen by the local authority to deploy the COVID-19 serology, where 50 individuals were tested. From there, 32% (n=16) presented reagent results for antibodies related to COVID-19.ConclusionParticipatory surveillance is an effective epidemiological method to complement the traditional surveillance system in response to the COVID-19 pandemic by adding real-time spatial data to detect priority areas for COVID-19 testing.
Radiofrequency Monitoring of Intracranial Hemorrhage in the Neurological Intensive Care Unit: A Pilot Trial of the SENSE Device
Authors: Korfhagen Joseph J. , Shaw George J. , Flaherty Matthew L. , Adeoye Opeolu , Knight William A. 
Published: May 2020

AbstractIntracerebral hemorrhage (ICH) is a devastating form of stroke, with substantial mortality and morbidity. Hemorrhage expansion (HE) occurs in ~40% of patients and portends worse neurologic outcome and mortality. Currently, ICH patients are admitted to the intensive care unit (ICU) and monitored for HE with neurologic exam and neuroimaging. By the time a change is detected, it may be too late to mitigate HE. There is a clinical need for a non-invasive bedside monitor of ICH.The SENSE consists of a 9-antenna array mounted around the head with driving electronics. A 913 MHz signal is transmitted by a given antenna, crosses the intracranial region, and received by the remaining 8 antennae. A complete measurement consists of one cycle with each antenna serving as the transmitting antenna. It was hypothesized that HE of 3 ml would be detected by the device.Ten ICH subjects admitted within 24 hours of stroke onset were enrolled. All patients received a diagnostic head CT (baseline), and a repeat head CT at 12 (+/-6) hours. ICH volumes were determined by blinded neuroradiologist reading, and a significant HE from baseline was considered ≥ 3 ml. Subjects were scanned with the device every 10 minutes for up to 72 hours.Data from one subject was lost from operator error. Among the remaining nine, two experienced HE of ≥ 3ml (3 and 8.2 ml respectively). SENSE device readings were 100% concordant with the CT scan results.
Understanding Spatial Heterogeneity of COVID-19 Pandemic Using Shape Analysis of Growth Rate Curves
Authors: Srivastava Anuj , Chowell Gerardo 
Published: May 2020

AbstractThe growth rates of COVID-19 across different geographical regions (e.g., states in a nation, countries in a continent) follow different shapes and patterns. The overall summaries at coarser spatial scales that are obtained by simply averaging individual curves (across regions) obscure nuanced variability and blurs the spatial heterogeneity at finer spatial scales. We employ statistical methods to analyze shapes of local COVID-19 growth rate curves and statistically group them into distinct clusters, according to their shapes. Using this information, we derive the so-called elastic averages of curves within these clusters, which correspond to the dominant incidence patterns. We apply this methodology to the analysis of the daily incidence trajectory of the COVID-pandemic at two spatial scales: A state-level analysis within the USA and a country-level analysis within Europe during mid-February to mid-May, 2020. Our analyses reveal a few dominant incidence trajectories that characterize transmission dynamics across states in the USA and across countries in Europe. This approach results in broad classifications of spatial areas into different trajectories and adds to the methodological toolkit for guiding public health decision making at different spatial scales.HighlightsCoarsely summarizing epidemic data collected at finer spatial scales can result in a loss of heterogenous spatial patterns that exist at finer scales. For instance, the average curves may give the impression that the epidemic’s trajectory is declining when, in fact, the trajectory of the epidemic is increasing in certain areas.Shape analysis of COVID-19 growth rate curves discovers significant heterogeneity in epidemic spread patterns across spatial areas which can be statistically clustered into distinct groups.At a higher level, clustering spatial patterns into distinct groups helps discern broad trends, such as rapid growth, leveling off, and slow decline in epidemic growth curves resulting from local transmission dynamics. At a finer level, it helps identify temporal patterns of multiple waves that characterize rate curves for different clusters.Quantitative methods for characterizing the spatial-temporal dynamics of evolving epidemic emergencies provide an objective framework to understand transmission dynamics for public health decision making.
In-depth phenotyping of human peripheral blood mononuclear cells in convalescent COVID-19 patients following a mild versus severe disease course
Authors: Chu Chang-Feng , Sabath Florian , Sun Shan , Chao Ying-Yin , Zielinski Christina E. 
Published: May 2020

AbstractBackgroundCovid-19, the disease caused by infection with SARS-CoV-2, has developed to a pandemic causing more than 239, 000 deaths worldwide as of 6th May according to the World Health Organization (WHO). It presents with a highly variable disease course ranging from a large proportion of asymptomatic cases to severe respiratory failure in 17-29% of cases even in the absence of apparent comorbidities 1, 2. This implies a diverse host immune response to SARS-CoV-2. The immunological characteristics underlying these divergent disease courses, however, still remain elusive. While insights into abrogations of innate immunity begin to emerge, adaptive immune responses towards SARS-CoV-2 are poorly investigated, although they serve as immune signatures of protection and vaccine responses. We therefore set out to characterize immune signatures of convalescent COVID-19 patients stratified according to their disease severity.MethodsWe performed high-dimensional flow cytometric profiling of peripheral blood mononuclear cells of convalescent COVID-19 patients who we stratified according to their disease severity by a physician-assisted questionnaire based assessment of COVID-19 symptoms.ResultsSurprisingly, we did not observe any difference in the relative proportions of any major immune cell type in convalescent patients presenting with different severity of COVID-19 disease except for a reduction in monocytes. The frequency of Tnaive T cells was significantly reduced in CD4+ and CD8+ T cells, whereas other T cell differentiations states (TCM, TEM, TEMRA) remained relatively unaffected by COVID-19 severity as assessed approximately two weeks after infection.ConclusionsIn our COVID-19 patient cohort, which is characterized by absence of comorbidities and therapeutic interventions other than symptomatic antipyretics, the immunophenotype is similar irrespective of a highly variable disease severity. Convalescence is therefore associated with a rather uniform immune signature. Abrogations, which were previously identified in the innate and adaptive immune compartment of COVID-19 patients should be scrutinized for direct associations with a preconditioned immune system shaped and made vulnerable for SARS-CoV-2 by preexisting comorbidities.