bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics and predictors of hospitalization and death in the first 9,519 cases with a positive RT-PCR test for SARS-CoV-2 in Denmark: A nationwide cohort
Authors: Reilev Mette , Kristensen Kasper Bruun , Pottegård Anton , Lund Lars Christian , Hallas Jesper , Ernst Martin Thomsen , Christiansen Christian Fynbo , Sørensen Henrik Toft , Johansen Nanna Borup , Brun Nikolai Constantin , Voldstedlund Marianne , Støvring Henrik , Thomsen Marianne Kragh , Christensen Steffen , Gubbels Sophie , Krause Tyra Grove , Mølbak Kåre , Thomsen Reimar Wernich 
Published: May 2020

AbstractObjectiveTo provide population-level knowledge on individuals at high risk of severe and fatal coronavirus disease 2019 (COVID-19) in order to inform targeted protection strategies in the general population and appropriate triage of hospital contacts.Design, Setting, and ParticipantsNationwide population-based cohort of all 228.677 consecutive Danish individuals tested (positive or negative) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA from the identification of the first COVID-19 case on February 27th, 2020 until April 30th, 2020.Main Outcomes and MeasuresWe examined characteristics and predictors of inpatient hospitalization versus community-management, and death versus survival, adjusted for age-, sex- and number of comorbidities.ResultsWe identified 9,519 SARS-CoV-2 PCR-positive cases of whom 78% were community-managed, 22% were hospitalized (3.2% at an intensive care unit) and 5.5% had died within 30 days. Median age varied from 45 years (interquartile range (IQR) 31-57) among community-managed cases to 82 years (IQR 7589) among those who died. Age was a strong predictor of fatal disease (odds ratio (OR) 14 for 70-79-year old, OR 26 for 80-89-year old, and OR 82 for cases older than 90 years, when compared to 50-59-year old and adjusted for sex and number of comorbidities). Similarly, the number of comorbidities was strongly associated with fatal disease (OR 5.2, for cases with ≥4 comorbidities versus no comorbidities), and 82% of fatal cases had at least 2 comorbidities. A wide range of major chronic diseases were associated with hospitalization with ORs ranging from 1.3-1.4 (e.g. stroke, ischemic heart disease) to 2.2-2.7 (e.g. heart failure, hospital-diagnosed kidney disease, chronic liver disease). Similarly, chronic diseases were associated with mortality with ORs ranging from 1.2-1.3 (e.g. ischemic heart disease, hypertension) to 2.4-2.7 (e.g. major psychiatric disorder, organ transplantation). In the absence of comorbidities, mortality was relatively low (5% or less) in persons aged up to 80 years.Conclusions and RelevanceIn this first nationwide population-based study, increasing age and number of comorbidities were strongly associated with hospitalization requirement and death in COVID-19. In the absence of comorbidities, the mortality was, however, lowest until the age of 80 years. These results may help in accurate identification, triage and protection of high-risk groups in general populations, i.e. when reopening societies.
AIDCOV: An Interpretable Artificial Intelligence Model for Detection of COVID-19 from Chest Radiography Images
Authors: Zokaeinikoo Maryam , Kazemian Pooyan , Mitra Prasenjit , Kumara Soundar 
Published: May 2020

AbstractAs the Coronavirus Disease 2019 (COVID-19) pandemic continues to grow globally, testing to detect COVID-19 and isolating individuals who test positive remains to be the primary strategy for preventing community spread of the disease. The current gold standard method of testing for COVID-19 is the reverse transcription polymerase chain reaction (RT-PCR) test. The RT-PCR test, however, has an imperfect sensitivity (around 70%), is time-consuming and labor-intensive, and is in short supply, particularly in resource-limited countries. Therefore, automatic and accurate detection of COVID-19 using medical imaging modalities such as chest X-ray and Computed Tomography, which are more widely available and accessible, can be beneficial as an alternative diagnostic tool. We develop a novel hierarchical attention neural network model to classify chest radiography images as belonging to a person with either COVID-19, other infections, or no pneumonia (i.e., normal). We refer to this model as Artificial Intelligence for Detection of COVID-19 (AIDCOV). The hierarchical structure in AIDCOV captures the dependency of features and improves model performance while the attention mechanism makes the model interpretable and transparent. Using a publicly available dataset of 5801 chest images, we demonstrate that our model achieves a mean cross-validation accuracy of 97.8%. AIDCOV has a sensitivity of 99.3%, a specificity of 99.98%, and a positive predictive value of 99.6% in detecting COVID-19 from chest radiography images. AIDCOV can be used in conjunction with or instead of RT-PCR testing (where RT-PCR testing is unavailable) to detect and isolate individuals with COVID-19 and prevent onward transmission to the general population and healthcare workers.
Intraluminal Prucalopride Increases Propulsive Motor Activities in the Human Colon
Authors: Shokrollahi Mitra , Wang Xuan-Yu , Milkova Natalija , Huizinga Jan D , Chen Ji-Hong 
Published: May 2020

ABSTRACTBackgroundLuminal application of 5-HT4receptor agonists can increase peristalsis in the guinea pig, mouse, rat and rabbit colon. Our aim in the present study was to test the effects of intraluminal prucalopride on motor patterns in the human colon.MethodsColonic motor patterns were studied in vivo in a healthy volunteer using High-Resolution Colonic Manometry (HRCM) with an 84-sensor water perfused catheter with 1cm spacing. 5-HT and 5-HT4receptor immunohistochemistry was performed on human tissue biopsies throughout the colon.Key resultsActivating mucosal 5-HT4receptors via intraluminal prucalopride enhanced propulsive motor activity in the human colon by increasing occurrence and amplitude of propulsive motor patterns including high-amplitude propagating pressure waves (HAPWs), pancolonic simultaneous pressure waves (SPWs) and HAPW-SPWs. Prucalopride-induced motor patterns had a close temporal association with a significant degree of anal sphincter relaxation and some were accompanied by a strong urge to defecate. Biopsies showed 100% colocalization of the 5-HT4receptor to enterochromaffin cells throughout the colon and rectum.Conclusions and inferencesActivating luminal 5-HT4receptors on enterochromaffin cells by intraluminal prucalopride increased propulsive motor activity. 5-HT4receptors were found only on enterochromaffin cells and not ubiquitous on all epithelial cells. Our data support incorporation of prucalopride in colon-specific drug delivery systems as a prokinetic to treat colonic hypomotility disorders.50 word abstractHigh-resolution colonic manometry and biopsy immunohistochemistry revealed that 5-HT4receptors in the lumen of the human colon are present exclusively on enterochromaffin cells and that the 5-HT4agonist prucalopride evokes all major propulsive motor patterns, associated with significant anal sphincter relaxation, when given intraluminally.250-character clinical messageActivating luminal 5-HT4receptors on enterochromaffin cells by intraluminal prucalopride increased propulsive motor activity in the human colon. Colon-specific delivery systems with a 5-HT4agonist may become the preferred colon prokinetic.
Epidemic Model Guided Machine Learning for COVID-19 Forecasts in the United States
Authors: Zou Difan , Wang Lingxiao , Xu Pan , Chen Jinghui , Zhang Weitong , Gu Quanquan 
Published: May 2020

AbstractWe propose a new epidemic model (SuEIR) for forecasting the spread of COVID-19, including numbers of confirmed and fatality cases at national and state levels in the United States. Specifically, the SuEIR model is a variant of the SEIR model by taking into account the untested/unreported cases of COVID-19, and trained by machine learning algorithms based on the reported historical data. Besides providing basic projections for confirmed and fatality cases, the proposed SuEIR model is also able to predict the peak date of active cases, and estimate the basic reproduction number (). In particular, the forecasts based on our model suggest that the peak date of the US, New York state, and California state are 06/01/2020, 05/10/2020, and 07/01/2020 respectively. In addition, the estimatedof the US, New York state, and California state are 2.5, 3.6 and 2.2 respectively. The prediction results for all states in the US can be found on our project website:https://covid19.uclaml.org, which are updated on a weekly basis, and have been adopted by the Centers for Disease Control and Prevention (CDC) for COVID-19 death forecasts (https://www.cdc.gov/coronavirus/2019-ncov/covid-data/forecasting-us.html).
Evaluating Quality Adjusted Life Years in the Absence of Standard Utility Values- A Dynamic Joint Modelling Approach
Authors: Deo Vishal , Grover Gurprit 
Published: May 2020

AbstractEstimation of Quality Adjusted Life Years (QALYs) is pivotal towards cost-effectiveness analysis (CEA) of medical interventions. Most of the CEA studies employ multi-state decision analytic modelling approach, where fixed utility values are assigned to each disease state and total QALYs are calculated on the basis of total lengths of stay in each state.In this paper, we have formulated a new approach to CEA by defining utility as a function of a longitudinal covariate which is significantly associated with disease progression. Association parameter between the longitudinal covariate and survival times is estimated through joint modelling of the longitudinal linear mixed effects model and the Weibull accelerated failure time survival model. Metropolis-Hastings algorithm and Monte Carlo integration are used to predict expected survival times of each censored case using the joint model. Fitted longitudinal model is further used to project values of the longitudinal covariate at all time points for each patient. Utility values calculated using these projected covariate values are used to evaluate QALYs for each patient.Retrospective survival data of HIV/ AIDS patients undergoing treatment at the Antiretroviral Therapy centre of Ram Manohar Lohia hospital in New Delhi is used to demonstrate the implementation of the proposed methodology. A simulation exercise is also carried out to gauge the predictive capability of the joint model in projecting the values of the longitudinal covariate.The proposed dynamic approach to calculate QALY provides a promising alternative to the popular multi-state decision analytic modelling approach, especially when the standard utility values for different stages of the concerned disease are not available.
Mild Behavioral Impairment and Subjective Cognitive Decline predict Mild Cognitive Impairment
Authors: Ismail Zahinoor , McGirr Alexander , Gill Sascha , Hu Sophie , Forkert Nils D. , Smith Eric E. 
Published: May 2020

AbstractObjectiveBetter methods for detecting preclinical neuropathological change are required for prevention of dementia. Mild behavioral impairment (MBI) and subjective cognitive decline (SCD) can represent neurobehavioral and neurocognitive axes of early stage neurodegenerative processes, which are represented in Stage 2 of the NIA-AA Alzheimer’s disease research framework. Both MBI and SCD may offer an opportunity for premorbid detection. We test the hypothesis that MBI and SCD confer additive risk for incident cognitive decline.MethodsParticipants were cognitively normal older adults followed up approximately annually at Alzheimer’s Disease Centers. Logistic regression was used to determine the relationship between baseline classification (MBI+, SCD+, neither (MBI-SCD-), or both (MBI+SCD+)) and cognitive decline, defined by Clinical Dementia Rating (CDR) total score, at 3 years.ResultsOf 2769 participants (mean age=76; 63% females), 1536 were MBI-SCD-, 254 MBI-SCD+, 743 MBI+SCD-, and 236 MBI+SCD+. At 3-years, 349 individuals (12.6%) developed cognitive decline to CDR>0. Compared to SCD-MBI-, we observed an ordinal progression in risk, with ORs [95% CI] as follows: 3.61 [2.42-5.38] for MBI-SCD+ (16.5% progression), 4.76 [3.57-6.34] for MBI+SCD-, (20.7% progression) and 8.15 [5.71-11.64] for MBI+SCD+ (30.9% progression).ConclusionMBI in older adults alone or in combination with SCD is associated with a higher risk of incident cognitive decline at 3 years. The highest rate of progression to MCI is observed in those with both MBI and SCD. Used in conjunction, MBI and SCD could be simple and scalable methods to identify patients at high risk for cognitive decline for prevention studies.
Early Impact of COVID-19 Pandemic on Paediatric Surgical Practice in Nigeria: a National Survey of Paediatric Surgeons
Authors: Ogundele I.O. , Alakaloko F.M. , Nwokoro C.C. , Ameh E.A. 
Published: May 2020

ABSTRACTIntroductionThe novel Coronavirus disease has had significant impact on healthcare globally. Knowledge of this virus is evolving, definitive care is not yet known, and mortality is increasing. We assessed its initial impact on paediatric surgical practice in Nigeria, creating a benchmark for recommendations and future reference.MethodsSurvey of 120 paediatric surgeons from 50 centres to assess socio-demographics and specific domains of impact of COVID-19 on their services and training in Nigeria. Seventy four surgeons adequately responded. Responses have been analysed. Duplicate submissions for centres were excluded by combining and averaging the responses from centres with multiple respondents.ResultsForty-six (92%) centres had suspended elective surgeries. All centres continued emergency surgeries but volume reduced in March by 31%. Eleven (22%) centres reported 13 suspended elective cases presenting as emergencies in March, accounting for 3% of total emergency surgeries. Nine (18%) centres adopted new modalities for managing selected surgical conditions: non-operative reduction of intussusception in 1(2%), antibiotic management of uncomplicated acute appendicitis in 5(10%), more conservative management of trauma and replacement of laparoscopic appendectomy with open surgery in 3(6%) respectively. Low perception of adequacy of Personal Protective Equipment (PPE) was reported in 35(70%) centres. Forty (80%) centres did not offer telemedicine for patients follow up. Twenty-nine (58%) centres had suspended academic training. Perception of safety to operate was low in 37(50%) respondents, indifferent in 24% and high in 26%.ConclusionMajority of paediatric surgical centres reported cessation of elective surgeries whilst continuing emergencies. There is however an acute decline in the volume of emergency surgeries. Adequate PPE need to be provided and preparations towards handling backlog of elective surgeries once the pandemic recedes. Further study is planned to more conclusively understand the full impact of this pandemic on children’s surgery.What is already known and what this study addsAnecdotal evidence suggests that elective surgeries in children have been suspended due to COVID-19 pandemic.Our study shows that most centres have suspended elective surgeries. All centres continued emergency surgeries but the volume reduced by 31% in March 2020. Moreover, 3% of the emergency surgeries were some of the suspended elective cases presenting as emergencies. Almost 20% of centres have newly adopted non-operative modalities for managing selected emergency surgical conditions.This data shows an urgent need for consensus guidelines for emergency services and protocols for handling backlog of elective surgeries in children once the pandemic recedes. Outcome of the modifications in treatment may be subject to future research.
Decoding the architecture of the varicella-zoster virus transcriptome
Authors: Braspenning Shirley E. , Sadaoka Tomohiko , Breuer Judith , Verjans Georges M.G.M , Ouwendijk Werner J.D. , Depledge Daniel P. 
Published: May 2020

SummaryVaricella-zoster virus (VZV), a double-stranded DNA virus, causes varicella, establishes lifelong latency in ganglionic neurons, and reactivates later in life to cause herpes zoster, commonly associated with chronic pain. The VZV genome is densely packed and produces multitudes of overlapping transcripts deriving from both strands. While 71 distinct open reading frames (ORFs) have thus far been experimentally defined, the full coding potential of VZV remains unknown. Here, we integrated multiple short-read RNA sequencing approaches with long-read direct RNA sequencing on RNA isolated from VZV-infected cells to provide a comprehensive reannotation of the lytic VZV transcriptome architecture. Through precise mapping of transcription start sites, splice junctions, and polyadenylation sites, we identified 136 distinct polyadenylated VZV RNAs that encode canonical ORFs, non-canonical ORFs, and ORF fusions, as well as putative non-coding RNAs (ncRNAs). Furthermore, we determined the kinetic class of all VZV transcripts and observed, unexpectedly, that transcripts encoding the ORF62 protein, previously designated asimmediate-early,were expressed withlatekinetics. Our work showcases the complexity of the VZV transcriptome and provides a comprehensive resource that will facilitate future functional studies of coding RNAs, ncRNAs, and the biological mechanisms underlying the regulation of viral transcription and translation during lytic VZV infection.
Features Of Hippocampal Astrocytic Domains And Their Spatial Relation To Excitatory And Inhibitory Neurons
Authors: Refaeli Ron , Doron Adi , Benmelech-Chovav Aviya , Groysman Maya , Kreisel Tirzah , Loewenstein Yonatan , Goshen Inbal 
Published: May 2020

SUMMARYThe mounting evidence for the involvement of astrocytes in neuronal circuits function and behavior stands in stark contrast to the lack of detailed anatomical description of these cells and the neurons in their domains. To fill this void, we imaged >30,000 astrocytes in cleared hippocampi, and employed converging genetic, histological and computational tools to determine the elaborate structure, distribution and neuronal content of astrocytic domains. First, we characterized the spatial distribution of >19,000 astrocytes across CA1 lamina, and analyzed the detailed morphology of thousands of reconstructed domains. We then determined the excitatory content of CA1 astrocytes, averaging above 13 pyramidal neurons per domain and increasing towards CA1 midline. Finally, we discovered that somatostatin neurons are found in close proximity to astrocytes, compared to parvalbumin and VIP inhibitory neurons. This resource expands our understanding of fundamental hippocampal design principles, and provides the first quantitative foundation for neuron-astrocyte interactions in this region.
Predicting Individual Variability in Task-Evoked Brain Activity in Schizophrenia
Authors: Tik Niv , Livny Abigail , Gal Shachar , Gigi Karny , Tsarfaty Galia , Weiser Mark , Tavor Ido 
Published: May 2020

AbstractBACKGROUNDPatients suffering from schizophrenia demonstrate abnormal brain activity, as well as alterations in patterns of functional connectivity assessed by functional magnetic resonance imaging (fMRI). Previous studies in healthy participants suggest a strong association between resting-state functional connectivity and task-evoked brain activity that could be detected at an individual level, and show that brain activation in various tasks could be predicted from task-free fMRI scans. In the current study we aimed to predict brain activity in patients diagnosed with schizophrenia, using a prediction model based on healthy individuals exclusively. This offers novel insights regarding the interrelations between brain connectivity and activity in schizophrenia.METHODSWe generated a prediction model using a group of 80 healthy controls that performed the well-validated N-back task, and used it to predict individual variability in task-evoked brain activation in 20 patients diagnosed with schizophrenia.RESULTSWe demonstrated a successful prediction of individual variability in the task-evoked brain activation based on resting-state functional connectivity. The predictions were highly sensitive, reflected by high correlations between predicted and actual activation maps (Median= 0.589,SD= 0.193) and specific, evaluated by a Kolomogrov-Smirnov test (D= 0.25,p< 0.0001).CONCLUSIONSA Successful prediction of brain activity from resting-state functional connectivity highlights the strong coupling between the two. Moreover, our results support the notion that even though resting-state functional connectivity and task-evoked brain activity are frequently reported to be altered in schizophrenia, the relations between them remains unaffected. This may allow to generate task activity maps for clinical populations without the need the actually perform the task.
Characterising the Behaviour of the CtenophorePleurobrachia pileusin a Laboratory Aquaculture System
Authors: Courtney Amy , Merces George O.T. , Pickering Mark 
Published: May 2020

AbstractNeurobiological research focuses on a small number of model organisms, broadening the pool of animals used in research may lead to important insights into the evolution of nervous systems. The ctenophore is emerging as a promising model, but we are currently lacking an understanding into the relationship between behaviour and environment which is in part due to a lack of a standardised long-term laboratory husbandry system. We established a collection and husbandry system for wild caughtPleurobrachia pileus. We examined the behavioural profile of the animals over time in this controlled environment. We could reliably catch them on a seasonal basis, and we could keep the animals alive in our specialised aquarium system for months at a time.P. pileusspends most of the time in an inactive ‘drifting’ state which is interspersed with periods of one of 5 active behaviours. The most common active behaviours are tentacle resetting and feeding. The longest duration behaviours include swimming up or down. Time of day does not appear to alter their behavioural profile. Gaining a better understanding of the behaviour of these animals has important implications for systems and evolutionary neuroscience.
4-hydroxy-2-nonenal antimicrobial toxicity is neutralized by an intracellular pathogen
Authors: Tabakh Hannah , McFarland Adelle P. , Pollock Alex J. , Glover Rochelle C. , Woodward Joshua J. 
Published: May 2020

AbstractPathogens encounter numerous antimicrobial responses, including the reactive oxygen species (ROS) burst. ROS-mediated oxidation of host membrane poly-unsaturated fatty acids (PUFAs) generates the toxic alpha-beta carbonyl 4-hydroxy-2-nonenal (4-HNE). Though studied extensively in the context of sterile inflammation, 4-HNE’s role during infection remains limited. Here we found that 4-HNE is generated during bacterial infection and that the intracellular pathogenListeria monocytogenesinduces a specific set of genes in response to 4-HNE exposure. A component of theL. monocytogenes4-HNE response is the expression of the genesrha1andrha2which code for two NADPH-dependent oxidoreductases that collectively counter 4-HNE toxicity. Heterologous expression ofrha1/2inBacillus subtilissignificantly increased bacterial resistance to 4-HNE bothin vitroand following phagocytosis by murine macrophages. Our work demonstrates that 4-HNE is a previously unappreciated component of ROS-mediated toxicity and thatL. monocytogeneshas evolved specific countermeasures to survive within its presence.