bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide association study identifies risk variants for sporadic Creutzfeldt-Jakob disease in STX6 and GAL3ST1
Authors: Jones Emma , Hummerich Holger , Viré Emmanuelle , Uphill James , Dimitriadis Athanasios , Speedy Helen , Campbell Tracy , Norsworthy Penny , Quinn Liam , Whitfield Jerome , Linehan Jacqueline , Jaunmuktane Zane , Brandner Sebastian , Jat Parmjit , Nihat Akin , Mok Tze How , Ahmed Parvin , Collins Steven , Stehmann Christiane , Sarros Shannon , Kovacs Gabor , Geschwind Michael , Golubjatnikov Aili , Fronztek Karl , Budka Herbert , Aguzzi Adriano , Karamujić-Čomić Hata , van der Lee Sven , Ibrahim-Verbaas Carla A , Van Duijn Cornelia , Sikorska Beata , Golanska Ewa , Liberski Pawel , Calero Miguel , Calero Olga , Juan Pascual Sanchez , Salas Antonio , Martinón-Torres Federico , Bouaziz-Amar Elodie , Haik Stephane , Laplanche Jean-Louis , Brandel Jean-Phillipe , Amouyel Phillipe , Lambert Jean-Charles , Parchi Piero , Bartoletti-Stella Anna , Capellari Sabina , Poleggi Anna , Ladogana Anna , Pocchiari Maurizio , Aneli Serena , Matullo Giuseppe , Knight Richard , Zafar Saima , Zerr Inga , Booth Stephanie , Coulthart Michael B , Jansen Gerard H , Glisic Katie , Blevins Janis , Gambetti Pierluigi , Safar Jiri , Appleby Brian , Collinge John , Mead Simon 
Published: April 2020

AbstractMammalian prions are lethal pathogens composed of fibrillar assemblies of misfolded prion protein. Human prion diseases are rare and usually rapidly fatal neurodegenerative disorders, the most common being sporadic Creutzfeldt-Jakob disease (sCJD). Variants in the gene that encodes prion protein (PRNP) are strong risk factors for sCJD, but although the condition has heritability similar to other neurodegenerative disorders, no other risk loci have yet been confirmed. By genome-wide association in European ancestry populations, we found three replicated loci (cases n=5208, within PRNP, STX6, and GAL3ST1) and two further unreplicated loci were significant in gene-wide tests (within PDIA4, BMERB1). Exome sequencing in 407 sCJD cases, conditional and transcription analyses suggest that associations at PRNP and GAL3ST1 are likely to be caused by common variants that alter the protein sequence, whereas risk variants in STX6 and PDIA4 associate with increased expression of the major transcripts in disease-relevant brain regions. Alteration of STX6 expression does not modify prion propagation in a neuroblastoma cell model of mouse prion infection. We went on to analyse the proteins histologically in diseased tissue and examine the effects of risk variants on clinical phenotypes using deep longitudinal clinical cohort data. Risk SNPs in STX6, a protein involved in the intracellular trafficking of proteins and vesicles, are shared with progressive supranuclear palsy, a neurodegenerative disease associated with the misfolded protein tau. We present the first evidence of statistically robust associations in sporadic human prion disease that implicate intracellular trafficking and sphingolipid metabolism.
Human monoclonal antibodies block the binding of SARS-CoV-2 spike protein to angiotensin converting enzyme 2 receptor
Authors: Chen Xiangyu , Li Ren , Pan Zhiwei , Qian Chunfang , Yang Yang , You Renrong , Zhao Jing , Liu Pinghuang , Gao Leiqiong , Li Zhirong , Huang Qizhao , Xu Lifan , Tang Jianfang , Tian Qin , Yao Wei , Hu Li , Yan Xiaofeng , Zhou Xinyuan , Wu Yuzhang , Deng Kai , Zhang Zheng , Qian Zhaohui , Chen Yaokai , Ye Lilin 
Published: April 2020

AbstractThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of novel corona virus disease (COVID-19). To date, no prophylactic vaccines or approved therapeutic agents are available for preventing and treating this highly transmittable disease. Here we report two monoclonal antibodies (mAbs) cloned from memory B cells of patients recently recovered from COVID-19, and both mAbs specifically bind to the spike (S) protein of SARS-CoV-2, block the binding of receptor binding domain (RBD) of SARS-CoV-2 to human angiotensin converting enzyme 2 (hACE2), and effectively neutralize S protein-pseudotyped virus infection. These human mAbs hold the promise for the prevention and treatment of the ongoing pandemic of COVID-19.
Epigenome-wide analyses identify DNA methylation signatures of dementia risk
Authors: Walker Rosie M. , Bermingham Mairead L. , Vaher Kadi , Morris Stewart W. , Clarke Toni-Kim , Bretherick Andrew D. , Zeng Yanni , Amador Carmen , Rawlik Konrad , Pandya Kalyani , Hayward Caroline , Campbell Archie , Porteous David J. , McIntosh Andrew M. , Marioni Riccardo E. , Evans Kathryn L. 
Published: April 2020

AbstractINTRODUCTIONDementia pathogenesis begins years before clinical symptom onset, necessitating the understanding of premorbid risk mechanisms. Here, we investigated potential pathogenic mechanisms by assessing DNA methylation associations with dementia risk factors in Alzheimer’s disease (AD)-free participants.METHODSAssociations between dementia risk measures (family history, genetic risk score (GRS), and dementia risk scores (combining lifestyle, demographic and genetic factors) and whole-blood DNA methylation were assessed in discovery and replication samples (n=∼400 – ∼5,000) from Generation Scotland.RESULTSAD genetic risk and two risk scores were associated with differential methylation. The GRS predominantly associated with methylation differences in cis but also identified a genomic region implicated in Parkinson’s disease. Loci associated with the risk scores were enriched for those previously associated with body mass index and alcohol consumption.DISCUSSIONDementia risk measures show widespread association with blood-based methylation, which indicates differences in the processes affected by genetic and demographic/lifestyle risk factors.
To mask or not to mask: Modeling the potential for face mask use by the general public to curtail the COVID-19 pandemic
Authors: Eikenberry Steffen E. , Mancuso Marina , Iboi Enahoro , Phan Tin , Eikenberry Keenan , Kuang Yang , Kostelich Eric , Gumel Abba B. 
Published: April 2020

AbstractFace mask use by the general public for limiting the spread of the COVID-19 pandemic is controversial, though increasingly recommended, and the potential of this intervention is not well understood. We develop a compartmental model for assessing the community-wide impact of mask use by the general, asymptomatic public, a portion of which may be asymptomatically infectious. Model simulations, using data relevant to COVID-19 dynamics in the US states of New York and Washington, suggest that broad adoption of even relatively ineffective face masks may meaningfully reduce community transmission of COVID-19 and decrease peak hospitalizations and deaths. Moreover, mask use decreases the effective transmission rate in nearly linear proportion to the product of mask effectiveness (as a fraction of potentially infectious contacts blocked) and coverage rate (as a fraction of the general population), while the impact on epidemiologic outcomes (death, hospitalizations) is highly nonlinear, indicating masks could synergize with other non-pharmaceutical measures. Notably, masks are found to be useful with respect to both preventing illness in healthy persons and preventing asymptomatic transmission. Hypothetical mask adoption scenarios, for Washington and New York state, suggest that immediate near universal (80%) adoption of moderately (50%) effective masks could prevent on the order of 17–45% of projected deaths over two months in New York, while decreasing the peak daily death rate by 34–58%, absent other changes in epidemic dynamics. Even very weak masks (20% effective) can still be useful if the underlying transmission rate is relatively low or decreasing: In Washington, where baseline transmission is much less intense, 80% adoption of such masks could reduce mortality by 24–65% (and peak deaths 15–69%), compared to 2–9% mortality reduction in New York (peak death reduction 9–18%). Our results suggest use of face masks by the general public is potentially of high value in curtailing community transmission and the burden of the pandemic. The community-wide benefits are likely to be greatest when face masks are used in conjunction with other non-pharmaceutical practices (such as social-distancing), and when adoption is nearly universal (nation-wide) and compliance is high.
Infoveillance based on Social Sensors to Analyze the impact of Covid19 in South American Population
Authors: Saire Josimar E. Chire 
Published: April 2020

ABSTRACTInfoveillance is an application from Infodemiology field with the aim to monitor public health and create public policies. Social sensor is the people providing thought, ideas through electronic communication channels(i.e. Internet). The actual scenario is related to tackle the covid19 impact over the world, many countries have the infrastructure, scientists to help the growth and countries took actions to decrease the impact. South American countries have a different context about Economy, Health and Research, so Infoveillance can be a useful tool to monitor and improve the decisions and be more strategical. The motivation of this work is analyze the capital of Spanish Speakers Countries in South America using a Text Mining Approach with Twitter as data source. The preliminary results helps to understand what happens two weeks ago and opens the analysis from different perspectives i.e. Economics, Social.
Oxygen needs in austere environment : French military health service experience
Authors: Cungi Pierre-Julien , Mathais Quentin , D’Aranda Erwan , Cardinale Mickael , Goutorbe Philippe , Bordes Julien , Meaudre Eric 
Published: April 2020

AbstractINTRODUCTIONManagement of Oxygen supplies is a recurring problem for the intensivists and anesthesiologists working in an austere environment. The French military health service has chosen oxygen concentrators (OC) as the primary source of oxygen.OBJECTIVESThe main objective was to evaluate the feasibility of using OC as the main source of 02for intensive care patients. We assess the need to use pressurized 02during the ICU hospitalization. The secondary objectives were to identify the causes of the use of pressurized 02.MATERIAL AND METHODWe realize an interventional cohort study at the French role 3 hospitals located in the Republic of Djibouti. The criteria of inclusion were all patients aged over 18 years, requiring oxygen and admitted to intensive care.RESULTSWe include 35 patients over 6-month period for 251 days of oxygenation, including 142 days of invasive mechanical ventilation. The population include 21 (60%) men, aged of 35 (30 - 49) years. Twenty-eight (80%) patients benefits of invasive ventilation. Median 02administration duration was 6 (3-10) days, and the median duration of mechanical ventilation was 3 (1-5) days. Nineteen pressurized O2 treatments were required over 251 days of oxygen therapy, or 7.5% of the total oxygen therapy time. The causes of recourse were in 10 cases (52.6%) severe ARDS, in 6 cases (31.6%) an emergency orotracheal intubation and in 3 cases (15.8%) a transfer. Only one OC dysfunction occurred during the study.CONCLUSIONOC can be used as a primary source for intensive care patients in an austere environment. The use of pressurized 02remains imperative in the event of an electrical failure and the need to use high Fi02over 60%.
The efficiency in the ordinary hospital bed management in Italy: an in-depth analysis of intensive care unit in the areas affected by COVID-19 before the outbreak
Authors: Pecoraro Fabrizio , Clemente Fabrizio , Luzi Daniela 
Published: April 2020

AbstractIn the first months of 2020 an increasing number of individuals worldwide are infected by the coronavirus disease 2019 (COVID-19). A particularly severe diffusion of the virus has affected Italy and in particular its northern regions. This is resulting in a high demand of hospitalization with a particular attention on the intensive care units (ICUs). Hospitals are suffering the high degree of patients to be treated for respiratory diseases and the majority of the structures located in the north of Italy are or are going to be saturated. This has led the actual and past national and regional governments to be heavily criticized for reducing in the past years the number of beds, in particular those located in the ICUs across the country. Aim of this study is to analyse the availability of hospital beds across the country as well as to determine their management in terms of complexity and performance of cases treated at regional level. The results of this study underlines that, despite the reduction of beds for the majority of the hospital wards, ICUs availabilities did not change between 2010 and 2017. Moreover, this study confirms that the majority of the Italian regions efficiently manage these structural facilities allowing hospitals to treat patients without the risk of having an overabundance of patients and a scarcity of beds. In fact, this analysis shows that, in normal situations, the management of hospital and intensive care beds has no critical levels.
Outbreak dynamics of COVID-19 in China and the United States
Authors: Peirlinck Mathias , Linka Kevin , Costabal Francisco Sahli , Kuhl Ellen 
Published: April 2020

AbstractOn March 11, 2020, the World Health Organization declared the coronavirus disease 2019, COVID19, a global pandemic. In an unprecedented collective effort, massive amounts of data are now being collected worldwide to estimate the immediate and long-term impact of this pandemic on the health system and the global economy. However, the precise timeline of the disease, its transmissibility, and the effect of mitigation strategies remain incompletely understood. Here we integrate a global network model with a local epidemic SEIR model to quantify the outbreak dynamics of COVID-19 in China and the United States. For the outbreak in China, in n = 30 provinces, we found a latent period of 2.56±0.72 days, a contact period of 1.47±0.32 days, and an infectious period of 17.82±2.95 days. We postulate that the latent and infectious periods are disease-specific, whereas the contact period is behavior-specific and can vary between different provinces, states, or countries. For the early stages of the outbreak in the United States, in n = 50 states, we adopted the disease-specific values from China, and found a contact period of 3.38±0.69 days. Our network model predicts that–without the massive political mitigation strategies that are in place today–the United states would have faced a basic reproduction number of 5.3±0.95 and a nationwide peak of the outbreak on May 10, 2020 with 3 million infections. Our results demonstrate how mathematical modeling can help estimate outbreak dynamics and provide decision guidelines for successful outbreak control. We anticipate that our model will become a valuable tool to estimate the potential of vaccination and quantify the effect of relaxing political measures including total lock down, shelter in place, and travel restrictions for low-risk subgroups of the population or for the population as a whole.
Human ACE2 receptor polymorphisms predict SARS-CoV-2 susceptibility
Authors: Stawiski Eric W. , Diwanji Devan , Suryamohan Kushal , Gupta Ravi , Fellouse Frederic A. , Sathirapongsasuti J. Fah , Liu Jiang , Jiang Ying-Ping , Ratan Aakrosh , Mis Monika , Santhosh Devi , Somasekar Sneha , Mohan Sangeetha , Phalke Sameer , Kuriakose Boney , Antony Aju , Junutula Jagath R. , Schuster Stephan C. , Jura Natalia , Seshagiri Somasekar 
Published: April 2020

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease (COVID-19) that has resulted in a global pandemic. It is a highly contagious positive strand RNA virus and its clinical presentation includes severe to critical respiratory disease that appears to be fatal in ∼3-5% of the cases. The viral spike (S) coat protein engages the human angiotensin-converting enzyme2 (ACE2) cell surface protein to invade the host cell. The SARS-CoV-2 S-protein has acquired mutations that increase its affinity to human ACE2 by ∼10-15-fold compared to SARS-CoV S-protein, making it highly infectious. In this study, we assessed if ACE2 polymorphisms might alter host susceptibility to SARS-CoV-2 by affecting the ACE2 S-protein interaction. Our comprehensive analysis of several large genomic datasets that included over 290,000 samples representing >400 population groups identified multiple ACE2 protein-altering variants, some of which mapped to the S-protein-interacting ACE2 surface. Using recently reported structural data and a recent S-protein-interacting synthetic mutant map of ACE2, we have identified natural ACE2 variants that are predicted to alter the virus-host interaction and thereby potentially alter host susceptibility. In particular, human ACE2 variants S19P, I21V, E23K, K26R, T27A, N64K, T92I, Q102P and H378R are predicted to increase susceptibility. The T92I variant, part of a consensus NxS/T N-glycosylation motif, confirmed the role of N90 glycosylation in immunity from non-human CoVs. Other ACE2 variants K31R, N33I, H34R, E35K, E37K, D38V, Y50F, N51S, M62V, K68E, F72V, Y83H, G326E, G352V, D355N, Q388L and D509Y are putative protective variants predicted to show decreased binding to SARS-CoV-2 S-protein. Overall, ACE2 variants are rare, consistent with the lack of selection pressure given the recent history of SARS-CoV epidemics, however, are likely to play an important role in altering susceptibility to CoVs.
Currently available intravenous immunoglobulin (Gamunex®-C and Flebogamma®DIF) contains antibodies reacting against SARS-CoV-2 antigens
Authors: Díez José-María , Romero Carolina , Gajardo Rodrigo 
Published: April 2020

AbstractBackgroundThere is a critical need for effective therapies that are immediately available to control the spread of COVID-19 disease. In this study, we assessed currently marketed intravenous immunoglobulin (IVIG) products for antibodies against human common coronaviruses that may cross-react with the SARS-CoV-2 virus.MethodsGamunex®-C and Flebogamma®DIF (Grifols) IVIG were tested against several betacoronaviruses antigens using ELISA techniques: HCoV (undetermined antigen), HCoV-HKU1 (N protein), SARS-CoV (culture lysate), MERS-CoV (N protein; S1 protein/RBD; S protein), and SARS-CoV-2 (S1 protein).ResultsBoth IVIG products showed consistent reactivity to components of the tested viruses. Positive cross-reactivity was seen in SARS-CoV, MERS-CoV, and SARS-CoV-2. For SARS-CoV-2, positive reactivity was observed at IVIG concentrations ranging from 100 μg/mL with Gamunex-C to 1 mg/mL with Flebogamma 5% DIF.ConclusionGamunex-C and Flebogamma DIF IVIG contain antibodies reacting against SARS-CoV-2 antigens. These preparations may be useful for immediate treatment of COVID-19 disease.
ESTIMATION OF COVID-19 CASES IN FRANCE AND IN DIFFERENT COUNTRIES: HOMOGENEISATION BASED ON MORTALITY
Authors: Dhenain Marc 
Published: April 2020

AbstractEvery day the authorities of different countries provide an estimate of the number of persons affected by Covid-19 and a count of fatality. We propose to use the fatality reported in each country to provide a better estimate (Ct0-estimated) of the number of cases at a given time t0.
With Ft0: number of actual fatalities reported in a country at time t0; Fr-est: estimated fatality rate; C(est-d): estimated fatalities 18 days before t0; C(est-3d): estimated fatalities 21 days before t0.Based on Ct0-estimated calculated using a fatality rate of 2%, we assessed the number of cases April 10th, 2020 in Belgium, China, France, Germany, Iran, Italy, South Korea, Netherlands, Spain, United Kingdom and USA. This number reached 2,872,097 in France and 924,892 persons in Germany. The proposed formulas also make it possible to evaluate the impact of policies to prevent the spread of epidemic on the appearance of new cases.
Modelling the impact of COVID-19 in Australia to inform transmission reducing measures and health system preparedness
Authors: Moss R , Wood J , Brown D , Shearer F , Black AJ , Cheng AC , McCaw JM , McVernon J 
Published: April 2020

ABSTRACTBackgroundThe ability of global health systems to cope with increasing numbers of COVID-19 cases is of major concern. In readiness for this challenge, Australia has drawn on clinical pathway models developed over many years in preparation for influenza pandemics. These models have been used to estimate health care requirements for COVID-19 patients, in the context of broader public health measures.MethodsAn age and risk stratified transmission model of COVID-19 infection was used to simulate an unmitigated epidemic with parameter ranges reflecting uncertainty in current estimates of transmissibility and severity. Overlaid public health measures included case isolation and quarantine of contacts, and broadly applied social distancing. Clinical presentations and patient flows through the Australian health care system were simulated, including expansion of available intensive care capacity and alternative clinical assessment pathways.FindingsAn unmitigated COVID-19 epidemic would dramatically exceed the capacity of the Australian health system, over a prolonged period. Case isolation and contact quarantine alone will be insufficient to constrain case presentations within a feasible level of expansion of health sector capacity. Overlaid social restrictions will need to be applied at some level over the course of the epidemic to ensure that systems do not become overwhelmed, and that essential health sector functions, including care of COVID-19 patients, can be maintained. Attention to the full pathway of clinical care is needed to ensure access to critical care.InterpretationReducing COVID-19 morbidity and mortality will rely on a combination of measures to strengthen and extend public health and clinical capacity, along with reduction of overall infection transmission in the community. Ongoing attention to maintaining and strengthening the capacity of health care systems and workers to manage cases is needed.FundingAustralian Government Department of Health Office of Health Protection, Australian Government National Health and Medical Research Council
Simplified model of the number of Covid-19 patients in the ICU: update April 6, 2020
Authors: Cividjian A. , Wallet F , Guichon C. , Martin O. , Couray-Targe S. , Rimmelé T , Wey PF 
Published: April 2020

ABSTRACTINTRODUCTIONPredicting the number of Covid-19 patients in the Intensive Care Units (ICU) could be useful to avoid the breaking point. We attempted to deduce a formula in order to model the number of the ICU patients in France from the official data and patient turnover in the ICU.METHODSThe Covid-19 ICU patient turnover was calculated using a recurrence relation from the internal data provided by Hospices Civils de Lyon. The number of new Covid-19 cases detected daily was modelized to fit with the last known data in France and extrapolated for the coming days using two scenarios following the existing data in China (best scenario) and Italy (worst scenario). The number of daily admissions in ICU was calculated as the sum of 13.7% of the new Covid-19 cases detected on a given day and 7.8% of the average of the total new Covid-19 cases recorded in the last week. Approximately 39.7% of patients admitted to the ICU were non-intubated with an average ICU length of stay of 4 days. Conversely, 60.3% of patients were intubated and for those who died among them (14.44%) the ICU length of stay was of 4 days for 78.3% of them and of 15 days for 21.7% of them. For the intubated patients that were discharged alive, the ICU length of stay was of 6 days for 44.4% of them and of 20 days for 55.6% of them.RESULTSWe predict a peak of 7072 – 8043 patients for the overall French territory.CONCUSIONDespite a simplified mathematical model, the strength of our study is a narrow possible range of predicted total number of ICU patients.