bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phenotyping genetic differences in aldehyde dehydrogenase 2 after an alcohol challenge in humans
Authors: White Joseph R. , Rwere Freeborn , Zeng Xiaocong , McNeil Leslie , Zhou Kevin , Angst Martin S. , Chen Che-Hong , Mochly-Rosen Daria , Gross Eric R. 
Published: June 2020

AbstractInefficient aldehyde metabolism by an aldehyde dehydrogenase 2 (ALDH2) genetic variant, ALDH2*2 (rs671), increases the risk of esophageal cancer with alcohol consumption. Here we tested the hypothesis that additional genetic differences in ALDH2 besides ALDH2*2 exist resulting in inefficient acetaldehyde metabolism after alcohol consumption.Human volunteers were recruited who self-reported flushing after alcohol. The first stage recruited East Asians and the second stage non-East Asians. After phone screening and ALDH2 sequencing, volunteers were subjected to an alcohol challenge (0.25g/kg). Physiological parameters and breath acetaldehyde levels were assessed.Twenty-six participants were given an alcohol challenge. In the first stage, when comparing the ALDH2*1/*2 genotype to ALDH2*1/*1 genotype, tachycardia (104±3* versus 73±4 beats per minute), increases in facial skin temperature (99.6±0.4* versus 95.9±0.50F), and increases in breath acetaldehyde (peak: 2.1±0.4* versus 0.2±0.3ppm, n=8/group, *p<0.01) occurred after alcohol consumption. In the second stage, heterozygotes for an ALDH2 intron variant (rs4646777, G>A) caused increases in facial skin temperature (98±1* versus 94±10F, n=4, *p<0.01) without tachycardia or acetaldehyde accumulation after alcohol consumption. Subjects self-identifying as non-East Asian genotyped with an ALDH2*1/*2 variant also displayed a characteristic ALDH2*1/*2 phenotype after alcohol consumption. Further, ALDH2 point mutations rs747096195 (R101G) and rs190764869 (R114W) showed reduced acetaldehyde metabolism and increases in facial skin temperature after an alcohol challenge relative to wild type ALDH2 subjects.Taken together, we developed a method to non-invasively phenotype genetic differences for ALDH2 in humans including quantifying aldehyde metabolism in single subjects. We also discovered genetic differences besides ALDH2*2 that cause inefficient aldehyde metabolism.Brief SummaryWe developed a method to phenotype genetic differences in ALDH2 and we discovered novel ALDH2 mutations that result in inefficient acetaldehyde metabolism after alcohol consumption.
Idiopathic and acquired pedophilia as two distinct disorders: an insight from neuroimaging
Authors: Scarpazza Cristina , Finos Livio , Genon Sarah , Masiero Laura , Bortolato Elena , Cavaliere Camilla , Pezzaioli Jessica , Monaro Merylin , Navarin Nicolò , Umberto Battaglia , Pietrini Pietro , Ferracuti Stefano , Sartori Giuseppe , Ciani Andrea S. Camperio 
Published: June 2020

AbstractObjectivePedophilia is a disorder of public concern because of its association with child sexual offense and recidivism. Previous neuroimaging studies identified inconsistent brain abnormalities underlying pedophilic behavior both in idiopathic and acquired (i.e., emerging following brain damage) pedophilia. This study sought to explore the neural underpinnings of pedophilic behavior and to determine the extent to which brain alterations may be related to distinct psychopathological features in pedophilia.MethodsA coordinate based meta-analysis on previously published papers reporting whole brain analysis and a lesion network analysis using brain lesions as seeds in a resting state connectivity analysis were run to investigate the presence of consistent neural basis of idiopathic and acquired pedophilic behavior, respectively. The behavioral profiling approach was applied to link identified regions with corresponding psychological processes.ResultsWhile no consistent neuroanatomical alterations have been identified in idiopathic pedophilia, the current results support that all the lesions causing acquired pedophilia localized to a shared resting state network including posterior midlines structures, right inferior temporal gyrus and bilateral orbitofrontal cortex. These regions are associated with action inhibition and social cognition, abilities that are consistently described as severely impaired in acquired pedophiles.ConclusionsThis study suggests that idiopathic and acquired pedophilia may be two distinct disorders, in line with their distinctive clinical features, including age of onset, reversibility and modus operandi. Understanding the neurobiological underpinnings of pedophilic behavior may contribute to a more comprehensive characterization of these individuals on a clinical ground and to develop more efficient therapeutic rehabilitation strategies.
From predictions to prescriptions: A data-driven response to COVID-19
Authors: Bertsimas Dimitris , Boussioux Leonard , Cory-Wright Ryan , Delarue Arthur , Digalakis Vasileios , Jacquillat Alexandre , Kitane Driss Lahlou , Lukin Galit , Li Michael , Mingardi Luca , Nohadani Omid , Orfanoudaki Agni , Papalexopoulos Theodore , Paskov Ivan , Pauphilet Jean , Lami Omar Skali , Stellato Bartolomeo , Bouardi Hamza Tazi , Carballo Kimberly Villalobos , Wiberg Holly , Zeng Cynthia 
Published: June 2020

The COVID-19 pandemic has created unprecedented challenges worldwide. Strained healthcare providers make difficult decisions on patient triage, treatment and care management on a daily basis. Policy makers have imposed social distancing measures to slow the disease, at a steep economic price. We design analytical tools to support these decisions and combat the pandemic. Specifically, we propose a comprehensive data-driven approach to understand the clinical characteristics of COVID-19, predict its mortality, forecast its evolution, and ultimately alleviate its impact. By leveraging cohort-level clinical data, patient-level hospital data, and census-level epidemiological data, we develop an integrated four-step approach, combining descriptive, predictive and prescriptive analytics. First, we aggregate hundreds of clinical studies into the most comprehensive database on COVID-19 to paint a new macroscopic picture of the disease. Second, we build personalized calculators to predict the risk of infection and mortality as a function of demographics, symptoms, comorbidities, and lab values. Third, we develop a novel epidemiological model to project the pandemic’s spread and inform social distancing policies. Fourth, we propose an optimization model to reallocate ventilators and alleviate shortages. Our results have been used at the clinical level by several hospitals to triage patients, guide care management, plan ICU capacity, and re-distribute ventilators. At the policy level, they are currently supporting safe back-to-work policies at a major institution and equitable vaccine distribution planning at a major pharmaceutical company, and have been integrated into the US Center for Disease Control’s pandemic forecast.Significance StatementIn the midst of the COVID-19 pandemic, healthcare providers and policy makers are wrestling with unprecedented challenges. How to treat COVID-19 patients with equipment shortages? How to allocate resources to combat the disease? How to plan for the next stages of the pandemic? We present a data-driven approach to tackle these challenges. We gather comprehensive data from various sources, including clinical studies, electronic medical records, and census reports. We develop algorithms to understand the disease, predict its mortality, forecast its spread, inform social distancing policies, and re-distribute critical equipment. These algorithms provide decision support tools that have been deployed on our publicly available website, and are actively used by hospitals, companies, and policy makers around the globe.
A Small Molecule Fluorogenic Probe for the Detection of Sphingosine in Living Cells
Authors: Rudd Andrew K. , Mittal Neel , Lim Esther W. , Metallo Christian M. , Devaraj Neal K. 
Published: June 2020

ABSTRACTThe single-chained sphingolipid sphingosine is an essential structural lipid and signaling molecule. Abnormal sphingosine metabolism is observed in several diseases, including cancer, diabetes, and Alzheimer’s. Despite its biological importance, there are a lack of tools for detecting sphingosine in living cells. This is likely due to the broader challenge of developing highly selective and live-cell compatible affinity probes for hydrophobic lipid species. In this work, we have developed a small molecule fluorescent turn-on probe for labeling sphingosine in living cells. This probe utilizes a selective reaction between sphingosine and salicylaldehyde esters to fluorescently label sphingosine molecules. We demonstrate that this probe exhibits a dose-dependent response to sphingosine and is able to detect endogenous pools of sphingosine. Using our probe, we successfully detected sphingosine accumulation in live Niemann-Pick type C1 (NPC1) patient cells, a lipid transport disorder in which increased sphingosine mediates disease progression. This work provides a simple and accessible method for the detection of sphingosine and should facilitate study of this critical signaling lipid in biology and disease.
The Atlas of the In Vivo HIV CD4 T Cell Reservoir
Authors: Neidleman Jason , Luo Xiaoyu , Frouard Julie , Xie Guorui , Hsiao Feng , Ma Tongcui , Morcilla Vincent , Lee Ashley , Telwatte Sushama , Thomas Reuben , Tamaki Whitney , Wheeler Benjamin , Hoh Rebecca , Somsouk Ma , Vohra Poonam , Milush Jeffrey , James Katherine Sholtis , Archin Nancie M. , Hunt Peter W. , Deeks Steven G. , Yukl Steven A. , Palmer Sarah , Greene Warner C. , Roan Nadia R. 
Published: June 2020

ABSTRACTThe latent reservoir is a main barrier for curing HIV. But because latently-infected cells cannot be phenotyped directly, the features of the in vivo reservoir have remained elusive. Here, we describe a method that leverages high-dimensional phenotyping using CyTOF to trace latently-infected cells reactivated ex vivo to their original pre-activation states. Our results suggest that contrary to common assumptions, the reservoir is not randomly distributed among cell subsets, and is remarkably conserved between individuals. However, reservoir composition differs between tissues and blood, as do cells successfully reactivated by different latency reversing agents. Most importantly, by selecting 8-10 of our 39 original CyTOF markers, we were able to isolate highly purified populations of unstimulated in vivo latent cells, thereby validating the PP-SLIDE approach for reservoir characterization. These purified populations were highly enriched for replication-competent and intact provirus, transcribed HIV, and displayed clonal expansion. The ability to isolate unstimulated latent cells from infected individuals enables previously impossible studies of HIV persistence.
THE EXPERIENCE OF UK BLADDER CANCER PATIENTS DURING THE COVID-19 PANDEMIC: A SURVEY-BASED SNAPSHOT
Authors: Spencer-Bowdage Sarah , Rigby Jeannie , O’Kelly Jackie , Kelly Phil , Page Mark , Raw Caroline , Allchorne Paula , Harper Peter , Crew Jeremy , Kockelbergh Roger , Knight Allen , Bryan Richard T 
Published: June 2020

ABSTRACTThe Covid-19 pandemic has placed unprecedented strain on healthcare systems worldwide. Within this context, UK cancer services have undergone significant disruption to create capacity for the National Health Service. As a charity that endeavours to support bladder cancer (BC) patients and improve outcomes, Action Bladder Cancer UK (ABCUK) designed and administered a SurveyMonkey survey to investigate the prevalence of such disruption for BC patients. From 22nd April to 18th June 2020, 142 BC patients responded. Across all patient groups, 46.8% of patients described disruption to their treatment or follow-up. For non-muscle-invasive BC (NMIBC) patients, disruptions included postponement of: initial transurethral resection of bladder tumour (TURBT) (33.3%), subsequent TURBT (40.0%), and surveillance cystoscopy (58.1%). For NMIBC patients undergoing intravesical therapy, 68.4% experienced treatment postponements or curtailments. For muscle-invasive BC patients, 57.1% had experienced postponement of cystectomy and 14.3% had been changed from cystectomy to radiotherapy. Half of patients undergoing systemic chemotherapy also experienced disruption. Despite the survey’s limitations, we have demonstrated considerable disruption to the care of BC patients during the UK Covid-19 pandemic. To avoid a repeat, the UK BC community should define effective contingent ways of working ready for a possible ‘second wave’ of Covid-19, or any other such threat.
A Modelling Study for Designing a Multi-layered Surveillance Approach to Detect the Potential Resurgence of SARS-CoV-2
Authors: Liu Yang , Gong Wenfeng , Clifford Samuel , Sundaram Maria E. ,   CMMID-COVID19 Working Group, Jit Mark , Flasche Stefan , Klepac Petra 
Published: June 2020

AbstractBackgroundCountries achieving control of COVID-19 after an initial outbreak will continue to face the risk of SARS-CoV-2 resurgence. This study explores surveillance strategies for COVID-19 containment based on polymerase chain reaction tests.MethodsUsing a dynamic SEIR-type model to simulate the initial dynamics of a COVID-19 introduction, we investigate COVID-19 surveillance strategies among healthcare workers, hospital patients, and community members. We estimate surveillance sensitivity as the probability of COVID-19 detection using a hypergeometric sampling process. We identify test allocation strategies that maximise the probability of COVID-19 detection across different testing capacities. We use Beijing, China as a case study.FindingsSurveillance subgroups are more sensitive in detecting COVID-19 transmission when they are defined by more COVID-19 specific symptoms. In this study, fever clinics have the highest surveillance sensitivity, followed by respiratory departments. With a daily testing rate of 0.07/1000 residents, via exclusively testing at fever clinic and respiratory departments, there would have been 598 [95% eCI: 35, 2154] and 1373 [95% eCI: 47, 5230] cases in the population by the time of first case detection, respectively. Outbreak detection can occur earlier by including non-syndromic subgroups, such as younger adults in the community, as more testing capacity becomes available.InterpretationA multi-layer approach that considers both the surveillance sensitivity and administrative constraints can help identify the optimal allocation of testing resources and thus inform COVID-19 surveillance strategies.FundingBill & Melinda Gates Foundation, National Institute of Health Research (UK), National Institute of Health (US), the Royal Society, and Wellcome Trust.
Cancer inpatient with COVID-19: a report from the Brazilian National Cancer Institute
Authors: de Melo Andreia C. , Thuler Luiz C.S. , Silva Jesse L. da , de Albuquerque Lucas Z. , Pecego Ana C. , Rodrigues Luciana de O.R. , da Conceição Magda S. , Garrido Marianne M. , Quintella Mendes Gelcio L. , Mendes Pereira Ana Cristina P. , Soares Marcelo A. , Viola João P.B. 
Published: June 2020

AbstractBrazil has been recording a frightening exponential curve of confirmed cases of SARS-CoV-2 infection. Cancer patients with COVID-19 are likely to have a greater risk of complications and death. A retrospective search in the electronic medical records of cancer inpatients admitted to the Brazilian National Cancer Institute from April 30, 2020 to May 26, 2020 granted identification of 181 patients with COVID-19 confirmed by RT-PCR method. The mean age was 55.3 years (SD ±21.1). The most prevalent solid tumors were breast (40 [22.1%]), gastrointestinal (24 [13.3%]), and gynecological (22 [12.2%]). Among hematological malignancies, lymphoma (20 [11%]) and leukemia (10 [5.5%]) predominated. The most common complications were respiratory failure (70 [38.7%]), septic shock (40 [22.1%]) and acute kidney injury (33 [18.2%]). A total of 60 (33.1%) patients died due to COVID-19 complications. By multivariate analysis, cases with admission due to symptoms of COVID-19 (p = 0.027) and with two or more metastatic sites (p <0.001) showed a higher risk of COVID-19-specific death. This is the first study in a cohort of Brazilian cancer patients with COVID-19. The rates of complications and COVID-19-specific death were significantly high. Our data prompts urgent and effective public policies for this group of especially vulnerable patients.Statement of SignificanceCOVID-19-specific mortality in cancer inpatients is markedly higher than in the general population and the cases with advanced cancer are particularly in a more vulnerable group. Adaptations of cancer management guidelines and more intensive preventive measures should be a priority for this group of patients.
Health care seeking behaviour and financial protection of patients with hypertension: a cross-sectional study in rural West Bengal, India
Authors: Chakraborty Sandipta , Rai Rajesh Kumar , Biswas Asit Kumar , Barik Anamitra , Gurung Preeti , Praveen Devarsetty 
Published: June 2020

AbstractBackgroundElevated blood pressure or hypertension is responsible for around 10 million annual deaths globally, and people residing in low and middle-income countries are disproportionately affected by it. India is no exception, where low rate of treatment seeking for hypertension coupled with widespread out-of-pocket payments (OOPs) have been a challenge. This study assessed the pattern of health care seeking and financial protection along with the associated factors among hypertensive individuals in a rural district of West Bengal, India.Method and findingsA cross-sectional study was conducted in Birbhum district of the state of West Bengal, India during 2017-2018, where 300 individuals with hypertension were recruited randomly from a pre-defined list of individuals with hypertension in the district. Healthcare seeking along with two instance of financial protection –OOPs and relative expense, were analysed. Findings indicated that, of all hypertensives, 47% were not on treatment, 80% preferred private healthcare, and 91% of them had wide-spread OOPs. Cost of medication being a major share of expenses followed by significant transport cost to access public health care facility. Multivariable logistic regression analysis indicated longer duration of disease and private health care seeking were associated with more incident of OOPs. Results from linear regression modelling (generalized linear model) demonstrated association of co-morbidities with higher relative expenditure. Individuals belonging to poor economic group suffered from a high relative expense, compared to the richest.ConclusionThis study suggested that individuals with hypertension had poor health care seeking, preferred private health care and had suboptimal financial protection. Hypertensives from economically poorer section had higher burden of health expenditure for treatment of hypertension, which indicated gaps in equitable health care for the control of hypertension.
Beta regression with spatio-temporal effects as a tool for hospital impact analysis of initial phase epidemics: the case of COVID-19 in Spain
Authors: Jannes Gil , Barreal Jesús 
Published: June 2020

AbstractCOVID-19 has put an extraordinary strain on medical staff around the world, but also on hospital facilities and the global capacity of national healthcare systems. In this paper, Beta regression is introduced as a tool to analyze the rate of hospitalization and the proportion of Intensive Care Unit admissions over both hospitalized and diagnosed patients, with the aim of explaining as well as predicting, and thus allowing to better anticipate, the impact on hospital resources during an early-phase epidemic. This is applied to the initial phase COVID-19 pandemic in Spain and its different regions from 20-Feb to 08-Apr of 2020. Spatial and temporal factors are included in the Beta distribution through a precision factor. The model reveals the importance of the lagged data of hospital occupation, as well as the rate of recovered patients. Excellent agreement is found for next-day predictions, while even for multiple-day predictions (up to 12 days), robust results are obtained in most cases in spite of the limited reliability and consistency of the data.
Nf2 fine-tunes proliferation and tissue alignment during closure of the optic fissure in the embryonic mouse eye
Authors: Sun Wesley R. , Ramirez Sara , Spiller Kelly E. , Zhao Yan , Fuhrmann Sabine 
Published: June 2020

AbstractUveal coloboma represents one of the most common congenital ocular malformations accounting for up to 10% of childhood blindness (1~ in 5,000 live birth). Coloboma originates from defective fusion of the optic fissure (OF), a transient gap that forms during eye morphogenesis by asymmetric, ventral invagination. Genetic heterogeneity combined with the activity of developmentally regulated genes suggest multiple mechanisms regulating OF closure. The tumor suppressor and FERM domain protein neurofibromin 2 (NF2) controls diverse processes in cancer, development and regeneration, via Hippo pathway and cytoskeleton regulation. In humans,NF2mutations can cause ocular abnormalities, including coloboma, however, its actual role in OF closure is unknown. Using conditional inactivation in the embryonic mouse eye, our data indicates that loss ofNf2function results in a novel underlying cause for coloboma. In particular, mutant eyes show substantially increased RPE proliferation in the fissure region with concomitant acquisition of RPE cell fate. Cells lining the OF margin can maintain RPE fate ectopically and fail to transition from neuroepithelial to cuboidal shape. In the dorsal RPE of the optic cup,Nf2inactivation leads to a robust increase in cell number, with local disorganization of the cytoskeleton components F-actin and pMLC2. We propose that RPE hyperproliferation is the primary cause for the observed defects causing insufficient alignment of the OF margins inNf2mutants and failure to fuse properly, resulting in persistent coloboma. Our findings indicate that limiting proliferation particularly in the RPE layer is a critical mechanism during optic fissure closure.
Monocyte CD169 expression as a biomarker in the early diagnosis of COVID-19
Authors: Bedin Anne-Sophie , Makinson Alain , Picot Marie-Christine , Mennechet Frank , Malergue Fabrice , Pisoni Amandine , Nyiramigisha Esperance , Montagnier Lise , Bollore Karine , Debiesse Ségolène , Morquin David , Bourgoin Penelope , Veyrenche Nicolas , Renault Constance , Foulongne Vincent , Bret Caroline , Bourdin Arnaud , Le Moing Vincent , Van de Perre Philippe , Tuaillon Edouard 
Published: June 2020

AbstractWe assessed the expression of the cell adhesion molecule Sialoadhesin (CD169), a type I interferon-inducible receptor, on monocytes (mCD169) in 53 adult patients admitted to the hospital during the COVID-19 outbreak for a suspicion of SARS-CoV-2 infection. mCD169 was strongly overexpressed in 30 out of 32 (93.7%) confirmed COVID-19 cases, compared to three out of 21 (14.3%) patients for whom the diagnosis of COVID-19 was finally ruled out. mCD169 was associated with the plasma interferon alpha level and thrombocytopenia. mCD169 testing may be helpful for the rapid triage of suspected COVID-19 patients during an outbreak.