bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dosing Of Thromboprophylaxis And Mortality In Critically Ill Covid-19 Patients
Authors: Jonmarker Sandra , Hollenberg Jacob , Dahlberg Martin , Stackelberg Otto , Litorell Jacob , Everhov Åsa H , Järnbert-Pettersson Hans , Söderberg Mårten , Grip Jonathan , Schandl Anna , Günther Mattias , Cronhjort Maria 
Published: September 2020

ABSTRACTBackgroundA substantial proportion of critically ill COVID-19 patients develop thromboembolic complications, but it is unclear whether higher doses of thromboprophylaxis are associated with lower mortality rates. The purpose of the study was to evaluate the association of initial dosing strategy of thromboprophylaxis in critically ill COVID-19 patients and the risk of death, thromboembolism, and bleeding.MethodAll critically ill COVID-19 patients admitted to two intensive care units in March and April 2020 were eligible. Patients were categorized into three groups according to initial daily dose of thromboprophylaxis; low (2500-4500 IU tinzaparin or 2500-5000 IU dalteparin), medium (>4500 IU but <175 IU/kilogram, kg, of body weight tinzaparin or >5000 IU but <200 IU/kg of body weight dalteparin), and high dose (≥ 175 IU/kg of body weight tinzaparin or ≥200 IU/kg of body weight dalteparin). Thromboprophylaxis dosage was based on local standardized recommendations, not on degree of critical illness or risk of thrombosis. Cox proportional hazards regression was used to estimate hazard ratios with corresponding 95% confidence intervals of death within 28 days from ICU admission. Multivariable models were adjusted for sex, age, body-mass index, Simplified Acute Physiology Score III, invasive respiratory support, and initial dosing strategy of thromboprophylaxis.ResultsA total of 152 patients were included; 67 received low, 48 medium, and 37 high dose thromboprophylaxis. Baseline characteristics did not differ between groups. Mortality was lower in high (13.5%) vs medium (25.0%) and low dose thromboprophylaxis (38.8%) groups, p=0.02. The hazard ratio of death was 0.33 (95% confidence intervals 0.13 – 0.87) among those who received high dose, respectively 0.88 (95% confidence intervals 0.43 – 1.83) among those who received medium dose, as compared with those who received low dose thromboprophylaxis. There were fewer thromboembolic events in the high (2.7%) vs medium (18.8%) and low dose thromboprophylaxis (17.9%) groups, p=0.04, but no difference in the proportion of bleeding events, p=0.16.ConclusionsAmong critically ill COVID-19 patients with respiratory failure, high dose thromboprophylaxis was associated with a lower risk of death and a lower cumulative incidence of thromboembolic events compared with lower doses.Trial registrationClinicaltrials.govNCT04412304 June 2 2020, retrospectively registered
Heterogeneous distribution of tau pathology in the behavioral variant of Alzheimer’s disease
Authors: Singleton Ellen H. , Hansson Oskar , Pijnenburg Yolande A. M. , Joie Renaud La , Mantyh William G. , Tideman Pontus , Stomrud Erik , Leuzy Antoine , Johansson Maurits , Strandberg Olof , Smith Ruben , Berendrecht Evi , Miller Bruce , Iaccarino Leonardo , Edwards Lauren , Storm Amelia , Wolters Emma , Coomans Emma M. , Visser Denise , Golla Sandeep S.V. , Tuncel Hayel , Bouwman Femke , Swieten John van , Papma Janne M. , Berckel Bart van , Scheltens Philip , Dijkstra Anke A. , Rabinovici Gil , Ossenkoppele Rik 
Published: September 2020

ABSTRACTObjectiveThe clinical phenotype of the rare behavioral variant of Alzheimer’s disease (bvAD) is insufficiently understood. Given the strong clinico-anatomical correlations of tau pathology in AD, we investigated the distribution of tau deposits in bvAD,in-vivoandex-vivo, using PET and postmortem examination.MethodsFor the tau PET study, seven amyloid-P positive bvAD patients underwent [18F]flortaucipir or [18F]RO948 PET. We converted tau PET uptake values into standardized (W-)scores, by adjusting for age, sex and MMSE in a “typical” memory-predominant AD (n=205) group. W-scores were computed within entorhinal, temporoparietal, medial and lateral prefrontal, insular and whole-brain regions-of-interest, frontal-to-entorhinal and frontal-to-parietal ratios and within intrinsic functional connectivity network templates. For the postmortem study, the percentage of AT8 (tau)-positive area in hippocampus CA1, temporal, parietal, frontal and insular cortices were compared between autopsy-confirmed bvAD (n=8) and typical AD (n=7) patients.ResultsRegional W-scores ≥1.96 (corresponding to p<0.05) were observed in three cases, i.e. case #5: medial prefrontal cortex (W=2.13) and anterior default mode network (W=3.79), case #2: lateral prefrontal cortex (W=2.79) and salience network (W=2.77), and case #7: frontal-to-entorhinal ratio (W=2.04). The remaining four cases fell within the normal distributions of the typical AD group. Postmortem AT8 staining indicated no regional differences in phosphorylated tau levels between bvAD and typical AD (all p>0.05).ConclusionBothin-vivoandex-vivo, bvAD patients showed heterogeneous patterns of tau pathology. Since key regions involved in behavioral regulation were not consistently disproportionally affected by tau pathology, other factors are more likely driving the clinical phenotype in bvAD.
Large-Scale Hypothesis Testing for Causal Mediation Effects with Applications in Genome-wide Epigenetic Studies
Authors: Liu Zhonghua , Shen Jincheng , Barfield Richard , Schwartz Joel , Baccarelli Andrea A. , Lin Xihong 
Published: September 2020

AbstractIn genome-wide epigenetic studies, it is of great scientific interest to assess whether the effect of an exposure on a clinical outcome is mediated through DNA methylations. However, statistical inference for causal mediation effects is challenged by the fact that one needs to test a large number of composite null hypotheses across the whole epigenome. Two popular tests, the Wald-type Sobel’s test and the joint significant test using the traditional null distribution are underpowered and thus can miss important scientific discoveries. In this paper, we show that the null distribution of Sobel’s test is not the standard normal distribution and the null distribution of the joint significant test is not uniform under the composite null of no mediation effect, especially in finite samples and under the singular point null case that the exposure has no effect on the mediator and the mediator has no effect on the outcome. Our results explain why these two tests are underpowered, and more importantly motivate us to develop a more powerful Divide-Aggregate Composite-null Test (DACT) for the composite null hypothesis of no mediation effect by leveraging epigenome-wide data. We adopted Efron’s empirical null framework for assessing statistical significance of the DACT test. We showed analytically that the proposed DACT method had improved power, and could well control type I error rate. Our extensive simulation studies showed that, in finite samples, the DACT method properly controlled the type I error rate and outperformed Sobel’s test and the joint significance test for detecting mediation effects. We applied the DACT method to the US Department of Veterans Affairs Normative Aging Study, an ongoing prospective cohort study which included men who were aged 21 to 80 years at entry. We identified multiple DNA methylation CpG sites that might mediate the effect of smoking on lung function with effect sizes ranging from −0.18 to − 0.79 and false discovery rate controlled at level 0.05, including the CpG sites in the genes AHRR and F2RL3. Our sensitivity analysis found small residual correlations (less than 0.01) of the error terms between the outcome and mediator regressions, suggesting that our results are robust to unmeasured confounding factors.
Relationship of TSH levels with cardiometabolic risk factors in US youth aged 12-18 years and population-based reference percentiles for thyroid function tests
Authors: Chen Xinlei , Deng Shuliang , Sena Cecilia , Zhou Chuhan , Thaker Vidhu V. 
Published: September 2020

AbstractContextThyroid hormones play an important role in the metabolic homeostasis of the body and have been associated with cardiometabolic risk.ObjectiveTo examine the association of cardiometabolic risk factors (CMRF) with TSH levels in youth at population level in the US.Design & SettingCross-sectional study of youth aged 12-18 years without known thyroid abnormalities from National Health and Nutrition Examination Survey 1999-2012. Subclinical hypothyroidism (SH) was defined as TSH levels 4.5-10 mIU/L. Assessed CMRF included abdominal obesity (waist circumference > 90thpercentile), hypertriglyceridemia (TG ≥ 130 mg/dL), low HDL cholesterol (HDL-C < 40 mg/dL), elevated blood pressure (SBP and DBP ≥ 90thpercentile), hyperglycemia (FBG ≥ 100 mg/dL, or known diabetes), insulin resistance (HOMA-IR > 3.16) and elevated alanine transferase (ALT ≥50 U/L for boys and ≥44 U/L for girls). Age and sex-specific percentiles for thyroid parameters were calculated for youth with normal weight.ResultsIn this cohort of youth (51.3% male), 31.2% had overweight/obesity. The prevalence of SH was 2.0 % (95% CI 1.2-3.1). The median TSH levels were higher in youth with overweight/obesity (p<.001). Adjusting for age, sex, race/ethnicity and level of obesity, youth with TSH in the 4thquantile had higher odds of abdominal obesity (OR 2.53 [1.43-4.46], p = .002), higher HOMA-IR (OR 2.82 [1.42-5.57], p=.003) and ≥ 2 CMRF (OR 2.20 [1.23-3.95], p=.009).ConclusionsThe prevalence of SH is low in US youth. The higher odds of insulin resistance and CMRF in youth with TSH levels > 75thpercentile requires further study.
Surgery versus external beam radiotherapy for hepatocellular carcinoma involving the inferior vena cava or right atrium: A systematic review and meta-analysis
Authors: Lee Han-Ah , Park Sunmin , Seo Yeon Seok , Yoon Won Sup , Shin In-Soo , Rim Chai Hong 
Published: September 2020

AbstractPurposeAs the treatment efficacy of systemic therapy for patients with advanced-stage HCC is insufficient, locoregional therapies are performed in the clinical practice. We investigated the efficacy and safety of two most potent therapies, surgery and external beam radiotherapy (EBRT), in patients with HCC involving the IVC and/or right atrium (RA) through comparative meta-analysis.MethodA systematic search of Pubmed, MEDLINE, EMBASE, and the Cochrane library was performed for entries up to July 2020. The primary endpoints were 1- and 2-year overall survival (OS) rates, while secondary endpoints were response rate, local control rate, and grade ≥3 toxicities.ResultsEighteen studies with 22 cohorts were included, encompassing 755 patients. The pooled median OS and 1-and 2-year OS rates were 14.2 months, 55.6%, and 27.4%, respectively. The pooled median OS in the surgery and EBRT arms were 15.3 and 11.7 months, respectively. The pooled 1-year OS rate of the surgery arm was significantly higher than that of the EBRT arm (62.4%, 95% CI: 53.8–70.3 vs. 48.8%, 95% CI: 40.9–56.8; p=0.023). However, the 2-year OS rates were comparable (26.9%, 95% CI: 20.7–34.2 vs. 27.5%, 95% CI: 19.7–37.1; p=0.913). The pooled response and local control rates in the EBRT arm were 74.3% and 87.2%, respectively. In the surgical arm, the perioperative mortality and grade ≥3 complication rates were 0–7.6% and 3.9–67%, respectively. Grade ≥3 complications and radiation-induced liver disease were rarely observed in the EBRT arm.ConclusionsBoth surgery and EBRT are effective treatment options for patients with HCC involving IVC/RA invasion. Outcomes and safety should be further evaluated in well-controlled clinical trials.
Potentials of constrained sliding mode control as an intervention guide to manage COVID19 spread
Authors: Nuñez Sebastián , Inthamoussou Fernando A. , Valenciaga Fernando , De Battista Hernán , Garelli Fabricio 
Published: September 2020

AbstractThis work evaluates the potential of using sliding mode reference conditioning (SMRC) techniques as a guide for non-pharmaceutical interventions and population confinement to control the COVID-19 pandemic. SMRC technique allows robustly delimiting a given variable in dynamical systems. In particular, for the epidemio-logical problem addressed here, it can be used to compute day by day the contact rate reduction requirement in order to limit the intense care units occupancy to a given threshold. What is more, it could impose a given approaching rate to the health care system limits. Simulations are performed using the well-known SEIR model fitted to the Argentinian case to demonstrate what this control strategy sug-gests, while the effect of realistic period transitions between different confinement levels are also considered.
Post-operative day 3 Procalcitonin predicts post-operative infectious complications in pancreatic surgery – A systemic review and updated meta-analysis
Authors: Vasavada Bhavin , Patel Hardik 
Published: September 2020

AbstractAim of studyAim of this meta-analysis is to evaluate post-operative procalcitonin as a marker to predict post-operative infectious complications after pancreatic surgeries.Material and MethodsSystemic literature search was performed using MEDLINE, EMBASE and to identify studies evaluating the diagnostic accuracy of Procalcitonin (PCT) as a predictor for detecting infectious complications on postoperative days (POD) 3 and 5 following pancreatic surgery. A meta-analysis was performed using random effect model and pooled predictive parameters for POD 3 and 5 were derived. Geometric means were calculated for PCT cut offs.Results6 studies included day 3 PCT analysis, 2 studies included both day 3 and day 5 analysis. Total data of 471 patients were derived. 161 patients developed infectious complications. Pooled sensitivity, specificity, pooled area under curve, diagnostic odds ratio (DOR), positive and negative like hood ratio of day 3 PCT were 74%,79%,0.8453, 11.03,3.17 and 0.31 respectively. Pooled sensitivity, specificity, diagnostic odds ratio (DOR), positive and negative like hood ratio of day 5 PCT were 83%,70%,12.91,2.91 and 0.25 respectively. Geometric means for PCT cut off for day 3 and 5 were 0.80 and 0.43.ConclusionPostoperative procalcitonin particularly day 3 procalcitonin levels predict post-operative infectious complications following pancreatic surgeries.
Features of patients that died for COVID-19 in a Hospital in the south of Mexico: A observational cohort study
Authors: Ruíz-Quiñonez Jesús Arturo , Guzmán-Priego Crystell Guadalupe , Nolasco-Rosales German Alberto , Tovilla-Zarate Carlos Alfonso , Flores-Barrientos Oscar Israel , Narváez-Osorio Víctor , del Carmen Baeza-Flores Guadalupe , Gonzalez-Castro Thelma Beatriz , Ramón López-Brito Carlos , Denis-García Carlos Alberto , Pérez-García Agustín , Juárez-Rojop Isela Esther 
Published: September 2020

AbstractBackgroundDue to the wide spread of SARS-CoV2 around the world, the risk of death in individuals with metabolic comorbidities has dangerously increased. Mexico has a high number of infected individuals and deaths by COVID-19, as well as an important burden of metabolic diseases. However, reports about features of Mexican individuals with COVID-19 are scarce. The aim of this study was to evaluate demographic features, clinical characteristics, and the pharmacological treatment of individuals who died by COVID-19 in the south of Mexico.MethodsWe performed an observational study including 185 deceased individuals with confirmed diagnosis of COVID-19. Data were retrieved from medical records. Categorical data was expressed as proportions (%) and numerical data were expressed as mean ± standard deviation. Comorbidities and overlapping symptoms where plotted as Venn diagrams. Drug clusters were plotted as dendrograms.ResultsThe mean age was 59.53 years. There was a male predominance (60.1%). The mean hospital stay was 4.75 ± 4.43 days. The most frequent symptoms were dyspnea (88.77%), fever (71.42%) and dry cough (64.28%). Present comorbidities were diabetes (60.63%), hypertension (59.57%) and obesity (43.61%). The main drugs used were azithromycin (60.6%), hydroxychloroquine (53.0%) and oseltamivir (27.3%).ConclusionsMexican individuals who died of COVID-19 had shorter hospital stays, higher frequency of shortness of breath, and higher prevalence of diabetes compared with individuals from other countries. Also, there was a high frequency of off-label use of drugs for their treatment.
Seroprevalence of immunoglobulin M and G antibodies against SARS-CoV-2 in ophthalmic patients
Authors: Li Shengjie , Qiu Yichao , Tang Li , Wang Zhujian , Cao Wenjun , Xu Gezhi , Sun Xinghuai 
Published: September 2020

AbstractUsing serological test to estimate the prevalence and infection potential of coronavirus disease 2019 in ocular diseases patients help understand the relationship between ocular diseases and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We conducted a cross-sectional study assaying the IgG and IgM antibodies in 1331 individuals with ocular diseases by using a magnetic chemiluminescence enzyme immunoassay kit, during the period from February 2020 to May 2020. In our study, the seroposivity in total ocular disease patients was 0.83% (11/1331). The patients with different ocular diseases including xerophthalmia, keratitis, conjunctival cyst, cataract, glaucoma, refractive error, strabismus and others had seroposivity of 2.94%, 12.5%, 25%, 4.41%, 2.63%, 1.6%, 2.22% and 0%, respectively. Among that, two ocular surface disease groups (keratitis and conjunctival cyst) had higher seroprevalence compared with others. All the participants were reverse transcription polymerase chain reaction negative for SARS-CoV-2 from throat swabs. Our study evaluated the seroprevalence in patients with different ocular diseases, which will help us understand the relationship between ocular disease and SARS-CoV-2 infection. Furthermore, the serological test for the presence of IgM and/or IgG antibodies against SARS-CoV-2 might provide accurate estimate of the prevalence of SARS-CoV-2 infection in patients with ocular diseases.
Discrete escape responses are generated by neuropeptide-mediated circuit logic
Authors: Imambocus Bibi Nusreen , Wittich Annika , Tenedini Federico , Zhou Fangmin , Hu Chun , Sauter Kathrin , Varela Ednilson Macarenhas , Herédia Fabiana , Casimiro Andreia P. , Macedo André , Schlegel Philipp , Yang Chung-Hui , Miguel-Aliaga Irene , Pankratz Michael J. , Gontijo Alisson M. , Cardona Albert , Soba Peter 
Published: September 2020

AbstractAnimals display a plethora of escape behaviors when faced with environmental threats. Selection of the appropriate response by the underlying neuronal network is key to maximize chances of survival. We uncovered a somatosensory network inDrosophilalarvae that encodes two escape behaviors through input-specific neuropeptide action. Sensory neurons required for avoidance of noxious light and escape in response to harsh touch, each converge on discrete domains of the same neuromodulatory hub neurons. These gate harsh touch responses via short Neuropeptide F, but noxious light avoidance via compartmentalized, acute Insulin-like peptide 7 action and cognate Relaxin-family receptor signaling in connected downstream neurons. Peptidergic hub neurons can thus act as central circuit elements for first order processing of converging sensory inputs to gate specific escape responses.One Sentence SummaryCompartment-specific neuropeptide action regulates sensory information processing to elicit discrete escape behavior inDrosophilalarvae.
A population-based seroprevalence survey of severe acute respiratory syndrome coronavirus 2 infection in Beijing, China
Authors: Wang Xiaoli , Gao Wenjing , Cui Shujuan , Zhang Yi , Zheng Ke , Ke Ji , Lv Jun , Yu Canqing , Sun Dianjianyi , Wang Quanyi , Li Liming 
Published: September 2020

ABSTRACTBACKGOUNDThe spread of Coronavirus Disease 2019 (COVID-19) had been controlled in China. The seroprevalence of COVID-19 in Beijing has not been evaluated.METHODSIn April, residents in Beijing were randomly enrolled. Blood samples were collected and antibodies to SARS- CoV-2 were tested by two colloidal gold kits. All colloidal gold positive serums were then tested by Micro- neutralization assay.RESULTSNone of 2,184 residents participated was tested positive by micro-neutralization assay. The seroprevalence of COVID-19 in Beijing was estimated < 0.17%.CONCLUSIONSThe seroprevalence of COVID-19 was low in April suggesting that community-wide spread was prevented in Beijing.
AUDIT Scotland 10 years on: explaining how funding decisions link to increased risk for drug related deaths among the poor
Authors: McPhee Iain , Sheridan Barry 
Published: September 2020

Purpose
In response to Scottish Government assertions that an ageing cohort explained increases in drug-related death (DRD), the previous research by the authors established that socio-economic inequalities were additional risk factors explaining the significant increases in DRD in Scotland. This paper aims to subject the drug policy narratives provided by Scottish Government in relation to the governance of drug and alcohol services to critical scrutiny and reveal the social consequences of the funding formula used to direct funding to services via NHS Scotland Boards, and Alcohol and Drug Partnerships (ADP).

Design/methodology/approach
The paper provides a narrative review in the context of the AUDIT Scotland reports “Drug and Alcohol Services in Scotland” from 2009 and follow-up report published in 2019. The authors refer to the recommendations made in the 2009 report on effectiveness of drug and alcohol services and subject Scottish Government funding processes, and governance of drug and alcohol services to critical scrutiny.

Findings
This analysis provides robust evidence that Scottish Government funding processes and governance of drug and alcohol services increased risk to vulnerable drug users and document evidence that link these risk factors to increased DRD.

Research limitations/implications
The authors have focused on Scottish drug policy and drug services funding. Alcohol services funding is not subject to critical analysis due to limitations of time and resources.

Practical implications
This case study investigates AUDIT Scotland’s recommendations in 2009 to Scottish Government to provide researchers, government policy advisors and media with robust critical analysis that links drug policy decisions to increased DRD.

Social implications
Drug policy governance by the Scottish Government and NHS Scotland since 2009 have disproportionately affected communities of interest and communities of place already experiencing stark inequalities. These budget decisions have resulted in widening inequalities, and increased DRD within communities in Scotland. The authors conclude that in diverging politically and ideologically from Public Health England, and the Westminster Parliament, Scottish Government drug policy and financial governance of drugs services contributes to increased risk factors explaining DRD within deprived communities.

Originality/value
The 2009 AUDIT Scotland recommendations to Scottish Government subject their governance of drug services to critical scrutiny. This analysis provides a counterpoint to the explanations that rising DRD are unconnected to drug policy and drug services governance.