bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thromboembolism risk among patients with diabetes/stress hyperglycemia and COVID-19
Authors: Calvisi Stefania L , Ramirez Giuseppe A , Scavini Marina , Da Prat Valentina , Di Lucca Giuseppe , Laurenzi Andrea , Gallina Gabriele , Cavallo Ludovica , Borio Giorgia , Farolfi Federica , Pascali Maria , Castellani Jacopo , Lampasona Vito , D’Angelo Armando , Landoni Giovanni , Ciceri Fabio , Querini Patrizia Rovere , Tresoldi Moreno , Piemonti Lorenzo 
Published: April 2021

AbstractPurposeIndividuals with diabetes/stress hyperglycemia carry an increased risk for adverse clinical outcome in case of SARS-CoV-2 infection. The purpose of this study was to evaluate whether this risk is, at least in part, modulated by an increase of thromboembolic complications.MethodsWe prospectively followed 180 hospitalized patients with confirmed COVID-19 pneumonia admitted to the Internal Medicine Units of San Raffaele Hospital. Data from 11 out of 180 patients were considered incomplete and excluded from the analysis. We analysed inflammation, tissue damage biomarkers, hemostatic parameters, thrombotic events (TEs) and clinical outcome according to the presence of diabetes/stress hyperglycemia.ResultsAmong 169 patients, 51 (30.2%) had diabetes/stress hyperglycemia. Diabetes/stress hyperglycemia and fasting blood glucose (FBG) were associated with increased inflammation and tissue damage circulating markers, higher D-dimer levels, increased prothrombin time and lower antithrombin III activity. Forty-eight venous and 10 arterial TEs were identified in 49 (29%) patients. Diabetes/stress hyperglycemia (HR 2.71, p=0.001), fasting blood glucose (HR 4.32, p<0.001) and glucose variability (HR 1.6, p < 0.009) were all associated with an increased risk of thromboembolic complication. TEs significantly increased the risk for an adverse clinical outcome only in the presence of diabetes/stress hyperglycemia (HR 3.05, p=0.01) or fasting blood glucose ≥ 7 mmol/l (HR 3.07, p=0.015).ConclusionsThromboembolism risk is higher among patients with diabetes/stress hyperglycemia and COVID-19 pneumonia and is associated to poor clinical outcome. In case of SARS-Cov-2 infection patients with diabetes/stress hyperglycemia could be considered for a more intensive prophylactic anticoagulation regimen.
Health effects of European colonization: An investigation of skeletal remains from 19th to early 20th century migrant settlers in South Australia
Authors: Gurr Angela , Kumaratilake Jaliya , Brook Alan Henry , Ioannou Stella , Pate F. Donald , Henneberg Maciej 
Published: April 2021

AbstractNineteenth century medical understanding of human metabolism was limited, therefore, the incidence of metabolic deficiencies was not fully recorded. In addition, the transition from agricultural based mode of life to the industrial one significantly changed the pattern of these metabolic deficiencies. They were further altered by colonisation of distant continents. Palaeopathological study of skeletal remains from the early industrialised colonial era allowed light to be shed on the metabolic stresses produced by this new mode of life. Aims of this study were to investigate manifestations of disease in skeletal remains from 65 (20 adults, 45 sub-adults) migrant settlers buried in the “free ground” of St Mary’s Anglican Church Cemetery (1847 to 1927). An area allocated for burials paid for by the South Australian Government. Skeletal manifestations were determined and interpreted in terms of their multiple aetiologies. Findings were compared with those published for two 19thcentury British samples. Skeletal manifestations, commonly related to metabolic deficiencies, were observed. Areas of abnormal porosity of bone cortices were seen in 9 adults and 12 sub-adults, flaring of metaphyses was seen in one sub-adult, flaring of costochondral junctions of the ribs was seen in one sub-adult. Porous lesions of orbital roof bones (Types 3 to 5) were seen on three sub-adults. Micro-CT scans of tooth samples located interglobular dentine in three individuals. Comparison of St Mary’s findings with St Martins, Birmingham, and St Peter’s, Wolverhampton, UK, showed more individuals from St Mary’s had areas of abnormal porosity of bone cortices possibly related to vitamin C deficiency. However, St Mary’s sample displayed fewer changes attributable to vitamin D deficiency as expected in a country with greater UV irradiation. This indicates that, although the early industrialisation produced metabolic stresses, change of the environment through colonisation of new continents altered the distribution of metabolic deficiencies.
Differences in estimates for ten-year risk of cardiovascular disease in Black versus white persons with identical risk factor profiles using pooled cohort equations
Authors: Vasan Ramachandran S. , van den Heuvel Edwin 
Published: April 2021

AbstractBackgroundSex- and race-specific pooled cohort equations (PCE) are recommended for estimating the 10-year risk of cardiovascular disease (CVD), with an absolute risk >7.5% indicating a clinical decision threshold.MethodsWe generated in silico 30,565 risk profiles in men and 29,515 in women by combining numerical (age, total and high-density lipoprotein cholesterol, systolic blood pressure) and binary risk factors (smoking, diabetes, antihypertensive treatment). We compared PCE-estimated 10-year CVD risk in Black versus white individuals with identical risk profiles. We performed similar comparisons in participants in the Framingham Third Generation cohort and the National Health and Nutrition Examination Survey 2017-2018.ResultsThere were 6357 risk profiles associated with 10-year CVD risk >7.5% for Black but not for white men (median risk difference [RD] 6.25%, range 0.15-22.8%; median relative risk [RR] 2.40, range 1.02-12.6). There were 391 profiles with 10-year CVD risk >7.5% for white but not for Black men (median RD 2.68%, range 0.07-16.9%; median RR 1.42, range 1.01-3.57). There were 6543 risk profiles associated with 10-year estimated CVD risk >7.5% for Black but not for white women (median RD 6.14%, range 0.35-26.8%; median RR 2.29, range 1.05-12.6). There were 318 profiles with 10-year CVD risk >7.5% for white but not for Black women (median RD 3.71%, range 0.22-20.1%; median RR 1.66, range 1.03-5.46). The population-based samples demonstrated similar risk differences.ConclusionsThe PCE may generate substantially divergent CVD risk estimates for Black versus white individuals with identical risk profiles, which could introduce race-related variations in clinical recommendations for CVD prevention.
Awareness-dependent normalization framework of visual bottom-up attention
Authors: Wang Shiyu , Huang Ling , Chen Qinglin , Wang Jingyi , Xu Siting , Zhang Xilin 
Published: April 2021

AbstractAlthough bottom-up attention can improve visual performance with and without awareness, whether they are governed by a common neural computation remains unclear. Using a modified Posner paradigm with backward masking, we found that both the attention-triggered cueing effect with and without awareness displayed a monotonic gradient profile (Gaussian-like). The scope of this profile, however, was significantly wider with than without awareness. Subsequently, for each subject, the stimulus size was manipulated as their respective mean scopes with and without awareness while stimulus contrast was varied in a spatial cueing task. By measuring the gain pattern of contrast-response functions, we observed changes in the cueing effect consonant with changes in contrast gain for bottom-up attention with awareness and response gain for bottom-up attention without awareness. Our findings indicate an awareness-dependent normalization framework of visual bottom-up attention, placing a necessary constraint, namely, awareness, on our understanding of the neural computations underlying visual attention.
Identification of clinical features associated with mortality in COVID-19 patients
Authors: Eskandarian Rahimeh , Sani Zahra Alizadeh , Behjati Mohaddeseh , Zahmatkesh Mehrdad , Haddadi Azadeh , Kakhi Kourosh , Roshanzamir Mohamad , Shoeibi Afshin , Alizadehsani Roohallah , Hussain Sadiq , Khozeimeh Fahime , Keyvani Vahideh , Khosravi Abbas , Nahavandi Saeid , Shariful Islam Sheikh Mohammed 
Published: April 2021

SummaryBackgroundTo prevent infectious diseases, it is necessary to understand how they are spread and their clinical features. Early identification of risk factors and clinical features is needed to identify critically ill patients, provide suitable treatments, and prevent mortality.MethodsWe conducted a prospective study on COVID-19 patients referred to a tertiary hospital in Iran between March and November 2020. Of the 3008 patients (mean age 59.3±18.7 years, range 1 to 100 years), 1324 were women. We investigated COVID-19 related mortality and its association with clinical features including headache, chest pain, symptoms on CT, hospitalization, time to infection, history of neurological disorders, having a single or multiple risk factors, fever, myalgia, dizziness, seizure, abdominal pain, nausea, vomiting, diarrhoea and anorexia.FindingsThere was a significant association between COVID-19 mortality and old age, headache, chest pain, respiratory distress, low respiratory rate, oxygen saturation less than 93%, need for a mechanical ventilator, having symptoms on CT, hospitalization, time to infection, history of hypertension, neurological disorders, cardiovascular diseases and having a risk factor or multiple risk factors. In contrast, there was no significant association between mortality and gender, fever, myalgia, dizziness, seizure, abdominal pain, nausea, vomiting, diarrhoea and anorexia.InterpretationOur results might help identify early symptoms related to COVID-19 and better manage patients clinically.
Post-COVID-19 syndrome in outpatients: a cohort study
Authors: Desgranges Florian , Tadini Eliana , Munting Aline , Regina Jean , Filippidis Paraskevas , Viala Benjamin , Karachalias Eleftherios , Suttels Véronique , Haefliger David , Kampouri Eleftheria , Van Singer Mathias , Tschopp Jonathan , Stettler Laurence Rochat , Schaad Siméon , Brahier Thomas , Hugli Olivier , Chabloz Yolanda Mueller , Gouveia Alexandre , Opota Onya , Carron Pierre-Nicolas , Guery Benoît , Papadimitriou-Olivgeris Matthaios , Boillat-Blanco Noémie ,   the RegCOVID research group
Published: April 2021

ABSTRACTBackgroundAfter mild COVID-19, some outpatients experience persistent symptoms. However, data are scarce and prospective studies are urgently needed.ObjectivesTo characterize the post-COVID-19 syndrome after mild COVID-19 and identify predictors.ParticipantsOutpatients with symptoms suggestive of COVID-19 with (1) PCR-confirmed COVID-19 (COVID-positive) or (2) SARS-CoV-2 negative PCR (COVID-negative).DesignMonocentric cohort study with prospective phone interview between more than three months to ten months after initial visit to the emergency department and outpatient clinics.Main MeasuresData of the initial visits were extracted from the electronic medical file. Predefined persistent symptoms were assessed through a structured phone interview. Associations between long-term symptoms and PCR results, as well as predictors of persistent symptoms among COVID-positive, were evaluated by multivariate logistic regression adjusted for age, gender, smoking, comorbidities, and timing of the survey.Key resultsThe study population consisted of 418 COVID-positive and 89 COVID-negative patients, mostly young adults (median age of 41 versus 36 years in COVID-positive and COVID-negative, respectively; p=0.020) and health care workers (67% versus 82%; p=0.006). Median time between the initial visit and the phone survey was 150 days in COVID-positive and 242 days in COVID-negative patients. Persistent symptoms were reported by 223 (53%) COVID-positive and 33 (37%) COVID-negative patients (p=0.006). Overall, 21% COVID-positive and 15% COVID-negative patients (p=0.182) attended care for this purpose. Four surveyed symptoms were independently associated with COVID-19: fatigue (adjusted odds ratio [or] 2.14, 95%CI 1.04-4.41), smell/taste disorder (26.5, 3.46-202), dyspnea (2.81, 1.10-7.16) and memory impairment (5.71, 1.53-21.3). Among COVID-positive, female gender (1.67, 1.09-2.56) and overweight/obesity (1.67, 1.10-2.56) were predictors of persistent symptoms.ConclusionsMore than half of COVID-positive outpatients report persistent symptoms up to ten months after a mild disease. Only 4 of 14 symptoms were associated with COVID-19 status. The symptoms and predictors of the post-COVID-19 syndrome need further characterization as this condition places a significant burden on society.
CSF infusion of TrkB agonist, 7,8-dihydroxyflavone, is ineffective in promoting remyelination in cuprizone and EAE models of multiple sclerosis
Authors: Fletcher Jessica L , Wood Rhiannon J , Prawdiuk Alexa R , O’Rafferty Ryan , Ehrlich Ophelia , Gonsalvez David G , Murray Simon S 
Published: April 2021

AbstractSmall molecular weight functional mimetics of brain-derived neurotrophic factor (BDNF) which act via the TrkB receptor have been developed to overcome the pharmacokinetic limitations of BDNF as a therapeutic for neurological disease. Activation of TrkB on oligodendrocytes has been identified as a potential strategy for myelin repair in demyelinating conditions. Here, we tested the efficacy of intracerebroventricular infusion of TrkB agonist 7,8-dihydroxyflavone (DHF) to promote myelin repair in the cuprizone model and alter the course of experimental autoimmune encephalomyelitis (EAE). In these two distinct mouse models used for the preclinical testing of remyelinating therapeutics, we found that DHF infusion increased the percentage of myelin basic protein and density of oligodendrocyte progenitor cells (OPCs) in the corpus callosum of female C57BL/6 mice after cuprizone demyelination. However, DHF did not alter the percentage of axons myelinated or increase the density of post-mitotic oligodendrocytes in this model. Direct cerebrospinal fluid infusion of DHF also had no effect on the clinical course of EAE, and examination of the lumbar spinal cord after 21 days of treatment revealed extensive demyelination. These results indicate that direct cerebrospinal fluid infusion of DHF is ineffective at promoting myelin repair in toxin-induced and inflammatory models of demyelination.
Spatially resolved analysis ofPseudomonas aeruginosabiofilm proteomes measured by laser ablation sample transfer
Authors: Pulukkody Aruni Chathurya , Yung Yeni P. , Donnarumma Fabrizio , Murray Kermit K. , Carlson Ross P. , Hanley Luke 
Published: April 2021

AbstractHeterogeneity in the distribution of nutrients and O2gradients during biofilm growth gives rise to changes in phenotype. There has been long term interest in identifying spatial differences during biofilm development including clues that identify chemical heterogeneity. Laser ablation sample transfer (LAST) allows site-specific sampling combined with label free proteomics to distinguish radially and axially resolved proteomes forPseudomonas aeruginosabiofilms. Specifically, differential protein abundances on oxic vs. anoxic regions of a biofilm was observed by combining LAST with bottom up proteomics. This study reveals active metabolism in the anoxic region of the biofilm with respect to the oxic region inP. aeruginosa, an aerobe by nature. Protein abundance data related to cellular acclimations to chemical gradients include identification of glucose catabolizing proteins, high abundance of proteins from arginine and polyamine metabolism, and proteins that could also support virulence and environmental stress mediation on the anoxic region. Finally, this methodology requires only a few mm2of biofilm area to identify hundreds of proteins.
Vocal correlates of arousal in bottlenose dolphins (Tursiopsspp.) in human care
Authors: Probert Rachel , Bastian Anna , Elwen Simon H. , James Bridget S. , Gridley Tess 
Published: April 2021

AbstractHuman-controlled regimes can entrain behavioural responses and may impact animal welfare. Therefore, understanding the impact of schedules on animal behaviour can be a valuable tool to improve welfare, however information on overnight behaviour and behaviour in the absence of husbandry staff remains rare. Bottlenose dolphins (Tursiopsspp.) are highly social marine mammals and the most common cetacean found in captivity. They communicate using frequency modulated signature whistles which are individually distinctive and used as a contact call. We investigated the vocal behaviour of ten dolphins housed in three social groups at uShaka Sea World dolphinarium to determine how acoustic behavioural patterns link to dolphinarium routines. Investigation focused on overnight behaviour, housing decisions, weekly patterns, and transitional periods between presence and absence of husbandry staff. Recordings were made from 17h00 – 07h00 over 24 nights, spanning May to August 2018. Whistle production rate decreased soon after husbandry staff left the facility, was low over night, and increased upon arrival. Results indicated elevate arousal states associated with the morning arrival and presence of husbandry staff and heightened excitement associated with feeding. Housing in pool configurations which limited visual contact between certain groups were characterised by lower vocal production rates. Production of signature whistles was greater over the weekends compared to weekdays however total whistle production did not differ between weekends and weekdays. Heightened arousal associated with staff arrival was reflected in the structural characteristics of signature whistles, particularly maximum frequency, frequency range and number of whistle loops. Overall, these results revealed a link between scheduled activity and associated behavioural responses, which can be used as a baseline for future welfare monitoring where changes in normal behaviour may reflect shifts in welfare state.
Multiparametric Platform for Profiling Lipid Trafficking in Human Leukocytes: Application for Hypercholesterolemia
Authors: Pfisterer Simon G. , Brock Ivonne , Kanerva Kristiina , Hlushchenko Iryna , Paavolainen Lassi , Ripatti Pietari , Islam Mohammad M. , Kyttälä Aija , Di Taranto Maria D. , di Frega Annalisa Scotto , Fortunato Giuliana , Kuusisto Johanna , Horvath Peter , Ripatti Samuli , Laakso Markku , Ikonen Elina 
Published: April 2021

SummarySystematic insight into cellular dysfunctions can improve understanding of disease etiology, risk assessment and patient stratification. We present a multiparametric high-content imaging platform enabling quantification of low-density lipoprotein (LDL) uptake and lipid storage in cytoplasmic droplets of primary leukocyte subpopulations. We validated this platform with samples from 65 individuals with variable blood LDL-cholesterol (LDL-c) levels, including familial hypercholesterolemia (FH) and non-FH subjects. We integrated lipid storage data into a novel readout, lipid mobilization, measuring the efficiency with which cells deplete lipid reservoirs. Lipid mobilization correlated positively with LDL uptake and negatively with hypercholesterolemia and age, improving differentiation of individuals with normal and elevated LDL-c. Moreover, combination of cell-based readouts with a polygenic risk score for LDL-c explained hypercholesterolemia better than the genetic risk score alone. This platform provides functional insights into cellular lipid trafficking from a few ml’s of blood and is applicable to dissect metabolic disorders, such as hypercholesterolemia.MotivationWe have limited information on how cellular lipid uptake and processing differ between individuals and influence the development of metabolic diseases, such as hypercholesterolemia. Available assays are labor intensive, require skilled personnel and are difficult to scale to higher throughput, making it challenging to obtain systematic functional cell-based data from individuals. To overcome this problem, we established a scalable automated analysis pipeline enabling reliable quantification of multiple cellular readouts, including lipid uptake, storage and mobilization, from different white blood cell populations. This approach provides new personalized insights into the cellular basis of hypercholesterolemia and obesity.Graphical Abstract
Multivariate analysis reveals shared genetic architecture of brain morphology and human behavior
Authors: de Vlaming R. , Slob Eric A.W. , Jansen Philip R. , Dagher Alain , Koellinger Philipp D. , Groenen Patrick J.F. , Rietveld Cornelius A. 
Published: April 2021

AbstractHuman variation in brain morphology and behavior are related and highly heritable. Yet, it is largely unknown to what extent specific features of brain morphology and behavior are genetically related. Here, we introduce multivariate genomic-relatedness restricted maximum likelihood (MGREML) and provide estimates of the heritability of grey-matter volume in 74 regions of interest (ROIs) in the brain. We map genetic correlations between these ROIs and health-relevant behavioral outcomes including intelligence. We find four genetically distinct clusters in the brain that are aligned with standard anatomical subdivision in neuroscience. Behavioral traits have distinct genetic correlations with brain morphology which suggests trait-specific relevance of ROIs.
Ultrapotent SARS-CoV-2 neutralizing antibodies with protective efficacy against newly emerged mutational variants
Authors: Li Tingting , Han Xiaojian , Gu Chenjian , Guo Hangtian , Zhang Huajun , Wang Yingming , Hu Chao , Wang Kai , Liu Fengjiang , Luo Feiyang , Zhang Yanan , Hu Jie , Wang Wang , Li Shenglong , Hao Yanan , Shen Meiying , Huang Jingjing , Long Yingyi , Song Shuyi , Wu Ruixin , Mu Song , Chen Qian , Gao Fengxia , Wang Jianwei , Long Shunhua , Li Luo , Wu Yang , Gao Yan , Xu Wei , Cai Xia , Qu Di , Zhang Zherui , Zhang Hongqing , Li Na , Gao Qingzhu , Zhang Guiji , He Changlong , Wang Wei , Ji Xiaoyun , Tang Ni , Yuan Zhenghong , Xie Youhua , Yang Haitao , Zhang Bo , Huang Ailong , Jin Aishun 
Published: April 2021

AbstractAccumulating mutations in the SARS-CoV-2 Spike (S) protein can increase the possibility of immune escape, challenging the present COVID-19 prophylaxis and clinical interventions. Here, 3 receptor binding domain (RBD) specific monoclonal antibodies (mAbs), 58G6, 510A5 and 13G9, with high neutralizing potency blocking authentic SARS-CoV-2 virus displayed remarkable efficacy against authentic B.1.351 virus. Each of these 3 mAbs in combination with one neutralizing Ab recognizing non-competing epitope exhibited synergistic effect against authentic SARS-CoV-2 virus. Surprisingly, structural analysis revealed that 58G6 and 13G9, encoded by the IGHV1-58 and the IGKV3-20 germline genes, both recognized the steric region S470-495 on the RBD, overlapping the E484K mutation presented in B.1.351. Also, 58G6 directly bound to another region S450-458 in the RBD. Significantly, 58G6 and 510A5 both demonstrated prophylactic efficacy against authentic SARS-CoV-2 and B.1.351 viruses in the transgenic mice expressing human ACE2 (hACE2), protecting weight loss and reducing virus loads. These 2 ultrapotent neutralizing Abs can be promising candidates to fulfill the urgent needs for the prolonged COVID-19 pandemic.