bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transmembrane protein DCBLD2 is correlated with poor prognosis and affects phenotype by regulating epithelial-mesenchymal transition in human glioblastoma cells
Authors: Cheng Shuai , Wang Liang-Yan , Wang Chuan-Hui , Wang Fa-Kai , Zhu Bing , Zhang Peng , Wang Guo-Hua 
Published: March 2021

Objective
We attempt to investigate the biological function of the discoidin, complement C1r/C1s,Uegf, and Bmp1 and Limulus factor C, Coch, and Lgl domain-containing 2 (DCBLD2) in glioblastoma, as well as its effect on the epithelial-mesenchymal transition (EMT) process.

Methods
The public expression data of glioblastoma samples and normal brain samples from The Cancer Genome Atlas database, Genotype-Tissue Expression database and Chinese Glioma Genome Atlas database were used to analyze the expression of DCBLD2 and its relationship with the survival of patients with glioblastoma. Quantitative real-time PCR and western blot were used to evaluate mRNA and protein levels of DCBLD2. Cell viabilities were tested using Cell Counting Kit-8 and clone formation assays. Cell invasive and migratory abilities were measured by transwell assays.

Results
DCBLD2 expression was upregulated in glioblastoma and has a significantly positive correlation with the WHO classification. In addition, high expression of DCBLD2 was closely correlated with poor prognosis in primary and recurrent patients with glioblastoma. What is more, we found that knockdown of DCBLD2 notably reduced the cell proliferative, invasive and migratory capacities by elevating the expression of E-cadherin and inhibiting the expression of vimentin, snail, slug and twist. However, overexpression of DCBLD2 presented the opposite results.

Conclusion
The current study reveals that high expression of DCBLD2 is closely related to poor prognosis in glioblastoma and can significantly enhance the tumor cell viability and metastasis by activating the EMT process, suggesting that DCBLD2 may be a possible biomarker for glioblastoma treatment.
Decreased levels of γ-aminobutyric acid in temporal lobe of children with 47,XYY syndrome
Authors: Roberts Timothy P.L. , Bloy Luke , Miller Judith S. , Blaskey Lisa , Ross Judith 
Published: March 2021

Background
47,XYY syndrome (XYY) is a male sex chromosome disorder where subjects have one X chromosome and two copies of the Y chromosome. XYY is associated with a physical phenotype and carries increased risk of neurodevelopmental disorders such as autism spectrum disorder (ASD). Imbalance of excitation and inhibition has been proposed as a putative biological basis of disorders such as ASD [1–3] and several studies have reported atypical brain γ-aminobutyric acid (GABA) levels in this population. Given the male preponderance in the prevalence of ASD, the unique presence of the Y chromosome in males leads to the intriguing possibility of investigating boys with XYY syndrome as a model of excess Y-chromosome genes.

Method
In this study, we investigated the associations of genotype and clinical phenotype with levels of GABA, estimated by regionally localized edited magnetic resonance spectroscopy in boys with 47, XYY syndrome compared to age-matched typically developing (XY) peers.

Results
Overall, we observed a decrease in GABA levels in XYY vs. XY, which appeared more significant in the left compared to the right hemisphere. There was no additional significant modulation of GABA levels in XYY according to presence/absence of ASD diagnosis. Interestingly, a positive correlation between bilateral GABA levels and testosterone levels was observed in pubescent XY boys that was not observed in XYY.

Conclusion
The inhibitory neurotransmitter GABA appears to be reduced in boys with 47,XYY, especially in the left hemisphere. Further, the typical association between GABA and testosterone levels, observed in older typically developing control boys was not evident in boys with 47,XYY.
Using Random Forests with Asymmetric Costs to Predict Hospital Readmissions
Authors: Bleich Justin , Cole Brian , Kapelner Adam , Baillie Charles A. , Gupta Rohit , Hanish Asaf , Calgua Erwin , Umscheid Craig A. , Berk Richard 
Published: March 2021

AbstractBackgroundSufficiently accurate predictions of hospital readmissions are necessary for the allocation of scare clinical resources to reduce preventable readmissions. We describe the use of a data-driven approach that relies on machine learning algorithms to predict readmission at the time of discharge.MethodsWe employ random forests to clinical and administrative electronic health record data available from a cohort of 103,688 patients discharged from the acute inpatient settings of the University of Pennsylvania Health System between June 25th, 2011 and June 30th, 2013. We predict both 30-day all-cause readmissions and 7-day unplanned readmissions using only predictors available by the time of discharge. Using oversampling and undersampling of the different outcome classes of readmission and no readmission, we incorporate into our models the asymmetric costs of a false negative relative to a false positive from the perspective of a hospital. We calculate variable importance scores for included predictors. Our approach was derived and validated using split-sample internal validation.ResultsWe developed a machine learning-based model using random forests with a 5:1 relative cost ratio for 30-day all-cause readmissions that achieves a sensitivity of 65% and specificity of 71% on validation data, as well as a random forests model with a 20:1 cost ratio for 7-day unplanned readmissions that achieves a sensitivity of 62% and specificity of 66% on validation data. Prior health system utilization, clinical discharging service, and vital sign information were most predictive of readmissions.ConclusionBy modeling the complex relationships between many predictor variables and readmission data for a large health system, we demonstrate successful predictive models that can be used upon discharge to flag patients at high risk of readmission.
SARS-CoV-2 pandemic dynamics and infection tracing in Denmark
Authors: Jørgensen Morten W.N. , Høiby Niels , Ziock Hans J. , Rasmussen Steen 
Published: March 2021

AbstractWe model and simulate the COVID-19 infection and healthcare dynamics in Denmark from the onset till March 5, 2021. The simulation is matched and calibrated to hospital and death data as well as antibody population measurement. In this work we focus on comparing the time evolution of the estimated infection level with the daily identified infected individuals based on the national testing and contact tracing program. We find that the national testing program on average identifies 1/3 of the infected individuals July 1, 2020 - March 5, 2021. Our investigations indicate the current program does not have a proper balance between random probing, focused contact tracing, and testing prioritization. Too much of the program operates as a semi-random daily sampling of part of the population. We propose a policy with a focus on local infection tracing and interventions.
Curtailing Covid-19 on a Dollar-a-Day in Malawi: Implications for the Ongoing Pandemic
Authors: Kohler Iliana V. , Kämpfen Fabrice , Ciancio Alberto , Mwera James , Mwapasa Victor , Kohler Hans-Peter 
Published: March 2021

AbstractUtilizing population-based data from the Covid-19 phone survey (N = 2, 262) of the Malawi Longitudinal Study of Families and Health (MLSFH) collected during June 2nd–August 17th, 2020, we investigate behavioral, economic and social responses to Covid-19 and focus on the crucial role that community leadership and trust in institutions play towards shaping these responses. We argue that the effective response of Malawi to limit the spread of the virus was facilitated by the engagement of local leaders to mobilize communities to adapt and adhere to Covid-19 prevention strategies. Village heads (VHs) played pivotal role in shaping individual’s knowledge about the pandemic and the adaption of preventive health behaviors and were crucial for mitigating the negative economic and health consequences of the pandemic. We further show that trust in institutions is of particular importance in shaping individuals’ behavior during the pandemic, and these findings highlight the pivotal role of community leadership in fostering better compliance and adoption of public health measures essential to contain the virus. Overall, our findings point to distinctive patterns of pandemic response in a low-income sub-Saharan African rural population that emphasized local leadership as mediators of public health messages and policies. These lessons from the first pandemic wave remain relevant as in many low-income countries behavioral responses to Covid-19 will remain the primary prevention strategy for a foreseeable future.
Community mobilisation approaches to preventing and reducing adolescent multiple risk behaviour: a realist review protocol
Authors: Tinner Laura , Caldwell Deborah , Campbell Rona 
Published: March 2021

AbstractBackgroundAdolescent multiple risk behaviour (MRB) continues to be a global health issue, contributing to the burden of non-communicable diseases. Most interventions have focused on the proximal causes of adolescent MRB such as peer or family influence, rather than targeting the wider environmental or structural context. There is increasing recognition that community mobilisation approaches that extend beyond individually-focused educational programmes could be beneficial for adolescent health. Despite this, there are gaps in the current literature, theory and implementation that would benefit from a realist approach due to the suitability of this methodology to analysing complex interventions. In this protocol, we outline our study that aims to understand ‘how, why, for whom and in what circumstances and time periods do community mobilisation interventions work to prevent and/or reduce adolescent multiple risk behaviour?’MethodsA realist review was chosen as the most suitable review method as it is theory-driven and seeks to understand how, why and for whom interventions work to produce intended and unintended outcomes. A six-stage iterative process is outlined, which includes initial development of a programme theory, systematic searching, study selection and appraisal, data extraction and data synthesis. We will engage with stakeholders at different stages in this process to aid the development of the programme theory.DiscussionThe goal of this realist review is to identify and refine a programme theory for community mobilisation approaches to the prevention and/or reduction of adolescent multiple risk behaviour. Our aim is that the findings surrounding the programme theory refinement can be used to develop and implement adolescent multiple risk behaviour interventions and maintain collaboration between local policy makers, researchers and community members.RegistrationThis realist review is registered on the PROSPERO database (registration number: CRD42020205342).
Modelling the laminar connectome of the human brain
Authors: Shamir Ittai , Tomer Omri , Krupnik Ronnie , Assaf Yaniv 
Published: March 2021

AbstractThe human connectome is the complete structural description of the network of connections and elements that form the ‘wiring diagram’ of the brain. Due to the current scarcity of information regarding laminar end points of white matter tracts inside cortical grey matter, tractography remains focused on cortical partitioning into regions, while ignoring radial partitioning into laminar components. To overcome this biased representation of the cortex as a single homogenous unit, we use a recent data-derived model of cortical laminar connectivity, which has been further explored and corroborated in the macaque brain by comparison to published studies. The model integrates multimodal MRI imaging datasets of both white matter connectivity and grey matter laminar composition into a laminar-level connectome. In this study we model the laminar connectome of healthy human brains (N=30) and explore them via a set of neurobiologically meaningful complex network measures. Our analysis demonstrates a subdivision of network hubs that appear in the standard connectome into each individual component of the laminar connectome, giving a fresh look into the role of laminar components in cortical connectivity and offering new prospects in the fields of both structural and functional connectivity.
Weak humoral immune reactivity among residents of long-term care facilities following one dose of the BNT162b2 mRNA COVID-19 vaccine
Authors: Brockman Mark A. , Mwimanzi Francis , Sang Yurou , Ng Kurtis , Agafitei Olga , Ennis Siobhan , Lapointe Hope , Young Landon , Umviligihozo Gisele , Burns Laura , Brumme Chanson , Leung Victor , Montaner Julio S.G. , Holmes Daniel , DeMarco Mari , Simons Janet , Niikura Masa , Pantophlet Ralph , Romney Marc G. , Brumme Zabrina L. 
Published: March 2021

ABSTRACTBackgroundSeveral Canadian provinces are extending the interval between COVID-19 vaccine doses to increase population vaccine coverage more rapidly. However, immunogenicity of these vaccines after one dose is incompletely characterized, particularly among the elderly, who are at greatest risk of severe COVID-19.MethodsWe assessed SARS-CoV-2 humoral responses pre-vaccine and one month following the first dose of BNT162b2 mRNA vaccine, in 12 COVID-19 seronegative residents of long-term care facilities (median age, 82 years), 18 seronegative healthcare workers (HCW; median age, 36 years) and 4 convalescent HCW. Total antibody responses to SARS-CoV-2 nucleocapsid (N) and spike protein receptor binding domain (S/RBD) were assessed using commercial immunoassays. We quantified IgG and IgM responses to S/RBD and determined the ability of antibodies to block S/RBD binding to ACE2 receptor using ELISA. Neutralizing antibody activity was also assessed using pseudovirus and live SARS-CoV-2.ResultsAfter one vaccine dose, binding antibodies against S/RBD were ∼4-fold lower in residents compared to HCW (p<0.001). Inhibition of ACE2 binding was 3-fold lower in residents compared to HCW (p=0.01) and pseudovirus neutralizing activity was 2-fold lower (p=0.003).While six (33%) seronegative HCW neutralized live SARS-CoV-2, only one (8%) resident did (p=0.19). In contrast, convalescent HCW displayed 7- to 20-fold higher levels of binding antibodies and substantial ability to neutralize live virus after one dose.InterpretationExtending the interval between COVID-19 vaccine doses may pose a risk to the elderly due to lower vaccine immunogenicity in this group. We recommend that second doses not be delayed in elderly individuals.
Characterising post-COVID syndrome more than 6 months after acute infection in adults; prospective longitudinal cohort study, England
Authors: Amin-Chowdhury Zahin , Harris Ross J , Aiano Felicity , Zavala Maria , Bertran Marta , Borrow Ray , Linley Ezra , Ahmad Shazaad , Parker Ben , Horsley Alex , Hallis Bassam , Flood Jessica , Brown Kevin E , Amirthalingam Gayatri , Ramsay Mary E , Andrews Nick , Ladhani Shamez N 
Published: March 2021

AbstractBackgroundMost individuals with COVID-19 will recover without sequelae, but some will develop long- term multi-system impairments. The definition, duration, prevalence and symptoms associated with long COVID, however, have not been established.MethodsPublic Health England (PHE) initiated longitudinal surveillance of clinical and non-clinical healthcare workers for monthly blood sampling for SARS-CoV-2 antibodies in March 2020. Eight months after enrolment, participants completed an online questionnaire including 72 symptoms in the preceding month. Symptomatic mild-to-moderate cases with confirmed COVID-19 were compared with asymptomatic, seronegative controls. Multivariable logistic regression was used to identify independent symptoms associated with long COVID.ResultsAll 2,147 participants were contacted and 1,671 (77.8%) completed the questionnaire, including 140 (8.4%) cases and 1,160 controls. At a median of 7.5 (IQR 7.1-7.8) months after infection, 20 cases (14.3%) had ongoing (4/140, 2.9%) or episodic (16/140, 11.4%) symptoms. We identified three clusters of symptoms associated with long COVID, those affecting the sensory (ageusia, anosmia, loss of appetite and blurred vision), neurological (forgetfulness, short-term memory loss and confusion/brain fog) and cardiorespiratory (chest tightness/pain, unusual fatigue, breathlessness after minimal exertion/at rest, palpitations) systems. The sensory cluster had the highest association with being a case (aOR 5.25, 95% CI 3.45-8.01). Dermatological, gynaecological, gastrointestinal or mental health symptoms were not significantly different between cases and controls.ConclusionsMost persistent symptoms reported following mild COVID-19 were equally common in cases and controls. While all three clusters identified had a strong association with previous COVID-19 infection, the sensory cluster had the highest specificity and strength of association.Key pointsCompared to controls, we identified three clusters of symptoms affecting the sensory, neurological and cardiorespiratory systems that were more prevalent among cases. Notably, gastrointestinal and dermatological symptoms and symptoms related to mental health were as prevalent among cases as controls.
Alpha-1 blockers and susceptibility to COVID-19 in benign prostate hyperplasia patients : an international cohort study
Authors: Nishimura Akihiko , Xie Junqing , Kostka Kristin , Duarte-Salles Talita , Fernández Bertolín Sergio , Aragón María , Blacketer Clair , Shoaibi Azza , DuVall Scott L , Lynch Kristine , Matheny Michael E , Falconer Thomas , Morales Daniel R , Conover Mitchell M , You Seng Chan , Pratt Nicole , Weaver James , Sena Anthony G , Schuemie Martijn J , Reps Jenna , Reich Christian , Rijnbeek Peter R , Ryan Patrick B , Hripcsak George , Prieto-Alhambra Daniel , Suchard Marc A 
Published: March 2021

AbstractAlpha-1 blockers, often used to treat benign prostate hyperplasia (BPH), have been hypothesized to prevent COVID-19 complications by minimising cytokine storms release. We conducted a prevalent-user active-comparator cohort study to assess association between alpha-1 blocker use and risks of three COVID-19 outcomes: diagnosis, hospitalization, and hospitalization requiring intensive services. Our study included 2.6 and 0.46 million users of alpha-1 blockers and of alternative BPH therapy during the period between November 2019 and January 2020, found in electronic health records from Spain (SIDIAP) and the United States (Department of Veterans Affairs, Columbia University Irving Medical Center, IQVIA OpenClaims, Optum DOD, Optum EHR). We estimated hazard ratios using state-of-the-art techniques to minimize potential confounding, including large-scale propensity score matching/stratification and negative control calibration. We found no differential risk for any of COVID-19 outcome, pointing to the need for further research on potential COVID-19 therapies.
Inferring livestock movement networks from archived data to support infectious disease control in developing countries
Authors: Muwonge A. , Bessell P.R. , Porphyre T. , Motta P. , Rydevik G. , Devailly G. , Egbe N.F. , Kelly R.F. , Handel I.G. , Mazeri S. , Bronsvoort B.M.deC. 
Published: March 2021

AbstractThe use of network analysis to support livestock disease control in low middle-income countries (LMICs) has historically been hampered by the cost of generating empirical data in the absence of animal movement recording schemes. To fill this gap, methods which exploit freely available demographic and archived molecular data can be used to generate livestock networks based on gravity and phylogeographic modelling techniques, respectively. However, questions remain on the performance of these methods in capturing the topology of empirical networks. Here, we compare output from these network methodologies to a network constructed from either empirical data or randomly generated data. To facilitate this comparison, the spread of infectious diseases was simulated, it is this evaluation that demonstrates their potential utility to inform robust livestock disease control strategies.The molecular network was the closest approximation to the empirical network, both in relation to topological and epidemic characteristics, whereas size of epidemics in the gravity network tended to be larger, better agreement across all three networks was observed when; a) total nodes infected, b) percentage infection take off were compared. These methods consistently identified the same important animal movement and trade hotspots as the empirical networks. We therefore consider this proof-of-concept that demographic data such as censuses and archived molecular data could be repurposed to inform livestock disease management in LMICs.Author summaryLive animal movements in Africa represent a significant risk of transmission and spread of infectious diseases in livestock populations, and therefore, have direct implications on the food security of the continent. Here we explore the potential utility of available data to support control strategies, by comparing movement networks inferred from such data i.e. census and pathogen molecular data using gravity modelling and phylogeography respectively. Their utility is evaluated by comparing their topology and disease spread characteristics to empirical live animal movement. Based on our results, we posit that archived data can be repurposed to support infectious disease control on the African continent.
Diet-derived antioxidants do not decrease the risk of ischemic stroke: a Mendelian Randomization Study in over 1 million participants
Authors: Martens Leon G , Luo Jiao , Dijk Ko Willems van , Jukema J Wouter , Noordam Raymond , Heemst Diana van 
Published: March 2021

AbstractBackgroundIntake, either as dietary components or as supplements, and blood concentrations of vitamin E, C, lycopene and carotenoids have been associated with a lower risk of incident (ischemic) stroke. However, causality cannot not be inferred from these associations. Here, we investigated causality by analyzing the associations between genetically-influenced antioxidant levels in blood and ischemic stroke using Mendelian Randomization (MR).MethodsFor each circulating antioxidant (vitamin E, C, lycopene, β-carotene and retinol), which were assessed as either absolute blood levels and/or high-throughput metabolite levels, genetic instrumental variables were generated from earlier genome wide association studies. We used summary statistics for SNP-stroke associations from three European-ancestry cohorts (cases/controls): MEGASTROKE (67,162/454,450), UK Biobank (2,404/368,771) and FinnGen study (8,046/164,286). MR analyses were performed on each exposure per outcome cohort using inverse-variance weighted analyses, and subsequently meta-analyzed.ResultsIn a combined sample of 1,065,119 individuals (77,612 cases), none of the genetically-influenced absolute antioxidants or antioxidant metabolite concentrations were causally associated with a lower risk of ischemic stroke. For absolute antioxidants levels, the odds ratios (95% CI) ranged between 0.94 (95% CI: 0.85 to 1.05) for vitamin C and 1.04 (95% CI: 0.99 to 1.08) for lycopene. For metabolites, odds ratios ranged between 1.01 (95% CI: 0.98 to 1.03) for retinol and 1.12 (95% CI: 0.88 to 1.42) for vitamin E.ConclusionThis study did not provide evidence for a causal association between dietary-derived antioxidant levels and ischemic stroke. Therefore, antioxidant supplements to increase circulating levels are unlikely to be of clinical benefit to prevent ischemic stroke.