bluuebunny/crossref_metadata_2025_split huggingface dataset:
Post-translational modifications glycosylation and phosphorylation of the major hepatic plasma protein fetuin-A are associated with severity of CNS inflammation in children
Authors: Ricken Frederik , Can Ahu Damla , Gräber Steffen , Häusler Martin , Jahnen-Dechent Willi 
Published: May 2022

AbstractBackgroundFetuin-A is a liver derived plasma protein showing highest serum concentrations in utero, preterm infants and neonates. Fetuin-A is also present in cerebrospinal fluid (CSF). The origin of CSF fetuin-A, blood-derived via the blood brain barrier or synthesized intrathecally, is presently unclear. Fetuin-A prevents ectopic calcification by stabilizing calcium and phosphate as colloidal calciprotein particles mediating their transport and clearance. Thus, fetuin-A plays a suppressive role in inflammation. Fetuin-A is a negative acute-phase protein, serving as a biomarker for MS. Here we studied the association of pediatric inflammatory CNS diseases with fetuin-A glycosylation and phosphorylation.MethodsPaired blood and CSF samples from 66 children were included in the study. Concentration measurements were performed using a commercial human fetuin-A/AHSG ELISA. Of 60 pairs, 23 pairs were analyzed by SDS-PAGE following glycosidase digestion with PNGase-F and Sialidase-AU. Phosphorylation was analyzed in 30 pairs by Phos-Tag™ acrylamide electrophoresis following alkaline phosphatase digestion.Results and DiscussionMean serum and CSF fetuin-A levels were 0.30 ± 0.06 mg/ml and 0.644 ± 0.55 µg/ml, respectively. This study showed that serum fetuin-A levels decreased in inflammation corroborating its role as a negative acute-phase protein. Blood-brain barrier disruption was associated with elevated fetuin-A in CSF. A strong positive correlation was found between the CSF fetuin-A/serum fetuin-A ratio and the CSF albumin/serum albumin ratio, suggesting predominantly transport across the blood-brain barrier rather than intrathecal fetuin-A synthesis. Sialidase digestion showed increased asialofetuin-A levels in serum and CSF samples from children with neuroinflammatory diseases. Desialylation enhanced hepatic fetuin-A clearance via the asialoglycoprotein receptor thus rapidly reducing serum levels during inflammation. Phosphorylation of fetuin-A was more abundant in serum samples than in CSF, suggesting that phosphorylation may regulate fetuin-A influx into the CNS. These results may help establish Fetuin-A as a potential biomarker for neuroinflammatory diseases.
Repurposing EEG monitoring of general anaesthesia for building biomarkers of brain ageing: An exploratory study
Authors: Sabbagh David , Cartailler Jérôme , Touchard Cyril , Joachim Jona , Mebazaa Alexandre , Vallée Fabrice , Gayat Étienne , Gramfort Alexandre , Engemann Denis A. 
Published: May 2022

BackgroundEEG is a common tool for monitoring anaesthetic depth but is rarely reused at large for biomedical research. This study sets out to explore repurposing of EEG during anaesthesia to learn biomarkers of brain ageing in the absence of consciousness.MethodsWe focused on brain age estimation as an example. Using machine learning, we reanalysed 4-electrodes EEG of 323 patients under propofol and sevoflurane. We included spatio-spectral features from stable anaesthesia for EEG-based age prediction applying recently published reference methods. Anaesthesia was considered stable when 95% of the total power was below a frequency between 8Hz and 13Hz.ResultsWe considered moderate-risk patients (ASA <= 2) with propofol anaesthesia to explore predictive EEG signatures. Average alpha-band power (8-13Hz) was informative about age. Yet, state-of-the-art prediction performance was achieved by analysing the entire power spectrum from all electrodes (MAE = 8.2y, R2 = 0.65). Clinical exploration revealed that brain age was systematically linked with intra-operative burst suppression – commonly associated with age-related postoperative cognitive issues. Surprisingly, the brain age was negatively correlated with burst suppression in high-risk patients (ASA = 3), pointing at unknown confounding effects. Secondary analyses revealed that brain-age EEG signatures were specific to propofol anaesthesia, reflected by limited prediction performance under sevoflurane and poor cross-drug generalisation.ConclusionsEEG from general anaesthesia may enable state-of-the-art brain age prediction. Yet, differences between anaesthetic drugs can impact the effectiveness of repurposing EEG from anaesthesia. To unleash the dormant potential of repurposing EEG-monitoring for clinical and health research, in the absence of consciousness, collecting larger datasets with precisely documented drug dosage will be key enabling factors.
The I-SPY COVID Adaptive Platform Trial for COVID-19 Acute Respiratory Failure: Rationale, Design and Operations
Authors: Files D. Clark , Matthay Michael A. , Calfee Carolyn S. , Aggarwal Neil , Asare Adam L. , Beitler Jeremy R. , Berger Paul A. , Burnham Ellen L. , Cimino George , Coleman Melissa H. , Crippa Alessio , Discacciati Andrea , Gandotra Sheetal , Gibbs Kevin W. , Henderson Paul T. , Ittner Caroline A.G. , Jauregui Alejandra , Khan Kashif T. , Koff Jonathan L. , Lang Julie , LaRose Mary , Levitt Joe , Lu Ruixiao , McKeehan Jeffrey D. , Meyer Nuala J. , Russell Derek W. , Thomas Karl W. , Eklund Martin , Esserman Laura J. , Liu Kathleen D. 
Published: May 2022

AbstractIntroductionThe COVID-19 pandemic brought an urgent need to discover novel effective therapeutics for patients hospitalized with severe COVID-19. The ISPY COVID trial was designed and implemented in early 2020 to evaluate investigational agents rapidly and simultaneously on a phase 2 adaptive platform. This manuscript outlines the design, rationale, implementation, and challenges of the ISPY COVID trial during the first phase of trial activity from April 2020 until December 2021.Methods and analysisThe ISPY COVID Trial is a multi-center open label phase 2 platform trial in the United States designed to evaluate therapeutics that may have a large effect on improving outcomes from severe COVID-19. The ISPY COVID Trial network includes academic and community hospitals with significant geographic diversity across the country. Enrolled patients are randomized to receive one of up to four investigational agents or a control and are evaluated for a family of two primary outcomes—time to recovery and mortality. The statistical design uses a Bayesian model with “stopping” and “graduation” criteria designed to efficiently discard ineffective therapies and graduate promising agents for definitive efficacy trials. Each investigational agent arm enrolls to a maximum of 125 patients per arm and is compared to concurrent controls. As of December 2021, 11 investigational agent arms had been activated, and 8 arms were complete. Enrollment and adaptation of the trial design is ongoing.Ethics and disseminationISPY COVID operates under a central institutional review board via Wake Forest School of Medicine IRB00066805. Data generated from this trial will be reported in peer reviewed medical journals.Trial registration numberClinicaltrials.gov registration number NCT04488081Strengths and limitations of this studyThe ISPY COVID Trial was developed in early 2020 to rapidly and simultaneously evaluate therapeutics for severe COVID-19 on an adaptive open label phase 2 platformThe ISPY COVID Adaptive Platform Trial Network is an academic-industry partnership that includes academic and community hospitals spanning a wide geographic area across the United StatesOf December 2021, 11 investigational agent arms have been activated on the ISPY COVID Trial PlatformThe ISPY COVID Trial was designed to identify therapeutic agents with a large clinical effect for further testing in definitive efficacy trials—limitations to this approach include the risk of a type 2 error
Impaired visual processing in psychosis patients with a predisposition for visual hallucinations
Authors: van Ommen Marouska , Marsman Jan Bernard , Renken Remco , Bruggeman Richard , van Laar Teus , Cornelissen Frans W. 
Published: May 2022

AbstractPsychosis is frequently associated with the occurrence of visual hallucinations (VH), but their etiology remains largely unknown. While patients with psychosis show deficits on various behavioral visual and attentional tasks, previous studies have not specifically related these deficits to the presence of VH. This suggests that tasks used in these studies do not target the visual-cognitive neural mechanisms that mediate VH, which in turn limits the development of effective therapies. We therefore designed a study to target these mechanisms directly. In this case control study we asked patients with psychosis who had previously experienced VH to indicate when they recognized objects that were gradually emerging from dynamic visual noise, while scanning their brains using functional Magnetic Resonance Imaging. In a previous study, this recognition task was used to identify the neural basis of VH in patients with Parkinson’s Disease. Based on this earlier work, we decided to test the following hypothesis: when compared to psychosis patients not experiencing VH and age-matched healthy controls, psychosis patients with VH show reduced occipital activity and frontal activity around the moment of recognition (known as pop-out). For all groups, neuroimaging revealed increased activity in all examined visual areas around pop-out. However, psychosis patients with VH showed reduced occipital responsiveness, especially in the inferior part of the bilateral lateral occipital complex, a region known to play a key role in object recognition. We did not observe altered frontal or prefrontal activity before pop-out in this group. A possible explanation is that the relatively sustained activation of the visual memory-related angular gyri around pop-out may have compensated for the impaired early visual processing in psychosis patients with VH. We discuss our results in terms of current theories of visual hallucinations, such as predictive coding and contextual modulation. Our study is the first to show that visual processing deficits contribute to the occurrence of VH in psychosis. These findings could be used to develop tests to identify the visual-cognitive mechanisms that mediate VH in this group.
Construction of a short version of the Montreal Cognitive Assessment (MoCA) rating scale using Partial Least Squares analysis
Authors: Hemrungrojn Solaphat , Amrapala Arisara , Maes Michael 
Published: May 2022

AbstractBackgroundThe Montreal Cognitive Assessment (MoCA) rating scale is frequently used to assess cognitive impairments in amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD).ObjectivesThe aims of this study are to a) evaluate the construct validity of the MoCA and its subdomains or whether the MoCA can be improved by feature reduction, and b) develop a short version of the MoCA (MoCA-Brief).MethodsWe recruited 181 participants, divided into 60 healthy controls, 61 aMCI, and 60 AD patients.ResultsThe construct reliability of the original MoCA was not optimal and could be improved by deleting one subdomain (Naming) and five items, namely Clock Circle, Lion, Digit Forward, Repeat 2nd Sentence, and Place, which showed inadequate loadings on the extracted latent vectors. To construct the MoCA-Brief, the reduced model underwent further reduction and feature selection based on model quality data of the outer models. We produced a MoCA-Brief rating scale comprising five items, namely Clock Time, Subtract 7, Fluency, Month, and Year. The first latent vector extracted from these five indicators showed adequate construct validity with an Average Variance Extracted of 0.599, composite reliability of 0.822, Cronbach’s alpha of 0.832 and rho_A of 0.833. The MoCA-Brief factor score showed a strong correlation with the total MoCA score (r=0.98, p<0.001) and shows adequate concurrent, test-retest, and inter-rater validity.ConclusionThe construct validity of the MoCA may be improved by deleting five items. The new MoCA-Brief rating scale deserves validation in independent samples and especially in other countries.
Factors associated with repeat childbirth among Adolescent Mothers in Soroti District, Teso sub-region, Uganda: A cross-sectional study
Authors: Mulalu Posiano , Wanume Benon , David Soita , Amongin Dinnah , Wandawa Gabriel Julius 
Published: May 2022

AbstractThe percentage of adolescent mothers aged 15 to 19 years with a repeat childbirth in Uganda (26.1%) is higher than the global estimate (18.5%). Soroti district tops Teso (a region with highest adolescent childbearing rate nationally) in adolescent childbearing. Adolescent repeat childbearing (ARC) is associated with poor health outcomes, increased risk of stillbirth, maternal and child mortality, thus a public health concern. The factors associated with, and the burden, of ARC remains unknown in Soroti district. Consequently, interventions which combat ARC in Soroti district have not been informed by empirical data. This study determined the proportion of adolescent mothers with, and factors associated with, repeat childbirth among adolescent mothers in Soroti district.We conducted a cross-sectional study involving mixed methods of data collection. Interviewer-administered structured interviews were conducted amongst 422 adolescent mothers.Demographic and socio-economic data of respondents, data regarding respondents’ family and peer related factors was collected. Chi-square was the test statistics used. Multivariate analysis was by logistic regression.Of the 422 respondents, 31.28% (132) were married. Proportion of respondents with repeat childbirth was at 30.81% (95%CI: 26.57%-35.39%). Risk factors of ARC were (a) being married, AOR 5.74 (95%CI: 3.08-10.68), (b) incorrect knowledge of rhythm method, AOR 2.15 (95%CI: 1.21-3.82), (c) Age at first birth, AOR 0.48 (95%CI: 0.36-0.63). Protective factors of ARC included (a) not drinking alcohol, AOR 0.41(95%CI: 0.21-0.77), not being raped, AOR 0.19(95%CI: 0.06-0.55), having first childbirth from health facility, AOR 0.38 (95%CI: 0.18-0.78) and father of first baby without multiple sexual partners, AOR 0.40(95%CI: 0.22-0.72).In conclusion, sexual partner characteristics were associated with ARC suggesting male involvement (for example in family planning) in prevention of ARC. In addition, strengthening the implementation of anti-teen marriage programs and alcohol consumption policies, and instating measures to delay age at first delivery among adolescent mothers are required. Further research is needed to validate these findings.
Datasets for a Simulated Family-Based Exome-Sequencing Study
Authors: Dona Nirodha Epasinghege , Graham Jinko 
Published: May 2022

AbstractWe present simulated exome-sequencing data for 150 families from a North American admixed population, ascertained to contain at least four members affected with lymphoid cancer. These data include information on the ascertained families as well as single-nucleotide variants on the exome of affected family members. We provide a brief overview of the simulation steps and links to the associated software scripts. The resulting data are useful to identify genomic patterns and disease inheritance in families with multiple disease-affected members.Specifications Table
TCR repertoire profiling revealed antigen-driven CD8+ T cell clonal groups shared in synovial fluid of patients with spondyloarthritis
Authors: Komech Ekaterina A. , Koltakova Anastasia D. , Barinova Anna A. , Minervina Anastasia A. , Salnikova Maria A. , Shmidt Evgenia I. , Korotaeva Tatiana V. , Loginova Elena Y. , Erdes Shandor F. , Bogdanova Ekaterina A. , Shugay Mikhail , Lukyanov Sergey , Lebedev Yury B. , Zvyagin Ivan V. 
Published: May 2022

ABSTRACTSpondyloarthritis (SpA) comprises a number of inflammatory rheumatic diseases with overlapping clinical manifestations. Strong association with several HLA-I alleles and T cell infiltration into an inflamed joint suggest involvement of T cells in SpA pathogenesis. In this study, we performed high-throughput T cell repertoire profiling of synovial fluid (SF) and peripheral blood (PB) samples collected from a large cohort of SpA patients. We showed that synovial fluid is enriched with expanded T cell clones that are shared between patients with similar HLA genotypes and persist during recurrent synovitis. Using the recently published algorithm we discovered antigen-driven CD8+ clonal groups associated with risk HLA-B*27 or HLA-B*38 alleles. These clonal groups were enriched in SF and had higher frequency in PB of SpA patients vs healthy donors, suggesting their relevance to joint inflammation. Several of the identified groups were shared among patients with ankylosing spondylitis and psoriatic arthritis, suggesting existence of a common immunopathological mechanism of the diseases. In summary, our results provide supporting evidence for the role of antigen-driven CD8+ T cell clones in pathogenesis of SpA.
STIMULATE-ICP-CAREINEQUAL - Defining usual care and examining inequalities in Long Covid support: protocol for a mixed-methods study (part of STIMULATE-ICP: Symptoms, Trajectory, Inequalities and Management: Understanding Long-COVID to Address and Transform Existing Integrated Care Pathways)
Authors: Ramasawmy Mel , Mu Yi , Clutterbuck Donna , Pantelic Marija , Lip Gregory Y. H. , van der Feltz-Cornelis Christina , Wootton Dan , Williams Nefyn H , Montgomery Hugh , Cookson Rita Mallinson , Attree Emily , Gabbay Mark , Heightman Melissa , Alwan Nisreen A , Banerjee Amitava , Lorgelly Paula ,   the STIMULATE-ICP consortium
Published: May 2022

AbstractIntroductionIndividuals with Long Covid represent a new and growing patient population. In England, fewer than 90 Long Covid clinics deliver assessment and treatment informed by NICE guidelines. However, a paucity of clinical trials or longitudinal cohort studies means that the epidemiology, clinical trajectory, healthcare utilisation and effectiveness of current Long Covid care are poorly documented, and that neither evidence-based treatments nor rehabilitation strategies exist. In addition, and in part due to pre-pandemic health inequalities, access to referral and care varies, and patient experience of the Long Covid care pathways can be poor.In a mixed methods study, we therefore aim to: (1) describe the usual healthcare, outcomes and resource utilisation of individuals with Long Covid; (2) assess the extent of inequalities in access to Long Covid care, and specifically to understand Long Covid patients’ experiences of stigma and discrimination.Methods and analysisA mixed methods study will address our aims. Qualitative data collection from patients and health professionals will be achieved through surveys, interviews and focus group discussions, to understand their experience and document the function of clinics. A patient cohort study will provide an understanding of outcomes and costs of care. Accessible data will be further analysed to understand the nature of Long Covid, and the care received.Ethics and disseminationEthical approval was obtained from South Central - Berkshire Research Ethics Committee (reference 303958). The dissemination plan will be decided by the patient and public involvement and engagement (PPIE) group members and study Co-Is, but will target 1) policy makers, and those responsible for commissioning and delivering Long Covid services, 2) patients and the public, and 3) academics.
Use of low-dose decitabine with or without tyrosine kinase inhibitors in advanced phase chronic myelogenous leukemia: a systemic review and metaanalysis
Authors: Comia Maureen Via M. , Sy Charles Eryll S. , Julian Jomell C. 
Published: May 2022

ABSTRACTRationaleProgression of Chronic Myelogenous Leukemia (CML) to more advanced phases can involve hypermethylation, which is correlated to resistance or intolerance to imatinib. This hypermethylation has also been found to be a negative prognostic factor independent of imatinib response and from CML phase, thus decitabine, a hypomethylating agent, can be an attractive treatment option for advanced phase CML.ObjectiveThis systemic review and meta-analysis aims to investigate the role of low-dose decitabine among patients with advanced phase CML.MethodologyThis was performed according to the statement of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)ResultsFour (4) studies from 86 articles screened were eligible to be assessed in this systemic review and meta-analysis. These were phase I/II trials involving 81 advanced phase CML patients and used low-dose decitabine (5 to 20 mg/m2), with two studies using tyrosine kinase inhibitors. Outcomes of hematologic and cytogenetic response, and survival were assessed in the meta-analysis; with hematologic response being favored among advanced phase CML patients upon exposure with low-dose decitabine (p=0.05). Survival was also favored among responders to low-dose decitabine, however this was not significant.Discussion and ConclusionLow-dose decitabine can be an effective and safe treatment option in advanced phase CML, especially in more frail patients that could not tolerate more intensive chemotherapy regimens. However, this study is limited by few studies available on this topic, thus further randomized controlled trials can be investigated to define the role of decitabine and its optimal dose among this subset of patients.
Comparing human and AI performance in medical machine learning: An open-source Python library for the statistical analysis of reader study data
Authors: McKinney Scott Mayer 
Published: May 2022

AbstractIn seeking to understand the potential effects of artificial intelligence (AI) on the practice of diagnostic medicine, many investigations involve collecting interpretations from several human experts on a common set of cases. In an effort to standardize the process of analyzing the data emerging from such studies, we have released an open-source Python library to perform applicable statistical procedures. The software implements the industry-standard Obuchowski-Rockette-Hillis (ORH) method for multi-reader multi-case (MRMC) studies. The tools can be used to compare a standalone algorithm against a panel of readers, or compare readers operating in two modalities (for example, with and without algorithmic assistance). The software supports both nonequivalence and noninferiority tests. Functions are also provided to simulate reader and model scores, useful for Monte Carlo power analysis. The code is publicly available in our Gitub repository at https://github.com/Google-Health/google-health/tree/master/analysis.