bluuebunny/crossref_metadata_2025_split huggingface dataset:
Action selection in early stages of psychosis: an active inference approach
Authors: Knolle Franziska , Sterner Elisabeth , Moutoussis Michael , Adams Rick A , Griffin Juliet D. , Haarsma Joost , Taverne Hilde ,   NSPN Consortium, Goodyer Ian M. , Fletcher Paul C. , Murray Graham K 
Published: May 2022

AbstractBackground and HypothesisIn order to interact successfully with our environment, we need to build a model, to make sense of noisy and ambiguous inputs. An inaccurate model, as suggested to be the case in psychosis, disturbs optimal action selection. Recent computational models, such as active inference (AI), have emphasized the importance of action selection, treating it as a key part of the inferential process. Based on an AI-framework, we examined prior knowledge and belief precision in an action-based task, given that alterations in these parameters have been linked to the development of psychotic symptoms. We further sought to determine whether task performance and modelling parameters would be suitable for classification of patients and controls.Study Design23 at-risk-mental-state individuals, 26 first-episode psychosis patients and 31 controls completed a probabilistic Go/NoGo task in which action choice (Go/ NoGo) was dissociated from outcome valence (gain/ loss). We examined group differences in performance and AI-model parameters, and then performed receiver operating characteristic (ROC) analyses to assess group-classification.Study ResultsWe found reduced overall performance in patients. AI-modelling revealed that patients showed increased forgetting, reduced confidence in policy selection and less optimal general choice behavior, with poorer action-state associations. Importantly, ROC-analysis revealed fair-to-good classification performances of all groups, when combining modelling parameters and performance measures.ConclusionFindings show that AI-modelling of this task not only provides further explanation for dysfunctional mechanisms underlying decision making in psychosis, but may also be highly relevant for future research on the development of biomarkers for early identification.
Social clustering of unvaccinated children: measles-mumps-rubella vaccination coverage in schools in the Netherlands
Authors: Klinkenberg Don , van Hoek Albert Jan , Veldhuijzen Irene , Hahné Susan , Wallinga Jacco 
Published: May 2022

AbstractBackgroundFor the measles-mumps-rubella (MMR) vaccine, the WHO-recommended coverage for herd protection is 95% for measles and 80% for rubella and mumps. However, a national vaccine coverage does not reflect social clustering of unvaccinated children, e.g. in schools of Orthodox Protestant or Anthroposophic identity in The Netherlands. To fully characterise this clustering, we estimated one-dose MMR vaccination coverages at all schools in the Netherlands.MethodsBy combining postcode catchment areas of schools and school feeder data, each child in the Netherlands was characterised by residential postcode, primary and secondary school (referred to as school career). Postcode-level vaccination data were used to estimate vaccination coverages per school career. These were translated to coverages per school, stratified by school identity.ResultsMost schools had vaccine coverages over 99%, but major exceptions were Orthodox Protestant schools (63% in primary and 58% in secondary schools) and Anthroposophic schools (67% and 78%).ConclusionsSchool-level vaccine coverage estimates reveal strong clustering of unvaccinated children. The school feeder data reveal strongly connected Orthodox Protestant and Anthroposophic communities, but separated from one another. This suggests that even at a national one-dose MMR coverage of 97.5%, thousands of children per cohort are not protected by herd immunity.
Pro-inflammatory innate-like T cells are expanded in the blood and inflamed intestine in Crohn’s Disease
Authors: Chiarolla Cristina M. , Schulz Axel R. , Meir Michael , Reu-Hofer Simone , Romero-Olmedo Addi J. , Lohoff Michael , Rosenwald Andreas , Chang Hyun-Dong , Schlegel Nicolas , Mei Henrik E. , Berberich-Siebelt Friederike 
Published: May 2022

ABSTRACTA complex and tissue-specific network of cells including T lymphocytes maintains intestinal homeostasis. To address disease and tissue-specific alterations, we performed a T cell-centric mass cytometry analysis of peripheral and intestinal lymphocytes from patients with Crohn’s disease (CD) and healthy donor PBMCs. We compared inflamed and not inflamed tissue areas of bowel resections. Chronic inflammation enforced activation, exhaustion and terminal differentiation of CD4+and CD8+T cells and an enrichment of CD4+Foxp3+cells (Tregs) in inflamed intestine. However, tissue-repairing Tregs decreased, while enigmatic rare Foxp3+T-cell subsets appeared upon inflammation. In vitro assays revealed that those subsets, e.g. CD4+Foxp3+HLA-DR+TIGIT−and CD4+Foxp3+CD56+, express pro-inflammatory IFN-γ. Some T-conventional (Tcon) cells tended towards innateness. In blood of CD patients, not well studied CD4+and CD8+subsets of CD16+CCR6+CD127+T cells appeared anew, a phenotype reproducible by incubation of healthy blood T cells with patient blood plasma. Together, these findings suggest a bias towards innate-like pro-inflammatory Tregs and innate-like Tcon, which act with less specific cytotoxicity. Most likely, this is both cause and consequence of intestinal inflammation during CD.Graphical Abstract
Real-world comparative effectiveness of mRNA-1273 and BNT162b2 vaccines among immunocompromised adults in the United States
Authors: Mues Katherine E. , Kirk Brenna , Patel Deesha A. , Gelman Alice , Chavers Scott , Talarico Carla , Esposito Daina B. , Martin David , Mansi James , Chen Xing , Gatto Nicolle M. , Van de Velde Nicolas 
Published: May 2022

AbstractIntroductionHead-to-head studies comparing COVID-19 mRNA vaccine effectiveness in immunocompromised individuals, who are vulnerable to severe disease are lacking, as large sample sizes are required to make meaningful inferences.MethodsThis observational comparative effectiveness study was conducted in closed administrative claims data from the US HealthVerity database (December 11, 2020-January 10, 2022, before omicron). A 2-dose mRNA-1273 versus BNT162b2 regimen was assessed for preventing medically-attended breakthrough COVID-19 diagnosis and hospitalizations among immunocompromised adults. Inverse probability of treatment weighting was applied to balance baseline characteristics between vaccine groups. Incidence rates from patient-level data and hazard ratios (HRs) using weighted Cox proportional hazards models were calculated.ResultsOverall, 57,898 and 66,981 individuals received a 2-dose regimen of mRNA-1273 or BNT161b2, respectively. Among the weighted population, mean age was 51 years, 53% were female, and baseline immunodeficiencies included prior blood transplant (8%-9%), prior organ transplant (7%), active cancer (12%-13%), primary immunodeficiency (25%-26%), HIV (20%-21%), and immunosuppressive therapy use (60%-61%). Rates per 1,000 person-years (PYs; 95% confidence intervals [CI]s) of breakthrough medically-attended COVID-19 were 25.82 (23.83-27.97) with mRNA-1273 and 30.98 (28.93, 33.18) with BNT162b2 (HR, 0.83; 95% CI, 0.75-0.93). When requiring evidence of an antigen or polymerase chain reaction test before COVID-19 diagnosis, the HR for medically-attended COVID-19 was 0.78 (0.67-0.92). Breakthrough COVID-19 hospitalization rates per 1,000 PYs (95% CI) were 3.66 (2.96-4.51) for mRNA-1273 and 4.68 (3.91-5.59) for BNT162b2 (HR, 0.78; 0.59-1.03). Utilizing open and closed claims for outcome capture only, or both cohort entry/outcome capture, produced HRs (95% CIs) for COVID-19 hospitalization of 0.72 (0.57-0.92) and 0.66 (0.58-0.76), respectively.ConclusionsAmong immunocompromised adults, a 2-dose mRNA-1273 regimen was more effective in preventing medically-attended COVID-19 in any setting (inpatient and outpatient) than 2-dose BNT162b2. Results were similar for COVID-19 hospitalization, although statistical power was limited when using closed claims only.Study RegistrationNCT05366322
Fear of Infection and Sufficient Vaccine Reservation Information Might Drive Rapid Coronavirus Disease 2019 Vaccination in Japan: Evidence from Twitter Analysis
Authors: Niu Qian , Liu Junyu , Kato Masaya , Aoyama Tomoki , Nagai-Tanima Momoko 
Published: May 2022

AbstractBackgroundThe global public health and socioeconomic impacts of coronavirus disease 2019 (COVID-19) have been substantial, making herd immunity by COVID-19 vaccination an important factor for protecting people and retrieving the economy. Among all the countries, Japan became one of the countries with the highest COVID-19 vaccination rate in several months, although the vaccine confidence in Japan is the lowest worldwide.ObjectiveWe attempted to find the reasons for the rapid coronavirus disease 2019 (COVID-19) vaccination in Japan under the lowest vaccine confidence in the world by Twitter analysis.Materials and methodsWe downloaded COVID-19 related Japanese tweets from a large-scale public COVID-19 Twitter chatter dataset within the timeline of February 1, 2021 and September 30, 2021. The daily number of vaccination cases was collected from the official website of the Prime Minister’s Office of Japan. After preprocessing, we applied unigram and bigram token analysis, then calculated the cross correlation and Pearson correlation coefficient (r) between the term frequency and daily vaccination cases. Then we identified vaccine sentiments and emotions of tweets and used the topic modeling to look deeper into the dominant emotions.ResultsWe selected 190,697 vaccine-related tweets after filtering. By n-gram token analysis, we discovered the top unigrams and bigrams over the whole period. In all the combinations of the top six unigrams, tweets with both keywords “reserve” and “venue” showed the largest r = 0.912 (P < 0.001) with the daily vaccination cases. In sentiment analysis, negative sentiment overwhelmed positive sentiment, and fear was the dominant emotion across the period. For the latent Dirichlet allocation model on tweets with fear emotion, the two topics were identified as “infect” and “vaccine confidence”. The expectation of the number of tweets generated from topic “infect” was larger than “vaccine confidence.”ConclusionOur work indicated that awareness of the danger of COVID-19 might increase the willingness to get vaccinated; With sufficient vaccine supply, effective vaccine reservation information delivery may be an important factor for people to get vaccinated; We didn’t find evidence for increased vaccine confidence in Japan during the period in our research. We recommend policymakers to share fair and prompt information about the infectious diseases and vaccination, and make efforts on smoother delivery of vaccine-reservation information.
Mapping the Regional Distribution of Molecular Tumor Board Patients and Identifying White Spots in our Catchment Area – a Joint Approach of the CCC WERA Alliance
Authors: Lüke Florian , Haller Florian , Utpatel Kirsten , Krebs Markus , Meidenbauer Norbert , Scheiter Alexander , Spörl Silvia , Heudobler Daniel , Keil Felix , Schubart Christoph , Tögel Lars , Einhell Sabine , Dietmaier Wolfgang , Huss Ralf , Dintner Sebastian , Sommer Sebastian , Jordan Frank , Goebeler Maria-Elisabeth , Metz Michaela , Haake Diana , Scheytt Mithun , Gerhard-Hartmann Elena , Maurus Katja , Brändlein Stephanie , Rosenwald Andreas , Hartmann Arndt , Märkl Bruno , Einsele Hermann , Mackensen Andreas , Herr Wolfgang , Kunzmann Volker , Bargou Ralf , Beckmann Matthias W. , Pukrop Tobias , Trepel Martin , Evert Matthias , Claus Rainer , Kerscher Alexander 
Published: May 2022

ABSTRACTBackgroundMolecular Tumor Boards (MTBs) are crucial instruments for discussing and allocating targeted therapies to suitable cancer patients based on genetic findings. Currently, limited evidence is available regarding the regional impact and the outreach component of MTBs.MethodsWe analyzed MTB patient data from four neighboring Bavarian tertiary care oncology centers in Würzburg, Erlangen, Regensburg, and Augsburg, together constituting the WERA Alliance. Absolute patient numbers and regional distribution across the WERA-wide catchment area were weighted with local population densities.ResultsHighest MTB patient numbers were found close to the four cancer centers. However, peaks in absolute patient numbers were also detected in more distant and rural areas. Moreover, weighting absolute numbers with local population density allowed us to identify regions within our catchment area relatively underrepresented in WERA MTBs.ConclusionInvestigating patient data from four neighboring cancer centers, we comprehensively assessed the regional impact of our MTBs. The results confirmed the success of existing collaborative structures with our regional partners. Additionally, our results help identifying potential white spots in precision oncology and establishing a joint WERA-wide outreach strategy.
Clinical validation of 3D-printed nasopharyngeal and oropharyngeal swabs for SARS-CoV-2 RT-PCR
Authors: Riis Åse Garløv , Røssland Tonje Merethe , Høyland Löhr Iren , Dalen Ingvild , Kåre Kleppe Lars , Sundal Jon , Berg Åse , Vadla May Sissel , Lenning Ole Bernt , Syre Heidi 
Published: May 2022

AbstractDue to limited access to commercially available flocked nasopharyngeal (NP) and oropharyngeal (OP) swabs during the SARS-COV-2 pandemic, we have evaluated the sensitivity of 3D-printed swabs compared to commercial swabs in a clinical setting. We included 35 subjects with known exposure to SARS-CoV-2. Participants were tested with commercial and prototype NP/OP swab pairs 8 and 22 days after exposure. At day 8, the sensitivity of the prototype was 96% for NP-samples (CI 81-99%) and 91% for OP-samples (CI 72-97%). The sensitivity of the commercial swab was 92% for NP-samples (CI 76-98%) and 91% for OP-samples (CI 72-97%). At day 22, the sensitivities of the commercial swab were 100% for NP-samples (CI 82-100%) and OP-samples (CI 77-100%), whereas sensitivity of the prototype was 61% for NP-samples (CI 39-80%) and 54% for OP-samples (CI 29-77%). In conclusion, the prototype might be an alternative to commercial swabs when used early in the course of infection.
Informing Variant Assessment using Structured Evidence from Prior Classifications (PS1, PM5, and PVS1 Sequence Variant Interpretation Criteria)
Authors: Bhat Vineel , Adzhubei Ivan A. , Fife James D. , Lebo Matthew , Cassa Christopher A. 
Published: May 2022

AbstractPurposeTo explore whether evidence of pathogenicity from prior variant classifications in ClinVar could be used to inform variant interpretation using the ACMG/AMP clinical guidelines.MethodsWe identify distinct SNVs which are either similar in location or in functional consequence to pathogenic variants in ClinVar, and analyze evidence in support of pathogenicity using three interpretation criteria.ResultsThousands of variants, including many in clinically actionable disease genes (ACMG SFv3.0), have evidence of pathogenicity from existing variant classifications, accounting for 2.5% of non-synonymous SNVs within ClinVar. Notably, there are many variants with uncertain or conflicting classifications which cause the same amino acid substitution as other pathogenic variants (PS1, N=323), variants which are predicted to cause different amino acid substitutions in the same codon as pathogenic variants (PM5, N=7,692), and LOF variants which are present in genes where many LOF variants are classified as pathogenic (PVS1, N=3,635). The majority of these variants have similar computational predictions of pathogenicity and splicing impact as their associated pathogenic variants.ConclusionBroadly, over 1.4 million SNVs exome-wide could make use of information from previously classified pathogenic variants. We have developed a pipeline to identify variants meeting these criteria, which may inform interpretation efforts.
Coding of Obesity-related Mortality Impacts Estimates of Obesity on U.S. Life Expectancy
Authors: Tilstra Andrea M. , Aburto José Manuel , Gutin Iliya , Dowd Jennifer Beam 
Published: May 2022

AbstractBackgroundHigh levels of obesity remain an important population health problem in the U.S. and a possible contributor to stalling life expectancy. However, reliable estimates of the contribution of obesity to mortality in the U.S. are lacking, because of inconsistent coding of obesity-related causes of death.MethodsWe compare five International Classification of Diseases version 10 (ICD-10) coding schemes for obesity-related mortality used in the literature and examine how the magnitude of obesity-related mortality burdens varies across different schemes. We use U.S. multiple cause of death data and population estimates for the Black, white, and Latino population in the years 2010, 2015, and 2020. In sex- and race/ethnic-stratified analyses, we estimate the potential years of life expectancy gained if obesity-related mortality had not occurred as measured by each coding scheme.ResultsWe estimate that obesity-related mortality contributes to up to 78 months (6.5 years) of lost U.S. life expectancy, though estimates range from as low as 0 months, with a median contribution across ICD-10 coding schemes of about 20 months (1.7 years). Despite substantial variation across coding schemes, obesity-related mortality consistently contributes more to life expectancy deficits for Black Americans compared to white and Latino Americans. Across all ICD-10 coding schemes, the age pattern of obesity follows a J-shaped curve, suggesting exponential increases in obesity-related mortality after age 25.ConclusionsThe estimation of the burden of obesity-related mortality on life expectancy in the United States varies widely depending on the causes of death used in analyses. This inconsistency may obscure our understanding of the contribution of obesity-related mortality to trends in life expectancy. We propose a standardization of the coding of obesity-related mortality for future studies and outline which causes should be included.
Performance and validation of an adaptable multiplex assay for detection of serologic response to SARS-CoV-2 infection or vaccination
Authors: Kenny Grace , Negi Riya , O’Reilly Sophie , Garcia-Leon Alejandro , Alalwan Dana , Gaillard Colette Marie , Saini Gurvin , Inzitari Rosana , Feeney Eoin R. , Yousif Obada , Cotter Aoife , de Barra Eoghan , Sadlier Corinna , Crispie Fiona , Doran Peter , Gautier Virginie , Mallon Patrick WG 
Published: May 2022

AbstractMeasurement of quantitative antibody responses are increasingly important in evaluating the immune response to infection and vaccination. In this study we describe the validation of a quantitative, multiplex serologic assay utilising an electrochemiluminescence platform, which measures IgG against the receptor binding domain (RBD), spike S1 and S2 subunits and nucleocapsid antigens of SARS-CoV-2. The assay displayed a sensitivity ranging from 73-91% and specificity from 90 to 96% in detecting previous infection with SARS-CoV-2 depending on antigenic target and time since infection, and this assay highly correlated with commercially available assays. The within-plate coefficient of variation ranged from 3.8-3.9% and the inter-plate coefficient of variation from 11-13% for each antigen.
Interrogating the causal effects of maternal circulating CRP on gestational duration and birth weight
Authors: Chen Jing , Navais Pol Sole , Xu Huan , Flatley Christopher , Bacelis Jonas , Monangi Nagendra , Kacerovsky Marian , Hallman Mikko , Teramo Kari , Lawlor Deborah A. , Murray Jeffrey C. , Jacobsson Bo , Muglia Louis J. , Zhang Ge 
Published: May 2022

AbstractBackgroundC-reactive protein (CRP) is an acute-phase marker of inflammation. Previous epidemiological studies have associated elevated maternal CRP levels during pregnancy with preterm birth risk and lower birth weight. However, the causal relationships behind these observed associations are not clear.Methods and FindingsWe utilized phenotype and genotype data on 10,734 mother/child pairs of European ancestry collected from six birth cohorts. We performed two-sample multivariate Mendelian Randomization (MR) using maternal non-transmitted alleles to interrogate the causal effect of maternal CRP on gestational duration and birth weight. Based on the non-transmitted alleles of 55 CRP associated single nucleotide polymorphisms (SNPs), a unit increase in log-transformed maternal CRP level was associated with a reduction of 1.58 days (95% CI: 0.23, 2.94, P = 0.022) in gestational duration and a reduction of 76.3g (95% CI: 18.2, 134.4, P = 0.010) in birth weight. The magnitude of the association between genetically increased CRP and birth weight was reduced after adjusting for gestational age. Utilizing the effect estimates of CRP-associated SNPs on birth weight from the UK Biobank genome-wide association (GWA) summary results, our results suggested one unit of genetically increased maternal CRP was associated with a decrease of 50.1g (95% CI: 24.7, 75.5, P = 9.6E-5) of birth weight (unadjusted by gestational age). We validated the results using a single genetic variant (rs2794520) near the CRP gene, which is less prone to horizontal pleiotropy bias.ConclusionsIncreased maternal CRP levels appear to causally reduce gestational duration and birth weight. The effect of maternal CRP on birth weight is partially due to its effect on gestational duration. The estimated causal effect sizes are consistent with previous epidemiological reports and this triangulation increases confidence in these results being causal.
Metabolomic Risk Predictors of Diabetic Foot Complications: a longitudinal observational study in Type 1 Diabetes
Authors: Andersen Jonas A. , Suvitaival Tommi , Trošt Kajetan , Romero-Lado María José , Theilade Simone , Mattila Ismo , Frimodt-Møller Marie , Rasmussen Anne , Rossing Peter , Legido-Quigley Cristina , Ahluwalia Tarunveer S. 
Published: May 2022

AbstractDiabetic foot complications (DFCs) comprising diabetic foot ulcer (DFU), charcot’s neuroarthropathy and amputations are a collective term used for the ailments of the foot that individuals with diabetes incur. Despite implementation of national and international guidelines, DFCs are still a growing challenge to the individual and society. Novel markers for the treatment and prevention of DFCs are thus needed. The aim of this study was to investigate circulating metabolites associated with the prevalence and incidence of DFCs in persons with type 1 diabetes (T1D). A panel of non-targeted serum metabolites (n=75) were analyzed using mass spectrometry in 637 individuals with T1D with a median follow up time of 10 years. Cross sectional associations between metabolites and DFCs were analysed by linear regression models at baseline, Cox proportional hazards model at follow-up and adjusted for relevant confounders (age, sex, HbA1c, systolic blood pressure, bmi, smoking, statin use, total cholesterol, plasma triglycerides, and renal function). The median (interquartile range) age was 55 (47, 64) years, diabetes duration of 35 (25, 44) years and HbA1clevels 64 (8%) (56, 72(7.3%, 8.7%)) mmol/mol. In the adjusted model, four amino acids (Proline, Threonine, Valine, and Leucine) were associated with a decreased incidence of Charcot’s arthropathy at baseline (p<0.05). In addition, circulating ribonic acid levels were associated with an increased risk of DFUs during follow-up (HR 1.38(1.06-1.8); p<0.05) which were validated in an independent cross-sectional T1D cohort (p<0.05). This study identifies novel circulating metabolites, as potential biomarkers for risk stratification of diabetic foot complications.