bluuebunny/crossref_metadata_2025_split huggingface dataset:
The subcortical morphology correlates of autistic traits in school-age children: a population-based neuroimaging study
Authors: Sharp T.H. , Elsabbagh M. , Pickles A. , Bedford R. 
Published: November 2021

AbstractBackgroundThere is emerging evidence that the neuroanatomy of autism forms a spectrum which extends into the general population. However, whilst several studies have identified cortical morphology correlates of autistic traits, it is not established whether morphological differences are present in the subcortical structures of the brain. Additionally, it is not clear to what extent previously reported structural associations may be confounded by co-occurring psychopathology. To address these questions, we utilised neuroimaging data from the Adolescent Brain Cognitive Development Study to assess whether a measure of autistic traits was associated with differences in child subcortical morphology, and if any observed differences persisted after adjustment for child internalising and externalising symptoms.MethodsOur analyses included data from 7,005 children aged 9-10 years (female: 47.19%) participating in the Adolescent Brain Cognitive Development Study. Autistic traits were assessed using scores from the Social Responsiveness Scale. Volumes of subcortical regions-of-interest were derived from structural magnetic resonance imaging data.ResultsOverall, we did not find strong evidence for an association of autistic traits with differences in subcortical morphology in this sample of school-aged children. Whilst lower absolute volumes of the nucleus accumbens and putamen were associated with higher scores of autistic traits, these differences did not persist once a global measure of brain size was accounted for.ConclusionsThese findings from our well-powered study suggest that other metrics of brain morphology, such as cortical morphology or shape-based phenotypes, may be stronger candidates to prioritise when attempting to identify robust neuromarkers of autistic traits.
A generic method and software to estimate the transmission advantage of pathogen variants in real-time : SARS-CoV-2 as a case-study
Authors: Bhatia Sangeeta , Wardle Jack , Nash Rebecca K , Nouvellet Pierre , Cori Anne 
Published: November 2021

AbstractRecent months have demonstrated that emerging variants may set back the global COVID-19 response. The ability to rapidly assess the threat of new variants in real-time is critical for timely optimisation of control strategies.We extend the EpiEstim R package, designed to estimate the time-varying reproduction number (Rt), to estimate in real-time the effective transmission advantage of a new variant compared to a reference variant. Our method can combine information across multiple locations and over time and was validated using an extensive simulation study, designed to mimic a variety of real-time epidemic contexts.We estimate that the SARS-CoV-2 Alpha variant is 1.46 (95% Credible Interval 1.44-1.47) and 1.29, (95% CrI 1.29-1.30) times more transmissible than the wild type, using data from England and France respectively. We further estimate that Beta and Gamma combined are 1.25 (95% CrI 1.24-1.27) times more transmissible than the wildtype (France data). All results are in line with previous estimates from literature, but could have been obtained earlier and more easily with our off-the-shelf open-source tool.Our tool can be used as an important first step towards quantifying the threat of new variants in real-time. Given the popularity of EpiEstim, this extension will likely be used widely to monitor the co-circulation and/or emergence of multiple variants of infectious pathogens.Significance StatementEarly assessment of the transmissibility of new variants of an infectious pathogen is critical for anticipating their impact and designing appropriate interventions. However, this often requires complex and bespoke analyses relying on multiple data streams, including genomic data. Here we present a novel method and software to rapidly quantify the transmission advantage of new variants. Our method is fast and requires only routinely collected disease surveillance data, making it easy to use in real-time. The ongoing high level of SARS-CoV-2 circulation in a number of countries makes the emergence of new variants highly likely. Our work offers a powerful tool to help public health bodies monitor such emerging variants and rapidly detect those with increased transmissibility.
It Takes Two to Tango: Combining Conventional Culture with Molecular Diagnostics Enhances Accuracy of Streptococcus pneumoniae Detection and Pneumococcal Serogroup/Serotype determination in Carriage
Authors: Miellet Willem R. , van Veldhuizen Janieke , Litt David , Mariman Rob , Wijmenga-Monsuur Alienke J. , Badoux Paul , Nieuwenhuijsen Tessa , Thombre Rebecca , Mayet Sanaa , Eletu Seyi , Sheppard Carmen , van Houten Marlies A. , Rots Nynke Y. , Miller Elizabeth , Fry Norman K. , Sanders Elisabeth A.M. , Trzciński Krzysztof 
Published: November 2021

ABSTRACTBackgroundThe specificity of molecular methods for the detection of Streptococcus pneumoniae carriage is under debate. We propose a procedure that increases the accuracy of molecular detection of live pneumococci in polymicrobial respiratory samples.MethodsCulture and qPCR methods were applied to detect S. pneumoniae and pneumococcal serotypes in 1549 nasopharyngeal samples collected in the Netherlands (n=972) and England (n=577) from 946 toddlers and 603 adults, and in paired oropharyngeal samples collected exclusively from 319 Dutch adults. Samples with no live pneumococci isolated at primary diagnostic culture yet generating pneumococcus-specific signal in qPCRs were re-examined with a second, qPCR-guided culture. Optimal Cq cut-offs for positivity in qPCRs were determined via receiver operating characteristic (ROC) curve analysis using isolation of live pneumococci from the primary and qPCR-guided cultures as reference.ResultsDetection of S. pneumoniae and pneumococcal serotypes with qPCRs in cultured (culture-enriched) nasopharyngeal samples exhibited near-perfect agreement with conventional culture (Cohen’s kappa: 0.95). Molecular methods also displayed increased sensitivity of detection for multiple serotype carriage. Among paired samples from adults, the sensitivity of S. pneumoniae detection in primary nasopharyngeal plus oropharyngeal cultures was significantly lower compared with molecular detection in both culture-enriched samples together (p<0.0001) and also in culture-enriched oropharyngeal samples alone (p<0.05).ConclusionsThe sensitivity of S. pneumoniae carriage surveillance can be greatly improved by complementing conventional culture with qPCR and vice versa. The specificity of molecular methods for the detection of live pneumococci can be enhanced by incorporating statistical procedures based on ROC curve analysis. The procedure we propose improves detection of S. pneumoniae carriage in adults in particular and enhances specificity of serotype carriage detection.
Can polygenic risk scores contribute to cost-effective cancer screening? A systematic review
Authors: Dixon Padraig , Keeney Edna , Taylor Jenny C. , Wordsworth Sarah , Martin Richard M. 
Published: November 2021

ABSTRACTPolygenic risk is known to influence susceptibility to cancer. The use of data on polygenic risk, in conjunction with other predictors of future disease status, may offer significant potential for preventative care through risk-stratified screening programmes. An important element in the evaluation of screening programmes is their cost-effectiveness.We undertook a systematic review of papers evaluating the cost-effectiveness of screening interventions informed by polygenic risk scores compared to more conventional screening modalities. We included papers reporting cost-effectiveness outcomes in the English language published as articles or uploaded onto preprint servers with no restriction on date, type of cancer or form of polygenic risk modelled. We excluded papers evaluating screening interventions that did not report cost-effectiveness outcomes or which had a focus on monogenic risk. We evaluated studies using the Quality of Health Economic Studies checklist.Ten studies were included in the review, which investigated three cancers: prostate (n=5), colorectal (n=3) and breast (n=2). All study designs were cost-utility papers implemented as Markov models (n=6) or microsimulations (n=4). Nine of ten papers scored highly (score >75 on a 0-100) scale) when assessed using the Quality of Health Economic Studies checklist. Eight of ten studies concluded that polygenic risk informed cancer screening was likely to be more cost-effective than alternatives. However, the included studies lacked robust external data on the cost of polygenic risk stratification, did not account for how very large volumes of polygenic risk data on individuals would be collected and used, did not consider ancestry-related differences in polygenic risk, and did not fully account for downstream economic sequalae stemming from the use of polygenic risk data in these ways. These topics merit attention in future research on how polygenic risk data might contribute to cost-effective cancer screening.FundingThis work was supported by Cancer Research UK under grant number C18281/A29019. PD and RM are members of the MRC Integrative Epidemiology Unit at the University of Bristol which is supported by the Medical Research Council and the University of Bristol (MC_UU_12013/1, MC_UU_12013/9). PD, EK ad RMM received support from a Cancer Research UK (C18281/A29019) programme grant (the Integrative Cancer Epidemiology Programme). SW and JCT receive funding from the Oxford NIHR Biomedical Research Centre.RegistrationProspectively registered on PROSPERO database before searches commenced. Available at https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=243659
Development of an electronic frailty index for hospitalized geriatric patients in Sweden
Authors: Mak Jonathan K. L. , Hägg Sara , Eriksdotter Maria , Annetorp Martin , Kuja-Halkola Ralf , Kananen Laura , Boström Anne-Marie , Kivipelto Miia , Metzner Carina , Jerlardtz Viktoria Bäck , Engström Malin , Johnson Peter , Lundberg Lars Göran , Åkesson Elisabet , Öberg Carina Sühl , Olsson Maria , Cederholm Tommy , Jylhävä Juulia , Religa Dorota 
Published: November 2021

ABSTRACTBackgroundFrailty assessment in the Swedish health system relies on the Clinical Frailty Scale (CFS), but it requires training, in-person evaluation, and is often missing in medical records. We aimed to develop an electronic frailty index (eFI) from routinely collected electronic health records (EHRs) and assess its predictive ability for adverse outcomes in geriatric patients.MethodsEHRs were extracted for 18,225 geriatric patients with unplanned admissions between 1/3/2020 and 17/6/2021 from nine geriatric clinics in Stockholm, Sweden. A 48-item eFI was constructed using diagnostic codes, functioning and other health indicators, and laboratory data. The CFS, Hospital Frailty Risk Score, and Charlson Comorbidity Index were used for comparative assessment of the eFI. We modelled in-hospital mortality and 30-day readmission using logistic regression; 30-day and 6-month mortality using Cox regression; and length of stay using linear regression.Results13,188 patients were included in analyses (mean age 83.1 years). A 10% increment in the eFI was associated with higher risks of in-hospital (odds ratio: 5.34; 95% confidence interval: 4.20-6.82), 30-day (hazard ratio [HR]: 3.28; 2.91-3.69), and 6-month mortality (HR: 2.70; 2.52-2.90) adjusted for age and sex. Of the frailty and comorbidity measures, the eFI had the best predictive accuracy for in-hospital mortality, yielding an area under receiver operating characteristic curve of 0.813. Higher eFI also predicted a longer length of stay, but had a rather poor discrimination for 30-day readmission.ConclusionsAn EHR-based eFI has good predictive accuracy for adverse outcomes, suggesting that it can be used in risk stratification in geriatric patients.
Performance of the Reported and Intended Behavior Scale among Colombian Adolescents
Authors: Campo-Arias A. , Ceballos-Ospino G. A. , Herazo E. 
Published: November 2021

ABSTRACTObjectiveTo establish the Reported and Intended Behavior Scale (RIBS) psychometric performance, a mental disorder-related stigma measurement, among Colombian adolescents.MethodsA validation study was carried out with 350 students aged between 10 and 17, 53.7% of whom were girls. The RIBS has two sub-scales -reported behaviors and intended behaviors, with four items each. Frequencies were estimated for reported behaviors, whereas internal consistency (Cronbach’s alpha and McDonald’s omega) and confirmatory factor analysis (CFA) were measured for intended behaviors.ResultsThe reported behavior sub-scale ranged from 10.0 to 24.9%, whereas the intended behavior sub-scale presented a Cronbach’s alpha of 0.88 (CI95% 0.86-0.90) and a McDonald omega of 0.88. For the CFA, KMO was 0.81; Bartlett chi squared, 771.1 (df=6, p=0.01); and Eigen value, 2.95 that explained 73.9% of the total variance. For the goodness-of-fit tests, chi squared was 21.9 (df=2, p=.001); RMSEA, 0.17 (CI90% 0.11-0.24); CFI, 0.97; TLI, 0.92; and SMSR, 0.03.ConclusionsThe RIBS can measure reported behaviors, and the intended behavior sub-scale shows high internal consistency. However, the dimensionality of the intended behavior sub-scale presents modest goodness-of-fit indexes. These findings need further replications.
DEVELOPMENT AND TESTING OF A LOW-COST INACTIVATION BUFFER THAT ALLOWS DIRECT SARS-COV-2 DETECTION IN SALIVA
Authors: Bustos-Garcia Brandon , Garza-Manero Sylvia , Cano-Dominguez Nallely , Lopez Sanchez Dulce Maria , Salgado Montes de Oca Gonzalo , Salgado-Aguayo Alfonso , Recillas-Targa Felix , Avila-Rios Santiago , Valdes Victor Julian 
Published: November 2021

ABSTRACTMassive testing is a cornerstone in efforts to effectively track infections and stop COVID-19 transmission, including places where good vaccination coverage has been achieved. However, SARS-CoV-2 testing by RT-qPCR requires specialized personnel, protection equipment, commercial kits, and dedicated facilities, which represent significant challenges for massive testing implementation in resource-limited settings. It is therefore important to develop testing protocols that facilitate implementation and are inexpensive, fast, and sufficiently sensitive. In this work, we optimized the composition of a buffer (PKTP) containing a protease, a detergent, and an RNase inhibitor, that is compatible with the RT-qPCR chemistry, allowing for direct testing of SARS-CoV-2 from saliva in an RNA extraction-independent manner. This buffer is compatible with heat-inactivation reducing the biohazard risk of handling the samples. We assessed the PKTP buffer performance in comparison to the RNA-extraction-based protocol of the US Centers for Disease Control and Prevention in saliva samples from 70 COVID-19 patients finding a good sensitivity (82.2% for the N1 and 84.4% for the N2 target, respectively) and correlations (R=0.77, p<0.001 for N1, and R=0.78, p<0.001 for N2). We also propose an auto-collection protocol for saliva samples and a multiplex reaction to reduce the number of PCR reactions per patient and further reduce overall costs while maintaining diagnostic standards in favor of massive testing.
Mural cell SRF controls pericyte migration, vessel patterning and blood flow
Authors: Orlich Michael Martin , Diéguez-Hurtado Rodrigo , Muehlfriedel Regine , Sothilingam Vithiyanjali , Wolburg Hartwig , Oender Cansu Ebru , Woelffing Pascal , Betsholtz Christer , Gaengel Konstantin , Seeliger Mathias , Adams Ralf H. , Nordheim Alfred 
Published: November 2021

AbstractRationalePericytes (PCs) and vascular smooth muscle cells (vSMCs), collectively known as mural cells (MCs), are recruited through PDGFB-PDGFRB signaling. MCs are essential for vascular integrity, and their loss has been associated with numerous diseases. Most of this knowledge is based on studies in which MCs are insufficiently recruited or fully absent upon inducible ablation. In contrast, little is known about the physiological consequences that result from impairment of specific MC functions.ObjectiveHere, we characterize the role of the transcription factor serum response factor (SRF) in MCs and study its function in developmental and pathological contexts.Methods and ResultsWe generated a mouse model of MC-specific inducible Srf gene deletion and studied its consequences during retinal angiogenesis. By postnatal day (P)6, PCs lacking SRF were morphologically abnormal and failed to properly co-migrate with angiogenic sprouts. As a consequence, PC-deficient vessels at the retinal sprouting front became dilated and leaky. By P12, also the vSMCs had lost SRF, which coincided with the formation of pathological arteriovenous (AV) shunts. Mechanistically, we show that PDGFB-dependent SRF activation is mediated via MRTF co-factors. We further show that MRTF-SRF signaling promotes pathological PC activation during ischemic retinopathy. RNA-sequencing, immunohistology, in vivo live imaging and in vitro experiments demonstrated that SRF regulates expression of contractile SMC proteins essential to maintain the vascular tone.ConclusionsSRF is crucial for distinct functions in PCs and vSMCs. SRF directs PC migration downstream of PDGFRB signaling and mediates pathological PC activation during ischemic retinopathy. In vSMCs, SRF is essential for expression of the contractile machinery, and its deletion triggers formation of AV shunts. These essential roles in physiological and pathological contexts provide a rational for novel therapeutic approaches through targeting SRF activity in MCs.
Time course of EEG power during creative problem-solving with insight or remote thinking
Authors: Bieth Théophile , Ovando-Tellez Marcela , Lopez-Persem Alizée , Garcin Beatrice , Hugueville Laurent , Lehongre Katia , Levy Richard , George Nathalie , Volle Emmanuelle 
Published: November 2021

AbstractProblem-solving often requires creativity and is critical in everyday life. However, the neurocognitive mechanisms underlying creative problem-solving remain poorly understood. Two mechanisms have been highlighted: forming new connections from and between the problem elements and insight solving (with a sudden realization of a solution). We examined EEG activity during an adapted version of a classical insight problem task, the Remote Associates Test, that requires finding a word connecting three words. It allowed us to explore remoteness in semantic connections (by varying the remoteness of the solution word across trials) and insight solving (identified as a “Eurêka” moment reported by the participants). Semantic remoteness was associated with a power increase in alpha band (8-12Hz) in a left parieto-temporal cluster, beta band (13-30Hz) in a right fronto-temporal cluster in the early phase of the task, and theta band (3-7Hz) in frontal cluster before the participants responded. Insight solving was associated with power increase preceding the response in alpha and gamma band (31-60Hz) in left temporal clusters and theta band in a frontal cluster. Source reconstructions show the brain regions associated with these clusters. Overall, our findings shed new light on the dynamic of some of the mechanisms involved in creative problem-solving.
More than meets the Kappa for Antibody Superantigen Protein L (PpL)
Authors: Ling Wei-Li , Yeo Joshua Yi , Ng Yuen-Ling , Wipat Anil , Gan Samuel Ken-En 
Published: November 2021

AbstractImmunoglobulin superantigens play an important role in the affinity purification of antibodies and underlie the microbiota-immune axis at mucosal areas Focussing on theStaphylococcalProtein A (SpA),StreptococcalProtein G (SpG), and theFinegoldiaProtein L (PpL) that were previously thought to bind to only specific regions of human antibodies, a systematic and holistic analysis of the antibody regions using 63 antibody permutations involving six Vκ and seven VH region IgG1 revealed showed novel PpL-antibody interactions. While SpA and SpG showed relatively consistent interactions with the antibodies, our findings showed PpL binding to certain VH-Vκ2, 5 and 6 interactions had contribution by other antibody regions. The findings of this have implications on PpL-based affinity antibody purifications and antibody design as well as provides novel insights to PpL-based microbiota-immune axis effects.
KRASmutations impact clinical outcome in metastatic non-small cell lung cancer
Authors: Eklund Ella A. , Wiel Clotilde , Fagman Henrik , Akyürek Levent M. , Raghavan Sukanya , Nyman Jan , Hallqvist Andreas , Sayin Volkan I. 
Published: November 2021

AbstractPurposeThere is an urgent need to identify new predictive biomarkers for treatment response to both platinum doublet chemotherapy (PD) and immune checkpoint blockade (ICB) with pembrolizumab. Here we evaluated whether treatment outcome could be affected byKRASmutational status in patients with metastatic (stage IV) non-small cell lung cancer (NSCLC).MethodsAll consecutive patients molecularly assessed and diagnosed between 2016-2018 with stage IV NSCLC in the region of West Sweden were included in this multi-center retrospective study. Primary study outcome was overall survival (OS).ResultsOut of 580 stage IV NSCLC patients, 35.5% harbored an activating mutation in theKRASgene (KRASMUT). Compared toKRASwild-type (KRASWT), KRASMUTwas a negative factor for OS (p= 0.014). On multivariate analysis, KRASMUTpersisted as a negative factor for OS (HR 1.288, 95% CI 1.091-1.521,p= 0.003). When treated with first-line platinum doublet (n= 195), KRASMUTis a negative factor for survival (p= 0.018) with median OS 9 months vs KRASWT11 months. On multivariate analysis, KRASMUTpersisted as a negative factor for OS (HR 1.564, 95%CI 1.124-2.177,p= 0.008). KRASMUTpatients with high PD-L1 expression (PD-L1high) had better OS than PD-L1highKRASWTpatients (p= 0.036). In response to first-line ICB, KRASMUTpatients had a significant (p= 0.006) better outcome than KRASWTwith a median OS 23 vs 6 months. On multivariable Cox analysis, KRASMUTstatus was an independent prognostic factor for better OS (HR 0.349, 95%CI 0.148-0.822,p= 0.016).ConclusionsKRASmutations is a positive predictive factor for treatment with pembrolizumab and a negative predictive factor for platinum doublet chemotherapy as well as general OS in stage IV NSCLC.