bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serology in Children with Multisystem Inflammatory Syndrome (MIS-C) associated with COVID-19
Authors: Rostad Christina A. , Chahroudi Ann , Mantus Grace , Lapp Stacey A. , Teherani Mehgan , Macoy Lisa , Rostad Bradley S. , Milla Sarah S. , Tarquinio Keiko M. , Basu Rajit K. , Kao Carol , Linam W. Matthew , Zimmerman Matthew G. , Shi Pei-Yong , Menachery Vineet D. , Oster Matthew E. , Edupuganti Sri , Anderson Evan J. , Suthar Mehul , Wrammert Jens , Jaggi Preeti 
Published: July 2020

ABSTRACTObjectivesWe aimed to measure SARS-CoV-2 serologic responses in children hospitalized with multisystem inflammatory syndrome (MIS-C) compared to COVID-19, Kawasaki Disease (KD) and other hospitalized pediatric controls.MethodsFrom March 17, 2020 - May 26, 2020, we prospectively identified hospitalized children at Children’s Healthcare of Atlanta with MIS-C (n=10), symptomatic PCR-confirmed COVID-19 (n=10), KD (n=5), and hospitalized controls (n=4). With IRB approval, we obtained prospective and residual blood samples from these children and measured SARS-CoV-2 spike (S) receptor binding domain (RBD) IgM and IgG binding antibodies by quantitative ELISA and SARS-CoV-2 neutralizing antibodies by live-virus focus reduction neutralization assay. We statistically compared the log-transformed antibody titers among groups and performed correlation analyses using linear regression.ResultsAll children with MIS-C had high titers of SARS-CoV-2 RBD IgG antibodies, which correlated strongly with neutralizing antibodies (R2=0.667, P<0.001). Children with MIS-C had significantly higher SARS-CoV-2 RBD IgG antibody titers (geometric mean titer [GMT] 6800, 95%CI 3495-13231) than children with COVID-19 (GMT 626, 95%CI 251-1563, P<0.001), children with KD (GMT 124, 95%CI 91-170, P<0.001) and other hospitalized pediatric controls (GMT 85 [all below assay limit of detection], P<0.001). All children with MIS-C also had detectable RBD IgM antibodies, indicating recent SARS-CoV-2 infection. RBD IgG titers correlated with erythrocyte sedimentation rate (ESR) (R2=0.512, P<0.046) and with hospital and ICU lengths of stay (R2=0.590, P=0.010).ConclusionQuantitative SARS-CoV-2 RBD antibody titers may have a role in establishing the diagnosis of MIS-C, distinguishing it from other similar clinical entities, and stratifying risk for adverse outcomes.Table of Contents SummaryChildren with MIS-C have high antibody titers to the SARS-CoV-2 spike protein receptor binding domain, which correlate with neutralization, systemic inflammation, and clinical outcomes.What’s Known on This SubjectAlthough the clinical features of a multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 have been recently described, the serologic features of MIS-C are unknown.What This Study AddsIn this case series, all hospitalized children with MIS-C had significantly higher SARS-CoV-2 binding and neutralizing antibodies than children with COVID-19 or Kawasaki Disease. SARS-CoV-2 antibodies correlated with metrics of systemic inflammation and clinical outcomes, suggesting diagnostic and prognostic value.
Two pathways to self-harm in adolescence
Authors: Uh Stepheni , Dalmaijer Edwin S. , Siugzdaite Roma , Ford Tamsin J. , Astle Duncan E. 
Published: July 2020

AbstractBackgroundThe behavioural and emotional profiles underlying adolescent self-harm, and its developmental risk factors, are relatively unknown. We aimed to identify sub-groups of young people who self-harm (YPSH) and longitudinal predictors leading to self-harm.MethodsParticipants were from the Millennium Cohort Study (n=10,827). A clustering algorithm identified sub-groups who self-harmed with different behavioural and emotional profiles at age 14. Feature selection analyses were then used to identify longitudinal predictors of self-harming behaviour.FindingsThere were two distinct sub-groups at age 14: a smaller group (n = 379) who reported a long history of psychopathology, and a second group (n = 905) without. Notably, both groups could be predicted almost a decade before the reported self-harm. They were similarly characterised by sleep problems and low self-esteem, but there was developmental differentiation. From an early age, the first group had poorer emotion regulation, were bullied, and their caregivers faced emotional challenges. The second group showed less consistency in early childhood, but later reported more willingness to take risks and less security with peers/family.InterpretationOur results uncover two distinct pathways to self-harm: a ‘psychopathology’ pathway, associated with early and persistent emotional difficulties and bullying; and an ‘adolescent risky behaviour’ pathway, where risk-taking and external challenges emerge later into adolescence and predict self-harm. These two pathways have long developmental histories, providing an extended window for interventions as well as potential improvements in the identification of children at risk, biopsychosocial causes, and treatment or prevention of self-harm.FundingThis study was supported by the UK Medical Research Council, Templeton World Charitable Foundation, and a Gates Cambridge Scholarship awarded to SU.
Histological correlates of hippocampal magnetization transfer images in drug-resistant temporal lobe epilepsy patients
Authors: Peixoto-Santos Jose Eduardo , Velasco Tonicarlo R , Carlotti Carlos Gilberto , Assirati Joao Alberto , de Souza e Rezende Gustavo Henrique , Kobow Katja , Coras Roland , Blümcke Ingmar , Salmon Carlos Ernesto Garrido , dos Santos Antonio Carlos , Leite Joao Pereira 
Published: July 2020

SummaryObjectiveTemporal lobe epilepsy patients (TLE) often present with hippocampal atrophy, increased T2 relaxation, and reduced magnetization transfer ratio (MTR) in magnetic resonance images (MRI). The histological correlates of the reduced MTR are so far unknown. Since MTR is dependent on the tissue’s macromolecules, our aim was to evaluate the correlations between cellular populations, extracellular matrix molecules and the MTR in TLE patients.MethodsPatients with TLE (n=27) and voluntaries (=20) were scanned in a 3 Tesla MRI scanner, and MTR images were calculated from 3DT1 sequences with magnetization pulse on resonance. Immunohistochemistry for neurons, reactive astrocytes, activated microglia, and extracellular matrix chondroitin sulfate were performed in formalin fixed, paraffin embedded tissues of TLE and autopsy controls (n=10). Results were considered significant at p<0.05.ResultsCompared to the respective controls, TLE patients had reduced hippocampal MTR, increased reactive astrocytes and activated microglia, increased extracellular chondroitin sulfate, and reduced neuron density, compares to controls. MTR correlated positively with neuron density in CA3 and with chondroitin sulfate in CA3 and CA1. Multiple linear regressions reinforced the correlations between chondroitin sulfate and MTR.SignificanceOur data indicate that extracellular matrix molecules are the most significant histological correlates of magnetization transfer ratio in the hippocampus of TLE patients.
The 4C Initiative (Clinical Care for Cardiovascular disease in the COVID-19 pandemic) – monitoring the indirect impact of the coronavirus pandemic on services for cardiovascular diseases in the UK
Authors:   4C Initiative of the CVD-COVID-UK consortium, Ball S , Banerjee A , Berry C , Boyle J , Bray B , Bradlow W , Chaudhry A , Crawley R , Danesh J , Denniston A , Falter F , Figueroa JD , Hall C , Hemingway H , Jefferson E , Johnson T , King G , Lee K , McKean P , Mason SM , Mills N , Pearson E , Pirmohamed M , Poon MTC , Priedon R , Shah A , Sofat R , Sterne J , Strachan F , Sudlow CLM , Szarka Z , Whiteley W , Wyatt M 
Published: July 2020

ABSTRACTBackgroundThe coronavirus (COVID-19) pandemic affects cardiovascular diseases (CVDs) directly through infection and indirectly through health service reorganisation and public health policy. Real-time data are needed to quantify direct and indirect effects. We aimed to monitor hospital activity for presentation, diagnosis and treatment of CVDs during the pandemic to inform on indirect effects.MethodsWe analysed aggregate data on presentations, diagnoses and treatments or procedures for selected CVDs (acute coronary syndromes, heart failure, stroke and transient ischaemic attack, venous thromboembolism, peripheral arterial disease and aortic aneurysm) in UK hospitals before and during the COVID-19 epidemic. We produced an online visualisation tool to enable near real-time monitoring of trends.FindingsNine hospitals across England and Scotland contributed hospital activity data from 28 Oct 2019 (pre-COVID-19) to 10 May 2020 (pre-easing of lockdown), and for the same weeks during 2018-2019. Across all hospitals, total admissions and emergency department (ED) attendances decreased after lockdown (23 March 2020) by 57.9% (57.1-58.6%) and 52.9% (52.2-53.5%) respectively compared with the previous year. Activity for cardiac, cerebrovascular and other vascular conditions started to decline 1-2 weeks before lockdown, and fell by 31-88% after lockdown, with the greatest reductions observed for coronary artery bypass grafts, carotid endarterectomy, aortic aneurysm repair and peripheral arterial disease procedures. Compared with before the first UK COVID-19 (31 January 2020), activity declined across diseases and specialties between the first case and lockdown (total ED attendances RR 0.94, 0.93-0.95; total hospital admissions RR 0.96, 0.95-0.97) and after lockdown (attendances RR 0.63, 0.62-0.64; admissions RR 0.59, 0.57-0.60). There was limited recovery towards usual levels of some activities from mid-April 2020.InterpretationSubstantial reductions in total and cardiovascular activities are likely to contribute to a major burden of indirect effects of the pandemic, suggesting they should be monitored and mitigated urgently.FundingBritish Heart Foundation, Health Data Research UK
Microbial ecology ofIxodes scapularisfrom Central Pennsylvania, USA
Authors: Sakamoto Joyce M. , Diaz Gabriel Enrique Silva , Wagner Elizabeth Anne 
Published: July 2020

Abstract(1) Background: Native microbiota represent a potential resource for biocontrol of arthropod vectors.Ixodes scapularisare mostly inhabited by the endosymbioticRickettsia buchneri,but the bacterial communty composition varies with life stage, fed status, and/or geographic location. We investigated sex-specific bacterial community diversity fromI. scapulariscollected from central Pennsylvania between populations within a small geographic range. (2) Methods: We sequenced the bacterial 16S rRNA genes from individuals and pooled samples and investigated the abundance or infection frequency of key taxa using taxon-specific PCR and/or qPCR. (3) Results: Bacterial communities were more diverse in pools of males than females. WhenR. buchneriwas not the dominant taxon, Coxiellaceae was dominant. We determined that the infection frequency ofBorrelia burgdorferiranged between 20 to 75%. Titers ofAnaplasma phagocytophilumwere significantly different between sexes. HighRickettsiellatiter in pools were likely due to a few heavily infected males. (4) Conclusion: Bacterial 16S sequencing is useful for establishing the baseline community diversity and focusing hypotheses for targeted experiments. However, care should be taken not to overinterpret data concerning microbial dominance between geographic locations based on a few individuals as this may not accurately represent the bacterial community within tick populations.
A Highly Immunogenic Measles Virus-based Th1-biased COVID-19 Vaccine
Authors: Hörner Cindy , Schürmann Christoph , Auste Arne , Ebenig Aileen , Muraleedharan Samada , Herrmann Maike , Schnierle Barbara , Mühlebach Michael D. 
Published: July 2020

AbstractThe COVID-19 pandemic is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and has spread world-wide with millions of cases and hundreds of thousands of deaths to date. The gravity of the situation mandates accelerated efforts to identify safe and effective vaccines. Here, we generated measles virus (MeV)-based vaccine candidates expressing the SARS-CoV-2 spike glycoprotein (S). Insertion of the full-length S protein gene in two different MeV genomic positions resulted in modulated S protein expression. The variant with lower S protein expression levels was genetically stable and induced high levels of effective Th1-biased antibody and T cell responses in mice after two immunizations. In addition to neutralizing IgG antibody responses in a protective range, multifunctional CD8+and CD4+T cell responses with S protein-specific killing activity were detected. These results are highly encouraging and support further development of MeV-based COVID-19 vaccines.Author ContributionsCH performed research, analyzed data, and wrote the paper; CS performed research and analyzed data; AA performed research and analyzed data; AE performed research and analyzed data; SM performed research, analyzed data, and wrote the paper; MH developed the bioinformatics pipeline and analyzed data; BS contributed new reagents and concepts; MDM designed and supervised research, analyzed data and wrote the paper; all authors read, corrected and approved the final manuscript.Significance StatementThe COVID-19 pandemic has caused hundreds of thousands of deaths, yet. Therefore, effective vaccine concepts are urgently needed. In search for such a concept, we have analysed a measles virus-based vaccine candidate targeting SARS-CoV-2. Using this well known, safe vaccine backbone, we demonstrate here induction of functional immune responses in both arms of adaptive immunity with the desired immune bias. Therefore, occurrence of immunopathologies such as antibody-dependent enhancement or enhanced respiratory disease is rather unlikely. Moreover, the candidate still induces immunity against the measles, recognized as a looming second menace, when countries are entrapped to stop routine vaccination campaigns in the face of COVID-19. Thus, a bivalent measles-based COVID-19 vaccine could be the solution for two significant public health threats.
Sensory neurons expressing the atypical olfactory receptor guanylyl cyclase D are required for the acquisition of odor preferences by mice in diverse social contexts
Authors: Zimmerman Arthur D. , Nagy Christina R. , Munger Steven D. 
Published: July 2020

ABSTRACTAnimals use social communication to learn important information from conspecifics that can guide appropriate behavioral choices. For example, during the social transmission of food preference (STFP), conspecific semiochemicals detected by mouse olfactory sensory neurons (OSNs) expressing the atypical olfactory receptor guanylyl cyclase D (GC-D+ OSNs) promote the acquisition of food preferences in the recipient animal, mitigating the risk of ingesting food contaminated with toxins or pathogens. However, it is unclear if GC-D+ OSNs mediate preference learning outside this specific context. Here, we report that GC-D+ OSNs are required for the acquisition of odor preferences by both adult and juvenile mice, and that GC-D-dependent preference could be formed for conditionally aversive odors. We used a two-choice olfactory behavioral test to assess odor preferences in adult Gucy2d +/+, +/- and -/- mice that encountered novel odors together with GC-D+ OSN stimuli (guanylin family peptides), during social investigation of a live conspecific, or during suckling as pups. Gucy2d +/+ and +/-mice (which express functional GC-D), but not Gucy2d -/- littermates, successfully acquire a preference for the demonstrated odor in any of these behavioral paradigms. Mice could even acquire a GC-D-dependent preference for odors to which they had recently formed a conditioned aversion. Together, these results demonstrate that GC-D+ OSNs mediate the acquisition of socially-transmitted odor preferences in different social and experiential contexts and at different life stages.
Immune evolution from preneoplasia to invasive lung adenocarcinomas and underlying molecular features
Authors: Dejima Hitoshi , Hu Xin , Chen Runzhe , Zhang Jiexin , Fujimoto Junya , Parra Edwin R. , Haymaker Cara , Hubert Shawna , Duose Dzifa , Solis Luisa M. , Su Dan , Fukuoka Junya , Tabata Kazuhiro , Pharm Hoa , Mcgranahan Nicholas , Zhang Baili , Ye Jie , Ying Lisha , Little Latasha , Gumbs Curtis , Chow Chi-Wan , Estecio Marcos Roberto , Godoy Myrna C.B. , Antonoff Mara B. , Sepesi Boris , Pass Harvey , Behrens Carmen , Zhang Jianhua , Vaporciyan Ara A. , Heymach John V. , Scheet Paul , Lee J. Jack , Futreal P. Andrew , Reuben Alexandre , Kadara Humam , Wistuba Ignacio , Zhang Jianjun 
Published: July 2020

SUMMARYHow anti-cancer immunity shapes early carcinogenesis of lung adenocarcinoma (ADC) is unknown. We characterized immune contexture of invasive lung ADC and its precursors by transcriptomic immune profiling, T cell receptor (TCR) sequencing and multiplex immunofluorescence. Our results demonstrated that anti-tumor immunity evolved as a continuum from lung preneoplasia, to preinvasive ADC, minimally-invasive ADC and frankly invasive lung ADC with a gradually less effective and more intensely regulated immune response including down-regulation of immune-activation pathways, up-regulation of immunosuppressive pathways, higher infiltration of CD4+ T cells, lower infiltration of CD8+ T cells, decreased T cell clonality, and lower frequencies of top T cell clones in later stages. Driver mutations, HLA loss, chromosomal copy number aberrations and DNA methylation changes may collectively impinge host immune responses and facilitate immune evasion as a potential mechanism underlying outgrowth of the most fit subclones in preneoplasia into dominant clones in invasive ADC.SIGNIFICANCEThere has been a drastic increase in the detection of lung nodules, many of which are lung ADC precursors. The management of these lung nodules is controversial. We discovered that immune activation and evasion have started at preneoplastic stage and lung ADC precursors may exhibit an overall better-preserved anti-tumor immune contexture suggesting therapeutic strategies reprograming the immune microenvironment in patients with lung ADC precursors prior to further immunosuppression in invasive lung cancers may be beneficial. These findings have served as the critical scientific rationale for our immunoprevention clinical trial IMPRINT-Lung (NCT03634241) recruiting individuals diagnosed with lung nodules at high risk developing invasive lung cancers.
The effectiveness of acupuncture point stimulation for the prevention of post-operative sore throat: a meta-analysis
Authors: Jau Pin-Yu , Chang Shang-Chih 
Published: July 2020

ABSTRACTBackgroundEnhanced recovery pathways can be further improved for postoperative sore throat (POST) which usually occurs after surgery with general anesthesia. Medications have shown some effectiveness in treating and preventing POST, but acupuncture or related techniques with better safety and less cost likely can be used as an alternative or adjuvant therapy to treat perioperative symptoms by stimulating acupuncture point (acupoint). Therefore, we aim to conduct a meta-analysis to assess whether acupoint stimulation help patients prevent or treat POST in adults undergoing tracheal intubation for general anesthesia.MethodsPublication in PubMed, the Cochrane Central Register, ScienceDirect, and ClinicalTrial.gov were surveyed from Jan. 2000 through Jan. 2020. Studies that compared intervention between point stimulation and none or sham point stimulation, were included. Primary outcomes were the incidence and severity of POST at 24h. Secondary outcomes were the incidence of postoperative nausea and vomiting, choking cough, and sputum.ResultsThree randomized control trials and one comparative study involving 1358 participants were included. Compared with control, acupoint stimulation was associated with a reduced incidence (risk ratio, 0.3; 95% confidence interval (CI), 0.2–0.45; p < 0.001) and severity (standardized mean difference, −2.21; 95% CI, −2.67 to −1.76; p < 0.001) of POST. Secondary outcomes are also in favor of acupoint stimulation. There were no significant adverse events related to acupoint stimulation. Subgroup, the sensitivity, and the trial sequence analyses confirmed that the finding for POST was adequate.ConclusionsAcupoint stimulation with various methods may reduce the occurrence of POST. It could be considered as one of nonpharmacological ways to prevent POST in enhanced recovery pathways. Further rigorous studies are needed to determine the effectiveness of acupoint stimulation.QuestionCan acupoint stimulation prevent postoperative sore throat after tracheal intubation?FindingsAcupoint stimulation by acupuncture or related techniques more significantly reduces the incidence and the severity of postoperative sore throat than non- /sham-treatment at 24 hours.MeaningAcupoint stimulation by acupuncture or related techniques could be an effective, nonpharmacological approach to prevent postoperative sore throat in enhanced recovery after tracheal intubation.
The Association of Serum Lipid and Lipoprotein Levels with Total and Differential Leukocyte Counts: Results of a Cross-sectional and Longitudinal Analysis of the UK Biobank
Authors: Tucker Bradley , Sawant Sonia , McDonald Hannah , Rye Kerry-Anne , Patel Sanjay , Ong Kwok Leung , Cochran Blake J 
Published: July 2020

AbstractBackground and aimsThere is some evidence of a cross-sectional, and possibly causal, relationship of lipid levels with leukocyte counts in mice and humans. This study investigates the cross-sectional and longitudinal relationship of blood lipid and lipoprotein levels with leukocyte counts in the UK Biobank cohort.MethodsThe primary cross-sectional analysis included 417,132 participants with valid data on lipid measures and leukocyte counts. A subgroup analysis was performed in 333,668 participants with valid data on lipoprotein(a). The longitudinal analysis included 9,058 participants with valid baseline and follow-up data on lipid and lipoprotein levels and leukocyte counts. The association of lipid and lipoprotein levels with leukocyte counts was analysed by multivariable linear regression.ResultsSeveral relationships were significant in both cross-sectional and longitudinal analysis. After adjustment for demographic, socioeconomic and other confounding factors a higher eosinophil count was associated with lower HDL cholesterol and apolipoproteinA-I concentration (p<0.001). Higher triglycerides levels were associated with higher total leukocyte, basophil, eosinophil, monocyte and neutrophil counts (all p<0.01). A higher lymphocyte count was associated with a higher apolipoprotein B level (p<0.001). In the longitudinal analysis lipoprotein(a) was inversely associated with basophil count in men but not women (p<0.001).ConclusionTriglyceride levels demonstrate a robust positive association with total and differential leukocyte counts suggesting they may be directly involved in leuokogenesis. However, unlike in murine models, the remainder of these relationships are modest which suggests that cholesterol and lipoproteins are minimally involved in leukogenesis in humans.