bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of uric acid or IL‐1β ameliorates respiratory syncytial virus immunopathology and development of asthma
Authors: Schuler Charles F. , Malinczak Carrie‐Anne , Best Shannon K. K. , Morris Susan B. , Rasky Andrew J. , Ptaschinski Catherine , Lukacs Nicholas W. , Fonseca Wendy 
Published: April 2020

AbstractBackgroundRespiratory syncytial virus (RSV) affects most infants early in life and is associated with increased asthma risk. The specific mechanism remains unknown.ObjectiveTo investigate the role of uric acid (UA) and IL‐1β in RSV immunopathology and asthma predisposition.MethodsTracheal aspirates from human infants with and without RSV were collected and analyzed for pro‐IL‐1β mRNA and protein to establish a correlation in human disease. Neonatal mouse models of RSV were employed, wherein mice infected at 6‐7 days of life were analyzed at 8 days postinfection, 5 weeks postinfection, or after a chronic cockroach allergen asthma model. A xanthine oxidase inhibitor or IL‐1 receptor antagonist was administered during RSV infection.ResultsHuman tracheal aspirates from RSV‐infected infants showed elevated pro‐IL‐1β mRNA and protein. Inhibition of UA or IL‐1β during neonatal murine RSV infection decreased mucus production, reduced cellular infiltrates to the lung (especially ILC2s), and decreased type 2 immune responses. Inhibition of either UA or IL‐1β during RSV infection led to chronic reductions in pulmonary immune cell composition and reduced type 2 immune responses and reduced similar responses after challenge with cockroach antigen.ConclusionsInhibiting UA and IL‐1β during RSV infection ameliorates RSV immunopathology, reduces the consequences of allergen‐induced asthma, and presents new therapeutic targets to reduce early‐life viral‐induced asthma development.
A novel whole blood gene expression signature for asthma, dermatitis, and rhinitis multimorbidity in children and adolescents
Authors: Lemonnier Nathanaël , Melén Erik , Jiang Yale , Joly Stéphane , Ménard Camille , Aguilar Daniel , Acosta‐Perez Edna , Bergström Anna , Boutaoui Nadia , Bustamante Mariona , Canino Glorisa , Forno Erick , Ramon González Juan , Garcia‐Aymerich Judith , Gruzieva Olena , Guerra Stefano , Heinrich Joachim , Kull Inger , Ibarluzea Maurolagoitia Jesús , Santa‐Marina Rodriguez Loreto , Thiering Elisabeth , Wickman Magnus , Akdis Cezmi , Akdis Mübeccel , Chen Wei , Keil Thomas , Koppelman Gerard H. , Siroux Valérie , Xu Cheng‐Jian , Hainaut Pierre , Standl Marie , Sunyer Jordi , Celedón Juan C. , Maria Antó Josep , Bousquet Jean 
Published: April 2020

AbstractBackgroundAllergic diseases often occur in combination (multimorbidity). Human blood transcriptome studies have not addressed multimorbidity. Large‐scale gene expression data were combined to retrieve biomarkers and signaling pathways to disentangle allergic multimorbidity phenotypes.MethodsIntegrated transcriptomic analysis was conducted in 1233 participants with a discovery phase using gene expression data (Human Transcriptome Array 2.0) from whole blood of 786 children from three European birth cohorts (MeDALL), and a replication phase using RNA Sequencing data from an independent cohort (EVA‐PR, n = 447). Allergic diseases (asthma, atopic dermatitis, rhinitis) were considered as single disease or multimorbidity (at least two diseases), and compared with no disease.ResultsFifty genes were differentially expressed in allergic diseases. Thirty‐two were not previously described in allergy. Eight genes were consistently overexpressed in all types of multimorbidity for asthma, dermatitis, and rhinitis (CLC,EMR4P, IL5RA, FRRS1, HRH4, SLC29A1,SIGLEC8, IL1RL1). All genes were replicated the in EVA‐PR cohort. RT‐qPCR validated the overexpression of selected genes. In MeDALL, 27 genes were differentially expressed in rhinitis alone, but none was significant for asthma or dermatitis alone. The multimorbidity signature was enriched in eosinophil‐associated immune response and signal transduction. Protein‐protein interaction network analysis identified IL5/JAK/STAT and IL33/ST2/IRAK/TRAF as key signaling pathways in multimorbid diseases. Synergistic effect of multimorbidity on gene expression levels was found.ConclusionA signature of eight genes identifies multimorbidity for asthma, rhinitis, and dermatitis. Our results have clinical and mechanistic implications, and suggest that multimorbidity should be considered differently than allergic diseases occurring alone.
Two cases of successful recanalization for acute cerebral artery embolism during perioperative period of radiofrequency ablation for atrial fibrillation
Authors: Xu Jin , Li Yana , Pu Jun 
Published: April 2020

AbstractTo explore the strategy of acute cerebral artery embolism after radiofrequency catheter ablation (RFA) for atrial fibrillation (AF). Reporting two cases with acute cerebral infarction after RFA for AF. Two patients were both with AF, and intracardiac thrombus was excluded through transesophageal echocardiogram (TEE) before procedure. Approach of ablation: circumferential pulmonary vein ablation in left atrium to isolate pulmonary vein plus linear ablation in the top and bottom of left atrium (BOX procedure). They both received Dabigatran Etexilate 110 mg twice daily, starting 6 hr after ablation. Symptoms of major stroke appeared 30 hr after ablation in Case 1. Occlusion was detected in M1 segment of the left middle cerebral artery by MRI 2 hr after symptoms onset. Intravenous thrombolysis was given immediately. In Case 2, the patient presented symptoms of major stroke 34 hr after ablation and occlusion in the basilar artery was confirmed by MRI 4.5 hr after symptoms onset. Although it was beyond the thrombolysis time window, mechanical thrombectomy was taken 7 hr after the symptoms onset. The culprit artery was successfully revascularized in both cases. In Case 1, NIHSS score was reduced from 8 (before thrombolysis) to 0 (24 hr after thrombolysis). In Case 2, NIHSS score decreased from 18 (before embolectomy) to 3 (24 hr after embolectomy). Both of the patients live a normal life without brain function impairment and hemorrhage until the last follow‐up. Timely recanalization could attained a good cure effect when acute stoke was happened after RFA for AF.
Evaluating alluvial stratigraphic response to cyclic and non‐cyclic upstream forcing through process‐based alluvial architecture modelling
Authors: Wang Youwei , Storms Joep E. A. , Martinius Allard W. , Karssenberg Derek , Abels Hemmo A. 
Published: April 2020

AbstractFormation of alluvial stratigraphy is controlled by autogenic processes that mix their imprints with allogenic forcing. In some alluvial successions, sedimentary cycles have been linked to astronomically‐driven, cyclic climate changes. However, it remains challenging to define how such cyclic allogenic forcing leads to sedimentary cycles when it continuously occurs in concert with autogenic forcing. Accordingly, we evaluate the impact of cyclic and non‐cyclic upstream forcing on alluvial stratigraphy through a process‐based alluvial architecture model, the Karssenberg and Bridge (2008) model (KB08). The KB08 model depicts diffusion‐based sediment transport, erosion and deposition within a network of channel belts and associated floodplains, with river avulsion dependent on lateral floodplain gradient, flood magnitude and frequency, and stochastic components. We find cyclic alluvial stratigraphic patterns to occur when there is cyclicity in the ratio of sediment supply over water discharge (Qs/Qw ratio), in the precondition that the allogenic forcing has sufficiently large amplitudes and long, but not very long, wavelengths, depending on inherent properties of the modelled basin (e.g. basin subsidence, size, and slope). Each alluvial stratigraphic cycle consists of two phases: an aggradation phase characterized by rapid sedimentation due to frequent channel shifting and a non‐deposition phase characterized by channel belt stability and, depending on Qs/Qw amplitudes, incision. Larger Qs/Qw ratio amplitudes contribute to weaker downstream signal shredding by stochastic components in the model. Floodplain topographic differences are found to be compensated by autogenic dynamics at certain compensational timescales in fully autogenic runs, while the presence of allogenic forcing clearly impacts the compensational stacking patterns.
Five‐year safety and efficacy data from a phase Ib study of nivolumab and chemotherapy in advanced non‐small‐cell lung cancer
Authors: Kanda Shintaro , Ohe Yuichiro , Goto Yasushi , Horinouchi Hidehito , Fujiwara Yutaka , Nokihara Hiroshi , Yamamoto Noboru , Yamamoto Takanori , Tamura Tomohide 
Published: April 2020

AbstractCombination antiprogrammed death 1/programmed death‐ligand 1 Ab and platinum‐based chemotherapy is standard first‐line treatment for advanced non‐small‐cell lung cancer without targetable oncogene alterations. We describe the long‐term safety and efficacy data from a previously reported phase Ib study of nivolumab and chemotherapy. Japanese patients with non‐small‐cell lung cancer were assigned to a treatment arm based on histology and treatment history. Nivolumab (10 mg/kg, i.v.) and chemotherapy (4 arms) were given every 3 weeks: arm A, 4 cycles of cisplatin and gemcitabine (first‐line); arm B, 4 cycles of cisplatin and pemetrexed followed by pemetrexed maintenance therapy (first‐line); arm C, 4‐6 cycles of carboplatin, paclitaxel, and bevacizumab followed by bevacizumab (first‐line); and arm D, docetaxel (second‐ or third‐line). Study treatments were continued every 3 weeks as maintenance therapy until disease progression. Minimum follow‐up period was 57.9 months. Median progression‐free survival (median [range, plus sign indicates censored data]) was 6.3 (0.7+‐47.8), 11.8 (1.4‐65.1+), 40.7 (5.3‐60.8+), and 3.2 (1.9‐10.9) months, and 5‐year progression‐free survival was observed in 0/6, 1/6, 1/6, and 0/6 patients in arms A, B, C, and D, respectively. Median overall survival was 13.2 (11.0‐55.4), 28.5 (14.6‐66.2+), not reached (24.2‐67.4+), and 12.5 (9.8‐16.9) months; the number of patients surviving 5 years were 0/6, 1/6, 4/6, and 0/6 in arms A, B, C, and D, respectively. No unexpected severe adverse events or treatment‐related deaths occurred. Nivolumab and platinum‐based chemotherapy combinations showed long‐term tolerability. A moderate proportion of patients in arm C showed 5‐year progression‐free and overall survival.
Monocyte-derived dendritic cells display a highly activated phenotype and altered function in patients with familial Mediterranean fever
Authors: Funk T , Fuchs A R , Altdörfer V S , Klein R , Autenrieth S E , Müller M R , Salih H R , Henes J , Grünebach F , Dörfel D 
Published: April 2020

Summary
Dendritic cells (DCs) are sentinels of the immune system that bridge innate and adaptive immunity. By capturing antigens in peripheral tissue, processing and presenting them with concurrent expression of co-stimulatory molecules and cytokine secretion they control and modulate immune reactions. Through pattern recognition receptors, DCs sense molecules that are associated with infection or tissue damage, frequently resulting in the formation of inflammasomes upon intracellular stimulation. The inherited autoinflammatory familial Mediterranean fever (FMF) is associated with deregulated activity of the pyrin inflammasome leading to acute inflammatory episodes. However, differentiation and function of DCs in this disease are as yet unclear. Therefore, we first determined DC subpopulation frequency in peripheral blood of a cohort of FMF patients. Joint evaluation without classification according to specific patient characteristics, such as mutational status, did not disclose significant differences compared to healthy controls. For the further examination of phenotype and function, we used immature and mature monocyte-derived DCs (imMo-DCs, mMo-DCs) that were generated in vitro from FMF patients. Immunophenotypical analysis of imMo-DCs revealed a significantly elevated expression of CD83, CD86 and human leukocyte antigen D-related (HLA-DR) as well as a significant down-regulation of CD206, CD209 and glycoprotein NMB (GPNMB) in our FMF patient group. Furthermore, FMF imMo-DCs presented a significantly higher capacity to migrate and to stimulate the proliferation of unmatched allogeneic T cells. Finally, the transition towards a more mature, and therefore activated, phenotype was additionally reinforced by the fact that peripheral blood DC populations in FMF patients exhibited significantly increased expression of the co-stimulatory molecule CD86.
Diagnostic revisions in multiple sclerosis
Authors: de Seabra Mafalda M. L. , Abreu Pedro M. P. , Mendonça Maria T. S. , Reis Joaquim J. C. S. , Sá Maria J. P. M. , Guimarães Ferreira Almeida Joana C. 
Published: April 2020

AbstractObjectivesThe diagnostic criteria for inflammatory demyelinating diseases of the central nervous system have evolved over the past years. Close follow up and accurate multiple sclerosis (MS) diagnosis are key to optimal treatment. We retrospectively reviewed the patients who had a diagnostic revision.MethodsThe medical records of patients referred to our MS clinic (Centro Hospitalar Universitário de São João, Porto, Portugal) (n = 635) between 2009 and 2016 were reviewed. A total of 62 patients were identified, 44 were misdiagnosed with MS; 18 had another diagnosis, later redefined as MS. A total of 44 controls (with MS diagnosis) were matched to the 44 misdiagnosed cases, and a statistical analysis was carried out to determine the predictors of misdiagnosis.ResultsThe mean age of our population (n = 44) was 51 ± 11 years; 77% were women. The mean duration of misdiagnosis was 13 years. Optic neuritis was the most frequent presenting symptom (25%), followed by spinal cord syndrome and non‐specific neurological symptoms (20% each). The most frequent MS misdiagnoses were non‐specific white matter hyperintensities, optic neuritis and cerebrovascular disease. The mean Extended Disability Status Scale and Multiple Sclerosis Severity Score was 0 (SD 2) and 0.6 (SD 2), respectively, in the misdiagnosed group, and 3.5 (SD 5.4) and 3.2 (SD 5.6), respectively, in the control group. From all the variables analyzed, we found that the presence of black holes and spinal cord lesions were predictors of a correct MS diagnosis (P < 0,05).ConclusionsOur series underlines the need to continuously rethink an MS diagnosis and to thoughtfully use paraclinical tests (oligoclonal bands and magnetic resonance imaging) avoiding an unfounded diagnosis. The first event might not be atypical, as has been reported in other series.
Perspectives on area‐based conservation and its meaning for future biodiversity policy
Authors: Bhola Nina , Klimmek Helen , Kingston Naomi , Burgess Neil D. , van Soesbergen Arnout , Corrigan Colleen , Harrison Jerry , Kok Marcel T. J. 
Published: April 2020

AbstractDuring 2021, Parties to the Convention on Biological Diversity (CBD) are expected to meet in Kunming, China, to agree on a new global biodiversity framework aimed at halting and reversing biodiversity loss, encouraging the sustainable use of biodiversity, and ensuring the equitable sharing of its benefits. As the post‐2020 global biodiversity framework evolves, parties to the convention are being exposed to a range of perspectives on the conservation and sustainable use of biodiversity, relating to the future framework as a whole or to aspects of it. Area‐based conservation measures are one such aspect, and there are diverse perspectives on how new targets might be framed in relation to these measures. These perspectives represent different outlooks on the relationship between human and nonhuman life on Earth. However, in most cases there is a lack of clarity on how they would be implemented in practice, the implications this would have for biodiversity and human well‐being, and how they would contribute to achieving the 2050 Vision for Biodiversity of “living in harmony with nature.” We sought to clarify these issues by summarizing some of these perspectives in relation to the future of area‐based biodiversity conservation. We identified these perspectives through a review of the literature and expert consultation workshops and compiled them into 4 main groups: Aichi+, ambitious area‐based conservation perspectives, new conservation, and whole‐earth conservation. We found that although the perspectives Aichi+ and whole earth are in some cases at odds with one another, they also have commonalities, and all perspectives have elements that can contribute to developing and implementing the post‐2020 global biodiversity framework and achieving the longer term CBD 2050 Vision.
Diagnostic accuracy of computed tomography colonography in patients at high risk for colorectal cancer: a meta‐analysis
Authors: Bai W. , Yu D. , Zhu B. , Yu X. , Duan R. , Li Y. , Yu W. , Hua W. , Kou C. 
Published: April 2020

AbstractAimThe aim was to explore the diagnostic value of computed tomographic colonography (CTC) compared with conventional colonoscopy in individuals at high risk for colorectal cancer.MethodPubMed, Embase, the Cochrane Library and the Web of Science were searched by two independent reviewers for potentially eligible studies published up to 31 October 2018 that were based on a per‐patient analysis. stata, meta‐disc and revman were used to perform this meta‐analysis. A random‐effect model was used, and a subgroup analysis was conducted to explore the sources of heterogeneity.ResultsA total of 14 full‐text articles, involving 3578 patients, were included in this meta‐analysis. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and the area under the summary receiver operating characteristic curve of CTC for detecting polyps ≥ 6 mm were 0.87 (95% CI 0.83–0.90), 0.90 (95% CI 0.86–0.93), 9.08 (95% CI 6.28–13.13), 0.14 (95% CI 0.11–0.18) and 0.94 (95% CI 0.92–0.96), respectively. For polyps ≥ 10 mm, the pooled sensitivity, specificity, positive likelihood ratio and negative likelihood ratio of CTC were 0.91 (95% CI 0.86–0.94), 0.98 (95% CI 0.95–0.99), 40.36 (95% CI 19.16–85.03), 0.90 (95% CI 0.06–0.14) and 0.98 (95% CI 0.96–0.99), respectively.ConclusionIn this meta‐analysis, CTC had high diagnostic accuracy for detecting polyps ≥ 6 mm and ≥ 10 mm in patients at high risk of developing colorectal cancer and it had a higher sensitivity and specificity for detecting polyps ≥ 10 mm than polyps ≥ 6 mm. However, the results should be used cautiously due to the significant heterogeneity.
Modeling early stages of endoderm development in epiblast stem cell aggregates with supply of extracellular matrices
Authors: Inamori Sachiko , Fujii Mai , Satake Sayaka , Iida Hideaki , Teramoto Machiko , Sumi Tomoyuki , Meno Chikara , Ishii Yasuo , Kondoh Hisato 
Published: April 2020

AbstractEndoderm precursors expressing FoxA2 and Sox17 develop from the epiblast through the gastrulation process. In this study, we developed an experimental system to model the endoderm‐generating gastrulation process using epiblast stem cells (EpiSCs). To this end, we established an EpiSC line i22, in which enhanced green fluorescent protein is coexpressed with Foxa2. Culturing i22 EpiSCs as aggregates for a few days was sufficient to initiate Foxa2 expression, and further culturing of the aggregates in Matrigel promoted the sequential activation of transcription factor genes involved in endoderm precursor development, e.g., Eomes, Gsc, and Sox17. In aggregation culture of i22 cells for 3 days, all cells expressed POU5F1, SOX2, and E‐cadherin, a signature of the epiblast, whereas expression of GATA4 and SOX17 was also activated moderately in dispersed cells, suggesting priming of these cells to endodermal development. Embedding the aggregates in Matrigel for further 3 days elicited migration of the cells into the lumen of laminin‐rich matrices covering the aggregates, in which FOXA2 and SOX17 were expressed at a high level with the concomitant loss of E‐cadherin, indicating the migratory phase of endodermal precursors. Prolonged culturing of the aggregates generated three segregating cell populations found in post‐gastrulation stage embryos: (1) definitive endoderm co‐expressing high SOX17, GATA4, and E‐cadherin, (2) mesodermal cells expressing a low level of GATA4 and lacking E‐cadherin, and (3) primed epiblast cells expressing POU5F1, SOX2 without E‐cadherin. Thus, aggregation of EpiSCs followed by embedding of aggregates in the laminin‐rich matrix models the gastrulation‐dependent endoderm precursor development.
Body maps in the infant brain: implications for neurodevelopmental disabilities
Authors: Marshall Peter J , Meltzoff Andrew N 
Published: April 2020

This review and synthesis discusses recent work that has utilized brain imaging methods, such as the electroencephalogram (EEG) and magnetoencephalogram, to provide insights into the ways that the body is represented in the infant brain. One aspect of body representation concerns somatotopic maps of the body surface in somatosensory cortex. A good deal is known about the properties of these maps in adults, but there has been relatively little developmental work. Recent studies have provided new insights into the organization of infant neural body maps and have laid the foundations for examining their plasticity in relation to behavioral development. Other work has suggested that neural body maps may be involved in the registration of correspondences between self and other, with implications for early social development. Here, body representations are discussed in the context of preterm birth and autism spectrum disorder, providing novel perspectives relevant to developmental medicine and child neurology.What this paper adds

Somatotopic body maps develop prenatally through intrinsic and activity‐dependent mechanisms.

There is increasing interest in understanding postnatal plasticity in body maps.

Body representations may be involved in the registration of preverbal, interpersonal relationships.
Paediatric‐onset hereditary spastic paraplegias: a retrospective cohort study
Authors: Schiavoni Silvia , Spagnoli Carlotta , Rizzi Susanna , Salerno Grazia G , Frattini Daniele , Pisani Francesco , Fusco Carlo 
Published: April 2020

AimTo describe the clinical and neurogenetic spectrum of paediatric‐onset hereditary spastic paraplegias (HSPs) diagnosed in our unit.MethodWe report on 47 patients (30 males, 17 females; mean [SD] age 12y 7mo [6y 2mo], range 4–34y) clinically diagnosed with an HSP at the Child Neurology Unit, IRCCS‐ASMN (Reggio Emilia, Italy) between 1990 and 2018, who were genetically investigated by means of single‐gene direct sequencing and/or next‐generation sequencing technologies (targeted panels, whole‐exome sequencing [WES]).ResultsComplex forms prevailed slightly (n=26), autosomal dominant being the main inheritance pattern (n=11), followed by recessive (n=5) and X‐linked (n=1). A definite genetic diagnosis was achieved in 17 patients. Spastic paraplegia 3A (n=4) was the most frequent cause of autosomal dominant HSP in our cohort, while no genetic variant prevailed in autosomal recessive forms and pathogenic/likely pathogenic variants were disclosed in a wide range of different genes.InterpretationWe found wide phenotypic and genetic heterogeneity. With increasing accessibility to WES, a higher number of patients receive a diagnosis, allowing detection of variants in ultra‐rare disease‐causing genes and refining genotype–phenotype correlations.What this paper adds

A genetic diagnosis of paediatric‐onset hereditary spastic paraplegia was achieved in one‐third of patients.

Pathogenic/likely pathogenic variants in rare genes were found.

Genotypic and phenotypic heterogeneity favours targeted panel/whole‐exome sequencing for diagnosis.