bluuebunny/crossref_metadata_2025_split huggingface dataset:
Performance of the 2019 ACR/EULAR classification criteria for IgG4-related disease and clinical phenotypes in a Spanish multicentre registry (REERIGG4)
Authors: Fernández-Codina Andreu , Pinilla Blanca , Pinal-Fernández Iago , Carballo Iago , Feijoo-Massó Carlos , Toledano-Macías María , de Miguel-Campo Borja , Fonseca-Aizpuru Eva , Sáez-Comet Luis , López-Dupla Miguel , Hernández-Rodríguez José , Martínez-Valle Fernando 
Published: April 2020

Abstract

Objectives
Several IgG4-related disease (IgG4-RD) phenotypes have been proposed and the first set of classification criteria have been recently created. Our objectives were to assess the phenotype distribution and the performance of the classification criteria in Spanish patients as genetic and geographical differences may exist.

Methods
We performed a cross-sectional multicentre study (Registro Español de Enfermedad Relacionada con la IgG4, REERIGG4) with nine participating centres from Spain. Patients were recruited from November 2013 to December 2018. The 2019 American College of Rheumatology/European League Against Rheumatism classification criteria (AECC) were used.

Results
We included 105 patients; 88% had Caucasian ethnicity. On diagnosis, 86% met the international pathology consensus while 92% met the Japanese comprehensive criteria. The phenotype distribution was head and neck 25%, Mikulicz and systemic (MS) 20%, pancreato-hepato-biliary (PHB) 13%, retroperitoneal and aorta (RA) 26%. Sixteen per cent had an undefined phenotype. Seventy-seven per cent of the cases met the AECC. From the 24 patients not meeting the AECC, 33% met exclusion criteria, and 67% did not get a score ≥20 points. Incomplete pathology reports were associated to failure to meet the AECC.

Conclusions
The PHB phenotype was rare among Spanish IgG4-RD patients. The MS phenotype was less frequent and the RA phenotype was more prevalent than in other, Asian patient series. An undefined phenotype should be considered as some patients do not fall into any of the categories. Three quarters of the cases met the 2019 AECC. Incomplete pathology reports were the leading causes of failure to meet the criteria.
Association Between Childhood Green Space, Genetic Liability, and the Incidence of Schizophrenia
Authors: Engemann Kristine , Pedersen Carsten Bøcker , Agerbo Esben , Arge Lars , Børglum Anders Dupont , Erikstrup Christian , Hertel Ole , Hougaard David Michael , McGrath John J , Mors Ole , Mortensen Preben Bo , Nordentoft Merete , Sabel Clive Eric , Sigsgaard Torben , Tsirogiannis Constantinos , Vilhjálmsson Bjarni Jóhann , Werge Thomas , Svenning Jens-Christian , Horsdal Henriette Thisted 
Published: April 2020

AbstractChildhood exposure to green space has previously been associated with lower risk of developing schizophrenia later in life. It is unclear whether this association is mediated by genetic liability or whether the 2 risk factors work additively. Here, we investigate possible gene–environment associations with the hazard ratio (HR) of schizophrenia by combining (1) an estimate of childhood exposure to residential-level green space based on the normalized difference vegetation index (NDVI) from Landsat satellite images, with (2) genetic liability estimates based on polygenic risk scores for 19 746 genotyped individuals from the Danish iPSYCH sample. We used information from the Danish registers of health, residential address, and socioeconomic status to adjust HR estimates for established confounders, ie, parents’ socioeconomic status, and family history of mental illness. The adjusted HRs show that growing up surrounded by the highest compared to the lowest decile of NDVI was associated with a 0.52-fold (95% confidence interval [CI]: 0.40 to 0.66) lower schizophrenia risk, and children with the highest polygenic risk score had a 1.24-fold (95% CI: 1.18 to 1.30) higher schizophrenia risk. We found that NDVI explained 1.45% (95% CI: 1.07 to 1.90) of the variance on the liability scale, while polygenic risk score for schizophrenia explained 1.01% (95% CI: 0.77 to 1.46). Together they explained 2.40% (95% CI: 1.99 to 3.07) with no indication of a gene–environment interaction (P = .29). Our results suggest that risk of schizophrenia is associated additively with green space exposure and genetic liability, and provide no support for an environment-gene interaction between NDVI and schizophrenia.
Adaptive Estimation for Epidemic Renewal and Phylogenetic Skyline Models
Authors: Parag Kris V , Donnelly Christl A 
Published: April 2020

AbstractEstimating temporal changes in a target population from phylogenetic or count data is an important problem in ecology and epidemiology. Reliable estimates can provide key insights into the climatic and biological drivers influencing the diversity or structure of that population and evidence hypotheses concerning its future growth or decline. In infectious disease applications, the individuals infected across an epidemic form the target population. The renewal model estimates the effective reproduction number, R, of the epidemic from counts of observed incident cases. The skyline model infers the effective population size, N, underlying a phylogeny of sequences sampled from that epidemic. Practically, R measures ongoing epidemic growth while N informs on historical caseload. While both models solve distinct problems, the reliability of their estimates depends on p-dimensional piecewise-constant functions. If p is misspecified, the model might underfit significant changes or overfit noise and promote a spurious understanding of the epidemic, which might misguide intervention policies or misinform forecasts. Surprisingly, no transparent yet principled approach for optimizing p exists. Usually, p is heuristically set, or obscurely controlled via complex algorithms. We present a computable and interpretable p-selection method based on the minimum description length (MDL) formalism of information theory. Unlike many standard model selection techniques, MDL accounts for the additional statistical complexity induced by how parameters interact. As a result, our method optimizes p so that R and N estimates properly and meaningfully adapt to available data. It also outperforms comparable Akaike and Bayesian information criteria on several classification problems, given minimal knowledge of the parameter space, and exposes statistical similarities among renewal, skyline, and other models in biology. Rigorous and interpretable model selection is necessary if trustworthy and justifiable conclusions are to be drawn from piecewise models. [Coalescent processes; epidemiology; information theory; model selection; phylodynamics; renewal models; skyline plots]
BDNF‐Induced Arc Expression Was Enhanced by PIC in Neuronal Cells Treated with High Glucose and Amyloid Beta
Authors: CHA HEEYUN , Kim Se Lin , Heo Sumin , Park Sol Been , Han Yeo Gyeong , Yang Soo Jin 
Published: April 2020

ObjectivesHyperglycemia has been shown to be associated with Alzheimer’s disease and impairment of cognitive function. Alzheimer’s disease is characterized by the excessive formation of amyloid‐beta (Aβ) and neurofibrillary tangle. Aβ is generated by cutting amyloid precursor protein (APP) by β‐secretase (BACE1) and γ‐secretase. Brain‐derived neurotrophic factor (BDNF) is the important molecule that is involved in synaptic plasticity and neuronal survival. BDNF binds to trkB receptor and activates PI3K/Akt/mTOR pathway, and it increases synaptic efficacy by inducing expression of activity‐regulated cytoskeleton‐associated protein (Arc) which is the marker of plastic changes of the brain. Suppression of BDNF is related to the pathogenesis of Alzheimer’s disease. Piceatannol (PIC) is a polyphenolic compound that has similar structure to resveratrol having neuroprotective efficacy. Thus, we investigated the effects of PIC treatment on amyloidogenesis and BDNF signaling in neuronal cells treated with high glucose and Aβ.MethodsThe SH‐SY5Y cells were treated with 25 mM D‐glucose and 10 μM Aβ in order to induce the cell culture model of high glucose‐induced Alzheimer’s disease. And then, cells were treated with 20 μM PIC for 24 h. Relative gene expression levels of amyloidogenesis‐ and BDNF signaling‐related markers were analyzed. Aβ concentrations were measured by ELISA to examine whether PIC alters the levels of Aβ deposit. One‐way analysis of variance (ANOVA) was performed to assign statistical significance followed by Fisher’s Least Significant Difference (LSD) post‐hoc analysis using SPSS software (IBM SPSS Statistics 24).ResultsIn the condition of high glucose‐induced Alzheimer’s disease, PIC treatment significantly increased the relative gene expression of BACE1 (P = 0.003). The presenilin 1 expression tended to rise up by PIC in this condition. The concentrations of Aβ were significantly lower in cells treated with high glucose, Aβ, and PIC compared with those without PIC (P < 0.001). The relative expression levels of BDNF in high glucose group treated with PIC tended to be higher than those without PIC. PIC treatment significantly increased the relative gene expression of BDNF in cells treated with high glucose and Aβ (P = 0.002). The Arc expression was also significantly increased by PIC in those cells (P = 0.038).ConclusionsWe found that PIC improves the pathological alterations by high glucose and Aβ, which is accompanied by decreased Aβ formation and upregulation of BDNF and Arc expressions in high glucose and Aβ‐treated neuronal cells. Therefore, PIC may have a therapeutic effect on the pathological conditions of hyperglycemia‐induced Alzheimer’s disease.
Student Attention in the Modern Classroom: An Eye‐Tracking Field Study
Authors: Santiago Kevin , Wilson Timothy D. 
Published: April 2020

BackgroundMultitasking, commonly perceived to be a method of increasing productivity and maximizing time, is increasingly commonplace among student populations. However, considering recent work examining split attention and the cognitive demands of multitasking behaviour, multitasking is negatively associated with several key learning outcomes in laboratory environments such as information retention, comprehension and academic performance. To better characterize multitasking behaviours in modern classrooms, a field study was conducted using self‐reported student data coupled with gaze behaviour on attention during lectures. Specifically, this study contrasts graduate (GS) and undergraduate (UGS) students’ self‐assessments to in‐class attention to explore whether students are self‐aware of multitasking behaviours.MethodsAn online questionnaire was developed and distributed to a large mixed didactic anatomy class of GS and UGS. The survey was an amalgamation of three validated questionnaires, Media Use Questionnaire, Media Multitasking Class Index (MMCI), and the Attitudes Scale towards multitasking behaviours. In addition, a subset of students (GS & UGS) wore a single‐eye gaze tracking device during 2 lectures (Arrington Research Viewpoint) throughout the fall term. Students’ (n=4) visual fields were characterized as an index of attention to On‐task (course‐related) and Off‐task (non‐course related) activities. The gaze‐tracked location and duration of multitasking activities were identified off‐line and normalized to a percentage of class time to characterize the extent to which students engage in On‐ and Off‐task activities during lecture.ResultsInitial analysis of the MMCI survey section (n=105) indicates GS (n=69) estimated spending 7% less class time on on‐task activities than UGS (n=36) (74±0.2 vs 81±0.1, p < 0.02). Gaze tracking indicates GS (n=1) spent 37% more time engaging in multitasking (off‐task) behaviours than UGS (n=3) (45% vs 8% respectively). The UGS MMCI off‐task behaviours compared to that cohort’s gaze tracking suggests students estimate their multitasking behaviours accurately in the classroom (7±0.1% vs 8±0.0%). Through further analysis of attentional time dedicated to on‐task activities (75±0.0%), students largely focused on their notes (54±0.1%), multimedia presentation (11±0.1%), and then the professor (0.4±0.0%) of total class time. Of the time spent in off‐task activities (8±0.0%), distractors to attention included activities such as doodling, adjusting clothes and observing neighbours (7±0.0%), text messaging (0.3±0.0%), and consuming food and/or liquids (0.3±0.0%).This is the first field study of this kind indicating how multitasking is a part of student behaviour and how attention is allocated in the modern anatomy lecture hall through gaze‐tracking. As midterm grades become available, we will correlate both real and perceived behaviours to class performance.
Peripherally Restricted Dual Cannabinoid Receptor Agonist Modifies Mitochondrial Signaling and Inhibits Atrial Electrical Remodeling in a Tachypaced Ex Vivo Rat Model
Authors: Lee Danielle I. , Murninkas Michael , Elyagon Sigal , Etzion Yoram , Anderson Hope D. 
Published: April 2020

Atrial fibrillation (AF) leads to rate‐dependent changes, which progressively increase the risk for recurrence and persistence of the arrhythmia (collectively defined as atrial remodelling). Atrial effective refractory period (AERP) shortening and conduction velocity prolongation are hallmarks of atrial remodelling markedly promoting AF substrate. The molecular mechanisms underlying atrial remodelling are not fully elucidated and therapeutic strategies to reduce AF burden by preventing atrial remodelling are not yet available. Cannabinoid (CB) receptor ligands exert cardioprotective effects. We hypothesized that CB13, a peripherally restricted dual CB receptor agonist with limited brain penetration, would reduce atrial remodelling.Sprague Dawley (SD) rat hearts were excised and hung on a Langendorff set‐up, and supplemented with CB13 (1μM) or without (control) (paced and non‐paced). Coronary pressure of 60–80 mmHg was maintained. Electrophysiological (EP) parameters were measured by placing a mini‐hook platinum‐iridium quadrupole electrode on the right atrium (RA) for pacing and atrial recording (CB13 n=8; control n=8). RA were tachypaced for 90 min at double diastolic threshold and a cycle length of 5 ms higher than failed 1:1 atrial capture. S1S2 stimulation protocol was used to measure AERP, defined as the longest interval with failed 1:1 capture. The effects of CB13 on atrial refractoriness and AF substrate were assessed by analysis of high resolution electrogram recordings and protein expression via western blot.Post‐tachypacing EP recordings showed reduced AERP in control compared to pre‐tachypacing (54.38±3.05 vs. 44.75±3.67 ms; p<0.01). AERP post‐tachypacing in CB13‐treated hearts remained unchanged compared to pre‐tachypacing (55.25±3.46 vs. 55.50±2.67 ms; ns). Thus, CB13‐treatment resulted in preservation of AERP compared to control (103.6±9.2 vs. 82.3±4.4 % of baseline; p<0.05). Protein expression of PGC1α was significantly increased by CB13 compared to controls (paced and non‐paced). Upregulation of mitochondrial biogenesis may be related to increased phosphorylation of AMPKα at residue threonine 172 (compared to total AMPKα, p=0.12, CB13 vs. control paced). Furthermore, gap junction connexin 43 was significantly downregulated in paced controls vs. non‐paced controls, while CB13 remained upregulated (no significance vs. controls).CB13 exposure during tachypacing prevents AERP reduction and gap junction downregulation probably through mechanisms involving mitochondrial biogenesis. Thus, by inhibiting atrial remodeling CB13 and the subsequent activation of CB receptors may be a viable treatment strategy for AF.Support or Funding InformationThis work was supported by studentships from the Canadian Institutes of Health Research and Mitacs (D.L.)
Characterization of Collagen Metabolism in Normal and Chronic Obstructive Pulmonary Diseased Human Lung Fibroblasts Reared in Serum‐free Medium
Authors: Otto Ashley Maria , Mattioli Patrisia , Musiol Joseph , Popper Hannah , Graham Morgan , Laird Patrick , Maloney Trevor J. , Geary Kyla , Daghigh Farzaneh , Borghaei Ruth , D’Angelo Marina 
Published: April 2020

The structural integrity of the human lung is maintained by a healthy extracellular matrix (ECM). One of the main components, collagen type I is produced by fibroblasts and provides strength and structure to the cells and the function of the lung. A careful balance of collagen degradation and production is controlled by matrix metalloproteases (MMPs). In diseased states such as Chronic Obstructive Pulmonary Disease (COPD), two collagenases, MMP‐8 and MMP‐12, are upregulated. In this study we measure collagen metabolism of human lung fibroblasts (HLFs) reared in serum‐free media (subconfluent normal (NHLF) and COPD diseased (DHLF)). Commercially available early passage human lung fibroblasts established from lung tissue, obtained during biopsy, were cultured and passaged in our laboratory through P4 and P5 for both the NHLF and DHLF. Both normal and diseased HLF cells were viable when cultured at subconfluence for 24 hours in serum free medium. They produced detectable quantities of intact collagen type I secreted and incorporated in the ECM. The amount of intact collagen decreased between passage 4 and 5 (p<0.01) in both cell types indicating there is a limit to the passages that can be utilized to measure ECM alterations. Degraded collagen type I was present in the cell layer fractions of both cell types, but was 10 fold higher in the cell layer of diseased HLF cells. This indicates that the expected ECM profile of diseased HLF can be demonstrated in serum‐free culture. Both cell types produced detectable levels of MMP‐8 and MMP‐12 collagenases. In this study we have demonstrated that normal and diseased HLF can be cultured in serum‐free conditions while maintaining their metabolic profile. The production of MMPs and collagens provides an experimental system in which we can test potential therapeutics that may alter the fibrotic response during COPD.Support or Funding InformationThis work is supported by a grant from the PCOM Alumni and the Division of Research at PCOM.
Impaired Female Reproductive Function in A Novel Estrogen Receptor Alpha Hypomorphic Mouse Model
Authors: Saito Kenji , Rodeghiero Samuel R. , Dickey Jacob E. , Paradee William J. , Cui Huxing 
Published: April 2020

IntroductionEstrogen signaling plays an important role in the regulation of both energy homeostasis and reproductive function. Human and animal studies indicate that the metabolic actions of estrogen signaling are primarily mediated by estrogen receptor alpha (ERα). Both human and mouse ERα genes show remarkable heterogeneity due to complicated alternative splicing, which results in a wide variety of variant transcripts with different protein products or a common protein. However, functional significance of this ERα genomic complexity has not been well documented. Here we generated a novel mouse model in which ERα expression was differentially affected in various tissues, and examined their body weight change and reproduction.MethodUsing CRISPR/Cas9 technology, we introduced a loxP‐flanked sequence containing En2 splice acceptor, a green fluorescent marker with mitochondrial localization signal and DNA translation stop signals before the first coding exon of mouse ERα gene for the potential restoration of the ERα expression.ResultsERα protein expressions were significantly reduced in pituitary (~37%) and ovary (~67%), but not in brain, of the homozygous mutant female compared to those of controls, indicating that unknown elements important for ERα tissue‐specific expression were affected. In contrast to body weight gain observed in previous studies of ERα knockout female mice, our hypomorphic mutant females did not show significant body weight gain. On the other hand, virginal smears from the mutant females rarely showed typical estrus stage. Uterine wet weight was significantly lower in the mutant female mice compared to the controls, indicating abnormal reproductive system. Continuous mating study further confirmed delayed pregnancy and inability to have alive newborns in the mutant female mice.ConclusionEstrogen receptor alpha protein expression varies among tissues in terms of the level and pattern of splicing variants. Splicing variant‐specific ERα functions are not fully elucidated. Our results suggest that a particular variant affected in our mouse model is less critical for proper functioning of systems involved in estrogen‐regulated energy metabolism, but indispensable for some aspects of female reproductive function.
SPARC: Effect of Waveform on Kilohertz Frequency Nerve Block
Authors: Pena Edgar , Pelot Nicole A. , Grill Warren M. 
Published: April 2020

There is growing interest in delivering kilohertz frequency (KHF) electrical signals to block conduction in autonomic nerves as a therapy to treat various diseases. Previous computational modeling, preclinical, and clinical studies used multiple different KHF waveforms to achieve block of the sciatic, vagus, and pudendal nerves. However, it remains unclear how the choice of waveform affects clinically relevant nerve block parameters. To address this knowledge gap, we quantified the effects of waveform on KHF block in vivo for the rat sciatic nerve, as well as in computational models of the rat sciatic nerve and the human vagus nerve. We compared block thresholds and onset responses across KHF sinusoids and charge‐balanced rectangular waveforms with different symmetries and duty cycles.Block thresholds were strongly dependent on the waveform shape. Experimentally, symmetric rectangular waveforms with full duty cycles had lower current thresholds for block than sinusoids, but they used slightly more power at threshold. Further, lower duty cycles yielded higher block thresholds, such that the log‐transformed block thresholds increased in an approximately linear manner as duty cycle decreased. The results from computational models were consistent with the in vivo block threshold relationships, although the models underestimated the increase in threshold with decreased duty cycle.While waveform selection had a clear and distinct effect on thresholds, it did not consistently affect in vivo onset response. Onset magnitude was similar across waveforms when normalized to block threshold. We also observed a history‐dependent reduction in onset response across all waveforms, from earlier trials with larger onset responses to later trials with reduced onsets during the course of a given experiment.Waveform had substantial effects on block thresholds but not on onset response. These quantitative data inform choice of waveform in subsequent studies and clinical applications. Such an understanding of the direct effects of KHF signal parameters on neural activity will enhance its effective use in therapeutic applications and facilitate the design of KHF stimulation parameters that achieve block with minimal undesired onset responses.Support or Funding InformationNIH SPARC OT2 OD025340