bluuebunny/crossref_metadata_2025 huggingface dataset:
Budesonide Oral Suspension Significantly Improves Eosinophilic Esophagitis Histology Scoring System Results
Authors: Collins Margaret H. , Dellon Evan S. , Katzka David A. , Hirano Ikuo , Williams James , Lan Lan
Published: September 2019

Budesonide oral suspension (BOS) is a novel topical corticosteroid, which has been shown to improve symptoms and endoscopic appearance, and reduce peak eosinophil counts in patients with eosinophilic esophagitis (EoE). This trial evaluated the effect of BOS or placebo on the severity (grade) and extent (stage) of 8 histopathologic features observed in EoE, using the validated eosinophilic esophagitis histologic scoring system (EoE HSS). Patients with EoE aged 11 to 40 years with dysphagia were randomized to receive either BOS (2.0 mg twice daily) or placebo for 12 weeks. Mean (SD) EoE HSS grade and stage total scores at baseline for placebo and BOS groups were: grade, 0.42 (0.16) and 0.49 (0.14), respectively; stage: 0.38 (0.14) and 0.46 (0.11), respectively. These scores significantly decreased (improved) from baseline for patients receiving BOS versus placebo (grade: least squares mean change [SE]: placebo vs. BOS, −0.04 [0.03] vs. −0.24 [0.02]; P<0.0001; stage: −0.01 [0.02] vs. −0.19 [0.02]; P<0.0001). EoE HSS total scores improved for 6 of the 8 and 5 of the 8 histopathologic features for grade and stage, respectively, versus placebo. Change in EoE HSS total scores correlated moderately but significantly with change in endoscopic severity (endoscopic reference score; grade: R=0.5349; stage: R=0.5416; both P<0.0001). Change in EoE HSS stage total score correlated weakly with change in Dysphagia Symptom Questionnaire scores (grade: R=0.1925; P=0.0740; stage: R=0.2135; P=0.0471). These data demonstrate that the EoE HSS is a valuable endpoint of treatment response in randomized clinical trials and should be considered for future trials for EoE.
Force distribution and multiscale mechanics in the mussel byssus
Authors: Cohen Noy , Waite J. Herbert , McMeeking Robert M. , Valentine Megan T.
Published: September 2019

The byssi of sessile mussels have the extraordinary ability to adhere to various surfaces and withstand static and dynamic loadings arising from hostile environmental conditions. Many investigations aimed at understanding the unique properties of byssal thread–plaque structures have been conducted and have inspired the enhancement of fibre coatings and adhesives. However, a systems-level analysis of the mechanical performance of the composite materials is lacking. In this work, we discuss the anatomy of the byssus and the function of each of the three components (the proximal thread portion, the distal thread portion and the adhesive plaque) of its structures. We introduce a basic nonlinear system of springs that describes the contribution of each component to the overall mechanical response and use this model to approximate the elastic modulus of the distal thread portion as well as the plaque, the response of which cannot be isolated through experiment alone. We conclude with a discussion of unresolved questions, highlighting areas of opportunity where additional experimental and theoretical work is needed.

This article is part of the theme issue ‘Transdisciplinary approaches to the study of adhesion and adhesives in biological systems’.
Graph combinatorics based group-level network inference
Authors: Chen Shuo , Wu Qiong , Hong L. Elliot
Published: September 2019

We consider group-level statistical inference for networks, where outcomes are multivariate edge variables constrained in an adjacency matrix. The graph notation is used to represent a network, where nodes are identical biological units (e.g. brain regions) shared across subjects and edge-variables indicate the strengths of interactive relationships between nodes. Edge-variables vary across subjects and may be associated with covariates of interest. The statistical inference for multivariate edge-variables is challenging because both localized inference on individual edges and the joint inference of a combinatorial of edges (network-level) are desired. Different from conventional multivariate variables (e.g. omics data), the inference of a combinatorial of edges is closely linked with network topology and graph combinatorics. We propose a novel objective function with 𝓁0 norm regularization to robustly capture subgraphs/subnetworks from the whole brain connectome and thus reveal the latent network topology of phenotype-related edges. Our statistical inferential procedure and theories are constructed based on graph combinatorics. We apply the proposed approach to a brain connectome study to identify latent brain functional subnetworks that are associated with schizophrenia and verify the findings using an independent replicate data set. The results demonstrate that the proposed method achieves superior performance with remarkably increased replicability.
IL-10 Promotes Endothelial Progenitor Cell Driven Wound Neovascularization and Enhances Healing via STAT3
Authors: Balaji Swathi , Steen Emily , Wang Xinyi , Vangapandu Hima V. , Templeman Natalie , Blum Alexander J. , Moles Chad M. , Li Hui , Narmoneva Daria A. , Crombleholme Timothy M. , Butte Manish J. , Bollyky Paul L. , Keswani Sundeep G.
Published: September 2019

Evidence from prior studies of cutaneous trauma, burns, and chronic diabetic wound repair demonstrates that endothelial progenitor cells (EPCs) contribute tode novoangiogenesis, anti-inflammatory reactions, tissue regeneration, and remodeling. We have shown that IL-10, a potent anti-inflammatory cytokine, promotes regenerative tissue repair in an adult model of dermal scar formation via the regulation of fibroblast-specific hyaluronan synthesis in a STAT3 dependent manner. While it is known that IL-10 drives EPC recruitment and neovascularization after myocardial infarction, its specific mode of action, particularly in dermal wound healing and neovascularization in both control and diabetic wounds remains to be defined. Here we show that IL-10 promotes EPC recruitment into the dermal wound microenvironment to facilitate neovascularization and wound healing of control and diabetic (db/db) wounds via vascular endothelial growth factor (VEGF) and stromal-cell derived factor 1 (SDF-1α) signaling. Inducible skin-specific STAT3 knockout (KO) mice were studied to determine whether the impact of IL-10 on the neovascularization and wound healing is STAT3 dependent. We found that IL-10 treatment significantly promotes dermal wound healing with enhanced wound closure, robust granulation tissue formation and neovascularization. This was associated with elevated wound EPC counts as well as increased VEGF and high SDF-1α levels in control mice, an effect that was abrogated in STAT3 KO transgenic mice. These findings were supportedin vitro, wherein IL-10-enhanced VEGF and SDF-1α synthesis in primary murine dermal fibroblasts. IL-10-conditioned fibroblast media was shown to promote sprouting and network formation in aortic ring assays. We conclude that overexpression of IL-10 in the wound-specific milieu recruits EPCs and promote neovascularization, which occurs in a STAT3-dependent manner via regulation of VEGF and SDF-1α levels. Collectively, our studies demonstrate that IL-10 increases EPC recruitment leading to enhanced neovascularization and healing of dermal wounds.
Transcriptomic learning for digital pathology
Authors: Schmauch Benoît , Romagnoni Alberto , Pronier Elodie , Saillard Charlie , Maillé Pascale , Calderaro Julien , Sefta Meriem , Toldo Sylvain , Zaslavskiy Mikhail , Clozel Thomas , Moarii Matahi , Courtiol Pierre , Wainrib Gilles
Published: September 2019

Deep learning methods for digital pathology analysis have proved an effective way to address multiple clinical questions, from diagnosis to prognosis and even to prediction of treatment outcomes. They have also recently been used to predict gene mutations from pathology images, but no comprehensive evaluation of their potential for extracting molecular features from histology slides has yet been performed. We propose a novel approach based on the integration of multiple data modes, and show that our deep learning model, HE2RNA, can be trained to systematically predict RNA-Seq profiles from whole-slide images alone, without the need for expert annotation. HE2RNA is interpretable by design, opening up new opportunities for virtual staining. In fact, it provides virtual spatialization of gene expression, as validated by double-staining on an independent dataset. Moreover, the transcriptomic representation learned by HE2RNA can be transferred to improve predictive performance for other tasks, particularly for small datasets. As an example of a task with direct clinical impact, we studied the prediction of microsatellite instability from hematoxylin & eosin stained images and our results show that better performance can be achieved in this setting.
Defining the adult hippocampal neural stem cell secretome: in vivo versus in vitro transcriptomic differences and their correlation to secreted protein levels
Authors: Denninger JK. , Chen X. , Turkoglu AM. , Sarchet P. , Volk AR. , Yan P. , Kirby ED.
Published: September 2019

Recent evidence shows that adult hippocampal neural stem and progenitor cells (NSPCs) secrete a variety of proteins that affect tissue function. Though several individual NSPC-derived proteins have been shown to impact cellular processes like neuronal maturation and stem cell maintenance, a broad characterization of NSPC-secreted factors is lacking. Secretome profiling of low abundance stem cell populations is typically achieved via proteomic characterization of in vitro, isolated cells. Here, we analyzed the in vitro NSPC secretome using conditioned media from cultured adult mouse hippocampal NSPCs and detected over 200 different bioactive proteins with an antibody array. We next assessed the NSPC secretome on a transcriptional level with RNA sequencing (RNAseq) of cultured NSPCs. This comparison revealed that quantification of gene expression did not accurately predict relative protein abundance for several factors. Furthermore, comparing our transcriptional data with previously published single cell RNA sequencing datasets of freshly isolated hippocampal NSPCs, we found key differences in gene expression of secreted proteins between cultured and acutely isolated NSPCs. Understanding the components and functions of the NSPC secretome is essential to understanding how these cells may modulate the hippocampal neurogenic niche, as well as how they can be applied therapeutically. Cumulatively, our data emphasize the importance of using proteomic analysis in conjunction with transcriptomic studies and highlights the need for better methods of global unbiased secretome profiling.
Intracranial pressure elevation alters CSF clearance pathways
Authors: Vinje Vegard , Eklund Anders , Mardal Kent-Andre , Rognes Marie E. , Støverud Karen-Helene
Published: September 2019

Background

Infusion testing is a common procedure to determine whether shunting will be beneficial in patients with normal pressure hydrocephalus. The method has a well-developed theoretical foundation and corresponding mathematical models that describe the CSF circulation from the choroid plexus to the arachnoid granulations. Here, we investigate to what extent the proposed glymphatic or paravascular pathway (or similar pathways) modifies the results of the traditional mathematical models.

Methods

We used a two-compartment model consisting of the subarachnoid space and the paravascular spaces. For the arachnoid granulations, the cribriform plate, capillaries and paravascular spaces, resistances were calculated and used to estimate flow before and during an infusion test. Next, pressure in the subarachnoid space and paravascular spaces were computed. Finally, different variations to the model were tested to evaluate the sensitivity of selected parameters.

Results

At baseline, we found a very small paravascular flow directed into the subarachnoid space, while 60% of the fluid left through the arachnoid granulations and 40% left through the cribriform plate. However, during the infusion, paravascular flow reversed and 25% of the fluid left through these spaces, while 60% went through the arachnoid granulations and only 15% through the cribriform plate.

Conclusions

The relative distribution of CSF flow to different clearance pathways depends on intracranial pressure (ICP), with the arachnoid granulations as the main contributor to outflow. As such, ICP increase is an important factor that should be addressed when determining the pathways of injected substances in the subarachnoid space.
Variational Autoencoder Modular Bayesian Networks (VAMBN) for Simulation of Heterogeneous Clinical Study Data
Authors: Gootjes-Dreesbach Luise , Sood Meemansa , Sahay Akrishta , Hofmann-Apitius Martin , Fröhlich Holger
Published: September 2019

In the area of Big Data one of the major obstacles for the progress of biomedical research is the existence of data “silos”, because legal and ethical constraints often do not allow for sharing sensitive patient data from clinical studies across institutions. While federated machine learning now allows for building models from scattered data, there is still the need to investigate, mine and understand clinical data that cannot be accessed directly. Simulation of sufficiently realistic virtual patients could be a way to fill this gap.

In this work we propose a new machine learning approach (VAMBN) to learn a generative model of longitudinal clinical study data. VAMBN considers typical key aspects of such data, namely limited sample size coupled with comparable many variables of different numerical scales and statistical properties, and many missing values. We show that with VAMBN we can simulate virtual patients in a sufficiently realistic manner while making theoretical guarantees on data privacy. In addition, VAMBN allows for simulating counterfactual scenarios. Hence, VAMBN could facilitate data sharing as well as design of clinical trials.
SLR-superscaffolder: a de novo scaffolding tool for synthetic long reads using a top-to-bottom scheme
Authors: Guo Lidong , Xu Mengyang , Wang Wenchao , Gu Shengqiang , Zhao Xia , Chen Fang , Wang Ou , Xu Xun , Fan Guangyi , Deng Li , Liu Xin
Published: September 2019

Synthetic long reads (SLR) with long-range co-barcoding information have been recently developed and widely applied in genomics researches. We proposed a scaffolding model of the co-barcoding information and developed a scaffolding tool with adopting a top-to-bottom scheme to make full use of the complementary information in SLR datasets and a screening algorithm to reduce negative effects from misassembled contigs in an input assembly. In comparison with other available SLR scaffolding tools, our tool obtained the best quality improvement for different input assemblies, especially for those assembled by the next-generation sequencing reads, where the improvement of contiguity is about several hundred-folds.
Simultaneous Quantitative Determination of Amphetamines, Opiates, Ketamine, Cocaine and Metabolites in Human Hair: Application to Forensic Cases of Drug Abuse
Authors: Zhuo Yue , Wang Xin , Wu Jingjie , Zhang Sujing , Deng Hongxiao , Liu Wei , Wu Hejian , Xiang Ping , Shen Min
Published: September 2019

A method using liquid chromatography–tandem mass spectrometry (LC–MS/MS) to simultaneously quantify amphetamines, opiates, ketamine, cocaine, and metabolites in human hair is described. Hair samples (50 mg) were extracted with methanol utilizing cryogenic grinding. Calibration curves for all the analytes were established in the concentration range 0.05–10 ng/mg. The recoveries were above 72%, except for AMP at the limit of quantification (LOQ), which was 48%. The accuracies were within ±20% at the LOQ (0.05 ng/mg) and between −11% and 13.3% at 0.3 and 9.5 ng/mg, respectively. The intraday and interday precisions were within 19.6% and 19.8%, respectively. A proficiency test was applied to the validated method with z‐scores within ±2, demonstrating the accuracy of the method for the determination of drugs of abuse in the hair of individuals suspected of abusing drugs. The hair concentration ranges, means, and medians are summarized for abused drugs in 158 authentic cases.
Functional lumen imaging probe in gastrointestinal motility diseases
Authors: Chen Hui Min , Li Bai Wen , Li Lian Yong , Xia Liang , Chen Xiang Bo , Shah Rushikesh , Abdelfatah Mohamed M. , Jain Anand , Cassani Lisa , Massaad Julia , Keilin Steve , Cai Qiang
Published: September 2019

Dysfunction of gastrointestinal (GI) sphincters, including the lower esophageal sphincter (LES) at the esophagogastric junction (EGJ) and the pyloric sphincter, plays a vital role in GI motility disorders, such as achalasia, gastroesophageal reflux disease (GERD), gastroparesis, and fecal incontinence. Using multi‐detector high‐resolution impedance planimetry, the functional luminal imaging probe (FLIP) system measures simultaneous data on tissue distensibility and luminal geometry changes in the sphincter in a real‐time manner. In this review we focus on the emerging data on FLIP, which can be used as an innovative diagnostic method during endoscopic or surgical procedures in GI motility disorders. Subsequent large, prospective, standardizing studies are needed to validate these findings before it can be put to routine clinical use.
Can Employee Stock Options Contribute to Less Risk‐Taking?
Authors: Billings Bruce K. , Moon James R. , Morton Richard M. , Wallace Dana M.
Published: September 2019

The executive compensation literature presumes that shareholders offer risk‐averse managers stock options to entice them to take on more risk, resulting in riskier investment decisions and thus a greater return on investment. However, recent empirical work challenges this assumption, and theoretical research even argues that high levels of option‐based compensation for generally under‐diversified managers may actually lead to greater risk aversion. We evaluate the incentive structure of employee stock options by examining the level of R&D investment and the return on that investment conditional on the portfolio “vega,” which captures the sensitivity of option value to stock price volatility. Our results suggest that both investment in R&D and the return on R&D, as measured by future earnings and patent awards, varies concavely with vega. That is, low to moderate levels of vega correspond to increasing investment in and returns on R&D, consistent with vega inducing more profitable investments, but marginal returns decline as vega increases. Collectively, these results, bolstered by several supplemental analyses, suggest that this surprising relation between vega and risky investment is driven by greater risk aversion at higher levels of vega. Overall, our results imply that employee stock options may not always align the incentives of managers and shareholders.
Effects of grazing regime on the relative body mass of the endangered pygmy bluetongue lizard (Tiliqua adelaidensis)
Authors: Nielsen Torben Peiter , Bull Christopher Michael
Published: September 2019

Many animals rely on fat reserves, to keep them alive through extended periods of food shortage, such as the winter, and to provide additional energy for reproduction. Fat reserves, measured relative to an animal's size, are often referred to as the animal's body condition. The present study investigated how different levels of grazing by domestic stock in native grassland habitat affect the body condition of the pygmy bluetongue lizard (Tiliqua adelaidensis), and if these effects are related to changes in the abundance and size of grasshoppers which are the lizards primary source of food. The initial hypothesis was that lizards would have the highest body condition in moderately grazed paddocks, because those paddocks would have more grasshoppers than heavily grazed paddocks, and better visual conditions for lizards to catch those grasshoppers than in ungrazed paddocks. The results, however, showed that both lizard body condition and the abundance of grasshoppers increased with decreasing grazing intensity. The connection between lizard body condition and abundance of grasshoppers was complex. Within an activity season, lizard body condition generally declined from spring to summer, while the number of grasshoppers grew. The mean size of grasshoppers seemed to be more important, as lizard body condition was higher in spring, the time of year with the largest grasshoppers. These results show that the intensity of grazing by domestic stock influences the body condition of pygmy bluetongue lizards, but that this effect is not entirely due to the reduction in the number of grasshoppers resulting from grazing.
A homozygous mutation in CMAS causes autosomal recessive intellectual disability in a Kazakh family
Authors: Qu Ronggui , Sang Qing , Wang Xueqian , Xu Yao , Chen Biaobang , Mu Jian , Zhang Zhihua , Jin Li , He Lin , Wang Lei
Published: September 2019

Intellectual disability (ID) describes a wide range of serious human diseases caused by defects in central nervous system development and function. Some mutant genes have been found to be associated with these diseases, but not all cases can be explained, thus suggesting that other disease‐causing genes have not yet been discovered. Sialic acid is involved in a number of key biological processes, including embryo formation, nerve cell growth, and cancer cell metastasis, and very recently it has been suggested that N‐acetylneuraminic acid synthase‐mediated synthesis of sialic acid is required for brain and skeletal development. CMP‐sialic acid synthetase (CMAS) is one of four enzymes involved in NeuNAc metabolism, as it catalyzes the formation of CMP‐NeuNAc. Before the present study, no links between mutations in CMAS and incidences of human ID had been reported. In the current study, we recruited a recessive nonsyndromic ID pedigree with consanguineous marriage in which all patients have typical clinical manifestations of ID. We identified the NM_018686.3:c.563G > A (p.Arg188His) substitution in CMAS as being responsible for the disease in this family. Conservation analysis, structural prediction, and enzyme activity experiments demonstrated that (p.Arg188His) influences protein dimerization and alters CMAS enzyme activity. Our results offer a new orientation for future research and clinical diagnosis.
Dementia as a source of social disadvantage and exclusion
Authors: Biggs Simon , Carr Ashley , Haapala Irja
Published: September 2019

Objective

To explore perceptions of the impacts of dementia on people living with the condition and those close to them and examine the relationship between dementia, disadvantage and social exclusion.

Methods

Semi‐structured in‐depth interviews were conducted with 111 participants: people with dementia (n = 19), carers (n = 28), health‐care professionals (n = 21), social workers (n = 23) and service professionals (n = 20). NVivo 11 was used to code descriptions and identify impact areas.

Results

Participants described social, psychological, carer, material, service‐based and disparity impacts associated with the experience of dementia. Some of these impacts correspond to social exclusion associated with age, but some are distinctive to dementia.

Discussion

It is argued that dementia generates its own forms of social disadvantage and exclusion. This is in addition to being subject to structural risk factors. The implications of the active effects of dementia as a social phenomenon should give rise to new policy and practice priorities.
Introduction: East Asia's Contested Security Order
Authors: Bisley Nick , Strating Rebecca
Published: September 2019

East Asia's security environment is changing rapidly. Over the past five years or so, the security order has become increasingly unsettled as it is buffeted by a complex array of forces. The region is entering a period of growing rivalry and animosity states are uncertain over the strategic intentions of great and rising powers, nationalism is an increasingly pervasive force, and military spending has been ramping up in many countries over the past decade. That the security environment is changing is unarguable. But what is the extent of these changes? And what are the implications of these shifts for regional states? This paper introduces the special issue “East Asia's Contested Security Order”. It begins by discussing the broad contours of the changing East Asian security order and what is at stake for regional powers. It then introduces the seven articles in this edition that challenge existing conceptualisations of the East Asian security order, articulate diverse perspectives on that order held by regional, middle and smaller powers, examine their complex and different security strategies that contribute to shaping the regional order, and consider the extent to which the regional security order may be said to be “contested”.
Offsetting Uncertainty: Reassurance with Two‐Sided Incomplete Information
Authors: Haynes Kyle , K. Yoder Brandon
Published: September 2019

Conventional models of bargaining and reassurance under incomplete information assume that actors' behavioral signals are objectively cooperative or noncooperative. Even if actors are uncertain of each other's preferences, they know what types of actions the other will view as cooperative. Yet on many real‐world issues, cooperation is subjective, and what constitutes a cooperative action is conditional on the receiver's preferences. We present a formal model showing that in these cases, two‐sided incomplete information actually incentivizes honest behavior and facilitates credible signaling. Because uncertain senders do not know whether a particular action will be interpreted as cooperative, they have little incentive to misrepresent, and instead honestly pursue their true goals. Thus, where cooperation is subjective, mutual uncertainty is “offsetting,” such that credible signals allow actors to quickly and accurately update their beliefs. We illustrate this logic through a case study of the Sino–Soviet split, and highlight the model's implications for contemporary U.S.–China relations.
The association between clinically diagnosed insomnia and age‐related macular degeneration: a population‐based cohort study
Authors: Tsai Der‐Chong , Chen Hsi‐Chung , Leu Hsin‐Bang , Chen Shih‐Jen , Hsu Nai‐Wei , Huang Chin‐Chou , Chen Jaw‐Wen , Lin Shing‐Jong , Chou Pesus
Published: September 2019

Purpose

The decreased level of melatonin, the substance involved in the control of the sleep–wake cycle, has been reported among the patients with age‐related macular degeneration (AMD). However, knowledge about the relationship between sleep disturbance and AMD is still limited. This longitudinal case–control study aims to investigate the risk of incident AMD among the patients with clinically diagnosed insomnia using the Taiwan National Health Insurance Research Database.

Methods

The insomnia cohort (n = 15 465) consisted of newly diagnosed insomnia cases aged ≥55 years between 2000 and 2009. Subjects without insomnia, matched for age, gender and enrolment time, were randomly sampled as the control cohort (n = 92 790). Cox proportional hazard regressions were performed to calculate the hazard ratios (HR) of incident AMD for the two cohorts after adjusting for potential confounders.

Results

Of the 108 255 sampled subjects, 2094 (1.9%) were diagnosed with AMD, including 214 (0.2%) with neovascular AMD, during a mean follow‐up period of 5.1 ± 2.8 years. Insomnia patients were more likely to have subsequent AMD than those without insomnia (2.5% versus 1.8%, p < 0.001). Further, the incidence of exudative AMD was also higher in the insomnia cohort than the control cohort (0.3% versus 0.2%, p = 0.002). The adjusted HR was 1.33 (95% confidence interval [CI], 1.18–1.48, p < 0.001) for AMD and 1.67 (95% CI, 1.20–2.33, p = 0.002) for exudative AMD.

Conclusions

Clinically diagnosed insomnia is an independent indicator for the increased risk of subsequent AMD development.
Diet change from a system combining total mixed ration and pasture to confinement system (total mixed ration) on milk production and composition, blood biochemistry and behavior of dairy cows
Authors: Grille Lucía , Adrien Maria L. , Olmos Mara , Chilibroste Pablo , Damián Juan P.
Published: September 2019

This study aimed to determine if a diet change from a mixed system to a confinement system affects the milk production and composition, behavior and blood biochemistry of dairy cows. Cows were assigned randomly to one of the two treatments: cows fed with TMR (total‐mixed‐ration) (confined) throughout the period group fed TMR (GTMR, n = 15) and cows that changed their diet from pasture plus TMR to exclusive TMR at 70 ± 14 DIM (GCHD, n = 15). GTMR cows produced more milk and greater lactose and protein yield before the change of diet than GCHD cows (p ≤ .01), but these differences disappeared after the change. GCHD cows decreased the frequency of rumination and lying from before to after the change (p ≤ .03), but in GTMR cows no changes were observed. After diet change, GCHD cows had lower frequency of rumination and lying than GTMR cows (p ≤ .02). Before the change, GCHD cows had greater NEFA (non esterified fatty acids) concentrations than GTMR cows (p = .002). Abrupt change from a mixed system to a confined system was favorable on blood biochemical and milk variables of dairy cows. However, in relation to behavior, the cows expressed difficulties to adapt quickly to the abrupt change of system.
Crisponi/cold‐induced sweating syndrome: Differential diagnosis, pathogenesis and treatment concepts
Authors: Buers Insa , Persico Ivana , Schöning Lara , Nitschke Yvonne , Di Rocco Maja , Loi Angela , Sahi Puneet Kaur , Utine Gulen Eda , Bayraktar‐Tanyeri Bilge , Zampino Giuseppe , Crisponi Giangiorgio , Rutsch Frank , Crisponi Laura
Published: September 2019

Crisponi/cold‐induced sweating syndrome (CS/CISS) is an autosomal recessive disease characterized by hyperthermia, camptodactyly, feeding and respiratory difficulties often leading to sudden death in the neonatal period. The affected individuals who survived the first critical years of life, develop cold‐induced sweating and scoliosis in early childhood. The disease is caused by variants in the CRLF1 or in the CLCF1 gene. Both proteins form a heterodimeric complex that acts on cells expressing the ciliary neurotrophic factor receptor (CNTFR). CS/CISS belongs to the family of “CNTFR‐related disorders” showing a similar clinical phenotype. Recently, variants in other genes, including KLHL7, NALCN, MAGEL2 and SCN2A, previously linked to other diseases, have been associated with a CS/CISS‐like phenotype. Therefore, retinitis pigmentosa and Bohring‐Optiz syndrome‐like (KLHL7), Congenital contractures of the limbs and face, hypotonia, and developmental delay syndrome (NALCN), Chitayat‐Hall/Schaaf‐Yang syndrome (MAGEL2), and early infantile epileptic encephalopathy‐11 syndrome (SCN2A) all share an overlapping phenotype with CS/CISS, especially in the neonatal period. This review aims to summarize the existing literature on CS/CISS, focusing on the current state of differential diagnosis, pathogenesis and treatment concepts in order to achieve an accurate and rapid diagnosis. This will improve patient management and enable specific treatments for the affected individuals.
Winter virus season impact on acute dyspnoea in the emergency department
Authors: Christiaens Hanae , Charpentier Sandrine , Houze‐Cerfon Charles‐Henri , Balen Frederic
Published: September 2019

Objective

To compare the epidemiology of dyspnoea presented to emergency departments (EDs) during and of winter virus season (WVS).

Methods

This is a monocentric retrospective cohort study. All patients attending to the ED of the Rangueil University Hospital (Toulouse, France) for dyspnoea in September 2016 (off WVS period) and January 2017 (during WVS period) were included. The primary endpoint was the final diagnosis. The patients' medical profiles, care duration, seriousness and futures were studied as secondary endpoints.

Results

A total of 395 patients were studied: 125 patients during off‐peak influenza season and 270 patients during the peak influenza season. The incidence of patients attending because of dyspnoea increased significantly during WVS (4.2% of ED presentations during the off WVS period versus 8.4% during the WVS period, P < 0.001). Patients attending the ED because of dyspnoea during WVS period were significantly older with more extensive medical backgrounds and more serious diseases. Most of those patients were hospitalized (54%), and largely in the geriatrics department.

Conclusion

The incidence of patients attending because of dyspnoea doubled during the WVS period, with patients who were older and had more complex histories. This time‐consuming population largely requires hospitalization and may be one of the causes of the emergency department's overcrowding during epidemics.
Minimum absolute graft weight of 650 g predicts a good outcome in living donor liver transplant despite a graft recipient body weight ratio of less than 0.8
Authors: Agarwal Shaleen , Selvakumar Naganathan , Rajasekhar Kandagaddala , Dey Rajesh , Verma Sapana , Gupta Subhash
Published: September 2019

In living donor liver transplant (LDLT), it is recommended to have a minimum graft recipient body weight ratio (GRBWR) 0.8 for good outcomes. Recent reports have, however, shown that good outcomes can be obtained even with GRBWR less than 0.8. We hypothesized that in patients receiving a graft with GRWR less than 0.8 absolute graft weight rather than GRBWR may be more relevant for predicting good outcome. Early post‐transplant outcomes were assessed in adult patients undergoing elective right lobe LDLT. Patients were categorized as having good (survival) or poor (mortality) outcome. A ROC curve was drawn based on their graft weights and a cutoff value that provided the highest sensitivity and specificity for a good outcome was chosen. 147 patients received right lobe grafts with GRBWR less than 0.8. The 90‐day mortality rate was 13.6% (n = 20). AUROC was 67.7%. Graft weight cutoff of 643 g gave the best combination of sensitivity (51.2%) and specificity (77.8%). There were 15 (19.4%) deaths in group with graft weight less than 643 g compared to 5 (7.1%) patients with graft weight 643 g or above. This cutoff value of 643 g (rounded of to 650 g) gave a positive predictive value (PPV) of 94%.
Predictive value of transmitral A‐wave acceleration time for paroxysmal atrial fibrillation
Authors: Akilli Hakan , Aribas Alpay , İcli Abdullah , Tatar Sefa , Gurbuz Ahmet Seyfeddin
Published: September 2019

Background

It has been shown that transmitral A‐wave (TMAW) is affected in paroxysmal atrial fibrillation (PAF), and decreased left atrial contractions cause a decrease in the TMAW velocity. The relationship between TMAW acceleration time (TMAW‐AccT) and PAF is unknown. In this study, the predictive value of TMAW‐AccT for PAF was investigated.

Methods

Seventy PAF patients (mean age: 57.8 ± 11.0 years) and 70 control patients (mean age: 58.1 ± 10.5 years) were included in the study. Transthoracic echocardiography was performed in sinus rhythm in all patients. For TMAW‐AccT, the time between the basal point of the A‐wave and the highest point reached was measured.

Results

Transmitral A‐wave ‐AccT was significantly longer in the PAF group than the control group (TMAW‐AccT; 88.5 ± 18.1 vs 77.2 ± 16.4 ms, P = .000, respectively). The left atrial diameter and the left atrial volume index were similar between the groups (P = .07, P = .18, respectively). According to a multivariate logistic regression analysis, the TMAW‐AccT (OR: 1.02, 95% confidence interval 1.02–1.07, P < .001) was a predictor of PAF. A receiver operating characteristic curve analysis showed a cutoff value of TMAW‐AccT of >82 ms (sensitivity: 65.7%, specificity: 64.3%, positive predictive value: 64.8%, negative predictive value: 65.2%).

Conclusion

Transmitral A‐wave‐AccT can be used as an early marker in detecting PAF without dilated left atrium.
The effect of social and ecological factors on the time budget of wild vervet monkeys
Authors: Canteloup Charlotte , Borgeaud Christèle , Wubs Matthias , van de Waal Erica
Published: September 2019

Animals often have a limited time to perform different fitness‐enhancing activities, such as the trade‐off between socializing versus foraging in group‐living species. Many previous studies have focused on how ecological and social factors influence activity budget at the individual or group level in various species. However, few primate studies have focused on multiple study groups living within a similar habitat. Here, we analyse group, season and sex effects on the individual activity budget of wild vervet monkeys (Chlorocebus pygerythrus) living in four groups with overlapping home ranges. Generally, our findings support previous studies on primates. Our results indicate that intragroup competition may force larger groups to spend more time feeding and less time resting. We also found that seasonal variation, and therefore food availability, has a strong influence on the monkeys’ activity budget. Females, which are the philopatric sex in vervet monkeys, spent more time socializing while, in general, males spent more time resting. However, we did not find any difference on the time spent socializing between groups. Since there is evidence that not only time constraints and habitat quality but also group size influence individual behaviours and ultimately group living, we advise that future studies should focus on multiple groups of the same species living in the same habitat in order to better understand how all these variables are interlinked.
Complete upper airway collapse and apnoea during tethered swimming in horses
Authors: Jones S. , Franklin S. , Martin C. , Steel C.
Published: September 2019

Background

There is limited knowledge of the breathing strategy and impact on the patency of the upper respiratory tract (URT) in swimming horses.

Objectives

To describe the respiratory responses and endoscopic appearance of the URT during tethered swimming in horses.

Study design

Prospective descriptive study.

Methods

Ten race‐fit horses, with no history of URT obstruction, were examined during tethered swimming. Endoscopic examination, heart rate, sound recordings and above and below water video recordings were obtained. Plasma lactate concentration was measured before and 5 min after swimming and tracheal endoscopy was performed 30 min after exercise to assess for presence of blood or mucus. Four horses also underwent endoscopy during exercise on the track.

Results

Mean (±s.d.) breathing frequency was 28 ± 5 breaths/min during swimming, with a brief inspiration (mean ± s.d. TI = 0.51 ± 0.08 s), followed by a period of apnoea (1.59 ± 0.53 s) and then a short, forced expiration (TE = 0.42 ± 0.5 s). During apnoea all horses exhibited complete collapse of the URT including closure of the external nares, nasopharynx and rima glottidis (with bilateral adduction of the arytenoid cartilages and vocal folds) and, in two horses, epiglottic retroversion. No horses had URT collapse during overground exercise. Locomotor‐respiratory coupling was not observed during swimming. Median (IQR) plasma lactate post swim was 4.71 mmol/L (2.08–8.09 mmol/L) vs 0.68 mmol/L (0.65–0.71 mmol/L) preswim. Post swim endoscopy revealed grade 1 exercise‐induced pulmonary haemorrhage (EIPH) in 2 horses. Median mucus grade was 1 (range 0–3).

Main limitations

Overground endoscopy was not performed in all horses.

Conclusions

Horses experienced complete URT collapse associated with post inspiratory apnoea when swimming. The reason for this is unknown but may be to aid buoyancy or associated with the mammalian dive response – a survival reflex to preserve oxygen stores and prevent water entering the lungs.
Extended vertical lists for temporal pattern mining from multivariate time series
Authors: Kocheturov Anton , Momcilovic Petar , Bihorac Azra , Pardalos Panos M.
Published: September 2019

In this paper, the problem of mining complex temporal patterns in the context of multivariate time series is considered. A new method called the Fast Temporal Pattern Mining with Extended Vertical Lists is introduced. The method is based on an extension of the level‐wise property, which requires a more complex pattern to start at positions within a record where all of the subpatterns of the pattern start. The approach is built around a novel data structure called the Extended Vertical List that tracks positions of the first state of the pattern inside records and links them to appropriate positions of a specific subpattern of the pattern called the prefix. Extensive computational results indicate that the new method performs significantly faster than the previous version of the algorithm for Temporal Pattern Mining; however, the increase in speed comes at the expense of increased memory usage.
Psychological Resources, Constructive Conflict Management Behaviors, and Depressive Symptoms: A Dyadic Analysis
Authors: Lee Seonhwa , King Victoria , Wickrama Kandauda K. A. S. , O'Neal Catherine Walker
Published: September 2019

This study investigated the longitudinal associations between mastery, conflict management behaviors, and depressive symptoms using an actor–partner interdependence model with 371 middle‐aged couples over a span of 24 years. Results indicated that for both husbands and wives, individuals who possessed higher levels of mastery generally displayed more constructive conflict management behaviors during marital conflicts in middle years. In turn, individuals with more constructive behaviors averaged fewer depressive symptoms in their later adulthood. A partner effect was also noted, as individuals’ constructive behaviors were linked to their spouse's depressive symptoms. This finding emphasizes the importance of utilizing a dyadic context to understand intra‐individual and inter‐individual (or crossover) influences between husbands and wives in enduring marriages. A better understanding of how couples affect each other's mental health can inform the development and implementation of health promotion interventions and prevention efforts targeting middle‐aged couples.
Methadone poisonings: a seven‐year retrospective study of the French poison center network focusing on suicide attempts vs. misuses
Authors: Torrents Romain , Glaizal Mathieu , Sinno‐Tellier Sandra , Richard Nathalie , Nisse Patrick , Vodovar Dominique , Bloch Juliette , Simon Nicolas , de Haro Luc
Published: September 2019

Methadone has been prescribed in France as opioid substitution therapy as a syrup formulation since 1995 and as capsules since 2008. Following two publications showing on a national scale the high risk of methadone poisoning in children and the lack of difference in poisoning severity between both methadone formulations, French health authorities chose to benefit from the experience acquired by the network of French poison centres concerning poisoning by this substitution medication. The aim of this study was to identify and compare the main circumstances of methadone exposure collected by a poison centre on a national scale over a period of 7 years. Retrospective descriptive study of cases of methadone exposure was compiled by the network of French poison centres between 15 October 2010 and 15 October 2017. Analysis of 1415 files revealed two major circumstances: 47% misuse and 41% suicide attempts. Severity scores evaluated according to the PSS were higher for misuse than for suicidal behaviour, despite the supposed ingested dose being statistically higher in the latter. The results also confirmed the lack of significant difference in methadone exposure between both of the formulations (syrup and capsules). This series of methadone exposure on a national scale is one of the largest compiled series in international medical literature. On the one hand, it highlights the severity of methadone poisoning (in suicidal behaviour and even more so in misuse behaviour), and on the other hand, it confirms that the capsule formulation does not seem to represent a higher risk than the syrup formulation.
Rapid increase of platelet counts during antiviral therapy in patients with hepatitis C virus infection
Authors: Ishizu Yoji , Ishigami Masatoshi , Hayashi Kazuhiko , Honda Takashi , Kuzuya Teiji , Ito Takanori , Fujishiro Mitsuhiro
Published: September 2019

Aim

The cause of thrombocytopenia in patients with chronic hepatitis C virus (HCV) infection is multifactorial: hypersplenism, decreased thrombopoietin levels, and myelosuppression induced by HCV. Platelet counts increase after eradication of HCV; however, this mechanism is not fully understood. Therefore, the aim of this study was to determine the influence of these three factors on platelet counts.

Methods

We retrospectively analyzed data from 109 HCV‐infected patients with platelet counts ≤150 × 103/μL who achieved viral eradication using interferon‐free anti‐HCV therapy. Changes in hematological parameters, thrombopoietin levels, HCV titers, and spleen volumes, and the correlations among them were evaluated.

Results

HCV RNA levels significantly decreased at 4 weeks after initiating antiviral therapy. Platelet counts rapidly increased at 4 weeks from baseline (120 ± 35 vs. 106 ± 28 × 103/μL, P < 0.001), and remained at a plateau until 48 weeks after initiating antiviral therapy. Neutrophil counts showed the same pattern. Spleen volume was evaluated in 32 patients and, among them, it decreased in 21 patients, but remained unchanged in seven and increased in four. In addition to patients with decreased spleen volume, patients with unchanged spleen volume showed marginally increased platelet counts. Thrombopoietin levels did not correlate with platelet counts.

Conclusions

Platelet counts increased at 4 weeks after starting anti‐HCV treatment. Our results suggest that this rapid change was possibly caused by improvement of hypersplenism and HCV‐induced myelosuppression resulting from anti‐HCV therapy.
The diverse role of the Urological Surgical Care Practitioner: A brief examination
Authors: Fletcher Nicholas , Russell Bradley
Published: September 2019

Aim

To understand the different roles and aspects of the Surgical Care Practitioner (SCP) in delivering urology care to patients. To identify the different activities and various settings that SCP's are active in.

Method

Data collection was via online survey, distributed to 12 Urology SCP's from around the United Kingdom.

Results

83% response rate was recorded. The Majority of SCP's time is spent in the Operating Theatre setting with 90% stating they spent at least half or more of their time there, 80% stated less than quarter of their time in clinic and even less time spent involved with ward based activity.

The type of surgery SCP's were involved with most being Urology Oncology Open/Laparoscopic 80% and Robotic 80%. In comparison, Benign or Core urology surgery accounts for only 30%. None theatre activity was found to consist of assessment of new patients 40%, follow ups 60% and investigations 40%.

Conclusion

The SCP has become a recognized role in the theatre setting, assisting with and in some circumstances, under indirect supervision, carrying out surgical procedures. What this small survey has highlighted is the other facets to the role, demonstrating their input in Outpatient clinic assessment, follow up reviews and in some cases conducting investigations (Flexible Cystoscope and Urodynamic) on urology patients.