bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estrogen therapy may counterbalance eutrophic remodeling of coronary arteries and increase bradykinin relaxation in a rat model of menopausal hypertension
Authors: Matrai Mate , Hetthéssy Judit R. , Nadasy Gyorgy L. , Szekacs Bela , Mericli Metin , Acs Nandor , Monos Emil , Arbib Nissim , Varbiro Szabolcs 
Published: May 2016

Abstract

Objective:
Hypertension causes adverse remodeling and vasomotor alterations in coronaries. Hormones such as estrogen may help counterbalance some of these effects. The aim of this study was to analyze the effects of ovariectomy and estrogen therapy in a rat model of menopausal hypertension induced by angiotensin II (AII).

Methods:
We investigated diameter, tone, and mechanics of intramural coronaries taken from ovariectomized female rats (n = 11) that received chronic AII treatment to induce hypertension, and compared the results with those found in female rats that were also given estrogen therapy (n = 11). The “hypertensive control” group (n = 11) underwent an abdominal sham operation, and received AII. After 4 weeks of AII treatment, side branches of left anterior descendent coronary (approximately 200 μm in diameter) were isolated, cannulated with plastic microcannulas at both ends, and studied in vitro in a vessel chamber. The inner and outer diameter of the arteries were measured by microangiometry, and spontenuous tone, wall thickness, wall cross-sectional area, tangential stress, incremental distensibility, circumferential incremental elastic modulus, thromboxane agonist-induced tone, and bradykinin-induced dilation were calculated.

Results:
In hypertension, intramural small coronaries show inward eutrophic remodeling after ovariectomy comparing with hypertensive controls. Estrogen therapy had an opposite effect on vessel diameter. Hormone therapy led to an increase in spontaneous tone, allowing for greater dilatative capacity.

Conclusions:
Estrogen may therefore be considered to counterbalance some of the adverse changes seen in the wall of intramural coronaries in the early stages of chronic hypertension.
Histologic types of gastric cancer among migrants from the former Soviet Union and the general population in Germany: what kind of prevention do we need?
Authors: Jaehn Philipp , Holleczek Bernd , Becher Heiko , Winkler Volker 
Published: May 2016

Objective
The incidence of gastric cancer (GC) is high among migrants from Eastern Europe and Asia, but a detailed picture of disease characteristics is missing. Our study examined the incidence of histologic types among resettlers from the former Soviet Union and the general population in Germany to draw conclusions on risk factors and possible prevention strategies.

Methods
Between 1990 and 2009, all GC diagnoses among a cohort of 18 619 resettlers residing in the Saarland were identified in the Saarland Cancer Registry database. Age-standardized incidence rates (ASRs) of the entire Saarland population and standardized incidence ratios (SIRs) of resettlers compared with the Saarland population were calculated for types according to Laurén. In addition, ASRs and SIRs were modeled using Poisson’s regression to investigate time trends.

Results
The ASR of intestinal GC in the Saarland population decreased over time, whereas the ASR of diffuse GC remained unchanged. Resettlers’ incidence of intestinal GC was elevated among men [SIR: 3.04, 95% confidence interval (CI): 2.05–4.50] and women (SIR: 2.78, 95% CI: 1.61–4.79), whereas diffuse GC was elevated only among women (SIR: 1.98, 95% CI: 1.07–3.69). No time trends for SIRs could be observed in regression analysis.

Conclusion
Different trends of diffuse GC incidence in Germany and the USA underline the importance of environmental risk factors. The continuously elevated risk of GC among male resettlers is probably associated with risk factors affecting exclusively the intestinal type such as a low intake of fruit and vegetables and heavy alcohol consumption. Future prevention programs for resettlers should include dietary measures.
Clinical implications of new mechanistic insights into atopic dermatitis
Authors: Leung Donald Y.M. 
Published: May 2016

Purpose of review
The review will examine recent advances in our understanding of atopic dermatitis and how these mechanisms provide a framework for new approaches to the management of this common skin disease.

Recent findings
The mechanisms by which epithelial skin barrier and immune responses contribute to the complex clinical phenotypes found in atopic dermatitis are being elucidated. Atopic dermatitis often precedes food allergy because reduced skin barrier function allows environmental food allergens to penetrate the skin leading to systemic allergen sensitization. There is increasing evidence that atopic dermatitis is a systemic disease. New treatments are focused on intervention in polarized immune responses leading to allergic diseases. This includes antagonism of IL-4 and IL-13 effects. Prevention strategies involve maintaining normal skin barrier function with emollients to prevent allergens and microbes from penetrating the skin.

Summary
Recent work on the pathogenesis of atopic dermatitis has important implications for its clinical management, including the development of effective barrier creams and biologicals targeting specific polarized immune pathways resulting in skin inflammation.
Understanding autoimmunity of vitiligo and alopecia areata
Authors: Rork Jillian F. , Rashighi Mehdi , Harris John E. 
Published: May 2016

Purpose of review
Vitiligo and alopecia areata are common, disfiguring skin diseases. Treatment options are limited and include nontargeted approaches, such as corticosteroids, topical calcineurin inhibitors, narrow band ultraviolet B phototherapy, and other immune-modifying agents. The purpose of this article is to review shared, novel mechanisms between vitiligo and alopecia areata, as well as discuss how they inform the development of future targeted treatments.

Recent findings
Vitiligo and alopecia areata are both autoimmune diseases, and striking similarities in pathogenesis have been identified at the level of both the innate and adaptive immune system. Increased reactive oxygen species and high cellular stress level have been suggested as the initiating trigger of the innate immune system in both diseases, and genome-wide association studies have implicated risk alleles that influence both innate and adaptive immunity. Most importantly, mechanistic studies in mouse models of vitiligo and alopecia areata have specifically implicated an interferon (IFN)γ-driven immune response, including IFNγ, IFNγ-induced chemokines, and cytotoxic CD8+ T cells as the main drivers of disease pathogenesis. These recent discoveries may reveal an effective strategy to develop new treatments, and several proof-of-concept clinical studies support this hypothesis.

Summary
The identification of IFNγ-driven immune signaling pathways has enabled discoveries of potential new treatments for vitiligo and alopecia areata, and supports initiation of larger clinical trials.
Therapist Adherence to Good Psychiatric Practice in a Short-Term Treatment for Borderline Personality Disorder
Authors: Kolly Stéphane , Despland Jean-Nicolas , de Roten Yves , Marquet Pierre , Kramer Ueli 
Published: May 2016

Abstract
Therapist adherence describes the quality of interventions according to the imperatives of a treatment model. We examined the relationship between therapist adherence and symptom change in the context of a short-term treatment with respect good psychiatric management (GPM) principles. Based on a parent trial, borderline personality disorder patients (N = 40) benefited from a 10-session intervention. Adherence to GPM was assessed using a GPM Adherence Scale (GPMAS). The psychometric properties of the GPMAS were excellent, and the adherence to GPM explained 16% of the general symptom improvement (t(1) = 2.38, β = 0.40, p = 0.02) and 23% of the borderline symptom improvement (t(1) = 2.46, β = 0.48, p = 0.02). Because GPM adherence predicts the outcome after only 10 sessions, GPMAS is a valuable measure early on in psychiatric practice as part of an initial step to longer-term treatment, to quickly detect problems and correct them.
Explicit Facial Emotion Processing in Patients With Dissociative Seizures
Authors: Pick Susannah , Mellers John D.C. , Goldstein Laura H. 
Published: May 2016

ABSTRACT

Objective
There have, as yet, been few experimental studies of explicit facial affect recognition in patients with dissociative seizures (DS). The aim of the study was to examine explicit recognition and physiological responses to facial expressions in this group, relative to healthy controls.

Methods
Forty patients with DS and 43 controls completed a computerized test of facial affect recognition, including five basic expressions (happiness, anger, disgust, fear, neutral). Recognition accuracy, emotional intensity judgements, and skin conductance levels and responses were dependent measures. Analyses controlled for a range of potentially confounding variables, including anxiety, depression, and medication effects.

Results
The DS group was less accurate at identifying facial expressions than controls (p = .005, η
2
p = 0.10). No group difference emerged for intensity judgements (p = .72, η
2
p = 0.002). Mean skin conductance levels were higher in the DS group relative to controls (p = .046, η
2
p = 0.053). However, a subgroup of DS patients showed attenuated skin conductance responses to the facial stimuli, compared with controls (p = .015, η
2
p = 0.18). These differences could not be accounted for by possible confounding variables. Recognition accuracy for neutral faces correlated negatively with trauma scores (r = −0.486, p = .002) and abandonment concerns (r = −0.493, p = .002) in the DS group.

Conclusions
Patients with DS showed reduced recognition accuracy for facial affect, despite accurately perceiving its intensity. Elevated autonomic arousal may characterize patients with DS in general, alongside reduced phasic autonomic responses to facial expressions in some patients with the disorder.
The role of multiplex molecular panels for the diagnosis of gastrointestinal infections in immunocompromised patients
Authors: Liesman Rachael M. , Binnicker Matthew J. 
Published: May 2016

Purpose of review
An increasing number of laboratories have implemented multiplex molecular panels for the diagnosis of gastrointestinal infections. This review focuses on recent data addressing the performance of US Food and Drug Administration-cleared multiplex gastrointestinal panels and discusses the advantages and limitations of these tests in the immunocompromised population.

Recent findings
Testing for gastrointestinal pathogens using multiplex molecular panels increases sensitivity and detection of coinfections compared with routine testing methods. Furthermore, multiplex panels reduce turnaround time and may allow for more informed decisions regarding treatment and infection control measures. However, the routine use of multiplex gastrointestinal panels has led to an increase in the detection of certain organisms, such as enteroaggregative Escherichia coli and sapovirus, which many clinical laboratories did not specifically test for in the past. This has created a degree of confusion on how to best interpret the results of multiplex panels, especially in the immunocompromised host.

Summary
Multiplex molecular panels provide a rapid and sensitive tool for the diagnosis of infectious diarrhea, and may allow for more timely decisions regarding the management of immunosuppressed patients. However, there are limitations associated with multiplex panels, including the interpretation of results and the cost associated with testing. Clinical microbiologists should work closely with clinicians to develop evidence-based algorithms to guide test utilization in this area.
Stochastic simulation tools and continuum models for describing two-dimensional collective cell spreading with universal growth functions
Authors: Jin Wang , Penington Catherine J. , McCue Scott W. , Simpson Matthew J. 
Published: May 2016

AbstractTwo-dimensional collective cell migration assays are used to study cancer and tissue repair. These assays involve combined cell migration and cell proliferation processes, both of which are modulated by cell-to-cell crowding. Previous discrete models of collective cell migration assays involve a nearest-neighbour proliferation mechanism where crowding effects are incorporated by aborting potential proliferation events if the randomly chosen target site is occupied. There are two limitations of this traditional approach: (i) it seems unreasonable to abort a potential proliferation event based on the occupancy of a single, randomly chosen target site; and, (ii) the continuum limit description of this mechanism leads to the standard logistic growth function, but some experimental evidence suggests that cells do not always proliferate logistically. Motivated by these observations, we introduce a generalised proliferation mechanism which allows non-nearest neighbour proliferation events to take place over a template ofr≥ 1 concentric rings of lattice sites. Further, the decision to abort potential proliferation events is made using acrowding function, f(C), which accounts for the density of agents within a group of sites rather than dealing with the occupancy of a single randomly chosen site. Analysing the continuum limit description of the stochastic model shows that the standard logistic source term, λC(1 –C), where λ is the proliferation rate, is generalised to a universal growth function, λCf(C). Comparing the solution of the continuum description with averaged simulation data indicates that the continuum model performs well for many choices off(C) andr. For nonlinearf(C), the quality of the continuum-discrete match increases withr.
MODA: MOdule Differential Analysis for weighted gene co-expression network
Authors: Li Dong , Brown James B. , Orsini Luisa , Pan Zhisong , Hu Guyu , He Shan 
Published: May 2016

1SummaryGene co-expression network differential analysis is designed to help biologists understand gene expression patterns under different conditions. We have implemented an R package called MODA (Module Differential Analysis) for gene co-expression network differential analysis. Based on transcriptomic data, MODA can be used to estimate and construct condition-specific gene co-expression networks, and identify differentially expressed subnetworks as conserved or condition specific modules which are potentially associated with relevant biological processes. The usefulness of the method is also demonstrated by synthetic data as well as Daphnia magna gene expression data under different environmental stresses.
Markov models of the apo-MDM2 lid region reveal diffuse yet two-state binding dynamics and receptor poses for computational docking
Authors: Mukherjee Sudipto , Pantelopulos George A. , Voelz Vincent A. 
Published: May 2016

ABSTRACTMDM2 is a negative regulator of p53 activity and an important target for cancer therapeutics. The N-terminal lid region of MDM2 modulates interactions with p53 via competition for its binding cleft, exchanging slowly between docked and undocked conformations in the absence of p53. To better understand these dynamics, we constructed Markov State Models (MSMs) from large collections of unbiased simulation trajectories ofapo-MDM2, and find strong evidence for diffuse, yet two-state folding and binding of the N-terminal region to the p53 receptor site. The MSM also identifiesholo-like receptor conformations highly suitable for computational docking, despite initiating trajectories from closed-cleft receptor structures unsuitable for docking. Fixed-anchor docking studies using a test set of high-affinity small molecules and peptides show simulated receptor ensembles achieve docking successes comparable to cross-docking studies using crystal structures of receptors bound by alternative ligands. For p53, the best-scoring receptor structures have the N-terminal region lid region bound in a helical conformation mimicking the bound structure of p53, suggesting lid region association induces receptor conformations suitable for binding. These results suggest that MD+MSM approaches can sample binding-competent receptor conformations suitable for computational peptidomimetic design, and that inclusion of disordered regions may be essential to capturing the correct receptor dynamics.
Increasing tolerance of hospitalEnterococcus faeciumto hand-wash alcohols
Authors: Pidot Sacha J. , Gao Wei , Buultjens Andrew H. , Monk Ian R. , Guerillot Romain , Carter Glen P. , Lee Jean Y.H. , Lam Margaret M. C. , Grayson M. Lindsay , Ballard Susan A. , Mahony Andrew A. , Grabsch Elizabeth A. , Kotsanas Despina , Korman Tony M. , Coombs Geoffrey W. , Robinson J. Owen , Gonçalves da Silva Anders , Seemann Torsten , Howden Benjamin P. , Johnson Paul D. R. , Stinear Timothy P. 
Published: May 2016

AbstractAlcohol-based hand rubs are international pillars of hospital infection control, restricting transmission of pathogens such asStaphylococcus aureus. Despite this success, health care infections caused byEnterococcus faecium(Efm) - another multidrug resistant pathogen - are increasing. We tested alcohol tolerance of 139 hospital Efm isolates, obtained between 1997 and 2015 and found Efm post-2010 were 10-fold more tolerant to alcohol killing than older isolates. Using a mouse infection control model, we then showed that alcohol tolerant Efm resisted standard 70% isopropanol surface disinfection and led to gastrointestinal colonization significantly more often than alcohol sensitive Efm. We next looked for bacterial genomic signatures of adaptation. Tolerant Efm have independently accumulated mutations modifying genes involved in carbohydrate uptake and metabolism. Mutagenesis confirmed their roles in isopropanol tolerance. These findings suggest bacterial adaptation and complicate infection control recommendations. Additional policies and procedures to prevent Efm spread are required.
Cerebellar learning using perturbations
Authors: Bouvier Guy , Aljadeff Johnatan , Clopath Claudia , Bimbard Célian , Ranft Jonas , Blot Antonin , Nadal Jean-Pierre , Brunel Nicolas , Hakim Vincent , Barbour Boris 
Published: May 2016

AbstractThe cerebellum aids the learning and execution of fast coordinated movements, with acquired information being stored by plasticity of parallel fibre—Purkinje cell synapses. According to the current consensus, erroneously active parallel fibre synapses are depressed by complex spikes arising when climbing fibres signal movement errors. However, this theory cannot solve thecredit assignment problemof using the limited information from a global movement evaluation to optimise behaviour by guiding the plasticity in numerous neurones. We identify the possible implementation of an algorithm solving this problem, whereby spontaneous complex spikes perturb ongoing movements, create an eligibility trace for plasticity and signal resulting error changes to guide plasticity. These error changes are extracted by adaptively cancelling the average error. This framework,stochastic gradient descent with estimated global errors, generates specific predictions for synaptic plasticity rules that contradict the current consensus. However, in vitro plasticity experiments under physiological conditions verified our predictions, highlighting the sensitivity of plasticity studies to unphysiological conditions. Using numerical and analytical approaches we demonstrate the convergence and estimate the capacity of learning in our implementation. Finally, a similar mechanism may operate during optimisation of action sequences by the basal ganglia, where dopamine could both initiate movements and signal rewards, analogously to the dual perturbation and correction role of the climbing fibre outlined here.
Excess of Deleterious Mutations around HLA Genes Reveals Evolutionary Cost of Balancing Selection
Authors: Lenz Tobias L. , Spirin Victor , Jordan Daniel M. , Sunyaev Shamil R. 
Published: May 2016

AbstractDeleterious mutations are expected to evolve under negative selection and are usually purged from the population. However, deleterious alleles segregate in the human population and some disease-associated variants are maintained at considerable frequencies. Here we test the hypothesis that balancing selection may counteract purifying selection in neighboring regions and thus maintain deleterious variants at higher frequency than expected from their detrimental fitness effect. We first show in realistic simulations that balancing selection reduces the density of polymorphic sites surrounding a locus under balancing selection, but at the same time markedly increases the population frequency of the remaining variants, including even substantially deleterious alleles. To test the predictions of our simulations empirically, we then use whole exome sequencing data from 6,500 human individuals and focus on the most established example for balancing selection in the human genome, the major histocompatibility complex (MHC). Our analysis shows an elevated frequency of putatively deleterious coding variants in non-HLA genes localized in the MHC region. The mean frequency of these variants declined with physical distance from the classical HLA genes, indicating dependency on genetic linkage. These results reveal an indirect cost of the genetic diversity maintained by balancing selection, which has hitherto been perceived as mostly advantageous, and have implications both for the evolution of recombination and also for the epidemiology of various MHC-associated diseases.
What cliff is your business headed for? Are you listening and are the right people talking?
Authors: Ballman Paul 
Published: May 2016

Purpose
This paper addresses one particular type of cliff edge – “Unknown Knowns” that organizations are often headed for and suggests ways in which it can be avoided.

Design/methodology/approach
The paper reports lessons learned through the author’s experience and draws on relevant literature.

Findings
Apparently unforeseen cliffs are actually well known about, deep in the organization, well ahead of time and either nobody is talking or nobody is listening.

Practical Implications
People need to change their cultures to ensure that the “Cassandras” (people who can be seen as “negative” and problem rather than solution focused) are genuinely listened to.

Originality/value
New scandals break every month. At the time of writing, the latest is Volkswagen (VW) emissions testing, itself a classic example of an unknown-known cliff.