bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inequity of care provision and outcome disparity in autoimmune hepatitis in the United Kingdom
Authors: Dyson Jessica K. , Wong Lin Lee , Bigirumurame Theophile , Hirschfield Gideon M. , Kendrick Stuart , Oo Ye H. , Lohse Ansgar W , Heneghan Michael A. , Jones David E. J. ,   the UK‐AIH Consortium
Published: September 2018

SummaryBackgroundTreatment paradigms in autoimmune hepatitis (AIH) have remained largely unchanged for decades. Studies report ≤20% of patients have sub‐optimal treatment response with most requiring long‐term therapy.AimThe United Kingdom Autoimmune Hepatitis (UK‐AIH) study was established to evaluate current treatment practice and outcomes, determine the unmet needs of patients, and develop and implement improved treatment approaches.MethodsThe United Kingdom Autoimmune Hepatitis study is a cross‐sectional cohort study examining secondary care management of prevalent adult patients with a clinical diagnosis of autoimmune hepatitis. Enrolment began in March 2014. Prevalent cases were defined as having been diagnosed and treated for >1 year. Demographic data, biochemistry, treatment history and response, and care location were collected.ResultsIn total, 1249 patients were recruited; 635 were cared for in transplant units and 614 in non‐transplant centres (81% female with median age at diagnosis 50 years). Overall, 29 treatment regimens were reported and biochemical remission rate was 59%. Remission rates were significantly higher in transplant compared to non‐transplant centres (62 vs 55%, P = 0.028). 55% have ongoing corticosteroid exposure; 9% are receiving prednisolone monotherapy. Those aged ≤20 years at diagnosis were more likely to develop cirrhosis and place of care was associated with an aggressive disease phenotype.ConclusionsThere are significant discrepancies in the care received by patients with autoimmune hepatitis in the UK. A high proportion remains on corticosteroids and there is significant treatment variability. Patients receiving care in transplant centres were more likely to achieve and maintain remission. Overall poor remission rates suggest that there are significant unmet therapeutic needs for patients with autoimmune hepatitis.
From protectionism to inclusion: A New Zealand perspective on health‐related research involving adults incapable of giving informed consent
Authors: Douglass Alison , Ballantyne Angela 
Published: September 2018

AbstractThe revision of the Council of International Organizations of Medical Sciences (CIOMS) International ethical guidelines for health‐related research (2016) heralds a paradigm shift from the ‘protectionist’ policies that emerged following historical research atrocities of the 20th century, towards a more nuanced and inclusive approach to research participation. Adopting this modified approach will enable countries to secure the benefits of research for individuals and for society as a whole, while at the same time minimizing the potential for exploitation and research‐related harms. This article considers the potential impact of Guideline 16 of the CIOMS 2016 from a New Zealand perspective, with respect to research involving adults with impaired capacity and who are incapable of giving informed consent. While the CIOMS 2016 apply a ‘minimal risk’ threshold to guide research involving adults who lack capacity to consent, New Zealand law currently adopts a ‘best interests’ standard which significantly restricts the scope of permissible research that may be performed in this context. This article argues that the CIOMS 2016 should influence change to New Zealand’s legal framework for ethical review of research. CIOMS 2016 provides useful guidance for the necessary standards and processes to enable the responsible and ethical inclusion of adults with impaired capacity in research.
Suffering at the end of life
Authors: Varelius Jukka 
Published: September 2018

AbstractIn the end‐of‐life context, alleviation of the suffering of a distressed patient is usually seen as a, if not the, central goal for the medical personnel treating her. Yet it has also been argued that suffering should be seen as a part of good dying. More precisely, it has been maintained that alleviating a dying patient’s suffering can make her unable to take care of practical end‐of‐life matters, deprive her of an opportunity to ask questions about and find meaning in and for her existence, and detach her from reality. In this article, I argue that the aims referred to either do not support suffering or are better served by alleviating it. When the aims would be equally well served by enduring suffering and relieving it, the latter appears to be the preferable option, given that the distress a patient experiences has no positive intrinsic value. Indeed, as the suffering can be very distressing, it may not be worth bearing even if that was the best way to achieve the aims: the distress can sometimes be bad enough to outbalance the worth of achieving the goals. Having considered an objection to the effect that a patient can have a self‐regarding moral duty to endure the distress she faces at the end of life, I conclude that the burden of proof is on the side of those who maintain that the suffering experienced at the end of life ought to be endured as a part of dying well.
Mobile learning and student cognition: A systematic review of PK‐12 research using Bloom’s Taxonomy
Authors: Crompton Helen , Burke Diane , Lin Yi‐Ching 
Published: September 2018

AbstractThe rise of mobile learning in schools during the past decade has led to promises about the power of mobile learning to extend and enhance student cognitive engagement. The purpose of this study was to examine trends to determine the cognitive level students are involved in within mobile learning activities. This systematic review involved an aggregated and configurative synthesis of PK‐12 mobile learning studies from 2010 to 16 and used Bloom’s Taxonomy as a theoretical framework for categorizing the cognitive level of student activities. Major new findings include that students are involved in activities at all six levels of Bloom’s Taxonomy. This study shows that over 60% of researchers are developing activities that require high levels of cognitive processing, a large increase from past studies. Nonetheless, 40% are integrating mobile devices in ways that keep students working with minimal cognitive processing. In both elementary and secondary studies, there was a 40/60% split in the use of lower versus high level thinking opportunities. New findings show that mobile devices were integrated into science, mathematics, social studies, literacy, art and special education. Studies in science settings were the majority of the studies (40%), followed by literacy (24%).
Three‐dimensional electron microscopy techniques for unravelling mitochondrial dysfunction in heart failure and identification of new pharmacological targets
Authors: Daghistani Hussam M , Rajab Bodour S , Kitmitto Ashraf 
Published: September 2018

A hallmark of heart failure is mitochondrial dysfunction leading to a bioenergetics imbalance in the myocardium. Consequently, there is much interest in targeting mitochondrial abnormalities to attenuate the pathogenesis of heart failure. This review discusses (i) how electron microscopy (EM) techniques have been fundamental for the current understanding of mitochondrial structure–function, (ii) the paradigm shift in resolutions now achievable by 3‐D EM techniques due to the introduction of direct detection devices and phase plate technology, and (iii) the application of EM for unravelling mitochondrial pathological remodelling in heart failure. We further consider the tremendous potential of multi‐scale EM techniques for the development of therapeutics, structure‐based ligand design and for delineating how a drug elicits nanostructural effects at the molecular, organelle and cellular levels. In conclusion, 3‐D EM techniques have entered a new era of structural biology and are poised to play a pivotal role in discovering new therapies targeting mitochondria for treating heart failure.Linked ArticlesThis article is part of a themed section on Mitochondrial Pharmacology: Featured Mechanisms and Approaches for Therapy Translation. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.22/issuetoc
Insight into selective mechanism of class of I‐BRD9 inhibitors toward BRD9 based on molecular dynamics simulations
Authors: Su Jing , Liu Xinguo , Zhang Shaolong , Yan Fangfang , Zhang Qinggang , Chen Jianzhong 
Published: September 2018

AbstractRecently, bromodomain‐containing protein 9 (BRD9), 7 (BRD7), and 4 (BRD4) have been potential targets of anticancer drug design. Molecular dynamic simulations followed by molecular mechanics Poisson–Boltzmann surface area calculation were performed to study the selective mechanism of I‐BRD9 inhibitor H1B and its derivatives N1D, TVU, and 5V2 toward BRD9 and BRD4. The rank of our calculated binding free energies agrees with that of the experimental data. The results show that binding free energy of H1B to BRD7 is slightly lower than that of H1B to BRD9, and all four inhibitors bind more tightly to BRD9 than to BRD4. Decomposition of binding free energies into individual residues implies that Ile164 and Asn211 in BRD7 and Ile53 and Asn100 in BRD9 play a significant role in the selectivity of H1B toward BRD7 and BRD9. Besides, several key residues Phe44, Ile53, Asn100, Thr104 in BRD9 and Pro82, Lys91, Asn140, Asp144 in BRD4 that are located in the ZA‐loop and BC‐loop provide significant contributions to binding selectivity of inhibitors to BRD9 and BRD4. This study is expected to provide important theoretical guidance for rational designs of highly selective inhibitors targeting BRD9 and BRD4.
Comparative quantitative clinical, neuroimaging, and functional profiles in children with acute flaccid myelitis at acute and convalescent stages of disease
Authors: Gordon‐Lipkin Eliza , Muñoz Laura S , Klein Jessica L , Dean Janet , Izbudak Izlem , Pardo Carlos A 
Published: September 2018

AimTo quantify characteristics in acute flaccid myelitis (AFM) at acute and convalescent stages.MethodThis was a retrospective case series of children with AFM evaluated at a single institution in the USA (2014–2017). Acute inflammatory/ischemic myelopathies were excluded. Neurological assessments and segmental quantitative analysis of signal abnormalities on magnetic resonance imaging (MRI) of the brain and spinal cord were performed.ResultsSixteen patients (11 males, five females) were evaluated. Median age at onset was 4 years (interquartile range [IQR] 3–6y). All had parainfectious acute‐onset limb weakness, lower motor neuron examination, and spinal fluid pleocytosis. On acute spinal cord MRI, longitudinally extensive T2 hyperintensities were identified throughout the spinal cord mostly within grey matter; five out of 12 patients had dorsal brainstem T2 hyperintensities. At a median of 2 months follow‐up (IQR 2–3mo), spinal cord MRI improved in seven out of nine patients although focal T2 hyperintensities persisted in cervical and lumbar grey matter. At a median follow‐up of 4 months (IQR 2–6mo), Medical Research Council sum score rose from a median of 29 to 32; distal muscle groups improved more than proximal ones; four out of 16 patients were ventilator‐dependent; and two out of 16 patients were quadriplegic.InterpretationWhile patients may show marked improvement on neuroimaging from acute to convalescent stages, the majority of children with AFM have limited motor recovery and continued disability. Clinicians should consider the timing of clinical and neuroimaging exams when assessing diagnosis and prognosis.What this paper adds

During the 2014 to 2017 acute flaccid myelitis outbreak in the USA, clinical recovery was better in distal than proximal muscle groups.

Lumbar spinal cord showed more residual abnormalities at convalescence.
Empagliflozin reduces myocardial ketone utilization while preserving glucose utilization in diabetic hypertensive heart disease: A hyperpolarized 13C magnetic resonance spectroscopy study
Authors: Abdurrachim Desiree , Teo Xing Qi , Woo Chern Chiuh , Chan Wei Xin , Lalic Janise , Lam Carolyn S. P. , Lee Philip Teck Hock 
Published: September 2018

AimTo investigate the effects of the sodium‐glucose co‐transporter‐2 inhibitor empagliflozin on myocardial ketone body utilization in diabetic, obese rats with spontaneously hypertensive heart failure (SHHF), after 6 months of treatment.Materials and MethodsMyocardial ketone body utilization was measured in vivo real time using a novel ketone probe (hyperpolarized [3‐13C]acetoacetate) and magnetic resonance spectroscopy (MRS). Myocardial glucose utilization and cardiac function were also determined in vivo using hyperpolarized [1‐13C]pyruvate MRS and magnetic resonance imaging (MRI), respectively. Myocardial fatty acid uptake and liver ketogenesis were assessed via protein expression.ResultsAt baseline, myocardial ketone and glucose utilization were both higher in SHHF compared with control rats. Six months of empagliflozin treatment in SHHF rats was associated with less obesity, lower blood pressure, reduced blood glucose and insulin levels, and increased fasting blood β‐hydroxybutyrate levels, as expected. Contrary to the hypothesis, myocardial ketone body utilization was lower in empagliflozin‐treated SHHF rats, while glucose utilization and cardiac function were unaltered and hepatic congestion was reduced, compared with vehicle‐treated SHHF rats.ConclusionsIn diabetic hypertensive heart disease, empagliflozin reduces afterload without altering myocardial function and glucose utilization in the face of falling blood glucose levels, but does not enhance myocardial ketone utilization despite increased circulating levels.
Mineralocorticoid antagonism enhances brown adipose tissue function in humans: A randomized placebo‐controlled cross‐over study
Authors: Thuzar Moe , Law Weikiat Phillip , Dimeski Goce , Stowasser Michael , Ho Ken K. Y. 
Published: September 2018

AimTo investigate whether mineralocorticoid (MC) antagonism enhances brown adipose tissue (BAT) function in humans.Materials and MethodsIn a randomized double‐blind, cross‐over designed trial, 10 healthy adults (two men, eight women) underwent 2 weeks of spironolactone (100 mg/d) treatment and placebo, with an intervening 2‐week wash‐out period. BAT function was assessed in response to cooling and to a mixed meal. Metabolic activity was measured by fluoro‐deoxyglucose (FDG) uptake (maximal standardized uptake value, SUVmax) using PET‐CT. Thermogenic activity was measured by skin temperatures overlying supraclavicular (SCL) BAT depots using infrared thermography. Postprandial metabolism was measured by energy production rate (EPR) and lipid synthesis using indirect calorimetry.ResultsDuring cooling, BAT metabolic activity (SUV 6.30 ± 2.16 vs 3.98 ± 1.34; P < 0.05) and volume (54.9 ± 22.8 vs 21.6 ± 11.8 cm3; P < 0.05) were significantly higher, and mean SCL temperature decreased by a smaller degree (−0.3°C°± 0.2°C vs −0.9°C ± 0.2°C; P = 0.05) with spironolactone treatment. A mixed meal increased SCL temperature and EPR. The postprandial rise in SCL temperature (+0.4°C ± 0.1°C vs +0.1°C ± 0.1°C; P < 0.05) but not in EPR was greater during spironolactone treatment. Postprandial lipid synthesis occurred in three participants with placebo but in none with spironolactone treatment (P = 0.06).ConclusionMC antagonism enhanced human BAT function in response to cooling and to a meal during which lipid synthesis was suppressed. As postprandial EPR comprises energy dissipated as heat and energy required to store nutrients, the reduction in lipid synthesis during MC antagonism is a probable consequence of concurrent stimulation of BAT thermogenesis. The shift in energy usage from storage to heat dissipation indicates that MC antagonists may have therapeutic benefit for obesity.
Simplified apical four‐chamber view evaluation of relative apical sparing of longitudinal strain in diagnosing AL amyloid cardiomyopathy
Authors: Fikrle Michal , Palecek Tomas , Marek Josef , Kuchynka Petr , Linhart Ales 
Published: September 2018

Aim of the studyTo assess the diagnostic utility of a simplified approach to relative apical sparing of longitudinal strain (RAS LS) using only an apical four‐chamber view (A4C) in patients with AL amyloid cardiomyopathy (ALAC).MethodsWe retrospectively evaluated echocardiographic recordings of 20 patients with ALAC, 20 patients with Fabry disease‐related cardiomyopathy (FD), and 20 patients with concentric hypertensive left ventricular hypertrophy (HLVH) matched for mean LV mean thickness. Peak segmental LS values of the interventricular septum and lateral LV wall were measured in the A4C using two‐dimensional speckle‐tracking echocardiography. RAS LS was calculated as average apical LS/(average basal LS + average midventricular LS).ResultsRelative apical sparing of longitudinal strain values in patients with ALAC (1.23 ± 0.64) were significantly higher than those in FD patients (0.75 ± 0.19, P < 0.05) as well as in individuals with HLVH (0.75 ± 0.23, P < 0.05), but with a significant overlap. The optimal RAS LS value differentiating ALAC from FD and HLVH with 70% sensitivity and 75% specificity was 0.88 (AUC 0.79). In multivariate modeling, RAS LS was significantly additive to traditional predictors of ALAC (low QRS voltage and pseudoinfarct ECG patterns, pericardial effusion, E/e′ ratio, E‐wave deceleration time; P < 0.05 for all models).ConclusionsSimplified RAS LS evaluation represents an attractive approach for diagnostics of ALAC. However, because of considerable overlap with other disorders with hypertrophic phenotype, the analysis of RAS LS in the A4C should be combined with other traditional echocardiographic and ECG predictors in differentiating ALAC from other forms of concentric LV wall thickening.
Root and canal morphology of maxillary premolar teeth in an Egyptian subpopulation using two classification systems: a cone beam computed tomography study
Authors: Saber S. E. D. M. , Ahmed M. H. M. , Obeid M. , Ahmed H. M. A. 
Published: September 2018

AbstractAimTo investigate the number of roots and root canal configurations using two coding systems and the root canal diverging and merging levels in extracted maxillary premolars in an Egyptian subpopulation using cone beam computed tomography (CBCT).MethodologyA total of 700 maxillary premolars were examined using CBCT in an Egyptian subpopulation. The number of roots was identified, and root canal configurations were classified according to Vertucci's classification and a new system for classifying root and canal morphology. In addition, the position where roots bifurcated and the levels where canals merged or diverged were identified. Fisher's exact test and independent t‐test were used for statistical analysis, and the level of significance was set at 0.05 (P = 0.05).ResultsMore than half of maxillary first premolars were double‐rooted, and the majority of maxillary second premolars were single‐rooted (P < 0.001). Most of the double‐rooted samples had bifurcations in the middle of the root. According to the Vertucci classification, canal configuration type IV was the most common in both first and second maxillary premolars. According to the new system, the code 2FP B1 P1 was the most common for maxillary first premolars, whilst 2SP B1 P1, 1SP2 and 1SP2‐1 codes were the most common for maxillary second premolars. The three‐canalled morphology in double‐ and three‐rooted maxillary premolars had considerable variations. Root canal merging and diverging levels were comparable in both tooth types.ConclusionMaxillary premolars in this Egyptian subpopulation had a wide range of root and canal anatomical variations. Clinicians should be aware of where canals merge and diverge to facilitate the treatment of all canals. The new system for classifying canal morphology describes the root and canal configurations in a more accurate and practical manner compared to the Vertucci classification.
Regulatory T‐cells: receptors, repertoires and roles in disease
Authors: Altmann Daniel M. 
Published: September 2018

SummaryIn the 20‐or‐so years that immunologists have spent describing the mechanisms and functions of regulatory T‐cells, a very great deal has been learnt: a T‐cell subset once described for the generic ability to harness autoimmunity in vivo or diminish T‐cell proliferation in vitro is now appreciated to act on a plethora of cellular pathways using a diverse array of mechanisms. Recent studies have shed new light on basic and applied aspects of Treg function, including T‐cell receptor usage, specialist functions of tissue‐resident Tregs, and the therapeutic consequences of tuning Treg function up or down for applications in autoimmunity or cancer, respectively.
Modeling and solving the steelmaking and casting scheduling problem
Authors: Armellini Davide , Borzone Paolo , Ceschia Sara , Di Gaspero Luca , Schaerf Andrea 
Published: September 2018

AbstractWe propose a general model for the problem of planning and scheduling steelmaking and casting activities obtained by combining common features and constraints of the operations from a real plant and the literature. For tackling the problem, we develop a simulated annealing approach based on a solution space made of job permutations, which uses as submodule a chronological constructive procedure that assigns processing times and resources to jobs. Our technique, properly tuned in a statistically principled way, is able to find good solutions for a large range of different settings and horizons. In addition, it outperforms both a greedy procedure and a constraint‐based solver developed for comparison purposes on almost all instances. Finally, we have collected several real‐world instances that we make available on the web along with the solution validator and our best results.
Impact of cost uncertainty on supply chain competition under different confidence levels
Authors: Liu Zhibing , Zhou Chi , Chen Huiru , Zhao Ruiqing 
Published: September 2018

AbstractThis paper considers two competing supply chains that face cost uncertainty, each consisting of one supplier and one retailer. To address the uncertain cost information, we propose a decision rule based on confidence levels to measure the goals of the supply chain participants. We provide the new concept of the belief‐degree cost of a supply chain that embodies the decision maker's ability to comprehensively address information uncertainty and control the risk caused by information uncertainty. We find that regardless of which of the three games it is in – integrated, hybrid, or decentralized – a chain should order more and thereby gain more profit when its cost uncertainty increases or the competing chain's cost uncertainty decreases. The chain with a low or sufficiently low belief‐degree cost gains a competitive advantage on both quantity and profit. A chain's competitiveness can be enhanced by either decreasing its confidence level or increasing its rival's confidence level. Furthermore, we demonstrate that supply chain integration is the dominant strategy for given confidence levels. Nevertheless, a prisoner's dilemma occurs when the differences in the belief‐degree costs of the two supply chains are not significant and the competitive intensity is high. In addition, the magnitudes of the confidence levels can be changed to avoid or cause a prisoner's dilemma. Finally, under different confidence levels, the Stackelberg model for competing hybrid or decentralized supply chains is extended to the bargaining model, and the impact of bargaining power on supply chain competition is analyzed.