bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modelling hospital readmissions under frailty conditions for healthy aging
Authors: Graña Manuel , Lopez‐Guede Jose Manuel , Irazusta Jon , Labayen Idoia , Besga Ariadna 
Published: July 2019

AbstractIn the current context of an aging population in many developed countries, the issue of healthy aging is at the forefront of the political, scientific, and technological concerns. The frailty accompanying the late years of elderly people (>70 years old) deserves special consideration due to its great economical and personal costs and the workload imposed on the health care system. Hospital readmissions under a short time after hospital discharge are one of the sources of concern, and much effort is being devoted to their prediction for better care of the elder and optimized resource management. In this paper, we consider the prediction of readmissions for patients that are evaluated positively in the frailty scales. The computational experiments are carried out over a gender‐balanced cohort of 645 patients recruited at the University Hospital of Alava. We report machine‐learning prediction results of the readmission before the standard readmission limit of 30 days. We apply an upsampling technique to correct for class imbalance. Results are positive, encouraging further research and the creation of larger cohorts in international efforts.
Crack morphology models for fracture toughness and fatigue strength analysis
Authors: Carpinteri Andrea , Spagnoli Andrea , Terzano Michele 
Published: July 2019

AbstractPlanar cracks represent an approximation, largely adopted in fracture mechanics and fatigue problems, of the physical reality, where cracks feature complex geometric morphologies related to material microstructure, residual stresses, material properties dispersions and so on. In the present paper, firstly a model to describe the influence of roughness and friction of the crack surfaces is reviewed in relation to the resulting near‐tip stress field and the fracture resistance under monotonic loading. Such a model is based on the Distributed Dislocation Technique, and considers a periodic profile of the crack. Then, some approximate theoretical models describing periodically kinked cracks are reviewed in their application to the estimation of fatigue strength of materials. In particular, the influence of crack path meandering on fatigue propagation is analysed by modelling the crack profile as a piecewise linear periodic curve in two dimensions. The same type of model is discussed within the framework of self‐similar fractal geometries. In the paper, emphasis is given to the effect of crack size on the fracture resistance and fatigue strength, where such an effect depends on the ratio between the characteristic length of the crack morphology and the nominal length of the crack itself.
Monitoring of corrosion‐fatigue degradation of grade R4 steel using an electrochemical‐mechanical combined approach
Authors: Canut Felipe A. , Simões Alda M.P. , Reis Luis , Freitas Manuel , Bastos Ivan N. , Castro Fábio C. , Mamiya Edgar N. 
Published: July 2019

AbstractThe study deals with degradation and failure of mooring chains by the combined effect of corrosion and mechanical cyclic stresses on steel. Monitoring of the corrosion‐fatigue damage was carried out using electrochemical assessment during the application of the cyclic mechanical loading on grade R4 martensitic steel specimens, immersed in artificial seawater. The spontaneous potential of the steel specimens and Electrochemical Impedance Spectroscopy measurements were performed to assess the corrosion degradation. Tests conducted under fully reversed stress‐controlled loading have shown earlier failure caused by the corrosive environment when compared with the tests performed in ambient air. The corrosion potential response was used to identify the crack initiation and propagation stages.
Disrupted‐in‐schizophrenia 1 functional polymorphisms and D2/D3 receptor availability: A [11C]‐(+)‐PHNO imaging study
Authors: Dahoun Tarik , Nour Matthew M. , Adams Rick A. , Trossbach Svenja , Lee Sang H. , Patel Hamel , Curtis Charles , Korth Carsten , Howes Oliver D. 
Published: July 2019

AbstractThe disrupted‐in‐schizophrenia 1 (DISC1) protein has been implicated in a range of biological mechanisms underlying chronic mental disorders such as schizophrenia. Schizophrenia is associated with abnormal striatal dopamine signalling, and all antipsychotic drugs block striatal dopamine 2/3 receptors (D2/3Rs). Importantly, the DISC1 protein directly interacts and forms a protein complex with the dopamine D2 receptor (D2R) that inhibits agonist‐induced D2R internalisation. Moreover, animal studies have found large striatal increases in the proportion of D2R receptors in a high affinity state (D2highR) in DISC1 rodent models. Here, we investigated the relationship between the three most common polymorphisms altering the amino‐acid sequence of the DISC1 protein (Ser704Cys (rs821616), Leu607Phe (rs6675281) and Arg264Gln (rs3738401)) and striatal D2/3R availability in 41 healthy human volunteers, using [11C]‐(+)‐PHNO positron emission tomography. We found no association between DISC1 polymorphisms and D2/3R availability in the striatum and D2R availability in the caudate and putamen. Therefore, despite a direct interaction between DISC1 and the D2R, none of its main functional polymorphisms impact striatal D2/3R binding potential, suggesting DISC1 variants act through other mechanisms.
CRISPR/dCas9‐mediated activation of multiple endogenous target genes directly converts human foreskin fibroblasts into Leydig‐like cells
Authors: Huang Hua , Zou Xiangyu , Zhong Liang , Hou Yanping , Zhou Jin , Zhang Zhiyuan , Xing Xiaoyu , Sun Jie 
Published: July 2019

AbstractRecently, Leydig cell (LC) transplantation has been revealed as a promising strategy for treating male hypogonadism; however, the key problem restricting the application of LC transplantation is a severe lack of seed cells. It seems that targeted activation of endogenous genes may provide a potential alternative. Therefore, the aim of this study was to determine whether targeted activation of Nr5a1, Gata4 and Dmrt1 (NGD) via the CRISPR/dCas9 synergistic activation mediator system could convert human foreskin fibroblasts (HFFs) into functional Leydig‐like cells. We first constructed the stable Hsd3b‐dCas9‐MPH‐HFF cell line using the Hsd3b‐EGFP, dCas9‐VP64 and MS2‐P65‐HSF1 lentiviral vectors and then infected it with single guide RNAs. Next, we evaluated the reprogrammed cells for their reprogramming efficiency, testosterone production characteristics and expression levels of Leydig steroidogenic markers by quantitative real‐time polymerase chain reaction or Western blotting. Our results showed that the reprogramming efficiency was close to 10% and that the reprogrammed Leydig‐like cells secreted testosterone rapidly and, more importantly, responded effectively to stimulation with human chorionic gonadotropin and expressed Leydig steroidogenic markers. Our findings demonstrate that simultaneous targeted activation of the endogenous NGD genes directly reprograms HFFs into functional Leydig‐like cells, providing an innovative technology that may have promising potential for the treatment of male androgen deficiency diseases.
Patient‐assigned health utility values for controlled and uncontrolled pemphigus vulgaris and foliaceus
Authors: Hajdu K. , Brodszky V. , Stalmeier P.F.M. , Ruzsa G. , Tamási B. , Gulácsi L. , Péntek M. , Sárdy M. , Bata‐Csörgő Z. , Kinyó Á. , Szegedi A. , Rencz F. 
Published: July 2019

AbstractBackgroundThe assessment of health‐related quality of life (HRQoL) in patients with pemphigus is now of increasing interest due to the availability of highly effective new therapies. Preference‐based HRQoL values or health utilities required for medical and financial decision‐making are not yet available directly from pemphigus patients.ObjectiveTo obtain health utility values for current health and hypothetical health states from the perspective of pemphigus patients.MethodsA cross‐sectional questionnaire survey was carried out with pemphigus patients. Disease severity was rated by Autoimmune Bullous Skin Disorder Intensity Score (ABSIS). Patients were asked to evaluate their current health as well as three common hypothetical pemphigus health states [uncontrolled pemphigus vulgaris (PV), uncontrolled pemphigus foliaceus (PF) and controlled PV/PF] by using composite time trade‐off (cTTO). Multiple regression was applied to explore determinants of utility values.ResultsResponses of 108 patients (64.8% women, mean age 57.4 years) were analysed. Mean ABSIS score was 11.6. The mean utility values for the hypothetical uncontrolled PV, uncontrolled PF and controlled PV/PF health states were 0.41, 0.52 and 0.66 with cTTO. The mean cTTO scores for current health were higher compared with the hypothetical health states (0.76; P < 0.001). Patients with higher ABSIS, worse pain intensity scores and those having a caregiver reported lower utility values for current health (P < 0.05).ConclusionsIn pemphigus, HRQoL impairment expressed in utility values seems to be considerable, especially in comparison with other chronic dermatological conditions (e.g. psoriasis, atopic eczema, chronic hand eczema). These health utilities inform physicians, policymakers and funders about the overall extent of health loss in pemphigus and provide evidence to guide medical decisions and cost‐effectiveness analyses of treatment strategies. Future research is needed to evaluate the caregiver burden in pemphigus.
Lichen planus: a comprehensive evidence‐based analysis of medical treatment
Authors: Husein‐ElAhmed H. , Gieler U. , Steinhoff M. 
Published: July 2019

AbstractLichen planus (LP) is a chronic‐relapsing inflammatory skin disease. Although many drugs have been used for the management of LP, some of them lack the backup by strong therapeutic evidence, while others are not suitable for some patients due to safety profile issues. The aim of this study was to review the recent status of available medical therapies for LP to help physicians make better decisions upon best medical practice while facing patients with this condition. A review of published articles on management of LP was conducted with the MEDLINE and PubMed databases. The quality of the evidence was graded as high, moderate, low or very low. A total of 1366 articles were retrieved, and 219 (16%) were included in the final analysis. Twenty‐one different treatment modalities were analysed. The quality of evidence was high for topical steroid and calcineurin inhibitor, while it was moderate for oral steroids. All the other modalities reached low or very low quality of evidence. Topical steroids and calcineurin inhibitors are the current first‐line therapies, while for other therapies the strength of recommendation is not so evident. Unfortunately, larger randomized, controlled trials to support the efficacy, safety and tolerability of other therapies in LP are lacking, and many of them are recommended based on studies with small sample sizes, lack of standardized outcome measures or lack of controlled duration or even in anecdotal evidence. Thus, large‐scale randomized clinical trials are still warranted to establish the exact benefits of other topical treatments, phototherapy, immunosuppressant and new immunomodulators for an optimized treatment of LP.
Influence of experimental set‐up and methodology for measurements of metabolic rates and critical swimming speed in Atlantic salmon Salmo salar
Authors: Hvas Malthe , Oppedal Frode 
Published: July 2019

AbstractIn this study, swim‐tunnel respirometry was performed on Atlantic salmon Salmo salar post‐smolts in a 90 l respirometer on individuals and compared with groups or individuals of similar sizes tested in a 1905 l respirometer, to determine if differences between set‐ups and protocols exist. Standard metabolic rate (SMR) derived from the lowest oxygen uptake rate cycles over a 20 h period was statistically similar to SMR derived from back extrapolating to zero swim speed. However, maximum metabolic rate (MMR) estimates varied significantly between swimming at maximum speed, following an exhaustive chase protocol and during confinement stress. Most notably, the mean (±SE) MMR was 511 ± 15 mg O2 kg−1 h−1 in the swim test which was 52% higher compared with 337 ± 9 mg O2 kg−1 in the chase protocol, showing that the latter approach causes a substantial underestimation. Performing group respirometry in the larger swim tunnel provided statistically similar estimates of SMR and MMR as for individual fish tested in the smaller tunnel. While we hypothesised a larger swim section and swimming in groups would improve swimming performance, Ucrit was statistically similar between both set‐ups and statistically similar between swimming alone v. swimming in groups in the larger set‐up, suggesting that this species does not benefit hydrodynamically from swimming in a school in these conditions. Different methods and set‐ups have their own respective limitations and advantages depending on the questions being addressed, the time available, the number of replicates required and if supplementary samplings such as blood or gill tissues are needed. Hence, method choice should be carefully considered when planning experiments and when comparing previous studies.
The ARRIVE Trial: Interpretation from an Epidemiologic Perspective
Authors: Carmichael Suzan L. , Snowden Jonathan M. 
Published: July 2019

AbstractThe findings of the ARRIVE trial (A Randomized Trial of Induction Versus Expectant Management) were recently published. This multisite randomized trial was designed to provide evidence regarding whether labor induction or expectant management is associated with increased adverse perinatal outcomes and risk of cesarean birth among healthy nulliparous women at term. The trial reported that the primary outcome, a composite of adverse neonatal outcomes, was not significantly different between the 2 groups; the principal secondary outcome, cesarean birth, was significantly more common among women whose pregnancy was expectantly managed than among women whose labor was induced at 39 weeks. These results have the potential to change existing practice. Several aspects of the study design may influence its potential internal and external validity and should be considered in order to make sound causal inferences from this trial, which will in turn affect how its findings are translated to practice. Although chance and confounding are of minimal concern, given the sample size and randomization used in the study, selection bias may be a concern. Studies are vulnerable to selection bias when the sample population differs from eligible nonparticipants, including in randomized controlled trials. External validity is defined as the extent to which the study population and setting are representative of the larger source population the study intends to represent. External validity may be limited given the characteristics of the women enrolled in the ARRIVE trial and the practice settings where the study was conducted. This brief report provides concrete suggestions for further analyses that could help solidify conclusions from the trial, and for further research questions that will continue advancement toward answering this complex question of how best to manage labor and birth decisions at full term among low‐risk women.
Cellular models of alpha‐synuclein toxicity and aggregation
Authors: Delenclos Marion , Burgess Jeremy D. , Lamprokostopoulou Agaristi , Outeiro Tiago F. , Vekrellis Kostas , McLean Pamela J. 
Published: July 2019

AbstractMisfolding and aggregation of alpha‐synuclein (α‐synuclein) with concomitant cytotoxicity is a hallmark of Lewy body related disorders such as Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy. Although it plays a pivotal role in pathogenesis and disease progression, the function of α‐synuclein and the molecular mechanisms underlying α‐synuclein‐induced neurotoxicity in these diseases are still elusive. Many in vitro and in vivo experimental models mimicking α‐synuclein pathology such as oligomerization, toxicity and more recently neuronal propagation have been generated over the years. In particular, cellular models have been crucial for our comprehension of the pathogenic process of the disease and are beneficial for screening of molecules capable of modulating α‐synuclein toxicity. Here, we review α‐synuclein based cell culture models that reproduce some features of the neuronal populations affected in patients, from basic unicellular organisms to mammalian cell lines and primary neurons, to the cutting edge models of patient‐specific cell lines. These reprogrammed cells known as induced pluripotent stem cells (iPSCs) have garnered attention because they closely reproduce the characteristics of neurons found in patients and provide a valuable tool for mechanistic studies. We also discuss how different cell models may constitute powerful tools for high‐throughput screening of molecules capable of modulating α‐synuclein toxicity and prevention of its propagation.
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This article is part of the Special Issue “Synuclein”.
Parkinson’s disease biomarkers based on α‐synuclein
Authors: Fayyad Muneera , Salim Safa , Majbour Nour , Erskine Daniel , Stoops Erik , Mollenhauer Brit , El‐Agnaf Omar M. A. 
Published: July 2019

AbstractParkinson’s disease is the second most common neurodegenerative disorder after Alzheimer’s disease and is estimated to affect approximately 1–4% of individuals aged over 60 years old. Although considerable efforts have been invested into developing disease‐modifying therapies for Parkinson’s disease, such efforts have been confounded by the difficulty in accurately diagnosing Parkinson’s disease during life to enable accurate patient stratification for clinical trialling of candidate therapeutics. Therefore, the search for effective biomarkers that can be accurately evaluated during life with non‐invasive means is a pressing issue in the field. Since the discovery of α‐synuclein (α‐syn) as a protein linked to a familial form of Parkinson’s disease, later identified as the major protein component of the neuropathological hallmark of idiopathic Parkinson’s disease, considerable interest has focused on this protein and its distinct conformers. We describe here the progress that has been made in the area of Parkinson’s disease biomarker discovery with a focus on α‐synuclein. In particular, we highlight the novel assays that have been employed and the increasing complexity in evaluating α‐synuclein with regard to the considerable diversity of conformers that exist in the biofluids and peripheral tissues under disease conditions.
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“This article is part of the Special Issue Synuclein.”
A Systematic Review on the Conceptualization and Operationalization of Students' Levels of Processing in Functional Magnetic Resonance Imaging Studies
Authors: Catrysse Leen , Gijbels David , Donche Vincent 
Published: July 2019

ABSTRACTIn educational research, there is a growing interest in functional magnetic resonance imaging (fMRI) to examine students' levels of processing. As there is a growing interest in the use of fMRI, a systematic review was conducted to examine how deep and surface levels of processing are operationalized within the neuroscientific field. In addition, we investigated how this operationalization impacts on the conceptualization of levels of processing within fMRI research. A systematic search was conducted within the MEDLINE, PubMed, ERIC, and Web of Science databases, and 25 studies were identified for this review. With regard to the operationalization, the review indicates that levels of processing were examined under highly controlled conditions with decontextualized and simplified language stimuli. Analysis of these studies revealed that there is a lack of conceptual clarity as, in half of the cases, no theoretical framework was explicitly mentioned, and no clear definition was given regarding levels of processing.
The information distortion bias: implications for medical decisions
Authors: Boyle Peter J , Purdon Michael 
Published: July 2019

ContextEvery diagnosis involves an act of decision making, which requires proper evaluation of information. However, even seemingly objective information can require interpretation, often without our conscious awareness. In this cross‐cutting edge article we describe the phenomenon of leader‐driven information distortion (ID) and its implications for medical education.Information distortionRecent research indicates that one threat to good decisions is a biased interpretation of information to favour one alternative course of action over another. Once an alternative emerges as a leader during a decision there is a strong tendency to evaluate subsequent information as supporting that option. This can occur when deciding between two competing diagnoses. It is particularly a concern if diagnostic tests provide potentially ambiguous results. This leader‐driven ID is pre‐decisional in nature, in that it develops during a decision and involves the interpretation of information available prior to the final decision or diagnosis, with different interpretations possible depending on whichever alternative is the leader. Studies reveal that the distortion bias is pervasive in decisions, and that awareness of the act of distortion is low in decision makers.Application to medical educationEmpirical research has confirmed the presence of leader‐driven ID in hypothetical diagnoses made by physicians. ID creates two threats to medical decisions: First, it can make a diagnosis sticky in that it is resistant to being overturned by contradictory information. Second, it can promote unwarranted certainty in a diagnosis. The outcome may be premature closure, unnecessary testing or incorrect treatment, resulting in delayed or missed diagnoses.MethodsThis paper summarises research related to leader‐driven ID in medical and professional decisions and discusses various approaches directed towards reducing ID. A framework and language are provided for thinking about and discussing ID in medical decisions and medical education. Courses of action for mitigating the effects of ID are suggested.
Effects of endogenous levels of master regulator PrgX and peptide pheromones on inducibility of conjugation in the enterococcal pCF10 system
Authors: Erickson Rebecca J. B. , Manias Dawn A. , Hu Wei‐Shou , Dunny Gary M. 
Published: July 2019

SummaryEnterococcal pheromone responsive conjugative plasmids like pCF10 promote horizontal spread of antibiotic resistance genes following induction of plasmid‐containing cells by potential recipients. Transcription of conjugation genes from promoter PQ is inhibited by the master regulator PrgX, further repressed when PrgX is in complex with the inhibitory I peptide, and allowed when PrgX is in complex with the C inducing peptide. Single‐cell analysis has shown that heterogeneity in the pheromone response is prevalent. Here, we systematically varied levels of regulatory molecules to better understand why some individual cells have increased propensity for induction. In this study, PrgX was confirmed to repress PQ in the absence of exogenous peptides in vivo, but cells with increased levels of PrgX were shown to be more prone to induction. Further, ablation of endogenous I reduced PrgX levels, resulting in reduced basal repression and loss of inducibility. Reduction of both endogenous peptides by washing increased the inducibility of cells. Together, these results show that endogenous PrgX, C, and I levels can impact the induction potential of a cell and establish the importance of basal I for regulation. These results also suggest that PrgX/C complexes may directly activate prgQ transcription, contrary to a long‐standing working model.