bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of digital rectal exam on the 4Kscore for aggressive prostate cancer
Authors: Maccini Michael A. , Westfall Nicholas J. , Van Bokhoven Adrie , Lucia Marshall Scott , Poage Wendy , Maroni Paul D. , Wilson Shandra S. , Glodé Leonard Michael , Arangua Paul , Newmark Jay , Steiner Mitchell , Werahera Priya N. , Crawford Elward David 
Published: February 2018

BackgroundThe 4Kscore is a new commercially available blood‐based diagnostic test which predicts risk for aggressive, clinically significant prostate cancer on prostate biopsy. The 4Kscore is currently restricted to patients who have not had a digital rectal exam (DRE) in the previous 96 h, owing to prior mixed data suggesting that prostate specific antigen (PSA) isoforms may increase by a statistically significant—if not necessarily clinically significant—amount shortly after DRE. Our primary objective was to determine if 4Kscore test results are affected by a preceding DRE.MethodsParticipants at a Prostate Cancer Awareness Week screening event sponsored by the Prostate Conditions Education Council filled out clinical history questionnaires and had blood samples for 4Kscore testing drawn prior to DRE, then 15‐45 min following DRE. Patients with prior cancer diagnosis, 5‐alpha reductase inhibitor medication use, or lower urinary tract procedures in the prior 6 months were excluded, resulting in a population of 162 participants for analysis. Values were then compared to determine if there was a significant difference in 4Kscore following DRE.ResultsA statistically significant increase was seen in levels of 3 kallikreins measured (total PSA, free PSA, and intact PSA; median <0.03 ng/mL for all). This resulted in a small but statistically significant decrease in post‐DRE 4Kscore (median absolute score decrease 0.43%). Using a 4Kscore cutoff of 7.5% resulted in reclassification of 10 patients (6.2%), nine of whom were “downgraded” from above the cutoff to below.ConclusionsIf the blood draw for the 4 K score is performed after a screening DRE, there is a statistically significant difference in the 4 K score results, but in the vast majority of cases it would not affect clinical decision making.
The androgen receptor malignancy shift in prostate cancer
Authors: Copeland Ben T. , Pal Sumanta K. , Bolton Eric C. , Jones Jeremy O. 
Published: February 2018

BackgroundAndrogens and the androgen receptor (AR) are necessary for the development, function, and homeostatic growth regulation of the prostate gland. However, once prostate cells are transformed, the AR is necessary for the proliferation and survival of the malignant cells. This change in AR function appears to occur in nearly every prostate cancer. We have termed this the AR malignancy shift.MethodsIn this review, we summarize the current knowledge of the AR malignancy shift, including the DNA‐binding patterns that define the shift, the transcriptome changes associated with the shift, the putative drivers of the shift, and its clinical implications.ResultsIn benign prostate epithelial cells, the AR primarily binds consensus AR binding sites. In carcinoma cells, the AR cistrome is dramatically altered, as the AR associates with FOXA1 and HOXB13 motifs, among others. This shift leads to the transcription of genes associated with a malignant phenotype. In model systems, some mutations commonly found in localized prostate cancer can alter the AR cistrome, consistent with the AR malignancy shift. Current evidence suggests that the AR malignancy shift is necessary but not sufficient for transformation of prostate epithelial cells.ConclusionsReinterpretation of prostate cancer genomic classification systems in light of the AR malignancy shift may improve our ability to predict clinical outcomes and treat patients appropriately. Identifying and targeting the molecular factors that contribute to the AR malignancy shift is not trivial but by doing so, we may be able to develop new strategies for the treatment or prevention of prostate cancer.
Race affects SVR12 in a large and ethnically diverse hepatitis C‐infected patient population following treatment with direct‐acting antivirals: Analysis of a single‐center Department of Veterans Affairs cohort
Authors: Benhammou Jihane N. , Dong Tien S. , May Folasade P. , Kawamoto Jenna , Dixit Ram , Jackson Samuel , Dixit Vivek , Bhattacharya Debika , Han Steven B. , Pisegna Joseph R. 
Published: February 2018

AbstractHepatitis C virus (HCV) infection is a major cause of chronic liver disease. HCV cure has been linked to improved patient outcomes. In the era of direct‐acting antivirals (DAAs), HCV cure has become the goal, as defined by sustained virological response 12 weeks (SVR12) after completion of therapy. Historically, African‐Americans have had lower SVR12 rates compared to White people in the interferon era, which had been attributed to the high prevalence of non‐CC interleukin 28B (IL28B) type. Less is known about the association between race/ethnicity and SVR12 in DAA‐treated era. The aim of the study is to evaluate the predictors of SVR12 in a diverse, single‐center Veterans Affairs population. We conducted a retrospective study of patients undergoing HCV therapy with DAAs from 2014 to 2016 at the VA Greater Los Angeles Healthcare System. We performed a multivariable logistic regression analysis to determine predictors of SVR12, adjusting for age, HCV genotype, DAA regimen and duration, human immunodeficiency virus (HIV) status, fibrosis, nonalcoholic fatty liver disease (NAFLD) fibrosis score, homelessness, mental health, and adherence. Our cohort included 1068 patients, out of which 401 (37.5%) were White people and 400 (37.5%) were African‐American. Genotype 1 was the most common genotype (83.9%, N = 896). In the adjusted models, race/ethnicity and the presence of fibrosis were statistically significant predictors of non‐SVR. African‐Americans had 57% lower odds for reaching SVR12 (adj.OR = 0.43, 95% CI = 1.5‐4.1) compared to White people. Advanced fibrosis (adj.OR = 0.40, 95% CI = 0.26‐0.68) was also a significant predictor of non‐SVR. In a single‐center VA population on DAAs, African‐Americans were less likely than White people to reach SVR12 when adjusting for covariates.
Ageing by feet? Regional migration, neighbourhood choice and local demographic change in German cities
Authors: Neumann Uwe 
Published: February 2018

AbstractIn countries with an ageing population, regional migration affects the local consequences of demographic change. This paper investigates whether ageing implicates a more distinct residential segregation by age and results in an accelerated “ageing by feet” in urban districts not favoured by younger people. The large urban regions of North Rhine‐Westphalia in Germany serve as a case study that comprises both growing and stagnating cities. Thriving cities in the Rhineland (Bonn, Cologne and Düsseldorf) contrast with the Ruhr, where the population stagnates and ageing proceeds even more rapidly than in Germany as a whole. Intraurban variation in demographic change over the period 1998–2008 is examined using municipal statistics. The underlying segregation process is studied on the basis of a discrete choice model of neighbourhood sorting, using microdata from a representative survey carried out in the Ruhr in 2010. The analysis shows that in the course of an urban revival during the 1990s and 2000s, it was typical of individuals aged under 30 to prefer residence close to city centres. However, in the Ruhr, young adults were not underrepresented in households moving to ageing neighbourhoods that are located within a certain distance to centres either. It appears, therefore, that regional ageing will not necessarily lead to a self‐reinforcing agglomeration of young adults in the most popular central city quarters. Given a continued desire for urban centrality, however, it will become difficult for households with children to find suitable and affordable accommodation in the more central parts of large cities.
Hypolipidemic activity and mechanisms of the total phenylpropanoid glycosides from Ligustrum robustum (Roxb.) Blume by AMPK‐SREBP‐1c pathway in hamsters fed a high‐fat diet
Authors: Yang Runmei , Chu Xinxin , Sun Le , Kang Zhuoying , Ji Min , Yu Ying , Liu Ying , He Zhendan , Gao Nannan 
Published: February 2018

The aim of this study was to evaluate the hypolipidemic effect and mechanisms of total phenylpropanoid glycosides extracted from Ligustrum robustum (Roxb.) Blume (LRTPG) in hamsters fed a high‐fat diet and to discover bioactive components in HepG2 cell model induced by oleic acid. LRTPG of high (1.2 g/kg), medium (0.6 g/kg), and low (0.3 g/kg) doses was administrated daily for 21 consecutive days in hamsters. We found that in hamsters fed a high‐fat diet, LRTPG effectively reduced the concentrations of plasma triglycerides (TG), free fatty acid, total cholesterol, low‐density lipoprotein cholesterol, and hepatic TG and total cholesterol. And the compounds acteoside, ligupurpuroside A, ligupurpuroside C, and ligupurpuroside D significantly inhibited lipid accumulation in HepG2 cell at the concentration of 50 μmol/L. Mechanism research demonstrated that LRTPG increased the levels of phospho–AMP‐activated protein kinase and phospho‐sterol regulatory element binding protein‐1c in liver, further to suppress the downstream lipogenic genes as stearoyl‐CoA desaturase 1, glycerol‐3‐phosphate acyltransferase, 1‐acylglycerol‐3‐phosphate O‐acyltransferase 2, and diacylglycerol acyltransferase 2. In addition, LRTPG increased the hydrolysis of circulating TG by up‐regulating lipoprotein lipase activities. These results indicate that LRTPG prevents hyperlipidemia via activation of hepatic AMP‐activated protein kinase‐sterol regulatory element binding protein‐1c pathway.
A global scheme for controlling the mean and standard deviation of a process based on the optimal design of gauges
Authors: Mosquera Jaime , Aparisi Francisco , Epprecht Eugenio Kahn 
Published: February 2018

AbstractControl charts for variables are a reference tool for the statistical monitoring of a quantitative variable. However, there are processes in which the exact measurement of the variable is highly complex or costly. In these cases, one option is to base the monitoring on the number of units that are classified by a gauge as being above, below, or between a pair of reference limits. With this approach, the process control achieves the economy and agility of control by attributes. In the literature, one can find different alternatives to such schemes. In this paper, a more general formulation is introduced that subsumes many of the previously proposed schemes into a new control scheme by means of an additional parameter. Through a specially designed optimization procedure, it is possible to obtain the parameters that maximize the scheme's performance against a specified process shift.
Impact of Glutathione Modulation on Stability and Pharmacokinetic Profile of Redox‐Sensitive Nanogels
Authors: Drude Natascha , Winz Oliver H. , Mottaghy Felix M. , Roller Marion , Königs Hiltrud , Möller Martin , Singh Smriti , Morgenroth Agnieszka 
Published: February 2018

AbstractNanoparticles degradable upon external stimuli combine pharmacokinetic features of both small molecules as well as large nanoparticles. However, despite promising preclinical results, several redox responsive disulphide‐linked nanoparticles failed in clinical translation, mainly due to their unexpected in vivo behavior. Glutathione (GSH) is one of the most evaluated antioxidants responsible for disulfide degradation. Herein, the impact of GSH on the in vivo behavior of redox‐sensitive nanogels under physiological and modulated conditions is investigated. Labelling of nanogels with a DNA‐intercalating dye and a radioisotope allows visualization of the redox responsiveness at the cellular and the systemic levels, respectively. In vitro, efficient cleavage of disulphide bonds of nanogels is achieved by manipulation of intracellular GSH concentration. While in vivo, the redox‐sensitive nanogels undergo, to a certain extent, premature degradation in circulation leading to rapid renal elimination. This instability is modulated by transient inhibition of GSH synthesis with buthioninsulfoximin. Altered GSH concentration significantly changes the in vivo pharmacokinetics. Lower GSH results in higher elimination half‐life and altered biodistribution of the nanogels with a different metabolite profile. These data provide strong evidence that decreased nanogel degradation in blood circulation can limit the risk of premature drug release and enhance circulation half‐life of the nanogel.
Cover Image, Volume 9, Issue 2
Authors: Ng Adolf K.Y. , Andrews Jonathan , Babb David , Lin Yufeng , Becker Austin 
Published: February 2018

The cover image, by Adolf K.Y. Ng et al., is based on the Advanced Review Implications of climate change for shipping: Opening the Arctic seas, DOI: 10.1002/wcc.507. Photo Credit: Koi Yu Adolf Ng.
image
Embryonic neurogenesis in echinoderms
Authors: Hinman Veronica F. , Burke Robert D. 
Published: February 2018

The phylogenetic position of echinoderms is well suited to revealing shared features of deuterostomes that distinguish them from other bilaterians. Although echinoderm neurobiology remains understudied, genomic resources, molecular methods, and systems approaches have enabled progress in understanding mechanisms of embryonic neurogenesis. Even though the morphology of echinoderm larvae is diverse, larval nervous systems, which arise during gastrulation, have numerous similarities in their organization. Diverse neural subtypes and specialized sensory neurons have been identified and details of neuroanatomy using neuron‐specific labels provide hypotheses for neural function. The early patterning of ectoderm and specification of axes has been well studied in several species and underlying gene regulatory networks have been established. The cells giving rise to central and peripheral neural components have been identified in urchins and sea stars. Neurogenesis includes typical metazoan features of asymmetric division of neural progenitors and in some cases limited proliferation of neural precursors. Delta/Notch signaling has been identified as having critical roles in regulating neural patterning and differentiation. Several transcription factors functioning in pro‐neural phases of specification, neural differentiation, and sub‐type specification have been identified and structural or functional components of neurons are used as differentiation markers. Several methods for altering expression in embryos have revealed aspects of a regulatory hierarchy of transcription factors in neurogenesis. Interfacing neurogenic gene regulatory networks to the networks regulating ectodermal domains and identifying the spatial and temporal inputs that pattern the larval nervous system is a major challenge that will contribute substantially to our understanding of the evolution of metazoan nervous systems.This article is categorized under:

Comparative Development and Evolution > Model Systems
Comparative Development and Evolution > Body Plan Evolution
Early Embryonic Development > Gastrulation and Neurulation
Intermediate layer as measure against rolling bearing creep
Authors: Schiemann T. , Pörsch S. , Leidich E. , Sauer B. 
Published: February 2018

AbstractRolling bearings are a part of every wind‐turbine transmission. In terms of bearing design, the bearing rings are of particular interest. The current trend for increasing power and dynamic stress, together with the associated increases in specific loads, have brought creep―an irreversible relative motion between bearing rings and shafts or housings―to the forefront. Creep leads to wear and can cause shaft displacements with serious consequences for the meshing of teeth in gearboxes, for example. In fact, many insurance companies cite the creep of bearing rings as one of the main causes of wind‐turbine gearbox failures.This article presents a complex kinematic 3D FE multi‐body simulation of a rolling bearing. This simulation makes a detailed analysis of the relative motion or creep of bearing rings possible for the first time.It also presents options, based on materials technology and design, for reducing or eliminating creep in existing systems or at the product‐development phase. The 2 key solutions, both based on an additional layer between bearing and housing, that show best results are presented within this article. This gives the user specific information for optimizing the bearing structure with respect to the choice of bearing and bearing ring design to ensure that future damage is prevented.
Modelling damage equivalent loads in wind turbines from general operational signals: Exploration of relevant input selection methods using aeroelastic simulations
Authors: Pérez‐Campuzano Darío , Gómez de las Heras‐Carbonell Enrique , Gallego‐Castillo Cristóbal , Cuerva Alvaro 
Published: February 2018

AbstractFatigue represents a critical issue in many structural applications, and wind turbines are not an exception. Their dynamic response over the years determines the turbine's lifespan, meaning that fatigue loads have a clear impact on the Cost of Energy. Since the direct experimental determination of the loading state is complex or expensive, estimations arising from general operational signals can be explored as an indirect way to acquire knowledge of fatigue loading levels. A case study based on 10‐minute aeroelastic simulations of a wind turbine dynamics is used to develop a Damage Equivalent Load estimation model using operational signals (typically recorded by SCADA systems) as inputs. The focus is on both the input selection and the model configuration, seeking the combination which reaches the lowest error. Three filters and two innovative wrappers (exploration and optimization) were considered within the selection. Linear and Artificial Neural Network models were implemented and compared. Results showed performances in Damage Equivalent Load estimation below 4% in terms of Normalized Root Mean Squared Error, which is promising as compared with related work. Additional conclusions were obtained concerning appropriate Artificial Neural Network configurations (net type, architecture and training algorithm), likewise the potential contribution of a proposed genetic algorithm.
Effect of Rear Wheel Suspension on Tilt‐in‐Space Wheelchair Shock and Vibration Attenuation
Authors: Hischke Molly , Reiser Raoul F. 
Published: February 2018

AbstractBackgroundSuspension systems are designed to reduce shock and vibration exposure. An aftermarket rear‐wheel suspension system is now available for manual tilt‐in‐space wheelchairs.ObjectiveTo compare quantifiable shock and vibration on a rigid manual tilt‐in‐space wheelchair to published data on manual wheelchairs and to determine whether aftermarket rear suspension system will significantly decrease shock exposure when traversing common obstacles.DesignCross‐sectional.SettingResearch laboratory.ParticipantsTen healthy non‐wheelchair users.MethodsSubjects seated in a manual tilt‐in‐space wheelchair were pushed over 4 different obstacles (an exterior door threshold, truncated domes, 2‐cm descent, and 2‐cm ascent) with the chair as manufactured and with the suspension system installed.Main Outcome MeasurementsSuperior/inferior and anterior/posterior accelerations were assessed at the seat pan with and without the use of ISO 2631‐1 standards. Peak accelerations were analyzed from the door threshold, 2‐cm descent and 2‐cm ascent. Root mean square acceleration (RMSa) values were analyzed from the truncated domes, and vibration dose value (VDV) was analyzed for all surfaces.ResultsThere were no differences in time spent over the 4 obstacles between rigid and suspended conditions (P.064). Suspension decreased the peak acceleration at the rear wheel when it initially impacted the door threshold, and when the rear wheel traversed the 2‐cm descent and ascent (P.043). ISO 2631‐1 frequency weighting, placing emphasis on frequencies most harmful to humans, also supports suspension reducing peak accelerations at the rear wheel both when it initially impacted and left the door threshold, and when the rear wheel descended 2 cm (P.049). Suspension also reduced the truncated dome RMSa as well as the door threshold, 2‐cm descent, and total VDV (P.041).ConclusionsThe results indicate that rigid manual tilt‐in‐space wheelchairs respond to rough surfaces in a similar fashion to previously studied rigid wheelchairs. Furthermore, the aftermarket suspension system reduces some aspects of shock and vibration exposure, also consistent with previously studied suspension systems.Level of EvidenceNA
Osteomielite crônica pós-operatória nos ossos longos – O que sabemos e como conduzir esse problema
Authors: Heitzmann Lourenço Galizia , Battisti Raphael , Rodrigues Ayres Fernando , Lestingi Juliano Valente , Cavazzana Cinthya , Queiroz Roberto Dantas 
Published: February 2018

ResumoA osteomielite crônica pós-operatória é um problema de saúde importante devido à sua morbidade significativa e baixa taxa de mortalidade. Essa patologia se apresenta como um desafio do ponto de vista de compreensão da patogenia e também de escolha da estratégia de tratamento. O objetivo deste artigo foi revisar o tema proposto quanto à sua definição, patogenia, aspectos clínicos, diagnóstico e tratamento, e reunir todas essas informações em uma única publicação brasileira de caráter de atualização.Foram feitas buscas nas bases de dados PubMed, Lilacs e Cochrane Library com palavras-chave pertinentes ao tema, e foram escolhidos trabalhos atuais e de relevância.Este trabalho permitiu reunir informações clássicas e inovações relacionadas à osteomielite crônica e seu tratamento, e oferecer material de atualização para auxiliar os profissionais envolvidos no tratamento dessa doença na tomada de decisão terapêutica.
On a unified breaking onset threshold for gravity waves in deep and intermediate depth water
Authors: Barthelemy X. , Banner M. L. , Peirson W. L. , Fedele F. , Allis M. , Dias F. 
Published: February 2018

We revisit the classical but as yet unresolved problem of predicting the breaking onset of 2D and 3D irrotational gravity water waves. Based on a fully nonlinear 3D boundary element model, our numerical simulations investigate geometric, kinematic and energetic differences between maximally tall non-breaking waves and marginally breaking waves in focusing wave groups. Our study focuses initially on unidirectional domains with flat bottom topography and conditions ranging from deep to intermediate depth (depth to wavelength ratio from 1 to 0.2). Maximally tall non-breaking (maximally recurrent) waves are clearly separated from marginally breaking waves by their normalised energy fluxes localised near the crest tip region. The initial breaking instability occurs within a very compact region centred on the wave crest. On the surface, this reduces to the local ratio of the energy flux velocity (here the fluid velocity) to the crest point velocity for the tallest wave in the evolving group. This provides a robust threshold parameter for breaking onset for 2D wave packets propagating in uniform water depths from deep to intermediate. Further targeted study of representative cases of the most severe laterally focused 3D wave packets in deep and intermediate depth water shows that the threshold remains robust. These numerical findings for 2D and 3D cases are closely supported by our companion observational results. Warning of imminent breaking onset is detectable up to a fifth of a carrier wave period prior to a breaking event.