bluuebunny/crossref_metadata_2025_split huggingface dataset:
Common Variants Coregulate Expression of GBA and Modifier Genes to Delay Parkinson's Disease Onset
Authors: Schierding William , Farrow Sophie , Fadason Tayaza , Graham Oscar E.E. , Pitcher Toni L. , Qubisi Sara , Davidson Alan J. , Perry Jo K. , Anderson Tim J. , Kennedy Martin A. , Cooper Antony , O'Sullivan Justin M. 
Published: June 2020

AbstractBackgroundGBA mutations are numerically the most significant genetic risk factor for Parkinson's disease (PD), yet these mutations have low penetrance, suggesting additional mechanisms.ObjectivesThe objective of this study was to determine if the penetrance of GBA in PD can be explained by regulatory effects on GBA and modifier genes.MethodsGenetic variants associated with the regulation of GBA were identified by screening 128 common single nucleotide polymorphisms (SNPs) in the GBA locus for spatial cis‐expression quantitative trail locus (supported by chromatin interactions).ResultsWe identified common noncoding SNPs within GBA that (1) regulate GBA expression in peripheral tissues, some of which display α‐synuclein pathology and (2) coregulate potential modifier genes in the central nervous system and/or peripheral tissues. Haplotypes based on 3 of these SNPs delay disease onset by 5 years. In addition, SNPs on 6 separate chromosomes coregulate GBA expression specifically in either the substantia nigra or cortex, and their combined effect potentially modulates motor and cognitive symptoms, respectively.ConclusionsThis work provides a new perspective on the haplotype‐specific effects of GBA and the genetic etiology of PD, expanding the role of GBA from the gene encoding the β‐glucocerebrosidase (GCase) to that of a central regulator and modifier of PD onset, with GBA expression itself subject to distant regulation. Some idiopathic patients might possess insufficient GBA‐encoded GCase activity in the substantia nigra as the result of distant regulatory variants and therefore might benefit from GBA‐targeting therapeutics. The SNPs’ regulatory impacts provide a plausible explanation for the variable phenotypes also observed in GBA‐centric Gaucher's disease and dementia with Lewy bodies. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, LLC on behalf of International Parkinson and Movement Disorder Society.
Gluten‐Free Diet in IBD: Time for a Recommendation?
Authors: Weaver Kimberly N. , Herfarth Hans 
Published: June 2020

AbstractPatients and providers alike are highly interested in identifying potentially useful dietary interventions in the management of inflammatory bowel diseases (IBD). This review examines the clinical associations of celiac disease (CeD), non‐celiac gluten sensitivity (NCGS), and IBD with a focus on available data of the therapeutic efficacy of gluten‐free diet (GFD) or low‐gluten‐containing diets in the therapy of IBD. There is a strong association between CeD and microscopic colitis, but the prevalence of CeD among IBD patients is similar to that of the general population. Interestingly, in cross‐sectional studies nearly one‐third of IBD patients report a diagnosis of NCGS, and many follow a GFD. Although animal studies have shown that gluten ingestion may promote intestinal inflammation and increase intestinal permeability, there have been no prospective studies evaluating the role of a GFD in the induction and maintenance of Crohn's disease and ulcerative colitis. Several cross‐sectional reports suggest that a GFD may improve symptoms in IBD patients, but due to a lack of high‐quality prospective clinical studies, current data do not support the universal use of a GFD in IBD.
Brain nitric oxide induces facilitation of the micturition reflex through brain glutamatergic receptors in rats
Authors: Ono Hideaki , Shimizu Takahiro , Zou Suo , Yamamoto Masaki , Shimizu Yohei , Aratake Takaaki , Hamada Tomoya , Nagao Yoshiki , Shimizu Shogo , Higashi Youichirou , Saito Motoaki 
Published: June 2020

AbstractAimBrain nitric oxide (NO) have been reported in regulation of the sympatho‐adrenomedullary system, which can affect voiding and storage functions. Therefore, we investigated effects of intracerebroventricularly (icv) administered 3‐(4‐morpholinyl)sydnonimine, hydrochloride (SIN‐1) (NO donor) on the micturition reflex, focusing on their dependence on the sympatho‐adrenomedullary system and on brain N‐methyl‐D‐aspartate (NMDA) and α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionate (AMPA) receptors in urethane‐anesthetized (0.8 g/kg, ip) male Wistar rats.MethodsPlasma noradrenaline and adrenaline were measured just before and 5 minutes after SIN‐1 administration. Evaluation of urodynamic parameters was started 1 hour before SIN‐1 administration or intracerebroventricular pretreatment with other drugs.ResultsSIN‐1 (100 and 250 µg/animal) elevated plasma adrenaline and reduced intercontraction interval ([ICI] values; 110.5% [SIN‐1, 0 µg] and 54.9% [SIN‐1, 250 µg] during 15 minutes after SIN‐1 administration [P < .05; η2 = 0.59]) without affecting plasma noradrenaline or maximal voiding pressure. SIN‐1 (250 µg/animal) reduced single‐voided volume and bladder capacity without affecting post‐voiding residual volume. The SIN‐1 (250 µg/animal)‐induced adrenaline elevation and ICI reduction were attenuated by 2‐(4‐carboxyphenyl)‐4,4,5,5‐tetramethylimidazoline‐1‐oxyl‐3‐oxide, sodium salt (carboxy‐PTIO) (NO scavenger, icv) (ICI values; 44.7% [vehicle + SIN‐1] and 77.5% [carboxy‐PTIO + SIN‐1] during 15 minutes after SIN‐1 administration [P < .05; η2 = 0.51]). Acute bilateral adrenalectomy abolished SIN‐1‐induced adrenaline elevation, while showed no effect on the SIN‐1‐induced ICI reduction. The ICI reduction was attenuated by MK‐801 (NMDA receptor antagonist, icv) (ICI values; 47.0% [vehicle + SIN‐1] and 87.6% [MK‐801 + SIN‐1] during 15 minutes after SIN‐1 administration [P < .05; η2 = 0.61]), but not by DNQX (AMPA receptor antagonist, icv).ConclusionBrain NO is involved in facilitation of the rat micturition reflex through brain NMDA receptors, independently of the sympatho‐adrenomedullary outflow modulation.
Good urodynamic practice adaptations during the COVID‐19 pandemic
Authors: Hashim Hashim , Thomas Laura , Gammie Andrew , Farullo Giuseppe , Finazzi‐Agrò Enrico 
Published: June 2020

AbstractUrodynamics testing forms the cornerstone of investigations when it comes to lower urinary tract dysfunction. It has to be done to the highest standards by following the International Continence Society Good Urodynamics Practice protocols. However, with the COVID‐19 pandemic, certain adaptations to the urodynamics procedure need to be considered especially when it comes to quality control. This article aims to define these adaptations to help urodynamicists in their daily practice.
Factors involved in the persistence of stress urinary incontinence from postpartum to 12 years after first delivery
Authors: Diez‐Itza Irene , Zubikarai Maitane , Galan Claudia , Ginto Leire , Saro Javier , Arrue Miren 
Published: June 2020

AbstractAimsThe aim of this study was to investigate constitutional‐, pregnancy‐, labor‐, and delivery‐related factors involved in the long‐term persistence of stress urinary incontinence (SUI) from 6 months postpartum to 12 years after first delivery. We also evaluated severity and impact on quality of life of persistent SUI.MethodsThis was a longitudinal study including primigravid women who gave birth at our Public Health Hospital during 2007. Urinary symptoms were investigated at inclusion, 6 months and 12 years after delivery. Persistent SUI was defined as SUI reported both at 6 months postpartum and 12 years after first delivery. The International Consultation on Incontinence‐Urinary Incontinence‐Short Form (ICIQ‐UI‐SF) and the Incontinence Severity Index (ISI) were used to evaluate SUI.ResultsDuring the inclusion period, 479 pregnant women were interviewed, 381 attended the 6‐month follow‐up visit, and 315 formed the study group. SUI persisted in 36 out of 44 (81.8%) women. With the ISI, 52.8% of these women were categorized as having slight, 41.7% moderate, and 5.6% severe incontinence. The mean ICIQ‐UI‐SF score was 7.13 (SD 3.51). Pregnancy SUI (odds ratio [OR], 4.54; 95% confidence interval [CI], 2.10‐9.80) and active second stage of labor more than or equal to 1 hour (OR, 3.68; 95% CI, 1.21‐11.14) were independently associated with persistent SUI.ConclusionsWomen who reported SUI during pregnancy, and those who had pushed for more than or equal to 1 hour in the second stage of labor were at greater risk of SUI persisting from 6 months postpartum to long after delivery. We found this independent association after controlling for several constitutional‐, pregnancy‐, labor‐, and delivery‐related variables.
Reliability of a two‐dimensional demand‐based networked system with multistate components
Authors: Xiao Hui , Yi Kunxiang , Kou Gang , Xing Liudong 
Published: June 2020

AbstractExisting research on multistate system reliability has mainly focused on one‐dimensional systems such as parallel systems, linear sliding window systems, and linearly consecutively connected systems. However, two‐dimensional networked systems widely exist in real‐world applications such as lighting systems, monitoring systems, and computer network systems. This research considers a two‐dimensional networked system consisting of multistate components. The system fails if the cumulative performance of any row or any column cannot meet a predetermined demand. A novel reliability evaluation algorithm is proposed for the considered two‐dimensional networked system by extending the universal generating function technique. Furthermore, the proposed model and reliability evaluation algorithm are extended to a two‐dimensional networked system with phased missions. The proposed models and algorithms are illustrated by a matrix heating system in a thermoforming machine.
Patients’ perspective of attending nursing consultations—A pilot and feasibility study
Authors: Graarup Jytte , Højskov Ida Elisabeth 
Published: June 2020

AbstractAimThe aims were to explore: (a) how patients with advanced heart and lung failure accept the overall framework of the nursing consultations and (b) the patients’ acceptability and applicability of the nursing consultations.DesignQualitative study.MethodsInterviews were conducted in an holistic frame and analysed using Graneheim and Lundman's qualitative content thematic analysis. Patients were interviewed between April and May 2018 regarding their general view of the nursing consultation and their experience of the framework inspired by R. R. Parse.ResultsThe overall theme was A confidential moment with the nurse to deal with and become more aware of what is important, based on following subthemes: “An option that makes sense,” “Scheduled time with the nurse is important” and “To find a new normality in everyday life.” The framework addressed a space of freedom requested by the informants, for whom attending nursing consultations was useful and meaningful, enabling them to reflect on everyday challenges.
A combined hybrid mixed element method for incompressible miscible displacement problem with local discontinuous Galerkin procedure
Authors: Zhang Jiansong , Han Huiran , Guo Hui , Shen Xiaomang 
Published: June 2020

AbstractIn this article, we propose a combined hybrid discontinuous mixed finite element method for miscible displacement problem with local discontinuous Galerkin method. Here, to obtain more accurate approximation and deal with the discontinuous case, we use the hybrid mixed element method to approximate the pressure and velocity, and use the local discontinuous Galerkin finite element method for the concentration. Compared with other combined methods, this method can improve the efficiency of computation, deal with the discontinuous problem well and keep local mass balance. We study the convergence of this method and give the corresponding optimal error estimates inL∞(L2)for velocity and concentration and the super convergence inL∞(H1)for pressure. Finally, we also present some numerical examples to confirm our theoretical analysis.
Anti‐tumour effects of PIM kinase inhibition on progression and chemoresistance of hepatocellular carcinoma
Authors: Leung Ming‐Sum , Chan Kristy Kwan‐Shuen , Dai Wen‐Juan , Wong Cheuk‐Yan , Au Kwan‐Yung , Wong Pik‐Ying , Wong Carmen Chak‐Lui , Lee Terence Kin‐Wah , Ng Irene Oi‐Lin , Kao Weiyuan John , Lo Regina Cheuk‐Lam 
Published: June 2020

AbstractHepatocellular carcinoma (HCC) is a biologically aggressive cancer. Targeted therapy is in need to tackle challenges in the treatment perspective. A growing body of evidence suggests a promising role of pharmacological inhibition of PIM (proviral integration site for Moloney murine leukaemia virus) kinase in some human haematological and solid cancers. Yet to date, the potential application of PIM inhibitors in HCC is still largely unexplored. In the present study we investigated the pre‐clinical efficacy of PIM inhibition as a therapeutic approach in HCC. Effects of PIM inhibitors on cell proliferation, migration, invasion, chemosensitivity, and self‐renewal were examined in vitro. The effects of PIM inhibitors on tumour growth and chemoresistance in vivo were studied using xenograft mouse models. Potential downstream molecular mechanisms were elucidated by RNA sequencing (RNA‐seq) of tumour tissues harvested from animal models. Our findings demonstrate that PIM inhibitors SGI‐1776 and PIM447 reduced HCC proliferation, metastatic potential, and self‐renewal in vitro. Results from in vivo experiments supported the role of PIM inhibition in suppressing of tumour growth and increasing chemosensitivity of HCC toward cisplatin and doxorubicin, the two commonly used chemotherapeutic agents in trans‐arterial chemoembolisation (TACE) for HCC. RNA‐seq analysis revealed downregulation of the MAPK/ERK pathway upon PIM inhibition in HCC cells. In addition, LOXL2 and ICAM1 were identified as potential downstream effectors. Taken together, PIM inhibitors demonstrated remarkable anti‐tumourigenic effects in HCC in vitro and in vivo. PIM kinase inhibition is a potential approach to be exploited in formulating adjuvant therapy for HCC patients of different disease stages. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
A new PARAFAC‐based algorithm for HPLC–MS data treatment: herbal extracts identification
Authors: Turova Polina , Rodin Igor , Shpigun Oleg , Stavrianidi Andrey 
Published: June 2020

AbstractIntroductionRole of highly informative high‐performance liquid chromatography mass spectrometry (HPLC–MS) methods in quality control is increasing. Complex herbal products and formulations can simultaneously contain extracts from different plants. Therefore, due to the leads to lack of commercial standards it is important to develop novel approaches for comprehensive treatment of big datasets.ObjectiveThe aim of this study is to create a straightforward and information‐saving algorithm for the identification of plants extracts in commercial products.Material and methodsIn total, 34 samples, including Glycyrrhiza glabra and Panax ginseng dried roots; and Abrus precatorius dried leaves, their double and triple mixtures and flavoured oolong tea samples were analysed by HPLC–MS and combined in a three‐dimensional dataset (retention time–mass‐to‐charge ratio (m/z)–samples). This dataset was subjected to smoothing and denoising techniques and further decomposed using parallel factor analysis (PARAFAC).ResultsSamples were divided into eight clusters; loading matrices were interpreted and the presence of the most characteristic triterpene glycoside groups was demonstrated and supported by the characteristic chromatogram approach. The occurrence of Abrus precatorius and G. glabra additives in flavoured tea was confirmed.ConclusionDeveloped HPLC–MS‐PARAFAC method is potentially reliable and an efficient tool for handling untreated experimental data and its future development may lead to more comprehensive evaluation of chemical composition and quality control of food additives and other complex mixtures.
Adherence and barriers to general and respiratory exercises in cystic fibrosis
Authors: Santuzzi Cíntia Helena , Liberato Fernanda Mayrink Gonçalves , Morau Samilly Ariany Corrêa , de Oliveira Néville Ferreira Fachini , Nascimento Lucas Rodrigues 
Published: June 2020

AbstractObjectivesTo investigate the adherence and the self‐reported barriers to general and respiratory exercises reported by individuals with cystic fibrosis (CF).Study DesignAn exploratory, experimental study.MethodsCommunity‐dwelling individuals aged 16 years and over, diagnosed with CF, who were accompanied in referral centers were included. Information regarding adherence to exercises was obtained by a questionnaire and reported as a ratio between prescribed exercises and self‐reported adherence. The weekly frequency was used to verify adherence to exercise initiation, and the amount of session duration concluded was used to verify adherence to exercise duration. Values above 0.70 were considered as high adherence. Eight demographic and clinical factors were examined to explore their relationships with adherence, and the barriers to exercises were also collected by questionnaire.ResultsThirty‐four participants met the inclusion criteria. Overall, adherence to exercise initiation was 0.40 (standard deviation [SD] = 0.3) for general exercises and 0.63 (SD = 0.4) for respiratory exercises. Adherence to exercise duration was 0.76 (SD = 0.4) for general exercises and 0.73 (SD = 0.4) for respiratory exercises. Forced vital capacity (r = 0.39; P = .02) was associated with adherence to the duration of general exercises, and body mass index (r = −0.33; P = .05) was associated with adherence to the duration of respiratory exercises. The main reported barriers were lack of interest, motivation and time, tiredness, noncommitment, and do not recognize the benefits of exercises.ConclusionsIndividuals with CF minded completing the sessions of prescribed exercises once they have initiated it, but most of the days they did not practice general or respiratory exercises.
Skull metastases revealing a hepatocellular carcinoma: Case report and literature review
Authors: Essadi Ismail , Lalya Issam , Kaakoua Mohamed , Arsalane Adil , Elomrani Abdelhamid , Khouchani Mouna , Belbaraka Rhizlane 
Published: June 2020

AbstractIntroductionHepatocellular carcinoma (HCC) revealed by skull metastasis is very rare situation. This would mean that the patient was probably misdiagnosed allowing the disease to progress to an advanced stage, for which no curative treatment can be envisaged.Case PresentationWe report the case of a 70‐years‐old Moroccan male, treated by interferon since 2014 for viral hepatitis C. He reported a gradual installation of scalp masses, which have grown in size and become painful. Surgical biopsy with histopathologic and immunohistochemical studies established the diagnosis of metastasis of HCC. This case was managed by palliative radiotherapy and is currently under treatment by Sorafenib.ConclusionCranial metastasis as first symptom of HCC, represents an exceptional situation, which must not delay the diagnosis allowing a fast and effective management to have access to an optimal therapeutic outcome.
A mechanistic view of enzyme evolution
Authors: Yang Gloria , Miton Charlotte M. , Tokuriki Nobuhiko 
Published: June 2020

AbstractNew enzyme functions often evolve through the recruitment and optimization of latent promiscuous activities. How do mutations alter the molecular architecture of enzymes to enhance their activities? Can we infer general mechanisms that are common to most enzymes, or does each enzyme require a unique optimization process? The ability to predict the location and type of mutations necessary to enhance an enzyme's activity is critical to protein engineering and rational design. In this review, via the detailed examination of recent studies that have shed new light on the molecular changes underlying the optimization of enzyme function, we provide a mechanistic perspective of enzyme evolution. We first present a global survey of the prevalence of activity‐enhancing mutations and their distribution within protein structures. We then delve into the molecular solutions that mediate functional optimization, specifically highlighting several common mechanisms that have been observed across multiple examples. As distinct protein sequences encounter different evolutionary bottlenecks, different mechanisms are likely to emerge along evolutionary trajectories toward improved function. Identifying the specific mechanism(s) that need to be improved upon, and tailoring our engineering efforts to each sequence, may considerably improve our chances to succeed in generating highly efficient catalysts in the future.
The generalized Ekman model for the tropical cyclone boundary layer revisited: The myth of inertial stability as a restoring force
Authors: Smith Roger K. , Montgomery Michael T. 
Published: June 2020

AbstractWe revisit the linear boundary‐layer approximation that expresses a generalized Ekman balance and use it to clarify a range of interpretations in the previous literature on the tropical cyclone boundary layer. Some of these interpretations relate to the reasons for inflow in the boundary layer and others relate to the presumed effects of inertial stability on boundary‐layer dynamics. Inertial stability has been invoked, for example, to explain aspects of boundary‐layer behaviour, including the frontogenetic nature of the boundary layer and its relationship to vortex spin‐up. Our analysis exposes the fallacy of invoking inertial stability as a resistance to radial inflow in the boundary layer. The analysis shows also that the nonlinear acceleration terms become comparable to the linear Coriolis acceleration terms in relatively narrow vortices that are inertially stable above the boundary layer. Estimates of the nonlinear accelerations using the linear solutions are expected to underestimate the actual contribution in a nonlinear boundary‐layer model, cautioning against neglecting the nonlinear terms in diagnostic or prognostic models.
A hybrid homogeneously weighted moving average control chart for process monitoring
Authors: Adeoti Olatunde Adebayo , Koleoso Sunday Olawale 
Published: June 2020

AbstractSeveral modifications and enhancements to control charts in increasing the performance of small and moderate process shifts have been introduced in the quality control charting techniques. In this paper, a new hybrid control chart for monitoring process location is proposed by combining two homogeneously weighted moving average (HWMA) control charts. The hybrid homogeneously weighted moving average (HHWMA) statistic is derived using two smoothing constants λ1 and λ2. The average run length (ARL) and the standard deviation of the run length (SDRL) values of the HHWMA control chart are obtained and compared with some existing control charts for monitoring small and moderate shifts in the process location. The results of study show that the HHWMA control chart outperforms the existing control charts in many situations. The application of the HHWMA chart is demonstrated using a simulated data.