bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of the Brussels Infant and Toddler Stool Scale (‘BITSS’): protocol of the study
Authors: Vandenplas Yvan , Szajewska Hania , Benninga Marc , Di Lorenzo Carlo , Dupont Christophe , Faure Christophe , Miqdadi Mohamed , Osatakul Seksit , Ribes-Konickx Carmen , Saps Miguel , Shamir Raanan , Staiano Annamaria 
Published: March 2017

IntroductionThe Bristol Stool Form Scale (BSS) which consists of 7 photographs of different stool forms allows assessment of stool consistency (scale 1 for hard lumps to scale 7 for watery stools), in an objective manner in adults. The BSS is also sometimes used to characterise the stools of infants and young children. Despite its use, there is general agreement among paediatric gastroenterologists that the BSS is not adequate to be used in infants and young children who wear diapers; thus, a new scale specifically designed for this population is needed. Our aim is to develop a paediatric stool scale, the Brussels Infant and Toddler Stool Scale (‘BITSS’), and to evaluate the interobserver agreement of stool assessment with the BITSS between the patient's parent and healthcare providers (physicians and nurses).Methods and analysisThis study has two phases. In the first phase, 11 key-opinion leaders in the field of paediatric gastroenterology representing different areas of the world selected seven coloured photographs of infants and/or young children wearing diapers to match the original descriptors of the BSS. The selected photographs were used to create a new scale in which the drawings of stools of the BSS were replaced by infant/toddlers stool photographs. In phase II, we aim at demonstrating that parents, nurses and primary healthcare physicians interpret the stool-pictures of the BITSS with a high degree of consensus and that the agreement is independent of whether it is a parent or a healthcare provider. Interobserver variability of stool assessment with the BITSS between the patient's parent and healthcare providers will be assessed.Ethics and disseminationThe study will be approved by the Ethics Committee of the participating centres. The findings of this study will be submitted to a peer-reviewed journal. Abstracts will be submitted to national and international conferences.Trial registration numberNCT02913950.
Predicting late-onset sepsis by routine neonatal screening for colonisation by gram-negative bacteria in neonates at intensive care units: a protocol for a systematic review
Authors: Harder Thomas , Seidel Juliane , Eckmanns Tim , Weiss Bettina , Haller Sebastian 
Published: March 2017

IntroductionHospitals conduct extensive screening procedures to assess colonisation of the body surface of neonates by gram-negative bacteria to avoid complications like late-onset sepsis. However, the benefits of these procedures are controversially discussed. Until now, no systematic review has investigated the value of routine screening for colonisation by gram-negative bacteria in neonates for late-onset sepsis prediction.Methods and analysisWe will conduct a systematic review, considering studies of any design that include infants up to an age of 12 months. We will search MEDLINE and EMBASE (inception to 2016), reference lists and grey literature. Screening of titles, abstracts and full texts will be conducted by two independent reviewers. We will extract data on study characteristics and study results. Risk of bias will be assessed using Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) and Quality in Prognosis Studies (QUIPS) tools. Subgroup analyses are planned according to characteristics of studies, participants, index tests and outcome. For quantitative data synthesis on prognostic accuracy, sensitivity and specificity of screening to detect late-onset sepsis will be calculated. If sufficient data are available, we will calculate summary estimates using hierarchical summary receiver operating characteristics and bivariate models. Applying a risk factor approach, pooled summary estimates will be calculated as relative risk or OR, using fixed-effects and random-effects models. I-squared will be used to assess heterogeneity. All calculations will be performed in Stata V14.1 (College Station, Texas, USA). The results will be used to calculate positive and negative predictive value and number needed to be screened to prevent one case of sepsis. Grading of Recommendations Assessment, Development and Evaluation (GRADE) will be used to assess certainty in the evidence. The protocol follows the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guideline.Ethics and disseminationThis study will not require ethical approval since it is not carried out in humans. The systematic review will be published in an open-access peer-reviewed journal.Trial registration numberCRD42016036664.
HNRNPLL, a newly identified colorectal cancer metastasis suppressor, modulates alternative splicing of CD44 during epithelial-mesenchymal transition
Authors: Sakuma Keiichiro , Sasaki Eiichi , Kimura Kenya , Komori Koji , Shimizu Yasuhiro , Yatabe Yasushi , Aoki Masahiro 
Published: March 2017

ObjectiveDespite the recent advances in treatment of colon cancer, the prognosis is unfavourable for patients with distant metastases. The aim of this study was to identify targets for prevention and/or therapy of colon cancer metastasis.DesignCMT93 cells, a murine rectal cancer cell line with poor metastasising activity, were transduced with lentiviral shRNA library and transplanted into the rectum of syngeneic C57BL/6 mice. Genomic DNA was collected from metastatic lesions, and the integrated shRNA were retrieved by PCR for sequencing, followed by identification of the candidate genes targeted by the shRNA.ResultsThe genome-wide shRNA library screen identified Hnrnpll (heterogeneous nuclear ribonucleoprotein L-like) encoding a pre-mRNA splicing factor as a candidate metastasis suppressor gene. Knockdown of Hnrnpll enhanced matrigel invasion activity of colon cancer cells in vitro, as well as their metastatic ability in vivo. An RNA-immunoprecipitation analysis showed Hnrnpll-binding to Cd44 pre-mRNAs, and the level of Cd44 variable exon 6 (Cd44v6), a poor prognosis marker of colorectal cancer, was increased by knocking down Hnrnpll. A neutralising Cd44v6 antibody suppressed the matrigel invasion ability induced by Hnrnpll knockdown. HNRNPLL expression was downregulated when colon cancer cells were induced to undergo epithelial-mesenchymal transition (EMT). Immunohistochemistry of clinical samples indicated that colorectal cancer cells with low E-cadherin expression at the invasion front exhibited decreased HNRNPLL expression.ConclusionsHNRNPLL is a novel metastasis suppressor of colorectal cancer, and modulates alternative splicing of CD44 during EMT.
CHK2 overexpression and mislocalisation within mitotic structures enhances chromosomal instability and hepatocellular carcinoma progression
Authors: Carloni Vinicio , Lulli Matteo , Madiai Stefania , Mello Tommaso , Hall Andrew , Luong Tu Vinh , Pinzani Massimo , Rombouts Krista , Galli Andrea 
Published: March 2017

ObjectiveChromosomal instability (CIN) is the most common form of genomic instability, which promotes hepatocellular carcinoma (HCC) progression by enhancing tumour heterogeneity, drug resistance and immunity escape. CIN per se is an important factor of DNA damage, sustaining structural chromosome abnormalities but the underlying mechanisms are unknown.DesignDNA damage response protein checkpoint kinase 2 (Chk2) expression was evaluated in an animal model of diethylnitrosamine-induced HCC characterised by DNA damage and elevated mitotic errors. Chk2 was also determined in two discrete cohorts of human HCC specimens. To assess the functional role of Chk2, gain on and loss-of-function, mutagenesis, karyotyping and immunofluorescence/live imaging were performed by using HCT116, Huh7 and human hepatocytes immortalised with hTERT gene (HuS).ResultsWe demonstrate that mitotic errors during HCC tumorigenesis cause lagging chromosomes/DNA damage and activation of Chk2. Overexpression/phosphorylation and mislocalisation within the mitotic spindle of Chk2 contributes to induce lagging chromosomes. Lagging chromosomes and mitotic activity are reversed by knockdown of Chk2. Furthermore, upregulated Chk2 maintains mitotic activity interacting with Aurora B kinase for chromosome condensation and cytokinesis. The forkhead-associated domain of Chk2 is required for Chk2 mislocalisation to mitotic structures. In addition, retinoblastoma protein phosphorylation contributes to defective mitoses. A cohort and independent validation cohort show a strong cytoplasm to nuclear Chk2 translocation in a subset of patients with HCC.ConclusionsThe study reveals a new mechanistic insight in the coinvolvement of Chk2 in HCC progression. These findings propose Chk2 as a putative biomarker to detect CIN in HCC providing a valuable support for clinical/therapeutical management of patients.
Euthanasing treatable patients
Authors: Coghlan Simon 
Published: March 2017

THIS series gives readers the opportunity to consider and contribute to discussion of some of the ethical dilemmas that can arise in veterinary practice. Each month, a case scenario is presented, followed by discussion of some of the issues involved.In addition, a possible way forward is suggested; however, there is rarely a cut‐and‐dried answer in such cases, and readers may wish to suggest an alternative approach. This month's dilemma, ‘Euthanasing treatable patients’, was submitted and is discussed by Simon Coghlan. Readers with comments to contribute are invited to send them as soon as possible, so that they can be considered for publication in the next issue.The series is being coordinated by Steven McCulloch, a practising vet with a PhD in the ethics of veterinary policy. It aims to provide a framework that will help practitioners find solutions when facing similar dilemmas.
Intracranial venous pressures under conscious sedation and general anesthesia
Authors: Raper Daniel M S , Buell Thomas J , Chen Ching-Jen , Ding Dale , Starke Robert M , Liu Kenneth C 
Published: March 2017

IntroductionVenous outflow obstruction has been implicated in the pathophysiology of a subset of patients with idiopathic intracranial hypertension (IIH), and venous sinus stenting (VSS) has emerged as an effective treatment. However, the effect of anesthesia on venous sinus pressure measurements is unpredictable. A more thorough understanding of the effect of the level of anesthesia on intracranial venous pressures might help to better define patients who might benefit most from stent placement.ObjectiveTo compare, in a retrospective cohort study, intracranial venous pressures measured under conscious (CS) sedation versus general anesthesia (GA) and to assess the relationship between anesthetic-dependent venous pressures and outcomes after VSS.MethodsWe performed a retrospective review of a prospectively maintained database to identify patients undergoing angiographic evaluation and VSS for intracranial venous stenosis. Mean venous pressures (MVPs) and trans-stenosis pressure gradients obtained under CS were compared with those measured under GA.ResultsThe maximal MVP was significantly lower under GA (19.8 mm Hg) than CS (21.9 mm Hg; p=0.029). The MVPs in the superior sagittal sinus, torcula, and transverse sinus were lower under GA, but were significantly higher in the sigmoid sinus and jugular bulb under GA (p<0.001). The mean trans-stenosis pressure gradient was also significantly lower under GA (8.6 mm Hg) than CS (12.1 mm Hg; p<0.001). Patients with a larger difference between maximum MVP under GA versus CS were more likely to have normalization of the MVP after VSS (p=0.0008).ConclusionsIntracranial venous pressures are markedly affected by GA. In order to obtain an accurate measurement of MVPs and trans-stenosis gradients, patients undergoing investigation for IIH should undergo cerebral angiography and venous manometry under CS, which provides more reliable data for outcomes after VSS.
Monitoring rheumatoid arthritis using an algorithm based on patient-reported outcome measures: a first step towards personalised healthcare
Authors: Hendrikx Jos , Fransen Jaap , van Riel Piet L C M 
Published: March 2017

ObjectivesThe objective of this proof of concept study was to evaluate alerts generated by a patient-reported outcome measure (PROM)-based algorithm for monitoring patients with rheumatoid arthritis (RA).MethodsThe algorithm was constructed using an example PROM score of an equally weighted mean of visual analogue scale (VAS) general health, VAS disease activity and VAS pain. Based on the PROM score, red flags are generated in 2 instances: the target level of disease activity is not met; change in disease activity surpasses an early alert threshold. To reduce false alarms, 3 consecutive red flags are needed to trigger an alert to the physician. Time series data from patients included consecutively in the practice-based Nijmegen Early RA cohort were analysed to select an appropriate autoregressive integrated moving average (ARIMA) model. This allowed for advanced interpolation of PROM scores and weekly data evaluation. Alerts were evaluated against disease-modifying antirheumatic drug (DMARD)/biologic medication intensification registered in the cohort.ResultsData of 165 patients followed in their second year postdiagnosis were analysed. In 89.8% of 716 visits, the algorithm did not generate an alert and medication was not escalated. Positive predictive value, sensitivity and specificity were 24.6%, 55.6% and 69.7%, respectively. Comparable performance was found when analyses were stratified for baseline Disease Activity Score 28-joint count (DAS28) level.ConclusionsWhen using the algorithm to screen scheduled visits, the overall chance of missing patients in need of medication intensification is low. These findings provide evidence that an off-site monitoring system could aid in optimising the number and timing of face-to-face consultations of patients with their rheumatologists.
Patient participation as an integral part of patient-reported outcomes development ensures the representation of the patient voice: a case study from the field of rheumatology
Authors: de Wit M P T , Kvien T K , Gossec L 
Published: March 2017

IntroductionPatient-reported outcomes (PROs) are important instruments to evaluate healthcare interventions, both in clinical practice and clinical research.ObjectiveTo describe how representation of the perspective of people with psoriatic arthritis was obtained through active participation on different levels in the development of PROs.MethodsThis case study focuses on the methods of involving patients in the elaboration and validation of the Psoriatic Arthritis Impact of Disease (PsAID) score. We used the concept of the participation ladder and the European League Against Rheumatism (EULAR) recommendations for the involvement of patient representatives in scientific projects to analyse the variety of ways patients participated in this process.ResultsTwo patient experts were part of the steering group. 12 patient research partners, coming from 12 different European countries, participated in identifying domains, formulating items for the questionnaire and determining the number of items, the recall period and the questionnaire format. They also helped with the translation of the items into different European languages. Then, 139 patients took part in ranking and prioritising the domains for importance; 65 patients were involved in cognitive debriefing interviews; 499 new patients were recruited for the validation study. Challenges of patient participation in PRO development, such as the representation of patients, are discussed.ConclusionsMaking patient participation an integral part of the PRO development and validation process is an important requisite for outcome research. The variety of patient contributions at different phases in this case study resulted in an instrument with high face validity.
Ultrasound-detectable grey scale synovitis predicts future fulfilment of the 2010 ACR/EULAR RA classification criteria in patients with new-onset undifferentiated arthritis
Authors: Horton Sarah C , Tan Ai Lyn , Wakefield Richard J , Freeston Jane E , Buch Maya H , Emery Paul 
Published: March 2017

ObjectiveTo determine the clinical outcomes for patients with new-onset undifferentiated arthritis (UA), not fulfilling the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) rheumatoid arthritis (RA) classification criteria, and the clinical and imaging predictors of disease progression in these patients.MethodsA prospective observational study was conducted in treatment-naïve UA patients. Baseline ultrasound involved semiquantitative assessment of grey scale (GS) synovitis and power Doppler activity (PD) at 26 joints. Outcomes were fulfilment of 2010 RA criteria (joint involvement determined clinically) and initiation of methotrexate over 12 months. Cox proportional hazards analysis was used to investigate predictors of outcome.ResultsOf 60 patients, 13(22%) progressed to RA and 32(53%) ever received methotrexate. Analyses of predictors of outcome were conducted in the subgroup (n=41) of patients with complete baseline data. The presence of GS was associated with progression to RA and methotrexate use: HRs (95% CI) were 1.25(1.07 to 1.45) and 1.16(1.02 to 1.32), respectively, for the number of joints with GS≥ grade 2 after adjustment for swollen joints. PD was not predictive in the low levels at which it was observed. Progression to RA was also associated with fulfilment of the 2010 criteria using ultrasound synovitis for enumerating joint involvement, higher baseline disability and radiographic erosion.ConclusionsThis is the first report of ultrasound findings in early UA (defined by presence of clinical synovitis and non-fulfilment of 2010 RA criteria). A significant proportion of patients with UA progressed to RA and/or required methotrexate. GS synovitis was predictive of disease progression.
Rangeomorph classification schemes and intra-specific variation: are all characters created equal?
Authors: Kenchington Charlotte G. , Wilby Philip R. 
Published: March 2017

Abstract

Rangeomorphs from the Ediacaran of Avalonia are among the oldest known complex macrofossils and our understanding of their ecology, ontogeny and phylogenetic relationships relies on accurate and consistent classification. There are a number of disparate classification schemes for this group, which dominantly rely on a combination of their branching characters and shape metrics. Using multivariate statistical analyses and the diverse stemmed, multifoliate rangeomorphs in Charnwood Forest (UK), we assess the taxonomic usefulness of the suite of characters currently in use. These techniques allow us to successfully discriminate taxonomic groupings without
a priori
assumptions or weighting of characters and to document a hitherto unrecognized level of variation within single taxonomic groups. Variation within the currently defined genus
Primocandelabrum
is too great to be realistically assigned to different species and may instead reflect primary character diversity, ontogenetic changes in character state or ecophenotypic variability. Its recognition cautions against generic-level diagnoses based on single differences in character state and will be crucial in understanding the mode of growth of these enigmatic organisms.

Supplementary material:
Data tables, definition of the characters used in the analyses, and detailed descriptions and breakdowns of methods and results are available at
https://doi.org/10.6084/m9.figshare.c.3726937
Hydraulic conductivity of bedding-parallel cracks in shale as a function of shear and normal stress
Authors: Rutter Ernest H. , Mecklenburgh Julian 
Published: March 2017

Abstract
Conductivity of fluids along fractures in all rocks is reduced by increasing normal stress. For sandstones and other hard rocks the onset of shear failure along planar cracks is thought to enhance fluid flow owing to a small amount of dilatancy, yet such effects are poorly quantified. Here we determine experimentally how independently increasing normal and shear stress affects fluid flow along fractures in shale. Gas flow along bedding-parallel planar interfaces was measured for flow parallel and normal to the shear direction. Increasing shear stress causes accelerating reduction of conductivity, even before the onset of macroscopic slip. Such reduction in fluid flow rate is non-recoverable, and the combined effects of normal and shear stress can reduce fracture conductivity by more than 3 orders of magnitude over the range of shale reservoir conditions. Bedding plane-parallel slip is common in shales; it can result in a large enhancement of permeability anisotropy, because flow across bedding planes becomes inhibited. This can impact upon the geometry of developing hydraulic fractures, encouraging complexity and favouring lateral relative to vertical growth. The results will facilitate modelling of fluid flow through fracture networks.

Supplementary material:
A CSV file containing all experimental conditions and tabulations of results is available at
https://doi.org/10.6084/m9.figshare.c.3721831
.
Testosterone Prevents Cutaneous Ischemia and Necrosis in Males Through Complementary Estrogenic and Androgenic Actions
Authors: Chenu Caroline , Adlanmerini Marine , Boudou Frederic , Chantalat Elodie , Guihot Anne-Laure , Toutain Céline , Raymond-Letron Isabelle , Vicendo Patricia , Gadeau Alain-Pierre , Henrion Daniel , Arnal Jean-François , Lenfant Françoise 
Published: March 2017

Objective—
Chronic nonhealing wounds are a substantial medical concern and are associated with morbidity and mortality; thus, new treatment strategies are required. The first step toward personalized/precision medicine in this field is probably in taking sex differences into account. Impaired wound healing is augmented by ischemia, and we previously demonstrated that 17β-estradiol exerts a major preventive effect against ischemia-induced skin flap necrosis in female mice. However, the equivalent effects of testosterone in male mice have not yet been reported. We then investigated the role of steroid hormones in male mice using a skin flap ischemia model.

Approach and Results—
Castrated male mice developed skin necrosis after ischemia, whereas intact or castrated males treated with testosterone were equally protected. Testosterone can (1) activate the estrogen receptor after its aromatization into 17β-estradiol or (2) be reduced into dihydrotestosterone, a nonaromatizable androgen that activates the androgen receptor. We found that dihydrotestosterone protected castrated wild-type mice by promoting skin revascularization, probably through a direct action on resistance arteries, as evidenced using a complementary model of flow-mediated outward remodeling. 17β-estradiol treatment of castrated male mice also strongly protected them from ischemic necrosis through the activation of estrogen receptor-α by increasing skin revascularization and skin survival. Remarkably, 17β-estradiol improved skin survival with a greater efficiency than dihydrotestosterone.

Conclusions—
Testosterone provides males with a strong protection against cutaneous necrosis and acts through both its estrogenic and androgenic derivatives, which have complementary effects on skin survival and revascularization.