bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modification of The Paris System for urinary tract washing specimens using diagnostic cytological features
Authors: Suh J. , Go H. , Sung C. , Baek S. , Hwang H. , Jeong S. , Cho Y. 
Published: August 2017

ObjectiveThe Paris System (TPS), which was recently introduced, emphasised the key features of malignant urine cytology: a high nuclear to cytoplasmic ratio, nuclear hyperchromasia, irregular nuclear membranes and coarse chromatin. Although other diagnostic features have been described, the diagnostic significance of such features and their application to TPS have not been fully defined for urinary tract washing specimens.MethodsA total of 142 cases of urinary tract washing specimens with corresponding surgical pathology samples were examined for the key features of TPS and 13 previously described features. The diagnostic performance of TPS and our proposed modification of TPS was compared with that of the current system.ResultsIn addition to the key features of TPS, in the present study, high‐grade urothelial carcinoma (HGUC) frequently exhibited tumour diathesis, a ragged edge of urothelial cell groups, anisonucleosis, India ink nuclei, apoptotic bodies and pleomorphism. As anisonucleosis and India ink nuclei remained independent predictors of HGUC for the multivariate analysis, they were used to modify TPS. The reporting rate of the atypical urothelial cell (AUC) category decreased from 25.3% in the current system to 14.8% in TPS and 11.3% in our proposed modification of TPS. The sensitivity increased from 59.4% in the current system to 70.8% in TPS and 90.0% in this study. The diagnostic accuracy increased from 0.786 in the current system and 0.754 in TPS to 0.859 in this study.ConclusionsTPS is a useful diagnostic system for urinary tract washing specimens by decreasing the number of AUC cases and increasing sensitivity. In this study, anisonucleosis and India ink nuclei improved the diagnostic accuracy of HGUC.
Efficacy and safety of using premedication with simethicone/Pronase during upper gastrointestinal endoscopy examination with sedation: A single center, prospective, single blinded, randomized controlled trial
Authors: Zhang Ling‐Ye , Li Wen‐Yan , Ji Ming , Liu Fu‐Kun , Chen Guang‐Yong , Wu Shan‐Shan , Hao Qian , Zhai Hui‐Hong , Zhang Shu‐Tian 
Published: August 2017

Background and AimTo investigate the efficacy and safety of premedication with simethicone/Pronase during esophagogastroduodenoscopy (EGD) with sedation.MethodsSix hundred and ten patients were randomly allocated to two groups based on type of premedication given. Premedication used in the control group was 10 mL lidocaine hydrochloride mucilage (LHM, N = 314) and premedication used in the intervention group was 80 mL simethicone/Pronase solution plus 10 mL lidocaine hydrochloride mucilage (SP/LHM, N = 296). EGD was done under sedation. Visibility scores, number of mucosal areas that needed cleansing, water consumption for cleansing, time taken for examination, diminutive lesions, pathological diagnosis, patients’ gag reflex and oxygenation (pulse oximetry) were recorded.ResultsSP/LHM has significantly lower total visibility score than LHM (7.978 ± 1.526 vs 6.348 ± 1.097, P < 0.01). During the procedure, number of intragastric areas that needed cleansing and amount of water consumed were significantly less in the SP/LHM than in the LHM group (P < 0.01). In SP/LHM (P = 0.01), endoscopy procedure duration was significantly longer. Although there was no significant difference in rate of detection of diminutive lesions between LHM and SP/LHM, the endoscopist carried out more biopsies in SP/LHM. This led to a higher rate of diagnosis of atrophic gastritis (P = 0.014) and intestinal metaplasia (P = 0.024). There was no significant difference in gag reflex (P = 0.604) and oxygenation during the endoscopy procedure for either group of patients.ConclusionRoutine use of premedication with simethicone/Pronase should be recommended during EGD with sedation.
Generation of animal form by the Chordin/Tolloid/BMP gradient: 100 years after D'Arcy Thompson
Authors: De Robertis Edward M. , Moriyama Yuki , Colozza Gabriele 
Published: August 2017

The classic book “On Growth and Form” by naturalist D'Arcy Thompson was published 100 years ago. To celebrate this landmark, we present experiments in the Xenopus embryo that provide a framework for understanding how simple, quantitative transformations of a morphogen gradient might have affected evolution and morphological diversity of organisms. D'Arcy Thompson proposed that different morphologies might be generated by modifying physical parameters in an underlying system of Cartesian coordinates that pre‐existed in Nature and arose during evolutionary history. Chordin is a BMP antagonist secreted by the Spemann organizer located on the dorsal side of the gastrula. Chordin generates a morphogen gradient as first proposed by mathematician Alan Turing. The rate‐limiting step of this dorsal–ventral (D‐V) morphogen is the degradation of Chordin by the Tolloid metalloproteinase in the ventral side. Chordin is expressed at gastrula on the dorsal side where BMP signaling is low, while at the opposite side peak levels of BMP signaling are reached. In fishes, amphibians, reptiles and birds, high BMP signaling in the ventral region induces transcription of a secreted inhibitor of Tolloid called Sizzled. By depleting Sizzled exclusively in the ventral half of the embryo we were able to expand the ventro‐posterior region in an otherwise normal embryo. Conversely, ventral depletion of Tolloid, which stabilizes Chordin, decreased ventral and tail structures, phenocopying the tolloid zebrafish mutation. We explain how historical constraints recorded in the language of DNA become subject to the universal laws of physics when an ancestral reaction‐diffusion morphogen gradient dictates form.
Gliptin therapy reduces hepatic and myocardial fat in type 2 diabetic patients
Authors: Kosi‐Trebotic Lana , Thomas Anita , Harreiter Jürgen , Chmelik Marek , Trattnig Siegfried , Kautzky‐Willer Alexandra 
Published: August 2017

AbstractBackgroundIncreased hepatic fat and cardiac fat are common in patients with type 2 diabetes mellitus (T2DM) and are associated with a greater risk of liver fibrosis and cardiovascular (CV) events. Sex‐specific differences of dipeptidyl peptidase‐four (DPP‐4) inhibitor effects on hepatic (HCL) and myocardial fat content (MYCL) have not yet been evaluated.MethodForty‐one T2DM patients (20 male, 21 female) received a gliptin add‐on therapy if HbA1c goals were not reached under metformin monotherapy. They underwent cardiac and liver magnetic resonance tomography and spectroscopy before and 6 months after therapy initiation. Plasma samples were analysed for the growth differentiation factor 15 (GDF‐15), a novel marker for cardiovascular risk.ResultsThirty‐eight patients on gliptin therapy completed the study. We observed a positive correlation between MYCL and HCL before therapy (R = 0·41, P = 0·05). After 6 months of therapy, we noticed a significant weight reduction in women only (P = 0·02) whereas waist circumference decreased similarly in both sexes. HbA1c sunk significantly in both sexes (P = 0·002). HCL decreased significantly (P = 0·0004), with women featuring higher basal HCL (P < 0·05). MYCL decreased in women only (P = 0·01) and GDF‐15 comparably in both sexes (P < 0·05).Conclusions6 months of DPP‐4‐therapy led to a significant overall decrease in HCL and body weight such as a reduction of MYCL only in women. This preliminary data set could implicate that gliptin may be a feasible therapy option in fatty liver patients with diabetes potentially including positive effects on cardiovascular function particularly in women.
Glucose‐dependent leucocyte activation in familial hypercholesterolemia
Authors: Koks Natasja , de Vries Marijke A. , Birnie Erwin , Alipour Arash , Castro Cabezas Manuel 
Published: August 2017

AbstractBackgroundLeucocyte activation is an obligatory factor in the development of atherosclerosis. The postprandial situation has been associated to increased leucocyte activation in several disorders, such as type 2 diabetes mellitus and familial combined hyperlipidaemia. Our study aim was to evaluate the effect of post‐OGTT hyperglycaemia on leucocyte activation in patients with familial hypercholesterolemia (FH).Materials and methodsPatients who met the diagnostic criteria for heterozygous FH and healthy volunteers were asked to undergo an oral glucose tolerance test. Leucocyte activation markers CD11b and CD66b were determined by flow cytometry. Post‐OGTT changes were calculated as area under the curve (AUC) and the incremental area under the curve corrected for baseline values (dAUC). The impact of being an FH patient and using statins on the time‐dependent profile of the leucocyte activation markers was studied with repeated measurements analysis.ResultsThirteen FH patients using statins, nine FH patients without statins and 14 healthy volunteers were included. FH subjects on statins had a slightly higher HbA1c than those not using these drugs or controls. Post‐OGTT glucose levels were significantly higher in patients with FH when compared to healthy controls (P = 0·001). These effects were independent from the use of statins.ConclusionsSurprisingly, our study shows impaired post‐OGTT glucose excursions in patients with FH compared to healthy volunteers. Post‐OGTT hyperglycaemia may be related to persistent post‐OGTT activation of monocytes in FH patients compared to healthy controls, and therefore, it may contribute to the development of cardiovascular disease in patients with FH.
A whole lot of misery: Adorno's negative Aristotelianism—Replies to Allen, Celikates, and O'Connor
Authors: Freyenhagen Fabian 
Published: August 2017

AbstractCan one both be an Aristotelian in ethics and a negativist, whereby the latter involves subscribing to the view that the good cannot be known in our social context but that ethical guidance is nonetheless possible in virtue of a pluralist conception of the bad (of which this context and human history provide us ample knowledge)? Moreover, is it possible to combine Aristotelianism with a thoroughly historical outlook? I have argued that such combinations are, indeed, possible, and that we can find an example of them in Adorno's work. In this paper, I reply to three critics (Allen, Celikates and O'Connor) who cast doubt on this proposal. I also reply to other concerns they raise, regarding immanent critique, negativism, the role of social theory in Adorno's work, and the danger of being co‐opted. I stress the holism of Adorno's position, and, amid some more deflationary moves, insist on the distinctiveness of the Aristotelian position that results.
Neglect and aphasia in the acute phase as predictors of functional outcome 7 years after ischemic stroke
Authors: Gerafi J. , Samuelsson H. , Viken J. I. , Blomgren C. , Claesson L. , Kallio S. , Jern C. , Blomstrand C. , Jood K. 
Published: August 2017

Background and purposeVisuospatial inattention (VSI) and language impairment (LI) are often present early after stroke and associations with an unfavorable short‐term functional outcome have been reported. The purpose of this study was to investigate whether a screening of VSI and LI as indicators of cortical symptoms early after stroke could predict long‐term functional outcomes.MethodsA consecutive cohort of 375 patients with ischemic stroke was assessed for the occurrence of VSI at a median of 7 days after admission (interquartile range, 1–5 days) using the Star Cancellation Test and for LI (within the first 7 days) with the language item in the Scandinavian Stroke Scale. Seven years later, functional outcomes were assessed by the modified Rankin scale and Frenchay Activities Index in 235 survivors without recurrent stroke. Relationships between baseline predictors and functional outcome at 7 years were analyzed with bivariate correlations and multiple categorical regressions with optimal scaling.ResultsThe regression model significantly explained variance in the modified Rankin scale (R2 = 0.435, P < 0.001) and identified VSI (P = 0.001) and neurological deficits (P < 0.001; Scandinavian Stroke Scale score without the language item) as the significant independent predictors. The model for Frenchay Activities Index was also significant (R2 = 0.269, P < 0.001) with VSI (P = 0.035) and neurological deficits (P < 0.001) as significant independent predictors.ConclusionsVisuospatial inattention at acute stroke has an independent impact on long‐term functional outcomes. Early recognition may enable targeted rehabilitative interventions.
Structural insight into the recognition of acetylated histone H3K56ac mediated by the bromodomain of CREB‐binding protein
Authors: Xu Li , Cheng Aimin , Huang Min , Zhang Jiahai , Jiang Yiyang , Wang Chongyuan , Li Fudong , Bao Hongyu , Gao Jia , Wang Na , Liu Jiuyang , Wu Jihui , Wong Catherine C.L. , Ruan Ke 
Published: August 2017

The acetylation of lysine 56 of histone H3 (H3K56ac) enhances the binding affinity of histone chaperones to H3–H4 dimers. CREB‐binding protein (CBP) possesses a bromodomain that recognizes H3K56 acetylation. CBP also possesses a histone acetyltransferase (HAT) domain, which has been shown to promote H3K56 acetylation of free histones to facilitate delivery of replication‐dependent chaperones to acetylated histones for chromatin assembly. However, the mechanism by which the CBP bromodomain recognizes H3K56ac and the context in which such recognition occurs remain elusive. Here, we solved the crystal structure of the CBP bromodomain in complex with an H3K56ac peptide. Our data demonstrate that the CBP bromodomain recognizes H3K56ac with high affinity. Structural and affinity analyses reveal that the CBP bromodomain prefers an aromatic residue at the −2 position and an arginine at the −4 position from the acetyl‐lysine, and that the CBP bromodomain selectively recognizes an extended conformation of the H3 αN helix that contains H3K56ac. We also demonstrate that the CBP bromodomain binds to H3K56ac in a recombinant H3–H4 dimer but not in a mono‐nucleosome. Our results suggest that the CBP bromodomain selectively recognizes an extended conformation of the K56‐acetylated H3 αN region within an H3–H4 dimer, which is expected to facilitate the HAT activity of CBP for subsequent H3K56 acetylation of free histones.DatabasesCoordinates of the CBP bromodomain in complex with H3K56ac as described in this article have been deposited in the PDB with accession number 5GH9.
Aligning digital CD8+ scoring and targeted next‐generation sequencing with programmed death ligand 1 expression: a pragmatic approach in early‐stage squamous cell lung carcinoma
Authors: Conde Esther , Caminoa Alejandra , Dominguez Carolina , Calles Antonio , Walter Stefan , Angulo Barbara , Sánchez Elena , Alonso Marta , Jimenez Luis , Madrigal Luis , Hernando Florentino , Sanz‐Ortega Julian , Jimenez Beatriz , Garrido Pilar , Paz‐Ares Luis , de Castro Javier , Hernandez Susana , Lopez‐Rios Fernando 
Published: August 2017

AimsTo study programmed death ligand 1 (PD‐L1) expression, tumour‐infiltrating T lymphocytes (TILs) and the molecular context in patients with early‐stage squamous cell lung carcinomas (SCCs).Methods and resultsThe study included samples from 40 patients (discovery cohort) and 29 patients (validation cohort) diagnosed with early‐stage SCC. PD‐L1 immunohistochemistry (IHC) was performed with three commercially available clones (E1L3N, SP263 and SP142). CD8+ TILs were scored with a digital algorithm. All tumours were analysed with targeted next‐generation sequencing (NGS). Additionally, TP53 mutations were investigated with direct sequencing. In both cohorts, we observed a significant association between CD8+ TILs density and high PD‐L1 IHC expression in tumour cells (TCs). Furthermore, high SP142 PD‐L1 expression in immune cells (ICs) was also associated significantly with CD8+ TILs density. Therefore, CD8+ TILs density discriminated between patients with high versus low PD‐L1 IHC expression with excellent sensitivity and specificity. Interestingly, the highest percentages of PD‐L1‐positive TCs with the three antibodies were found in samples with cyclin‐dependent kinase 6 (CDK6) amplification, with high amplification of proto‐oncogene C‐Myc (CMYC) or with cyclin D1–PI3 kinase subunit alpha (CCND1–PIK3CA) co‐amplification. High SP142 PD‐L1 IHC expression in ICs showed a non‐significant correlation with TP53 mutations. Conversely, most cases with fibroblast growth factor receptor 1 (FGFR1) amplification were negative for all PD‐L1 clones.ConclusionsOur preliminary results support the use of digital CD8+ TILs scoring and targeted NGS alongside PD‐L1 expression. The approach presented herein could help define patients with SCCs candidates to immune checkpoints inhibitors.
How to facilitate transition to adulthood? Innovative solutions from parents of young adults with profound intellectual disability
Authors: Gauthier‐Boudreault Camille , Couture Mélanie , Gallagher Frances 
Published: August 2017

BackgroundAt age 21, access to specialised services for youth with profound intellectual disability is reduced. Few studies have focused on parents' views concerning potential solutions to ease the transition to adulthood, and most existing solutions target young adults with less severe intellectual disability. The aim of this study is to propose realistic solutions to meet the needs of young adults with profound intellectual disability and their families during and after the transition to adulthood.MethodUsing a descriptive qualitative design, two individual semi‐structured interviews were conducted with 14 parents.ResultsIdeas for innovative solutions included responses to parents' informational, material, intellectual and emotional needs during and after transition period. The majority of these solutions involve knowledge sharing, improved inter‐institutional collaboration and social participation of young adults, and offering parents emotional support.ConclusionSome solutions could be implemented within existing transition planning programs, based on their strengths and limitations.
WWC2 is an independent prognostic factor and prevents invasion via Hippo signalling in hepatocellular carcinoma
Authors: Zhang Yijun , Yan Shumei , Chen Jiewei , Gan Caixia , Chen Dong , Li Yan , Wen Jiahuai , Kremerskothen Joachim , Chen Shilu , Zhang Jiangbo , Cao Yun 
Published: August 2017

AbstractWWC family proteins negatively regulate HEK293 cell proliferation and organ growth by suppressing the transcriptional activity of Yes‐associated protein (YAP), a major effector of the Hippo pathway. The function of the scaffolding protein WWC1 (also called KIBRA) has been intensively studied in cells and animal models. However, the expression and clinicopathologic significance of WWC2 in cancer are poorly characterized. This study aimed to clarify the biological function and mechanism of action of WWC2 in hepatocellular carcinoma (HCC). Retrospective analysis revealed WWC2 was significantly down‐regulated in 95 clinical HCC tissues compared to the paired adjacent non‐cancerous tissues. Moreover, loss of WWC2 expression was significantly associated with advanced clinicopathological features, including venous infiltration, larger tumour size and advanced TNM stage. Positive WWC2 expression was associated with significantly better 5‐year overall survival, and WWC2 was an independent prognostic factor for overall survival in HCC. Moreover, we confirmed WWC2 inhibits HCC cell invasive ability in vitro. Elevated YAP expression was also observed in the same cohort of HCC tissues. Pearson's correlation coefficient analysis indicated WWC2 expression correlated inversely with nuclear YAP protein expression in HCC. Mechanistically, we confirmed overexpression of WWC2 suppresses the invasive and metastatic potential of HCC cells by activating large tumour suppressor 1 and 2 kinases (LATS1/2), which in turn phosphorylates the transcriptional co‐activator YAP. Overall, this study indicates WWC2 functions as a tumour suppressor by negatively regulating the Hippo signalling pathway and may serve as a prognostic marker in HCC.
The impact of atopic dermatitis on work life – a systematic review
Authors: Nørreslet L.B. , Ebbehøj N.E. , Ellekilde Bonde J.P. , Thomsen S.F. , Agner T. 
Published: August 2017

AbstractAtopic dermatitis (AD) has considerable multidimensional personal and societal costs. However, the extend to which the patient's work life is affected due to AD is more sparsely described in the literature. The objective of this review was to examine the impact on work life for patients with AD, with a specific focus on choice of education and occupation, sick leave, social compensations and change of job due to AD. A systematic literature search was performed in PubMed, EMBASE and Web og Science up to 7 February 2017 for articles on the impact on work life for patients with AD. Results were summarized taking several measures of study quality into account. The search identified twenty‐three articles, whereof five studies assessed the influence of AD on educational or job choice, without any consistent conslusion, while eight of nine studies with respect to sick leave and two on disability pensions found AD to have a negative impact. Studies of change or loss of job and AD showed more diverse results, as not all studies documented a negative effect of AD on work life. Atopic dermatitis imposes a burden extending beyond personal, emotional and financial costs. This review strongly implies that AD affects sick leave, and though not fully clarified, possible also job choice, change or loss of job and even disability pensions for the more severe cases.
Connect‐Home: Transitional Care of Skilled Nursing Facility Patients and their Caregivers
Authors: Toles Mark , Colón‐Emeric Cathleen , Naylor Mary D. , Asafu‐Adjei Josephine , Hanson Laura C. 
Published: August 2017

BackgroundOlder adults that transfer from skilled nursing facilities (SNF) to home have significant risk for poor outcomes. Transitional care of SNF patients (i.e., time‐limited services to ensure coordination and continuity of care) is poorly understood.ObjectiveTo determine the feasibility and relevance of the Connect‐Home transitional care intervention, and to compare preparedness for discharge between comparison and intervention dyads.DesignA non‐randomized, historically controlled design‐enrolling dyads of SNF patients and their family caregivers.SettingThree SNFs in the Southeastern United States.ParticipantsIntervention dyads received Connect‐Home; comparison dyads received usual discharge planning. Of 173 recruited dyads, 145 transferred to home, and 133 completed surveys within 3 days of discharge.InterventionThe Connect‐Home intervention consisted of tools and training for existing SNF staff to deliver transitional care of patient and caregiver dyads.MeasurementsFeasibility was assessed with a chart review. Relevance was assessed with a survey of staff experiences using the intervention. Preparedness for discharge, the primary outcome, was assessed with Care‐Transitions Measure‐15 (CTM‐15).ResultsThe intervention was feasible and relevant to SNF staff (i.e., 96.9% of staff recommended intervention use in the future). Intervention dyads, compared to comparison dyads, were more prepared for discharge (CTM‐15 score 74.7 vs 65.3, mean ratio 1.16, 95% CI: 1.08, 1.24).ConclusionConnect‐Home is a promising transitional care intervention for older patients discharged from SNF care. The next step will be to test the intervention using a cluster randomized trial, with patient outcomes including re‐hospitalization.