bluuebunny/crossref_metadata_2025_split huggingface dataset:
Universal Mismatch Repair Protein Screening in Upper Tract Urothelial Carcinoma
Authors: Gayhart Matthew George , Johnson Nicole , Paul Asit , Quillin John M , Hampton Lance J , Idowu Michael O , Smith Steven Christopher 
Published: May 2020

AbstractObjectivesUniversal screening of upper tract urothelial carcinoma (UTUC) for Lynch syndrome by mismatch repair (MMR) protein immunohistochemistry (IHC) has been recommended by some investigators. Herein, we assess this recommendation retrospectively by simulating its performance on a retrospective, unselected cohort of UTUCs, with comparison to the established setting of colorectal and endometrial adenocarcinoma.MethodsWe assessed for complete loss of MMR protein (MLH1, MSH2, MSH6, and PMS2) IHC in 74 consecutive cases of UTUC and then tabulated clinical and pathologic factors. MMR findings from same-institution colorectal and endometrial adenocarcinomas were tabulated for comparison.ResultsWe observed loss of at least one MMR protein in 12% in our UTUC cohort (three MSH2/MSH6, three MSH6 only, one MLH1/PMS2, and two PMS2 only). Of these nine cases (seven males, two females, median age 67 years, five associated with colorectal adenocarcinoma), at least three (4% of the overall cohort) proved to be Lynch syndrome. Overall, MMR loss in UTUC was comparable to colorectal (11%; 50 of 471 cases) and endometrial (12%; 12 of 101 cases) adenocarcinomas.ConclusionsThe rate of MMR loss observed in UTUC was comparable to that in the established setting of colorectal and endometrial adenocarcinomas, supporting universal UTUC screening at our institution and others.
The origin of the giant ground beetleAplothorax burchellion St Helena Island
Authors: Sota Teiji , Hori Michio , Scholtz Clarke , Karagyan Gayane , Liang Hong-Bin , Ikeda Hiroshi , Takami Yasuoki 
Published: May 2020

AbstractSome highly isolated oceanic islands harbour endemic ground beetles that have lost the ability to fly. Here, we investigated the origin of the possibly extinct flightless giant ground beetle Aplothorax burchelli on St Helena Island in the South Atlantic. Aplothorax burchelli was initially considered to be a member of the subtribe Calosomina (=genus Calosoma) of the subfamily Carabinae (Coleoptera: Carabidae) closely related to the genus Ctenosta (=Calosoma subgenus Ctenosta), but this proposition was questioned due to its unique external and genital morphology. We conducted a phylogenetic analysis of mitogenome sequences using historical specimens of A. burchelli and samples of representative species of Carabinae. Our analysis of 13 protein-coding gene sequences revealed that A. burchelli is definitely a member of Calosomina, most closely related to a species of Ctenosta. Further analysis using NADH dehydrogenase subunit 5 gene sequences from most groups in Calosomina showed that A. burchelli formed a monophyletic group with Ctenosta species from Africa and Madagascar. Our results suggest that the ancestor of A. burchelli, which had the ability to fly, colonized St Helena from Africa after the emergence of the island 14 Mya, and has since undergone evolutionary changes in conjunction with loss of flight.
Subcellular Localization And Formation Of Huntingtin Aggregates Correlates With Symptom Onset And Progression In A Huntington’S Disease Model
Authors: Landles Christian , Milton Rebecca E , Ali Nadira , Flomen Rachel , Flower Michael , Schindler Franziska , Gomez-Paredes Casandra , Bondulich Marie K , Osborne Georgina F , Goodwin Daniel , Salsbury Grace , Benn Caroline L , Sathasivam Kirupa , Smith Edward J , Tabrizi Sarah J , Wanker Erich E , Bates Gillian P 
Published: May 2020

AbstractHuntington’s disease is caused by the expansion of a CAG repeat within exon 1 of the HTT gene, which is unstable, leading to further expansion, the extent of which is brain region and peripheral tissue specific. The identification of DNA repair genes as genetic modifiers of Huntington’s disease, that were known to abrogate somatic instability in Huntington’s disease mouse models, demonstrated that somatic CAG expansion is central to disease pathogenesis, and that the CAG repeat threshold for pathogenesis in specific brain cells might not be known. We have previously shown that the HTT gene is incompletely spliced generating a small transcript that encodes the highly pathogenic exon 1 HTT protein. The longer the CAG repeat, the more of this toxic fragment is generated, providing a pathogenic consequence for somatic expansion. Here, we have used the R6/2 mouse model to investigate the molecular and behavioural consequences of expressing exon 1 HTT with 90 CAGs, a mutation that causes juvenile Huntington’s disease, compared to R6/2 mice carrying ∼200 CAGs, a repeat expansion of a size rarely found in Huntington’s disease patient’s blood, but which has been detected in post-mortem brains as a consequence of somatic CAG repeat expansion. We show that nuclear aggregation occurred earlier in R6/2(CAG)90 mice and that this correlated with the onset of transcriptional dysregulation. Whereas in R6/2(CAG)200 mice, cytoplasmic aggregates accumulated rapidly and closely tracked with the progression of behavioural phenotypes and with end-stage disease. We find that aggregate species formed in the R6/2(CAG)90 brains have different properties to those in the R6/2(CAG)200 mice. Within the nucleus, they retain a diffuse punctate appearance throughout the course of the disease, can be partially solubilized by detergents and have a greater seeding potential in young mice. In contrast, aggregates from R6/2(CAG)200 brains polymerize into larger structures that appear as inclusion bodies. These data emphasize that a subcellular analysis, using multiple complementary approaches, must be undertaken in order to draw any conclusions about the relationship between HTT aggregation and the onset and progression of disease phenotypes.
Performance of Capsule Endoscopy and Cross-Sectional Techniques in Detecting Small Bowel Lesions in Patients with Crohn’s Disease
Authors: Calabrese Carlo , Diegoli Margherita , Dussias Nikolas , Salice Marco , Rizzello Fernando , Cappelli Alberta , Ricci Claudio , Gionchetti Paolo 
Published: May 2020

AbstractBackgroundCrohn’s disease (CD) can be classified according to endoscopic and cross-sectional imaging characteristics. Information regarding disease extent and phenotype may be provided by advanced endoscopic and imaging techniques. In this study, we compare the ability of capsule endoscopy (CE) and cross-sectional imaging techniques (CST) (MRE/Computer Tomography Enteroscopy [CTE]) in detecting small bowel (SB) lesions.MethodsWe retrospectively analyzed 102 patients with a diagnosis of CD who underwent both CE and CST. Only patients with at least a 12-month follow-up after CE were included.ResultsSensitivity and specificity for the detection of SB lesions were, respectively, 100% and 83.3% for CE, 55.1% and 80% for CTE, and 60% and 82.3% for MRE. CE detected proximal CD lesions in 73% of patients, whereas MRE and CTE detected proximal lesions in 41% and 16% of patients, respectively (P &lt; 0.001). Positive findings on CE led to management changes in all patients, in a median follow-up period of 58.7 months. During the follow-up period, 26.5% of patients underwent surgery. Multivariate analysis revealed that moderate-to-severe disease at CE was independently correlated with surgery (P = 0.03).ConclusionsCE has a superior sensitivity for detecting CD lesions in the proximal and medium SB compared with CST. In the terminal ileum, MRE and CTE displayed similar performance to CE.
Internalized Orientalism: Toward a Postcolonial Media Theory and De-Westernizing Communication Research from the Global South
Authors: Alahmed Anas M 
Published: May 2020

Abstract
This article applies the concept of internalized orientalism to explain how news representations reflect the power struggles and power relationships within postcolonial nations of the global South through Orientalist discourses. Introducing the concept of internalized orientalism to postcolonial media studies has the potential to de-westernize communication research by depicting the interplays of representations within the South. In this article, I analyze internalized orientalism as a communication theory by studying media representations of the Egyptian revolution in terms of four themes: (a) inability of southern people to rule themselves, (b) religious versus civil state, (c) social conflicts and the patriarchal state, and (d) dehumanization of people and reducing human agency. I argue that internalized orientalism demonstrates how media representations reflect a Western production of knowledge of the global South in the global South, working toward reproducing neocolonial power. At the same time, I argue, internalized orientalism offers a lens for understanding the politics of representations and knowledge production from the South.
Long-term Motor and Cognitive Function in the Children of Women With Inflammatory Bowel Disease
Authors: Friedman Sonia , Nielsen Jan , Jølving Line Riis , Nøhr Ellen A , Nørgård Bente Mertz 
Published: May 2020

Abstract

Introduction
Research on long-term outcomes of children exposed to inflammatory bowel disease [IBD] in utero is lacking. Maternal inflammation, IBD medications, or other factors may increase the risk of developmental disabilities in the offspring.

Methods
We used the Danish National Birth Cohort, an ongoing prospective study that includes 100 419 pregnancies of 92 274 women, in conjunction with the Danish National Registries, to evaluate cognitive and motor development of the children of women with and without IBD. We analysed basic measures of childhood development at 6-month and 18-month interviews with the mother and with validated questionnaires filled out by the parents when the child was 7 years old. We adjusted for multiple confounders, including preterm birth.

Results
At 6 months, we included 484 children of women with IBD and 69 571 unexposed children; at 18 months, 471 exposed and 66 018 unexposed; at 7 years, 391 exposed and 54 356 unexposed. At 18 months, exposed children were significantly less likely to ‘use word-like sounds’ but there was no difference between use of ‘sentences of 2 words’. At 6 and 18 months, there were no other obvious differences in language and motor development. At 7 years, cognitive scores [emotional, conduct, hyperactivity, peer, and social scores] and motor development [gross/fine motor skills and general coordination] were similar between the two groups.

Conclusions
Children exposed to IBD in utero and unexposed children scored similarly on survey-based tools assessing basic measures of neurodevelopment over 7 years. These results are reassuring for current and future parents with IBD.
Aortic root rupture during balloon-expandable transcatheter aortic valve replacement in a patient without recognized risk factors for aortic root rupture: a case report
Authors: Tsuda Masaki , Mizote Isamu , Mukai Takashi , Sakata Yasushi 
Published: May 2020

Abstract

Background
Aortic root rupture is a severe complication of balloon-expandable transcatheter aortic valve replacement (TAVR). Although previous studies have revealed several risk factors for this complication, predicting this complication is occasionally difficult.

Case summary
A 78-year-old male patient underwent TAVR via a transfemoral approach using a 29-mm balloon-expandable valve. No recognized risk factors for aortic root rupture existed in pre-procedural multi-detector computed tomography (MDCT) analysis. However, after the valve deployment, sudden haemodynamic collapse occurred. Transoesophageal echocardiography revealed pericardial effusion, which led to an immediate diagnosis of cardiac tamponade following aortic root rupture. Following pericardial drainage via a subxiphoid approach, the haemodynamics were immediately stabilized. After 10 days of close observation, the patient was discharged on Day 39 without additional problems. He was still alive at the 6-month follow-up without sequelae.

Discussion
Established risk factors for aortic root rupture include &gt;20% area oversizing, bicuspid aortic valve, small annulus (&lt;20 mm), shallow sinus of Valsalva (SOV) compared with the aortic annulus, and massive annular or subannular calcification. Our patient did not have any of the recognized risk factors for aortic root rupture, suggesting the existence of other factors. Pre-procedural MDCT showed a flat calcification orthogonal to the aortic root wall, and post-procedural MDCT revealed that this calcification penetrated the SOV with extravasation. Thus, we suggest that a flat calcification orthogonal to the aortic root wall might be an additional risk factor for aortic root rupture.
Repetitive out of hospital cardiac arrests following pregnancy: a case report of an unfortunate presentation of mitral annular disjunction
Authors: Van Berendoncks An , McGhie Jackie , Heidbuchel Hein , Roos-Hesselink Jolien W 
Published: May 2020

Abstract

Background
Mitral annular disjunction (MAD) is an under-recognized cause of arrhythmic sudden cardiac death, especially in young women. The relation between MAD and the occurrence of arrhythmia during pregnancy has not yet been explored. We would like to stress the importance of careful echocardiographic examination and the vulnerable peripartum period.

Case summary
A 29-year-old woman survived an out of hospital cardiac arrest 4 months after delivery of her first child. The diagnosis was not clear and an implantable cardioverter-defibrillator (ICD) as secondary prevention was implanted. Her second pregnancy and delivery were uneventful. The 12-lead electrocardiogram demonstrated sinus rhythm with right bundle branch block, ventricular extra systoles (premature ventricular contractions), and a right superior axis, i.e. origin in the inferolateral basal left ventricle. Transthoracic 2D echocardiography showed myxomatous mitral valve disease with moderate mitral valve insufficiency with normal left and right heart dimensions and function. However, 4 weeks after delivery she experienced a sudden syncope at home. Implantable cardioverter-defibrillator reading revealed primary ventricular fibrillation, induced by a ventricular premature beat (VPB), terminated with a successful ICD shock. A frame-by-frame echocardiographic analysis of the mitral valve using biplane echocardiographic analysis allowed diagnosis of MAD with detachment of the root of the annulus from the posterolateral ventricular myocardium during systole.

Conclusion
Mitral annular disjunction is an under-recognized cause of arrhythmic sudden cardiac death. Biplane echocardiographic analysis of the mitral annulus can identify MAD and as such may help for risk stratification and sudden cardiac death prevention. Careful follow-up is necessary especially during pregnancy and the postpartum period.
The PKGIα/VASP pathway is involved in insulin- and high glucose-dependent regulation of albumin permeability in cultured rat podocytes
Authors: Rachubik Patrycja , Szrejder Maria , Audzeyenka Irena , Rogacka Dorota , Rychłowski Michał , Angielski Stefan , Piwkowska Agnieszka 
Published: May 2020

Abstract
Podocytes, the principal component of the glomerular filtration barrier, regulate glomerular permeability to albumin via their contractile properties. Both insulin- and high glucose (HG)-dependent activation of protein kinase G type Iα (PKGIα) cause reorganization of the actin cytoskeleton and podocyte disruption. Vasodilator-stimulated phosphoprotein (VASP) is a substrate for PKGIα and involved in the regulation of actin cytoskeleton dynamics. We investigated the role of the PKGIα/VASP pathway in the regulation of podocyte permeability to albumin. We evaluated changes in high insulin- and/or HG-induced transepithelial albumin flux in cultured rat podocyte monolayers. Expression of PKGIα and downstream proteins was confirmed by western blot and immunofluorescence. We demonstrate that insulin and HG induce changes in the podocyte contractile apparatus via PKGIα-dependent regulation of the VASP phosphorylation state, increase VASP colocalization with PKGIα, and alter the subcellular localization of these proteins in podocytes. Moreover, VASP was implicated in the insulin- and HG-dependent dynamic remodelling of the actin cytoskeleton and, consequently, increased podocyte permeability to albumin under hyperinsulinaemic and hyperglycaemic conditions. These results indicate that insulin- and HG-dependent regulation of albumin permeability is mediated by the PKGIα/VASP pathway in cultured rat podocytes. This molecular mechanism may explain podocytopathy and albuminuria in diabetes.
Inter-Population Similarities and Differences in Predation Efficiency of a Mosquito Natural Enemy
Authors: Cuthbert Ross N , Dalu Tatenda , Wasserman Ryan J , Weyl Olaf L F , Froneman P William , Callaghan Amanda , Dick Jaimie T A 
Published: May 2020

AbstractPredation is a critical factor that mediates population stability, community structure, and ecosystem function. Predatory natural enemies can contribute to the regulation of disease vector groups such as mosquitoes, particularly where they naturally co-occur across landscapes. However, we must understand inter-population variation in predatory efficiency if we are to enhance vector control. The present study thus employs a functional response (FR; resource use under different densities) approach to quantify and compare predatory interaction strengths among six populations of a predatory temporary pond specialist copepod, Lovenula raynerae, from the Eastern Cape of South Africa preying on second instar Culex pipiens complex mosquito larvae. All individuals from the sampled populations were predatory and drove significant mortality through per capita predation rates of 0.75–1.10 mosquitoes/h at maximum densities over a 5-h feeding time. Individuals from all copepod populations exhibited Type II FRs with no significant differences in attack rates. On the other hand, there were significant differences in handling times, and therefore also maximum feeding rates (maximum experimental prey density: 32), suggesting possible genetic differences among populations that influenced predation. Owing to a widespread distribution in arid landscapes, we propose that predatory calanoid copepods such as L. raynerae play a key regulatory role at the landscape scale in the control of disease vector mosquito populations. We propose that these ecosystems and their specialist biota should thus be conserved and enhanced (e.g., via selective breeding) owing to the ecosystem services they provide in the context of public health.
Identification of functionally distinct and interacting cancer cell subpopulations from glioblastoma with intratumoral genetic heterogeneity
Authors: Guo Min , van Vliet Marjolein , Zhao Jian , de Ståhl Teresita Díaz , Lindström Mikael S , Cheng Huaitao , Heller Susanne , Nistér Monica , Hägerstrand Daniel 
Published: May 2020

AbstractBackgroundGlioblastomas display a high level of intratumoral heterogeneity with regard to both genetic and histological features. Within single tumors, subclones have been shown to communicate with each other to affect overall tumor growth. The aim of this study was to broaden the understanding of interclonal communication in glioblastoma.MethodsWe have used the U-343 model, consisting of U-343 MG, U-343 MGa, U-343 MGa 31L, and U-343 MGa Cl2:6, a set of distinct glioblastoma cell lines that have been derived from the same tumor. We characterized these with regard to temozolomide sensitivity, protein secretome, gene expression, DNA copy number, and cancer cell phenotypic traits. Furthermore, we performed coculture and conditioned media-based experiments to model cell-to-cell signaling in a setting of intratumoral heterogeneity.ResultsTemozolomide treatment of a coculture composed of all 4 U-343 cell lines presents a tumor relapse model where the least sensitive population, U-343 MGa 31L, outlives the others. Interestingly, the U-343 cell lines were shown to have distinct gene expression signatures and phenotypes although they were derived from a single tumor. The DNA copy number analysis revealed both common and unique alterations, indicating the evolutionary relationship between the cells. Moreover, these cells were found to communicate and affect each other’s proliferation, both via contact-dependent and -independent interactions, where NOTCH1, TGFBI, and ADAMTS1 signaling effects were involved, respectively.ConclusionsThese results provide insight into how complex the signaling events may prove to be in a setting of intratumoral heterogeneity in glioblastoma and provide a map for future studies.
Semantic Deflationism and Meta-Ontological Deflationism
Authors: Marschall Benjamin , Schindler Thomas 
Published: May 2020

AbstractDeflationary positions have been defended in many areas of philosophy. Most prominent are semantic deflationism about truth and reference, and meta-ontological deflationism, according to which existence has no deep nature and the standard neo-Quinean approach to ontology is misguided. Although both kinds of views have generated much discussion, surprisingly little attention has been paid to the question of how they relate to each other. Are they independent, is it advisable to hold them all at once, or do they even entail each other? One exception is Amie Thomasson, who has argued that semantic deflationism actually entails meta-ontological deflationism. This is unexpected, since semantic deflationism is usually regarded as much less controversial than meta-ontological deflationism. In our paper, we will argue that Thomasson’s argument fails though, and that the connection between the views is in fact weaker than she makes them out to be.
Psychological and self-management support for people with vasculitis or connective tissue diseases: UK health professionals’ perspectives
Authors: Robson Joanna C , Shepherd Michael , Harper Lorraine , Ndosi Mwidimi , Austin Keziah , Flurey Caroline , Logan Sarah , Dures Emma 
Published: May 2020

Abstract

Objectives
CTD and systemic vasculitis impact on health-related quality of life. Treatment can be complex, involving multiple medical specialities. The aim of this study was to investigate psychological and self-management support for patients in secondary care.

Methods
An online survey of health professionals in the UK, including 45 multiple-choice and free-text questions, was analysed descriptively. Free-text survey responses were analysed thematically to identify health professionals’ perceptions of best practice and unmet needs.

Results
The online survey included 120 health professionals (34% specialist nurses, 51% doctors and 12% allied health professionals), predominantly working in rheumatology (52.9%) and nephrology (21.5%) departments. Access to self-management programmes or clinics for people with CTD or vasculitis was available in 23% of rheumatology and 8% of nephrology departments. In response to ‘How well is your team providing self-management support to people with CTD or vasculitis?’, 38% of respondents reported ‘not very well’ or ‘not well at all’. Direct access to psychological support was available in 76.9% of nephrology and 32.8% of rheumatology departments. More than 80% of respondents would like additional training. Key themes from the qualitative data (free-text survey responses) included the importance of: dedicated psychological support and self-management programmes for people with CTD and vasculitis, a whole-team approach (specialist teams empowering people to manage their own care), staff training (e.g. brief psychological interventions) and signposting to resources, including patient charities.

Conclusion
People with CTD and vasculitis have complex needs, and improvements in self-management and psychological support are required in UK rheumatology and nephrology departments.