bluuebunny/crossref_metadata_2025_split huggingface dataset:
Status of treatment strategies for Hutchinson–Gilford progeria syndrome with a focus on prelamin: A posttranslational modification
Authors: Chen Xue , Yao Haidong , Andrés Vicente , Bergo Martin O. , Kashif Muhammad 
Published: July 2022

AbstractHutchinson–Gilford progeria syndrome (HGPS) is a rare genetic disorder characterized by premature ageing and early death at a mean age of 14.7 years. At the molecular level, HGPS is caused by a de novo heterozygous mutation in LMNA, the gene encoding A‐type lamins (mainly lamin A and C) and nuclear proteins, which have important cellular functions related to structure of the nuclear envelope. The LMNA mutation leads to the synthesis of a truncated prelamin A protein (called progerin), which cannot undergo normal processing to mature lamin A. In normal cells, prelamin A processing involves four posttranslational processing steps catalysed by four different enzymes. In HGPS cells, progerin accumulates as a farnesylated and methylated intermediate in the nuclear envelope where it is toxic and causes nuclear shape abnormalities and senescence. Numerous efforts have been made to target and reduce the toxicity of progerin, eliminate its synthesis and enhance its degradation, but as of today, only the use of farnesyltransferase inhibitors is approved for clinical use in HGPS patients. Here, we review the main current strategies that are being evaluated for treating HGPS, and we focus on efforts to target the posttranslational processing of progerin.
Elevated gamma‐glutamyl transferase levels are associated with stroke recurrence after acute ischemic stroke or transient ischemic attack
Authors: Li Siqi , Wang Anxin , Tian Xue , Zuo Yingting , Meng Xia , Zhang Yumei 
Published: July 2022

AbstractAimsGamma‐glutamyl transferase (GGT) is considered a marker of oxidative stress in vivo. In this study, we aimed to examine the association of serum GGT levels with 3‐month and 1‐year stroke recurrence in patients with acute ischemic stroke or transient ischemic attack (TIA).MethodsWe conducted a large and multicenter cohort study. Participants with ischemic stroke or TIA who had a baseline GGT measurement were enrolled in the China National Stroke Registry‐3 study from August 2015 to March 2018. They were divided into four groups according to sex‐specific quartiles of GGT levels. The effect of GGT on stroke recurrence and other vascular events was examined during the 1‐year follow‐up period. Multivariate Cox regression models were performed to evaluate the association. Discrimination tests were used to examine the degree to which incorporating GGT into the conventional model predicted stroke adverse outcomes.ResultsA total of 12,504 patients were enrolled. At both the 3‐month and 1‐year follow‐ups, patients in the highest quartile group of GGT levels exhibited a higher risk of stroke recurrence [HR 1.32 (95% CI 1.07–1.63), HR 1.34 (95% CI 1.13–1.60)], ischemic stroke [HR 1.37 (95% CI 1.10–1.71), HR 1.37 (95% CI 1.14–1.64)], and combined vascular events [HR 1.34 (95% CI 1.09–1.65), HR 1.34 (95% CI 1.13–1.59)] than those in the lowest quartile group. Moreover, the Kaplan–Meier curves revealed that the incidence rates of stroke adverse outcomes were quite different in the four groups. The highest quartile group showed the highest cumulative incidence, while the lowest quartile group showed the lowest cumulative incidence. After applying discrimination tests, adding GGT into the conventional model resulted in slight improvements in predicting stroke adverse outcomes (NRI: 10%–14%).ConclusionThis study demonstrated that elevated GGT levels were positively associated with an increased risk of stroke adverse outcomes, namely, recurrence, ischemic stroke, and combined vascular events.
The severity of nutrition and pneumonia predicts survival in patients with aspiration pneumonia: A retrospective observational study
Authors: Yanagita Yorihide , Arizono Shinichi , Tawara Yuichi , Oomagari Masaki , Machiguchi Hikaru , Yokomura Koshi , Katagiri Norimasa , Iida Yuki 
Published: July 2022

AbstractIntroductionAspiration pneumonia is a common problem among older adults; it has a high mortality rate and the prevalence is increasing. Reports on the risk factors for mortality in patients with aspiration pneumonia are limited. This study aimed to evaluate the risk factors for 90‐day survival in patients with aspiration pneumonia.MethodsThis retrospective observational study was conducted at Seirei Mikatahara General Hospital between 1 April 2015 and 31 March 2016. Patients with aspiration pneumonia who had dysphagia or aspiration confirmed by modified water swallow test or VideoEndoscopic examination of swallowing were included. The primary endpoint was 90‐day survival. We performed univariate and multivariate logistic regression analyses with survival and non‐survival at 90 days as the independent variables.ResultsA total of 276 patients were recruited for this study. The A‐DROP score (odds ratio [OR] = 2.440; 95% confidence interval [CI], 1.400–4.270; p < 0.01), Geriatric Nutritional Risk Index score (OR = 0.383; 95% CI, 0.178–0.824; p < 0.05) and sex (OR = 0.365; 95% CI, 0.153–0.869; p < 0.05) were independent early predictors of mortality.ConclusionThe results suggest that nutritional status and the severity of pneumonia are important factors that predict life expectancy in patients with aspiration pneumonia.
Incidence of immune checkpoint inhibitor mediated cardiovascular toxicity: A systematic review and meta‐analysis
Authors: Malaty Michael M. , Amarasekera Anjalee Thanuja , Li Cindy , Scherrer‐Crosbie Marielle , Tan Timothy C. 
Published: July 2022

AbstractBackgroundImmune checkpoint inhibitors (ICI) are a novel class of anti‐cancer therapy becoming increasingly associated with fatal cardiovascular toxicities (CVTs). The aim is to determine the incidence of CVTs in cohorts treated with ICIs as sole anti‐cancer therapy.MethodsA systematic literature search of scientific and medical databases was performed using PRISMA principles to identify relevant cohorts (PROSPERO registration CRD42021272470). Data for specific CVTs (pericardial disease, myocarditis, heart failure, arrhythmia, myocardial infarction/ischaemia and angina), CVT‐related death and CV risk factors were extracted. Presence of CVTs in ICI‐monotherapy versus combination‐ICI therapy, and programmed death 1/programmed death ligand 1‐ (PD1/PDL1‐) versus cytotoxic T‐lymphocyte‐associated protein 4‐ (CTLA4‐) inhibitor groups were dichotomised and meta‐analysed using random‐effect models.ResultsForty‐eight studies (11,207 patients) were identified, from which 146 CVTs were observed (incidence 1.30%). ICI‐monotherapy led to more CVTs than combination therapy (119/9009; 1.32% vs. 18/2086; 0.86%). Across monotherapies, PD1/PDL1‐inhibitors had lower incidence of CVTs compared to CTLA4‐inhibitors (62/6950; 0.89% vs. 57/2059; 2.77%). Based on eight studies that were meta‐analysed, no significant difference was observed comparing monotherapy versus combination‐ICI therapy (RR‐0.69, 95% CI −1.47 to 0.09) for all CVTs, or PD1/PDL1‐ to CTLA4‐inhibitors (RR‐0.27, 95% CI −2.06 to 1.53), for all CVTs including CVT‐death. CV risk factors could not be attributed to an ICI group as data was population based rather than individual based.ConclusionICI‐mediated CVTs are rare and potentially fatal. The role of CV risk factors in their development remains unclear.
Merchants and missionaries: Chinese evangelical networks and the transnational resacralization of European urban spaces
Authors: Cao Nanlai 
Published: July 2022

AbstractThis article sheds new light on the diverse modes in which migration and religion intersect in shaping everyday transnational practices by exploring the articulations of religion and business migration in an emerging Chinese‐led transnational mission field. Drawing on multisited ethnographic fieldwork conducted in Wenzhou, Rome and Paris, I show how a large group of transnational Chinese merchants has adopted a vigorous homegrown evangelical Christianity as the spiritual and social anchor of their territorial mercantile culture in diaspora. These merchants have actively engaged in producing religious activities and events that link China to Europe and in resacralizing secular real estate and attaching evangelistic meanings to Europe's historic urban spaces. For rural‐originated migrants who embrace a global hierarchy of places, the evangelical discursive distinction between the mundane and the transcendent spheres finds expression in their perceived opposition between the peripheral local and the modern global centre in the global market economy.
Reimagining consumer involvement: Resilient system indicators in the COVID‐19 pandemic response in New South Wales, Australia
Authors: Shih Patti , Hallam Laila , Clay‐Williams Robyn , Carter Stacy M. , Brown Anthony 
Published: July 2022

AbstractBackgroundReflections on the response to the COVID‐19 pandemic often evoke the concept of ‘resilience’ to describe the way health systems adjusted and adapted their functions to withstand the disturbance of a crisis, and in some cases, improve and transform in its wake. Drawing from this, this study focuses on the role of consumer representatives in healthcare services in initiating changes to the way they participated in the pandemic response in the state of New South Wales in Australia.MethodsIn‐depth interviews were conducted with two cohorts of consumer representatives. Cohort A included experienced and self‐identified consumer leaders, who worked together in a COVID‐19 Consumer Leaders Taskforce; Cohort B included participants outside of this group, and purposively included consumer representatives from rural and regional areas, and culturally and linguistically diverse communities.ResultsThe pause in consumer engagement to support health service decision‐making in responding to the pandemic forced consumer representatives to consider alternative approaches to participate. Some initiated networking with each other, forming new collaborations to produce consumer‐led research and guidelines on pandemic‐related patient care. Others mobilized support from community and politicians to lobby for specific healthcare issues in their local areas.ConclusionThe response to the COVID‐19 pandemic made visible the brittle nature of previous engagement processes of involving consumers in organizational design and governance. However, the momentum for proactive self‐organization in an unexpected crisis created space for consumer representatives to reset and reimagine their role as active partners in health services. Their ability to adapt and adjust ways of working are key assets for a resilient health system.Patient or Public ContributionThis project is a collaborative study between academic researchers and health consumer (patient and public) representatives. It followed the principles of codesign and coresearch, whereby both consumer representatives and academic researchers contributed equally to all stages of the project. The study was cofunded by both academic institutions and consumer representative organizations.
Clinical, pathological genetics and intratumoral immune milieu of serrated adenocarcinoma of the colon
Authors: Yılmaz Osman , Crabbe Andrew , Neyaz Azfar , Pankaj Amaya , Lee Soo Hyun , Hosseini Sahar , Rickelt Steffen , Cerda Sandra , Zhao Qing , Leijsen Lieve , Dineaux Anne , Shroff Stuti G , Crotty Rory , Zhang M Lisa , Yilmaz Omer H , Patil Deepa T , Berger David , Deshpande Vikram 
Published: July 2022

AbstractBackgroundSerrated adenocarcinoma (SAC), a recognised WHO variant of colonic adenocarcinoma, is the purported end‐product of serrated neoplasia. However, the diagnosis of SAC is infrequently rendered, and little is known about its prognosis, immune microenvironment and molecular alterations.Materials and methodsWe assessed 903 consecutive colon carcinomas and recognised tumours with ≥ 5% (n = 77) serrated and ≥ 50% serrated patterns (n = 13). We assessed precursor polyps and synchronous polyps. We recorded demographic/clinical parameters, histological features and mismatch repair (MMR) status. We performed immunohistochemistry and quantification on tissue microarray for HLA class I/II proteins, B2MG, CD8, CD163, LAG3, FoxP3, PD‐L1 and BRAF V600E.ResultsWe identified ≥ 5% epithelial serration prevalence in 8.5% of cases and ≥ 50% epithelial serration prevalence in 1.4% of cases. Precursor lesions were present in 21.4% of cases; these were mostly tubular adenomas with two traditional serrated adenomas identified. SAC with ≥ 5% serrations exhibited lower numbers of CD8‐positive lymphocytes (P = 0.002) and lower B2MG expression (P = 0.048), although neither value was significant at ≥ 50% serration threshold. There was no difference in HLA class I/II, or PD‐L1 expression on tumour cells and no difference in PD‐L1, LAG3, FoxP3 and CD163 expression on immune cells. There was no association with MMR status, or BRAFV600E relative to conventional adenocarcinoma. There was improved disease‐specific survival on univariate (but not multivariate) analysis between carcinomas with serrated pattern and non‐mucinous conventional colonic carcinomas at ≥ 5% epithelial serrations (P = 0.04).ConclusionSAC category shows a limited impact on survival, and this phenotype may harbour a unique immunological milieu.
Patterns and lived realities: Exploring informal social protection across race and education
Authors: Oppel Annalena 
Published: July 2022

AbstractInformal social protection (ISP) has been recognised as a source of livelihood support for the poor and a critical element of the welfare mix in the global South. While the potential of ISP in contributing to economic welfare is well‐documented, less is known about its role in responding to and maintaining horizontal inequalities. Group‐based inequality is a key concern of transformative social protection, particularly discriminatory practices and exclusion that shape them. By using a mixed‐method approach to social networks, and including non‐poor and poor individuals, I provide insights into how support practices differ across race and education in urban Namibia thereby reflecting continued economic inequalities. I argue that ISP plays an important role in understanding transformative approaches to social protection; both by highlighting the importance of exploring ISP beyond a conceptual lens on poverty as well as its potential in maintaining power imbalances in a stratified, unequal society.
Research activities in general medicine: a scoping survey by the Internal Medicine Society of Australia and New Zealand
Authors: Aung Ar K. , Pickles Robert , Knight Anne , Shannon Leigh‐anne , Bowers Andrew , Donnelly Sinead , Johnson Douglas F. , Scott Ian A. , Potter Elizabeth L. ,   Internal Medicine Society of Australia and New Zealand Research Network (IMSANZ‐RN) Working Group
Published: July 2022

AbstractBackgroundIn developing an effective framework for a collaborative research network (RN) that supports members involved in research, the Internal Medicine Society of Australia and New Zealand (IMSANZ) required a better understanding of the current level of research activity and engagement by general physicians, and factors influencing such engagement.AimsTo explore the current research landscape amongst general physicians in Australia and Aotearoa New Zealand.MethodsA questionnaire exploring research participation, scope, research enablers and barriers was disseminated to IMSANZ members over a 3‐month period. Core functions of IMSANZ‐RN, research priorities, potential solutions to perceived barriers and required level of support were also evaluated.ResultsA total of 82 members, mostly senior medical staff (74.4%), responded to the survey (11.8% response rate). More than 70% were involved in impactful research across multiple disciplines, encompassing a wide range of research themes and topics. However, there is limited support and resources available to conduct research, with most projects being self‐instigated and self‐funded. There is overwhelming support to increasing the profile of research in general medicine through the establishment of IMSANZ‐RN, whose principal purposes, as identified by respondents, are to foster collaboration, promote research, provide research education and training, and share information among general physicians. Quality improvement studies (56.1%) and clinical trials (41.5%) were also identified as priority research types.ConclusionsThis study has profiled the constraints faced by general physicians in conducting high‐quality collaborative research and provides insights into what is needed to support greater research engagement, through development of a discipline‐specific clinical RN.
PARD3gene variation as candidate cause of nonsyndromic cleft palate only
Authors: Cui Renjie , Chen Dingli , Li Na , Cai Ming , Wan Teng , Zhang Xueqiang , Zhang Meiqin , Du Sichen , Ou Huayuan , Jiao Jianjun , Jiang Nan , Zhao Shuangxia , Song Huaidong , Song Xuedong , Ma Duan , Zhang Jin , Li Shouxia 
Published: July 2022

AbstractNonsyndromic cleft palate only (NSCP) is a common congenital malformation worldwide. In this study, we report a three‐generation pedigree with NSCP following the autosomal‐dominant pattern. Whole‐exome sequencing and Sanger sequencing revealed that only the frameshift variant c.1012dupG [p. E338Gfs*26] inPARD3cosegregated with the disease. In zebrafish embryos, ethmoid plate patterning defects were observed with PARD3 ortholog disruption or expression of patient‐derived N‐terminal truncatingPARD3(c.1012dupG), which implicated PARD3 in ethmoid plate morphogenesis. PARD3 plays vital roles in determining cellular polarity. Compared with the apical distribution of wild‐type PARD3, PARD3‐p. E338Gfs*26 mainly localized to the basal membrane in 3D‐cultured MCF‐10A epithelial cells. The interaction between PARD3‐p. E338Gfs*26 and endogenous PARD3 was identified by LC–MS/MS and validated by co‐IP. Immunofluorescence analysis showed that PARD3‐p. E338Gfs*26 substantially altered the localization of endogenous PARD3 to the basement membrane in 3D‐cultured MCF‐10A cells. Furthermore, seven variants, including one nonsense variant and six missense variants, were identified in the coding region ofPARD3in sporadic cases with NSCP. Subsequent analysis showed that PARD3‐p. R133*, like the insertion variant of c.1012dupG, also changed the localization of endogenous full‐length PARD3 and that its expression induced abnormal ethmoid plate morphogenesis in zebrafish. Based on these data, we revealPARD3gene variation as a novel candidate cause of nonsyndromic cleft palate only.
Susceptibility assessment and mapping of Ips typographus (L.) (Coleoptera: Curculionidae) in oriental spruce forests in Artvin, Turkey
Authors: Alkan Akıncı Hazan , Genç Çağla , Akıncı Halil 
Published: July 2022

AbstractIps typographus, which was first identified in 1984 in the oriental spruce forests of Artvin, Turkey, has killed millions of cubic metres of trees. Severe outbreaks of I. typographus following storms resulting in fallen trees and salvage logging done as a part of control activities have caused gaps in the stand canopy of oriental spruce forests. These forests, which have many important functions, such as supplying water, soil conservation and preventing natural disasters in the area they spread, have a fragmented structure because of beetle damages and various traditional utilization practices of the local community. In this study, the local spread of I. typographus in the forests of Hatila Valley National Park and the neighbouring Taşlıca Forest Sub‐District was evaluated, and the areas susceptible to the beetle were determined using the frequency ratio method. A total of 120 pheromone traps were employed in the study. A beetle density map of the study area was produced using the inverse distance weighting interpolation method based on the total number of beetles caught by the traps. Then, the correlation between the regions with high I. typographus density and environmental factors that contributed to this situation were determined using the frequency ratio method. An average 6528.70 beetles were caught by the pheromone traps as a result of this study. The density of the beetles was high in 60.64% of the study area, and an average 10,844.25 beetles were caught by the pheromone traps in these areas. The difference in the total number of beetles between areas with high beetle density and those with low or medium beetle density was significant. It was determined that 32.53% of the study area had very high or high susceptibility to I. typographus. Different parameters such as altitude, slope, aspect, distance to forest roads, stand type, topographic wetness index and area solar radiation were found to be associated with the susceptibility of an area to I. typographus.
Which factors may influence the implementation of drug dispensing in community pharmacies? A qualitative study
Authors: Cerqueira‐Santos Sabrina , Rocha Kérilin S. S. , Araújo Dyego C. S. A. , Santos Júnior Genival A. , Menezes Pedro W. S. , Sanchez Júlia M. , Mesquita Alessandra R. , Lyra Júnior Divaldo P. 
Published: July 2022

AbstractRationale, Aims and ObjectivesImplementation of clinical pharmacy services, such as drug dispensing, is a complex process. It is necessary to understand the challenges associated with this practice from the perspective of the actors involved to help ensure optimal service provision. Thus, this study aimed to understand the factors that may influence the implementation of drug dispensing in community pharmacies, according to the perceptions of pharmacists.MethodThis qualitative study was based on semistructured, face‐to‐face interviews. The participants were pharmacists who worked in a chain of community pharmacies in Brazil, selected based on their direct participation in the implementation process. The interview recordings were transcribed full verbatim and were independently analyzed using thematic analysis, followed by consensus meetings between researchers. The factors identified by the participants were classified according to the Apoteca framework. This study was approved by the Committee of Ethics in Research and all participants signed an informed consent form.ResultsWe conducted 18 interviews, with 47 factors that may influence the implementation of drug dispensing in community pharmacies being identified. These factors were allocated to seven categories: support from community pharmacy chain (4), pharmacy infrastructure (11), characteristics of the pharmacy, medicines and other health products (4), pharmacist (16), dispensing work process (2), pharmacy team (2) and patient (8). The classification of factors according to the Apoteca framework allocated most of them to administrative (14) and technical (15) domains, followed by attitudinal (13) and political (5) domains.Conclusion(s)This study identified several factors that can influence the implementation of drug dispensing and classified them according to the domains of the Apoteca framework, highlighting the multifactorial nature of the implementation process. The results of this study can guide the planning of strategies aimed at providing efficient drug dispensing in community pharmacies.