bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unpacking economic programme theory for supervision training: Preliminary steps towards realist economic evaluation
Authors: Rees Charlotte E. , Foo Jonathan , Nguyen Van N. B. , Edouard Vicki , Maloney Stephen , Ottrey Ella , Palermo Claire 
Published: November 2021

AbstractIntroductionCost studies are increasingly popular given resource constraints. While scholars stress the context‐dependent nature of cost, and the importance of theory, cost studies remain context‐blind and atheoretical. However, realist economic evaluation (REE) privileges context and the testing/refinement of economic programme theory. This preliminary REE serves to test and refine economic programme theory for supervision training programmes of different durations to better inform future programme design/implementation.MethodsOur preliminary REE unpacked how short (half‐day) and extended (12 week) supervision training programmes in Victoria, Australia, produced costs and outcomes. We employed mixed methods: qualitative realist and quantitative cost methods. Economically optimised programme models were developed guided by identified cost‐sensitive mechanisms and contexts.ResultsAs part of identified context‐mechanism‐outcome configurations (CMOCs) for both training programmes, we found a wider diversity of positive outcomes but greater costs for the extended programme (11 outcomes; AU$3069/learner) compared with the short programme (7 outcomes; $385/learner). We identified four shared cost‐sensitive mechanisms for both programmes (training duration, learner protected time, learner engagement, and facilitator competence) and one shared cost‐sensitive context (learners' supervisory experience). We developed two economically optimised programme models: (1) short programme for experienced supervisors facilitated by senior educators ($406/learner); and (2) extended programme for inexperienced supervisors facilitated by junior educators ($2104/learner).DiscussionOur initial economic programme theory was somewhat supported, refuted and refined. Results were partly consistent with previous research, but also extended it through unpacking cost‐sensitive mechanisms and contexts. Although our preliminary REE fills a pressing gap in the methodology literature, conducting REE was challenging given our desire to integrate economic and realist analyses fully, and remain faithful to realist principles. Attention to training duration and experience levels of the facilitator–learner dyad may help to balance the cost and outcomes of training programmes.
Dysbiosis of skin mycobiome in atopic dermatitis
Authors: Tao Rong , Li Ruoyu , Wang Ruojun 
Published: November 2021

AbstractAtopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease with an increasing prevalence worldwide. The aetiology and pathogenesis of AD have not been fully elucidated. Previous studies have suggested the role of fungi as a triggering factor in the development AD. Here we conducted a systematic review to investigate the skin mycobiome profiles in AD and to address whether there is an association between fungal dysbiosis and AD. We searched Medline/PubMed, Embase and Web of Science for research studies published in English between January 1st, 2010 and April 21st, 2021. A total of 11 human studies and 3 animal studies were included in this analysis. Fungal dysbiosis was observed in AD lesions with a depleted amount of Malassezia and a higher abundance of filamentous fungi. A positive correlation between Candida and Staphylococcus was also demonstrated in AD. We supposed that specific species of Malassezia spp. and Candida spp. may play a role in the pathogenesis of AD by interacting with the pathogenic bacteria. Topical application of emollients could improve the skin barrier function and restore the skin fungal flora by increasing the amount of Malassezia. Further studies focusing on the complex interplay between specific skin fungi and the host can provide better insight into the role of microorganisms in the pathogenesis of AD.
Non‐coding regulatory elements: Potential roles in disease and the case of epilepsy
Authors: Pagni Susanna , Mills James D. , Frankish Adam , Mudge Jonathan M. , Sisodiya Sanjay M. 
Published: November 2021

AbstractNon‐coding DNA (ncDNA) refers to the portion of the genome that does not code for proteins and accounts for the greatest physical proportion of the human genome. ncDNA includes sequences that are transcribed into RNA molecules, such as ribosomal RNAs (rRNAs), microRNAs (miRNAs), long non‐coding RNAs (lncRNAs) and un‐transcribed sequences that have regulatory functions, including gene promoters and enhancers. Variation in non‐coding regions of the genome have an established role in human disease, with growing evidence from many areas, including several cancers, Parkinson's disease and autism. Here, we review the features and functions of the regulatory elements that are present in the non‐coding genome and the role that these regions have in human disease. We then review the existing research in epilepsy and emphasise the potential value of further exploring non‐coding regulatory elements in epilepsy. In addition, we outline the most widely used techniques for recognising regulatory elements throughout the genome, current methodologies for investigating variation and the main challenges associated with research in the field of non‐coding DNA.
Alpha adaptins show isoform‐specific association with neurofibrillary tangles in Alzheimer's disease
Authors: Srinivasan Sukanya , Gal Jozsef , Bachstetter Adam , Nelson Peter T. 
Published: November 2021

AbstractAimsThe heterotetrameric assembly protein complex 2 (AP‐2) is a central hub for clathrin‐dependent endocytosis. The AP‐2 α‐adaptin subunit has two major isoforms, encoded by two separate genes: AP2A1 and AP2A2. Endocytosis has been implicated in the pathogenesis of neurodegenerative disease, and recent studies linked α‐adaptins (gene variants, splicing defects and altered expression) with late‐onset Alzheimer's disease (LOAD) risk. Here, we used multiple antibodies to investigate α‐adaptin isoforms and their localization in human brains.MethodsThe specificities of 10 different α‐adaptin antibodies were evaluated using immunoblots after human AP2A1 and AP2A2 plasmid transfection in cultured cells. Additional immunoblot analyses were then performed on protein homogenates from control and LOAD subjects. Formalin‐fixed, paraffin‐embedded brain sections from control and LOAD subjects were immunohistochemically stained, and immunofluorescence experiments were performed for quantitation of colocalisation with digital image analysis.ResultsEight of the 10 evaluated antibodies recognised transfected α‐adaptin proteins on immunoblots. The α‐adaptin subspecies were relatively uniformly expressed in five different human brain regions. The α‐adaptins were present in the detergent‐insoluble fraction from cognitively impaired, but less so in control, brains. Immunohistochemical analyses showed colocalisation of AP2A1 with tau pathology in LOAD brains. By contrast, AP2A2 colocalised with microglial cells.ConclusionsThese observations provide evidence of isoform‐specific changes of α‐adaptins in the brains of LOAD subjects. Antibodies that were verified to recognise AP2A1, but not AP2A2, labelled neurofibrillary tangles of LOAD patients. The findings extend our understanding of AP‐2 proteins in the human brain in healthy and diseased states.
Showcasing Copleston and Lonergan
Authors: O'Collins Gerald 
Published: November 2021

AbstractFor twelve of the years during which he spent a semester lecturing as a visiting professor at the Gregorian University (Rome), Frederick Copleston enjoyed close contacts with Bernard Lonergan. He was one of the two ‘house’ censors of Insight. He also wrote a very positive review of the book for the Oxford-based Journal of Theological Studies, which was then co-edited by Henry Chadwick. The personal and professional contacts between Copleston and Lonergan have been widely neglected; they call for further study and evaluation.
Effect of methylphenidate at different doses on new bone formation with rapid maxillary expansion: A micro‐CT and histomorphometric study in rats
Authors: Dursun S. , Sezen Erhamza T. , Önder M. E. , Erdoğan Düzcü S. 
Published: November 2021

AbstractObjectivesThis study aimed to evaluate the effect of systemically administered methylphenidate hydrochloride (MPH) on new bone formation in premaxillary suture after rapid maxillary expansion (RME).Setting and Sample PopulationThirty‐three Wistar rats were divided into four groups: Group 1 (high dose, 30/60 mg/kg MPH), Group 2 (low dose, 4/10 mg/kg MPH), Group 3 (positive control) and Group 4 (negative control).MethodsRME was applied on the 70th day of the study. A 5‐day RME period was followed by a 12‐day retention period. The experiment was terminated on the 87th day. Micro‐CT for radiological evaluation, haematoxylin‐eosin and Masson's trichrome staining methods were used for histomorphometric evaluation.ResultsAmong experimental groups with RME, the lowest number of osteoblasts and capillaries in Group 1 (P < .05). New bone formation, fibrous callus formation, distal osteotomy line, proximal osteotomy union and cortex remodelling were observed to be lower in Group 1 and Group 2 than Group 3 (P < .05). There was a statistically significant difference between Group 4 and each of the other groups (P = .000) in the evaluation of the results for bone mineral density, bone volume, bone volume percentage, trabecular thickness and trabecular number.ConclusionsMPH reduces cellular activity for new bone formation in suture in RME groups. Before performing rapid maxillary expansion in patients using MPH, the use of the drug should be postponed after a multidisciplinary decision process or clinical doses should be lowered.
Sun exposure and protection habits in transplant athletes: An international survey
Authors: Navarrete‐De Gálvez M , Ruiz Sánchez JM , Navarrete‐De Gálvez E , Aguilera J , Rivas‐Ruiz F , de Troya‐Martín M , Herrera‐Ceballos E , de Gálvez MV 
Published: November 2021

AbstractBackgroundTransplant recipients are particularly prone to the development of skin cancer, and overexposure to UV radiation during outdoor activities increases the risk of carcinogenesis.ObjectiveThe aim of this study was to analyze sun‐related behaviors and knowledge in transplant athletes, examine the frequency of sunburns, and explore associations with a history of skin cancer.Materials and methodsCross‐sectional descriptive study. Participants (n = 170) in the XXI World Transplant Games from >50 countries completed a questionnaire on sun protection habits and knowledge, type of transplant, immunosuppressive therapy, and personal history of skin cancer.ResultsThe most common transplanted organs were the kidney (n = 79), the liver (n = 33), and the heart (n = 31). Overall, 61.3% of athletes had been doing sport for >15 years and 79.5% spent >1–2 h a day outdoors. Fifteen % of athletes had a history of skin cancer. The prevalence of sunburn in the previous year was 28.9%, higher in athletes aged <50 years (37.2%); without a primary school education (58.3%), not taking cyclosporin (32.6%), and athletes who played basketball (75%). The main sun protection measures used were sunscreen (68.9%) and sunglasses (67.3%). Use of a hat or cap was the only measure significantly associated with a reduced prevalence of sunburn.ConclusionsDespite high awareness that sun exposure increases the risk of skin cancer, sunburn was common in transplant athletes. Efforts should be made to strengthen multidisciplinary sun protection education strategies and ensure periodic dermatologic follow‐up to prevent sun‐induced skin cancer in this population.
Clostridioides difficile infection in solid organ and hematopoietic stem cell transplant recipients: A prospective multinational study
Authors: Blumberg Emily A. , Collins Gary , Young Jo‐Anne H. , Nguyen M. Hong , Michonneau David , Temesgen Zelelem , Origȕen Julia , Barcan Laura , Obeid Karam M. , Belloso Waldo H. , Gras Julien , Corbelli Giulio Maria , Neaton James D. , Lundgren Jens , Snydman David R. , Molina Jean‐Michel ,   for the INSIGHT Clostridioides difficile Study Group
Published: November 2021

AbstractBackgroundClostridioides difficile infection (CDI) is a significant cause of morbidity and mortality in recipients of solid organ transplant (SOT) or hematopoietic stem cell transplant (HSCT). In retrospective single center analyses, severe disease and relapse are common. We undertook an international, prospective cohort study to estimate the response to physician determined antibiotic treatment for CDI in patients with SOT and HSCT.MethodsAdults with a first episode of CDI within the first 2 years of SOT or HSCT were enrolled. Demographics, comorbidities, and medication history were collected, and over 90 days of follow‐up clinical cure, recurrences, and complications were assessed. Logistic regression was used to study associations of baseline predictors of clinical cure and recurrence. Odds ratios (ORs) and 95% confidence intervals (CIs) are cited.ResultsA total of 132 patients, 81 SOT and 51 HSCT (32 allogeneic), were enrolled with a median age of 56 years; 82 (62%) were males and 128 (97%) were hospitalized at enrollment. One hundred and six (80.3%) were diagnosed by DNA assay. CDI occurred at a median of 20 days post‐transplant (interquartile range, IQR: 6–133). One hundred and eight patients (81.8%) were on proton pump inhibitors; 126 patients (95.5%) received antibiotics within the 6 weeks before CDI. The most common initial CDI treatments prescribed, on or shortly before enrollment, were oral vancomycin alone (50%) and metronidazole alone (36%). Eighty‐three percent (95% CI: 76, 89) of patients had clinical cure; 18% (95% CI: 12, 27) of patients had recurrent CDI; global clinical cure occurred in 65.2%. Of the 11 patients who died, two (1.5% of total) were related to CDI. In multivariable logistic regression analyses, the type of initial treatment was associated with clinical cure (p = .009) and recurrence (p = .014). A history of cytomegalovirus (CMV) after transplant was associated with increased risk of recurrence (44% with versus 13% without CMV history; OR: 5.7, 95% CI: 1.5, 21.3; p = .01).ConclusionsAmong adults who develop CDI after SOT or HSCT, despite their immunosuppressed state, the percentage with clinical cure was high and the percentage with recurrence was low. Clinical cure and recurrence varied by type of initial treatment, and CMV viremia/disease was associated with an increased risk of recurrence.
ATP‐sensitive potassium channels in zebrafish cardiac and vascular smooth muscle
Authors: Singareddy Soma S. , Roessler Helen I. , McClenaghan Conor , Ikle Jennifer M. , Tryon Robert C. , van Haaften Gijs , Nichols Colin G. 
Published: November 2021

AbstractATP‐sensitive potassium channels (KATP channels) are hetero‐octameric nucleotide‐gated ion channels that couple cellular metabolism to excitability in various tissues. In the heart, KATP channels are activated during ischaemia and potentially during adrenergic stimulation. In the vasculature, they are normally active at a low level, reducing vascular tone, but the ubiquitous nature of these channels leads to complex and poorly understood channelopathies as a result of gain‐ or loss‐of‐function mutations. Zebrafish (ZF) models of these channelopathies may provide insights to the link between molecular dysfunction and complex pathophysiology, but this requires understanding the tissue dependence of channel activity and subunit specificity. Thus far, direct analysis of ZF KATP expression and functional properties has only been performed in pancreatic β‐cells. Using a comprehensive combination of genetically modified fish, electrophysiology and gene expression analysis, we demonstrate that ZF cardiac myocytes (CM) and vascular smooth muscle (VSM) express functional KATP channels of similar subunit composition, structure and metabolic sensitivity to their mammalian counterparts. However, in contrast to mammalian cardiovascular KATP channels, ZF channels are insensitive to potassium channel opener drugs (pinacidil, minoxidil) in both chambers of the heart and in VSM. The results provide a first characterization of the molecular properties of fish KATP channels and validate the use of such genetically modified fish as models of human Cantú syndrome and ABCC9‐related Intellectual Disability and Myopathy syndrome.Key points
Zebrafish cardiac myocytes (CM) and vascular smooth muscle (VSM) express functional KATP channels of similar subunit composition, structure and metabolic sensitivity to their mammalian counterparts.
In contrast to mammalian cardiovascular KATP channels, zebrafish channels are insensitive to potassium channel opener drugs (pinacidil, minoxidil) in both chambers of the heart and in VSM.
We provide a first characterization of the molecular properties of fish KATP channels and validate the use of such genetically modified fish as models of human Cantú syndrome and ABCC9‐related Intellectual Disability and Myopathy syndrome.
Determining the Influence of Casing Vibrational Behavior on Rotordynamics
Authors: Amer Mona , Paehr Martin , Scheidt Lars Panning-von , Seume Joerg R. , Schmied Joachim 
Published: November 2021

Abstract
Casings of machinery and support structures have an influence on the rotordynamic behavior, which is commonly considered by simplified models (e.g., one degree-of-freedom models). These are in many cases insufficient. Hence, more accurate modeling approaches are required, which can be used in the design process or the rotordynamic calculation to achieve a better representation of the overall vibrational behavior. To study the effects of casing and supporting structures on rotordynamics, the casing modal parameters of an axial compressor are determined by an experimental modal analysis. In parallel, a numerical model is established. As experimental data are rarely found in the literature, this work focuses on the parameter identification of the casing structure. The results are subsequently incorporated into a model updating strategy, in order to tune and improve the numerical model. Experimental and numerical data are compared to assess the quality of the data and the results gained. The ultimate objective is a reduced order model, which can be integrated in existing rotordynamic tools via an interface while keeping the calculation time low.
Gas Flow in Occluded Respiratory Tree: A New Matrix-Based Approach
Authors: Soni Bharat , Kumar Nayak Ameeya , Miguel Antonio F. 
Published: November 2021

AbstractStudies suggest that both the size of airways and the number of bifurcations of the respiratory tree provide the best structural design to accomplish its function. However, constrictions and occlusions due to inflammation and pulmonary edema of the airways can inhibit normal air flowing through the respiratory tree, affecting gas exchange. It results in heterogeneity in gas exchange (and pulmonary perfusion) with adverse risk factors. In this study, we propose a methodology based on the airway tree admittance (reciprocal of impedance) to study this problem. This methodology is distinct from the traditional quantification, based on overall impedance using lump parameter models, and applies to a matrix formed by admittances of each airway of the entire conducting part of the bronchial tree. The generated system admittance matrix is highly sparse in nature, and thus to solve the same system, a modified block-based LU decomposition method is proposed to improve the space–time tradeoff. Our approach enables the determination of the local ventilation pattern and reduces the misevaluation, mainly in the cases that characterize the early-stage obstructive disorders. The key finding of the present study is to show that how the position and intensity of local obstruction in an airway can affect the overall as well as regional ventilation which can lead to impaired gas exchange.
Impact of Face Masks on Exercise Capacity and Lactate Thresholds in Healthy Young Adults
Authors: Rudi Wolf-Stephan , Maier Florian , Schüttler Dominik , Kellnar Antonia , Strüven Anna Katharina , Hamm Wolfgang , Brunner Stefan 
Published: November 2021

Background:Although many countries have introduced strict guidelines regarding mouth and nose coverage in public to contain infection rates during the SARS-CoV-2 pandemic, more information is needed regarding the impact of wearing face masks on lactate thresholds (LT) and performance parameters during exercise.Methods:Ten healthy male and 10 healthy female subjects (age = 33.4 [10.26] y, body mass index = 23.52 [2.36] kg/m2) performed 3 incremental performance tests, wearing no mask (NM), surgical mask (SM), and filtering face piece mask class 2 (FFP2), with a cycle ergometer. The authors analyzed changes in the LT, in blood gas parameters, and in the rating of perceived exertion (RPE).Results:Performance at LT remained unchanged in subjects wearing SM or FFP2 in comparison with NM (162.5 [50.6] vs 167.2 [58.9] vs 162.2 [58.4] W with NM, SM, and FFP2, respectively,P = .24). However, the peak performance was significantly reduced wearing FFP2 compared with NM (213.8 [71.3] vs 230.5 [77.27] W, FFP2 vs NM, respectively,P < .001). Capillary pCO2 was increased while wearing SM as well as FFP2 compared with NM (29 [3.1] vs 33.3 [4] vs 35.8 [4.9] mmHg with NM, SM, and FFP2, respectively;P < .001), and pO2 decreased under maximum performance (84 [6.7] vs 79.1 [7.5] vs 77.3 [8.2] mmHg with NM, SM, and FFP2,P < .01). Importantly, rating of perceived exertion was significantly increased by wearing FFP2 compared with NM at LT according to Mader (16.7 [2.7] vs 15.3 [1.8] FFP2 vs NM, respectively,P < .01).Conclusion:Wearing face masks during exercise showed no effect on LT, limited maximum performance, and induced discrete changes in capillary pCO2 and pO2 within the physiologic range while increasing RPE at LT.
Paediatric tic-like presentations during the COVID-19 pandemic
Authors: Buts Sarah , Duncan Morvwen , Owen Tamsin , Martino Davide , Pringsheim Tamara , Byrne Susan , McWilliams Andrew , Murphy Tara , Malik Osman , Liang Holan , Heyman Isobel , Hedderly Tammy 
Published: November 2021

Background and aimClinical centres have seen an increase in tic-like movements during the COVID-19 pandemic. A series of children and adolescents are described.MethodsA retrospective chart review of 34 consecutive paediatric patients presenting with sudden onset tic-like movements, seen over 6 months.Results94% of patients were female, with an average age of sudden onset or increase of tic-like movements of 13.7 years. 44% had a previous diagnosis of tics, and 47% initially presented to an emergency department. Comorbid psychiatric and neurodevelopmental disorders were reported in 91% with 68% reporting anxiety.ConclusionWe highlight a dramatic presentation of sudden onset functional tic-like movements in predominantly female adolescents to help inform identification and management. There is need to research the neurobiological underpinnings and environmental exacerbating factors leading to these presentations and to explore effective therapeutic strategies.