bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting TDP‐43 proteinopathy with drugs and drug‐like small molecules
Authors: Buratti Emanuele 
Published: May 2020

Following the discovery of the involvement of the ribonucleoprotein TDP‐43 in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), a major research focus has been to develop treatments that can prevent or alleviate these disease conditions. One pharmacological approach has been to use TDP‐43‐based disease models to test small molecules and drugs already known to have some therapeutic effect in a variety of neurodegenerative conditions. In parallel, various disease models have been used to perform high‐throughput screens of drugs and small compound libraries. The aim of this review will be to provide a general overview of the compounds that have been described to alter pathological characteristics of TDP‐43. These include expression levels, cytoplasmic mis‐localization, post‐translational modifications, cleavage, stress granule recruitment and aggregation. In parallel, this review will also address the use of compounds that modify the autophagic/proteasome systems that are known to target TDP‐43 misfolding and aggregation.LINKED ARTICLESThis article is part of a themed issue on Recent advances in ALS pathogenesis and therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.6/issuetoc
Does staff‐assessed care quality predict early failure of dental fillings? A prospective study
Authors: Berthelsen Hanne , Owen Mikaela , Wretlind Katharina , Westerlund Hugo 
Published: May 2020

AbstractObjectivesThe aim of this study was to evaluate staff‐assessed care quality as an indicator of register‐based measures of care quality at dental clinics, more specifically register‐based measures of survival of dental fillings and initiation of preventive treatments for caries patients.MethodsThis prospective study includes data from cross‐sectional workplace psychosocial risk assessment surveys at dental clinics and register data on survival of dental fillings, and initiation of preventive treatment for caries patients obtained from the Swedish Quality Registry for Caries and Periodontal Disease (SKaPa) Demographic background data on the age, gender, income level and place of birth of patients was obtained from Statistics Sweden (SCB). The data were analysed using discrete‐time multilevel survival analysis and multiple linear regression analysis.ResultsThe results showed that staff‐assessed care quality rated by the total staff or by dental nurses at the clinic predicted the risk of replacement of dental fillings made due to a caries diagnosis during the 3‐year follow‐up period, controlling for potential confounding due to patient demographic characteristics (age, sex, income and country of birth). In contrast, the better the staff‐assessed care quality at the clinic, the smaller the proportion of the patients received preventive care in addition to operative caries therapy when controlling for potential confounding due to patient demographics. Care quality assessed by dentists at the clinic did not predict either of these outcome measures.ConclusionsPremature failure of dental fillings is costly for both patients and society, which leads to a need for relevant measures for following dental care quality. Our findings indicate that staff‐assessed care quality – a cheap and easy measure to collect and follow continuously in dental practice – can be used to monitor aspects of quality in real time in order to facilitate continuous improvement and quickly amend quality problems. Also, it can be used for integrating quality improvement in systematic work environment risk management.
The use of vitamin D in preventing post‐thyroidectomy hypocalcemia: An endocrinologist survey study
Authors: Pinardo Heinrich , Rubin Samuel J. , Hashemi Sean , DePietro Joseph , Pearce Elizabeth N. , Ananthakrishnan Sonia , Alexanian Sara M. , Steenkamp Devin W. , Noordzij Jacob Pieter 
Published: May 2020

AbstractObjectiveTo evaluate the use of preoperative vitamin D levels and postoperative vitamin D supplementation among endocrinologists for the prevention of post‐thyroidectomy hypocalcaemia.MethodsEndocrinologist members of the American Thyroid Association (ATA) were contacted via email to complete a 21‐question survey, which included both questions about demographic information, and preventing and managing postoperative hypocalcaemia after thyroidectomy. Univariate and multivariate analysis was performed to determine the respondents' use of preoperative vitamin D levels, dose and duration of preoperative vitamin D repletion, decision to delay surgery for low vitamin D levels in the case of a benign or malignant disease, and routine prescription of postoperative calcium or vitamin D supplementation.Results225 endocrinologists who were ATA members responded to the questionnaire. When compared to endocrinologists practicing in other countries, those that practice in the United States were 2.5 times more likely to check preoperative vitamin D levels (95% CI[1.404, 4.535], P = .002), significantly more likely to replete vitamin D deficient patients with high‐dose vitamin D (ie ≥50K IU/week), 4.458 times more likely to prescribe prophylactic supplemental calcium (95% CI[2.446, 8.126]; P < .0001) and 3.48 more likely to prescribe supplemental vitamin D (95% CI [1.906, 6.355]; P < .0001). Endocrinologists who have been in practice for >10 years were also 1.915 times more likely to prescribe supplemental vitamin D (95% CI (1.080, 3.395); P = .0263). Physicians that treat >50 thyroidectomy cases/year were 2.083 more likely to recommend a vitamin D repletion duration of >1 month than those that treat ≤50 cases/year ([1.036, 4.190], P = .0395). Lastly, if the patient has low preoperative vitamin D levels, 47.05% of respondents chose to delay surgery in a benign disease, while only 11.61% of respondents would do so in a case of malignant disease.ConclusionsApproximately one‐half of surveyed endocrinologists reported using preoperative vitamin D levels to assess a patient's risk for post‐thyroidectomy hypocalcaemia. Endocrinologists practicing in the United States, compared to those practicing in other countries, were more likely to both test for preoperative vitamin D levels and to recommend prophylactic post‐thyroidectomy calcium and vitamin D supplementation.
Risk factors of radiation pneumonitis in patients with NSCLC treated with concomitant chemoradiotherapy––Are we underestimating diabetes?––Turkish oncology group (TOG)/Lung cancer study group
Authors: Ergen Sefika A. , Dincbas Fazilet O. , Yücel Birsen , Altınok Pelin , Akyurek Serap , Korkmaz Kıraklı Esra , Ulger Sukran , Etiz Durmus , Yilmaz Ufuk , Kılıc Diclehan , Bozcuk Hakan 
Published: May 2020

AbstractIntroductionTo evaluate the clinical and dosimetric parameters that increase the risk of radiation pneumonitis (RP) in locally advanced non‐small cell lung cancer (NSCLC) patients treated with concomitant chemoradiotherapy of nationwide multicentric data analysis.MethodsAll data of 268 patients who underwent definitive chemoradiotherapy were retrospectively collected from eight institutes participating in this study. Patient, tumor and treatment‐related factors and dosimetric parameters were analyzed for grade ≥2 RP. The toxicity scoring system of The Radiation Therapy Oncology Group used for grading the severity of pneumonitis. A relationship with the risk of RP with potential predictive factors were evaluated by univariate and multivariate analyses. A recursive partition analysis (RPA) was applied to stratify patients according to the risk of developing RP.ResultsThere were 90 (33.6%) patients who had grade ≥2 RP. The median time to pneumonitis after treatment was 4 months (range:1‐6 months). In univariate analysis, diabetes mellitus (DM), use of cisplatin/etoposide, total and daily radiotherapy (RT) fraction dose, the planning target volume (PTV) size, mean lung dose, V5, V10 and RT technique were associated with the development of pneumonitis. In multivariate analysis, only DM (P = 0.008) was found to be independent risk factors for RP. According to RPA, the risk of developing RP was highest in patients with DM.ConclusionsIn our study, besides the known dosimetric factors, DM was found to be the most important risk factor causing RP development in multivariate analysis and RPA. The risk is tripled compared to patients without DM.
Application errors associated with topical treatment of scabies: an observational study
Authors: Nemecek Romina , Stockbauer Anna , Lexa Martina , Poeppl Wolfgang , Mooseder Gerhard 
Published: May 2020

SummaryBackgroundIn recent years, there has been a significant increase in scabies infestations throughout German‐speaking countries. Given the high frequency of treatment failures, the question arises as to whether topical permethrin treatment is always performed correctly.Patients and methodsOur department uses a fluorescent test cream to teach patients on how to correctly apply topical permethrin. In the context of a prospective observational study of 21 patients, we systematically assessed and analyzed potential application errors.ResultsNone of the participants succeeded in adequately applying the cream to the entire skin as previously instructed. The median number of regions left untreated was six (minimum: 2; maximum: 18), which included a median body surface area of 6 % (minimum: 2 %; maximum: 30 %). With regard to predilection sites of scabies, the ankles were left untreated in 62 % of cases, followed by the interdigital spaces (toes) (33 %) and the sacral region (24 %). All patients considered the pretreatment training to be very useful.ConclusionsThe present findings clearly demonstrate potential shortcomings when it comes to the application of topical antiscabies treatment. This may provide a (potentially underestimated) explanation for the large number of reports on treatment failures in this regard, which falsely suggest potential treatment resistance.
Estimation of elastic‐plastic strain response at two‐dimensional notches
Authors: Ball Dale L. 
Published: May 2020

AbstractIt is widely recognized that the accuracy of notch fatigue calculations can be improved significantly when those calculations are based on the elastic‐plastic response strain at the notch root, as opposed to the remotely applied loads or stresses. Two of the most widely used approximations for this response are Neuber's rule and Glinka's equivalent strain energy density method. In the present work, a survey of some of the many published evaluations of these methods was first conducted, and then, additional detailed comparisons with elastic‐plastic finite element analyses for a series of semicircular and V‐shaped notch configurations were performed. Based on the observed limitations of both the Neuber and Glinka approaches, and with the guidance of the elastic‐plastic finite element results, a new (and more robust) approach for the estimation of notch response strains is proposed. This approach calls for the definition of a generalized notch response curve (GNRC), which is dependent on both the material stress–strain curve and the notch geometry. Once defined, the GNRC allows the determination of the response strain for any applied stress.
Signals 1, 2 and B cell fate or: Where, when and for how long?
Authors: Turner Jackson S. , Benet Zachary L. , Grigorova Irina L. 
Published: May 2020

AbstractDiverse B cell responses are important for generating antibody‐mediated protection against highly variable pathogens. While some antigens can trigger T‐independent B cell proliferation and short‐term antibody production, development of long‐term humoral immunity requires T‐dependent B cell responses. The “two‐signal” model of B cell activation has long been invoked to explain alternate B cell recruitment into immune response to foreign antigens vs. induction of tolerance to self‐antigens. However, a number of other factors appear to influence the fate of mature B cells responding to antigen in vivo. In this review, we will discuss how various spatiotemporal scenarios of antigen access into secondary lymphoid organs, antigen valency and cellular environment of antigen acquisition by B cells, duration of B cell access to antigen and the timing of T cell help may affect follicular B cell fate, including death, survival, anergy, and recruitment into T‐dependent responses. We will also highlight unresolved questions related to B cell activation and tolerance in vivo that may have important implications for vaccine development and autoimmunity.
Melatonin modulates mitophagy, innate immunity and circadian clocks in a model of viral‐induced fulminant hepatic failure
Authors: Crespo Irene , Fernández‐Palanca Paula , San‐Miguel Beatriz , Álvarez Marcelino , González‐Gallego Javier , Tuñón María Jesús 
Published: May 2020

AbstractThe haemorrhagic disease virus (RHDV) is a non‐cultivable virus that promotes in rabbits an acute disease which accomplishes many characteristics of an animal model of fulminant hepatic failure (FHF). Beneficial effects of melatonin have been reported in RHDV‐infected rabbits. This study investigated whether protection against viral‐derived liver injury by melatonin is associated with modulation of mitophagy, innate immunity and clock signalling. Rabbits were experimentally infected with 2 × 104 haemagglutination units of a RHDV isolate and killed at 18, 24 and 30 hours after infection (hpi). Melatonin (20 mg/kg body weight ip) was administered at 0, 12 and 24 hpi. RHDV infection induced mitophagy, with the presence of a high number of mitophagosomes in hepatocytes and increased expression of mitophagy genes. Greater expression of main innate immune intermediaries and inflammasome components was also found in livers with RHDV‐induced FHF. Both mitophagy and innate immunity activation was significantly hindered by melatonin. FHF induction also elicited an early dysregulation in clock signalling, and melatonin was able to prevent such circadian disruption. Our study discloses novel molecular routes contributing to RHDV‐induced damage progression and supports the potential of melatonin as a promising therapeutic option in human FHF.
Plac8‐mediated autophagy regulates nasopharyngeal carcinoma cell function via AKT/mTOR pathway
Authors: Huang Mao‐Ling , Qi Cheng‐Lin , Zou You , Yang Rui , Jiang Yang , Sheng Jian‐Fei , Kong Yong‐Gang , Tao Ze‐Zhang , Chen Shi‐Ming 
Published: May 2020

AbstractTo explore the relationship between autophagy and cell function, we investigated how PLAC8‐mediated autophagy influences proliferation, apoptosis and epithelial‐mesenchymal transition (EMT) in NPC. Colony formation analyses and CCK8 assays were used to assess the proliferative capacity of NPC cells. Transmission electron microscopy (TEM) was used to identify autophagosomes. Autophagic flux was monitored using the tandem monomeric RFP‐GFP‐tagged LC3 (tfLC3) assay. The rate of apoptosis in NPC cells was analysed by flow cytometry. Western blot analysis was used to evaluate the activation of autophagy and the signalling status of the AKT/mTOR pathway. Our study reveals that knocking out PLAC8 (koPLAC8) induces autophagy and apoptosis, while suppressing NPC cell proliferation and EMT. However, inhibition of autophagy with 3‐methyladenine or by knocking down Beclin‐1 reverses the cell proliferation, apoptosis and EMT influenced by koPLAC8. We find that koPLAC8 inhibits the phosphorylation of AKT and its downstream target, mTOR. Moreover, immunofluorescence and co‐immunoprecipitation reveal complete PLAC8/AKT colocalization and PLAC8/AKT interaction, respectively. Furthermore, knockout of PLAC8 induced autophagy and inactivated AKT/mTOR signalling pathway of NPC xenografts. Overall, our findings demonstrate that koPLAC8 induces autophagy via the AKT/mTOR pathway, thereby inhibiting cell proliferation and EMT, and promoting apoptosis in NPC cells.
Communication skills teaching for student dietitians using experiential learning and simulated patients
Authors: Knight A. , Baldwin C. , Reidlinger D. P. , Whelan K. 
Published: May 2020

AbstractBackgroundDietitians require communication competencies for effective dietetic practice. There is little evidence on how student dietitians experience and value communication skills teaching. The present study aimed to measure attitudes of student dietitians with respect to communication skills teaching and how experiential learning using simulated patients impacts confidence in their communication skills.MethodsCommunication skills teaching adopting an experiential skills‐based approach including practice with simulated patients, feedback and reflection were developed. A 67‐item questionnaire with three sections: (i) views regarding the importance of communication skills to dietetic practice; (ii) attitudes to learning communication skills using a modified Communication Skills Attitude Scale; and (iii) confidence in their own communication skills, was completed by students before and after the course, with responses recorded on a five‐point Likert scale and analysed pairwise using McNemar’s test.ResultsOver three academic years, 112 students (91.8% response rate) completed the evaluation. After training, students rated communication skills as important for patient satisfaction (100%) and relationships with patients (99.1%). Student dietitians had positive attitudes to learning communication skills with positive attitudes scale score before teaching of mean (SD) 53.6 (5.3) and after of 54.0 (5.8) (P = 0.162). Following experiential teaching, the proportion of students feeling ‘very or extremely confident’ in understanding a patient’s perspective increased from 27.7% to 41.1% (P = 0.008) and for reaching agreement with a patient from 4.5% to 17.9% (P = 0.001).ConclusionsStudent dietitians consider communication skills important for dietetic practice. They receive teaching positively and an experiential skills‐based approach can improve self‐rated confidence.
Proposal for a new compilation system for metal ores in economy wide material flow accounting
Authors: West James , Lieber Mirko , Lutter Stephan , Schandl Heinz 
Published: May 2020

AbstractThe authors of this article propose a major revision of the processes used for assembling the metal ores component of economy wide material flow accounts (EW‐MFA). The case for doing this is built by describing in detail important shortcomings of current metal ores reporting systems, introducing the key features of the revised system being proposed, and then illustrating the way in which the new system both solves old shortcomings and adds important new capacities. The new capacities added are of particular interest with regard to organizing the data required for a range of practical resource and environmental monitoring and management tasks, at national and smaller scale. The various components of the case for change are explained largely using illustrative examples. The direct motivations behind this work are twofold. First, the proposed system will improve the accuracy and fitness for current uses of the metal ores accounts being assembled. Second, and more importantly, the additional capabilities of the revised system as a resource and environmental management tool will make the process of assembling EW‐MFA accounts more clearly relevant to the concerns of developing countries, which are increasingly being prevailed upon to compile these accounts. In addition to the direct benefits of improved resources and environmental management that should be enabled by the revised system, it is expected that expanding the utility derived from the EW‐MFA process will provide a stronger incentive for its institutionalization and maintenance by individual nations.
Histology and pneumaticity of Aoniraptor libertatem (Dinosauria, Theropoda), an enigmatic mid‐sized megaraptoran from Patagonia
Authors: Aranciaga Rolando Mauro , Garcia Marsà Jordi , Novas Fernando 
Published: May 2020

AbstractAoniraptor libertatem is a mid‐sized megaraptoran that comes from the Late Cretaceous (Turonian) Huincul Formation at Río Negro province, Patagonia, Argentina. In this study, we conducted a detailed analysis of pneumaticity of the sacrum and tail of Aoniraptor. This shows a complex structure within these vertebrae, being composed by small diverticulae surrounding large pneumatic canals and a central chamber that opens outside through pleurocoels or pneumatic canals. Further, we carried out a histologic analysis which confirms the pneumatic nature of these anatomical features. Both analyses found that chevrons in Aoniraptor were invaded by pneumaticity, a feature that appears to be unique to this taxon. In addition, a comparative analysis between Aoniraptor and other theropods (e.g. Gualicho and other megaraptorans) was carried out. This resulted in the modification of previous schemes about the evolution of pneumaticity through Theropoda, the finding of some evolutionary pneumatic traits through Megaraptora, and the usefulness of pneumatic traits as a taxonomic tool.
Negative Spillovers Across Partnerships for Responsible Innovation: Evidence from the 2014 Ebola Outbreak
Authors: Arslan Birgul , Tarakci Murat 
Published: May 2020

AbstractHumanity faces ongoing and contemporaneous grand challenges. Occasionally, abrupt shocks escalate a grand challenge’s salience over others. Prior research has advocated forming partnerships to address grand challenges via responsible innovation. Yet, it remains unclear how temporal changes in the salience of a grand challenge impact innovation performances of partnerships. We address this research gap by bridging the literature on issue salience, responsible innovation and interorganizational relationships. We argue that shocks either aid or harm the performance of partnerships for responsible innovation depending on whether their domains are directly or indirectly affected. The Ebola outbreak in 2014 sets the empirical context to test our theory. We find that while the innovation performance of Ebola partnerships formed after the outbreak rose eleven‐fold, the performance of partnerships treating Influenza fell by 84.9 per cent. Our theory and findings have immediate implications for today’s COVID‐19 outbreak, cautioning against salience shifts among concurrent grand challenges.