bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epigenetic regulation of epithelial dectin‐1 through an IL‐33‐STAT3 axis in allergic disease
Authors: Yong Hwan Mee , Gour Naina , Sharma Deepika , Khalil Syed Muaz , Lane Andrew P. , Lajoie Stephane 
Published: May 2021

AbstractAllergic diseases arise in susceptible individuals in part because of decrements in protective pathways. The mechanism by which these anti‐inflammatory molecules become repressed remains unclear. We have previously reported that epithelial dectin‐1 prevents aberrant type 2 responses and is downregulated in the epithelium of allergic patients. Here, we report that dectin‐1 is constitutively expressed by the respiratory epithelium in humans and that IL‐33 specifically acts as a repressor of dectin‐1. Mechanistically, this occurs via IL‐33‐dependent STAT3 activation and the subsequent repression of the dectin‐1 gene, CLEC7A. We have identified a novel enhancer region upstream of the proximal promoter of CLEC7A that is only accessible in epithelial cells, but not in hematopoietic cells. Epigenetic repression of CLEC7A through this newly identified locus, downstream of an aberrant IL‐33‐STAT3 axis, occurs in the epithelium of allergic individuals. Collectively, our data identify a mechanism of epigenetic fine‐tuning of dectin‐1 expression in epithelial cells that may participate in allergenicity.
Fire safety and emergency evacuation guidelines for intensive care units and operating theatres: for use in the event of fire, flood, power cut, oxygen supply failure, noxious gas, structural collapse or other critical incidents
Authors: Kelly F. E. , Bailey C. R. , Aldridge P. , Brennan P. A. , Hardy R. P. , Henrys P. , Hussain A. , Jenkins M. , Lang A. , McGuire N. , McNarry A. , Osborn M. , Pittilla L. , Ralph M. , Sarkar S. , Taft D. 
Published: May 2021

SummaryThe need to evacuate an ICU or operating theatre complex during a fire or other emergency is a rare event but one potentially fraught with difficulty: Not only is there a risk that patients may come to harm but also that staff may be injured and unable to work. Designing newly‐built or refurbished ICUs and operating theatre suites is an opportunity to incorporate mandatory fire safety features and improve the management and outcomes of such emergencies: These include well‐marked manual fire call points and oxygen shut off valves (area valve service units); the ability to isolate individual zones; multiple clear exit routes; small bays or side rooms; preference for ground floor ICU location and interconnecting routes with operating theatres; separate clinical and non‐clinical areas. ICUs and operating theatre suites should have a bespoke emergency evacuation plan and route map that is readily available. Staff should receive practical fire and evacuation training in their clinical area of work on induction and annually as part of mandatory training, including ‘walk‐through practice’ or simulation training and location of manual fire call points and fire extinguishers, evacuation routes and location and operation of area valve service units. The staff member in charge of each shift should be able to select and operate fire extinguishers and lead an evacuation. Following an emergency evacuation, a network‐wide response should be activated, including retrieval and transport of patients to other ICUs if needed. A full investigation should take place and ongoing support and follow‐up of staff provided.
Early childhood circumcision in Australia: Trends over 20 years and interrupted time series analysis
Authors: Qin Kirby R. , Paynter Jessica A. , Wang Luke C. , Mollah Taha , Qu Liang G. 
Published: May 2021

AbstractBackgroundMale circumcision is one of the most common surgical procedures performed in the Australian private sector. This study examines the trends in childhood circumcision throughout the early 21st century.MethodsCircumcisions performed between 2000 and 2019 amongst preschool‐aged Australian boys (0–4 years) were obtained from the Medicare Benefits Schedule. Quarterly data for Victoria and South Australia were divided into three phases separated by (i) state‐wide bans of non‐therapeutic circumcision in the public sector (2007) and (ii) a disfavouring of non‐therapeutic circumcisions by the Royal Australasian College of Physicians (2010). Interrupted time series analyses determined differences between pre‐ban (2000–2007), post‐ban (2007–2010) and reversal (2010–2019) phases.ResultsAltogether, 478 717 circumcisions were performed on preschool‐aged boys. Incidence progressed from 2675 per 100 000 preschoolers in 2000 to 3140 in 2008 to 1875 in 2019. In Victoria, the baseline (Q1‐2000) rate of circumcision was 294.9 per 100 000. This rose by +1.3 (1.1 to 4.1, p < 0.001) per quarter pre‐ban and +6.6 (3.0 to 10.3, p = 0.001) post‐ban before decreasing by −13.1 (−16.4 to −9.8, p < 0.001) in the reversal phase. In South Australia, the initial rate was 745.2 per 100 000 and increased by +1.4 (0.0 to 2.8, p = 0.045) per quarter pre‐ban, +7.6 (0.5 to 14.7, p = 0.035) post‐ban and retracted by −20.8 (−27.9 to −13.7, p < 0.001) during the reversal phase.ConclusionThe incidence of childhood circumcisions in Australia observed a significant rise and fall throughout the early 21st century. Medical and surgical authorities may have played an important role in the gradual reduction of procedures over the last decade.
Review article: the evolution of endpoint assessments for chemotherapy‐induced nausea and vomiting and post‐operative nausea and vomiting—a perspective from the US Food and Drug Administration
Authors: Gabby Maegan E. , Bugin Kevin , Lyons Erica 
Published: May 2021

SummaryBackgroundNausea and vomiting can result in decreased compliance with oncologic therapies for patients with chemotherapy‐induced nausea and vomiting (CINV); and increase complications and recovery time for patients with post‐operative nausea and vomiting (PONV). CINV refers to nausea and vomiting after antineoplastic therapy administration and PONV is nausea and/or vomiting that occurs in the post‐anaesthesia care unit or during the 24 hours following surgery.AimTo analyse the evolution of endpoint assessments utilised in clinical trials to support FDA approval of CINV and PONV therapeutics.MethodsA review supported by the US FDA analysed 31 approved New Drug Applications, respective clinical trial protocols and product labelling for CINV or PONV therapeutics with an emphasis on primary endpoint selection.ResultsAnalysis revealed primary endpoints have become more refined and now often include the assessment of both vomiting and rescue medication use (ie, Complete Response). Additionally, the visual analogue scale was recognised as the most prevalent instrument to assess nausea as 58% of reviewed applications included this assessment. An imbalance between available therapies for adults and paediatric patients was also identified as only 39% of the reviewed approved products were indicated for paediatric use.ConclusionThe goal of this research was to inform and identify future opportunities for enhanced clinical trial design. Nausea assessment was identified as an opportunity for continued research and development due to the large heterogeneity of instruments used. Furthermore, there is a need for the development of safe and efficacious antiemetic treatments for paediatric patients.
Development and characterization of two novel 68Ga‐labelled neuropeptide Y short analogues with potential application in breast cancer imaging
Authors: Cardoso María Elena , Tejería Emilia , Zirbesegger Kevin , Savio Eduardo , Terán Mariella , Rey Ríos Ana María 
Published: May 2021

AbstractIn vivo receptor targeting with radiolabelled peptide‐based probes is an attractive approach for the development of novel radiotracers for molecular imaging. This work presents the development and characterization of two novel neuropeptide Y analogues labelled with a positron emitter 68Ga, for potential use in breast cancer imaging. Both analogues share the same amino acid sequence and were derivatized with NOTA through either a lysine linker (L1) or an acetylated lysine (L2). In both cases, a single product with radiochemical purity higher than 95% was obtained. The two complexes were hydrophilic, showed remarkable in vitro stability, good cellular uptake, binding affinity in the nanomolar range and high cellular internalization rate. Biodistribution studies revealed low blood uptake and elimination through the urinary tract. The addition of an acetyl group in the spacer increased the lipophilicity of C2 and modified the reactivity of the ε‐amino group of the lysine which resulted in lower protein binding and lower percentage of injected dose in bladder and urine. The tumour versus muscle ratio was (3.8 ± 0.4) for 68Ga‐L1 and (4.7 ± 0.4) for 68Ga‐L2. These results encourage performing further studies in order to complete the evaluation of both tracers as potential radiopharmaceutical for breast cancer imaging.
Bone mineral density at extremely low weight in patients with anorexia nervosa
Authors: Bemer Pauline , Di Lodovico Laura , Haykanush Ohanyan , Théodon Hélène , Briot Karine , Carlier Robert , Dicembre Marika , Duquesnoy Maéva , Melchior Jean‐Claude , Hanachi Mouna 
Published: May 2021

AbstractObjectiveLow bone mineral density (BMD) is a frequent and invalidating consequence of chronic undernourishment in patients with anorexia nervosa (AN). The aim of this study was to assess prevalence and clinic‐biological correlates of low BMD and fractures in extremely undernourished inpatients with AN.DesignRetrospective cohort study.Patients and measurementsThis study included 97 extremely malnourished female inpatients with AN consecutively admitted over 2 years. Clinical‐biological variables, history of fractures and BMD by dual‐energy X‐ray absorptiometry (DXA) were examined to find predictors of low BMD and fractures.ResultsThe prevalence of low BMD was of 51% for lumbar spine and 38% for femoral neck. Z‐scores were lower at lumbar spine (−2.2 ± 1.2 SD) than at femoral neck (−1.9 ± 0.9 SD) (P<.01). Fragility fractures were reported by 10% of patients. BMD was mainly predicted by FFM, illness duration, age at onset and restricting AN (P<.05). Fractures were predicted by sodium concentrations, femoral neck Z‐score and illness duration (P<.03).ConclusionExtremely severe patients with AN have high prevalence of low BMD, predicted by severity and chronicity of malnutrition.
Autogenous Mineralized Dentin versus Xenograft granules in Ridge Preservation for Delayed Implantation in Post‐extraction Sites: A Randomized controlled clinical trial with an 18 months follow‐up
Authors: Santos Alexandre , Botelho João , Machado Vanessa , Borrecho Gonçalo , Proença Luís , Mendes José João , Mascarenhas Paulo , Alcoforado Gil 
Published: May 2021

AbstractObjectivesTo test primary stability of delayed implants placed in post‐extraction ridges preserved with autogenous mineralized dentin matrix (MDM) versus xenograft granules. Clinical, histological and pain experience outcomes were further assessed.Material and MethodsFrom March 2018 to July 2020, patients requiring ridge preservation in preparation for delayed implant placement in post‐extraction sites were included. Participants were randomly allocated to either the test (MDM) or control group (xenograft granules) prior to ridge preservation. Visual analogue scale and analgesic consumption were measured every day for a week. Six months after preservation, trephine cores were harvested for histomorphometry prior to implant placement. Implants were then placed, and implant stability was measured immediately as well as two months after placement. Marginal bone loss and presence of mucositis/peri‐implantitis were registered up to 18 months after prosthetic loading.ResultsFifty‐two patients (66 implants) completed the study. MDM and xenograft groups presented similar primary (77.1 ± 6.9 versus. 77.0 versus. 5.9) and secondary (81.8 ± 5.1 versus. 80.1 ± 3.8) implant stabilities. The percentage of newly formed bone in MDM (47.3%) was significantly higher than xenograft (34.9%) (p < .001), and the proportion of residual graft was significantly lower (12.2% in MDM and 22.1% in xenograft) (p < .001). No significant differences were found as far as clinical, radiographic and patient‐related outcomes.ConclusionsImplants placed in sites preserved with MDM had similar primary stability in comparison to xenograft granules. MDM showed a significantly higher quantity of newly formed bone and lower amount of residual graft in histomorphometry results and equal clinical and patient‐related outcomes.
Climate adaptation interventions for iconic fauna
Authors: Mason Claire , Hobday Alistair J. , Alderman Rachael , Lea Mary‐Anne 
Published: May 2021

AbstractClimate adaptation is an emerging practice in biodiversity conservation, but little is known about the scope, scale, and effectiveness of implemented actions. Here, we review and synthesize published reports of climate adaptation interventions for iconic fauna. We present a systematic map of peer‐reviewed literature databases (Web of Science and Scopus); however, only nine climate adaptation actions targeting iconic fauna were returned. In the grey and informal literature, there were many instances of practical intervention within our scope, that were not uncovered during traditional systematic search methods. The richness of actions reported in commercial news, government and non‐government organization media outlets and other online sources vastly outweighs the limited studies that have been robustly evaluated and reported in the scientific literature. From our investigation of this emerging field of conservation practice, we draw insights and pen a series of recommendations for the field moving forward. Key recommendations for future adaptation interventions include: the sharing and publishing of climate‐related conservation interventions, the use of standardized metrics for reporting outcomes, the implementation of experimental controls for any actions undertaken, and reporting and evaluation of both failures and successes.
Effect of difelikefalin, a selective kappa opioid receptor agonist, on respiratory depression:A randomized, double‐blind, placebo‐controlled trial
Authors: Viscusi Eugene R. , Torjman Marc C. , Munera Catherine L. , Stauffer Joseph W. , Setnik Beatrice S. , Bagal Sukirti N. 
Published: May 2021

AbstractDifelikefalin, a selective kappa opioid receptor agonist designed to limit central nervous system (CNS) penetration, is under development for the treatment of pruritus. Its hydrophilic, small‐peptidic structure limits CNS entry, minimizing potential CNS‐mediated adverse events (AEs). This study assessed the effect of difelikefalin on key relevant measures of respiratory depression in healthy volunteers. This single‐center, randomized, double‐blind, placebo‐controlled, three‐way crossover study enrolled healthy, nonsmoking volunteers. Subjects were randomized to 1 of 3 treatment sequences of difelikefalin (1.0 or 5.0 mcg/kg i.v.) or placebo on sequential days with an intervening 24 (±2) h washout period. The primary end points included incidence of increased end‐tidal carbon dioxide (ETCO2) greater than or equal to 10 mm Hg versus baseline or a level greater than 50 mm Hg sustained greater than or equal to 30 seconds, and incidence of reduction in saturation of peripheral oxygen (SpO2) to less than 92% sustained greater than or equal to 30 seconds. Secondary end points included incidence of reduced respiratory rate and other safety assessments. Fifteen subjects were randomized and completed the study. No subject on placebo or difelikefalin met the increased ETCO2or reduced SpO2primary end point criteria for respiratory depression. All respiratory measures in each group remained near baseline values during 4‐h postdose observations. No subject met the reduced respiratory rate criterion or experienced clinically significant changes in ETCO2, SpO2, or respiratory rate. The most commonly reported treatment‐emergent AEs (TEAEs; ≥20% of subjects) were paresthesia, hypoesthesia, and somnolence in the difelikefalin arms. All TEAEs were mild and resolved without intervention. Difelikefalin 1.0 and 5.0 mcg/kg i.v. did not produce respiratory depression.
Effects of 5‐HT₃ receptor antagonists on cisplatin‐induced kidney injury
Authors: Goda Mitsuhiro , Kanda Masaya , Yoshioka Toshihiko , Yoshida Ami , Murai Yoichi , Zamami Yoshito , Aizawa Fuka , Niimura Takahiro , Hamano Hirofumi , Okada Naoto , Yagi Kenta , Chuma Masayuki , Izawa‐Ishizawa Yuki , Ishizawa Keisuke 
Published: May 2021

AbstractNausea, vomiting, and renal injury are the common adverse effects associated with cisplatin. Cisplatin is excreted via the multidrug and toxin release (MATE) transporter, and the involvement of the MATE transporter in cisplatin‐induced kidney injury has been reported. The MATE transporter is also involved in the excretion of ondansetron, but the effects of 5‐HT3 receptor antagonists used clinically for cisplatin‐induced renal injury have not been elucidated. Therefore, the aim of this study was to investigate the effects of 5‐HT3 receptor antagonists in a mouse model of cisplatin‐induced kidney injury and to validate the results using medical big data analysis of more than 1.4 million reports and a survey of 3000 hospital medical records. The concomitant use of a first‐generation 5‐HT3 receptor antagonist (ondansetron, granisetron, or ramosetron) significantly increased cisplatin accumulation in the kidneys and worsened renal damage. Conversely, the concomitant use of palonosetron had no effect on renal function compared with the use of cisplatin alone. Furthermore, an analysis of data from the US Food and Drug Administration Adverse Event Reporting System and retrospective medical records revealed that the combination treatment of cisplatin and a first‐generation 5‐HT3 receptor antagonist significantly increased the number of reported renal adverse events compared with the combination treatment of cisplatin and a second‐generation 5‐HT3 receptor antagonist. These results suggest that compared with the first‐generation antagonists, second‐generation 5‐HT3 receptor antagonists do not worsen cisplatin‐induced acute kidney injury. The findings should be validated in a prospective controlled trial before implementation in clinical practice.
Quality of life assessment in amyloid transthyretin (ATTR) amyloidosis
Authors: Aimo Alberto , Rapezzi Claudio , Perfetto Federico , Cappelli Francesco , Palladini Giovanni , Obici Laura , Merlini Giampaolo , Di Bella Gianluca , Serenelli Matteo , Zampieri Mattia , Milani Paolo , Licordari Roberto , Teresi Lucio , Ribarich Nicolò , Castiglione Vincenzo , Quattrone Filippo , De Rosis Sabina , Vergaro Giuseppe , Panichella Giorgia , Emdin Michele , Passino Claudio 
Published: May 2021

AbstractBackgroundAmyloid transthyretin (ATTR) amyloidosis is caused by the systemic deposition of transthyretin molecules, either normal (wild‐type ATTR, ATTRwt) or mutated (variant ATTR, ATTRv). ATTR amyloidosis is a disease with a severe impact on patients’ quality of life (QoL). Nonetheless, limited attention has been paid to QoL so far, and no specific tools for QoL assessment in ATTR amyloidosis currently exist. QoL can be evaluated through patient‐reported outcome measures (PROMs), which are completed by patients, or through scales, which are compiled by clinicians. The scales investigate QoL either directly or indirectly, i.e., by assessing the degree of functional impairment and limitations imposed by the disease.DesignSearch for the measures of QoL evaluated in phase 2 and phase 3 clinical trials on ATTR amyloidosis.ResultsClinical trials on ATTR amyloidosis have used measures of general health status, such as the Short Form 36 Health Survey (SF‐36), or tools developed in other disease settings such as the Kansas City Cardiomyopathy Questionnaire (KCCQ) or adaptations of other scales such as the modified Neuropathy Impairment Score +7 (mNIS+7).ConclusionsScales or PROMs for ATTR amyloidosis would be useful to better characterize newly diagnosed patients and to assess disease progression and response to treatment. The ongoing ITALY (Impact of Transthyretin Amyloidosis on Life qualitY) study aims to develop and validate 2 PROMs encompassing the whole phenotypic spectrum of ATTRwt and ATTRv amyloidosis, that might be helpful for patient management and may serve as surrogate endpoints for clinical trials.
Evaluation of head and neck cancer education at European dental schools
Authors: Poelman Marcella R. , Brand Henk S. , Foppen Laura , de Visscher Jan G.A.M. , Jager Derk H. Jan 
Published: May 2021

AbstractAimIn Europe, approximately 150.000 patients are diagnosed with head and neck cancer annually. Dentists play an important role in prevention and detection at an early stage when survival rates are best. This study aims to evaluate content of head and neck cancer education curricula of European dental schools.Materials and MethodsA questionnaire, comprising 20 questions about content of curricula and teaching methods, was distributed to the deans of all 234 members of the Association for Dental Education in Europe.ResultsThe response rate was 24%. All dental schools included head and neck cancer screening practices in their curricula, two‐thirds had their students perform this screening on all patients routinely and education was mostly divided over various courses (65%). A variation in content of education in screening practices and counselling patients about various risk factors was reported. Alcohol and tobacco use were included in most curricula as risk factors for head and neck cancer (98%), gastro‐oesophageal reflux was less frequently included (41%). The human papillomavirus (HPV) as a risk factor for oropharyngeal cancer was included in 94% of curricula and 87% also contained education about strategies to discuss prevention of HPV‐related cancer. No association was found between curricula containing strategies about discussing HPV‐related cancer and inclusion of the HPV vaccine in national immunisation programmes.ConclusionHead and neck cancer teaching programmes show a considerable variation across European dental schools. Development of a unified teaching programme suitable for all European dental schools seems warranted.
Gendered bureaucracies: Women mayors and the size and composition of local governments
Authors: Alberti Carla , Diaz‐Rioseco Diego , Visconti Giancarlo 
Published: May 2021

AbstractWhile women are underrepresented in politics, recent improvements in women's representation in legislative and executive bodies have spurred academic interest in the effects of electing women on a wide array of outcomes. Effects on bureaucracies, however, have received less attention. Do women mayors reform local bureaucracies differently than their men counterparts? We take advantage of rich administrative data from Chile to explore the effects of having a woman mayor on the size and gender composition of municipal bureaucracies. Using a regression discontinuity design in close electoral races, we find that women mayors reduce the size of local bureaucracies while simultaneously increasing the share of women public employees. Our findings thus show that women mayors' approach to bureaucratic reform once in office differs from that of their men counterparts, and contribute to existing research on the consequences of electing women.