bluuebunny/crossref_metadata_2025_split huggingface dataset:
CaMK4 promotes abortion‐related Th17 cell imbalance by activating AKT/mTOR signaling pathway
Authors: Chang Shuo , Yin Tailang , He Fan , Ding Jinli , Shang Ye , Yang Jing 
Published: August 2020

AbstractProblemThe balance of the immune microenvironment along the maternal‐fetal interface is closely related to pregnancy outcomes, with excessive inflammatory reactions leading to the occurrence of pathological pregnancy outcomes such as abortion. CaMK4 has been reported to play a significant role in autoimmune diseases through the regulation of Th17 cells. However, whether CaMK4 is associated with spontaneous abortion or the immune microenvironment along the maternal‐fetal interface remains unclear.Methods of studyIn this study, we constructed normal pregnancy and LPS‐induced abortion models in mice, and a CaMK4 inhibitor called KN‐93 was administered to investigate the changes in and mechanisms of the immune response. The expression of CaMK4 was evaluated in the uteroplacental complex and spleen. Furthermore, the infiltration and function of Th17 cells were estimated in peripheral tissues and the uteroplacental complex.ResultsThe expression of CaMK4 in the uteroplacental complex and spleen was significantly higher in the LPS‐treated group than in the normal pregnancy group. KN‐93, the CaMK4 inhibitor, reversed fetal resorption and excessive inflammation. In detail, KN‐93 led to reduced infiltration of Th17 cells into peripheral tissues and the uteroplacental complex, and the functions of Th17 cells were inhibited. In addition, CaMK4 promoted the AKT/mTOR signaling pathway, which is one of the mechanisms that regulate the immune microenvironment.ConclusionCaMK4 is a critical regulator that promotes the expansion of Th17 cells and enhances their functions through the AKT/mTOR signaling pathway. The inhibition of CaMK4 can reverse the immune imbalance along the maternal‐fetal interface and improve pregnancy outcomes.
Modeling the conversion between specific IgE test platforms for nut allergens in children and adolescents
Authors: Hoang Jennifer A. , Celik Alper , Lupinek Christian , Valenta Rudolf , Duan Lucy , Dai Ruixue , Brydges May G. , Dubeau Aimée , Lépine Claire , Wong Samantha , Alexanian‐Farr Mara , Magder Ahuva , Subbarao Padmaja , Upton Julia E. M. , Schmidthaler Klara , Szépfalusi Zsolt , Ramani Arun , Eiwegger Thomas 
Published: August 2020

AbstractBackgroundMultiplex tests allow for measurement of allergen‐specific IgE responses to multiple extracts and molecular allergens and have several advantages for large cohort studies. Due to significant methodological differences, test systems are difficult to integrate in meta‐analyses/systematic reviews since there is a lack of datasets with direct comparison. We aimed to create models for statistical integration of allergen‐specific IgE to peanut/tree nut allergens from three IgE test platforms.MethodsPlasma from Canadian and Austrian children/adolescents with peanut/tree nut sensitization and a cohort of sensitized, high‐risk, pre‐school asthmatics (total n = 166) were measured with three R&D multiplex IgE test platforms: Allergy Explorer version 1 (ALEX) (Macro Array Dx), MeDALL‐chip (Mechanisms of Development of Allergy) (Thermo Fisher), and EUROLINE (EUROIMMUN). Skin prick test (n = 51) and ImmunoCAP (Thermo Fisher) (n = 62) results for extracts were available in a subset. Regression models (Multivariate Adaptive Regression Splines, local polynomial regression) were applied if >30% of samples were positive to the allergen. Intra‐test correlations between PR‐10 and nsLTP allergens were assessed.ResultsUsing two regression methods, we demonstrated the ability to model allergen‐specific relationships with acceptable measures of fit (r2 = 94%‐56%) for peanut and tree nut sIgE testing at the extract and molecular‐level, in order from highest to lowest: Ara h 2, Ara h 6, Jug r 1, Ana o 3, Ara h 1, Jug r 2, and Cor a 9.ConclusionOur models support the notion that quantitative conversion is possible between sIgE multiplex platforms for extracts and molecular allergens and may provide options to aggregate data for future meta‐analysis.
Late‐onset hypogonadism: Reductio ad absurdum of the cardiovascular risk‐benefit of testosterone replacement therapy
Authors: Sesti Franz , Pofi Riccardo , Minnetti Marianna , Tenuta Marta , Gianfrilli Daniele , Isidori Andrea M. 
Published: August 2020

AbstractBackgroundLow testosterone (T) level is considered a marker of poor cardiovascular health. Ten years ago, the Testosterone in Older Men with Mobility Limitations (TOM) trial was discontinued due to a higher number of adverse events in men receiving T compared with placebo. Since then, several studies have investigated the risks of T replacement therapy (TRT) in late‐onset hypogonadism (LOH).ObjectiveTo review the mechanism by which TRT could damage the cardiovascular system.Materials and methodsComprehensive literature search of recent clinical and experimental studies.ResultsThe mechanisms of T‐mediated coronary vasodilation were reviewed with emphasis on calcium‐activated and ATP‐sensitive potassium ion channels. We showed how T regulates endothelial nitric oxide synthase (eNOS) and phosphoinositide 3‐kinase/protein kinase B/eNOS signaling pathways in vessel walls and its direct effects on cardiomyocytes via β1‐adrenergic and ryanodine receptors and provided data on myocardial infarction and heart failure. Vascular smooth muscle senescence could be explained by the modulation of growth factors, matrix metalloproteinase‐2, and angiotensin II by T. Furthermore, leukocyte trafficking, facilitated by changes in TNF‐α, could explain some of the effects of T on atheromatous plaques. Conflicting data on prothrombotic risk linked to platelet aggregation inhibition via NO‐triggered arachidonate synthesis or increased aggregability due to enhanced thromboxane A in human platelets provide evidence regarding the hypotheses on plaque maturation and rupture risk. The effects of T on cardiac electrophysiology and oxygen delivery were also reviewed.DiscussionThe effects of TRT on the cardiovascular system are complex. Although molecular studies suggest a potential benefit, several clinical observations reveal neutral or occasionally detrimental effects, mostly due to confounding factors.ConclusionsAttempts to demonstrate that TRT damages the cardiovascular system via systematic analysis of the putative mechanisms led to the contradiction of the initial hypothesis. Current evidence indicates that TRT is safe once other comorbidities are addressed.
Nitric oxide added to the sweep gas of the oxygenator during cardiopulmonary bypass in infants: A pilot randomized controlled trial
Authors: Niebler Robert A. , Chiang‐Ching Huang , Daley Kevin , Janecke Rae , Jobe Shawn M. , Mitchell Michael E. , Varner Caleb , Woods Katherine , Scott John P. 
Published: August 2020

AbstractOur objective was to assess the effect of nitric oxide added to the sweep gas of the oxygenator during cardiopulmonary bypass (CPB) in infants on platelet count, platelet function, clinical outcomes, and safety. A randomized, double‐blinded, placebo‐controlled clinical trial in infants less than a year of age undergoing cardiac surgery requiring CPB was undertaken. Nitric oxide at a dose of 20 ppm was added to the sweep gas in the treatment group. Blood was collected at baseline and prior to separation from CPB to measure platelet count and function as determined by responsiveness to specific agonists. Clinical outcomes were observed through hospital discharge. Methemoglobin levels were measured preoperatively, at the conclusion of CPB, and upon admission to the ICU. Forty patients consented and were randomized in the trial. Eighteen patients were randomized to the treatment group and 22 were included in the placebo group. The groups were similar in terms of age, weight, gender, and surgical complexity. No significant differences were found in measures of platelet count, platelet response to agonist, or clinical outcomes. Patients in the treatment group had higher methemoglobin levels after receiving nitric oxide, but no levels approached toxicity (maximum 2.4%). Nitric oxide added to the sweep gas of the oxygenator during CPB in infants did not have an appreciable effect on the preservation of platelet count, platelet responsiveness to agonist, or clinical outcomes. Methemoglobin levels were increased after receiving nitric oxide but were far below a toxic level of 15%.
Using pharmacy dispensing data to predict falls in older individuals
Authors: Gemmeke Marle , Koster Ellen S. , Pajouheshnia Romin , Kruijtbosch Martine , Taxis Katja , Bouvy Marcel L. 
Published: August 2020

AimsAssociations between individual medication use and falling in older individuals are well‐documented. However, a comprehensive risk score that takes into account overall medication use and that can be used in daily pharmacy practice is lacking. We, therefore, aimed to determine whether pharmacy dispensing records can be used to predict falls.MethodsA retrospective cohort study was conducted using pharmacy dispensing data and self‐reported falls among 3454 Dutch individuals aged ≥65 years. Two different methods were used to classify medication exposure for each person: the drug burden index (DBI) for cumulative anticholinergic and sedative medication exposure as well as exposure to fall risk‐increasing drugs (FRIDs). Multinomial regression analyses, adjusted for age and sex, were conducted to investigate the association between medication exposure and falling classified as nonfalling, single falling and recurrent falling. The predictive performances of the DBI and FRIDs exposure were estimated by the polytomous discrimination index (PDI).ResultsThere were 521 single fallers (15%) and 485 recurrent fallers (14%). We found significant associations between a DBI ≥1 and single falling (adjusted odds ratio: 1.30 [95% confidence interval {CI}: 1.02–1.66]) and recurrent falling (adjusted odds ratio: 1.60 [95%CI: 1.25–2.04]). The PDI of the DBI model was 0.41 (95%CI: 0.39–0.42) and the PDI of the FRIDs model was 0.45 (95%CI: 0.43–0.47), indicating poor discrimination between fallers and nonfallers.ConclusionThe study shows significant associations between medication use and falling. However, the medication‐based models were insufficient and other factors should be included to develop a risk score for pharmacy practice.
Antidopaminergic antiemetics and trauma‐related hospitalization: A population‐based self‐controlled case series study
Authors: Bezin Julien , Noize Pernelle , Mansiaux Yohann , Jarne Ana , Pariente Antoine 
Published: August 2020

AimsThe aim of this study was to evaluate the risk of trauma associated with the use of antidopaminergic antiemetics in a real‐world setting.MethodsA self‐controlled case series analysis was performed using the EGB database, the representative sample of the French national healthcare insurance system database. All subjects aged 18 years and over who presented with at least 1 trauma‐related hospitalization and 1 supply for domperidone, metoclopramide or metopimazine between 2009 and 2014 were included in the study. Associations were evaluated by incidence rate ratios.ResultsIncluded exposed cases were 7610 for domperidone cohort, 2189 for metoclopramide and 3911 for metopimazine. Incidence rate ratio for trauma‐related hospitalization during the first 7 days of exposure period compared to unexposed period was 1.53 (95% confidence interval 1.29–1.80) for domperidone, 2.00 (1.37–2.91) for metoclopramide and 2.30 (1.71–3.09) for metopimazine.ConclusionWe found an increased risk of hospitalizations for traumatic injuries for the main marketed antidopaminergic antiemetics during the first days of use. The highest risk was observed for metopimazine, which could relate to its pharmacological profile and central effects.
Protein kinase inhibitors for amyotrophic lateral sclerosis therapy
Authors: Palomo Valle , Nozal Vanesa , Rojas‐Prats Elisa , Gil Carmen , Martinez Ana 
Published: August 2020

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder that causes the progressive loss of motoneurons and, unfortunately, there is no effective treatment for this disease. Interconnecting multiple pathological mechanisms are involved in the neuropathology of this disease, including abnormal aggregation of proteins, neuroinflammation and dysregulation of the ubiquitin proteasome system. Such complex mechanisms, together with the lack of reliable animal models of the disease have hampered the development of drugs for this disease. Protein kinases, a key pharmacological target in several diseases, have been linked to ALS as they play a central role in the pathology of many diseases. Therefore several inhibitors are being currently trailed for clinical proof of concept in ALS patients. In this review, we examine the recent literature on protein kinase inhibitors currently in pharmaceutical development for this diseaseas future therapy for AS together with their involvement in the pathobiology of ALS.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
Child Effects on Parental Negativity: The Role of Heritable and Prenatal Factors
Authors: Liu Chang , Ji Linying , Chow Sy‐Miin , Kang Boyoung , Leve Leslie D. , Shaw Daniel S. , Ganiban Jody M. , Natsuaki Misaki N. , Reiss David , Neiderhiser Jenae M. 
Published: August 2020

This study examined two possible mechanisms, evocative gene–environment correlation and prenatal factors, in accounting for child effects on parental negativity. Participants included 561 children adopted at birth, and their adoptive parents and birth parents within a prospective longitudinal adoption study. Findings indicated child effects on parental negativity, such that toddlers’ negative reactivity at 18 months was positively associated with adoptive parents’ over‐reactive and hostile parenting at 27 months. Furthermore, we found that child effects on parental negativity were partially due to heritable (e.g., birth mother [BM] internalizing problems and substance use) and prenatal factors (e.g., BM illicit drug use during pregnancy) that influence children’s negative reactivity at 18 months. This study provides critical evidence for “child on parent” effects.
Explaining Individual Differences in Trajectories of Simultaneous Bilingual Development: Contributions of Child and Environmental Factors
Authors: Lauro Justin , Core Cynthia , Hoff Erika 
Published: August 2020

Effects of child and environmental factors in moderating the course of bilingual development were investigated using longitudinal data, from age 2.5 to 5 years, on 126 U.S.‐born children with early exposure to Spanish and English. Multilevel models of Spanish and English expressive vocabulary identified children’s phonological memory ability as a significant predictor of both outcomes, while also replicating the effect of the relative amount of language exposure. In addition, nonverbal IQ was a significant predictor of English vocabulary; birth order and maternal education in Spanish were significant predictors of Spanish vocabulary. These findings expand our understanding of the sources of the wide heterogeneity in bilingual development and of the requirements that language acquisition makes of learners and their environments.
Prevalence of latent and overt polyautoimmunity in autoimmune thyroid disease: A systematic review and meta‐analysis
Authors: Botello Alejandro , Herrán María , Salcedo Valentina , Rodríguez Yhojan , Anaya Juan‐Manuel , Rojas Manuel 
Published: August 2020

AbstractBackgroundThyroid autoimmunity is the most frequent condition involved in polyautoimmunity (PolyA). However, the frequency of latent and overt PolyA in patients with autoimmune thyroid disease (AITD) as the index condition is unknown. Therefore, the purpose of this study was to determine the prevalence of these types of PolyA in patients with AITD as the index condition.MethodsThis study adhered to the relevant sections of the Preferred Reporting Items for Systematic Reviews and Meta‐analyses (PRISMA) guideline. Searches through MEDLINE, Embase and LILACS were done to find articles in Spanish and English. Relevant vocabulary terms and key terms related to AITD and other autoimmune diseases were used. Two investigators independently screened the eligible studies, extracted data and assessed the quality and risk of bias. Fixed and random effect models were used accordingly. Cluster analysis was used to determine similarities among diseases in the articles included (based on Jaccard index).ResultsA total of 56 articles fulfilled the inclusion criteria. Of these, 25 were case‐controls, 17 were cohorts, and 14 were cross‐sectional studies. These studies included a total of 47 509 patients. Female was the predominant gender and included 38 950 patients (81.23%, 95% CI: 80.85‐81.60). Graves’ disease (GD) was the most common type of thyroid autoimmunity (69.16%, 95% CI: 68.23‐70.07). Globally, overt PolyA was found in 13.46% of the patients with AITD. This type of PolyA was represented mainly by type 1 diabetes and autoimmune gastritis. Latent PolyA was presented in 17.45% of the patients, and anti‐proinsulin, anti‐parietal cells and dsDNA antibodies were the most common. HT had the highest frequency of overt PolyA in Europe (15.60%, 95% CI: 14.72‐16.53), whereas latent PolyA was most common in patients with GD in Asia (21.03%, 95% CI: 17.76‐24.71). Overt and latent PolyA were associated with gastrointestinal and endocrinological ADs in most of cases and clustered with rheumatological, dermatological and neurological ADs.ConclusionsLatent and overt PolyA are common in patients with AITD. These results provide insightful information for early diagnosis and management of concurrent ADs in patients with AITD. Aggregation of ADs in different clusters may help to define different phenotypes associated with thyroid autoimmunity that are critically relevant in clinical settings.
Trends in tonsillectomy surgery in children in Scotland 2000‐2018
Authors: Kubba Haytham , Downie Laura S. 
Published: August 2020

AbstractBackgroundTonsillectomy is one of the most common surgical procedures in children but indications and surgical practice change over time.ObjectivesWe aimed to identify trends in tonsillectomy procedures in children, in particular the number of procedures performed, the age of child undergoing tonsillectomy and the type of hospital in which the surgery was performed.DesignReview of Scottish Morbidity Records data (SMR01) which are routinely collected after everyday case procedure or overnight stay in all Scottish NHS hospitals.SettingAll NHS hospitals in all 14 Scottish health boards.ParticipantsAll children (0‐16 years) undergoing tonsillectomy, 2000‐2018.Main outcome measuresNumber of tonsillectomy procedures; rate of tonsillectomy per 1000 children in the population; number of children aged 0‐2 years and 3‐4 years undergoing tonsillectomy; health board in which the surgery occurred; diagnostic coding for these episodes; length of stay and readmission within 30 days of surgery.ResultsDuring 2000‐2018, there were 50,208 tonsillectomies performed in children in Scotland (mean 2642/year). The number of tonsillectomies per year remained constant (R = 0.322, P = .178) but tonsillectomies performed in children 0‐2 years rose from 0.41 to 1.56 per 1000 (R = 0.912, P < .001), and 3‐4 years from 3.06 to 6.93 per 1000 (R = 0.864, P < .001). The proportion of all children's tonsillectomies performed up to age 4 rose from 20.6% to 35.9% and up to age 2 from 2.4% to 8.1%. All specialist children's hospitals showed a significant increase in surgery in very young children.ConclusionsTonsillectomy rates remained static between 2000 and 2018, despite a falling population. More tonsillectomies are now performed for obstructive sleep apnoea, at a young age and in regional children's hospitals. This has important implications for the workload of these specialist hospitals.
Quality‐of‐life changes following three‐dimensional printing of prosthesis for large nasal septal perforations—Our experience of 13 patients
Authors: Medikeri Gaurav S. , Khong Grace C. , Fleming Sarah , Malhotra Taran , Leong Samuel C. 
Published: August 2020

AbstractNasal septal perforations can be caused by a number of aetiology including intra‐nasal drug abuse, trauma and iatrogenic causes.
Improvement of the experience of colorectal cancer patients in Sweden with a regional cancer plan
Authors: Sjövall A. , Söderqvist L. , Martling A. , Buchli C. 
Published: August 2020

AbstractAimThe Stockholm‐Gotland Regional Cancer Plan was launched in 2012 to improve cancer care. A personal contact nurse (CN), an individual written care plan (IWCP) and a standardized care pathway (SCP) were introduced. The aim of the current study was to evaluate whether these efforts have resulted in an improved experience for patients treated for colorectal cancer.MethodPatients treated with bowel resection for colorectal cancer in the Stockholm‐Gotland region between 1 January 2013 and 31 December 2017 were identified through the Swedish Colorectal Cancer Registry. Six to eight months postoperatively, the patients received a patient‐reported experience questionnaire. Patients were classified as ‘satisfied’ or ‘not satisfied’.ResultsThe questionnaire was sent to 4465 patients, and 3154 (70.64%) responded. The proportion of patients assigned a CN increased over time (79.84%–88.44%) and so did the proportion of patients receiving an IWCP (39.36%–70.00%). The waiting times were significantly shortened during the study period. In multivariable analysis, access to a CN and an IWCP was independently associated with increased patient satisfaction (OR 3.03, 95% CI 2.28–4.02 and OR 1.64, 95% CI 1.38–1.94). Patients with a long waiting time were significantly less satisfied than patients with a short waiting time (OR 0.72, 95% CI 0.60–0.88).ConclusionImplementation of a CN, IWCP and SCP has been successful, measured by a higher proportion of patients gaining access to these assets and shortened waiting times. This has led to an improved patient experience in patients treated for colorectal cancer in the Stockholm‐Gotland region.
CEO outside directorships and managerial efficiency: The role of host board capital
Authors: Mutlu Canan C. , Mutlu Sunay , Sauerwald Steve 
Published: August 2020

AbstractResearch Question/IssueDo CEO outside board directorships improve or reduce CEO managerial efficiency? What is the role of host board capital in this relationship?Research Findings/InsightsWe explore the value of CEO outside directorships on managerial efficiency by identifying a unique empirical setting where a CEO's number of outside board seats is exogenously decreased by a merger that eliminates the board of a host firm the CEO is serving on. Using this event as our empirical instrument, we find that outside directorships decrease a CEO's managerial efficiency while host board capital reduces this effect.Theoretical/Academic ImplicationsProponents view outside board service as a valuable leadership development tool to mentor the CEO while others promulgating an agency view argue that outside board service detracts from the CEO's ability to improve the efficiency of the home firm as it leads to busyness of the CEO. We shed light on this debate by arguing that CEO outside directorships might reduce CEO's managerial efficiency; however, this effect might be contingent on the characteristics of the host board.Practitioner/Policy ImplicationsOur findings offer insights to practitioners about the value of multiple directorships and the importance of the host board capital while informing policy makers about the potential restrictions on outside board assignments.