bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting risk of suicidal behaviour after initiation of selective serotonin reuptake inhibitors in children, adolescents and young adults: protocol for development and validation of clinical prediction models
Authors: Lagerberg Tyra , Virtanen Suvi , Kuja-Halkola Ralf , Hellner Clara , Lichtenstein Paul , Fazel Seena , Chang Zheng 
Published: August 2023

IntroductionThere is concern regarding suicidal behaviour risk during selective serotonin reuptake inhibitor (SSRI) treatment among the young. A clinically useful model for predicting suicidal behaviour risk should have high predictive performance in terms of discrimination and calibration; transparency and ease of implementation are desirable.Methods and analysisUsing Swedish national registers, we will identify individuals initiating an SSRI aged 8–24 years 2007–2020. We will develop: (A) a model based on a broad set of predictors, and (B) a model based on a restricted set of predictors. For the broad predictor model, we will consider an ensemble of four base models: XGBoost (XG), neural net (NN), elastic net logistic regression (EN) and support vector machine (SVM). The predictors with the greatest contribution to predictive performance in the base models will be determined. For the restricted predictor model, clinical input will be used to select predictors based on the top predictors in the broad model, and inputted in each of the XG, NN, EN and SVM models. If any show superiority in predictive performance as defined by the area under the receiver-operator curve, this model will be selected as the final model; otherwise, the EN model will be selected. The training and testing samples will consist of data from 2007 to 2017 and from 2018 to 2020, respectively. We will additionally assess the final model performance in individuals receiving a depression diagnosis within 90 days before SSRI initiation.The aims are to (A) develop a model predicting suicidal behaviour risk after SSRI initiation among children and youths, using machine learning methods, and (B) develop a model with a restricted set of predictors, favouring transparency and scalability.Ethics and disseminationThe research is approved by the Swedish Ethical Review Authority (2020–06540). We will disseminate findings by publishing in peer-reviewed open-access journals, and presenting at international conferences.
Improving wound swab collection in paediatric patients: a quality improvement project
Authors: Leonard Sean H , Chin-Yee Ian , Delport Johan , Crozier Abby , Abdulsatar Farah 
Published: August 2023

Microbiology sample swabs may be unsuccessful or rejected for a variety of reasons. Typically, errors occur in the preanalytical phase of sample collection. Errors with collection, handling and transport can lead to the need to repeat specimen collection. Unsuccessful specimens contribute to delays in diagnosis, increased patient stress and increased healthcare costs. An audit of sample swabs from London Health Sciences Centre Children’s Hospital from August through October 2021 yielded complete success rates of 100% for ear and eye culture swabs, 98.1% for methicillin-resistantStaphylococcus aureusswabs and 88.9% for wound swabs. This project aimed to improve wound swab success to 95% on the paediatric inpatient and paediatric emergency departments by May 2022.Stakeholders from paediatric clinical services including physicians, nurses and the laboratory medicine team at our centre were engaged to guide quality improvement interventions to improve specimen success rate. Based on feedback, we implemented visual aids to our electronic laboratory test information guide. Additionally, visual reminders of correct sample collection equipment were placed in high traffic areas for nursing staff.After the interventions were implemented, a three-month follow-up showed that wound swab success rate rose to 95.3%. This study achieved its aim of improving wound swab success rate to 95%. It adds to the growing pool of evidence that preanalytical phase intervention such as visual aids can increase swab success rates, in healthcare settings.
Managing moderate-to-severe paediatric asthma: a scoping review of the efficacy and safety of fluticasone propionate/salmeterol
Authors: Pitrez Paulo Marcio , Nanthapisal Sira , Castro Ana Paula Beltran Moschione , Teli Chirag , P G Abhijith 
Published: August 2023

BackgroundFluticasone propionate/salmeterol xinafoate (FP/SAL) is an inhaled corticosteroid (ICS) and long-acting β2-agonist (LABA) combination, indicated for the regular treatment of children (aged >4 years) with asthma that is inadequately controlled with ICS monotherapy plus as-needed short-acting β2-agonists, or already adequately controlled with ICS/LABA.ObjectiveCompared with the adult population, fewer clinical studies have investigated the efficacy of FP/SAL in paediatric patients with moderate and moderate-to-severe asthma. In this review, we synthesise the available evidence for the efficacy and safety of FP/SAL in the paediatric population, compared with other available therapies indicated for asthma in children.Eligibility criteriaA literature review identified randomised controlled trials and observational studies of FP/SAL in the paediatric population with moderate-to-severe asthma.Sources of evidenceThe Medline database was searched using PubMed (https://pubmed.ncbi.nlm.nih.gov/), with no publication date restrictions. Search strategies were developed and refined by authors.Charting methodsSelected articles were screened for clinical outcome data (exacerbation reduction, nocturnal awakenings, lung function, symptom control, rescue medication use and safety) and a table of key parameters developed.ResultsImprovements in asthma outcomes with FP/SAL include reduced risk of asthma-related emergency department visits and hospitalisations, protection against exercise-induced asthma and improvements in measures of lung function. Compared with FP monotherapy, greater improvements in measures of lung function and asthma control are reported. In addition, reduced incidence of exacerbations, hospitalisations and rescue medication use is observed with FP/SAL compared with ICS and leukotriene receptor antagonist therapy. Furthermore, FP/SAL therapy can reduce exposure to both inhaled and oral corticosteroids.ConclusionsFP/SAL is a reliable treatment option in patients not achieving control with ICS monotherapy or a different ICS/LABA combination. Evidence shows that FP/SAL is well tolerated and has a similar safety profile to FP monotherapy. Thus, FP/SAL provides an effective option for the management of moderate-to-severe asthma in the paediatric population.
Barriers and facilitators to implementation of musculoskeletal injury mitigation programmes for military service members around the world: a scoping review
Authors: Bullock Garrett S , Dartt Carolyn E , Ricker Emily A , Fallowfield Joanne L , Arden Nigel , Clifton Daniel , Danelson Kerry , Fraser John J , Gomez Christina , Greenlee Tina A , Gregory Alexandria , Gribbin Timothy , Losciale Justin , Molloy Joseph M , Nicholson Kristen F , Polich Julia-Grace , Räisänen Anu , Shah Karishma , Smuda Michael , Teyhen Deydre S , Allard Rhonda J , Collins Gary S , de la Motte Sarah J , Rhon Daniel I 
Published: August 2023

IntroductionMusculoskeletal injury (MSK-I) mitigation and prevention programmes (MSK-IMPPs) have been developed and implemented across militaries worldwide. Although programme efficacy is often reported, development and implementation details are often overlooked, limiting their scalability, sustainability and effectiveness. This scoping review aimed to identify the following in military populations: (1) barriers and facilitators to implementing and scaling MSK-IMPPs; (2) gaps in MSK-IMPP research and (3) future research priorities.MethodsA scoping review assessed literature from inception to April 2022 that included studies on MSK-IMPP implementation and/or effectiveness in military populations. Barriers and facilitators to implementing these programmes were identified.ResultsFrom 132 articles, most were primary research studies (90; 68.2%); the remainder were review papers (42; 31.8%). Among primary studies, 3 (3.3%) investigated only women, 62 (69%) only men and 25 (27.8%) both. Barriers included limited resources, lack of stakeholder engagement, competing military priorities and equipment-related factors. Facilitators included strong stakeholder engagement, targeted programme design, involvement/proximity of MSK-I experts, providing MSK-I mitigation education, low burden on resources and emphasising end-user acceptability. Research gaps included variability in reported MSK-I outcomes and no consensus on relevant surveillance metrics and definitions.ConclusionDespite a robust body of literature, there is a dearth of information about programme implementation; specifically, barriers or facilitators to success. Additionally, variability in outcomes and lack of consensus on MSK-I definitions may affect the development, implementation evaluation and comparison of MSK-IMPPs. There is a need for international consensus on definitions and optimal data reporting elements when conducting injury risk mitigation research in the military.
Correlation of low numbers of intratumoral FOXP3+ cells with worse progression-free survival in angioimmunoblastic T cell lymphoma
Authors: Liu Hung-Lin , Weng Shao-Wen , Chou Chih-Chi , You Huey-Ling , Wang Ming-Chung , Ma Ming-Chun , Huang Wan-Ting 
Published: August 2023

AimsAngioimmunoblastic T cell lymphoma (AITL) is a T cell lymphoma with aberrant immune activity. It is characterised by inflammatory and immune reactions. However, the impact of regulatory T (Treg) cells on AITL remains unclear.MethodsWe retrospectively collected 46 AITL cases and performed immunohistochemical analysis of forkhead box P3 (FOXP3) expression. The number of immunostained FOXP3 cells was determined using a digital pathology system with whole-slide imaging. The average number of FOXP3+ cells per high-power field (HPF) was determined by randomly counting 20 HPFs. AITL cases were categorised into high-expression and low-expression groups based on the median count of FOXP3+ cells in all analysed samples. The relationship between FOXP3 expression and clinicopathological features was assessed.ResultsAmong the studied patients, 14 (30.4%) were females and 32 (69.6%) were males, and the median age at diagnosis was 64.1 years. The median expression of FOXP3 was 84.9 positive cells/HPF. FOXP3 expression negatively correlated with Epstein-Barr virus-encoded small RNA positivity in tumour (p=0.041). The patients with low FOXP3 expression presented with aggressive clinical behaviour, including advance-staged diseases (p=0.043), splenomegaly (p=0.008), B symptoms (p=0.019) and extranodal involvement (p=0.019). The neutrophil-to-lymphocyte ratio was higher in the patients with low FOXP3 expression, compared with those with high FOXP3 expression. Low FOXP3 expression had an adverse effect on progression-free survival (PFS, p=0.033), and increased the risk of recurrence 2.320-fold (HR 2.320 (95% CI 1.109 to 4.856); p=0.025).ConclusionsPatients with AITL with low FOXP3 expression tend to have aggressive clinical presentation and shortened PFS. These findings may help with risk stratification and determination of new treatment strategy.
Clustering by multiple long-term conditions and social care needs: a cross-sectional study among 10 026 older adults in England
Authors: Khan Nusrat , Chalitsios Christos V , Nartey Yvonne , Simpson Glenn , Zaccardi Francesco , Santer Miriam , Roderick Paul J , Stuart Beth , Farmer Andrew J , Dambha-Miller Hajira 
Published: August 2023

Background   People with multiple long-term conditions (MLTC) face health and social care challenges. This study aimed to classify people by MLTC and social care needs (SCN) into distinct clusters and quantify the association between derived clusters and care outcomes.Methods A cross-sectional study was conducted using the English Longitudinal Study of Ageing, including people with up to 10 MLTC. Self-reported SCN was assessed through 13 measures of difficulty with activities of daily living, 10 measures of mobility difficulties and whether health status was limiting earning capability. Latent class analysis was performed to identify clusters. Multivariable logistic regression quantified associations between derived MLTC/SCN clusters, all-cause mortality and nursing home admission.ResultsOur study included 9171 people at baseline with a mean age of 66.3 years; 44.5% were men. Nearly 70.8% had two or more MLTC, the most frequent being hypertension, arthritis and cardiovascular disease. We identified five distinct clusters classified as high SCN/MLTC through to low SCN/MLTC clusters. The high SCN/MLTC included mainly women aged 70–79 years who were white and educated to the upper secondary level. This cluster was significantly associated with higher nursing home admission (OR=8.71; 95% CI: 4.22 to 18). We found no association between clusters and all-cause mortality.ConclusionsWe have highlighted those at risk of worse care outcomes, including nursing home admission. Distinct clusters of individuals with shared sociodemographic characteristics can help identify at-risk individuals with MLTC and SCN at primary care level.
Causal effect of shifting from precarious to standard employment on all-cause mortality in Sweden: an emulation of a target trial
Authors: Matilla-Santander Nuria , Matthews Anthony A , Gunn Virginia , Muntaner Carles , Kreshpaj Bertina , Wegman David H , Sánchez-Martínez Néstor , Hernando-Rodriguez Julio C , Albin Maria , Balogh Rebeka , Davis Letitia , Bodin Theo 
Published: August 2023

BackgroundWe aimed at estimating the causal effect of switching from precarious to standard employment on the 6-year and 12-year risk of all-cause mortality among workers aged 20-55 years in Sweden.MethodsWe emulated a series of 12 target trials starting every year between 2005 and 2016 using Swedish register data (n=251 273). We classified precariously employed individuals using a multidimensional approach at baseline as (1) remaining in precarious employment (PE) (73.8%) and (2) shifting to standard employment (26.2%). All-cause mortality was measured from 2006 to 2017. We pooled data for all 12 emulated trials and used covariate-adjusted pooled logistic regression to estimate intention-to-treat and per-protocol effects via risk ratios (RRs) and standardised risk curves (the parametric g-formula).ResultsShifting from precarious to standard employment decreases the 12-year risk of death by 20% on the relative scale (RR: 0.82, 95% CI: 0.73; 0.93), regardless of what happens after the initial shift. However, we estimated a 12-year risk reduction of 30% on the relative scale for workers shifting from precarious to standard employment and staying within this employment category for the full 12 years (RR: 0.71, 95% CI: 0.54; 0.95).ConclusionsThis study finds that shifting from low to higher-quality employment conditions (ie, stable employment, sufficient income levels and high coverage by collective agreements) decreases the risk of death. Remaining in PE increases the risk of premature mortality. Our results emphasise the necessity of ensuring decent work for the entire working population to accomplish the 2030 Agenda for Sustainable Development.
Early minimally invasive intracerebral hemorrhage evacuation: a phase 2a feasibility, safety, and promise of surgical efficacy study
Authors: Kleinig Timothy J , Abou-Hamden Amal , Laidlaw John , Churilov Leonid , Kellner Christopher Paul , Wu Teddy , Mocco J , Lau Hui , Adamides Alexios , Kavar Bhadrakant , Dimou James , Cranefield Jennifer , McDonald Amy , Plummer Stephanie , Davis Stephen , Campbell Bruce C V 
Published: August 2023

BackgroundSurgical treatment of intracerebral hemorrhage (ICH) is unproven, although meta-analyses suggest that both early conventional surgery with craniotomy and minimally invasive surgery (MIS) may be beneficial. We aimed to demonstrate the safety, feasibility, and promise of efficacy of early MIS for ICH using the Aurora Surgiscope and Evacuator.MethodsWe performed a prospective, single arm, phase IIa Simon’s two stage design study at two stroke centers (10 patients with supratentorial ICH volumes ≥20 mL and National Institutes of Health Stroke Scale (NIHSS) score of ≥6, and surgery commencing <12 hours after onset). Positive outcome was defined as ≥50% 24 hour ICH volume reduction, with the safety outcome lack of significant ICH reaccumulation.ResultsFrom December 2019 to July 2020, we enrolled 10 patients at two Australian Comprehensive Stroke Centers, median age 70 years (IQR 65–74), NIHSS score 19 (IQR 19–29), ICH volume 59 mL (IQR 25–77), at a median of 227 min (IQR 175–377) post-onset. MIS was commenced at a median time of 531 min (IQR 437–628) post-onset, had a median duration of 98 min (IQR 77–110), with a median immediate postoperative hematoma evacuation of 70% (IQR 67–80%). A positive outcome was achieved in 5/5 first stage patients and in 4/5 second stage patients. One patient developed significant 24 hour ICH reaccumulation; otherwise, 24 hour stability was observed (median reduction 71% (IQR 61–80), 5/9 patients <15 mL residual). Three patients died, unrelated to surgery. There were no surgical safety concerns. At 6 months, the median modified Rankin Scale score was 4 (IQR 3–6) with 30% achieving a score of 0–3.ConclusionIn this study, early ICH MIS using the Aurora Surgiscope and Evacuator appeared to be feasible and safe, warranting further exploration.Trial registration numberACTRN12619001748101.
APE1 regulates mitochondrial DNA damage repair after experimental subarachnoid haemorrhage in vivo and in vitro
Authors: Dai Kun , Wang Zongqi , Gao Bixi , Li Longyuan , Gu Feng , Tao Xinyu , You Wanchun , Wang Zhong 
Published: August 2023

Background

Subarachnoid haemorrhage
(SAH) can result in a highly unfavourable prognosis. In recent years, the study of SAH has focused on early brain injury (EBI), which is a crucial progress that contributes to adverse prognosis. SAH can lead to various complications, including mitochondrial dysfunction and DNA damage. Apurinic/apyrimidinic endonuclease 1 (APE1) is an essential protein with multifaceted functionality integral to DNA repair and redox signalling. However, the role of APE1 in mitochondrial DNA damage repair after SAH is still unclear.

Methods
Our study involved an in vivo endovascular perforation model in rats and an in vitro neuron oxyhaemoglobin intervention. Then, the effects of APE1 on mitochondrial DNA damage repair were analysed by western blot, immunofluorescence, quantitative real-time PCR, mitochondrial bioenergetics measurement and neurobehavioural experiments.

Results
We found that the level of APE1 decreased while the mitochondria DNA damage and neuronal death increased in a rat model of SAH. Overexpression of APE1 improved short-term and long-term behavioural impairment in rats after SAH. In vitro, after primary neurons exposed to oxyhaemoglobin, APE1 expression significantly decreased along with increased mitochondrial DNA damage, a reduction in the subunit of respiratory chain complex levels and subsequent respiratory chain dysfunction. Overexpression of APE1 relieved energy metabolism disorders in the mitochondrial of neurons and reduced neuronal apoptosis.

Conclusion
In conclusion, APE1 is involved in EBI after SAH by affecting mitochondrial apoptosis via the mitochondrial respiratory chain. APE1 may potentially play a vital role in the EBI stage after SAH, making it a critical target for treatment.
George Gamow and Ralph Alpher: a review of their cosmological collaboration as mentor and protégé 1942–1955
Authors: Alpher Victor S. , Mitton Simon A. 
Published: August 2023

AbstractGeorge Antonovich Gamow (1904–1968) and Ralph Asher Alpher (1921–2007) were associates from 1942 until 1968. In this paper, we examine an intense period of collaboration at George Washington University. Our inquiry pivots on a collection of 53 letters and postcards in the Library of Congress (LoC) that Alpher received from Gamow during his absences from Washington DC. In order to set our examination of the letters in their historical context, we present brief biographies of Gamow and Alpher, summarise the state that nuclear astrophysics had already reached by 1945, and examine the initial impact of the αβγ paper. We conducted detailed analysis of twenty of the LoC letters which documents successive attempts by Alpher and Gamow to address the deficiencies in their model of primordial element building by neutron-capture in the big bang. We give a detailed account of the interactions between Gamow writing from Los Alamos, New Mexico, and his two co-workers Alpher and Robert Herman in Washington DC. The correspondence brings their enthusiasm and commitment to life as they react to the advances and setbacks they encountered. Our narrative illustrates the remarkable partnership that Gamow and Alpher shared, a this was, infused with friendship and therein scientific discovery.
Pro-905, a Novel Purine Antimetabolite, Combines with Glutamine Amidotransferase Inhibition to Suppress Growth of Malignant Peripheral Nerve Sheath Tumor
Authors: Lemberg Kathryn M. , Ali Eunus S. , Krecmerova Marcela , Aguilar Joanna Marie H. , Alt Jesse , Peters Diane E. , Zhao Liang , Wu Ying , Nuha Naziba , Asara John M. , Staedtke Verena , Pratilas Christine A. , Majer Pavel , Rais Rana , Ben-Sahra Issam , Slusher Barbara S. 
Published: August 2023

Abstract

Malignant peripheral nerve sheath tumors (MPNST) are highly aggressive soft-tissue sarcomas that arise from neural tissues and carry a poor prognosis. Previously, we found that the glutamine amidotransferase inhibitor JHU395 partially impeded tumor growth in preclinical models of MPNST. JHU395 inhibits de novo purine synthesis in human MPNST cells and murine tumors with partial decreases in purine monophosphates. On the basis of prior studies showing enhanced efficacy when glutamine amidotransferase inhibition was combined with the antimetabolite 6-mercaptopurine (6-MP), we hypothesized that such a combination would be efficacious in MPNST. Given the known toxicity associated with 6-MP, we set out to develop a more efficient and well-tolerated drug that targets the purine salvage pathway. Here, we report the discovery of Pro-905, a phosphoramidate protide that delivered the active nucleotide antimetabolite thioguanosine monophosphate (TGMP) to tumors over 2.5 times better than equimolar 6-MP. Pro-905 effectively prevented the incorporation of purine salvage substrates into nucleic acids and inhibited colony formation of human MPNST cells in a dose-dependent manner. In addition, Pro-905 inhibited MPNST growth and was well-tolerated in both human patient-derived xenograft (PDX) and murine flank MPNST models. When combined with JHU395, Pro-905 enhanced the colony formation inhibitory potency of JHU395 in human MPNST cells and augmented the antitumor efficacy of JHU395 in mice. In summary, the dual inhibition of the de novo and purine salvage pathways in preclinical models may safely be used to enhance therapeutic efficacy against MPNST.