bluuebunny/crossref_metadata_2025_split huggingface dataset:
MIR31HG polymorphisms are related to steroid-induced osteonecrosis of femoral head among Chinese Han population
Authors: Wang Yuan , Wang Yexin , Liang Da , Hu Hongtao , Li Guangwei , Meng Xiaoguang , Zhu Bing , Zhong Wei 
Published: September 2022

AbstractBackgroundsMIR31host gene (MIR31HG) polymorphisms play important roles in the occurrence of osteonecrosis. However, the association ofMIR31HGpolymorphisms with the risk of steroid-induced osteonecrosis of the femoral head (SONFH) remains unclear. In this study, we aimed to investigate the correlation betweenMIR31HGpolymorphisms and SONFH susceptibility in the Chinese Han population.MethodsA total of 708 volunteers were recruited to detect the effect of seven single nucleotide polymorphisms (SNPs) in the MIR31HG gene on SONFH risk in the Chinese Han population. Genotyping of MIR31HG polymorphisms was performed using the Agena MassARRAY platform. The odds ratio (OR) and 95% confidence interval (95% CI) were used to evaluate the correlation between MIR31HG polymorphisms and SONFH risk using logistic regression model.ResultsAccording to the results of genetic model, rs10965059 inMIR31HGwas significantly correlated with the susceptibility to SONFH (OR = 0.56,p = 0.002). Interestingly, the stratified analysis showed that rs10965059 was associated with the reduced risk of SONFH in subjects aged > 40 years (OR = 0.30,p < 0.001) and male populations (OR = 0.35,p < 0 .001). Moreover, rs10965059 was associated with the reduced risk of bilateral SONFH (OR = 0.50,p = 0.002). Finally, multi-factor dimension reduction (MDR) results showed that the combination of rs1332184, rs72703442, rs2025327, rs55683539, rs2181559, rs10965059 and rs10965064 was the best model for predicting SONFH occurrence (p < 0.0001).ConclusionThe study indicated that rs10965059 could be involved in SONFH occurrence in the Chinese Han population, which might provide clues for investigating the role ofMIR31HGin the pathogenesis of SONFH.
Establishment of an optimized orthotopic bladder cancer model in mice
Authors: Cai Jinming , Xie Zhiwen , Yan Yilin , Huang Zhengnan , Tang Pengfei , Cao Xiangqian , Wang Zeyi , Yang Chenkai , Tan Mingyue , Zhang Fang , Shen Bing 
Published: September 2022

Abstract
Background
Bladder cancer (BC) is one of the most common malignancies of the genitourinary system. Animal models offer an important tool to explore tumour initiation, progression, and therapeutic mechanisms. Our aim is to construct an optimized orthotopic BC model which is predictable, reproducible, and convenient.

Methods
The optimized orthotopic BC model was constructed in male C57BL/6 mice utilizing microsyringes to inoculate them with a murine BC cell line (MB49). Anesthetised mice were inoculated with an MB49 cell suspension (10 µL) at approximately 5 × 106/mL. The whole process of modelling was observed and monitored every 3 days for 21 days utilizing HE staining and transabdominal ultrasonography (TUS).

Results
In this study, the model showed excellent success rates for tumour formation (96.67%) and metastatic rate (89.66%). Compared to the control group (sham operation), mice in the modelling group had serous cachexia, visible haematuresis and weight loss (all P < 0.05). The lungs, liver, ureter and kidneys were found to have tumour metastasis. Moreover, the average survival time (19.73 ± 1.69 d) of modelling mice was significantly shorter than that of the control mice (P < 0.05), which remained alive.

Conclusion
Our study established a method using microsyringes to inject murine BC cells into the bladder wall, creating a stable transplantable BC model in mice.
Comparative assessment of the Willems dental age estimation methods: a Chinese population-based radiographic study
Authors: Wang Jian , Fan Linfeng , Shen Shihui , Sui Meizhi , Zhou Jiaxin , Yuan Xiaoyan , Wu Yiwen , Zhong Pingping , Ji Fang , Tao Jiang 
Published: September 2022

Abstract
Background
The comparison of the two Willems dental age estimation methods (gender-specific (Willems I) and non-gender-specific (Willems II)) has not been fully investigated. Here we aimed to explore the applicability of the Willems dental age estimation in an Eastern Chinese population, which may cast light on the field of dental age estimation.

Methods
A total of 1211 oral panoramic radiographs (582 boys and 629 girls) of the Chinese Han population aged 11–16 years old were collected. Dental ages (DAs) were calculated using the Willems method. Statistical significance was set at a p-value < 0.05. Age differences between chronological age (CA) and dental age were analyzed by paired t-tests and mean absolute error (MAE).

Results
The differences between CA and DA determined by the Willems I method were + 0.44 and + 0.09 years for boys and girls, respectively. When using the Willems II method, these differences were + 0.57 and − 0.09. The MAEs of the Willems I method between DA and CA were 0.95 and 1.00 years in boys and girls, respectively. For Willems II, MAEs were 1.02 and 1.00 years in boys and girls.

Conclusions
This study showed that the Willems I method was more accurate than the Willems II method in the boys’ group for predicting age from a whole scale. In comparison, Willems II is more competitive in the girls' group. Neither method may be satisfactory for 11-to-16-year-old teenagers in Eastern China.
Comparing machine learning algorithms to predict 5-year survival in patients with chronic myeloid leukemia
Authors: Shanbehzadeh Mostafa , Afrash Mohammad Reza , Mirani Nader , Kazemi-Arpanahi Hadi 
Published: September 2022

Abstract
Introduction
Chronic myeloid leukemia (CML) is a myeloproliferative disorder resulting from the translocation of chromosomes 19 and 22. CML includes 15–20% of all cases of leukemia. Although bone marrow transplant and, more recently, tyrosine kinase inhibitors (TKIs) as a first-line treatment have significantly prolonged survival in CML patients, accurate prediction using available patient-level factors can be challenging. We intended to predict 5-year survival among CML patients via eight machine learning (ML) algorithms and compare their performance.

Methods
The data of 837 CML patients were retrospectively extracted and randomly split into training and test segments (70:30 ratio). The outcome variable was 5-year survival with potential values of alive or deceased. The dataset for the full features and important features selected by minimal redundancy maximal relevance (mRMR) feature selection were fed into eight ML techniques, including eXtreme gradient boosting (XGBoost), multilayer perceptron (MLP), pattern recognition network, k-nearest neighborhood (KNN), probabilistic neural network, support vector machine (SVM) (kernel = linear), SVM (kernel = RBF), and J-48. The scikit-learn library in Python was used to implement the models. Finally, the performance of the developed models was measured using some evaluation criteria with 95% confidence intervals (CI).

Results
Spleen palpable, age, and unexplained hemorrhage were identified as the top three effective features affecting CML 5-year survival. The performance of ML models using the selected-features was superior to that of the full-features dataset. Among the eight ML algorithms, SVM (kernel = RBF) had the best performance in tenfold cross-validation with an accuracy of 85.7%, specificity of 85%, sensitivity of 86%, F-measure of 87%, kappa statistic of 86.1%, and area under the curve (AUC) of 85% for the selected-features. Using the full-features dataset yielded an accuracy of 69.7%, specificity of 69.1%, sensitivity of 71.3%, F-measure of 72%, kappa statistic of 75.2%, and AUC of 70.1%.

Conclusions
Accurate prediction of the survival likelihood of CML patients can inform caregivers to promote patient prognostication and choose the best possible treatment path. While external validation is required, our developed models will offer customized treatment and may guide the prescription of personalized medicine for CML patients.
Understanding complex work using an extension of the resilience CARE model: an ethnographic study
Authors: Sanford Natalie , Lavelle Mary , Markiewicz Ola , Reedy Gabriel , Rafferty Anne Marie , Darzi Ara , Anderson Janet E. 
Published: September 2022

Abstract
Background
Resilient Healthcare research centres on understanding and improving quality and safety in healthcare. The Concepts for Applying Resilience Engineering (CARE) model highlights the relationships between demand, capacity, work-as-done, work-as-imagined, and outcomes, all of which are central aspects of Resilient Healthcare theory. However, detailed descriptions of the nature of misalignments and the mechanisms used to adapt to them are still unknown.

Objective
The objectives were to identify and classify types of misalignments between demand and capacity and types of adaptations that were made in response to misalignments.

Methods
The study involved 88.5 hours of non-participant ethnographic observations in a large, teaching hospital in central London. The wards included in the study were: two surgical wards, an older adult ward, a critical care unit, and the Acute Assessment Unit (AAU), an extension unit created to expedite patient flow out of the Emergency Department. Data were collected via observations of routine clinical work and ethnographic interviews with healthcare professionals during the observations. Field notes were transcribed and thematically analysed using a combined deductive-inductive approach based on the CARE model.

Results
A total of 365 instances of demand-capacity misalignment were identified across the five wards included in the study. Of these, 212 had at least one observed corresponding work adaptation. Misalignments identified include equipment, staffing, process, communication, workflow, and space. Adaptations identified include process, resource redistribution, and extra-role performance. For all misalignment types observed across the five in-patient settings, process adaptations were the most frequently used adaptations. The exception to this was for staffing misalignments, which were most frequently responded to with extra-role performance adaptations. Of the three process adaptations, hospital workers most often adapted by changing how the process was done.

Conclusions
This study contributes a new version of the CARE model that includes types of misalignments and corresponding adaptations, which can be used to better understand work-as-done. This affords insight into the complexity of the system and how it might be improved by reducing misalignments via work system redesign or by enhancing adaptive capacity.
Nigerian stakeholders’ perceptions of a pilot tier accreditation system for Patent and Proprietary Medicine Vendors to expand access to family planning services
Authors: OlaOlorun Funmilola M. , Jain Aparna , Olalere Emily , Daniel-Ebune Ene , Afolabi Kayode , Okafor Emeka , Dwyer Sara Chace , Ubuane Osimhen , Akomolafe Toyin O. , Baruwa Sikiru 
Published: September 2022

Abstract
Background
Community Pharmacists (CPs) and Patent and Proprietary Medicine Vendors (PPMVs) are often the first point of care for many Nigerians, and when sufficiently trained, they contribute to the expansion of family planning services. Nigeria’s task shifting policy and existing regulatory and licensing bodies provide the enabling environment for PPMVs to be stratified and trained. This study explored the perceptions of stakeholders toward the pilot three-tier accreditation system instituted by the Pharmacists Council of Nigeria with support from the IntegratE project.

Methods
Two rounds of qualitative phone interviews were conducted among stakeholders in Kaduna and Lagos states in 2020 and 2021. In addition, there were two rounds of phone interviews with CPs and PPMVs (program recipients) from Lagos and Kaduna states. All participants were purposively selected, based on their involvement in the IntegratE project activities. Interviews were recorded, transcribed, and coded using Atlas.ti software. Thematic analysis was conducted.

Results
Fifteen stakeholders and 28 program recipients and 12 stakeholders and 30 program recipients were interviewed during the first and second rounds of data collection respectively. The data are presented around three main themes: 1) the pilot three-tier accreditation system; 2) enabling environment; and 3) implementation challenges. The accreditation system that allows for the stratification and training of PPMVs to provide family planning services was perceived in a positive light by majority of participants. The integrated supportive supervision team that included representation from the licensing and regulatory body was seen as a strength. However, it was noted that the licensing process needs to be more effective. Implementation challenges that need to be addressed prior to scale up include bottlenecks in licensing procedures and the deep-rooted mistrust between CPs and PPMVs.

Conclusion
Scale up of the three-tier accreditation system has the potential to expand access to family planning services in Nigeria. In other resource-poor settings where human resources for health are in short supply and where drug shops are ubiquitous, identifying drug shop owners, training them to offer a range of family planning services, and providing the enabling environment for them to function may help to improve access to family planning services.
Safety of beta-blocker and calcium channel blocker antihypertensive drugs in pregnancy: a Mendelian randomization study
Authors: Ardissino Maddalena , Slob Eric A. W. , Rajasundaram Skanda , Reddy Rohin K. , Woolf Benjamin , Girling Joanna , Johnson Mark R. , Ng Fu Siong , Gill Dipender 
Published: September 2022

Abstract

Background
Beta-blocker (BB) and calcium channel blocker (CCB) antihypertensive drugs are commonly used in pregnancy. However, data on their relative impact on maternal and foetal outcomes are limited. We leveraged genetic variants mimicking BB and CCB antihypertensive drugs to investigate their effects on risk of pre-eclampsia, gestational diabetes and birthweight using the Mendelian randomization paradigm.

Methods
Genetic association estimates for systolic blood pressure (SBP) were extracted from summary data of a genome-wide association study (GWAS) on 757,601 participants. Uncorrelated single-nucleotide polymorphisms (SNPs) associated with SBP (p < 5 × 10−8) in BB and CCB drug target gene regions were selected as proxies for drug target perturbation. Genetic association estimates for the outcomes were extracted from GWASs on 4743 cases and 136,325 controls (women without a hypertensive disorder in pregnancy) for pre-eclampsia or eclampsia, 7676 cases and 130,424 controls (women without any pregnancy-related morbidity) for gestational diabetes, and 155,202 women (who have given birth at least once) for birthweight of the first child. All studies were in European ancestry populations. Mendelian randomization estimates were generated using the two-sample inverse-variance weighted model.

Results
Although not reaching the conventional threshold for statistical significance, genetically-proxied BB was associated with reduced risk of pre-eclampsia (OR per 10 mmHg SBP reduction 0.27, 95%CI 0.06–1.19, p = 0.08) and increased risk of gestational diabetes (OR per 10 mmHg SBP reduction 2.01, 95%CI 0.91–4.42, p = 0.08), and significantly associated with lower birthweight of first child (beta per 10 mmHg SBP reduction − 0.27, 95%CI − 0.39 to − 0.15, p = 1.90 × 10−5). Genetically-proxied CCB was associated with reduced risk of pre-eclampsia and eclampsia (OR 0.62, 95%CI 0.43–0.89, p = 9.33 × 10−3), and was not associated with gestational diabetes (OR 1.05, 95% CI 0.76–1.45, p = 0.76) or changes in birthweight of first child (beta per 10 mmHg SBP reduction 0.02, 95%CI − 0.04–0.07, p = 0.54).

Conclusions
While BB and CCB antihypertensive drugs may both be efficacious for lowering blood pressure in pregnancy, this genetic evidence suggests that BB use may lower birthweight. Conversely, CCB use may reduce risk of pre-eclampsia and eclampsia without impacting gestational diabetes risk or birthweight. These data support further study on the effects of BBs on birthweight.
The link between gestational diabetes and cardiovascular diseases: potential role of extracellular vesicles
Authors: Ormazabal Valeska , Nair Soumyalekshmi , Carrión Flavio , Mcintyre H. David , Salomon Carlos 
Published: September 2022

AbstractExtracellular vesicles are critical mediators of cell communication. They encapsulate a variety of molecular cargo such as proteins, lipids, and nucleic acids including miRNAs, lncRNAs, circular RNAs, and mRNAs, and through transfer of these molecular signals can alter the metabolic phenotype in recipient cells. Emerging studies show the important role of extracellular vesicle signaling in the development and progression of cardiovascular diseases and associated risk factors such as type 2 diabetes and obesity. Gestational diabetes mellitus (GDM) is hyperglycemia that develops during pregnancy and increases the future risk of developing obesity, impaired glucose metabolism, and cardiovascular disease in both the mother and infant. Available evidence shows that changes in maternal metabolism and exposure to the hyperglycemic intrauterine environment can reprogram the fetal genome, leaving metabolic imprints that define life-long health and disease susceptibility. Understanding the factors that contribute to the increased susceptibility to metabolic disorders of children born to GDM mothers is critical for implementation of preventive strategies in GDM. In this review, we discuss the current literature on the fetal programming of cardiovascular diseases in GDM and the impact of extracellular vesicle (EV) signaling in epigenetic programming in cardiovascular disease, to determine the potential link between EV signaling in GDM and the development of cardiovascular disease in infants.
Dapagliflozin improves myocardial flow reserve in patients with type 2 diabetes: the DAPAHEART Trial: a preliminary report
Authors: Leccisotti Lucia , Cinti Francesca , Sorice Gian Pio , D’Amario Domenico , Lorusso Margherita , Guzzardi Maria Angela , Mezza Teresa , Gugliandolo Shawn , Cocchi Camilla , Capece Umberto , Indovina Luca , Ferraro Pietro Manuel , Iozzo Patricia , Crea Filippo , Giordano Alessandro , Giaccari Andrea 
Published: September 2022

Abstract
Objective
Cardiovascular (CV) outcome trials have shown that in patients with type 2 diabetes (T2D), treatment with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) reduces CV mortality and hospital admission rates for heart failure (HF). However, the mechanisms behind these benefits are not fully understood. This study was performed to investigate the effects of the SGLT-2i dapagliflozin on myocardial perfusion and glucose metabolism in patients with T2D and stable coronary artery disease (coronary stenosis ≥ 30% and < 80%), with or without previous percutaneous coronary intervention (> 6 months) but no HF.

Methods
This was a single-center, prospective, randomized, double-blind, controlled clinical trial including 16 patients with T2D randomized to SGLT-2i dapagliflozin (10 mg daily) or placebo. The primary outcome was to detect changes in myocardial glucose uptake (MGU) from baseline to 4 weeks after treatment initiation by [(18)F]2-deoxy-2-fluoro-D-glucose (FDG) PET/CT during hyperinsulinemic euglycemic clamp. The main secondary outcome was to assess whether the hypothetical changes in MGU were associated with changes in myocardial blood flow (MBF) and myocardial flow reserve (MFR) measured by 13N-ammonia PET/CT. The study was registered at eudract.ema.europa.eu (EudraCT No. 2016-003614-27) and ClinicalTrials.gov (NCT 03313752).

Results
16 patients were randomized to dapagliflozin (n = 8) or placebo (n = 8). The groups were well-matched for baseline characteristics (age, diabetes duration, HbA1c, renal and heart function). There was no significant change in MGU during euglycemic hyperinsulinemic clamp in the dapagliflozin group (2.22 ± 0.59 vs 1.92 ± 0.42 μmol/100 g/min, p = 0.41) compared with the placebo group (2.00 ± 0.55 vs 1.60 ± 0.45 μmol/100 g/min, p = 0.5). Dapagliflozin significantly improved MFR (2.56 ± 0.26 vs 3.59 ± 0.35 p = 0.006 compared with the placebo group 2.34 ± 0.21 vs 2.38 ± 0.24 p = 0.81; pint = 0.001) associated with a reduction in resting MBF corrected for cardiac workload (p = 0.005; pint = 0.045). A trend toward an increase in stress MBF was also detected (p = 0.054).

Conclusions
SGLT-2 inhibition increases MFR in T2D patients. We provide new insight into SGLT-2i CV benefits, as our data show that patients on SGLT-2i are more resistant to the detrimental effects of obstructive coronary atherosclerosis due to increased MFR, probably caused by an improvement in coronary microvascular dysfunction.
Trial registration EudraCT No. 2016-003614-27; ClinicalTrials.gov Identifier: NCT03313752
Structural disruption of BAF chromatin remodeller impairs neuroblastoma metastasis by reverting an invasiveness epigenomic program
Authors: Jiménez Carlos , Antonelli Roberta , Nadal-Ribelles Mariona , Devis-Jauregui Laura , Latorre Pablo , Solé Carme , Masanas Marc , Molero-Valenzuela Adrià , Soriano Aroa , Sánchez de Toledo Josep , Llobet-Navas David , Roma Josep , Posas Francesc , de Nadal Eulàlia , Gallego Soledad , Moreno Lucas , Segura Miguel F. 
Published: September 2022

Abstract
Background
Epigenetic programming during development is essential for determining cell lineages, and alterations in this programming contribute to the initiation of embryonal tumour development. In neuroblastoma, neural crest progenitors block their course of natural differentiation into sympathoadrenergic cells, leading to the development of aggressive and metastatic paediatric cancer. Research of the epigenetic regulators responsible for oncogenic epigenomic networks is crucial for developing new epigenetic-based therapies against these tumours. Mammalian switch/sucrose non-fermenting (mSWI/SNF) ATP-dependent chromatin remodelling complexes act genome-wide translating epigenetic signals into open chromatin states. The present study aimed to understand the contribution of mSWI/SNF to the oncogenic epigenomes of neuroblastoma and its potential as a therapeutic target.

Methods
Functional characterisation of the mSWI/SNF complexes was performed in neuroblastoma cells using proteomic approaches, loss-of-function experiments, transcriptome and chromatin accessibility analyses, and in vitro and in vivo assays.

Results
Neuroblastoma cells contain three main mSWI/SNF subtypes, but only BRG1-associated factor (BAF) complex disruption through silencing of its key structural subunits, ARID1A and ARID1B, impairs cell proliferation by promoting cell cycle blockade. Genome-wide chromatin remodelling and transcriptomic analyses revealed that BAF disruption results in the epigenetic repression of an extensive invasiveness-related expression program involving integrins, cadherins, and key mesenchymal regulators, thereby reducing adhesion to the extracellular matrix and the subsequent invasion in vitro and drastically inhibiting the initiation and growth of neuroblastoma metastasis in vivo.

Conclusions
We report a novel ATPase-independent role for the BAF complex in maintaining an epigenomic program that allows neuroblastoma invasiveness and metastasis, urging for the development of new BAF pharmacological structural disruptors for therapeutic exploitation in metastatic neuroblastoma.