bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aberrant EVI1 splicing contributes to EVI1-rearranged leukemia
Authors: Tanaka Atsushi , Nakano Taizo A. , Nomura Masaki , Yamazaki Hiromi , Bewersdorf Jan P. , Mulet-Lazaro Roger , Hogg Simon , Liu Bo , Penson Alex , Yokoyama Akihiko , Zang Weijia , Havermans Marije , Koizumi Miho , Hayashi Yasutaka , Cho Hana , Kanai Akinori , Lee Stanley C. , Xiao Muran , Koike Yui , Zhang Yifan , Fukumoto Miki , Aoyama Yumi , Konuma Tsuyoshi , Kunimoto Hiroyoshi , Inaba Toshiya , Nakajima Hideaki , Honda Hiroaki , Kawamoto Hiroshi , Delwel Ruud , Abdel-Wahab Omar , Inoue Daichi 
Published: June 2022

Abstract
Detailed genomic and epigenomic analyses of MECOM (the MDS1 and EVI1 complex locus) have revealed that inversion or translocation of chromosome 3 drives inv(3)/t(3;3) myeloid leukemias via structural rearrangement of an enhancer that upregulates transcription of EVI1. Here, we identify a novel, previously unannotated oncogenic RNA-splicing derived isoform of EVI1 that is frequently present in inv(3)/t(3;3) acute myeloid leukemia (AML) and directly contributes to leukemic transformation. This EVI1 isoform is generated by oncogenic mutations in the core RNA splicing factor SF3B1, which is mutated in &gt;30% of inv(3)/t(3;3) myeloid neoplasm patients and thereby represents the single most commonly cooccurring genomic alteration in inv(3)/t(3;3) patients. SF3B1 mutations are statistically uniquely enriched in inv(3)/t(3;3) myeloid neoplasm patients and patient-derived cell lines compared with other forms of AML and promote mis-splicing of EVI1 generating an in-frame insertion of 6 amino acids at the 3′ end of the second zinc finger domain of EVI1. Expression of this EVI1 splice variant enhanced the self-renewal of hematopoietic stem cells, and introduction of mutant SF3B1 in mice bearing the humanized inv(3)(q21q26) allele resulted in generation of this novel EVI1 isoform in mice and hastened leukemogenesis in vivo. The mutant SF3B1 spliceosome depends upon an exonic splicing enhancer within EVI1 exon 13 to promote usage of a cryptic branch point and aberrant 3′ splice site within intron 12 resulting in the generation of this isoform. These data provide a mechanistic basis for the frequent cooccurrence of SF3B1 mutations as well as new insights into the pathogenesis of myeloid leukemias harboring inv(3)/t(3;3).
Genetically predicted higher educational attainment decreases the risk of stroke: a multivariable Mendelian randomization study
Authors: Zhang Weihao , Li Yuanjin , Li Yuming , Zheng Kai , Zou Shenghui , Jia Xing , Yang Hua 
Published: June 2022

Abstract
Background
The causal association between educational attainment (EA) and stroke remains unclear. Hence, a novel multivariable Mendelian randomization (MVMR) approach was applied to solve this issue.

Methods
The single nucleotide polymorphisms (SNPs) from a recent genome-wide association study (GWAS) on years of schooling served as instruments. Univariable mendelian randomization (MR) and MVMR analyses were performed to detect the relationship between genetically predicted EA and the stroke risk. In the MVMR, cigarette consumption, alcohol consumption, body mass index (BMI), intelligence, and hypertension were adjusted. The summary statistics for stroke from the MEGASTROKE consortium included 446,696 participants (40,585 cases of stroke and 34,217 cases of ischemic stroke), most of whom were of European descent.

Results
In the univariable MR, genetically predicated EA could decrease the risks of total stroke (OR = 0.66, 95% CI 0.61–0.72, P = 2.70 × 10–23), ischemic stroke (OR = 0.67, 95% CI 0.61–0.73, P = 2.58 × 10–18), large artery atherosclerosis (OR = 0.51, 95% CI 0.40–0.64, P = 1.80 × 10–8), small vessel stroke (OR = 0.60, 95% CI 0.49–0.73, P = 5.59 × 10–7), and cardioembolic stroke (OR = 0.81, 95% CI 0.68–0.96, P = 1.46 × 10–2) using the inverse-variance weighted (IVW) estimator. Higher EA might be negatively correlated with the odds of total stroke (OR = 0.62, 95% CI 0.50–0.77, P = 1.44 × 10–5), ischemic stroke (OR = 0.63, 95% CI 0.50–0.80, P = 1.41 × 10–4), and cardioembolic stroke (OR = 0.59, 95% CI 0.39–0.90, P = 0.01), but was not significant in large artery atherosclerosis (OR = 0.65, 95% CI 0.37–1.15, P = 0.14) and small vessel stroke (OR = 0.68, 95% CI 0.41–1.13, P = 0.14) after controlling other exposures.

Conclusions
We found that genetically predicated higher EA decreased the risks of total stroke, ischemic stroke, and cardioembolic stroke, independent of smoking, alcohol consumption, BMI, intelligence, and hypertension.
Application of high-frequency ultrasound to assess facial skin thickness in association with gender, age, and BMI in healthy adults
Authors: Meng Ying , Feng Lan , Shan Jiali , Yuan Zixu , Jin Lin 
Published: June 2022

Abstract
Background and objective
High-frequency ultrasound plays an extremely important role in normal skin measurement, skin disease diagnosis, and aesthetic medicine. This study aimed to estimate the epidermal and dermal thicknesses at eight different facial sites in healthy adults using high-frequency ultrasound, and to evaluate the correlation of epidermal and dermal thicknesses with age and body mass index (BMI).

Methods
Facial skin assessment was performed on 118 participants using high-frequency ultrasound. The epidermal and dermal thicknesses of forehead, glabella, temple, eyelid, nasal dorsum, zygoma, submandibular, and neck were measured. The correlation of the epidermal and dermal thicknesses with age and BMI was analyzed by the linear correlation analysis.

Results
The epidermal and dermal thicknesses in men were significantly higher than those in women (P < 0.05), except for the thicknesses of zygomatic epidermis and neck dermis. The dermal thickness on zygoma and submandibular in young women was significantly higher than in middle age and old women (P < 0.05). Overall, with the increase of age, the thickness of facial skin decreased in women, mainly in the forehead, glabella, zygoma, and submandibular. In women, the epidermal and dermal thicknesses of neck were correlated with BMI (r = 0.392, 0.241, P < 0.05, respectively). However, in men, the epidermal and dermal thicknesses were correlated with age only in zygoma dermis (r = − 0.327, P < 0.05), while there was no correlation between the epidermal and dermal thicknesses and BMI.

Conclusion
Gender, age, and BMI had significant effects on the epidermal and dermal thicknesses at different facial sites.
Managing acute presentations of atheromatous renal artery stenosis
Authors: de Bhailis Áine , Al-Chalabi Saif , Hagemann Rodrigo , Ibrahim Sara , Hudson Amy , Lake Edward , Chysochou Constantina , Green Darren , Kalra Philip A. 
Published: June 2022

Abstract
Background
Atherosclerotic renovascular disease (ARVD) often follows an asymptomatic chronic course which may be undetected for many years. However, there are certain critical acute presentations associated with ARVD and these require a high index of suspicion for underlying high-grade RAS (renal artery stenosis) to improve patient outcomes. These acute presentations, which include decompensated heart failure syndromes, accelerated hypertension, rapidly declining renal function, and acute kidney injury (AKI), are usually associated with bilateral high-grade RAS (> 70% stenosis), or high-grade RAS in a solitary functioning kidney in which case the contralateral kidney is supplied by a vessel demonstrating renal artery occlusion (RAO). These presentations are typically underrepresented in large, randomized control trials which to date have been largely negative in terms of the conferred benefit of revascularization.

Case presentation
Here we describe 9 individual patients with 3 classical presentations including accelerated phase hypertension, heart failure syndromes, AKI and a fourth category of patients who suffered recurrent presentations. We describe their response to renal revascularization. The predominant presentation was that consistent with ischaemic nephropathy all of whom had a positive outcome with revascularization.

Conclusion
A high index of suspicion is required for the diagnosis of RAS in these instances so that timely revascularization can be undertaken to restore or preserve renal function and reduce the incidence of hospital admissions for heart failure syndromes.
Self-rated health and quality of life among Syrian refugees in Ireland – data from a cross-sectional study
Authors: Collins Claire , Pericin Ivana , Larkin James , Diaz Esperanza 
Published: June 2022

Abstract
Introduction
As a response to the humanitarian crisis in Syria, the Irish government agreed to accept up to 4000 refugees for resettlement in Ireland in 2016. Prior to their arrival in Ireland, health screening was carried out by the International Organisation for Migration. However, no population-level measurement of the health status or needs takes place in Ireland to inform policy or health services requirements.

Methods
Cross-sectional data from a self-completed questionnaire among 194 Syrian Refugees aged 16 years and older resident in reception centres in Ireland in 2017/2018 is reported upon. The questionnaire measured self-reported health including quality of life and all study material were available in English and Arabic. The data was examined applying descriptive statistics and regression analysis.

Results
Syrian Refugees in Ireland consist of a relatively young cohort; in this study the majority of participants were younger than 35 years (69.5%). Two-thirds of the respondents reported their overall health status to be good or very good. The most common health condition was found to be headache and the most common medications used were painkillers. Chronic pain was experienced by one quarter of respondents; 27.5% were considered as suffering from anxiety and 10.0% had symptoms compatible with post-traumatic stress disorder (PTSD). A significant relationship was observed between chronic pain and self-rated health, as well as between chronic pain and anxiety. Quality of life (QoL) scores were lowest for the QoL environment domain.

Conclusions
Chronic pain is relatively widespread among these young and otherwise healthy refugees. Psychological distress and trauma are important factors in respondents’ quality of life scores. Chronic pain is associated with one’s mental health. Our findings and the literature suggests that the diagnosis and treatment of pain and providing care in a culturally sensitive manner should be a priority and included in the preparation and training of the relevant care providers. Additionally, the impact of living conditions on quality of life should not be underestimated.
Laparoscopic repair of perforated peptic ulcer: a multicenter, propensity score matching analysis
Authors: Kim Chang Woo , Kim Jong Wan , Yoon Sang Nam , Oh Bo Young , Kang Byung Mo 
Published: June 2022

Abstract
Background
Perforated peptic ulcer (PPU) is a common emergency condition requiring surgery using laparoscopy or open repair of the perforated site. The aim of this study was to assess the role of laparoscopic surgery (LS) based on the safety and efficacy for PPU.

Methods
Medical records of the consecutive patients who underwent LS or open surgery (OS) for PPU at five hospitals between January 2009 and December 2019 were retrospectively reviewed. After propensity score matching, short-term perioperative outcomes were compared between LS and OS in selected patients.

Results
Among the 598 patients included in the analysis, OS was more frequently performed in patients with worse factors, including older age, a higher American Society of Anesthesiologists score, more alcohol use, longer symptom duration, a higher Boey score, a higher serum C-reactive protein level, a lower serum albumin level, and a larger-diameter perforated site. After propensity score matching, 183 patients were included in each group; variables were well-balanced between-groups. Postoperative complications were not different between groups (24.6% LS group vs. 31.7% OS group, p = 0.131). However, postoperative length of hospital stay (10.03 vs. 12.53 days, respectively, p = 0.003) and postoperative time to liquid intake (3.75 vs. 5.26 days, p < 0.001) were shorter in the LS group.

Conclusions
LS resulted in better functional recovery than OS and can be safely performed for treatment of PPU. When performed by experienced surgeons, LS is an alternative option, even for hemodynamically unstable patients.
Exploring the formal assessment discussions in clinical nursing education: An observational study
Authors: Aase Ingunn , Akerjordet Kristin , Crookes Patrick , Frøiland Christina T. , Laugaland Kristin A. 
Published: June 2022

Abstract
Introduction
According to EU standards, 50% of the bachelor education program in nursing should take place in clinical learning environments. Consequently, this calls for high quality supervision, where appropriate assessment strategies are vital to optimize students’ learning, growth, and professional development. Despite this, little is known about the formal assessment discussions taking place in clinical nursing education.

Objective
The aim of this study was to explore the characteristics of the formal assessment discussions taking place during first-year students’ clinical education in nursing homes.

Method
An exploratory qualitative study was performed. The data consist of passive participant observations of 24 assessment discussions (12 mid-term and 12 final assessments) with first-year nursing students (n=12), their assigned registered nurse mentors (n=12) and nurse educators (n=5). The study was conducted in three public nursing homes in a single Norwegian municipality. Data were subjected to thematic analysis. The findings were reported using the Standards for Reporting of Qualitative Research.

Results
Three themes were identified regarding the characteristics of the formal assessment discussions: (1) adverse variability in structuring, weighting of theoretical content and pedagogical approach; (2) limited three-part dialogue constrains feedback and reflection; and (3) restricted grounds for assessment leave the nurse educators with a dominant role.

Conclusion
These characteristic signal key areas of attention to improve formal assessment discussions to capitalize on unexploited learning opportunities.
Acute association between heatwaves and stillbirth in six US states
Authors: Richards Megan , Huang Mengjiao , Strickland Matthew J. , Newman Andrew J. , Warren Joshua L. , D’Souza Rohan , Chang Howard H. , Darrow Lyndsey A. 
Published: June 2022

Abstract
Background
Heatwaves are becoming more frequent and may acutely increase the risk of stillbirth, a rare and severe pregnancy outcome.

Objectives
Examine the association between multiple heatwave metrics and stillbirth in six U.S. states.

Methods
Data were collected from fetal death and birth records in California (1996–2017), Florida (1991–2017), Georgia (1994–2017), Kansas (1991–2017), New Jersey (1991–2015), and Oregon (1991–2017). Cases were matched to controls 1:4 based on maternal race/ethnicity, maternal education, and county, and exposure windows were aligned (gestational week prior to stillbirth). County-level temperature data were obtained from Daymet and linked to cases and controls by residential county and the exposure window. Five heatwave metrics (1 categorical, 3 dichotomous, 1 continuous) were created using different combinations of the duration and intensity of hot days (mean daily temperature exceeding the county-specific 97.5th percentile) during the exposure window, as well as a continuous measure of mean temperature during the exposure window modeled using natural splines to allow for nonlinear associations. State-specific odds ratios (ORs) and 95% confidence intervals (CI) were estimated using conditional logistic regression models. State-specific results were pooled using a fixed-effects meta-analysis.

Results
In our data set of 140,428 stillbirths (553,928 live birth controls), three of the five heatwave metrics examined were not associated with stillbirth. However, four consecutive hot days during the previous week was associated with a 3% increase in stillbirth risk (CI: 1.01, 1.06), and a 1 °C average increase over the threshold was associated with a 10% increase in stillbirth risk (CI: 1.04, 1.17). In continuous temperature analyses, there was a slight increased risk of stillbirth associated with extremely hot temperatures (≥ 35 °C).

Discussion
Most heat wave definitions examined were not associated with acute changes in stillbirth risk; however, the most extreme heatwave durations and temperatures were associated with a modest increase in stillbirth risk.
Ultrasound-assisted brain delivery of nanomedicines for brain tumor therapy: advance and prospect
Authors: Zhang Shuo , Zhang Shuai , Luo Siyuan , Tang Peng , Wan Mingxi , Wu Daocheng , Gao Wei 
Published: June 2022

AbstractNowadays, brain tumors are challenging problems, and the key of therapy is ensuring therapeutic drugs cross the blood–brain barrier (BBB) effectively. Although the efficiency of drug transport across the BBB can be increased by innovating and modifying nanomedicines, they exert insufficient therapeutic effects on brain tumors due to the complex environment of the brain. It is worth noting that ultrasound combined with the cavitation effect of microbubbles can assist BBB opening and enhance brain delivery of nanomedicines. This ultrasound-assisted brain delivery (UABD) technology with related nanomedicines (UABD nanomedicines) can safely open the BBB, facilitate the entry of drugs into the brain, and enhance the therapeutic effect on brain tumors. UABD nanomedicines, as the main component of UABD technology, have great potential in clinical application and have been an important area of interest in the field of brain tumor therapy. However, research on UABD nanomedicines is still in its early stages despite the fact that they have been associated with many disciplines, including material science, brain science, ultrasound, biology, and medicine. Some aspects of UABD theory and technology remain unclear, especially the mechanisms of BBB opening, relationship between materials of nanomedicines and UABD technology, cavitation and UABD nanomedicines design theories. This review introduces the research status of UABD nanomedicines, investigates their properties and applications of brain tumor therapy, discusses the advantages and drawbacks of UABD nanomedicines for the treatment of brain tumors, and offers their prospects. We hope to encourage researchers from various fields to participate in this area and collaborate on developing UABD nanomedicines into powerful tools for brain tumor therapy.Graphical Abstract
Multistage nucleic acid amplification induced nano-aggregation for 3D hotspots-improved SERS detection of circulating miRNAs
Authors: Sun Yudie , Fang La , Yi Yang , Feng Aobo , Zhang Kui , Xu Jing-Juan 
Published: June 2022

AbstractCirculating miRNAs in the blood can regulate disease development and thus indicate disease states via their various expression levels. For these reasons, circulating miRNAs constitute useful biomarkers, and an approach to the accurate detection of circulating miRNAs is attractive in the diagnosis and treatment of diseases. However, methods for clinical detecting of circulating miRNA that take both sensitivity and practicality into account are still needed. Therefore, we aimed herein to solve some inherent problems in the actual detection using a robust surface-enhanced Raman scattering (SERS) platform with integrated nucleic acid amplification and nanoparticle aggregation to construct 3D hotspots for improving performance of analyzing circulating miRNAs. After target recognition and initial signal amplification by DNAzyme, we observed that release triggered an open hairpin DNA on gold nanoparticles (AuNPs), which then promote AuNP aggregation, causing the accumulation of a large number of hotspots in three-dimention. The SERS biosensor achieved a better performance than the sandwich-type separation detection, with a low detection limit (0.37 fM) and a broad linear range (1 fM–10 nM) in liquids. This SERS platform can be used as a powerful tool for the detection of circulating miRNAs, and it can be used to improve the sensitivity and accuracy of various clinical-disease diagnoses.
Graphical Abstract
Health system learning with Indigenous communities: a study protocol for a two-eyed seeing review and multiple case study
Authors: Milligan Crystal , Mantla Rosa , Blake Grace , Zoe John B. , Steinwand Tyanna , Greenland Sharla , Keats Susan , Nash Sara , Kakfwi-Scott Kyla , Veldhorst Georgina , Mashford-Pringle Angela , Stewart Suzanne , Chatwood Susan , Berta Whitney , Dobrow Mark J. 
Published: June 2022

Abstract
Background
It is well documented that Canadian healthcare does not fully meet the health needs of First Nations, Inuit or Métis peoples. In 1996, the Royal Commission on Aboriginal Peoples concluded that Indigenous peoples’ healthcare needs had to be met by strategies and systems that emerged from Indigenous worldviews and cultures. In 2015, the Truth and Reconciliation Commission also called on health organizations to learn from Indigenous knowledges and integrate Indigenous worldviews alongside biomedicine and other western ways of knowing. These calls have not yet been met. Meanwhile, the dynamic of organizational learning from knowledges and evidence within communities is poorly understood—particularly when learning is from communities whose ways of knowing differ from those of the organization. Through an exploration of organizational and health system learning, this study will explore how organizations learn from the Indigenous communities they serve and contribute to (re-)conceptualizing the learning organization and learning health system in a way that privileges Indigenous knowledges and ways of knowing.

Methods
This study will employ a two-eyed seeing literature review and embedded multiple case study. The review, based on Indigenous and western approaches to reviewing and synthesizing knowledges, will inform understanding of health system learning from different ways of knowing. The multiple case study will examine learning by three distinct government organizations in Northwest Territories, a jurisdiction in northern Canada, that have roles to support community health and wellness: Tłı̨chǫ Government, Gwich’in Tribal Council, and Government of Northwest Territories. Case study data will be collected via interviews, talking circles, and document analysis. A steering group, comprising Tłı̨chǫ and Gwich’in Elders and representatives from each of the three partner organizations, will guide all aspects of the project.

Discussion
Examining systems that create health disparities is an imperative for Canadian healthcare. In response, this study will help to identify and understand ways for organizations to learn from and respectfully apply knowledges and evidence held within Indigenous communities so that their health and wellness are supported. In this way, this study will help to guide health organizations in the listening and learning that is required to contribute to reconciliation in healthcare.