bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lipid control and stroke risk in atrial fibrillation patients treated with direct oral anticoagulants and statins
Authors: Ip Bonaventure , Yip Terry , Hung Trista , Yam Tsz-Fai , Yeung Carly , Ko Ho , Wong Grace , Leng Xinyi , Mok Vincent , Soo Yannie , Seiffge David , Shoamanesh Ashkan , Leung Thomas 
Published: August 2024

Introduction: The risk of ischemic stroke and intracerebral hemorrhage (ICH) with intensive lipid control by statins among patients with atrial fibrillation (AF) who require direct oral anticoagulants (DOAC) is unclear. We aimed to determine the risks of ischemic stroke and ICH in AF patients treated with DOAC and statins. Patients and methods: In a population-based retrospective cohort study, we identified AF patients concurrently on DOAC and statins from 2015 to 2021 in Hong Kong. Primary outcome was ischemic stroke. Secondary outcomes were ICH and death. We correlated study outcomes with low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) as time-varying, continuous variables with restricted cubic spline. In secondary analyses, the risks of study outcomes with statin intensity (low, moderate, high) were determined by multivariable time-dependent marginal structural Cox models. Results: We identified 32,752 AF patients co-prescribed with DOAC and statins. Lower LDL-C ( p < 0.001) and higher HDL-C ( p < 0.001) levels were associated with lower risk of ischemic stroke but not significantly associated with ICH. LDL-C of <1.8 mmol/L (70 mg/dL) was not associated with mortality (19.6% vs 18.4%, difference 1.2% [95% CI −0.35 to 2.13]). High-intensity statin was associated with a lower risk of ischemic stroke compared with low-intensity statin (weighted Cox-specific hazard ratio [95% CI]: 0.82 [0.67–0.99], p = 0.040) independent of LDL-C levels. Similar associations were found in 11,444 AF patients with a history of ischemic stroke. Discussion and conclusion: Intensive lipid control by high-intensity statins was associated with a lower risk of ischemic stroke in AF patients who required DOACs and did not appear to increase the risk of ICH.
Deletions in the MAL gene result in loss of Mal protein, defining the rare inherited AnWj-negative blood group phenotype
Authors: Tilley Louise A. , Karamatic Crew Vanja , Mankelow Tosti J. , AlSubhi Samah A. , Jones Benjamin , Borowski Abigail , Yahalom Vered , Finkel Lilach , Singleton Belinda K. , Walser Piers J. , Toye Ashley M. , Satchwell Timothy J. , Thornton Nicole M. 
Published: August 2024

Abstract
The genetic background of the high prevalence red blood cell antigen AnWj has remained unresolved since its identification in 1972, despite reported associations with both CD44 and Smyd1 histone methyltransferase. Development of anti-AnWj, which may be clinically significant, is usually due to transient suppression of antigen expression, but a small number of individuals with persistent, autosomally recessive inherited AnWj-negative phenotype have been reported. Whole-exome sequencing of individuals with the rare inherited AnWj-negative phenotype revealed no shared mutations in CD44H or SMYD1; instead, we discovered homozygosity for the same large exonic deletion in MAL, which was confirmed in additional unrelated AnWj-negative individuals. MAL encodes an integral multipass membrane proteolipid, myelin and lymphocyte protein (Mal), which has been reported to have essential roles in cell transport and membrane stability. AnWj-positive individuals were shown to express full-length Mal on their red cell membranes, which was not present on the membranes of AnWj-negative individuals, regardless of whether from an inherited or suppression background. Furthermore, binding of anti-AnWj was able to inhibit binding of anti-Mal to AnWj-positive red cells, demonstrating the antibodies bind to the same molecule. Overexpression of Mal in an erythroid cell line resulted in the expression of AnWj antigen, regardless of the presence or absence of CD44, demonstrating that Mal is both necessary and sufficient for AnWj expression. Our data resolve the genetic background of the inherited AnWj-negative phenotype, forming the basis of a new blood group system, further reducing the number of remaining unsolved blood group antigens.
The causal relationship between gut microbiota and constipation: a two-sample Mendelian randomization study
Authors: He Nan , Sheng Kai , Li Guangzhao , Zhang Shenghuan 
Published: August 2024

Abstract
Background
Constipation is one of the most common gastrointestinal disorders afflicting the population, with recent observational studies implicating dysfunction of the gut microbiota in constipation. Despite observational studies indicating a relationship, a clear causality remains unclear. This study aims to use two-sample Mendelian randomization (MR) to establish a clearer causal relationship between the two.

Methods
A two-sample Mendelian randomization (MR) study was performed using the gut microbiota summary Genome-Wide Association Studies (GWAS) statistics from MiBioGen consortium (n = 13,266) and constipation GWAS summary statistics from the IEU OpenGWAS database. The causality between gut microbiota and constipation is primarily analyzed using the inverse-variance weighted (IVW) method and reinforced by an additional four methods, including MR-Egger, Weighted Median, Simple Mode, and Weighted Mode. Finally, funnel plot, heterogeneity test, horizontal pleiotropy test, and leave-one-out test were used to evaluate the reliability of MR results.

Results
IVW estimates suggested that the bacterial species Anaerotruncus, Butyricimonas, and Hungatella were causally associated with constipation. The odds ratio (OR) values of Anaerotruncus, Butyricimonas, and Hungatella were 1.08 (95% CI = 1.02–1.13; P = 0.007), 1.07 (95% CI = 1.01–1.13; P = 0.015), 1.03 (95% CI = 1.00-1.06; P = 0.037) respectively. Meanwhile, Ruminiclostridium 9 and Intestinibacter have been shown to be associated with a reduced risk of constipation. The OR of Ruminiclostridium 9 = 0.75(95% CI = 0.73–0.78, P < 0.001 and Intestinibacter of OR = 0.89 (95% CI = 0.86–0.93, P < 0.001). Furthermore, validation by funnel plot, heterogeneity test, and horizontal pleiotropy test showed that MR results were reliable.

Conclusion
This is the first Mendelian randomization study to explore the causalities between specific gut microbiota taxa and constipation, and as such may be useful in providing insights into the unclear pathology of constipation which can in turn aid in the search for prevention and treatment.
Associations of family socioeconomic indicators and physical activity of primary school-aged children: a systematic review
Authors: Ziegeldorf Alexandra , Schoene Daniel , Fatum Alisa , Brauer Katharina , Wulff Hagen 
Published: August 2024

Abstract
Background
Family socioeconomic indicators (education, occupation, and household income) are key determinants influencing children’s physical activity (PA). This study aims to systematically review the current research about the association between family socioeconomic indicators and PA among primary school-aged children and to quantify the distribution of reported associations by childs’ and parents’ sex and according to analysis and assessment methods.

Methods
A systematic literature research in multiple scientific databases (MEDLINE via PubMed, Web of Science, ScienceDirect, SPORTDiscus and ERIC) was performed for literature published between 1st January 2010 and 31st March 2022. Only studies reporting statistical associations between an SES indicator of at least one parent (education, occupation, income, or an SES index) and different types and intensities of PA in primary school-aged children (6 to 12 years) were included in the analysis. The distributions of the reported associations were evaluated across and differentiated by sub-group analysis of assessment methods (objectively measured vs. self-reported PA) and analysis methods (univariate vs. multivariate models).

Results
Overall, 93 studies reported in 77 publications were included in this review. Most of the studies were conducted in Europe and used self-reports (questionnaires) to assess PA. Most studies used only a single SES indicator (commonly maternal education), and only two studies calculated an SES index. The majority of the studies focused on moderate-to-vigorous physical activity (MVPA), total physical activity (TPA), and organized physical activity (OPA). Results showed predominantly positive associations between SES indicators and OPA. In contrast, results regarding different intensities of daily PA (TPA, LPA, MPA, MVPA, VPA, LTPA) were heterogeneous, with overwhelmingly no associations.

Conclusion
Overall, the results expand the knowledge about the association between family socioeconomic indicators and children’s PA and disprove the hypothesis of a clear positive association. However, large multicenter studies are lacking using a real SES index as a predictor and analyzing gender-specific multivariate models.
Development and validation of a rapid five-minute nucleic acid extraction method for respiratory viruses
Authors: Wang Yu , Huang Yuanyuan , Peng Yuqing , Cao Qinglin , Liu Wenkuan , Zhou Zhichao , Xu Guangxin , Li Lei , Zhou Rong 
Published: August 2024

Abstract
Background
The rapid transmission and high pathogenicity of respiratory viruses significantly impact the health of both children and adults. Extracting and detecting their nucleic acid is crucial for disease prevention and treatment strategies. However, current extraction methods are laborious and time-consuming and show significant variations in nucleic acid content and purity among different kits, affecting detection sensitivity and efficiency. Our aim is to develop a novel method that reduces extraction time, simplifies operational steps, and ensures high-quality acquisition of respiratory viral nucleic acid.

Methods
We extracted respiratory syncytial virus (RSV) nucleic acid using reagents with different components and analyzed cycle threshold (Ct) values via quantitative real-time polymerase chain reaction (qRT-PCR) to optimize and validate the novel lysis and washing solution. The performance of this method was compared against magnetic bead, spin column, and precipitation methods for extracting nucleic acid from various respiratory viruses. The clinical utility of this method was confirmed by comparing it to the standard magnetic bead method for extracting clinical specimens of influenza A virus (IAV).

Results
The solution, composed of equal parts glycerin and ethanol (50% each), offers an innovative washing approach that achieved comparable efficacy to conventional methods in a single abbreviated cycle. When combined with our A Plus lysis solution, our novel five-minute nucleic acid extraction (FME) method for respiratory viruses yielded superior RNA concentrations and purity compared to traditional methods. FME, when used with a universal automatic nucleic acid extractor, demonstrated similar efficiency as various conventional methods in analyzing diverse concentrations of respiratory viruses. In detecting respiratory specimens from 525 patients suspected of IAV infection, the FME method showed an equivalent detection rate to the standard magnetic bead method, with a total coincidence rate of 95.43% and a kappa statistic of 0.901 (P < 0.001).

Conclusions
The FME developed in this study enables the rapid and efficient extraction of nucleic acid from respiratory samples, laying a crucial foundation for the implementation of expedited molecular diagnosis.
Targeting treatment resistance: unveiling the potential of RNA methylation regulators and TG-101,209 in pan-cancer neoadjuvant therapy
Authors: Zhou Yaoyao , Liu Ziyun , Gong Cheng , Zhang Jie , Zhao Jing , Zhang Xia , Liu Xiangyu , Li Bin , Li Rui , Shi Zhenyu , Xie Yongjie , Bao Li 
Published: August 2024

Abstract
Background
Tumor recurrence and mortality rates remain challenging in cancer patients despite comprehensive treatment. Neoadjuvant chemotherapy and immunotherapy aim to eliminate residual tumor cells, reducing the risk of recurrence. However, drug resistance during neoadjuvant therapy is a significant hurdle. Recent studies suggest a correlation between RNA methylation regulators (RMRs) and response to neoadjuvant therapy.

Methods
Using a multi-center approach, we integrated advanced techniques such as single-cell transcriptomics, whole-genome sequencing, RNA sequencing, proteomics, machine learning, and in vivo/in vitro experiments. Analyzing pan-cancer cohorts, the association between neoadjuvant chemotherapy/immunotherapy effectiveness and RNA methylation using single-cell sequencing was investigated. Multi-omics analysis and machine learning algorithms identified genomic variations, transcriptional dysregulation, and prognostic relevance of RMRs, revealing distinct molecular subtypes guiding pan-cancer neoadjuvant therapy stratification.

Results
Our analysis unveiled a strong link between neoadjuvant therapy efficacy and RNA methylation dynamics, supported by pan-cancer single-cell sequencing data. Integration of omics data and machine learning algorithms identified RMR genomic variations, transcriptional dysregulation, and prognostic implications in pan-cancer. High-RMR-expressing tumors displayed increased genomic alterations, an immunosuppressive microenvironment, poorer prognosis, and resistance to neoadjuvant therapy. Molecular investigations and in vivo/in vitro experiments have substantiated that the JAK inhibitor TG-101,209 exerts notable effects on the immune microenvironment of tumors, rendering high-RMR-expressing pan-cancer tumors, particularly in pancreatic cancer, more susceptible to chemotherapy and immunotherapy.

Conclusions
This study emphasizes the pivotal role of RMRs in pan-cancer neoadjuvant therapy, serving as predictive biomarkers for monitoring the tumor microenvironment, patient prognosis, and therapeutic response. Distinct molecular subtypes of RMRs aid individualized stratification in neoadjuvant therapy. Combining TG-101,209 adjuvant therapy presents a promising strategy to enhance the sensitivity of high-RMR-expressing tumors to chemotherapy and immunotherapy. However, further validation studies are necessary to fully understand the clinical utility of RNA methylation regulators and their impact on patient outcomes.
Trauma induced coagulopathy is limited to only one out of four shock induced endotheliopathy (SHINE) phenotypes among moderate-severely injured trauma patients: an exploratory analysis
Authors: Johansson Pär I. , Vigstedt Martin , Curry Nicola S. , Davenport Ross , Juffermans Nicole P. , Stanworth Simon J. , Maegele Marc , Gaarder Christine , Brohi Karim , Stensballe Jakob , Henriksen Hanne H. ,   for the Targeted Action for Curing Trauma-Induced Coagulopathy (TACTIC) Collaborators
Published: August 2024

Abstract
Background
Trauma induced coagulopathy remains to be an important cause of high transfusion requirements and mortality and shock induced endotheliopathy (SHINE) has been implicated.

Methods
European multicenter observational study of adult trauma patients with injury severity score ≥ 16 arriving within 2 h from injury to the trauma centers. Admission blood samples obtained were used for analysis of the SHINE biomarkers (syndecan-1, soluble thrombomodulin, adrenaline) and extensive analysis of coagulation, -and fibrinolytic factors together with collection of clinical data. Hierarchical clustering of the SHINE biomarkers was used to identify the SHINE phenotypes.

Results
The 313 patients clustered into four SHINE phenotypes. Phenotype 2, having the highest glycocalyx shedding, encompassing 22% of the whole cohort, had severe coagulopathy with lower levels of prothrombin, FV, IX, X, XI and severe hyperfibrinolysis with higher plasmin – alpha 2-antiplasmin (PAP) – and tPA levels and lower alpha2 – antiplasmin levels. This phenotype had significantly higher transfusion requirements and higher mortality (39% vs. 23%, 15% and 14%) but similar injury severity score (ISS) compared to the others phenotypes.

Conclusions
Hierarchical clustering identified four SHINE phenotype in a cohort of trauma patients. Trauma induced coagulopathy was confined to only one of the SHINE phenotypes, encompassing 22% of the total cohort. This phenotype was characterized by severe hypocoagulability and hyperfibrinolysis, which translated to significantly higher transfusion requirements and higher mortality compared to the other SHINE phenotypes with similar injury severity, warranting further investigation.
Benefits of osimertinib treat a lung adenocarcinoma patient with germline EGFR T790M, somatic EGFR 19-Del, TP53 and PIK3CA mutations
Authors: Li Yingxue , Li Guangqi , Zheng Zheng , Wen Wenjuan , Zhao Haihui , Liu Xia , Xie Jiaping , Han Lin 
Published: August 2024

Abstract
Background
Somatic mutations in the EGFR gene occur in about 50% of non-small cell lung cancers, with the T790M mutation significantly contributing to secondary resistance against EGFR-TKI drugs. However, EGFR T790M germline mutations rarely occur.

Case presentation
In this study, we report a case of a lung adenocarcinoma family lineage linked to a germline EGFR T790M mutation. The main subject was diagnosed with stage IV lung adenocarcinoma and experienced a 19-month period without disease progression while treated with Osimertinib. We collected both clinicopathological and familial data from a patient with lung adenocarcinoma. Next-generation sequencing of 40 key genes was performed on the proband’s tumor tissue. To detect EGFR germline mutations, Sanger sequencing was conducted on peripheral blood mononuclear cells from the proband and his two daughters. Mutations such as EGFR T790M, EGFR 19-Del, TP53, and PIK3CA were identified in the proband’s lung cancer tissue. Additionally, germline EGFR T790M mutations were confirmed in the proband and his daughters through sequencing of their peripheral blood samples. CT scans revealed multiple pulmonary nodules in both daughters.

Conclusions
These observations suggest that germline mutations in EGFR T790M could be strongly linked to a familial predisposition to lung cancer.
Identification of tumor rejection antigens and the immunologic landscape of medulloblastoma
Authors: Yang Changlin , Trivedi Vrunda , Dyson Kyle , Gu Tongjun , Candelario Kate M. , Yegorov Oleg , Mitchell Duane A. 
Published: August 2024

Abstract
Background
The current standard of care treatments for medulloblastoma are insufficient as these do not take tumor heterogeneity into account. Newer, safer, patient-specific treatment approaches are required to treat high-risk medulloblastoma patients who are not cured by the standard therapies. Immunotherapy is a promising treatment modality that could be key to improving survival and avoiding morbidity. For an effective immune response, appropriate tumor antigens must be targeted. While medulloblastoma patients with subgroup-specific genetic substitutions have been previously reported, the immunogenicity of these genetic alterations remains unknown. The aim of this study is to identify potential tumor rejection antigens for the development of antigen-directed cellular therapies for medulloblastoma.

Methods
We developed a cancer immunogenomics pipeline and performed a comprehensive analysis of medulloblastoma subgroup-specific transcription profiles (n = 170, 18 WNT, 46 SHH, 41 Group 3, and 65 Group 4 patient tumors) available through International Cancer Genome Consortium (ICGC) and European Genome-Phenome Archive (EGA). We performed in silico antigen prediction across a broad array of antigen classes including neoantigens, tumor-associated antigens (TAAs), and fusion proteins. Furthermore, we evaluated the antigen processing and presentation pathway in tumor cells and the immune infiltrating cell landscape using the latest computational deconvolution methods.

Results
Medulloblastoma patients were found to express multiple private and shared immunogenic antigens. The proportion of predicted TAAs was higher than neoantigens and gene fusions for all molecular subgroups, except for sonic hedgehog (SHH), which had a higher neoantigen burden. Importantly, cancer-testis antigens, as well as previously unappreciated neurodevelopmental antigens, were found to be expressed by most patients across all medulloblastoma subgroups. Despite being immunologically cold, medulloblastoma subgroups were found to have distinct immune cell gene signatures.

Conclusions
Using a custom antigen prediction pipeline, we identified potential tumor rejection antigens with important implications for the development of immunotherapy for medulloblastoma.
Deep-learning-enabled temporally super-resolved multiplexed fringe projection profilometry: high-speed kHz 3D imaging with low-speed camera
Authors: Chen Wenwu , Feng Shijie , Yin Wei , Li Yixuan , Qian Jiaming , Chen Qian , Zuo Chao 
Published: August 2024

AbstractRecent advances in imaging sensors and digital light projection technology have facilitated rapid progress in 3D optical sensing, enabling 3D surfaces of complex-shaped objects to be captured with high resolution and accuracy. Nevertheless, due to the inherent synchronous pattern projection and image acquisition mechanism, the temporal resolution of conventional structured light or fringe projection profilometry (FPP) based 3D imaging methods is still limited to the native detector frame rates. In this work, we demonstrate a new 3D imaging method, termed deep-learning-enabled multiplexed FPP (DLMFPP), that allows to achieve high-resolution and high-speed 3D imaging at near-one-order of magnitude-higher 3D frame rate with conventional low-speed cameras. By encoding temporal information in one multiplexed fringe pattern, DLMFPP harnesses deep neural networks embedded with Fourier transform, phase-shifting and ensemble learning to decompose the pattern and analyze separate fringes, furnishing a high signal-to-noise ratio and a ready-to-implement solution over conventional computational imaging techniques. We demonstrate this method by measuring different types of transient scenes, including rotating fan blades and bullet fired from a toy gun, at kHz using cameras of around 100 Hz. Experiential results establish that DLMFPP allows slow-scan cameras with their known advantages in terms of cost and spatial resolution to be used for high-speed 3D imaging tasks.
Approach to the Child and Adolescent With Adrenal Insufficiency
Authors: Patti Giuseppa , Zucconi Alice , Matarese Simona , Tedesco Caterina , Panciroli Marta , Napoli Flavia , Di Iorgi Natascia , Maghnie Mohamad 
Published: August 2024

Abstract
The management of adrenal insufficiency (AI) is challenging, and the overall goals of treatment are to prevent life-threatening adrenal crises, to optimize linear growth, to control androgen levels without overdosing in patients with congenital adrenal hyperplasia (CAH), and to improve quality of life in affected individuals. Standard glucocorticoid formulations fail to replicate the circadian rhythm of cortisol and control the adrenal androgen production driven by adrenocorticotropin. To personalize and tailor glucocorticoid therapy and to improve patient outcomes, new pharmacological strategies have been developed that best mimic physiological cortisol secretion. Novel therapeutic approaches in the management of AI include new ways to deliver circadian cortisol replacement as well as various adjunctive therapies to reduce androgen production and/or androgen action/effects. Preclinical studies are exploring the role of restorative cell-based therapies, and a first recombinant adeno-associated virus-based gene therapy is also being developed in humans with CAH. In this article, we present 3 illustrative cases of AI with different underlying etiologies and times of presentation. Diagnostic and management processes are discussed with an emphasis on treatment and outcomes. We have also provided the most up-to-date evidence for the tailored management of children and adolescents with AI.