bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estradiol-mediated enhancement of the human ectocervical epithelial barrier correlates with desmoglein-1 expression in the follicular menstrual phase
Authors: Bradley Frideborg , Stern Alexandra , Franzén Boger Mathias , Mousavian Zaynab , Dethlefsen Olga , Kaldhusdal Vilde , Lajoie Julie , Omollo Kenneth , Bergström Sofia , Månberg Anna , Nilsson Peter , Kimani Joshua , Burgener Adam D. , Tjernlund Annelie , Sundling Christopher , Fowke Keith R. , Broliden Kristina 
Published: October 2024

BackgroundThe cervicovaginal epithelial barrier is crucial for defending the female reproductive tract against sexually transmitted infections. Hormones, specifically estradiol and progesterone, along with their respective receptor expressions, play an important role in modulating this barrier. However, the influence of estradiol and progesterone on gene and protein expression in the ectocervical mucosa of naturally cycling women is not well understood.MethodsMucosal and blood samples were collected from Kenyan female sex workers at high risk of sexually transmitted infections. All samples were obtained at two time points, separated by two weeks, aiming for the follicular and luteal phases of the menstrual cycle. Ectocervical tissue biopsies were analyzed by RNA-sequencing and in situ immunofluorescence staining, cervicovaginal lavage samples (CVL) were evaluated using protein profiling, and plasma samples were analyzed for hormone levels.ResultsUnsupervised clustering of RNA-sequencing data was performed using Weighted gene co-expression network analysis (WGCNA). In the follicular phase, estradiol levels positively correlated with a gene module representing epithelial structure and function, and negatively correlated with a gene module representing cell cycle regulation. These correlations were confirmed using regression analysis including adjustment for bacterial vaginosis status. Using WGCNA, no gene module correlated with progesterone levels in the follicular phase. In the luteal phase, no gene module correlated with either estradiol or progesterone levels. Protein profiling on CVL revealed that higher levels of estradiol during the follicular phase correlated with increased expression of epithelial barrier integrity markers, including DSG1. This contrasted to the limited correlations of protein expression with estradiol levels in the luteal phase. In situ imaging analysis confirmed that higher estradiol levels during the follicular phase correlated with increased DSG1 expression.ConclusionWe demonstrate that estradiol levels positively correlate with specific markers of ectocervical epithelial structure and function, particularly DSG1, during the follicular phase of the menstrual cycle. Neither progesterone levels during the follicular phase nor estradiol and progesterone levels during the luteal phase correlated with any specific sets of gene markers. These findings align with the expression of estradiol and progesterone receptors in the ectocervical epithelium during these menstrual phases.
The global death and disability burden associated with a high BMI in children and adolescents, 1990–2019
Authors: Song Ying , Zhou Yuan , Feng Xiaojin , Fu Jieting , Liu Yongping 
Published: October 2024

ObjectiveExploring changing trends in the burden caused by overweight and obesity among children and adolescents from 1990 to 2019 at the global, regional, and national levels, based on data from the Global Burden of Disease study (GBD) 2019.MethodsThe annual number and rate of deaths and disability-adjusted life years (DALYs) associated with a high BMI among children and adolescents at global, regional, and national levels by age groups, sexes, and the sociodemographic index from 1990 to 2019 were collected from the GBD study 2019. Change percentage for number, and the estimated annual percentage changes (EAPCs) for rate were calculated to determine the temporal trends.ResultsFrom 1990 to 2019, global high BMI-related deaths decreased by 34% but DALYs increased by 48%. Death rates in females were higher than in males, although both showed decreasing trends. For the rate of DALYs, both sexes showed increasing trends, but since 1999, the rate in males has surpassed that in females. A high BMI had the greatest impact on children under 5 years of age, and the burden in other age groups continued to increase. Regionally, High-income Asia Pacific experienced the fastest decrease in death rate (EAPC=−9.57), and East Asia saw the fastest increase in the DALYs rate (EAPC= 3.47). Globally, as age increases, the proportion of disease burden attributed to a high BMI in females generally increases.ConclusionsOur findings emphasize the urgent need to improve efforts to prevent children and adolescents becoming overweight and obese.
Potential impact of ezetimibe on patients with NAFLD/NASH: a meta-analysis of randomized controlled trials
Authors: Jiao BoLun , Wang Bing , Liu BoYan , Zhao Jin , Zhang YunHao 
Published: October 2024

BackgroundNon-alcoholic fatty liver disease (NAFLD) is now the most common cause of chronic liver disease. Studies have found that ezetimibe may be utilized as a supplemental treatment for NAFLD. Additionally, many clinical trials reported the potential impacts of ezetimibe on patients with NAFLD, although some conclusions remain controversial. Therefore, this study aimed to evaluate the effects of ezetimibe on patients with NAFLD.MethodOnline search was conducted across databases including PubMed, Embase, Scopus, Web of Science, Cochrane Library, Wanfang, VIP, and CNKI to retrieve all relevant controlled studies on the treatment of NAFLD with ezetimibe from the inception of the databases until April 2024. This meta-analysis comprised 10 randomized controlled trials (RCTs). Statistical analysis was conducted using the Meta package in R v4.3.2.ResultsA total of ten RCTs were included in this study, encompassing 578 patients (290 in the ezetimibe group and 288 in the control group) diagnosed with NAFLD/non-alcoholic steatohepatitis (NASH). The results indicated that ezetimibe significantly reduced levels of aspartate aminotransferase (P &lt; 0.01), glutamyl transferase (γ-GT) (P &lt; 0.01), total cholesterol (P &lt; 0.01), low-density lipoprotein cholesterol (P &lt; 0.01), high-sensitivity C-reactive protein (P &lt; 0.01), and interleukin-6 (P &lt; 0.01), and markedly increased levels of glycated hemoglobin (P = 0.02).ConclusionsEzetimibe may partially improve transaminase levels and positively impact liver function in patients with NAFLD/NASH.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023461467.
Identification of plasma exosomal lncRNA as a biomarker for early diagnosis of gastric cancer
Authors: Wei Ye , Hu Xuming , Yuan Shuai , Zhao Yue , Zhu Chunhui , Guo Mingzhou , Cui Hengmi 
Published: October 2024

BackgroundThere were about 1,090,000 gastric cancer (GC) cases in 2020 in China. The incidence and mortality rates ranked the fifth and third among all kinds of cancers in China. Early diagnosis plays an important role in the treatment and prognosis of gastric cancer. In recent years, noninvasive diagnosis, especially plasma exosome lncRNAs, has become a promissing biomarkers with high specificity and sensitivity for early diagnosis of cancers.MethodsIn this study, plasma exosomes of patients with early gastric cancer were extracted efficiently by affinity membrane separation technology, including affinity adsorption, elution, affinity membrane regeneration and other steps. After identified by electron microscopy observation, particle size analysis and Western blot verification, the lncRNAs in the exosomes were extracted and were analysized by high-throughput RNA sequencing (RNA-Seq). The differentially expressed lncRNAs were verified by RT-qPCR in 93 patients with early gastric cancer and 49 normal controls.ResultsElectron microscopy, particle size analysis and Western blot showed that exosomes were successfully isolated from plasma. RNA-Seq results show that 76 lncRNAs were upregulated and 260 lncRNAs were downregulated in plasma exosomes of early gastric cancer patients compared with normal controls. RT-qPCR analysis indicated that a total of 6 lncRNAs were significantly and differentially expressed in gastric cancer patients compared to normal controls, with 2 (lncmstrg. 1319590, Lncmstrg. 2312697) highly expressed and 4 lowly expressed (lncmstr-g.1004024.1, lncmstrg. 2441832.8, lncmstrg. 315376.1, lncmstrg.907985.2,) (p &lt; 0.05). The survival curve analysis indicated that lncmstrg.2441832.8 and lncmstrg.2312697 had higher sensitivity and specificity for the diagnosis of gastric cancer, respectively and AUC curve areas were 0.6211 and 0.631, p &lt; 0.05, respectively, which were greater than the traditional clinical detection indexes CEA (0.61) and AFP (0.57). When combined lncmstrg.2441832.8 and lncmstrg.2312697 in gastric cancer diagnosis, AUC curve area reached 0.73, which was greater than CA199 (0.71).ConclusionLncmstrg.2441832.8 and lncmstrg.2312697 may be a potential and promissing biomarkers for early diagnosis of gastric cancer.
Genetic signatures of AKT1 variants associated with worse COVID-19 outcomes – a multicentric observational study
Authors: de Almeida Ingrid Marins , Tosta Bruna Ramos , Pena Laiane da Cruz , Silva Hatilla dos Santos , Reis-Goes Fabiane S. , Silva Nívia N. , Cruz João Victor Andrade , Silva Mailane dos Anjos , de Araújo Jéssica Francisco , Rodrigues Juliana Lopes , Oliveira Gabriella , Figueiredo Ricardo Gassmann , Vaz Sara Nunes , Montaño-Castellón Iris , Santana Daniele , Torres Alex , Beltrão Fabyan Esberard de Lima , Carneiro Valdirene Leão , Campos Gubio Soares , Brites Carlos , Fortuna Vitor , Figueiredo Camila Alexandrina , Trindade Soraya Castro , Ramos Helton Estrela , Costa Ryan dos Santos 
Published: October 2024

IntroductionThe COVID-19, triggered by the SARS-CoV-2 virus, has varied clinical manifestations, ranging from mild cases to severe forms such as fatal pneumonia and acute respiratory distress syndrome (ARDS). Disease severity is influenced by an exacerbated immune response, characterized by high pro-inflammatory cytokine levels. Inhibition of AKT can potentially suppress pathological inflammation, cytokine storm and platelet activation associated with COVID-19. In this study, we aimed to investigate the rs2494746 and rs1130214 variants in the AKT1 gene associated with severe COVID-19 outcomes.MethodsPeripheral blood samples and sociodemographic data from 508 individuals with COVID-19, measuring plasma cytokine concentrations using ELISA and genotyped the AKT1 variants.ResultsThe rs2494746-C allele was associated with severity, ICU admission, and death from COVID-19. The C allele at rs1130214 was linked to increased TNF and D-dimer levels. Moreover, both variants exhibited an increased cumulative risk of disease severity, ICU admission, and mortality caused by COVID-19. In the predictive analysis, the rs2494746 obtained an accuracy of 71%, suggesting a high probability of the test determining the severity of the disease.DiscussionOur findings contribute to understanding the influence of the AKT1 gene variants on the immunological damage in individuals infected with SARS-CoV-2.
Association between statin use and immune-related adverse events in patients treated with immune checkpoint inhibitors: analysis of the FAERS database
Authors: Yang Huaju , Huang Rendong , Zhang Ping , Liu Yingtong , Liu Zheran , He Jiagang , Peng Xingchen 
Published: October 2024

BackgroundUnderstanding the risk relationship between statin use and immune-related adverse events (irAEs) in patients undergoing immune checkpoint inhibitors (ICIs) therapy is crucial for optimizing oncological management.ObjectiveThis study aimed to investigate whether the use of statins increases the risk of irAEs in patients receiving ICI therapy.MethodsThis study primarily utilized data from FAERS database. Multivariable logistic regression was the principal method of analysis, and the Benjamini-Hochberg procedure was employed to adjust for multiple hypothesis testing.ResultsIn a group of 145,214 patients undergoing ICI therapy, 9,339 reported using statin medications. Multivariable analysis indicated an increased risk of irAEs among statin users (OR 1.199, 95% CI: 1.141-1.261; FDR p &lt; 0.001) in comparison to those not using statins. Notably, increased risks were observed particularly in patients diagnosed with lung, pancreatic, and renal cancers. The link between statin usage and increased irAEs risk remained consistent across various ICIs treatments.ConclusionsStatin medication usage is linked to an elevated probability of experiencing irAEs in patients enrolled in ICI therapy. In cancer patients receiving immune checkpoint inhibitors, careful consideration of statin use is essential to avoid potentially increased irAEs risk. These findings provide critical guidance for clinicians in developing treatment strategies that balance therapeutic efficacy and safety in oncological management.
Tofacitinib for child-onset systemic lupus erythematosus
Authors: Hou Ling , Zhou Peng , Zhao Chengguang , Wang Xiuli , Du Yue 
Published: October 2024

BackgroundSystemic lupus erythematosus (SLE) is a chronic autoimmune disease that can cause diverse clinical manifestations in multiple organ systems. Child-onset SLE (cSLE) is associated with significantly higher morbidity and mortality than adult-onset SLE. The traditional treatments for SLE (glucocorticoids, antimalarials, conventional and biological disease-modifying antirheumatic drugs) often have significant adverse effects and may not fully control disease activity. Tofacitinib is an oral Janus kinase (JAK) inhibitor that inhibits the JAK-STAT pathway and has the potential to reduce SLE severity.MethodscSLE patients who received tofacitinib and had at least one follow-up visit were retrospectively examined. Case histories, laboratory test results, and treatment regimens were analyzed at disease onset, initiation of tofacitinib treatment, and 1, 3, 6, 9, 12, 18, and 24 months after starting tofacitinib.ResultsWe examined 9 patients with refractory cSLE. All patients were female and the average age at diagnosis was 10.67 years. At initiation of tofacitinib, the average age was 13.28 years and the average disease duration was 2.62 years. Four patients experienced alleviation of symptoms and reduced their daily prednisone dosages; one of them also discontinued cyclosporine A and two of them also discontinued belimumab. The other 5 patients experienced no apparent benefit.ConclusionTofacitinib may provide clinical benefits for some patients with refractory cSLE, and can also allow reduction in the glucocorticoid dosage. Tofacitinib has the potential as an adjunctive treatment for some patients with cSLE.
The self-assembled nanoparticle-based multi-epitope influenza mRNA vaccine elicits protective immunity against H1N1 and B influenza viruses in mice
Authors: Di Yaxin , Zhang Chenchao , Ren Zilin , Jiang Renyue , Tang Jiafeng , Yang Songhui , Wang Ziliang , Yu Tong , Zhang Tong , Yu Ziping , Xu Zhiqiang , Zhuang Xinyu , Jin Ningyi , Tian Mingyao 
Published: October 2024

IntroductionThe influenza virus is recognized as the primary cause of human respiratory diseases, with the current influenza vaccine primarily offering strain-specific immunity and limited protection against drifting strains. Considering this, the development of a broad-spectrum influenza vaccine capable of inducing effective immunity is considered the future direction in combating influenza.MethodsThe present study proposes a novel mRNA-based multi-epitope influenza vaccine, which combines three conserved antigens derived from the influenza A virus. The antigens consist of M2 ion channel’s extracellular domain (M2e), the conserved epitope of located in HA2 of hemagglutinin (H1, H3, B), and HA1 of hemagglutinin. At the same time, trimeric sequences and ferritin were conjugated separately to investigate the immune effects of antigen multivalent presentation.ResultsImmunization studies conducted on C57BL/6 mice with these vaccines revealed that they can elicit both humoral immunity and CD4+ and CD8+ T cell responses, which collectively contribute to enhancing cross-protective effects. The virus challenge results showed that vaccinated groups had significantly reduced lung damage, lower viral loads in the lungs, nasal turbinates, and trachea, as well as decreased levels of pro-inflammatory cytokines.ConclusionThese findings clearly demonstrate the wide range of protective effects provided by these vaccines against H1N1 and B influenza viruses. The present finding highlights the potential of mRNA-based influenza vaccines encoding conserved proteins as a promising strategy for eliciting broad-spectrum protective humoral and cellular immunity against H1N1 and B influenza viruses.
Archaeal community from the Northern Hangzhou Bay to the East China Sea: biogeography, ecological processes, and functional potential
Authors: Tian Cunzhang , He Xinping , Zhou Hongwei , Liu Cheng , Gao Dengzhou , Chang Yongkai , Zhao Shanshan , Zhang Wensong , Zhang Zongxiao 
Published: October 2024

IntroductionArchaeal communities play a crucial role in marine ecosystems, yet our understanding of their ecological and functional traits remains incomplete. This study focuses on northern Hangzhou Bay to fill gaps in knowledge regarding the biogeography and functionality of archaeal groups.MethodsWe utilized a high-throughput sequencing dataset based on the 16S rRNA gene to characterize the archaeal community, aiming to identify biogeographic patterns and assess the influence of environmental factors on community structure.ResultsThe predominant phyla identified were Woesearchaeota, Thaumarchaeota, Euryarchaeota, and Crenarchaeota. Archaeal community structure in sediments showed a geographical pattern along the environmental gradient, influenced by factors such as salinity, ammonium, total phosphorus, pH, and total nitrogen content. Network analysis revealed nonrandom co-occurrence patterns, with associations changing along the salinity gradient. Additionally, this study directly proved the existence of dispersal limitation in this strongly connected marine ecological system through null model analyses. Variation in the archaeal community was attributed to both environmental constraints and stochastic processes due to dispersal limitation. Furthermore, our results revealed that the key biogeochemical functions of the archaeal community also exhibited a clear salinity gradient, the functional differences appear to be influenced by salinity, and the critical roles of archaeal diversity were highlighted.DiscussionAll these findings enhance our understanding of microbial ecology and element transformation in estuarine environments. The highlighted roles of archaeal diversity and the influence of environmental factors on community structure and function underscore the complexity of marine microbial ecosystems.
Analysis on the relationship between coastal tourism and marine pollution: an empirical analysis of China’s 11 coastal regions
Authors: Ji Xina , Ding Xingong 
Published: October 2024

IntroductionCoastal tourism has become an important pillar of economic growth in China's coastal regions, yet no quantitative research has analyzed the relationship between coastal tourism and marine pollution.MethodsThis study, within a multivariate framework, comprehensively examines the impact of coastal tourism on marine pollution by employing various econometric techniques and focusing on four different types of marine pollutant discharges: chemical oxygen demand (COD), petroleum (PET), ammonia nitrogen (NHN), and total phosphorus (TP).Results and discussionPanel cointegration tests confirm a long-term relationship between coastal tourism and these four types of marine pollutant discharges. In the long run, coastal tourism has a significantly negative impact on COD, NHN, and TP. The results of Pooled Mean Group (PMG), Fully Modified Ordinary Least Squares (FMOLS), and Dynamic Ordinary Least Squares (DOLS) estimators show that for every 1% increase in coastal tourism revenue (TOUR), COD decreases by 0.734%, 0.536%, and 0.952% respectively; NHN decreases by 0.746%, 0.340%, and 1.633%; and TP decreases by 5.169%, 0.899%, and 0.334% respectively. However, the impact of coastal tourism on PET is not significant. The Dumitrescu-Hurlin (D-H) panel causality test results indicate different causality patterns between coastal tourism and various marine pollutant discharges. Specifically, there is a bidirectional causality between coastal tourism and COD, NHN, and a unidirectional causality between coastal tourism and PET, TP. Moreover, heterogeneity analysis reveals that coastal tourism does not significantly reduce all marine pollutant discharges in low-and middle-income coastal regions. Furthermore, compared to the central and southern coastal regions, the coastal tourism of northern regions has not significantly reduced marine pollution. This study can provide policymakers with references for developing coastal tourism and reducing marine pollutant discharges.
Deep learning-driven ultrasound-assisted diagnosis: optimizing GallScopeNet for precise identification of biliary atresia
Authors: Niu Yupeng , Li Jingze , Xu Xiyuan , Luo Pu , Liu Pingchuan , Wang Jian , Mu Jiong 
Published: October 2024

BackgroundBiliary atresia (BA) is a severe congenital biliary developmental abnormality threatening neonatal health. Traditional diagnostic methods rely heavily on experienced radiologists, making the process time-consuming and prone to variability. The application of deep learning for the automated diagnosis of BA remains underexplored.MethodsThis study introduces GallScopeNet, a deep learning model designed to improve diagnostic efficiency and accuracy through innovative architecture and advanced feature extraction techniques. The model utilizes data from a carefully constructed dataset of gallbladder ultrasound images. A dataset comprising thousands of ultrasound images was employed, with the majority used for training and validation and a subset reserved for external testing. The model’s performance was evaluated using five-fold cross-validation and external assessment, employing metrics such as accuracy and the area under the receiver operating characteristic curve (AUC), compared against clinical diagnostic standards.ResultsGallScopeNet demonstrated exceptional performance in distinguishing BA from non-BA cases. In the external test dataset, GallScopeNet achieved an accuracy of 81.21% and an AUC of 0.85, indicating strong diagnostic capabilities. The results highlighted the model’s ability to maintain high classification performance, reducing misdiagnosis and missed diagnosis.ConclusionGallScopeNet effectively differentiates between BA and non-BA images, demonstrating significant potential and reliability for early diagnosis. The system’s high efficiency and accuracy suggest it could serve as a valuable diagnostic tool in clinical settings, providing substantial technical support for improving diagnostic workflows.