bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations between lipid-lowering drugs and urate and gout outcomes: a Mendelian randomization study
Authors: Liu Min , Yin Na , Zhu Yuhang , Du Aili , Cai Chunyuan , Leng Pengyuan 
Published: January 2025

ObjectiveGout is a common inflammatory arthritis and lipid metabolism plays a crucial role in urate and gout. Potential associations between urate and gout and lipid-lowering drugs have been revealed in observational studies. However, the effects of lipid-lowering drugs on urate and gout remain controversial. The aim of this study was to investigate the genetic association between lipid-lowering drugs and urate and gout.MethodsIn this study, two genetic proxies were employed to approximate lipid-lowering drug exposure: expression quantitative trait loci (eQTL) associated with drug-target genes and genetic variations proximal to or within genes targeted by these drugs, which are linked to low-density lipoprotein cholesterol (LDL-C) levels. The study’s exposures encompassed genetic variants within drug target genes (HMGCR, PCSK9, NPC1L1), each representing distinct lipid-lowering mechanisms. Causal effects were estimated using the inverse variance weighting (IVW) method, while the Summary Data-based Mendelian Randomization (SMR) method, leveraging pooled data, was applied to compute effect estimates. These estimates were further refined through various approaches including MR-Egger, the weighted median method, simple and weighted models, and leave-one-out analyses to conduct sensitivity analyses.ResultThe analytical outcomes utilizing the IVW method indicated that inhibitors of HMGCR were correlated with an elevated risk of developing gout (IVW: OR [95%CI] = 1.25 [1.03, 1.46], p=0.0436), while PCSK9 inhibitors were linked to heightened levels of urate (IVW: OR [95%CI] = 1.06 [1.01,1.10], p=0.0167). Conversely, no significant correlation between NPC1L1 inhibitors and the levels of urate or the risk of gout was established. Furthermore, the SMR analysis failed to identify significant associations between the expression levels of the HMGCR, PCSK9, and NPC1L1 genes and the risk of gout or elevated urate levels (SMR method: all P values &gt;0.05). Sensitivity analyses further confirmed the robustness of these results, with no significant heterogeneity or pleiotropy found.ConclusionThis study furnishes novel causal evidence supporting the potential genetic correlation between the use of lipid-lowering drugs and the incidence of gout as well as urate levels. The findings indicate that inhibitors targeting HMGCR may elevate the risk associated with the development of gout, while inhibitors targeting PCSK9 are likely to increase urate concentrations.
Increasing prevalence of thyroid autoimmunity in childhood type 1 diabetes in the pre-COVID but not during the COVID era
Authors: Herczeg Vivien , Muzslay Eszter , Czipó Diána , Terkovics Lili , Takács Johanna , Garai Réka , Kovács Fanni , Luczay Andrea , Körner Anna , Tóth-Heyn Péter 
Published: January 2025

IntroductionStudies assessing longitudinal changes in the prevalence of autoimmune thyroiditis (AIT) among the pediatric population are limited. During the COVID-19 era, several papers proposed a rise in AIT cases. Our study aimed to analyze the prevalence of thyroid autoimmunity (TA) over a 10-year period spanning pre-pandemic and pandemic years in a population who are regularly screened for thyroid disturbances.Materials and methodsThis single-center retrospective cohort study analyzed data from 1,361 children and young adults with type 1 diabetes (T1D) treated between 2013 and 2022 in Hungary’s largest pediatric endocrinology center. Results of anti-thyroid autoantibodies (anti-thyroid peroxidase/ATPO/and antithyroglobulin/ATG/), thyroid function tests (TFTs) and thyroid ultrasound examinations were obtained. Annual prevalence rates of TA and ultrasound-proven thyroiditis were calculated. Mean (± SD) follow-up period was 4.7 (± 2.8) years.ResultsThe overall prevalence of TA among our T1D children was 22.8% ([20.3;25.5], 310 cases) with significantly more girls affected (p&lt;0.001). From 2013 to 2022, TA prevalence rose from 15.9% to 20.6% (p=0.041). The increase was detected during the pre-pandemic years but not in the COVID-19 era. Ultrasound-confirmed thyroiditis was present in 80.0% of examined TA cases. Ultrasound positivity rate was stable during the study period. Among our children with TA, 28.5% exhibited clinically relevant thyroid-stimulating hormone (TSH) abnormalities (most commonly subclinical hypothyroidism) and/or were prescribed thyroid medication. Children with AIT had a significantly elevated risk of thyroid dysfunction compared to those with only thyroid autoantibody positivity (p&lt;0.001).ConclusionOur results show a rise in the prevalence of thyroid autoimmunity among T1D children over the past decade, but our data do not support the assumed role of SARS-CoV-2 in the development of the disease.
Association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio and serum thyroid function measures: Recent Findings from NHANES 2007–2012 and Mendelian randomization
Authors: Tan Mo-Yao , Zhang Ping , Wu Shan , Zhu Si-Xuan , Gao Ming 
Published: January 2025

ObjectiveThere is limited epidemiological data regarding the association of blood lipids with thyroid hormones. Thus, the present article aims to explore whether there is an association between non-high-density to high-density lipoprotein cholesterol ratio (NHHR) and thyroid hormones.MethodsWe analyzed samples from 3,881 adults aged 20 years and above who took part in the National Health and Nutrition Examination Survey (NHANES) spanning 2007 to 2012. The study tested for thyroid hormones, including total triiodothyronine (TT3), free triiodothyronine (FT3), total thyroxine (TT4), free thyroxine (FT4), as well as thyroid-stimulating hormone (TSH). Survey-weighted linear regression and restricted cubic spline (RCS) models were employed to investigate the relationship between NHHR and thyroid hormones. Subsequently, subgroup analyses were conducted. In Mendelian randomization (MR), the inverse variance weighting method (IVW) is used as the primary analytical approach.ResultsThis study finally comprised 3,881 adults aged 20 years and older. After extensive adjustments for covariables, the regression analysis revealed significant negative associations between NHHR and FT4 (β: -0.11, 95% confidence interval [CI]: -0.18, -0.04), FT4/FT3 (β: -0.06, 95% CI: -0.08, -0.04), and TT4/TT3 (β: -0.001, 95% CI: -0.001, 0.000). Both observational and Mendelian randomization studies suggest that high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total cholesterol may not significantly influence the risk of hyperthyroidism or hypothyroidism.ConclusionsThe study indicates negative associations between NHHR and FT4, as well as the ratios of FT4/FT3 and TT4/TT3. This suggests that NHHR may reflect changes in thyroid function, highlighting its potential clinical significance in assessing thyroid function and metabolic health.
Molecular testing stratifies the risk of structural recurrence in high risk differentiated thyroid cancer: a retrospective cohort study
Authors: Liu Jie , Gao Wensi , Zheng Xiong , Wu Shuping , Shi Yi , Wang Feng , Wu Yu 
Published: January 2025

BackgroundHigh-risk differentiated thyroid cancer in 2015 American Thyroid Association risk stratification system (ATA-RSS) exhibits a significantly increased probability of recurrence and poor outcomes. This study aimed to investigate the molecular profiles of high-risk differentiated thyroid cancer and to assess the role of molecular testing in enhancing prognostic risk stratification.MethodsIn a single-center study conducted at Fujian Cancer Hospital, Fujian Province, China, a consecutive cohort of differentiated thyroid cancer patients identified as high-risk under 2015 ATA-RSS criteria were retrospectively assessed, spanning from November 1, 2019, to March 31, 2022. Molecular characterize groups were conducted using an 18-gene next-generation sequencing assay. Patients harboring mutations in the TERT promoter, TP53, or PIK3CA genes were categorized as the high molecular risk group, while all others were assigned to the non-high molecular risk group.ResultsAmong the 108 cases, 32 (29.6%) fell into the high molecular risk group, characterized by a significantly older mean age (57.8 vs. 42.6 years, p &lt; 0.001), larger tumor size (3.1 cm vs. 2.0 cm, p = 0.003), a higher incidence of aggressive pathological subtypes (43.8% vs. 7.9%, p &lt; 0.001), and an increased occurrence of distant metastasis (34.4% vs. 7.9%, p = 0.001). Over a median follow-up period of 32.5 months, this high-risk group demonstrated an elevated risk of local recurrence (32.1% vs. 9.5%, HR: 3.18, 95% CI: 1.15-8.78) and metachronous distant metastasis (38.1% vs. 2.9%, HR: 12.54, 95% CI: 2.60-60.41). Multivariate COX regression analysis confirmed that molecular characterize groups (HR: 5.77, 95% CI: 2.18-15.23, p &lt; 0.001) and tumor size (HR: 1.32, 95% CI: 1.00-1.74, p = 0.047) independently predicted recurrence-free survival.ConclusionATA-RSS high-risk differentiated thyroid cancer often presents with late-hit genetic alterations, which are strongly associated with increased likelihood of structural recurrence. Molecular testing offers a precise approach to recurrence risk stratification in high-risk cases, enabling personalized follow-up and treatment strategies tailored to the specific prognostic profile.
Evaluation of nutrient loads conveyed to the deep subalpine lakes of Northern Italy through their main tributaries
Authors: Dezuanni Paolo , Copetti Diego , Dresti Claudia , Pella Nicolò , Buzzi Fabio , Fenocchi Andrea 
Published: January 2025

Nutrient pollution is a critical issue for lakes, leading to cultural eutrophication, which damages the ecosystem and prevents water uses. Proper watershed management practices must be put into action to effectively oppose eutrophication. Because of the complexities and the multiple layers of stakeholders involved in this process, the only factual way to evaluate improvements in watershed nutrient management is to directly estimate nutrient loads at watershed closing sections through available data from environmental monitoring. The Italian deep subalpine lakes (DSLs: Lake Como, Lake Garda, Lake Idro, Lake Iseo, Lake Maggiore) suffered from extensive eutrophication from the 1950s to the early 1980s. Their water quality improved in the 1980s and 1990s after national regulations were introduced to address nutrient pollution. After the turn of the century, increasingly pressing limits on nutrient disposal have been issued, yet steady if not worsening lake water quality conditions have been observed overall. To shed light on the issue, quantifying present and past external loads to these lakes based on direct measurements is essential. In this work, we focused on the main tributaries of the Italian DSLs, employing the observed time series of flowrate and nutrient concentrations to estimate the loading levels of nitrogen and phosphorus and their temporal evolution over a period ranging between 13 and 42 years according to data availability. The LOAD ESTimator (LOADEST) software was adopted to support the load quantification process. Results show that a general decrease in external nutrient loads is still occurring, albeit at a slow pace, the fastest reduction occurring for the Oglio River flowing into Lake Iseo, which has suffered from severe nutrient pollution till recently. Increasing loads have conversely been identified for the Sarca River flowing into Lake Garda. These outcomes highlight the beneficial actions carried out to reduce nutrient pollution, although a decorrelation analysis between external loads and flowrate is suggested for a clearer evaluation of its evolution across the DSLs.
Single-cell sequencing uncovers the mechanistic role of DAPK1 in glioma and its diagnostic and prognostic implications
Authors: Yu Tian-Hang , Ding Yan-Yu , Zhao Si-Guo , Zhao Jie-Hui , Gu Yu , Chen Dong-Hui , Zhang Fang , Hong Wen-Ming 
Published: January 2025

BackgroundWe conducted an investigation into the characteristics of single-cell differentiation data in gliomas, with a focus on developing DAPK1-based prognostic markers to predict patient outcomes. Dysregulated expression of DAPK1 has been associated with the invasive behavior of various malignancies, including gliomas. However, the precise role and underlying mechanisms of DAPK1 in gliomas remain inadequately understood.MethodsWe performed analyses on RNA-seq and microarray datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), in addition to single-cell RNA sequencing (scRNA-seq) data from glioma patients available in GEO. Utilizing the Seurat R package, we identified gene clusters associated with survival from the scRNA-seq data. Prognostic models were developed using LASSO and stepwise regression algorithms. Furthermore, we assessed the predictive potential of these genes within the immune microenvironment and their relevance in immunotherapy contexts.ResultsOur scRNA-seq data analysis revealed 32 distinct cell clusters corresponding to 10 cell types. Through dimensionality reduction and clustering, we identified three glial cell subpopulations based on their differentiation trajectories. DAPK1, serving as a marker gene for the terminal subpopulation, exhibited an association with poor prognosis.ConclusionsDAPK1-based prognostic models show promise for accurately predicting outcomes in glioblastoma and glioma. An in-depth examination of DAPK1’s specific mechanisms in glioblastoma could elucidate its role in immunotherapy response. Targeting the DAPK1 gene may offer therapeutic benefits for glioma patients.
Pan-cancer and experimental analyses reveal the immunotherapeutic significance of CST2 and its association with stomach adenocarcinoma proliferation and metastasis
Authors: Huang Dan , Li Jing , He Zhijun , Liang Wenjing , Zhong Likun , Huang Jun , Wu Yinteng , Zhao Shijian 
Published: January 2025

PurposeCystatin 2 (CST2) is a cysteine protease inhibitor, and recent research suggests its potential involvement in cancer development. However, its role in the occurrence, progression, and prognosis of pan-cancer has not been systematically investigated.Materials and methodsThis study comprehensively analyzes the differential expression of CST2 in pan-cancer. The expression distribution patterns of CST2 were examined using single-cell datasets. Furthermore, we conducted a comprehensive evaluation of the correlation between CST2 expression and various factors. These factors include prognosis, immune cell infiltration, immune-related genes, mutations, methylation, tumor mutation burden (TMB), and microsatellite instability (MSI). In addition, we analyzed the sensitivity of drugs dependent on CST2 expression. We utilized gene set enrichment analysis (GSEA) analysis to explore the biological functions of CST2 across different cancer types. Finally, in gastric cancer cell lines, we will investigate the impact of CST2 knockout on expression levels, clonal proliferation, cell apoptosis, and cell migration.ResultsCST2 exhibits abnormal overexpression in multiple tumors. Single-cell analysis reveals high expression of CST2 in fibroblasts. CST2 is closely associated with prognosis, immune cell infiltration, immune-related genes, mutations, methylation, TMB, and MSI. Enrichment analysis demonstrated a significant correlation between CST2 and immune-related pathways. In stomach adenocarcinoma (STAD), CST2-related risk models are associated with prognosis and demonstrate strong predictive capabilities, while also being closely linked to the immune microenvironment. Drug sensitivity analysis indicates the correlation between CST2 and 21 chemotherapy drugs. Finally, experimental validation revealed significantly elevated expression of CST2 in STAD, indicating its role as a driver gene in regulating malignant cell proliferation and migration.ConclusionCST2 serves as a potential tumor immune biomarker, playing a critical facilitating role in the proliferation and migration processes of STAD.
Efficacy of low-dose rituximab versus immunosuppressants in refractory orbital inflammatory pseudotumors with intracranial extension
Authors: Li Yuyu , Sun Mingming , Xu Xintong , Chen Biyue , Chen Xiyun , Wang Yuhang , Xu Quangang , Zhou Huanfen , Wei Shihui 
Published: January 2025

ObjectiveThe aim of this study was to compare the efficacy of low-dose rituximab (RTX) and immunosuppressants in treating orbital inflammatory pseudotumor (OIP) with intracranial extension, a refractory and high-relapse disease.MethodsPatients who had been diagnosed with refractory OIP with intracranial extension and who were refractory to systemic corticosteroids were retrospectively recruited at the Neuro-Ophthalmology Department at the Chinese People’s Liberation Army General Hospital between December 2018 and September 2022. After methylprednisolone pulse therapy, we added 2 mg of tacrolimus per day, 1500 mg of mycophenolate mofetil per day, or 200 mg of rituximab at days 1 and 15, and then monitored those with CD19+ B cells of under 1% as adjuvant therapy.ResultsEleven patients (six males and five females) were included, with a mean age of 45.5 ± 11.8 years (age range: 21–64 years). The average follow-up period was 3.8 years (range: 2–5). Eight patients (72.7%) had different levels of decreased vision at onset of the illness and four patients (36.4%) had severely impaired vision (three with no light perception, one with some light perception). Four patients (36.4%) showed clinical course worsening or lack of remission when treated with corticosteroids. Seven patients (63.6%) had a typical relapsing course, and the annual recurrence rate was higher than 7.36 ± 3.73 times. Of these seven, four (57.1%, 4/7) were able to undergo successful management with immunosuppressants. Three (42.9%, 3/7) failed with immunosuppressants but succeeded in controlling relapse with RTX.ConclusionOIP with intracranial extension is uncommon. More than half of patients with OIP with intracranial extension may be satisfactorily treated with corticosteroids combined with immunosuppressants. However, for patients who still experience recurrence or slow reduction of lesions after applying this combined therapy, RTX may be a better option.
Studies on the alleviating effect of Bifidobacterium lactis V9 on dextran sodium sulfate-induced colitis in mice
Authors: Duan Xiaoyan , Wu Rilige , Li Jianbo , Li Zeya , Liu Yanqi , Chen Ping , Wang Bangmao 
Published: January 2025

BackgroundInflammatory bowel disease (IBD) has become a global public health problem with complex pathogenesis and limited therapeutic options. We aimed to investigate the potential mechanisms by which Bifidobacterium lactis V9 (V9) alleviated colitis in a dextran sodium sulfate-induced colitis model mice.MethodsMice were induced to develop colitis by drinking DSS solution to induce colitis. The expression of the relevant factors in the blood supernatant of the mice was determined by ELISA. RT-qPCR and Western blotting were used to detect mRNA and protein expression of target genes. The fecal microbiota was analyzed by 16S rRNA sequencing. Intestinal metabolites were analyzed by untargeted metabolomics;ResultsV9 effectively improved the overall symptoms of the colitis model mice. H&amp;E showed that V9 re-stored the intestinal tissue structure. ELISA showed that V9 decreased the levels of IL-6, IL-22, and TNF-α and increased IL-10, SP, VIP, and 5-HT. V9 increased the expression of AHR, CYP1A1, MUC2, Claudin-3, Occludin, and ZO-1, and decreased 5-hydroxytryptamine transporter and Claudin-2. V9 increased the abundance of gut microbiota in colitis mice to promote the growth of beneficial bacteria. V9 increased tryptophan metabolites, and short-chain fatty acids, and improved gut inflammation.ConclusionV9 attenuates intestinal inflammation, improves the mucosal barrier, modulates intestinal microecology and exerts a protective effect in a mouse model of DSS-induced colitis.
Isolation, characterization and liposome-loaded encapsulation of a novel virulent Salmonella phage vB-SeS-01
Authors: Luo Yuhang , Mahillon Jacques , Sun Lin , You Ziqiong , Hu Xiaomin 
Published: January 2025

IntroductionSalmonella is a common foodborne pathogenic bacterium, displaying facultative intracellular parasitic behavior, which can help the escape against antibiotics treatment. Bacteriophages have the potential to control both intracellular and facultative intracellular bacteria and can be developed as antibiotic alternatives.MethodsThis study isolated and characterized vB-SeS-01, a novel Guernseyvirinae phage preying on Salmonella enterica, whose genome is closely related to those of phages SHWT1 and vB-SenS-EnJE1. Furthermore, nine phage-carrying liposome formulations were developed by film hydration method and via liposome extruder.Results and DiscussionPhage vB-SeS-01 displays strong lysis ability against 9 out of 24 tested S. enterica strains (including the pathogenic “Sendai” and “Enteritidis” serovars), high replicability with a burst size of 111 ± 15 PFU/ cell and a titre up to 2.1 × 1011 PFU/mL, and broad pH (4.0 ~ 13.0) and temperature (4 ~ 80°C) stabilities. Among the nine vB-SeS-01 liposome-carrying formulations, the one encapsulated with PC:Chol:T80:SA = 9:1:2:0.5 without sonication displayed the optimal features. This formulation carried up to 1011 PFU/mL, with an encapsulation rate of 80%, an average size of 172.8 nm, and a polydispersity index (PDI) of 0.087. It remained stable at 4°C and 23°C for at least 21 days and at 37°C for 7 days. Both vB-SeS-01 and vB-SeS-01-loaded liposomes displayed intracellular antimicrobial effects and could reduce the transcription level of some tested intracellular inflammatory factors caused by the infected S. enterica sv. Sendai 16,226 and Enteritidis 50041CMCC.
Unveiling early-life microbial colonization profile through characterizing low-biomass maternal-infant microbiomes by 2bRAD-M
Authors: Hou Shuwen , Jiang Yuesong , Zhang Feng , Cheng Tianfan , Zhao Dan , Yao Jilong , Wen Ping , Jin Lijian , Huang Shi 
Published: January 2025

IntroductionThe microbial composition of human breast milk and infant meconium offers critical insights into the early microbial colonization profile, and it greatly contributes to the infant’s immune system and long-term health outcomes. However, analyzing these samples often faces technical challenges and limitations of low-resolution using conventional approaches due to their low microbial biomass.MethodsHere, we employed the type IIB restriction enzymes site-associated DNA sequencing for microbiome (2bRAD-M) as a reduced metagenomics method to address these issues and profile species-level microbial composition. We collected breast milk samples, maternal feces, and infant meconium, comparing the results from 2bRAD-M with those from both commonly used 16S rRNA amplicon sequencing and the gold-standard whole metagenomics sequencing (WMS).ResultsThe accuracy and robustness of 2bRAD-M were demonstrated through its consistently high correlation of microbial individual abundance and low whole-community-level distance with the paired WMS samples. Moreover, 2bRAD-M enabled us to identify clinical variables associated with infant microbiota variations and significant changes in microbial diversity across different lactation stages of breast milk.DiscussionThis study underscores the importance of employing 2bRAD-M in future large-scale and longitudinal studies on maternal and infant microbiomes, thereby enhancing our understanding of microbial colonization in early life stages and demonstrating further translational potential.