bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations of maternal PM2.5 exposure with preterm birth and miscarriage in women undergoing in vitro fertilization: a retrospective cohort study
Authors: Chen Miaoxin , Chen Qiaoyu , Liao Gengze , Sun Chunyan , Liu Cong , Meng Xia , Li Wentao , Qiu Andong , Bukulmez Orhan , Kan Haidong , Wang Feng , Tse Lap Ah , Teng Xiaoming 
Published: January 2025

BackgroundExcessive exposure to PM2.5 can be detrimental to reproductive health. The objective of this study was to investigate the potential associations between ambient PM2.5 exposure during different periods and negative pregnancy outcomes, such as miscarriage and preterm birth, in patients who underwent assisted reproductive technology (ART).MethodsThis retrospective cohort study examined the outcomes of 2,839 infertile women aged ≤ 45 years who underwent their first fresh or frozen-thawed embryo transfer at the Shanghai First Maternity and Infant Hospital between April 2016 and December 2019. Satellite data were used to determine the daily average levels of PM2.5, and exposure was categorized as excessive if it exceeded the WHO’s interim target 2 level of 50 µg/m3. The analysis was conducted separately for seven different periods. Our study used multinomial logistic regression models to explore the potential associations between PM2.5 exposure and adverse pregnancy outcomes. Sensitivity analysis was conducted by excluding women who underwent blastocyst transfer.ResultsDaily PM2.5 exposure exceeding the threshold (50 µg/m3) was associated with an increased risk of miscarriage during the period after confirmation of clinical pregnancy or biochemical pregnancy, with adjusted odds ratios (AORs) of 2.22 (95% CI 1.75-2.81) and 2.23 (95% CI 1.68-2.96), respectively. Moreover, for each increase of 10 µg/m3 above the threshold for PM2.5, there was a 46% elevated risk of preterm birth (AOR = 1.46, 95% CI 1.09-1.94) during the period after the confirmation of clinical pregnancy and a 61% elevated risk of preterm birth (AOR = 1.61, 95% CI 1.16-2.23) during the period after the confirmation of biochemical pregnancy. Our stratified analyses revealed that women with an endometrial thickness &lt;11 mm or who underwent frozen embryo transfer were more vulnerable to PM2.5 exposure, leading to higher rates of preterm birth.ConclusionExcessive PM2.5 exposure after biochemical pregnancy or clinical pregnancy was associated with increased risks of preterm birth and miscarriage among women who underwent ART.
Relationship between triglyceride glucose-body mass index baselines and variation with future cardiovascular diseases risk in the middle-aged and elderly individuals
Authors: Qiao Junpeng , Chen Xueyu , Pang Jinhong , Fei Haicheng , Liu Zhang , Cheng Fang , Chen Qiaoqiao , Zhao Yingying , Shi Fengxue , Jia Hongying , Chi Weiwei 
Published: January 2025

BackgroundCardiovascular diseases (CVDs) are gradually becoming the leading cause of morbidity and mortality among chronic non-communicable diseases. Previous studies have found that the TyG index is an effective alternative indicator for insulin resistance (IR) and is associated with cardiovascular events. Additionally, obesity directly or indirectly increases the risk of developing CVDs. Up to now, studies on the combined effects of these factors are insufficient, and the conclusions are not yet consistent. This study aims to analyze whether the baseline levels and fluctuations of triglyceride glucose-body mass index (TyG-BMI) are associated with the incidence of CVDs and their subtypes in a prospective cohort of middle-aged and elderly individuals.MethodsThe data for this study were obtained from the China Health and Retirement Longitudinal Study (CHARLS), which is an ongoing nationally representative prospective cohort study. After excluding participants with partially missing variables that could affect the study results, this study ultimately included 7,072 participants, with data records spanning from 2011 to 2020. The exposures were TyG-BMI and the change in TyG-BMI from 2011 to 2015. The TyG-BMI index was calculated as TyG index multiply BMI. The change of TyG-BMI was categorized using K-means clustering and baseline TyG-BMI was grouped based on quartiles. We used Cox proportional hazards models to evaluate the relationship between baseline quartiles of the TyG-BMI index and its variability with CVDs and their subtypes.ResultsAmong the 7,072 participants (mean age of 59.1 ± 9.3 years), 3330 (47%) were male. During an average follow-up of 7.1 years, 1,774 (25.1%) participants developed new-onset cardiovascular diseases. After stratification by baseline TyG-BMI quartiles, higher TyG-BMI levels were associated with an increased risk of CVDs, The hazard ratio (HR) and 95% confidence interval (95% CI) for the highest quartile group were 1.69 (1.44-2.00). After adjusting for potential confounding factors, compared to participants with consistently low TyG-BMI levels, those with moderate TyG-BMI levels and a slowly increasing trend had an HR of 1.27 (95% CI 1.10-1.47), while those with the highest TyG-BMI levels and a slowly decreasing trend had an HR of 1.52 (95% CI 1.26-1.83).ConclusionMaterial changes in the TyG-BMI are independently associated with the risk of CVDs in middle-aged and elderly individuals. Detecting long-term changes in the TyG-BMI may aid in the early identification of high-risk individuals and help prevent the occurrence of various cardiovascular diseases.
Plasma IL-17A is increased in patients with critical MIS-C and associated to in-hospital mortality
Authors: de Farias Emmerson C. F. , Nascimento Luciana M. P. P. do , Pavão Junior Manoel J. C. , Pavão Dalila C. A. , Pinheiro Ana P. S. , Pinheiro Andreza H. O. , Alves Marília C. B. , Ferraro Kíssila M. M. M. , Aires Larisse F. Q. , Dias Luana G. , Machado Mayara M. M. , Serrão Michaelle J. D. , Gomes Raphaella R. , de Moraes Sara M. P. , Pontes Gabriela C. L. , Carvalho Railana D. F. P. , Silva Cristiane T. C. , Neves Carla M. A. das , Santos Joyce C. L. dos , de Sousa Adriana M. B. , da Silva Leda L. , de Mello Mary L. F. M. F. , Carvalho Patricia B. , Braga Renata de B. , Harada Kathia de O. , Justino Maria C. A. , Costa Iran B. , Brasil-Costa Igor , Monteiro Marta C. , Clemente Gleice , Terreri Maria Teresa 
Published: January 2025

BackgroundMultisystem inflammatory syndrome in children (MIS-C) is a rare and severe post-COVID-19 complication with multiple phenotypes.ObjectivesThe aim of this study is to study inflammatory biomarkers (cytokines and oxidative stress) in critical MIS-C patients and to observe if there is association between these biomarkers and mortality.MethodsA single-center prospective study enrolled patients with MIS-C (with positive molecular test), aged between 1 month and 18 years of age. Data was collected from 20 pediatric intensive care unit (PICU)’s bed. Inflammatory biomarkers (cytokines and oxidative stress markers) were performed on day 1 and 3 after hospitalization. Survival rate was calculated, and Kaplan-Meier curves were plotted. Univariate and multivariate Cox regression analyses were conducted. The ROC (Receiver Operating Characteristic) curve analysis was performed.Results and conclusionsA total of 41 patients out of 109 patients admitted at PICU with suspected MIS-C during the study period were included, of which 33 (80.5%) were male, 9 (22%) were under one year old, and 30 (73.2%) presented comorbidities. Among them, 16 (39%) did not survive. The mean survival time was shorter in patients with higher levels of IL-17A (≥ 19.71 pg/mL) on day 1 (115 vs 323 days, p = 0.004). Higher levels of IL-17A on day 1 were associated with mortality in both the crude model (HR 1.03, CI95% 1.004-1.057, p = 0.022) and the adjusted model (HR 1.043, CI95% 1.013-1.075, p = 0.012). ROC analysis revealed a cut-off value for the IL-17A of 14.32 pg/ml. The other immunological and inflammatory markers did not demonstrate an association with survival (p&gt;0.05). Our findings suggest that patients with high levels of IL-17A are at greater risk for death.
Antiviral therapy can effectively suppress irAEs in HBV positive hepatocellular carcinoma treated with ICIs: validation based on multi machine learning
Authors: Pan Shuxian , Wang Zibing 
Published: January 2025

BackgroundImmune checkpoint inhibitors have proven efficacy against hepatitis B-virus positive hepatocellular. However, Immunotherapy-related adverse reactions are still a major challenge faced by tumor immunotherapy, so it is urgent to establish new methods to effectively predict immunotherapy-related adverse reactions.ObjectiveMulti-machine learning model were constructed to screen the risk factors for irAEs in ICIs for the treatment of HBV-related hepatocellular and build a prediction model for the occurrence of clinical IRAEs.MethodsData from 274 hepatitis B virus positive tumor patients who received PD-1 or/and CTLA4 inhibitor treatment and had immune cell detection results were collected from Henan Cancer Hospital for retrospective analysis. Models were established using Lasso, RSF (RandomForest), and xgBoost, with ten-fold cross-validation and resampling methods used to ensure model reliability. The impact of influencing factors on irAEs (immune-related adverse events) was validated using Decision Curve Analysis (DCA). Both uni/multivariable analysis were accomplished by Chi-square/Fisher’s exact tests. The accuracy of the model is verified in the DCA curve.ResultsA total of 274 HBV-related liver cancer patients were enrolled in the study. Predictive models were constructed using three machine learning algorithms to analyze and statistically evaluate clinical characteristics, including immune cell data. The accuracy of the Lasso regression model was 0.864, XGBoost achieved 0.903, and RandomForest reached 0.961. Resampling internal validation revealed that RandomForest had the highest recall rate (AUC = 0.892). Based on machine learning-selected indicators, antiviral therapy and The HBV DNA copy number showed a significant correlation with both the occurrence and severity of irAEs. Antiviral therapy notably reduced the incidence of IRAEs and may modulate these events through regulation of B cells. The DCA model also demonstrated strong predictive performance. Effective control of viral load through antiviral therapy significantly mitigates the occurrence of irAEs.ConclusionICIs show therapeutic potential in the treatment of HBV-HCC. Following antiviral therapy, the incidence of severe irAEs decreases. Even in cases where viral load control is incomplete, continuous antiviral treatment can still mitigate the occurrence of irAEs.
Impact of chemoradiotherapy for first primary lung cancer on the prognosis and re-chemoradiotherapy sensitivity of second primary lung cancer
Authors: Chen Zhe , Wang Gaoming , Wang Nan , Liu Jiangjiang , Yao Yu , Ma Haitao , Luo Jing , Xie Kai 
Published: January 2025

BackgroundDespite undergoing surgery and chemoradiotherapy, patients with first primary lung cancer (FPLC) remain at risk for second primary lung cancer (SPLC), which is associated with a poor prognosis. The effects of FPLC chemoradiotherapy on SPLC prognosis and its sensitivity to re-chemoradiotherapy have not been adequately investigated.MethodsThis cohort study analyzed data from 23,827 patients who underwent FPLC surgery during 1973–2021, drawn from the Surveillance, Epidemiology, and End Results database. Among these, 5,302 FPLC patients developed SPLC within 5 years of their initial diagnosis. We employed the Fine-Gray competitive risk model, Cox proportional hazards model, and restricted mean survival time analysis to assess the effects of FPLC radiotherapy and chemotherapy on SPLC risk and survival differences.ResultsThe competitive risk model indicated that FPLC radiotherapy and chemotherapy did not significantly change the risk of developing SPLC. However, the Cox proportional hazards model revealed that FPLC radiotherapy was associated with decreased overall survival (OS; HR=1.251, P&lt;0.001) and cancer-specific survival (CSS; HR=1.228, P=0.001) in patients with SPLC. Conversely, FPLC chemotherapy was linked to improved OS (HR=0.881, P=0.012) in this population. Patients with SPLC who received combined chemoradiotherapy for FPLC exhibited significantly reduced survival times (OS: HR=1.157, P=0.030; CSS: HR=1.198, P=0.018), a finding confirmed across multiple models. For SPLC patients with prior FPLC chemoradiotherapy, subsequent SPLC radiotherapy significantly improved prognosis. Notably, this benefit is even more pronounced in patients who have not received prior chemoradiotherapy. While SPLC chemotherapy enhanced OS for patients who did not receive FPLC chemotherapy, it was associated with reduced CSS for those who had.ConclusionsOverall, FPLC chemoradiotherapy influences SPLC prognosis and influences sensitivity to treatment. Tailoring SPLC management to FPLC treatment regimens may improve survival outcomes.
Establishment of a prognostic signature and immune infiltration characteristics for uterine corpus endometrial carcinoma based on a disulfidptosis/ferroptosis-associated signature
Authors: Huang Yong , Li Huibin , Wei Zhifu , He Wanshan , Chen Bin , Cheng Shuang , Zhao Zhifang , Deng Lv , Chen Xiaohua , Lin Yu , Hong Xiaoshan 
Published: January 2025

BackgroundDisulfidptosis and ferroptosis are two different programmed cell death pathways, and their potential therapeutic targets have important clinical prospects. Although there is an association between the two, the role of genes associated with these two forms of cell death in the development of endometrial cancer remains unclear.MethodsIn this study, RNA sequencing (RNA-seq) and clinical data were obtained from public databases, and comprehensive analysis methods, including difference analysis, univariate Cox regression, and Least Absolute Shrinkage and Selection Operator (LASSO) analysis were used to construct a disulfidptosis/ferroptosis-related genes (DFRGs) prognostic signature. To further explore this new feature, pathway and functional analyses were performed, and the differences in gene mutation frequency and the level of immune cell infiltration between the high- and low-risk groups were studied. Finally, we validated the prognostic gene expression profile in clinical samples.ResultsWe identified five optimal DFRGs that were differentially expressed and associated with the prognosis of uterine corpus endometrial carcinoma (UCEC). These genes include CDKN2A, FZD7, LCN2, ACTN4, and MYH10. Based on these DFRGs, we constructed a robust prognostic model with significantly lower overall survival in the high-risk group than in the low-risk group, with differences in tumor burden and immune invasion between the different risk groups. The expression of two key genes, ACTN4 and LCN2, was verified by immunohistochemistry and RT-qPCR.ConclusionThis study established a clinical prognostic model associated with disulfidptosis/ferroptosis-related genes, and the expression characteristics of key genes were validated in clinical samples. The comprehensive assessment of disulfidptosis and ferroptosis provides new insights to further guide patient clinical management and personalized treatment.
Neoadjuvant immunotherapy for DNA mismatch repair proficient/microsatellite stable non-metastatic rectal cancer: a systematic review and meta-analysis
Authors: Zhang Huan , Huang Jing , Xu Huanji , Yin Nanhao , Zhou Liyan , Xue Jianxin , Ren Min 
Published: January 2025

BackgroundNeoadjuvant immunotherapy (NIT) has been endorsed by clinical guidelines for the management of DNA mismatch repair deficiency/microsatellite instability-high (dMMR/MSI-H) locally advanced rectal cancer (LARC). Nonetheless, the therapeutic efficacy of NIT in mismatch repair-proficient/microsatellite stable (pMMR/MSS) non-metastatic rectal cancer (RC) remain pending matters. Therefore, a meta-analysis was carried out to assess the efficacy and safety of NIT in patients with non-metastatic pMMR/MSS RC.MethodsPubMed, Embase, Web of Science, the Cochrane Library, ClinicalTrials.gov, ASCO and ESMO were searched to obtain related studies up to July 2024. Two reviewers independently screened the included articles and extracted the pertinent data. The risk of publication bias was assessed by Begg or Egger tests and in cases of publication bias, the trim and fill method was applied. Heterogeneity was assessed using I 2 statistics.ResultsThirteen articles including 582 eligible patients were analyzed. The pooled pCR, MPR, cCR and anus preservation rate were 37%, 57%, 26% and 77% separately and the incidence of irAEs≥3 grades and TRAEs≥3 grades were 3% and 29%, respectively. Non-metastatic pMMR/MSS RC receiving the short-course radiotherapy (SCRT) in neoadjuvant setting exhibited superior pooled pCR and MPR than long-course radiotherapy (LCRT) without upregulating the incidence of adverse effects. Furthermore, patients with MSS RC underwent neoadjuvant treatment with anti-PD-1 inhibitors demonstrated higher pooled pCR, MPR, cCR compared to those receiving PD-L1 inhibitors. Additionally, yielded improved pooled MPR and anal preservation rates compared to sequential immuno-radiotherapy (63.4% vs 51.2% and 88.5% vs 69.9%), without raising the incidence of irAEs≥3 grade. Interestingly, RC patients with lymph node metastasis showed a higher pooled pCR than those without lymph node metastasis (43% vs 35%).ConclusionNIT was linked to favorable response rates and anal preservation, alongside an acceptable safety profile. Non-metastatic pMMR/MSS RC patients receiving SCRT, PD-1 inhibitors, or concurrent immuno-radiotherapy in the neoadjuvant setting exhibited enhanced outcomes. This meta-analysis provides evidence for further exploration and application of NIT in non-metastatic pMMR/MSS RC and highlights the potential for organ preservation with this approach. The relatively small sample size and the uneven quality of included studies may have had some impact on the generality of the results. Therefore, further analysis with a higher number of high-quality studies is needed to verify the conclusions.Systematic review registrationhttps://inplasy.com/, identifier: INPLASY202470110.
Low dose ATG-Fresenius for GVHD prophylaxis: a comparative study with ATG-Thymoglobulin
Authors: Falicovich Itai , Nachmias Boaz , Elias Shlomo , Zimran Eran , Shaulov Adir , Stepensky Polina , Avni Batia , Grisariu Sigal 
Published: January 2025

BackgroundAnti-Thymocyte Globulin (ATG) is commonly used to prevent graft-versus-host disease (GVHD), but the optimal dosage and type of ATG remains to be determined.ObjectiveWe compared retrospectively the safety and efficacy outcomes of allogeneic transplantation using low-dose ATG-Fresenius (15mg/kg) and ATG-Thymoglobulin (10mg/kg) for GVHD prevention.Study designNinety-eight patients were included, with 46 in the ATG-T group and 52 in the ATG-F group. The median age was 48 years in the ATG-T group (range 20-71) and 50 years in the ATG-F group (range 18-73). Baseline characteristics were similar, with slightly more HLA mismatched donors and single-agent cyclosporine GVHD prophylaxis use in the ATG-T group. Additionally, the ATG-F group had more myeloid leukemia and myelodysplastic syndrome patients, while the ATG-T group had more lymphoma patients.ResultsThe cumulative incidence of acute GVHD (aGVHD) grade II-IV and chronic GVHD (cGVHD) showed no significant differences. Multivariate analysis indicated that donor HLA mismatch influenced aGVHD risk significantly (p=0.005), and myeloablative conditioning increased cGVHD risk. Bacteremia and CMV reactivation rates were similar, but EBV DNA viremia was higher in the ATG-T group (22% vs. 8%, p=0.047), with one case of Post-Transplant Lymphoproliferative Disorder (PTLD) in the ATG-T group. Cumulative incidence of overall survival (OS), relapse incidence, non-relapse mortality (NRM) and GVHD free, Relapse free Survival (GRFS) did not significantly differ.ConclusionsThis study highlights the safety and efficacy of low-dose ATG-F compared to a relatively high dose ATG-T. Prospective studies are necessary to validate the safety and efficacy of low dose ATG-F for GVHD prevention.
Unveiling immunogenic characteristics and neoantigens in endometrial cancer with POLE hotspot mutations for improved immunotherapy
Authors: Huang Jian , Song Shuangna , Yin Yihua , He Yinyan , Wang Huimin , Gu Ye , He Laman , Wang Xintao , Miao Xiaocao , Zhang Zhigang , Zhang Xueli , Li Yiran 
Published: January 2025

BackgroundImmunotherapy, especially with the use of immune checkpoint inhibitors, has demonstrated efficacy for a variety of malignant tumors. However, the potential of immunotherapy for endometrial cancer (EC) with POLE mutations remains underexplored.MethodsWe utilized multiple databases and clinical specimens to investigate the immunogenicity profiles of EC patients carrying POLE mutations. One particular hotspot mutation POLEP286R was identified and further studied. Consequently, by constructing human leukocyte antigen (HLA) tetramers and incubating them with patients’ peripheral blood mononuclear cells (PBMCs), T cells capable of recognizing the POLEP286R mutation were sorted for further transcriptomic, proteomic and T-cell receptor (TCR) sequencing analyses and for an organoid EC model.ResultsTumor- and immune-related pathways were shown to be activated in the POLEP286R mutant group. Importantly, by using an organoid model of EC, we further confirmed the antitumor potential of T cells that were specific to the POLEP286R mutation.ConclusionsOur study uncovers the pronounced immunogenicity of POLE-mutant EC and characterizes neoantigens that are unique to the POLEP286R mutation, thus providing a promising new immunotherapeutic strategy for EC.
Liposomal encapsulation of cholecalciferol mitigates in vivo toxicity and delays tumor growth
Authors: Ezcurra-Hualde Miriam , Zalba Sara , Bella Ángela , Arrizabalaga Leire , Risson Aline , García-Fuentes Román , Gomar Celia , Ardaiz Nuria , Belsue Virginia , Ruiz-Guillamon David , Serrano-Alcaide Alejandro , Salgado Ainara , Aranda Fernando , Garrido Maria J. , Berraondo Pedro 
Published: January 2025

IntroductionVitamin D3 (cholecalciferol) has demonstrated potential anticancer properties, but its clinical application is limited by associated toxicity at effective doses. This study investigated the use of liposomal encapsulation to increase the therapeutic efficacy of vitamin D3 while mitigating its toxicity.MethodsLiposomal vitamin D3 (VD-LP) was prepared via the film-hydration method and characterized for particle size, polydispersity index, encapsulation efficiency, and long-term stability. In vitro gene expression modulation was evaluated in monocytic THP-1 cells, and antiproliferative effects were assessed in HT29 (colorectal), BT474 (breast), and TRAMP-C1 (prostate) cancer cell lines. In vivo antitumor efficacy and toxicity were tested in a mouse model with subcutaneously implanted MC38 tumors. Tumor growth, survival rates, and serum calcium and phosphate levels were analyzed.ResultsVD-LP demonstrated high encapsulation efficiency and stability over 90 days, with a consistent particle size of approximately 83 nm. VD-LP modulated immune-related and metabolic gene expression in THP-1 cells, including upregulation of antimicrobial peptides and vitamin D receptor genes. VD-LP showed superior antiproliferative effects compared to free vitamin D3 in all tested cancer cell lines. In vivo, VD-LP delayed tumor growth and improved survival without causing hypercalcemia, highlighting its favorable toxicity profile.DiscussionLiposomal encapsulation of vitamin D3 significantly improves its anticancer efficacy while mitigating toxicity, making it a promising strategy for future cancer therapies. VD-LP shows potential for enhanced therapeutic applications with reduced adverse effects, warranting further clinical exploration.