bluuebunny/crossref_metadata_2025_split huggingface dataset:
AGD1/USP10/METTL13 complexes enhance cancer stem cells proliferation and diminish the therapeutic effect of docetaxel via CD44 m6A modification in castration resistant prostate cancer
Authors: Wang Hong , Cui Chunli , Li Weiyi , Wu Hui , Sha Jianjun , Pan Jiahua , Xue Wei 
Published: January 2025

Abstract

Background
Most patients with prostate cancer inevitably progress to castration-resistant prostate cancer (CRPC), at which stage chemotherapeutics like docetaxel become the first-line treatment. However, chemotherapy resistance typically develops after an initial period of therapeutic efficacy. Increasing evidence indicates that cancer stem cells confer chemotherapy resistance via exosomes. This study demonstrated that AGD1, derived from prostate cancer stem cells (PCSCs), enhanced the stemness of prostate cancer cells and reduced the therapeutic effect of docetaxel in CRPC.

Methods
Quantitative real-time PCR (qPCR) was employed to determine the expression levels of AGD1 and METTL13 mRNAs in PCSCs and exosomes. Protein expression levels were examined using western blots and dot blots. The potential functions of AGD1 and METTL13 in CRPC were investigated through cell proliferation assay, Transwell assay, EdU incorporation assays, Annexin V-FITC/PI staining, and sphere formation assays. To uncover the underlying mechanisms of AGD1, RNA pull-down assay, RIP, co-Immunoprecipitation (co-IP), mass spectrometry (MS), Methylated RNA immunoprecipitation (MeRIP) and single-base elongation and ligation-based qPCR amplification method (SELECT) were performed. The effects of AGD1 and METTL13 on CRPC development and metastasis under docetaxel treatment were analyzed using a xenograft mouse model and an organoid model. Additionally, liposomal-chitosan nanocomplex drug delivery systems were designed to explore AGD1’s role in regulating docetaxel treatment resistance in CRPC.

Results
AGD1 expression was upregulated in PCSCs and exosomes. Downregulating AGD1 enhanced the sensitivity of CRPC to docetaxel treatment by inhibiting their stemness, with the reverse also being true. RNA pull-down, combined with MS, co-IP and RIP assays, demonstrated that AGD1 binds to METTL13 and USP10, forming a complex that facilitates METTL13 protein accumulation through USP10-induced deubiquitination. MeRIP assay and SELECT assay revealed that METTL13 transcriptionally controls the mRNA decay of CD44 via m6A methylation. Additionally, this process activates the pSTAT3/PI3K-AKT signaling pathway. Organoid models and liposomal-chitosan nanocomplex drug delivery systems showed that reducing AGD1 expression enhanced the therapeutic effect of docetaxel in CRPC.

Conclusions
AGD1 mediates the stemness and apoptosis of PCSCs and promotes docetaxel treatment resistance by enhancing tumor growth and metastasis through USP10/METTL13-mediated CD44 mRNA decay in CRPC.
The prognostic value of systemic immune-inflammation index in patients with unresectable hepatocellular carcinoma treated with immune-based therapy
Authors: He Tian , Xu Bin , Wang Lu-Na , Wang Zi-Yi , Shi Huan-Chen , Zhong Cheng-Jie , Zhu Xiao-Dong , Shen Ying-Hao , Zhou Jian , Fan Jia , Sun Hui-Chuan , Hu Bo , Huang Cheng 
Published: January 2025

Abstract

Background
Predicting the efficacy of immune-based therapy in patients with unresectable hepatocellular carcinoma (HCC) remains a clinical challenge. This study aims to evaluate the prognostic value of the systemic immune-inflammation index (SII) in forecasting treatment response and survival outcomes for HCC patients undergoing immune-based therapy.

Methods
We analyzed a cohort of 268 HCC patients treated with immune-based therapy from January 2019 to March 2023. A training cohort of 93 patients received atezolizumab plus bevacizumab (T + A), while a validation cohort of 175 patients underwent treatment with tyrosine kinase inhibitors (TKIs) combined with anti-PD-(L)1 therapy. The SII cutoff value, determined using X-tile analysis based on overall survival (OS) in the training cohort, divided patients into high (> 752*109) and low (≤ 752*109) SII groups. Prognostic factors were identified through univariate and multivariate logistic and Cox regression analyses, and survival outcomes were assessed using Kaplan–Meier methods. The predictive accuracy of SII was evaluated using receiver operating characteristic (ROC) curves.

Results
An optimal SII cutoff of 752*109 stratified patients into high and low SII groups. Univariate and multivariate logistic regression indicated that SII was a significant predictor of the objective response rate (ORR), which was markedly different between the low and high SII subgroups (34.72% vs. 9.52%, P = 0.019). This finding was consistent in the validation cohort (34.09% vs. 16.28%, P = 0.026). SII also demonstrated prognostic value in Cox regression and Kaplan–Meier analyses. ROC curves confirmed that SII had superior predictive accuracy compared to common clinical indicators, with predictive relevance even in AFP-negative patients. Furthermore, a lower SII was associated with a higher T cell ratio and an increased number of CD8+ T cells and Granzyme B+ CD8+ T cells in peripheral blood.

Conclusion
SII is a promising predictor of both therapeutic efficacy and prognosis in HCC patients undergoing immune-based treatments. Its application may enhance clinical decision-making, thereby improving patient outcomes from immune-based therapy.
Effects on impulsivity and delay discounting of intermittent theta burst stimulation add-on to dialectical behavioral therapy in borderline personality disorder: a randomized, sham-controlled pilot trial
Authors: Kujovic Milenko , Bahr Christian , Riesbeck Mathias , Benz Daniel , Deiß Martina , Margittai Zsofia , Henges Sebastian , Reinermann Dirk , Plewnia Christian , Meisenzahl Eva 
Published: January 2025

Abstract

Background
Dialectical behavioral therapy (DBT) and repetitive transcranial magnetic stimulation (rTMS) are both effective in treating borderline personality disorder (BPD). Impulsivity and impaired decision-making are prominent features of BPD, and therapeutic interventions targeting these symptoms could lead to significant improvements.

Objective/Hypothesis
We hypothesized that intermittent theta burst stimulation (iTBS), a modified rTMS protocol that targets the left dorsolateral prefrontal cortex, would enhance the therapeutic effects of DBT, leading to greater improvements in impulsivity and decision-making compared with sham stimulation.

Methods
We performed a single-blind, randomized, sham-controlled pilot study to evaluate the efficacy of iTBS as an add-on to an 8-week DBT program for BPD in a routine inpatient setting. A total of 53 BPD patients were randomly assigned to receive either iTBS (n = 25) or sham stimulation (n = 28) during weeks 4 to 8 of DBT, and 36 patients met the inclusion criteria for the present analysis (≥ 16 of 20 iTBS/sham sessions and assessment of delay discounting). The study endpoints were the Barratt Impulsiveness Scale-15 for impulsivity and the Monetary Choice Questionnaire for decision-making/delay discounting.

Results
A mixed model repeated measures analysis with a 2 × 2 factorial between-subjects design showed a significant overall improvement over time in impulsivity but not in decision-making/delay discounting. No significant differences were found between iTBS and sham, although post hoc tests revealed significant changes in impulsivity in the iTBS group (meandiff = -4.7, p = .001, Cohen’s d = 0.68) but not in the sham group (meandiff = -2.1, p = .077, d = 0.31).

Conclusions
iTBS may offer long-term benefits as an add-on treatment to DBT for impulsivity in BPD, suggesting the need for further investigation in larger-scale studies.

Trial registration
Registered at drks.de (no. DRKS00020413) on January 13, 2020.
A systematic review of AI-enhanced techniques in credit card fraud detection
Authors: Hafez Ibrahim Y. , Hafez Ahmed Y. , Saleh Ahmed , Abd El-Mageed Amr A. , Abohany Amr A. 
Published: January 2025

Abstract
The rapid increase of fraud attacks on banking systems, financial institutions, and even credit card holders demonstrate the high demand for enhanced fraud detection (FD) systems for these attacks. This paper provides a systematic review of enhanced techniques using Artificial Intelligence (AI), machine learning (ML), deep learning (DL), and meta-heuristic optimization (MHO) algorithms for credit card fraud detection (CCFD). Carefully selected recent research papers have been investigated to examine the effectiveness of these AI-integrated approaches in recognizing a wide range of fraud attacks. These AI techniques were evaluated and compared to discover the advantages and disadvantages of each one, leading to the exploration of existing limitations of ML or DL-enhanced models. Discovering the limitation is crucial for future work and research to increase the effectiveness and robustness of various AI models. The key finding from this study demonstrates the need for continuous development of AI models that could be alert to the latest fraudulent activities.
Transformer enabled multi-modal medical diagnosis for tuberculosis classification
Authors: Kumar Sachin , Sharma Shivani , Megra Kassahun Tadesse 
Published: January 2025

Abstract
Recently, multimodal data analysis in medical domain has started receiving a great attention. Researchers from both computer science, and medicine are trying to develop models to handle multimodal medical data. However, most of the published work have targeted the homogeneous multimodal data. The collection and preparation of heterogeneous multimodal data is a complex and time-consuming task. Further, development of models to handle such heterogeneous multimodal data is another challenge. This study presents a cross modal transformer-based fusion approach for multimodal clinical data analysis using medical images and clinical data. The proposed approach leverages the image embedding layer to convert image into visual tokens, and another clinical embedding layer to convert clinical data into text tokens. Further, a cross-modal transformer module is employed to learn a holistic representation of imaging and clinical modalities. The proposed approach was tested for a multi-modal lung disease tuberculosis data set. Further, the results are compared with recent approaches proposed in the field of multimodal medical data analysis. The comparison shows that the proposed approach outperformed the other approaches considered in the study. Another advantage of this approach is that it is faster to analyze heterogeneous multimodal medical data in comparison to existing methods used in the study, which is very important if we do not have powerful machines for computation.
How urban welfare affects the hukou selection of rural migrants that belong to dual-hukou families in china
Authors: Lu Chen , Chen Jian , Li Jiewei , Wang Xuetong 
Published: January 2025

Abstract
Despite the Chinese government’s implementation of numerous policies aimed at promoting urbanization, the actual urbanization rate has not met expectations. Even when some rural migrants are presented with opportunities to convert to urban-hukou status, an increasing number of families opt to maintain a dual-hukou arrangement (where one spouse holds rural-hukou and the other holds urban-hukou). This phenomenon has garnered significant attention; however, the impact of diverse access to urban welfare on migrants’ hukou selection has been underexplored in existing research on hukou conversion. Access to urban welfare emerges as a critical factor influencing hukou selection decisions. This study constructs an analytical framework to examine the hukou arrangements of dual-hukou families, exploring the effects of various factors related to urban welfare acquisition on the hukou selection of rural migrants. Empirical results indicate that within dual-hukou families, migrants with rural-hukou status can obtain urban welfare through family support or market purchases. Consequently, to maximize family benefits, they prefer to retain their rural-hukou status rather than convert to urban-hukou. Conversely, possession of a qualification certificate from the host city negatively impacts rural-hukou retention. Additionally, rural migrants in dual-hukou families tend to favor cities with high-value hukou and express a desire to convert to local hukou status. These findings offer robust insights for policymaking, demonstrating resilience against sample self-selection bias and reverse causality.
The relationship between gallstone disease and the genetic variants of the sterol transporter adenosine triphosphate–binding cassette G8 and G5 in Egyptians
Authors: Hassan Menna A. , El-Khair Salwa M. Abo , Mesbah Noha M. , Abo-Elmatty Dina M. , Abdel-Hamed Asmaa R. 
Published: January 2025

Abstract

Background
Gallstones are abnormal lumps in the gallbladder or biliary tract due impaired cholesterol, bilirubin, or bile salt metabolism. The Adenosine triphosphate binding cassette transporter genes G5 and G8 (ABCG5, ABCG8) are two half transporters which work together as a heterodimer to regulate cholesterol levels in bile, and any alterations in their function can contribute to gallstone formation. The primary objective of this study was to evaluate the association between three specific polymorphisms—ABCG5 i7892T > C, ABCG5 Q604E, and ABCG8 D19H—and the risk of gallstone disease (GSD) in Egyptian females. These polymorphisms result from nucleotide substitutions in the gene sequences, which affect the transporter’s ability to efficiently regulate cholesterol secretion into the bile. This alteration can lead to cholesterol supersaturation in the bile, a key factor in the development of cholesterol gallstones. Additionally, the study aimed to examine the impact of these genetic variations on serum lipid profile to understand their role in modulating biochemical markers associated with GSD. Furthermore, the study sought to investigate haplotype patterns and explore their combined effects on disease susceptibility, providing deeper insight into the genetic factors that contribute to the development of GSD.

Methods
The study included 100 female patients diagnosed with gallstones and 100 healthy controls. Genotyping of single nucleotide polymorphisms (SNPs) was performed using allelic discrimination pre-designed TaqMan polymerase chain reaction method. Various laboratory investigations were measured using enzymatic colorimetric methods, and hematology analyzer was used for the whole blood count test.

Results
Between patients with gallstone disease and healthy controls, there were statistically significant differences in the distribution of these genes polymorphisms. Q604E CC genotype (OR = 15.2; P = 0.004) and C allele (OR = 2; P = 0.007) in ABCG5 (rs6720173) as well as D19H GC genotype (OR = 2.9; P = 0.002) and C allele (OR = 2; P = 0.004) in ABCG8 (rs11887534) were significantly more frequent in gallstone patients. The CCC haplotype is a statistically significant predictor of GSD.

Conclusions
This study suggests that ABCG8 D19H (G/C) and ABCG5 Q604E (C/C) genotypes may play a significant role in GSD susceptibility among Egyptian females.

Graphical abstract
Identifying genetic differences between bipolar disorder and major depression through multiple genome-wide association analyses
Authors: Panagiotaropoulou Georgia , Hellberg Kajsa-Lotta Georgii , Coleman Jonathan R. I. , Seok Darsol , Kalman Janos ,   the Bipolar Disorder Working Group of the Psychiatric Genomics Consortium,   the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium,   the iPSYCH Study Consortium, Mitchell Philip B. , Schofield Peter R. , Forstner Andreas J. , Bauer Michael , Scott Laura J. , Pato Carlos N. , Pato Michele T. , Li Qingqin S. , Kirov George , Landén Mikael , Jonsson Lina , Müller-Myhsok Bertram , Smoller Jordan W. , Binder Elisabeth B. , Brückl Tanja M. , Czamara Darina , Van der Auwera Sandra , Grabe Hans J. , Homuth Georg , Schmidt Carsten O. , Potash James B. , DePaulo J. Raymond , Goes Fernando S. , MacKinnon Dean F. , Mondimore Francis M. , Weissman Myrna M. , Shi Jianxin , Frye Mark A. , Biernacka Joanna M. , Reif Andreas , Witt Stephanie H. , Kahn René R. , Boks Marco M. , Owen Michael J. , Gordon-Smith Katherine , Mitchell Brittany L. , Martin Nicholas G. , Medland Sarah E. , Jones Lisa , Knowles James A. , Levinson Douglas F. , O'Donovan Michael C. , Lewis Cathryn M. , Breen Gerome , Werge Thomas , Schork Andrew J. , Ophoff Roel A. , Ripke Stephan , Olde Loohuis Loes 
Published: January 2025

Background
Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).

Aims
We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.

Method
Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.

Results
Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.

Conclusions
We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.
Vitiligo-like rash in a patient with lung cancer caused by sintilimab: A case report
Authors: Mao Xiao-Ming , Wang Wei-Hua 
Published: January 2025

BACKGROUND
This article discusses a case involving a 63-year-old man with non-small cell lung cancer, who was treated with a combination of chemotherapy and immunotherapy. The patient was treated with five cycles of chemotherapy (pemetrexed and carboplatin) combined with sintilimab, a programmed death 1 inhibitor.
CASE SUMMARY
After the fifth cycle of treatment, the patient developed skin itching and a vitiligo-like rash, which are known side effects of immunotherapy. Despite dermatological consultation and treatment with topical corticosteroids, the rash worsened while the itching subsided. The patient continued with the treatment, and after 15 cycles, the tumor showed a response with a reduction in size. The vitiligo-like rash increased, but the antitumor treatment remained effective.
CONCLUSION
The case highlights the use of immunotherapy in patients with non-small cell lung cancer and the potential side effect of vitiligo-like rash. The patient’s tumor responded well to the treatment, and despite the skin reaction, the treatment was not discontinued due to its effectiveness. The article suggests that further studies are needed to understand the mechanism behind vitiligo in patients with lung cancer receiving immune checkpoint inhibitors and whether the development of vitiligo-like rash after immune checkpoint inhibitor therapy is associated with improved prognosis. The case also underscores the importance of managing immune-related adverse events in the context of effective antitumor treatment.
Severe upper gastrointestinal hemorrhage due to milk protein allergy: A case report
Authors: Jiang Huan-Huan , Tang Qing , Huang Li , Yun Xiang , Shan Qing-Wen , Chen Xiu-Qi 
Published: January 2025

BACKGROUND
Upper gastrointestinal hemorrhage is a life-threatening manifestation of cow’s milk protein allergy (CMPA). We analyze the clinical characteristics of a case of milk protein allergy manifested as severe upper gastrointestinal hemorrhage.
CASE SUMMARY
The hospital admitted a 2-month-old male infant due to “melena for 6 days, hematemesis twice”. The main symptom was melena, initially occurring once or twice per day, then gradually increasing to five or six times per day at their peak. During the course of the illness, the infant vomited blood, but there were no reports of vomiting, fever, pale complexion, dyspnea, wheezing, or difficulty breathing. Laboratory tests showed hemoglobin level of 87 g/L, platelet count of 349 × 109/L, and eosinophil percentage of 0.031. Coagulation studies were normal. After avoiding certain foods and feeding with an amino acid formula for 2 weeks, a repeat gastroscopy revealed less bleeding. After six weeks, a positive oral food challenge test confirmed a severe CMPA. At the 4-month follow-up, there was no gastrointestinal bleeding, and the infant was growing and developing well.
CONCLUSION
The manifestations of milk protein allergy are diverse and nonspecific, with gastrointestinal bleeding being less common, especially in infants. When infants present with unexplained massive hematemesis, it’s critical to investigate the possibility of CMPA.
Maternal occupational exposures during early stages of pregnancy and adverse birth outcomes in the NINFEA birth-cohort
Authors: d’Errico Antonio , Popovic Maja , Pizzi Costanza , Moirano Giovenale , Moccia Chiara , Richiardi Lorenzo , Maule Milena 
Published: January 2025

Objectives
Maternal occupational exposures during early pregnancy can be detrimental to foetus health and have short- and long-term health effects on the child. This study examined their association with adverse birth outcomes.

Methods
The study included 3938 nulliparous women from the Italian NINFEA mother-child cohort. Their occupational exposures during the first trimester of pregnancy were assessed through prospectively collected questionnaire information and job-exposure matrices. Associations between maternal exposures and birthweight, preterm birth, and delivery by caesarean section were analysed by multivariable linear and logistic regression models. An exploratory factor analysis was carried out to explore co-exposure profiles in association with birth outcomes.

Results
Women exposed to passive smoking at work and those who reduced their working hours during pregnancy were found to have an increased likelihood of all analysed birth outcomes. Children of mothers performing a demanding work were less likely to be born preterm [OR 0.72 (95% CI 0.54 to 0.95)] and more likely to have a higher birthweight [β = 40.4 g (95% CI 7.5 to 73.4)]. Maternal exposures to heat and dust were associated with a lower birthweight [β = -160.1 g (95% CI -299.6 to -20.7)] and increased odds of caesarean section [OR 6.99 (95% CI 2.36 to 25.47)], respectively.

Conclusions
This study provides some evidence of the selection of healthy population into the workforce and of association between work-related passive smoking, heat and dust and adverse birth outcomes.