bluuebunny/crossref_metadata_2025 huggingface dataset:
Interaction of SLAMF8 and NINJ2 Promotes Neuroinflammation and Oxidative Stress by Activating the TLR4/NF-κB Pathway in Alzheimer’s Disease
Authors: Liu Shuo , He Yuze , Chen He , Zhao Wenwen , Xu Heman , Bai Tao , Feng Juan
Published: December 2024

Aims:
This study aimed to investigate the expression and role of Signaling Lymphocytic Activation Molecule Family Member 8 (SLAMF8) in Alzheimer’s disease (AD), particularly its interaction with NINJ2 in the TLR4/NF-κB signaling pathway.
Methods:
SLAMF8 expression levels in AD models were analyzed using the Gene Expression Omnibus (GEO) database. Validation of SLAMF8 expression was conducted through RT-PCR and Western blot in Aβ1−42-exposed SH-SY5Y cells, LPS-exposed HMC3 cells, and APP/PS1 transgenic mice. The interaction between SLAMF8 and NINJ2 was explored through co-immunoprecipitation, confocal immunofluorescence, and Western blot analyses, focusing on their roles in the TLR4/NF-κB signaling pathway.
Results:
SLAMF8 was significantly upregulated in AD models, and its overexpression activated the TLR4/NF-κB signaling pathway, leading to increased levels of pro-inflammatory cytokines and oxidative stress. NINJ2 was identified as a direct functional partner of SLAMF8, with co-localization observed in the cytoplasm. Knockout of NINJ2 abolished SLAMF8-mediated activation of the TLR4/NF-κB pathway, neuroinflammation, and oxidative stress.
Conclusion:
The SLAMF8-NINJ2-TLR4/NF-κB axis is a crucial signaling pathway in AD progression. SLAMF8 and NINJ2 emerge as potential therapeutic targets for managing AD, with significant implications for future research and clinical interventions.
Prevalence And Risk Factors of Gestational Diabetes Mellitus in A Tertiary Care Hospital
Authors: Sharma Sarita , Kirti ms , Vats Pallavi , Sharma Riya , Bhatia Ruby
Published: December 2024

Background
Gestational diabetes mellitus describes a hyperglycemic illness initially recognized during pregnancy. It is the most typical pregnancy-related medical problem and metabolic abnormality. GDM raises the risk of consequences such as obesity, poor glucose metabolism, and cardiovascular disease, which can result in T2DM. DIPSI recommends screening via OGTT in pregnant women for early detection of GDM.
Objective
To analyze the prevalence of gestational diabetes mellitus, and the trimester-specific risk factors associated thereby providing an understanding of the evolving risk landscape throughout pregnancy.
Material and Methods
This study was conducted for six months where around 150 Pregnant women (50 each trimester) visiting the outpatient department or admitted to the inpatient department within the MMIMSR Department of Obstetrics and Gynecology were included for Prevalence of Gestational Diabetes Mellitus and Trimester-Specific Risk Analysis through a survey of patient medical records an Observational Cross-Sectional Study was conducted.
Result
Of the 150 pregnant participants in this study, 24 (16.00%) received a positive diagnosis of GDM based on DIPSI criteria. Across trimesters containing 50 patients, each showed 3 (6%), 4 (8%), and 17 (34%) GDM cases observed in trimester 1 (1–13 weeks), trimester 2 (14–27 weeks), and trimester 3 (28–40 weeks) respectively. Risk factors such as Age, Blood Pressure, BMI, and Family history indicated a significant positive association with GDM incidence. However, a negative association between physical activity and the occurrence of GDM was found.
Conclusion
We observed a prevalence of 16.00% in the current study population, with a notable increase in risk during the third trimester. significant positive associations between GDM and various demographic and lifestyle factors, which include BMI, maternal age, Blood Pressure, smoking and alcohol consumption, and family history. Conversely, we also observed a negative correlation between physical activity and GDM, recommending higher levels of activity that may decrease the chance of developing GDM. Present study findings suggest that promoting healthy lifestyle choices and regular physical activity during pregnancy could be vital in reducing the risk of GDM.
A Systematic Review and Meta-Analysis of genotype data from India for 12 genetic variants and 20 clinical-physiological covariates with diabetic retinopathy
Authors: Mondal Ritisri , Sengupta Debmalya , Dutta Tithi , Bhattacharjee Samsiddhi , Sengupta Mainak
Published: December 2024

Background
Diabetic retinopathy (DR), a common microvascular complication of diabetes mellitus, is a leading cause of blindness worldwide. Conflicting results of association studies that have explored the contribution of genetic and environmental factors in conferring risk toward DR make it difficult to draw a plausible inference, thus necessitating a meta-analysis of all the concerned data on the risk factors documented from India.
Methods
Meta-analysis (using the R software package) was conducted on the genotype data of 3972 cases (DR), 3407 controls (diabetic individuals without retinopathy), and covariates from 16 studies from India selected through stringent text-mining from PubMed.
Results
Two SNPs out of 12 SNPs from 6 genes, namely rs833061 of the VEGF gene and rs2070600 of the AGER gene showed nominal association with DR that however, did not hold true after FDR (false discovery rate) correction. Analysis carried out on 20 common covariates from all the selected studies revealed a significant association of 17 clinical covariates with DR. A follow-up global meta-analysis of the associated SNPs revealed a suggestive significant association of rs2070600 with DR in the recessive model.
Conclusion
No significant association of polymorphic variants even in a meta-analysis among the Indians is probably indicative of the involvement of several rare variants with relatively low impact on DR susceptibility, at least in the Indian context.
Safety and Effectiveness of Ferric Carboxymaltose Intravenous Therapy in Pediatric Patients with Kidney Transplant
Authors: Torres Diletta Domenica , Moscogiuri Luigi Antonio , Fontò Giulia , Giordano Paolo , Carbone Vincenza , Martino Marida , Santangelo Luisa , Giordano Mario
Published: December 2024

Anemia is a frequent complication in pediatric kidney transplant recipients (KTR) with a variable reported prevalence between 20 and 80% depending on its definition. Causes of and risk factors for post-transplantation anemia (PTA) are multifactorial with iron deficiency being the primary cause of early PTA. Post transplant anemia therapy may be challenging and should be directed to the underlying causes. Iron supplementation may be indicated. Oral iron supplementation could be ineffective, and some studies demonstrated superior performance of intravenous iron over oral therapy. Ferric carboxymaltose (FCM) is an intravenous iron formulation allowing large single doses and rapid infusion time; its safety and efficacy has not been demonstrated so far in pediatric KTR. We report our experience with the use of FCM, effective and well-tolerated therapeutic option for KT pediatric patients affected by iron deficiency anemia.
Habitat Radiomics Analysis for Progression Free Survival and Immune-related Adverse Reaction Prediction in Non-small Cell Lung Cancer Treated by Immunotherapy
Authors: Guo Renhua , Wu Yuemin , Zhang Wei , Liang Xiao , Zhang Pengpeng , Zhang Mengzhe , Jiang Yuqin , Cui Yanan , Chen Yi , Zhou Wenxin , Liang Qi , Dai Jiali , Zhang Chen , Xu Jiali , Li Jun , Yu Tongfu , Zhang Zhihong
Published: December 2024

Background
Non-small cell lung cancer (NSCLC) is highly heterogeneous, leading to varied treatment responses and immune-related adverse reactions (irAEs) among patients. Habitat radiomics allows non-invasive quantitative assessment of intratumor heterogeneity (ITH). Therefore, our objective is to employ habitat radiomics techniques to develop a robust approach for predicting the efficacy of Immune checkpoint inhibitors (ICIs) and the likelihood of irAEs in advanced NSCLC patients.
Methods
In this retrospective two center study, two independent cohorts of patients with NSCLC were used to develop (n = 248) and validate signatures (n = 95). After applying four kinds of machine learning algorithms to select the key preoperative CT radiomic features, we used clinical, radiomics and habitat radiomic features to develop the clinical signature, radiomics signature and habitat radiomic signature for ICIs prognostics and irAEs prediction. By combining habitat radiomic features with corresponding clinicopathologic information, the nomogram signature was constructed in the training cohort. Next, the internal validation cohort (n = 75) of patients, and the external validation cohort (n = 20) of patients treated with ICIs were included to evaluate the predictive value of the four signatures, and their predictive performance was assessed by the area under operating characteristic curve (AUC).
Results
Our study introduces a radiomic nomogram model that integrates clinical and habitat radiomic features to identify patients who may benefit from ICIs or experience irAEs. The Radiomics Nomogram model exhibited superior predictive performance in the training, validation, and external validation sets, with AUCs of 0.923, 0.817, and 0.899, respectively. This model outperformed both the Whole-tumor Radiomics Signature model (AUCs of 0.870, 0.736, and 0.626) and the Habitat Signature model (AUCs of 0.900, 0.804, and 0.808). The radiomics model focusing on tumor sub-regional habitat showed better predictive performance than the model derived from the entire tumor. Decision Curve Analysis (DCA) and calibration curves confirmed the nomogram's effectiveness.
Conclusion
By leveraging machine learning to predict the outcomes of ICIs, we can move closer to achieving tailored ICIs for lung cancer. This advancement will assist physicians in selecting and managing subsequent treatment strategies, thereby facilitating clinical decision-making.
3D transformer-based dose prediction in HDR brachytherapy for cervical cancer
Authors: Guo Weiwei , Jian Wanwei , Zhu Lin , Zhang Bailin , He Qiang , Yang Geng , Wang Xuetao
Published: December 2024

Background
The clinical process of high-dose-rate brachytherapy (HDRBT) is time-consuming and reliant on user expertise and preference. Deep learning-based dose prediction can act as a quality assurance (QA) tool to identify suboptimal needle placement and enhance treatment planning efficiency in HDR interstitial brachytherapy. This study aims to introduce a 3D transformer-based deep learning method to automatically predict the dose distribution in HDR brachytherapy for cervical cancer.
Methods
We retrospectively analyzed 96 CT-based treatment plans from 24 cervical cancer patients who underwent interstitial HDRBT with needle insertion. The transformer mechanism was integrated into a convolutional neural network (CNN) to capture long-distance characteristics and global information. The prediction performance was evaluated by the mean error of Dose-Volume Histogram metrics between clinical and predicted dose maps, gamma analysis, and the Dice similarity coefficient (DSC) of the 1–30 Gy isodose volumes.
Results
The mean error of D90 and D95 for HRCTV was less than 0.1 Gy, and the mean D2cc for organs at risk (bladder, rectum, and bowel) was under 0.6 Gy. The mean DSC of the 1–30 Gy isodose volume was 0.87. The 3D transformer-based CNN model can predict dose maps that are highly consistent with the clinical treatment plans.
Conclusions
A novel 3D transformer-based deep learning model was successfully developed for dose prediction in HDR interstitial brachytherapy. This method can automatically generate accurate 3D dose distributions, exhibiting great clinical potential for improving treatment efficiency and standardizing brachytherapy treatment planning.
Trial registration:
No. ZF2020-084.2; Oct 16, 2020
Surgical myectomy prevents ascending aortic dilation in obstructive hypertrophic cardiomyopathy: A serial cardiac magnetic resonance study
Authors: Song Changpeng , Guo Xinli , Zheng Xinxin , Lu Jie , Cui Jingang , Wang Shuiyun , Huang Xiaohong
Published: December 2024

Background The impact of septal myectomy on the progression of ascending aortic (AAo) dilation in patients with obstructive hypertrophic cardiomyopathy (HOCM) remains uncertain. This study aimed to investigate the relationship between septal myectomy and AAo dilation in HOCM patients.
Methods A total of 69 patients with HOCM were enrolled. All the participants underwent sequential cardiac magnetic resonance scans at a mean interval of 5.13 ± 2.04 years, with each scan being more than 3 years apart.
Results At baseline, 17 patients with HOCM (25%) exhibited AAo dilation (Indexed AAo dimension> 19 mm/m²). Age (OR 1.10, 95%CI: 1.01-1.019, P = 0.026) and female (OR 4.80, 95%CI: 1.05-21.93, P = 0.043) were identified as independent risk factors for AAo dilation. In patients who underwent myectomy, the AAo dimension at follow-up was similar to that at baseline (32.47 ± 4.70mm vs. 32.81 ± 5.06mm, P=0.197). Furthermore, the rate of AAo dilation was lowere in patients with myectomy compared to those without myectomy (-0.06 ± 0.38mm/year vs. 0.18 ± 0.43mm/year, P=0.016). Additionally, moderate or severe mitral regurgitation was significantly associated with AAo dilation rate (B=0.273, P=0.032).
Conclusions These findings suggest that surgical myectomy may help prevent AAo dilation in patients with HOCM.
Therapeutic Rigid Bronchoscopy for Endobronchial Glomus Tumors: A Case Series
Authors: Ho Rong Lih , Jeong Byeong-Ho , Han Joungho , Kim Hojoong
Published: December 2024

Background
Glomus tumors (GTs) are rare, comprising only 2% of all soft tissue tumors. Pulmonary GTs are exceptionally rare, with fewer than 80 cases reported to date. Little is known about the therapeutic outcomes of rigid bronchoscopy for endobronchial GT.
Methods
This is a case series of four patients with endobronchial GT who underwent therapeutic rigid bronchoscopy between February 2021 and June 2024.
Results
The ages of the patients in our series ranged from 32–75 years, and all patients were male. Cough and blood-tinged sputum were present in all patients with endobronchial GT (n = 4). The tumor sizes ranged from 1–3 cm. Complete endoscopic resection and laser cauterization via rigid bronchoscopy were achieved in two patients. One patient had incomplete resection of a 3-cm tumor in the segmental bronchus that showed radiological evidence of bronchial wall invasion. This patient subsequently underwent lobectomy seven months after bronchoscopic resection. The fourth patient was lost to follow-up. There was no mortality throughout the follow-up periods that ranged from 1–29.7 months. Factors favoring successful rigid bronchoscopy resection for endobronchial GT include a benign tumor in the central airways without bronchial wall invasion.
Conclusion
Endoscopic resection and laser cauterization using rigid bronchoscopy may be a viable option for patients with endobronchial GT when surgery is not practical.
Clinical trial number : not applicable
The Utility of Endoscopic Ultrasound in Detecting Missed CBD stones
Authors: Farouk Mahmoud , Kaddah Mona , Mohamed Adnan Ahmed , Pawlak Katarzyna M. , Muktesh Gaurav , Karagyozov Petko , Tag-Aldeen Mohammed , Ghoneem Elsayed , Ahmed Rasha M M , Alansary Mahmoud , Ragab Khaled , El-hendawy Ramy El-Hendawy , Żorniak Michał , Okasha Hussein Hassan
Published: December 2024

Background: Precise techniques for identifying common bile duct (CBD) and pancreatic disorders are crucial to strategize appropriate interventions. This study aimed to assess the utility of endoscopic ultrasound (EUS) and magnetic resonance cholangiopancreatography (MRCP) in detecting CBD stones compared to endoscopic retrograde cholangiopancreatography (ERCP).
Methods: This prospective multicenter research included 200 patients over 18 years old with dilated CBD measuring 6-10 mm, unexplained elevated liver enzymes, and unexplained acute pancreatitis. The patients were evaluated using abdominal ultrasonography, MRCP, and EUS.
MRCP is performed just before the EUS and the ERCP being performed at a subsequent stage whenever indicated.
Results: Stones were detected in 39.5% of the patients using ERCP compared to 47% using MRCP and 43.5% using EUS. There was a strong agreement between ERCP findings and EUS findings (Kappa=0.837). EUS can significantly detect stones with a sensitivity of 94.9%, specificity of 90.1%, positive predictive value (PPV) of 86.2%, Negative predictive value (NPV) of 96.5%, and accuracy of 92%. There was a moderate agreement between ERCP findings and MRCP findings (Kappa=0.402). MRCP can significantly detect stones with a sensitivity of 72.2%, specificity of 69.4%, PPV of 60.6%, NPV of 79.2%, and accuracy of 70.5%. The accuracy of EUS was significantly higher than accuracy of MRCP.
Conclusions: EUS is a more accurate diagnostic tool for detecting stones compared to MRCP, and it has a strong agreement with ERCP findings, which is considered the gold standard??
Changes in hairiness of woven fabrics at the production and finishing stages
Authors: Krupincová Gabriela , Militký Jiří
Published: December 2024

Advances in the textile industry have led to a shift from using empirical experience to design fabrics to using computer-aided systems. Objective fabric properties related to appearance, feel, and comfort are predicted based on the physical models. The look and feel of fabrics are greatly influenced by their complex surface topology, which can be defined by two main properties: roughness and hairiness. In this study, a roughness contactless measurement system originally designed for evaluating only the surface roughness was extended to evaluating the hairiness, which is quantified by spatial parameters obtained by the quadrat method. The modified system of Roughness Contactless Measurement system was applied to assessing work shirts across five production stages, and the experimental results demonstrated variations between gray and treated woven fabrics that could be attributed to shrinkage during water-based processes, subsequent drying under tension, and singeing. The gray and pretreated fabrics exhibited the highest hairiness, which was greatly reduced by singeing and stabilized during the finishing stage by an easy-care treatment.
The bidirectional regulatory effect of TXNRD2 methylation in patients with chronic heart failure and its nonlinear dose-response relationship with key clinical parameters
Authors: Zhao Ruonan , Ma Lin , Wang Ruiping , Zhang Rongqiang
Published: December 2024

Objective
The research focused on examining CpG methylation within the TXNRD2 promoter area in chronic heart failure (CHF) patients, aiming to correlate methylation levels with clinical indexes to guide CHF treatment.
Methods
Whole blood samples from 20 CHF patients and 20 healthy controls were analyzed using MALDI-TOF-MS. Methylation levels of CpGs in the TXNRD2-FA42 region were compared between CHF patients, healthy controls, and CHF patients with varying cardiac functions.
Results
TXNRD2-FA42_CpG_3 methylation was lower in CHF patients (P=0.0407), while TXNRD2-FA42_CpG_8 was higher (P=0.0183) compared to controls.
Conclusion
TXNRD2 promoter methylation in CHF patients exhibited bidirectional regulation, potentially influencing coagulation, renal function, and blood routine. These results deepen understanding of CHF pathogenesis and suggest new treatment approaches.
Identification of TPST1 as a Promising Prognostic Biomarker in Head and Neck Squamous Cell Carcinoma
Authors: Chen Shuai , Chen Fei , Huang Shanying , Jia Wenming , Qian Ye
Published: December 2024

Head and neck squamous cell carcinoma (HNSC) is one of the most common cancers in the world, with poor prognosis and lack of effective biomarkers for early diagnosis. Tyrosylprotein sulfotransferase 1 (TPST1) has been implicated in a variety of biological processes and tumor progression. The differential expressions of TPST1 in human tumors and the clinical prognosis in HNSC were examined via multiple bioinformatics approaches, and verified in human HNSC tissues. In addition, a series of functional assays were performed to explore the biological role of TPST1 in HNSC.Our findings revealed that TPST1 expression in HNSC samples was considerably upregulated than that of normal tissues. High TPST1 expression was linked with clinicopathological characteristics and unfavorable prognosis of HNSC patients. Genetic mutation of TPST1 was involved in the development of HNSC. We identified TPST1 related co-expressed genes, which were mainly enriched in the Wnt signaling pathway associated with the tumorigenesis, leading to a poor prognosis of HNSC patients. we analyzed the correlation between TPST1 and pathways, and verified by experiments.The results showed that TPST1 is an oncogene and may function as a potential prognosis biomarker for HNSC patients, suggesting that TPST1 could be a promising therapy target against HNSC.
Synergistic effects of osseointegration and multifunctional properties: Mechanical and electrical performance of functionally graded ceramic composites before and after soaking in SBF for bone healing applications
Authors: Youness Rasha A. , Mostafa Essam B. , Taha Mohammed A.
Published: December 2024

This work presents the creation of functionally graded composite (FGC) intending to enhance bone healing, as traditional bone repair materials typically do not possess the necessary qualities for perfect healing. In this context, the FGC was fabricated by layering five layers of hydroxyapatite (HA), silicon carbide (SiC), and copper oxide (CuO) nanoparticles. Analysis was conducted using characterization techniques such as X-ray diffraction (XRD) and field emission scanning electron microscopy (FESEM). Furthermore, the osseointegration ability of all prepared FGC layers was assessed using simulated body fluid (SBF) and investigation by FESEM. The physical, mechanical, electrical, and dielectric properties were measured before and after soaking in the SBF solution. Additionally, the antibacterial effect and biocompatibility of these layers were evaluated. Sintered layers exhibit porosity values ​​ranging from 5–10%, similar to compact bone, which is essential for effective osseointegration. FESEM images showed good bioactive behavior across all FGC layers. Increasing the proportions of SiC and CuO improved the compressive strength to match cortical bone, reducing compression shielding. In addition, these additives significantly enhanced electrical conductivity and reduced dielectric properties, which are vital factors for bone regeneration. Significantly, soaking the prepared layers with SBF did not affect the mechanical properties, which indicates that there is no conflict between the biological activity of these layers and their mechanical properties. However, their electrical and dielectric properties changed slightly due to their soaking in the SBF solution. Notably, the sample with the highest SiC and CuO content exhibited a 75% reduction in weight loss. Importantly, CuO inclusion led to a considerable improvement in the antibacterial efficacy of the FGC layers without a noticeable cytotoxic effect. These findings indicate that the prepared FGC and its layers have promising multifunctional performance and are a suitable candidate for bone healing applications.
Comparison of the Efficacy of Robot-assisted Total Knee Arthroplasty in Patients with Knee Osteoarthritis with Varying Severity Deformity
Authors: Xing Pengfei , Qu Junsong , Feng Shuaijing , Guo Jiarong , Huang Tao
Published: December 2024

AIM: To evaluate the clinical efficacy and imaging outcomes of a domestically produced orthopedic surgical robot for total knee arthroplasty and to explore its applicability in patients with varying degrees of deformity.
Methods: This study retrospectively included 120 patients who underwent TKA at our hospital between February 2023 and June 2024. The patients were divided into a control group (conventional TKA surgery) and an observation group (robot-assisted TKA surgery), with 60 patients in each group. On the basis of different lower extremity alignment angles, each group was further subdivided into mild deformities (HKA deviation < 10°) and significant deformities (HKA deviation ≥ 10°). Preoperative and postoperative HKA angles, range of motion (ROM), visual analog scale (VAS) pain scores, and Knee Society (AKS) scores were recorded for both groups. Postoperative measurements included the posterior tibial slope angle (PSA), femoral coronal component angle (FFC), tibial coronal component angle (FTC), and femoral sagittal component angle (LFC), as well as the incidence of abnormal values for each angle, which were analyzed statistically.
Results: The operation time in the observation group was longer than that in the control group, but intraoperative blood loss was significantly lower in the observation group (P < 0.05). Postoperatively, the differences in the HKA and PSA angles and the incidence of abnormal values were significantly greater in the robot-assisted group than in the control group (P < 0.05). The other indicators did not significantly differ between the two groups. (P > 0.05). For patients with mild preoperative deformities, those in the robot-assisted group had significantly greater postoperative HKA angle deviations and rates of postoperative HKA angle outliers than did those in the conventional group. For patients with significant deformities, the robot-assisted group presented greater postoperative HKA and PSA angle deviations than did the control group; the postoperative HKA and PSA angle outlier rates were significantly lower in the robot-assisted group (P < 0.05).
Conclusion: The TINAVI robotic system demonstrated superior safety and efficacy in TKA surgery. Compared with conventional TKA, the robot-assisted system achieved significantly better outcomes in terms of prosthesis implantation accuracy and lower extremity alignment, with a particular advantage in patients with severe limb alignment deformities.
Peripheral players and gut bacteria modulate inflammatory bowel disease phenotype in patients with primary sclerosing cholangitis
Authors: Santos André , Pires David , Marques Vanda , Alesina Nicole , Herraez Elisa , Roudnický Pavel , Rodrigues Pedro , Godinho-Santos Ana , Bravo Ana , Gouveia Catarina , Saraiva Susana , Correia Luís , Crespo Ricardo , Silva João da , Cravo Marília , Potesil David , Zdráhal Zbyněk , Bañales Jesús , Marín José , Torres Joana , Rodrigues Cecília
Published: December 2024

Background & Aims:
Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease often associated with underlying inflammatory bowel disease (IBD). We aimed to study how the phenotype in PSC patients compares to IBD alone and its association with altered inflammatory immune responses.
Methods
A case-control study was conducted involving a cohort of 75 patients, including 16 with PSC (14 with concomitant IBD), 39 with IBD alone, and 20 control individuals. Fecal gut microbiota, colonic tissue proteomics and immune-related gene expression, serum proteomics and targeted metabolomics were analyzed.
Results
Intestinibacter taxa were increased in patients with PSC. Proinflammatory mRNA markers TWIST1, COX2, IL-8, and CCL2, and pro-oncogenic markers LGR5 and SNAIL were upregulated in colonic tissue from PSC patients. Additionally, a unique proinflammatory proteomic signature, elevated glycochenodeoxycholic acid (GCDCA), and increased miR-21 were identified in serum from PSC patients. Co-incubation of human-derived monocytes with miR-21 and GCDCA reproduced the inflammatory profile observed in PSC patients.
Conclusions
These findings suggest an interplay between gut microbiota dysbiosis and the proinflammatory peripheral immune response contributing to the unique PSC phenotype
LncRNA-mediated High Expression of TRIP13 Correlates with Poor Prognosis and Tumor Immune Infiltration of Hepatocellular Carcinoma
Authors: Cao Ya-wen , Ying Jiaxin , Ye Yong-qing
Published: December 2024

Background:
Hepatocellular carcinoma (HCC) accounts for approximately 90% of primary liver cancers and is charactered by poor prognosis. The identification of potential prognostic biomarkers is essential for HCC patients.
Methods: In this study, Gene Expression Profiling Interative Analysis (GEPIA) online tool was used to the different expression of TRIP13 and has-miR-29c-3p axis between tumor samples and normal samples in multiple cancers including hepatocellular carcinoma (HCC). The oncological value of TRIP13 and has-miR-29c-3p axis in cancer was revealed by Kaplan-Meier analysis. The upstream miRNAs of TRIP13 were predicted by the starBase database and Cytoscape software.
Results:
In this work, we identified that compared to normal tissues, the expression of TRIP13 was high in tumor samples by The Cancer Genome Atlas (TCGA) and Genotypic-Tissue Expression (GTEx) data. We further revealed that TRIP13 may be a potential oncogene in HCC. Subsequently, hsa-miR-29c-3p was responsible for TRIP13 overexpression, which was identified by expression analysis, correlation analysis and survival analysis of the target gene. Further, hsa-miR-29c-3p was associated with the poor prognosis of cancer patients. Moreover, the expression level of TRIP13 was positively correlated with tumor immune cell infiltration with high infiltrating level of B cells, CD4+ T cells, macrophages, exhausted CD8+ T cells and immune checkpoints including PD1, PD-L1 and CTLA-4.
Conclusions:
In general, our findings reveal that TRIP13 and hsa-miR-29c-3p promotes the malignant development of hepatocellular carcinoma, which is a potential new therapeutic target and a prognostic biomarker for HCC.
Preoperative hypoalbuminemia is associated with postoperative short- and long-term renal function deterioration in patients who underwent radical cystectomy for bladder cancer
Authors: Song Byeongdo , Lee Hakmin , Lee Sangchul , Hong Sung Kyu , Byun Seok-Soo , Oh Jong Jin
Published: December 2024

Radical cystectomy (RC), which is the standard of care for muscle-invasive and high-grade non-invasive bladder cancer, is accompanied with postoperative renal function detoriation. We aimed to evaluate the effect of hypoalbuminemia on the postoperative renal function decline after RC. A total of 272 patients with estimated glomerular filtration rate (eGFR) ≥ 60 mL/minute/1.73 m2 who underwent RC between October 2003 and December 2020 were included. Acute kidney injury (AKI) was defined according to Kidney Disease Improving Global Outcomes (KDIGO) criteria, while postoperative chronic kidney disease (CKD) progression was defined as eGFR < 60 mL/minute/1.73 m2 at ≥ 3 months after RC. In our cohort, 20 (7.4%) and 99 patients (36.4%) experienced AKI and CKD progression postoperatively, with a median follow-up period of 51.5 months. The median preoperative serum albumin level and eGFR were 4.1 g/dL and 82.0 mL/minute/1.73 m2, respectively. Preoperative hypoabluminemia < 4.1 g/dL was associated with postopeative AKI (odd ratio [OR] 3.37, p = 0.029) and CKD progression (OR 2.64, p < 0.001) after adjusting other factors. The patients with hypoalbuminemia < 4.1 g/dL are associated with short- and long-term renal function decline after RC, suggesting that neoadjuvant chemotherapy might be considered prior to RC for these patients.
BH3 Mimetics Augment Cytotoxic T Cell Killing of Acute Myeloid Leukemia via Mitochondrial Apoptotic Mechanism
Authors: Yee Cassian , Saxena Kapil , Ryu Esther , Hung Shao-Hsi , Singh Shailbala , Zhang Qi , Zeng Zhihong , Wang Zhe , Konopleva Marina
Published: December 2024

Adoptive cell therapy (ACT) can address an unmet clinical need for patients with relapsed/refractory acute myeloid leukemia (AML), but its effect is often modest in the setting of high tumor burden. In this study, we postulated that strategies to lower the AML apoptotic threshold will augment T cell killing of AML cells. BH3 mimetics, such as venetoclax, are a clinically approved class of compounds that predispose cells to intrinsic apoptosis by inhibiting anti-apoptotic mitochondrial proteins. We explored the anti-leukemic efficacy of BH3 mimetics combined with WT1-specific CD8 + T cells on AML cell lines and primary samples from patients with a diverse array of disease characteristics to evaluate if lowering the cellular apoptotic threshold via inhibition of anti-apoptotic mitochondrial proteins can increase leukemic cell sensitivity to T cell therapy. We found that the combination approach of BH3 mimetic and CD8 + T cells led to significantly increased killing of established AML lines as well as of adverse-risk primary AML leukemic blast cells. In contrast to the hypothesis that enhanced killing would be due to combined activation of the intrinsic and extrinsic apoptotic pathways, we found that CTL-mediated killing of AML cells was accomplished primarily through activation of the intrinsic/mitochondrial apoptotic pathway. This highly effective combinatorial activity due to convergence on the same apoptotic pathway was conserved across multiple AML cell lines and primary samples, suggesting that mitochondrial priming may represent a novel mechanism of optimizing adoptive cell therapy for AML patients.
Exposure to No 2 in Children’s Parks During a High Pollution Episode Based on Mesoscale Simulations
Authors: Simón-Moral Andrés , Herranz-Pascual Karmele , Padró Ales , Lertxundi Aitana , Yurrebaso Lexuri , Martilli Alberto
Published: December 2024

Air pollution is one of the greatest environmental risk factors for human health, especially worrying in urban areas, where children are one of the most vulnerable sectors. Continuous information of exposure to different air pollutants is therefore needed, especially in areas where children spend most of their time, as urban parks. In this study, we use 500 m horizontal resolution mesoscale simulations to assess children exposure to NO2 during a high pollution episode in five urban parks across Vitoria-Gasteiz. Children living at a maximum 5-minute walking time from each park is considered for exposure calculation. Results show that four parks exceed current hourly limit values, and all of them exceed the daily limits defined by the World Health Organization 2021 guideline. The use of hourly values instead of the daily mean for pollutant exposure calculation shows that the latter underestimates morning exposure and overestimates evening exposure. This result highlights the need for high time resolution to achieve better exposure assessment. The spatial resolution used in this study also shows the capacity to differentiate between parks, improving the exposure estimates respect the use of official air quality stations. This methodology provides continuous information to assess short term exposure, especially important in a high pollution episode, and allows for pollution gaps filling for long term exposure studies.
Acceptable survival of one-and-a-half-stage exchange arthroplasty with cement augmentation for periprosthetic joint infection
Authors: Song Sang Jun , Kim Young Kook , Kim Jin Woo , Park Cheol Hee
Published: December 2024

Purpose: To compare the aseptic survival of 1.5-stage exchange arthroplasty for periprosthetic joint infection (PJI) with and without cement augmentation using an autoclaved original femoral component and a new polyethylene insert (PE).
Methods: Among 1.5-stage exchange arthroplasties without reinfection, 42 cases with cement augmentation (Group C) and 88 cases without cement augmentation (Group N) were retrospectively reviewed. The cement augmentation technique was applied when joint stability could not be achieved using the thickest PE. Demographics were not significantly different between the groups. The hip-knee-ankle angle (HKA) and component positions were measured; the proportions of appropriate HKA and component positions (HKA≤0±3°, α≤95±3°, β≤90±3°, γ≤3±3°, and δ≤87±3°) were investigated. Survival and failure rates were analyzed, and failure was defined as reoperation owing to aseptic failure. The risk factors affecting survival were investigated in terms of demographics, cement augmentation, inappropriate HKA and component position for all patients in both groups.
Results: Although the average HKA and component positions were not different, appropriate proportion of coronal and sagittal PE position were significantly lower in the group C (appropriate β, 57.1% vs 90.9%; appropriate δ, 38.1% vs 77.3%; p<0.001, respectively). The 1-, 2-, and 5-year survival rates were 76.2%, 71.4%, and 71.4% in group C and 89.8%, 86.4%, and 81.6% in group N, respectively (p=0.063). The failure rate was not significantly different, despite the higher failure rate in group C (28.6% vs. 18.2%, p=0.253). The significant factor affecting the survival was only the inappropriate coronal positioning of the PE (β>90±3°) in overall cases (odds ratio=2.957, p=0.016).
Conclusion: The cement augmentation technique used to compensate for instability allows acceptable survival in 1.5 stage exchange arthroplasty. However, care is required when using this technique in the appropriate PE position to ensure favorable survival.
Major Glacial Cycle Change was not Driven by Removal of Slippery Sediment
Authors: Drew Matthew , Tarasov Lev
Published: December 2024

Past sea level change informs our predictions of future sea level rise [1] and, more broadly, the large scale climate changes that drove ice sheet growth and decay [2]. Approximately one million years ago, the relationship between orbitally-driven insolation and glacial cycle sea level change shifted – small, 40 thousand year cycles ceded to large, 100 thousand year cycles[3]. A leading hypothesis for this Mid-Pleistocene Transition is that the North American ice sheet grew resilient to deglaciation by removing its bed of slippery regolith, exposing the high friction bedrock underneath[4]. Our data constrained numerical experiments show that the North American ice sheet exposed bedrock over an area similar to present day by 1.5 million years ago, well before the Mid-Pleistocene Transition began. Thicker pre-glacial regolith does not simply delay its removal and thus the transition – it limits ice-ocean interaction by infilling shallow marine areas while cooling via the elevation-lapse rate feedback. Topographic changes over previously glaciated domains play a critical role in early Pleistocene glaciation – enabling larger ice sheets during warmer periods. This highlights the important and under-appreciated role topographic change plays in past sea
ISEBC: Using A Novel Breast Cancer Tertiary Lymphoid Structures Signature To Build An Immune-favourable Status Evaluator For Breast Cancer
Authors: Fan Xiaokai , Yu Xuan , Chen Liang
Published: December 2024

Tertiary lymphoid structures (TLSs), as a special type of immune-infiltrated region in tumor tissues, plays an important role in benefiting from immunotherapy or improving immune state of breast cancer patient. However, breast cancer-specific TLS signature gene sets are still lacking. Therefore, we extracted gene features with machine learning algorithm LightGBM, and differential expression genes with statistical test on multiple spatial transcriptome datasets, to finally obtain a novel breast cancer-specific TLS gene set (NBCTS). Compared with previous gene sets, it has stronger characterization ability of TLS in breast cancer samples. Since TLS have unique immune characteristics, we classified three different immune states using this gene set for breast cancer patients and get an immune state. To better facilitate evaluating this immune statuses of breast cancer patients or samples, we developed a user-friendly web tool (Immune State Evaluator for Breast Cancer, (ISEBC),www.omegene.tech:3838/ISEBC) to make it more convenient for researchers and clinicians to use.
Longitudinal analysis of peripheral blood immune status and prognosis dynamic prediction for advanced colon cancer with first-line chemotherapy
Authors: Wang Fan , Li Chun-xia , Liu Dong-Li , Zhao Jin-Yan , Wang Qing-Guo , Li Qi , Zhang Tao , Cai Xun
Published: December 2024

Background
The prognostic evaluation of advanced CRC patients places increased importance on longitudinal peripheral blood immune status. This study aimed to identify prognosis associated longitudinal immune markers and construct dynamic prognostic models for advanced CRC patients with first-line chemotherapy.
Methods
Metastatic CRC patients treated with standard first-line palliative chemotherapy were retrospectively collected at Shanghai General Hospital from May 2013 to May 2020. Lymphocyte subsets, inflammatory indices, and tumor markers in peripheral blood were repeatedly assessed before each chemotherapy cycle. Joint models were used to identify significant longitudinal prognostic markers. A dynamic prognostic model was established using random forests for time-dependent predictors, and internally validated using 10-fold cross-validation.
Results
Increased levels of CRP, CEA, CA199, and IL-6, as well as the CD4 + CD29 + cell proportion and the CD4 + CD45RO+/CD4 + ratio were identified as significant risk factors for overall survival (OS) in metastatic CRC patients. Conversely, the increased levels of CD3-CD19 + cell proportion and the CD4 + CD45RA+/CD4 + ratio were identified as favorable factors for OS. A dynamic prognostic model demonstrated good discriminative ability, with AUC values of 0.827, 0.787, 0.726, and 0.693 for 2-, 3-, 4-, and 5-year predictions, respectively. A high ratio of CD4 + CD45RA+/CD4 + before the 3rd to 4th chemotherapy cycle was associated with significantly better OS. Normal CRP and IL-6 levels in the early phase of first-line chemotherapy indicated a good prognosis.
Conclusion
This study highlights the prognostic significance of measuring longitudinal immune status in advanced CRC patients and provides a novel dynamic prediction tool for clinical practice.
Comparison of ground and aero magnetic anomalies: Two-dimensional crustal modelling of the Eastern Pontides (Türkiye) from integrated magnetic and gravity data
Authors: ÖZKAPTAN Murat , ÖZKAPTAN Tuğçe , BABACAN Ali Erden
Published: December 2024

Magnetic and gravity surveys are frequently used by earth scientists, given their ease of use and ability to provide rapid results. Various data platforms have integrated these data obtained from ground, sea, and airborne measurements on a global scale. The combining process reduces data resolution in some cases. In this study, aero and ground magnetic data in the Eastern Pontides were analysed to test this situation. The two magnetic data normalized for comparison show great similarities. It has also been suggested that carrying out ground magnetic survey at intervals of at most 10 km is sufficient for modelling large-scale deep structures. They were also used together with global gravity data to model the crustal structure of the Eastern Pontides. The results were compared with crustal models using gravity and seismological data in the literature. Contrary to the monotonic crustal thickness increase from north to south suggested in the literature, a gravity increase of approximately 50 mGal was determined in the south of the Eastern Pontides (axial zone) and it was suggested that the crust became thinner in this region. In addition, the crustal thickness variation was determined more clearly with the contribution of the two magnetic data sources.
Exploring the Impact of hsa_circ_0049168 on NSCLC Proliferation and Apoptosis via the miR-370/PIN1 Regulatory Network
Authors: Chen Shuangqun , Tian Yuan , Chen Mingzhi , Wu Yanjin , Zhu Ji , Li Zixuan , Yang Jian , Liu Hongcheng , Li Huafei
Published: December 2024

In this study, we explored the biological role and underlying mechanisms of hsa_circ_0049168 in NSCLC. Utilizing circRNA microarray analysis and bioinformatics analyzation, we identified a significant upregulation of hsa_circ_0049168 in both NSCLC tissues and cell lines. Our results demonstrate that hsa_circ_0049168, originating from the PIN1 gene, promotes tumor cell proliferation and inhibits apoptosis. Mechanistically, hsa_circ_0049168 functions by sponging miR-370, subsequently upregulating PIN1 expression, a key regulator of cellular proliferation and survival pathways. Through in vitro and in vivo experiments, we confirmed that knockdown of hsa_circ_0049168 leads to increased apoptosis and decreased proliferation of NSCLC cells. Moreover, the effects of hsa_circ_0049168 knockdown were reversed upon inhibition of miR-370, highlighting the specificity of the hsa_circ_0049168/miR-370/PIN1 regulatory axis in NSCLC. Notably, hsa_circ_0049168 was found to modulate key downstream targets, including β-catenin and cyclin D1, which play critical roles in cell cycle regulation and tumorigenesis. The clinical relevance of hsa_circ_0049168 was further underscored by its correlation with advanced tumor characteristics such as larger tumor size, poorer differentiation, and lymph node metastasis in NSCLC patients. Taken together, our findings suggest that hsa_circ_0049168 contributes to NSCLC progression via the miR-370/PIN1 axis and could serve as a promising biomarker for diagnosis and prognosis, as well as a potential therapeutic target in NSCLC.
Rehabilitation Outcomes in Patients With Complex Regional Pain Syndrome of the Ankle-foot Complex
Authors: Vacheva Danelina , Drumev Atanas
Published: December 2024

Background
Complex regional pain syndrome is a debilitating condition that often involves an injury or surgery, leading to chronic pain, swelling, and functional impairment in affected limbs, particularly in the ankle-foot complex. The management is challenging, as patients may experience prolonged symptoms that impact mobility and quality of life. While rehabilitation interventions aim to improve functional outcomes, their effectiveness in restoring full ankle function and mitigating long-term effects varies widely among patients. The purpose of this study was to evaluate the effectiveness of a structured rehabilitation program for functional recovery in patients with complex regional pain syndrome of the ankle-foot complex following trauma. Seventy-two patients presented with ankle-foot trauma, 23 of whom were diagnosed with CRPS.
Methods
Patients underwent a comprehensive rehabilitation program including kinesitherapy, cryotherapy, therapeutic massage, and electrotherapy. Functional recovery was assessed via goniometry, the symmetry index via the G-WALK inertial sensor, locomotor activity tests, and activities of daily life scoring, with the data analyzed via SPSS.
Results
Statistical analysis of the 23 patients with complex regional pain syndrome revealed significant improvements over three rehabilitation courses within five months. Initial assessments revealed hypotrophy of the thigh (2.5 cm) and lower leg muscles (1.5 cm), alongside swelling in the ankle joint (3.5 cm) and foot (2 cm). By the end of the rehabilitation period, hypotrophy decreased to 1 cm in the thigh and 1.5 cm in the calf, with swelling reduced to 1.5 cm in the ankle and 1 cm in the foot. Range of motion improved significantly, with dorsiflexion increasing by 10.83º and plantarflexion by 33.33º. The symmetry index improved from 64.88–80.8%, indicating partial restoration of gait symmetry. Pain levels decreased from an average of 15 (severe) to 7.5 (moderate), indicating substantial functional gains.
Conclusion
Complex regional pain syndrome following ankle-foot trauma requires a tailored rehabilitation program to restore mobility and functionality. While complete gait normalization may be prolonged, targeted rehabilitation enables significant improvements in daily activity performance.