bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Trichinella spiralis and its serine protease inhibitors on intestinal mucosal barrier function
Authors: Wang Ruibiao , Zhang Yuheng , Li Zhixin , Zhen Jingbo , Li Qiankun , Zhang Qi , Yang Yuqi , Liu Xueting , Lu Yixin 
Published: October 2024

Abstract

T. spiralis is a highly pathogenic zoonotic nematode that poses significant public health risks and causes substantial economic losses. Understanding its invasion mechanisms is crucial. This study explored the role of serine protease inhibitors (SPIs) secreted by T. spiralis in disrupting the host intestinal epithelial barrier. The effects of T. spiralis infection on the jejunal barrier function in mice were investigated. Histopathological analysis showed significant jejunal damage, peaking at day 7 post-infection (dpi). RT-qPCR and Western blotting revealed marked reductions in tight junction proteins (ZO-1, Occludin, Claudin-3), mucins (MUC-1, MUC-2), and anti-inflammatory cytokines (TGF-β, IL-10) from 1 to 15 dpi, along with increased expression of Toll-like receptors (TLR-1, TLR-2, TLR-4) and pro-inflammatory cytokines (TNF-α, IL-1β). Recombinant SPIs (rKaSPI, rAdSPI) were purified and co-cultured with intestinal epithelial cells (IPECs) and used in mouse models. The protein expression changes in IPECs and mice were consistent with those in T. spiralis-infected tissues. Both SPIs downregulated ZO-1, Occludin, Claudin-3, MUC-1, MUC-2, TGF-β, and IL-10, while upregulating TLR-4 and pro-inflammatory cytokines, disrupting the intestinal barrier and exacerbating inflammation. Notably, rAdSPI had a more pronounced effect. In summary, T. spiralis infection caused significant jejunal damage and disrupted the intestinal barrier. T. spiralis-secreted SPIs, especially AdSPI, played a pivotal role, facilitating invasion by compromising the host’s intestinal barrier and promoting inflammation. This study provides insights into T. spiralis invasion mechanisms and potential targets for trichinellosis prevention and control.
MR imaging findings of hepatic pseudolymphoma: common and rare features
Authors: Zhao Xiaoer , Li Junhao , Chen Lingli , Ji Yuan , Zeng Mengsu , Wang Mingliang 
Published: October 2024

Abstract

Purpose To summarize the common and rare MR imaging features of hepatic pseudolymphoma (HPL).
Methods This retrospective study was approved by our institutional review board. 35 patients (mean age, 53.2 years) with 50 HPLs underwent enhanced MR. MR images were retrospectively reviewed and analyzed.
Results There are 3 males and 32 females (8.6% vs 91.4%). 27 patients with single lesion and 8 patients with multiple lesions. Among the 50 HPLs, 90% of HPLs size ≤ 20mm, 92% were regular, and 92% were ill-defined. 7 and 5 patients had a history of malignant tumor and chronic liver disease. Tumor markers were negative in all patients. All 50 HPLs were low T1 SI, high T2 SI, high DWI SI, low ADC value, and adjacent to veins. 72% of HPLs were adjacent to the portal vein, 18% to the hepatic vein and 10% to the inferior vena cava. 72% of HPLs showed "linear sign" and "angular sign". There was a favorable agreement between "linear sign" and "angular sign" (kappa = 0.802, R < 0.001). 88% of HPLs showed “ring sign”. There were four enhancement patterns of HPLs (Table 2), wash out (46%), degressive (26%), persistent (18%) and progressive (10%). There were 2 patients with pathologically confirmed extra-hepatic pseudolymphomas. The largest HPL was 50mm in length with central cystic necrosis.
Conclusions The common features of HPL are small, single, regular, adjacent to veins, low T1 SI, high T2 SI, high DWI SI and low ADC value. “Linear sign”, “angular sign” and “ring sign” could be seen as common features of HPL. The rare features of HPL included extra-hepatic lesion and central cystic necrosis.
Combined inhibition of ribonucleotide reductase and WEE1 induces synergistic anticancer activity in Ewing's sarcoma cells
Authors: Ziener Judy , Henao-Restrepo Julián Andrés , Leonhardi Johanna , Sturm Max-Johann , Becker Sabine , Morales-Prieto Diana M. , Milde Till , Beck James F. , Sonnemann Jürgen 
Published: October 2024

Abstract

Background
Ewing's sarcoma is a childhood bone and soft tissue cancer with poor prognosis. Treatment outcomes for Ewing's sarcoma patients have improved only modestly over the past decades, making the development of new treatment strategies paramount. In this study, the combined targeting of ribonucleotide reductase (RNR) and WEE1 was explored for its effectiveness against Ewing's sarcoma cells.
Methods
The RNR inhibitor triapine and the WEE1 inhibitors adavosertib and ZN-c3 were tested in p53 wild-type and p53 mutant Ewing's sarcoma cells. The combination of adavosertib with the PARP inhibitors olaparib and veliparib was tested for comparison. Combinatorial effects were determined by flow cytometric analyses of cell death, loss of mitochondrial membrane potential and DNA fragmentation as well as by caspase 3/7 activity assay, immunoblotting and real-time RT-PCR. The drug interactions were assessed using combination index analysis.
Results
RNR and WEE1 inhibitors were weakly to moderately effective on their own, but highly effective in combination. The combination treatments were similarly effective in p53 wild-type and p53 mutant cells. They synergistically induced cell death and cooperated to elicit mitochondrial membrane potential decay, to activate caspase 3/7 and to trigger DNA fragmentation, evidencing the induction of the apoptotic cell death cascade. They also cooperated to boost CHK1 phosphorylation, indicating augmented replication stress after combination treatment. In comparison, the combination of adavosertib with PARP inhibitors produced weaker synergistic effects.
Conclusion
Our findings show that combined inhibition of RNR and WEE1 was effective against Ewing's sarcoma in vitro. They thus provide a rationale for the evaluation of the potential of combined targeting of RNR and WEE1 in Ewing's sarcoma in vivo.
Joint association of TyG index and LDL-C with all-cause and cardiovascular mortality among patients with cardio-renal-metabolic disease
Authors: Lai Wenguang , Lin Yucui , Gao Zhiyong , Huang Zhidong , Zhang Tingting 
Published: October 2024

Abstract

Background: Both the triglyceride-glucose (TyG) index, as a surrogate marker of insulin resistance, and low-density lipoprotein cholesterol (LDL-C) are independent risk factors for long-term prognosis among patients with cardio-renal-metabolic (CRM) disease. However, the co-exposures of TyG index and LDL-C to all-cause and cardiovascular death among patients with CRM remain unknown.
Methods:Patients with CRM from the National Health and Nutrition Examination Survey (NHANES) database (1999–2018) were included. The TyG index was calculated as Ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. Multivariable Cox and restricted cubic spline (RCS) regression models were used to estimate the individual and joint association of TyG index and LDL-C with the risk of all-cause and cardiovascular mortality. The interaction between the TyG index and LDL-C to mortality was also evaluated.
Results: During a median follow-up of 7.6 years, there were 1608 (22.8%) and 609 (8.4%) patients who died from all-cause and cardiovascular mortality, respectively. In patients with LDL-C<2.6 mmol/L, no significant differences were observed in all-cause and cardiovascular mortality when comparing higher TyG index to the lowest tertile (T1). Specifically, the hazard ratios (HRs) for all-cause mortality in the second (T2) and third tertiles (T3) were 0.81 (95%CI: 0.59–1.09) and 0.87 (95%CI: 0.62–1.22), respectively, with a P for trend of 0.468. For cardiovascular mortality, the HRs for T2 and T3 compared to T1 were 0.80 (95%CI: 0.48–1.32) and 0.72 (95%CI: 0.45–1.15), respectively, with a P for trend of 0.173. However, elevated TyG index was related to markedly increased risk of all-cause and cardiovascular mortality in patients with LDL-C≥2.6 mmol/L. Specifically, for all-cause mortality, HRs for T2 and T3 compared to T1 were 1.01 (95%CI: 0.79–1.28) and 1.38 (95%CI: 1.07–1.79), respectively, with a P for trend of 0.009. For cardiovascular mortality, the HRs were 1.09 (95% CI: 0.72–1.65) for T2 and 1.80 (95% CI: 1.18–2.75) for T3, with a P for trend of 0.005. Similar results were found in RCS and sensitivity analyses. Interactive analysis also demonstrated that a significant association of TyG index and LDL-C with the risk of all-cause (P for interaction=0.011) and cardiovascular (P for interaction=0.050) mortality was observed.
Conclusions: Our research demonstrated the co-exposure effects between the TyG index and LDL-C on all-cause and cardiovascular mortality. Elevated TyG index can significantly increase the risk of all-cause and cardiovascular mortality only among CRM patients with LDL-C ≥ 2.6 mmol/L, but not among patients with LDL-C < 2.6 mmol/L.
Disparities in Immunotherapy Access for Advanced Pancreatic Cancer across the United States
Authors: Khalid Abdullah , Faiz Zohaa , Shah Manav , Newman Elliot , King Daniel A. , DePeralta Danielle , Gholami Sepideh , Weiss Matthew J. , Melis Marcovalerio 
Published: October 2024

Abstract

Background:
Pancreatic ductal adenocarcinoma (PDAC), a highly lethal cancer with a poor prognosis, is expected to become the second deadliest cancer in the United States by 2030. Despite advancements in treatment modalities, the survival rates of patients with PDAC have remained low. Immunotherapy has emerged as a promising treatment for various cancers; however, its utilization in PDAC has been limited due to various challenges, including resistance mechanisms and the advanced stage at which most patients are diagnosed.
Methods:
We analyzed data from the National Cancer Database (NCDB) from 2010 to 2017, focusing on the impact of race, insurance status, and socioeconomic factors among patients with stage IV PDAC using logistic regression analyses.
Results:
Among 109,663 patients with stage IV PDAC, 421 (0.38%) received immunotherapy. The recipients were younger (median age 63 vs. 68 years, p < 0.001) and more likely to be white (87.4% vs. 82.1%). Patients with private insurance or Medicare (p < 0.001), and those earning more than $60k annually (51.0% vs. 36.4%, p < 0.001) were more likely to receive immunotherapy. Treatment was more likely in academic/research programs than in community cancer programs (53.0% vs. community, p < 0.001). On multivariate analysis, Black patients had lower odds of receiving immunotherapy than Caucasian patients (OR: 0.74 [95% CI: 0.601–0.882], p = 0.019). Higher income was also a significant predictor of immunotherapy utilization (highest vs. lowest income quartile: OR, 2.228 [95% CI: 1.422–3.491], p < 0.001).
Conclusions:
This study revealed significant disparities in immunotherapy access for stage IV PDAC based on race, socioeconomic status, and geographic location in the United States, highlighting the need for intervention to promote equitable access to this promising treatment modality.
Evaluation of vitamin D supplementation on treatment of Helicobacter pylori eradication in patients with dyspepsia, A randomized controlled trial
Authors: Zendehdel Abolfazl , Jamalimoghadamsiyahkali Saeidreza , Sharifi Alireza , Dabiri Koorosh , heidarizadi Somayeh 
Published: October 2024

Abstract

Objective:
Considering the effects of vitamin D on inflammation and various infections, this study aims to determine if combining vitamin D supplements with anti-Helicobacter pylori antibiotic treatment can improve treatment and eradication of Helicobacter pylori infection.
Method
This study was conducted as a randomised clinical trial (RCT) on 110 patients over 18 years of age with Helicobacter pylori infection. At the beginning of the study, each patient received an oral vitamin D supplement of 50,000 units weekly, while in the control group, each patient received a placebo vitamin D supplement.After 6 weeks, the patients were treated with anti-Helicobacter antibiotics for 5 days.
Results
The results of this study showed that in the group receiving vitamin D, compared to the control group, the negative rate of Helicobacter pylori antigen in stool and response to treatment was 2.8 times higher (p < 0.05).
Conclusion
This study, which is the first clinical trial on the effect of vitamin D supplementation in the treatment of Helicobacter pylori infection(At the time of this research), shows that antibiotic treatment of Helicobacter pylori infection significantly increased in the vitamin D-supplemented group.This means that vitamin D can be effective in improving Helicobacter pylori infection through anti-inflammatory mechanisms.
Trial registration
The trial registered at Iranian Registry of Clinical Trials (code# IRCT20180922041089N2). URL: https://www.irct.ir/trial/35683
Prevalence, Molecular Characterization, Pathogenicity and Antimicrobial Susceptibility Pattern of Clostridioides Difficile From Clinical Samples in South Eastern Nigeria.
Authors: Oghonyon Eddison Igho , Ugwu Malachy C. , Esimone Charles O. , Onah Anthony Ik 
Published: October 2024

Abstract

The prevalence, molecular characterization, pathogenicity and antibioticsensitivity pattern of Clostridioides difficile from clinical samples in South-Eastern Nigeria wereevaluated in this study. Stool samples (450) were collected from patientsinsome selected public and private-owned clinics in the five South-Eastern states. Standard bacteriological methods were employed for enumeration of total anaerobes. Culture of Clostridioides difficile isolates were performed on Clostridium difficile differential agar (supplemented with C. difficile selective supplement). Biochemical tests like catalase, oxidase and reverse CAMP test were conducted before extraction of genomic bacterial DNA for suspected C. difficile isolates. Purification and amplification of bacterial DNA was carried out on 2% agarose gel. Amplified bacteria DNA was sequenced and blasted on the National Centre for Biotechnology Information (NCBI) website. Antibiotics susceptibility was carried out for C. difficile isolates using the Kirby-Bauer disc diffusion technique. PCR technique was employed for the detection of virulence (tcdA, tcdB, cdtAandcdtB) and resistance genes (tetS, tetAandermB) in C. difficile isolates. Anaerobe counts for stool samples obtained showed that samples had a mean count of 5.63±0.09 log10CFU/g (Anambra state) while counts of 5.61±0.11 log10CFU/g and 5.65±0.07 log10CFU/g were obtained from Ebonyi and Enugu States. The antibacterial sensitivity revealed that the isolates were sensitive to gentamicin, meropenem and amoxicillin-clavulanic acid. The isolates were resistant to tetracyclines and erythromycin, and the multiple antibiotic resistance index of theisolates showed that the multi-drug resistant isolates had a MAR index of 0.44. All (14 C. difficile isolates) (100%) of C. difficile isolates were found to possess tcdBgenes, and 69.56% expressed tcdAgenes. One (4.34%) of the C. difficile isolatespossessed cdtAand cdtBgenes for binary toxin production.
YOLO-LF:A lightweight model for fire detection
Authors: Hu Jiusong , Liu Wang , Hou Tianmu , Zhou Chang , Zhong Hao , Li Zhaohui 
Published: October 2024

Abstract

In the domain of fire prevention and emergency response, precise and prompt flame identification is of paramount importance.However, existing methodologies confront challenges such as indistinct target boundaries, obscuration by smoke, detectionof small targets, and background clutter. To address these issues, this paper introduces YOLO-LF, a lightweight variant ofthe YOLO model, based on the YOLOv8 framework. Firstly, we incorporate StarNet, a lightweight network, as the backbone.StarNet leverages multiscale feature extraction and depthwise separable convolutions to capture the intricate edges of flames,thereby enhancing detection accuracy. Secondly, we introduce the Mixed Local Channel Attention (MLCA) mechanism,which automatically adjusts the weight distribution among channels, intensifying the representation of flame features andimproving detection performance in smoky environments. Thirdly, FasterBlock is integrated into the C2F module, augmentingthe effect of feature fusion and increasing sensitivity to small-scale flames. Lastly, EfficientDet serves as the detection head,combining multiscale feature fusion and attention mechanisms to accurately locate flames against complex backgrounds.Weconduct experiments using a custom dataset that includes challenging samples, built upon the publicly available DFS dataset.The results demonstrate that YOLO-LF outperforms comparable methods on both the public and custom datasets. Notably,compared to YOLOv8, YOLO-LF achieves a 4.3% improvement in accuracy on the public dataset, while reducing the number ofparameters by 40%, decreasing GFLOPs by 30%, and increasing frames per second (FPS) by 41%.
Molecular and Histological Responses to AOM in Apex1 Haploinsufficient Mice Reveal a Protective Role of Ape1 in Liver Tissue
Authors: Pérez-Pérez Carmen , Rodríguez-Muñoz Adlin , Mackenzie Gerardo G. , Matsukuma Karen , Castro-Achi María , Ayala-Peña Sylvette , Torres-Ramos Carlos A. 
Published: October 2024

Abstract

Strong evidence indicates that in liver diseases such as cirrhosis and hepatocellular carcinoma, there is a reduction of mitochondrial components, particularly mitochondrial DNA (mtDNA), thus suggesting that loss of mtDNA integrity plays an essential role in the development of liver pathologies. However, little is known about mtDNA repair's contribution to maintaining mtDNA and the prevention of liver-related diseases. We hypothesize that APE1, the main apurinic/apyrimidinic endonuclease that participates in base excision repair-mediated mtDNA repair, is required for the maintenance of mtDNA integrity after liver injury. To test this hypothesis, we used a mouse model with a heterozygous null mutation in the Apex1 gene, which encodes APE1. Liver tissue was evaluated for molecular and histological effects after treatment with the alkylating agent azoxymethane (AOM), a carcinogen widely used for the induction of colorectal cancer in rodents. AOM is bioactivated in the liver, thus this organ could represent a primary target of AOM action and a model for liver injury. We treated WT and Apex1+/− mice with AOM (10 mg/kg body weight) once a week for 4 weeks and liver tissue was harvested 24 weeks after the first dose. Using a PCR-based approach, we observe a 3.2-fold increase in mtDNA damage and a concomitant 55% decrease in mtDNA abundance only in tissue from Apex1+/− mice. To study the bioenergetics status of liver tissues after AOM treatment, we determined the relative protein levels of ATP5β (an oxidative phosphorylation marker) and GAPDH (a glycolysis marker). We observed a 1.5-fold increase and a 2.5-fold increase in the ATP5β/GAPDH in WT and Apex1+/− mice, respectively, indicative of increased oxidative phosphorylation in response to AOM-induced alkylation damage. The noted alterations occur within significant histological transformations, including increased nuclear inclusions and ductular proliferation in liver tissue triggered by AOM in both strains of mice. In contrast, indicators of inflammation and hepatocyte injury, such as portal inflammation and fibrosis, were attenuated only in Apex1+/− mice. In summary, these findings underscore the pivotal role of APE1 in the response of liver tissue to AOM-induced liver damage.
Bayesian Analysis of the Rate of Spontaneous Malignant Mesothelioma Among BAP1 Mutant Mice in the Absence of Asbestos Exposure
Authors: Nielsen Dahlia M. , Hsu Mei , Zapata Michael , Ciavarra Giovanni , Zyl Leonel 
Published: October 2024

Abstract

Cancers of the mesothelium, such as malignant mesothelioma (MM), historically have been attributed solely to exposure to asbestos. Recent large scale genetic and genomic functional studies now show that approximately 20% of all human mesotheliomas are causally linked to highly penetrant inherited (germline) pathogenic mutations in numerous cancer related genes. The rarity of these mutations in humans makes it difficult to perform statistically conclusive genetic studies to understand their biological effects. This has created a disconnect between functional and epidemiological studies. However, since the molecular pathogenesis of MM in mice accurately recapitulates that of human disease, this disconnect between functional and epidemiological studies can be overcome by using inbred mouse strains that harbor mutation(s) in genes involved in the disease. Most mouse studies have focused on the effect of asbestos exposure, leaving the effects of genetic mutations in the absence of exposure understudied. Here, using existing peer-reviewed studies, we investigate the rate of spontaneous MM among mice with and without germline genetic mutations, in the absence of asbestos exposure. We leveraged these published data to generate a historical control dataset (HCD) to allow us to improve statistical power and account for genetic heterogeneity between studies. Our Bayesian analyses indicate that the odds of spontaneous MM among germline BAP1 mutant mice is substantially larger than that of wildtype mice. These results support the existing biological study findings that mesotheliomas can arise in the presence of pathogenic germline mutations, independently of asbestos exposure.
PMFNet: Pyramid Parsing and Multi-Scale Feature Fusion Network for TBM Muck Image Segmentation
Authors: zhang yongzhuang , yuan baoxi , sun jingbo , yuan ziqi , guo jianxin 
Published: October 2024

Abstract

The Tunnel Boring Machine (TBM) is the main construction equipment for modern tunnel construction. The accurate segmentation of muck images is beneficial to improving the TBM excavation efficiency and ensuring construction safety. Existing muck image segmentation methods have some problems, including inadequate feature extraction capabilities, and poor segmentation results for images with dense muck fragments. To solve these problems, we propose a muck image segmentation method based on a convolutional neural network (CNN) encoder-decoder architecture, named Pyramid Parsing and Multiscale Feature Fusion Network (PMFNet). Our method uses a Pyramid Pooling Parsing module (PPP_Block) to enhance the network's ability to obtain global contextual information, while increasing the receptive field to extract multi-scale and spatial feature information in muck images. At the same time, we use the CARAFE_Block for upsampling to restore the spatial dimensions of the feature map. To better extract edge feature information of muck, we introduce an attention mechanism (Attention_Block) to enhance the segmentation ability of the network. Finally, we construct a multi-scale feature fusion module (MSFF_Block) to further obtain texture features and global contextual features. We conducted extensive experiments on a real muck image dataset obtained from the TBM excavation scene, and the results show that PMFNet achieves an Intersection over Union (IoU), pixel accuracy (PA), and F1-Score of 60.72%, 70.37%, and 73.94%, respectively, which are better than other methods. Our method has fewer computational parameters, faster inference speed, and reaches 52 FPS, which can meet the needs of actual TBM excavation sites.