bluuebunny/crossref_metadata_2025_split huggingface dataset:
Causal Relationship Between Glucose and Inflammatory Bowel Disease: A Bidirectional Two-Sample Mendelian Randomization Study
Authors: Cen JiePeng , Chen Kequan , Ni Ziyan , Dai QiJie , Lu Weipeng , Tao Heqing , Peng Liang 
Published: December 2023

Abstract

Background
Association between glucose and inflammatory bowel disease (IBD) was found in previous observational studies and in cohort studies. However, it is not clear whether these associations reflect causality. Thus, this study investigated whether there is such a causal relation between elevated glucose and IBD, Crohn’s disease (CD) and ulcerative colitis (UC).
Methods
We performed a two-sample Mendelian Randomization (MR) with the independent genetic instruments identified from the largest available genome-wide association study (GWAS) for IBD (5,673 cases; 213,119 controls) and its main subtypes, CD and UC. Summarized data for glucose which included 200,622 cases and glycemic traits including HbA1c and type 2 diabetes(T2DM) were obtained from different GWAS studies. Primary and secondary analyses were conducted by preferentially using the radial inverse-variance weighted (IVW) approach. A number of other meta-analysis approach and sensitivity analyses were carried out to assess the robustness of the results.
Results
We did not find a causal effect of genetically predicted glucose on IBD as a whole (OR 0.858; 95% CI 0.649–1.135; P = 0.286). In subtype analyses glucose was also suggestively not associated with Crohn's disease (OR 0.22; 95% CI 0.04-1.00; P = 0.05) and ulcerative colitis(OR 0.940; 95% CI 0.628–1.407; P = 0.762). In the other direction, IBD and it’s subtypes were not related to glucose and glycemic traits.
Conclusions
This MR study is not providing any evidence for a causal relationship between genetically predicted elevated glucose and IBD as well as it’s subtypes UC and CD. Regarding the other direction, no causal associations could be found. Future studies with robust genetic instruments are needed to confirm this conclusion.
A microphysiological system reveals neutrophil contact-dependent attenuation of pancreatic tumor progression by CXCR2 inhibition-based immunotherapy
Authors: Shao Shuai , Delk Nikki A. , Jones Caroline N. 
Published: December 2023

Abstract

Cancer cells recruit neutrophils from the bloodstream into the tumor tissue, where these immune cells promote the progression of numerous solid tumors. Studies in mice suggest that blocking neutrophil recruitment to tumors by inhibition of neutrophil chemokine receptor CXCR2 could be a potential immunotherapy for pancreatic cancer. Yet, the mechanisms by which neutrophils promote tumor progression in humans, as well as how CXCR2 inhibition could potentially serve as a cancer therapy, remain elusive. In this study, we developed a human cell-based microphysiological system to quantify neutrophil-tumor spheroid interactions in both “separated” and “contact” scenarios. We found that neutrophils promote the invasion of tumor spheroids through the secretion of soluble factors and direct contact with cancer cells. However, they promote the proliferation of tumor spheroids solely through direct contact. Interestingly, treatment with AZD-5069, a CXCR2 inhibitor, attenuates invasion and proliferation of tumor spheroids by blocking direct contact with neutrophils. Our findings show that CXCR2 inhibition reduces neutrophil migration toward tumor spheroids. These results shed new light on the tumor-promoting mechanisms of human neutrophils and the tumor-suppressive mechanisms of CXCR2 inhibition in pancreatic cancer and may aid in the design and optimization of novel immunotherapeutic strategies based on neutrophils.
Controlling the Nutritional Status Score: A New Tool for Predicting Postoperative Mortality in Patients with Infrarenal Abdominal Aortic Aneurysm Treated with Endovascular Aneurysm Repair
Authors: Ye Sheng−Lin , Xu Tian−Ze , Wang Chuang , Han Kang , Jiang Xu−Dong , Tang Tao , Song Bin , Hu Nan , Du Xiao−Long , Li Xiao−Qiang 
Published: December 2023

Abstract

Background
Abdominal aortic aneurysm is a fatal condition that commonly occurs during vascular surgery. In many diseases, nutritional status is closely associated with prognosis. Scores from the Controlling Nutritional Status (CONUT) screening tool have been shown to predict outcomes of certain malignancies and chronic diseases. However, the impact of nutritional status on abdominal aortic aneurysm (AAA) treated with endovascular aneurysm repair (EVAR) has not yet been reported. In this study, we explored the relationship between CONUT scores and postoperative prognoses of AAA patients treated with EVAR.
Methods
This was a retrospective review of 177 AAA patients treated with EVAR from June 2018 to November 2019 in a single center. Patient characteristics, nutritional status (CONUT scores), and postoperative status were collected. These patients were divided into groups A and B based on the CONUT scores. We compared the baseline characteristics of the two groups. Cox proportional risk and logistic regression analyses were used to determine the independent predictors of mid − term mortality and complications, respectively.
Results
Compared with group A, patients in group B had higher midterm mortality (P < 0.001). Univariate analysis showed that CONUT scores; respiratory diseases; stent types; preoperative hemoglobin (Hb), preoperative C − reactive protein, preoperative prothrombin time, and preoperative fibrinogen levels were risk factors for death. Multivariate analysis confirmed that CONUT score [hazard ratio, 1.276; 95% confidence interval (CI), 1.029–1.584; P = 0.027] was an independent risk factor for mortality. Logistic regression analysis showed that prior arterial disease, smoking, and D − dimer levels were risk factors, although multivariate analysis showed smoking (odds ratio, 3.492; 95% CI, 1.426–8.553; P = 0.006) was an independent risk factor. Kaplan − Meier curves showed that patients in group B had shorter mid − term survival than those in group A (log − rank P < 0.001).
Conclusion
Malnutrition was strongly associated with mid − term mortality in patients with infrarenal AAA treated with EVAR.
Single-cell analysis reveals heterogeneity in the molecular profile of the tumor microenvironment of biliary tract cancers
Authors: Lai Hua-ping , Mai Qicong , Tsauo Jiaywei , Wang Qi , Mo Zhiqiang , He Shunfa , Wang Senrui , Yang Yifan , Zhou Zejian , Yu Yilan , Wang Kejian , Zhang Jing , Mo Steven , Gou Qing 
Published: December 2023

Abstract
Background
Biliary tract cancers (BTCs) are heterogeneous malignancies with diverse tumor microenvironment (TME) cells that contribute to tumor progression. However, the characteristics of the TME among different subtypes of BTCs remain unclear.
Methods
We integrated single-cell RNA sequencing data from BTC patients (iCCA, GBC, and eCCA) and RNA sequencing data from cholangiocarcinoma samples to construct a cellular molecular atlas of BTCs. Through enrichment analysis, we explored signaling pathways in tumor and TME cells, identified developmental trajectories and characterized transcription factors regulating different cell subpopulations using pseudotime analysis and gene regulatory network analysis. Moreover, we analyzed the intercellular communication between tumor cells and TME cells in different BTCs and developed a prognostic model.
Results
Malignant cells in different BTCs displayed significant heterogeneity, with variations in immune cell composition, biological functions, and metabolic pathways. Notably, the iCCA subpopulation demonstrated enhanced invasive potential, while the eCCA and GBC subpopulations showed significant activation of energy metabolism-related pathways. The carcinoma-associated fibroblast subpopulations in eCCA and GBC may regulate tumor cell metabolism through metabolic reprogramming, thereby facilitating tumor proliferation. GBC specifically exhibited enrichment of CXCL13 + tumor-reactive CD8 + T cells, indicating a potentially favorable response to immune checkpoint blockade therapy. Additionally, as tumor progression occurred, macrophage subpopulations in all three BTCs displayed M1/M2 dichotomous polarization, and the antigen-presenting ability of monocyte-derived dendritic cells gradually decreased.
Conclusion
This study analyzed single-cell landscape heterogeneity across BTC subtypes, revealing complex intercellular communication within the TME. A prognostic model was developed, providing insights for personalized precision medicine.
A randomized controlled trial evaluating low-intensity shockwave therapy for treatment of persistent storage symptoms following transurethral surgery for benign prostatic obstruction
Authors: Elshal Ahmed , Hegazy Mohammed , Sheir Khaled , Gaballah Mohamed 
Published: December 2023

Abstract
Background: Low-intensity shockwave therapy (Li-SWT) can improve bladder function through enhancement of angiogenesis and nerve regeneration and suppression of inflammation and overactivity. In this trial, we aimed to evaluate the efficacy of Li-SWT on persistent storage symptoms after transurethral surgery (TUS) for benign prostatic obstruction (BPO).Methods: Between July 2020 and July 2022, 132 patients with persistent storage symptoms; urgency episodes/24 h ≥ 1 and daytime frequency ≥ 8, for at least three months after TUS for BPO were randomly allocated to Li-SWT versus sham versus solifenacin 10 mg/day in 3:1:1 ratio. The primary end point was the percent reduction from baseline in overactive bladder symptom score (OABSS) at 3-month follow-up. The changes in 3-day voiding diary parameters, quality of life (QoL) score, peak flow rate and residual urine at 3 and 6-month follow-up were compared. Treatment-related adverse effects were also evaluated.Results: Baseline data were comparable between groups. The percent reduction from baseline in OABSS at 3-month follow-up was significantly higher in Li-SWT compared to sham (-55% versus − 11%), and it was comparable between Li-SWT and solifenacin 10 mg (-55% versus − 60%). Li-SWT achieved significant improvement like solifenacin 10 mg in 3-day voiding diary parameters and QoL score at 3-month follow-up. This improvement remained comparable between Li-SWT and solifenacin-10 at 6-month follow-up. No adverse effects related to Li-SWT were noted apart from tolerable pain during the procedure. Solifenacin 10 mg was associated with bothersome adverse effects in 73% of the patients with 11.5% discontinuation rate.Conclusions: Li-SWT ameliorates persistent storage symptoms and promotes QoL after TUS for BPO, with comparable efficacy and better tolerance compared to solifenacin.
Classical Monocyte Marker Gene Signatures (CMMGS) Identified by Analysis of Single-Cell and Bulk-RNA Sequencing to Predict Prognosis and Immunotherapy Response in Lung Adenocarcinoma
Authors: LIN HAN , Huang Yuhan , Ren Shencheng , Ma Teng , Ge Di 
Published: December 2023

Abstract
Background Classical monocytes, pivotal in the innate immune response, wield considerable influence over cancer prognosis and response to immunotherapy. Our aim was to construct lung adenocarcinoma (LUAD) prognostic signature associated with Classical monocytes.Methods This study encompassed 1,822 samples drawn from diverse public datasets. Initially, we conducted an comprehensive analysis of lung adenocarcinoma (LUAD) single-cell RNA sequencing data obtained from the Gene Expression Omnibus (GEO), identifying 145 marker genes specific to classical monocyte. Univariate Cox regression and Least Absolute Shrinkage Operator (LASSO) analyses were performed on the TCGA training cohort to construct a signature for classical monocyte marker genes.Result Patients in the TCGA LUAD cohort were categorized into high- and low-risk groups based on polygenic prognostic signature derived from these marker genes. The predictive capacity of this signature was robustly validated across distinct clinical subgroups and GEO cohorts. Notably, this signature emerged as an independent prognostic indicator via multivariate analysis. Low-risk patients exhibited heightened immune cell infiltration, correlating inversely with inflammatory activity and risk score. Conversely, the low-risk group demonstrated amplified abundance and diversity in T-cell receptor (TCR) repertoires, higher Immunophenotype scores (IPS), and lower Tumor Immune Dysfunction and Exclusion (TIDE) scores. Significantly, an assessment across three GEO immunotherapy cohorts showcased superior immunotherapeutic response and prognosis among low-risk patients compared to their high-risk counterparts.Conclusion In summary, our study introduces a novel signature rooted in monocyte marker genes that proficiently prognosticates and predicts immunotherapeutic response in LUAD patients.Supplementary Information: Supplementary information is uploaded in the attached document.
Clinical Outcomes of Laser Hemorrhoidoplasty with Feeding Vessels Suture Ligation. A Retrospective Study in a Single Center
Authors: Chen Kai-Hsiang , Huang Yi-Ling , Lin Chun-Yu , Chen Ming-Cheng , Chiu Teng-Yi , Chiang Feng-Fan 
Published: December 2023

Abstract
Background
Laser hemorrhoidoplasty has demonstrated significant therapeutic effectiveness. In order to diminish postoperative bleeding and enhance overall outcomes, we have additionally adopted suture-ligating the feeding vessels.
This study aimed to investigate patients who underwent this procedure and to better understand the treatment outcomes and any associated complications.
Methods
This study included 173 patients who had grade II to III symptomatic hemorrhoids and had undergone laser hemorrhoidoplasty with feeding vessels suture ligation between September 1, 2020 and August 31, 2022 consecutively.
First, hemorrhoid-feeding vessels located approximately 2 cm above the dentate line were identified by grasping the hemorrhoid tissues. These vessels were then suture-ligated. Subsequently, diode laser shots were administered to each hemorrhoid.
Surgical-related information, short-term postoperative pain, discomfort following discharge, hemorrhoid recurrence and any complications were all obtained from inpatient records, outpatient follow-ups, and telephone interviews.
Results
173 patients were included in the study. The median pain score at four hours postoperatively was 3. Nine patients (5.2%) experienced bleeding. Six patients (3.5%) developed abscesses. Twelve patients (6.9%) reported a symptomatic recurrence, at an average time of 6.2 months. Three patients (1.7%) still experience a tenesmus sensation, while 6 (3.5%) have had a change in flatulence sensation which has now gradually improved. More than 90% of the patients were satisfied with the results, while 8.7% expressed dissatisfaction.
Limitations
This was a retrospective study at a single medical center. We cannot obtain long-term follow-up results due to the fact we began this procedure in 2020.
Conclusions
Laser hemorrhoidoplasty with feeding vessels suture ligation appears to be a promising minimally invasive treatment option for symptomatic grade II and III hemorrhoids.
Angels or Demons: Investigating and Detecting Decentralized Financial Traps on Ethereum Smart Contracts
Authors: Chen Jiachi , Hu Jiang , Xia Xin , Lo David , Grundy John , Gao Zhipeng , Chen Ting 
Published: December 2023

Abstract

Decentralized Finance (DeFi) uses blockchain technologies to transform traditional financial activities into decentralized platforms that run without intermediaries and centralized institutions. Smart contracts are programs that run on the blockchain, and by utilizing smart contracts, developers can more easily develop DeFi applications. Some key features of smart contracts -- self-executed and immutability -- ensure the trustworthiness, transparency and efficiency of DeFi applications, and have led to a fast-growing DeFi market. However, misbehaving developers can add traps or backdoor code snippets to a smart contract, which are hard for contract users to discover. We call these code snippets in a DeFi smart contract as ''DeFi Contract Traps" (DCTs). In this paper, we identify five DeFi contract traps and introduce their behaviors, describe how attackers use them to make unfair profits, and analyse their prevalence in the Ethereum platform. We propose a symbolic execution tool, DeFiDefender, to detect such traps and use a manually labeled small-scale dataset that consists of 700 smart contracts to evaluate it. Our results show that our tool is not only highly effective but also highly efficient. DeFiDefender only needs 0.48s to analyze one DeFi smart contract and obtains a high average accuracy (98.17%), precision (99.74%), and recall (89.24%). Among the five DeFi contract traps introduced in this paper, four of them can be detected through contract bytecode without the need for source code. We also apply DeFiDefender to a large-scale dataset that consists of 20,679 real DeFi related Ethereum smart contracts. We found that 52.13% of these DeFi smart contracts contain at least one contract trap. Although a smart contract that contains contract traps is not necessarily malicious, our finding suggests that DeFi related contracts have many centralized issues in a zero-trust environment and in the absence of a trusted party.
Inside the Matrix: A pancreas-derived hydrogel for the culture of hiPSC-derived pancreatic endocrine cells
Authors: Berger Constantin , Glaser Markus , Ziegler Anna-Lena , Neukel Valentina , Walz Fabiola , Zdzieblo Daniela 
Published: December 2023

Abstract

Stem cell-derived β-cells (SC-BCs) display a potential source for curing diabetes. Up to now, in vitro generated SC-BCs display an immature phenotype and lack important features in comparison to their bona-fide counterparts. Transplantation into a living animal promotes SC-BCs maturation, indicating that components of the in vivo microenvironment trigger final SC-BCs development. Here, we investigated whether cues of the pancreas specific extracellular matrix (ECM) can improve the differentiation of human induced pluripotent stem cells (hiPSCs) towards β-cells in vitro. To this aim, a pancreas specific ECM (PanMa) hydrogel was generated from decellularized pancreas of the pig and its effect on the differentiation and maturation of hiPSC-derived pancreatic hormone expressing cells (HECs) tested. The produced hydrogel solidified upon neutralization at 37°C with gelation kinetics similar to Matrigel. Cytocompatibility of the PanMa hydrogel was demonstrated for a culture duration of 21 days. Encapsulation and culture of HECs in the PanMa hydrogel over 7 days resulted in a stable gene and protein expression of β-cell markers, but did not improve β-cell maturation. In conclusion, the study describes the production of a PanMa hydrogel, which provides the basis for the development of ECM hydrogels that are more adapted to the demands of SC-BCs.
A Retrospective View on Triple Negative Breast Cancer Microenvironment: Novel Markers, Interactions, and Mechanisms of Tumor-Associated Components using public Single-cell RNA Seq Datasets
Authors: Kim Minsoo , Yang Wonhee , Hong Dawon , Won Hye Sung , Yoon Seokhyun 
Published: December 2023

Abstract
Purpose: Triple-negative breast cancer presents a significant clinical challenge due to its aggressive nature and limited treatment options. This subtype is notorious for a poorer prognosis compared to other breast cancer forms, primarily due to the lack of identifiable treatment targets.
Methods: In our study, we delve deep into the molecular landscape of TNBC using public single-cell RNA sequencing datasets. Our integrative analysis aims to identify unique markers specific to TNBC, unravel the intricate gene mechanisms they are involved in, and explore new avenues for potential therapeutic interventions.
Results: Employing three comprehensive datasets, our study offers a novel perspective on the tumor microenvironment of TNBC. Specifically, we found 12 marker genes, including DSC2 and CDKN2A, uniquely expressed in TNBC cells, marking an advancement in understanding this cancer subtype. A comparative analysis of these markers across various components of the tumor microenvironment, including both cancerous and normal cells, highlights a distinctive feature. A key discovery of our study is the interaction between DSC2 and DSG2 genes within TNBC cells, suggesting a novel pathway of intercellular communication exclusive to this cancer type.
Conclusion: This finding not only corroborates previous hypotheses but also lays the foundation for a new structural understanding of triple-negative breast cancer, as revealed through our single-cell analysis workflow.
Nighttime Driver Behavior Prediction Using Taillight Signal Recognition via CNN-SVM Classifier
Authors: Bagheri Elmira , Barshooi Amir Hossein 
Published: December 2023

Abstract

This paper aims to enhance the ability to predict nighttime driving behavior by identifying the taillights of both human-driven and autonomous vehicles. The proposed model incorporates a customized detector designed to accurately detect front-vehicle taillights on the road. At the beginning of the detector, a learnable pre-processing block is implemented, which extracts deep features from input images and calculates the data rarity for each feature. In the next step, drawing inspiration from soft attention, a weighted binary mask is designed that guides the model to focus more on predetermined regions. This research utilizes Convolutional Neural Networks (CNNs) to extract distinguishing characteristics from these areas, then reduces dimensions using Principal Component Analysis (PCA). Finally, the Support Vector Machine (SVM) is used to predict the behavior of the vehicles. To train and evaluate the model, a large-scale dataset is collected from two types of dash-cams and Insta360 cameras from the rear view of Ford Motor Company vehicles. This dataset includes over 12K frames captured during both daytime and nighttime hours. To address the limited nighttime data, a unique pixel-wise image processing technique is implemented to convert daytime images into realistic night images. The findings from the experiments demonstrate that the proposed methodology can accurately categorize vehicle behavior with 92.14% accuracy, 97.38% specificity, 92.09% sensitivity, 92.10% F1-measure, and 0.895 Cohen’s Kappa Statistic. Further details are available at https://github.com/DeepCar/Taillight_Recognition.