tbuckley/cabot-search huggingface dataset:
Genomic and immune microenvironment features influencing chemoimmunotherapy response in gastric cancer with peritoneal metastasis: a retrospective cohort study
Authors: Pengfei Yu, Guangyu Ding, Xingmao Huang, Chenxuan Wang, Jingquan Fang, Ling Huang, Zeyao Ye, Qi Xu, Xiaoying Wu, Junrong Yan, Qiuxiang Ou, Yian Du, Xiangdong Cheng
Journal: International Journal of Surgery (2024)

Background: Patients with peritoneal metastasis (PM) from gastric cancer (GC) exhibit poor prognosis. Chemoimmunotherapy offers promising clinical benefits; however, its efficacy and predictive biomarkers in a conversion therapy setting remain unclear. The authors aimed to retrospectively evaluate chemoimmunotherapy efficacy in a conversion therapy setting for GC patients with PM and establish a prediction model for assessing clinical benefits. Materials and methods: A retrospective evaluation of clinical outcomes encompassed 55 GC patients with PM who underwent chemoimmunotherapy in a conversion therapy setting. Baseline PM specimens were collected for genomic and transcriptomic profiling. Clinicopathological factors, gene signatures, and tumor immune microenvironment were evaluated to identify predictive markers and develop a prediction model. Results: Chemoimmunotherapy achieved a 41.8% objective response rate and 72.4% R0 resection rate in GC patients with PM. Patients with conversion surgery showed better overall survival (OS) than those without the surgery (median OS: not reached vs 7.82 m, P &lt;0.0001). Responders to chemoimmunotherapy showed higher ERBB2 and ERBB3 mutation frequencies, CTLA4 and HLA-DQB1 expression, and CD8+ T cell infiltration, but lower CDH1 mutation and naïve CD4+ T cell infiltration, compared to nonresponders. A prediction model was established integrating CDH1 and ERBB3 mutations, HLA-DQB1 expression, and naïve CD4+ T cell infiltration (AUC=0.918), which were further tested using an independent external cohort (AUC=0.785). Conclusion: This exploratory study comprehensively evaluated clinicopathological, genomic, and immune features and developed a novel prediction model, providing a rational basis for the selection of GC patients with PM for chemoimmunotherapy-involved conversion therapy.
ChatGPT in medicine: prospects and challenges: a review article
Authors: Songtao Tan, Xin Xin, Di Wu
Journal: International Journal of Surgery (2024)

It has been a year since the launch of Chat Generator Pre-Trained Transformer (ChatGPT), a generative artificial intelligence (AI) program. The introduction of this cross-generational product initially brought a huge shock to people with its incredible potential, and then aroused increasing concerns among people. In the field of medicine, researchers have extensively explored the possible applications of ChatGPT and achieved numerous satisfactory results. However, opportunities and issues always come together. Problems have also been exposed during the applications of ChatGPT, requiring cautious handling, thorough consideration and further guidelines for safe use. Here, we summarized the potential applications of ChatGPT in the medical field, including revolutionizing healthcare consultation, assisting patient management and treatment, transforming medical education and facilitating clinical research. Meanwhile, we also enumerated researchers’ concerns arising along with its broad and satisfactory applications. As it is irreversible that AI will gradually permeate every aspect of modern life, we hope that this review can not only promote people’s understanding of the potential applications of ChatGPT in the future, but also remind them to be more cautious about this “Pandora’s Box” in the medical field. It is necessary to establish normative guidelines for its safe use in the medical field as soon as possible.
An integrated proteomics and metabolomics approach to assess graft quality and predict early allograft dysfunction after liver transplantation: a retrospective cohort study
Authors: Yimou Lin, Haitao Huang, Jiaying Cao, Ke Zhang, Ruihan Chen, Jingyu Jiang, Xuewen Yi, Shi Feng, Jimin Liu, Shusen Zheng, Qi Ling
Journal: International Journal of Surgery (2024)

Background: Early allograft dysfunction (EAD) is a common complication after liver transplantation (LT) and is associated with poor prognosis. Graft itself plays a major role in the development of EAD. We aimed to reveal the EAD-specific molecular profiles to assess graft quality and establish EAD predictive models. Methods: A total of 223 patients who underwent LT were enrolled and divided into training ( n =73) and validation ( n =150) sets. In the training set, proteomics was performed on graft biopsies, together with metabolomics on paired perfusates. Differential expression, enrichment analysis, and protein–protein interaction network were used to identify the key molecules and pathways involved. EAD predictive models were constructed using machine learning and verified in the validation set. Results: A total of 335 proteins were differentially expressed between the EAD and non-EAD groups. These proteins were significantly enriched in triglyceride and glycerophospholipid metabolism, neutrophil degranulation, and the MET-related signaling pathway. The top 12 graft proteins involved in the aforementioned processes were identified, including GPAT1, LPIN3, TGFB1, CD59, and SOS1. Moreover, downstream metabolic products, such as lactate dehydrogenase, interleukin-8, triglycerides, and the phosphatidylcholine/phosphorylethanolamine ratio in the paired perfusate displayed a close relationship with the graft proteins. To predict the occurrence of EAD, an integrated model using perfusate metabolic products and clinical parameters showed areas under the curve of 0.915 and 0.833 for the training and validation sets, respectively. It displayed superior predictive efficacy than that of currently existing models, including donor risk index and D-MELD scores. Conclusions: We identified novel biomarkers in both grafts and perfusates that could be used to assess graft quality and provide new insights into the etiology of EAD. Herein, we also offer a valid tool for the early prediction of EAD.
How to assess the long-term recovery outcomes of patients with cauda equina syndrome before surgery: a retrospective cohort study
Authors: Qiushi Wang, Guangdong Hou, Mengyuan Wen, Zhongwu Ren, Wei Duan, Xin Lei, Zhou Yao, Shixian Zhao, Bin Ye, Zhipeng Tu, Peipei Huang, Fang Xie, Bo Gao, Xueyu Hu, Zhuojing Luo
Journal: International Journal of Surgery (2024)

Background: Factors influencing recovery after decompression surgery for cauda equina syndrome (CES) are not completely identified. We aimed to investigate the most valuable predictors (MVPs) of poor postoperative recovery (PPR) in patients with CES and construct a nomogram for discerning those who will experience PPR. Methods: 356 patients with CES secondary to lumbar degenerative diseases treated at *** Hospital were randomly divided into training (N=238) and validation (N=118) cohorts at a 2:1 ratio. Moreover, 92 patients from the **** Hospital composed the testing cohort. Least Absolute Shrinkage and Selection Operator regression (LASSO) was used for selecting MVPs. The nomogram was developed by integrating coefficients of MVPs in the logistic regression, and its discrimination, calibration, and clinical utility were validated in all three cohorts. Results: After 3 to 5 years of follow-up, the residual rates of bladder dysfunction, bowel dysfunction, sexual dysfunction, and saddle anesthesia were 41.9%, 44.1%, 63.7%, and 29.0%, respectively. MVPs included stress urinary incontinence, overactive bladder, low stream, difficult defecation, fecal incontinence, and saddle anesthesia in order. The discriminatory ability of the nomogram was up to 0.896, 0.919, and 0.848 in the training, validation, and testing cohorts, respectively. Besides, the nomogram showed good calibration and clinical utility in all cohorts. Furthermore, the optimal cut-off value of the nomogram score for distinguishing those who will experience PPR was 148.02, above which postoperative outcomes tend to be poor. Conclusion: The first pre-treatment nomogram for discerning CES patients who will experience PPR was developed and validated, which will aid clinicians in clinical decision-making.
Cost-effectiveness analysis of endovascular versus open repair in patients with abdominal aortic aneurysm in Iran: a cross-sectional study
Authors: Shahin Nargesi, Ali Abutorabi, Yousef Mohamadi, Javad Salimi, Masih Tajdini, Vahid Alipour
Journal: International Journal of Surgery (2024)

Objectives: Abdominal aortic aneurysm is one of the most important cardiovascular diseases, especially in the elderly. People with this disease are at risk of rupture of the abdominal aorta and death. The present study was conducted with the aim of analyzing the cost effectiveness of endovascular repair compared to open surgery in abdominal aortic aneurysm patients in Iran. Methods: A Markov chain model was developed based on the use of endovascular repair and open surgery. The base-case patient was defined as a 65-year-old man presenting with abdominal aortic aneurysm diameter greater than 5 cm. The determination of costs was from the perspective of the public sector provider. QALY was used to calculate the effectiveness. Incremental cost-effectiveness ratio (ICER) and TreeAge software were used for cost-effectiveness analysis. The follow-up period was 10 years and the willingness to pay (WTP) was determined as three times the Gross domestic product (GDP) per capita. Result: At the end of year 10, the endovascular aneurysm repair (EVAR) strategy gained 1,318,313,559 Iranian Rial (IRR) (67885.29$) in cost and 3.57 QALYs in effectiveness. In contrast, the use of the open surgery repair (OSR) strategy gained 1,186,761,858 IRR (61111.16$) in cost and 3·32 QALYs in effectiveness. The incremental cost-effectiveness ratio, comparing EVAR versus OSR, was 53, 346, 3757 IRR (178.36$) per QALYs, which is lower than the proposed WTP, indicating that EVAR is more expensive and more effective. Based on the Monte Carlo simulation test, EVAR is the preferred strategy in 58.6% of the population. Conclusion: Endovascular repair has a relative superiority compared to open surgery, and the probability of the effectiveness of endovascular repair compared to open surgery does not change with increasing willingness to pay.
Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline Update
Authors: John D. Gordan, Erin B. Kennedy, Ghassan K. Abou-Alfa, Eliza Beal, Richard S. Finn, Terence P. Gade, Laura Goff, Shilpi Gupta, Jennifer Guy, Hang T. Hoang, Renuka Iyer, Ishmael Jaiyesimi, Minaxi Jhawer, Asha Karippot, Ahmed O. Kaseb, R. Kate Kelley, Jeremy Kortmansky, Andrea Leaf, William M. Remak, Davendra P.S. Sohal, Tamar H. Taddei, Andrea Wilson Woods, Mark Yarchoan, Michal G. Rose
Journal: Journal of Clinical Oncology (2024)

To update an evidence-based guideline to assist in clinical decision-making for patients with advanced hepatocellular carcinoma (HCC).
Current perspectives and trend of computer-aided drug design: a review and bibliometric analysis
Authors: Zhenhui Wu, Shupeng Chen, Yihao Wang, Fangyang Li, Huanhua Xu, Maoxing Li, Yingjian Zeng, Zhenfeng Wu, Yue Gao
Journal: International Journal of Surgery (2024)

Computer-aided drug design (CADD) is a drug design technique for computing ligand-receptor interactions and is involved in various stages of drug development. To better grasp the frontiers and hotspots of CADD, we conducted a review analysis through bibliometrics.
An anti-infection and biodegradable TFRD-loaded porous scaffold promotes bone regeneration in segmental bone defects: experimental studies
Authors: Haixiong Lin, Zige Li, Zhenze Xie, Shengyao Tang, Minling Huang, Junjie Feng, Yuhan Wei, Zhen Shen, Ruoyu Zhou, Yuanlan Feng, Huamei Chen, Yueyi Ren, Feng Huang, Xiaotong Wang, Ziwei Jiang
Journal: International Journal of Surgery (2024)

Background: Addressing segmental bone defects remains a complex task in orthopedics, and recent advancements have led to the development of novel drugs to enhance the bone regeneration. However, long-term oral administration can lead to malnutrition and poor patient compliance. Scaffolds loaded with medication are extensively employed to facilitate the restoration of bone defects. Methods: Inspired by the local use of total flavonoids of Rhizoma Drynariae (TFRD) in the treatment of fracture, a novel 3D-printed HA/CMCS/PDA/TFRD scaffold with anti-infection, biodegradable and induced angiogenesis was designed, and to explore its preclinical value in segmental bone defect of tibia. Results: The scaffold exhibited good degradation and drug release performance. In vitro, the scaffold extract promoted osteogenesis by enhancing bone-related gene/protein expression and mineral deposition in BMSCs. It also stimulated endothelial cell migration and promoted angiogenesis through the upregulation of specific genes and proteins associated with cell migration and tube formation. This may be attributed to the activation of the PI3k/AKT/HIF-1α pathway, facilitating the processes of osteogenesis and angiogenesis. Furthermore, the HA/CMCS/PDA/TFRD scaffold was demonstrated to alleviate infection, enhance angiogenesis, promote bone regeneration, and increase the maximum failure force of new formed bone in a rat model of segmental bone defects. Conclusion: Porous scaffolds loaded with TFRD can reduce infection, be biodegradable, and induce angiogenesis, presenting a novel approach for addressing tibial segmental bone defects.
Compartmentalization into Outer and Inner Shells of Hollow Nanospheres for Antibiosis Based on Chemistry and Physical Damages
Authors: Chengju Sheng, Yanjun Ding, Mingming Guo
Journal: Advanced Healthcare Materials (2024)

Abstract There is a substantially ascending demand for nonantibiotic strategies to overcome the resistance of bacterial infections. Here, the discovery of a distinctive antibacterial structure is reported. The novel structure of nanoparticle strategy is proposed for appreciable bacteria killing by the smart design of the delayed addition of crosslinkers into the reaction mixture. [2‐(methacryloyloxy)ethyl]trimethylammonium chloride solution (MTCl), a water‐soluble ionic liquid (IL), has narrow‐size material distribution, good whiteness, and high weather resistance. The quaternary ammonium salt is utilized to efficiently permeate cell membranes through electrostatic interaction, accordingly, boasting a beneficiary of antibacterial properties. More importantly, it allows bacteria to attach the nanomaterials easily, especially the double‐shelled nanosphere. In light of the introduction of 9‐amino(9‐deoxy)ep‐quinine (QNNH 2 ) on its inner shell, it blocks the nucleic acid and glucose metabolism in bacteria, which is betterment of the antibacterial activity of double‐shelled structure nanoparticle compared to other structure of nanomaterials. This physical/chemical/biological triple antibacterial process eliminates the need for traditional antibiotics, and the fabrication strategies and material properties described here provide insights into the design of antibacterial nanomaterials based on chemical and physical effects.
FASN-mediated fatty acid biosynthesis remodels immune environment in Clonorchis sinensis infection-related intrahepatic cholangiocarcinoma
Authors: Lixia Xu, Ying Zhang, Zhilong Lin, Xinlang Deng, Xiaoxue Ren, Mingle Huang, Shangru Li, Qianying Zhou, Fei Fang, Qingxia Yang, Gaomin Zheng, Zebin Chen, Zhongdao Wu, Xi Sun, Jie Lin, Jingxian Shen, Jianping Guo, Xiaoxing Li, Tianchen Xue, Jing Tan, Xiaoxuan Lin, Li Tan, Hong Peng, Shunli Shen, Sui Peng, Shaoqiang Li, Lijian Liang, James M. Cleary, Jiaming Lai, Yubin Xie, Ming Kuang
Journal: Journal of Hepatology (2024)
Oncogenic cell tagging and single-cell transcriptomics reveal cell type-specific and time-resolved responses to Vhl inactivation in the kidney
Authors: Samvid Kurlekar, Joanna D.C.C. Lima, Ran Li, Olivia Lombardi, Norma Masson, Ayslan B. Barros, Virginia Pontecorvi, David R. Mole, Christopher W. Pugh, Julie Adam, Peter J. Ratcliffe
Journal: Cancer Research (2024)

Defining the initial events in oncogenesis and the cellular responses they entrain, even in advance of morphologic abnormality, is a fundamental challenge in understanding cancer initiation. As a paradigm to address this, we longitudinally studied the changes induced by loss of the tumor suppressor gene von Hippel Lindau (VHL), which ultimately drives clear cell renal cell carcinoma. Vhl inactivation was directly coupled to expression of a tdTomato reporter within a single allele, allowing accurate visualization of affected cells in their native context and retrieval from the kidney for single-cell RNA sequencing. This strategy uncovered cell type-specific responses to Vhl inactivation, defined a proximal tubular cell class with oncogenic potential, and revealed longer term adaptive changes in the renal epithelium and the interstitium. Oncogenic cell tagging also revealed markedly heterogeneous cellular effects including time-limited proliferation and elimination of specific cell types. Overall, this study reports an experimental strategy for understanding oncogenic processes in which cells bearing genetic alterations can be generated in their native context, marked, and analyzed over time. The observed effects of loss of Vhl in kidney cells provide insights into VHL tumor suppressor action and development of renal cell carcinoma.
Treatment and survival for patients with localized primary ocular adnexal extranodal marginal zone lymphoma
Authors: Lin-Rui Gao, Xin Li, Xinyue Wang, Yuanzheng Liang, Yunpeng Wu, Xiao-Li Feng, Wei Rao, Xin Liu, Yong-Wen Song, Hui Fang, Bo Chen, Jing Jin, Yue-Ping Liu, Hao Jing, Yuan Tang, Ning-Ning Lu, Shu-Lian Wang, Ye-Xiong Li, Liang Wang, Shu-Nan Qi
Journal: Leukemia (2024)
Tranexamic acid in variceal bleeding revisited
Authors: Krithivasan P. Raman, David Patch
Journal: Hepatology (2024)

Department of Hepatology, Royal Free London NHS Abbreviations: DIC, disseminated intravascular coagulation; GI, gastrointestinal; HCT, haematocrit; PT, prothrombin time; ROTEM, rotational thromboelastometry; TIPS, transjugular intrahepatic portosystemic shunt; TXA, tranexamic acid. Correspondence David Patch, Department of Hepatology, Royal Free Hospital, Pond Street, London NW3 2QG. Email: [email protected]
Finding the TRAIL to escape granzyme B–mediated liver injury in PSC
Authors: Maria Eugenia Guicciardi, Nidhi Jalan-Sakrikar
Journal: Hepatology (2024)

Division of Gastroenterology and Hepatology, Center for Cell Signaling in Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA Abbreviations: CD8+TEM, CD8+effector memory T cells; CITE-seq, cellular indexing of transcriptomes and epitopes by sequencing; Gzmb, Granzyme B; HLA, Human Leukocyte Antigen; IFNγ, Interferon gamma; PSC, Primary Sclerosing Cholangitis; scRNA-seq, single cell RNA sequencing; TRAIL, Tumor necrosis factor-related apoptosis-inducing ligand Correspondence Nidhi Jalan-Sakrikar, Assistant Professor of Medicine, Assistant Professor of Biochemistry and Molecular Biology, Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905. Email: [email protected] Correspondence Maria Eugenia Guicciardi, Assistant Professor of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905. Email: [email protected]
MASH clinical trials and drugs pipeline: An impending tsunami
Authors: Mazen Noureddin
Journal: Hepatology (2024)

Metabolic dysfunction–associated steatotic liver disease, formerly known as NAFLD, has ascended to prominence as the predominant chronic liver disease in Western countries and now stands as a leading cause of liver transplantations. In the more advanced stage, metabolic dysfunction–associated steatohepatitis (MASH) may lead to fibrosis, a gateway to cirrhosis, liver cancer, and liver failure. Despite extensive research and exploration of various drug mechanisms, the anticipation for the inaugural approved drug to materialize by 2024 is palpable, marking a significant milestone. Numerous pathways have been investigated for MASH treatment, exploring thyroid hormone receptors, glucagon-like peptides 1, peroxisome proliferator–activated receptors, and agents influencing hepatic steatosis synthesis, inflammatory pathways, genetic components, fibrosis mechanisms, and an array of other avenues. Over time, key regulatory directions have crystallized, now manifesting in 2 primary endpoints under investigation: resolution of steatohepatitis without worsening fibrosis and/or improvement of fibrosis stage without worsening of steatohepatitis, especially used in phase 3 clinical trials, while alternative noninvasive endpoints are explored in phase 2 trials. The prospect of proving efficacy in clinical trials opens doors to combination therapies, evaluating the ideal combination of drugs to yield comprehensive benefits, extending beyond the liver to other organs. Certain combination drug trials are already underway. In this review, we discuss the forefront of MASH drug research as of 2023/2024, illuminating mechanisms, outcomes, and future trajectories. Furthermore, we tackle the challenges confronting MASH trials and propose potential strategies for surmounting them.
Peak ADAMTS13 activity to assess ADAMTS13 conformation and risk of relapse in immune-mediated thrombotic thrombocytopenic purpura
Authors: Nithya Prasannan, Bertina Dragunaite, Maryam Subhan, Mari Thomas, Rens de Groot, Deepak Singh, Karen Vanhoorelbeke, Marie Scully
Journal: Blood (2024)
Use of automated conversational agents in improving young population mental health: a scoping review
Authors: Raluca Balan, Anca Dobrean, Costina R. Poetar
Journal: npj Digital Medicine (2024)

Automated conversational agents (CAs) emerged as a promising solution in mental health interventions among young people. Therefore, the objective of this scoping review is to examine the current state of research into fully automated CAs mediated interventions for the emotional component of mental health among young people. Selected databases were searched in March 2023. Included studies were primary research, reporting on development, feasibility/usability, or evaluation of fully automated CAs as a tool to improve the emotional component of mental health among young population. Twenty-five studies were included (N = 1707). Most automated CAs applications were standalone preventions targeting anxiety and depression. Automated CAs were predominantly AI-based chatbots, using text as the main communication channel. Overall, the results of the current scoping review showed that automated CAs mediated interventions for emotional problems are acceptable, engaging and with high usability. However, the results for clinical efficacy are far less conclusive, since almost half of evaluation studies reported no significant effect on emotional mental health outcomes. Based on these findings, it can be concluded that there is a pressing need to improve the existing automated CAs applications to increase their efficacy as well as conducting more rigorous methodological research in this area.