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Journal of Intelligent Learning Systems and Applications 2024年第1期16卷 12-22页

作者： Shadman Mahmood Khan Pathan Sakan Binte Imran Departmentof Electrical and Computer Engineering Old Dominion University Norfolk USA sir salimullah medical college Dhaka Bangladesh

Cardiovascular Diseases (CVDs) pose a significant global health challenge, necessitating accurate risk prediction for effective preventive measures. This comprehensive comparative study explores the performance of traditional Machine Learning (ML) and Deep Learning (DL) models in predicting CVD risk, utilizing a meticulously curated dataset derived from health records. Rigorous preprocessing, including normalization and outlier removal, enhances model robustness. Diverse ML models (Logistic Regression, Random Forest, Support Vector Machine, K-Nearest Neighbor, Decision Tree, and Gradient Boosting) are compared with a Long Short-Term Memory (LSTM) neural network for DL. Evaluation metrics include accuracy, ROC AUC, computation time, and memory usage. Results identify the Gradient Boosting Classifier and LSTM as top performers, demonstrating high accuracy and ROC AUC scores. Comparative analyses highlight model strengths and limitations, contributing valuable insights for optimizing predictive strategies. This study advances predictive analytics for cardiovascular health, with implications for personalized medicine. The findings underscore the versatility of intelligent systems in addressing health challenges, emphasizing the broader applications of ML and DL in disease identification beyond cardiovascular health.

关键词： Cardiovascular Disease Machine Learning Deep Learning Predictive Modeling Risk Assessment Comparative Analysis Gradient Boosting LSTM

Clinical profile and outcomes of hepatocellular carcinoma in primary Budd-Chiari syndrome

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 699-715页

作者： Ankit Agarwal Sagnik Biswas Shekhar Swaroop Arnav Aggarwal Ayush Agarwal Gautam Jain Anshuman Elhence Arun Vaidya Amit Gupte Ravi Mohanka Ramesh Kumar Ashwani Kumar Mishra Shivanand Gamanagatti Shashi Bala Paul Subrat Kumar Acharya Akash Shukla Shalimar Department of Gastroenterology and Human Nutrition All India Institute of Medical SciencesNew Delhi 110029DelhiIndia Department of Gastroenterology Seth Gordhandas Sunderdas Medical College and KEM HospitalMumbai 400012MaharashtraIndia Department of Gastroenterology Sir HN Reliance Foundation HospitalMumbai 400004India Department of Liver Transplant and HPB Sir HN Reliance Foundation HospitalMumbai 400004India Department of Gastroenterology All India Institute of Medical SciencesPatna 801507India Professor of Biostatistics National Drug Dependence Treatment Centre(NDDTC)All India Institute of Medical SciencesNew Delhi 110029India Department of Radiodiagnosis All India Institute of Medical SciencesNew Delhi 110029DelhiIndia

BACKGROUND There is scant literature on hepatocellular carcinoma(HCC)in patients with Budd-Chiari syndrome(BCS).AIM To assess the magnitude,clinical characteristics,feasibility,and outcomes of treatment in BCS-HCC.METHODS A total of 904 BCS patients from New Delhi,India and 1140 from Mumbai,India were included.The prevalence and incidence of HCC were determined,and among patients with BCS-HCC,the viability and outcomes of interventional therapy were evaluated.RESULTS In the New Delhi cohort of 35 BCS-HCC patients,18 had HCC at index presentation(prevalence 1.99%),and 17 developed HCC over a follow-up of 4601 person-years,[incidence 0.36(0.22-0.57)per 100 person-years].BCS-HCC patients were older when compared to patients with BCS alone(P=0.001)and had a higher proportion of inferior vena cava block,cirrhosis,and long-segment vascular obstruction.The median alpha-fetoprotein level was higher in patients with BCS-HCC at first presentation than those who developed HCC at follow-up(13029 ng/mL vs 500 ng/mL,P=0.01).Of the 35 BCS-HCC,26(74.3%)underwent radiological interventions for BCS,and 22(62.8%)patients underwent treatment for HCC[transarterial chemoembolization in 18(81.8%),oral tyrosine kinase inhibitor in 3(13.6%),and transarterial radioembolization in 1(4.5%)].The median survival among patients who underwent interventions for HCC compared with those who did not was 3.5 years vs 3.1 mo(P=0.0001).In contrast to the New Delhi cohort,the Mumbai cohort of BCS-HCC patients were predominantly males,presented with a more advanced HCC[Barcelona Clinic Liver Cancer C and D],and 2 patients underwent liver transplantation.CONCLUSION HCC is not uncommon in patients with BCS.Radiological interventions and liver transplantation are feasible in select primary BCS-HCC patients and may improve outcomes.

关键词： Budd chiari syndrome Cancer Cirrhosis Thrombosis Liver Varices Transarterial chemoembolization Hepatic venous outflow tract obstruction

Vonoprazan 10 mg or 20 mg vs. lansoprazole 15 mg as maintenance therapy in Asian patients with healed erosive esophagitis: A randomized controlled trial

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中华医学杂志(英文版) 2024年第8期137卷 962-971页

作者： Xiao Yinglian Qian Jiaming Zhang Shutian Dai Ning Chun Hoon Jai Chiu Chengtang Chong Chui Fung Funao Nobuo Sakurai Yuuichi Eisner Jessica D. Xie Li Chen Minhu Beijing 100006 Beijing Friendship Hospital Capital medical University Beijing 100050 sir Run Run Shaw Hospital School of Medicine Zhejiang University Hangzhou Zhejiang 310020 Department of Internal Medicine Korea University Anam Hospital Department of Gastroenterology Korea University college of Medicine 73 Goryeodae-ro Seongbuk-gu Seoul 02841 Republic of Korea Department of Gastroenterology & Hepatology Linkou medical Center Chang Gung Memorial Hospital Taoyuan The First Affiliated Hospital Taiwan 33353 Takeda Development Center Asia Singapore 018981 Singapore Takeda Pharmaceutical Company Chuo-ku Osaka 540-8645 Japan Takeda Pharmaceuticals International Company Cambridge Sun Yat-sen University MA 02142 USA China medical Team Takeda China Beijing 100027 Guangzhou Guangdong 510062 China Peking Union medical college Hospital Peking Union medical college Chinese Academy of medical Sciences

Background: Erosive esophagitis (EE) is a gastroesophageal reflux disease characterized by mucosal breaks in the esophagus. Proton pump inhibitors are widely used as maintenance therapy for EE, but many patients still relapse. In this trial, we evaluated the noninferiority of vonoprazanvs. lansoprazole as maintenance therapy in patients with healed EE.Methods: We performed a double-blind, double-dummy, multicenter, phase 3 clinical trial among non-Japanese Asian adults with endoscopically confirmed healed EE from April 2015 to February 2019. Patients from China, South Korea, and Malaysia were randomized to vonoprazan 10 mg or 20 mg once daily or lansoprazole 15 mg once daily for 24 weeks. The primary endpoint was endoscopically confirmed EE recurrence rate over 24 weeks with a noninferiority margin of 10% using a two-sided 95% confidence interval (CI). Treatment-emergent adverse events (TEAEs) were recorded.Results: Among 703 patients, EE recurrence was observed in 24/181 (13.3%) and 21/171 (12.3%) patients receiving vonoprazan 10 mg or 20 mg, respectively, and 47/184 (25.5%) patients receiving lansoprazole (differences: -12.3% [95% CI, -20.3% to-4.3%] and -13.3% [95% CI, -21.3% to -5.3%], respectively), meeting the primary endpoint of noninferiority to lansoprazole in preventing EE recurrence at 24 weeks. Evidence of superiority (upper bound of 95% CI <0%) was also observed. At 12 weeks, endoscopically confirmed EE recurrence was observed in 5/18, 2/20, and 7/20 of patients receiving vonoprazan 10 mg, vonoprazan 20 mg, and lansoprazole, respectively. TEAEs were experienced by 66.8% (157/235), 69.0% (156/226), and 65.3% (158/242) of patients receiving vonoprazan 10 mg, vonoprazan 20 mg, and lansoprazole, respectively. The most common TEAE was upper respiratory tract infection in 12.8% (30/235) and 12.8% (29/226) patients in vonoprazan 10 mg and 20 mg groups, respectively and 8.7% (21/242) patients in lansoprazole group.Conclusion: Vonoprazan maintenance therapy was well-tolerated and noninferior to lansoprazole f

关键词： Erosive esophagitis Lansoprazole Maintenance therapy Potassium-competitive acid blockers Vonoprazan

Therapeutic advances in atrial fibrillation based on animal models

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第2期25卷 135-152页

作者： Qian GONG Xuan LE Pengcheng YU Lenan ZHUANG Institute of Genetics and Reproduction College of Animal SciencesZhejiang UniversityHangzhou310058China Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province Department of CardiologySir Run Run Shaw HospitalSchool of MedicineZhejiang UniversityHangzhou310016China

Atrial fibrillation(AF)is the most prevalent sustained cardiac arrhythmia among humans,with its incidence increasing significantly with age.Despite the high frequency of AF in clinical practice,its etiology and management remain elusive.To develop effective treatment strategies,it is imperative to comprehend the underlying mechanisms of AF;therefore,the establishment of animal models of AF is vital to explore its pathogenesis.While spontaneous AF is rare in most animal species,several large animal models,particularly those of pigs,dogs,and horses,have proven as invaluable in recent years in advancing our knowledge of AF pathogenesis and developing novel therapeutic options.This review aims to provide a comprehensive discussion of various animal models of AF,with an emphasis on the unique features of each model and its utility in AF research and treatment.The data summarized in this review provide valuable insights into the mechanisms of AF and can be used to evaluate the efficacy and safety of novel therapeutic interventions.

关键词： Atrial fibrillation Animal model Therapeutic

Activation of glutamatergic neurons in the somatosensory cortex promotes remyelination in ischemic vascular dementia

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Fundamental Research 2024年第1期4卷 188-198页

作者： Yi-Ting Zhou Da-Dao An Yi-Xin Xu Ying Zhou Qing-Qing Li Hai-Bin Dai Xiang-Nan Zhang Yi Wang Min Lou Zhong Chen Wei-Wei Hu Department of Pharmacology and Department of Pharmacy of the Second Affiliated Hospital NHC and CAMS Key Laboratory of Medical NeurobiologySchool of Basic Medical SciencesCollege of Pharmaceutical SciencesZhejiang University School of MedicineHangzhou 310058China Department of Pharmacy Sir Run Run Shaw HospitalHangzhou 310012China Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province School of Pharmaceutical SciencesZhejiang Chinese Medical UniversityHangzhou 310053China Department of Neurology the Second Affiliated Hospital of Zhejiang UniversitySchool of MedicineHangzhou 310003China

Chronic cerebral hypoperfusion can cause progressive demyelination as well as ischemic vascular dementia,however no effective treatments are available.Here,based on magnetic resonance imaging studies of patients with white matter damage,we found that this damage is associated with disorganized cortical structure.In a mouse model,optogenetic activation of glutamatergic neurons in the somatosensory cortex significantly promoted oligodendrocyte progenitor cell(OPC)proliferation,remyelination in the corpus callosum,and recovery of cognitive ability after cerebral hypoperfusion.The therapeutic effect of such stimulation was restricted to the upper layers of the cortex,but also spanned a wide time window after ischemia.Mechanistically,enhancement of glutamatergic neuron-OPC functional synaptic connections is required to achieve the protection effect of activating cortical glutamatergic neurons.Additionally,skin stroking,an easier method to translate into clinical practice,activated the somatosensory cortex,thereby promoting OPC proliferation,remyelination and cognitive recovery following cerebral hypoperfusion.In summary,we demonstrated that activating glutamatergic neurons in the somatosensory cortex promotes the proliferation of OPCs and remyelination to recover cognitive function after chronic cerebral hypoperfusion.It should be noted that this activation may provide new approaches for treating ischemic vascular dementia via the precise regulation of glutamatergic neuron-OPC circuits.

关键词： Chronic cerebral hypoperfusion Optogenetic stimulation Oligodendrocyte progenitor cellIschemic vascular dementia Glutamatergic neuron Remyelination

AMachine Learning Approach to User Profiling for Data Annotation of Online Behavior

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Computers, Materials & Continua 2024年第2期78卷 2419-2440页

作者： Moona Kanwal Najeed AKhan Aftab A.Khan Computer Science and Information Technology Department NED University of Engineering and TechnologyKarachiPakistan Computer Engineering Department Sir Syed University of Engineering and TechnologyKarachiPakistan college of Education Health and Human ServicesLongwood UniversityFarmvilleVAUSA

The user’s intent to seek online information has been an active area of research in user profiling.User profiling considers user characteristics,behaviors,activities,and preferences to sketch user intentions,interests,and motivations.Determining user characteristics can help capture implicit and explicit preferences and intentions for effective user-centric and customized content presentation.The user’s complete online experience in seeking information is a blend of activities such as searching,verifying,and sharing it on social platforms.However,a combination of multiple behaviors in profiling users has yet to be considered.This research takes a novel approach and explores user intent types based on multidimensional online behavior in information acquisition.This research explores information search,verification,and dissemination behavior and identifies diverse types of users based on their online engagement using machine learning.The research proposes a generic user profile template that explains the user characteristics based on the internet experience and uses it as ground truth for data annotation.User feedback is based on online behavior and practices collected by using a survey method.The participants include both males and females from different occupation sectors and different ages.The data collected is subject to feature engineering,and the significant features are presented to unsupervised machine learning methods to identify user intent classes or profiles and their characteristics.Different techniques are evaluated,and the K-Mean clustering method successfully generates five user groups observing different user characteristics with an average silhouette of 0.36 and a distortion score of 1136.Feature average is computed to identify user intent type characteristics.The user intent classes are then further generalized to create a user intent template with an Inter-Rater Reliability of 75%.This research successfully extracts different user types based on their preferences in online content,platforms,crit

关键词： User intent cluster user profile online search information sharing user behavior search reasons

The clinical features and potential mechanisms of cognitive disorders in peripheral autoimmune and inflammatory diseases

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Fundamental Research 2024年第2期4卷 226-236页

作者： Ke-qi Fan Tao Huang Jian-shuai Yu Yi-yuan Li Jin Jin MOE Laboratory of Biosystem Homeostasis and Protection and Life Sciences InstituteZhejiang UniversityHangzhou 310058China Department of Gastroenterology Sir Run Shaw HospitalCollege of Medicine Zhejiang UniversityHangzhou 310016China Key Laboratory for Developmental Genes and Human Disease Ministry of EducationInstitute of Life SciencesJiangsu Province High-Tech Key Laboratory for Bio-Medical ResearchSoutheast UniversityNanjing 210096China

According to a study from World Health Organization’s Global Burden of Disease,mental and neurological disorders have accounted for 13%of global diseases in recent years and are on the rise.Neuropsychiatric conditions or neuroinflammatory disorders are linked by the presence of an exaggerated immune response both peripherally and in the central nervous system(CNS).Cognitive dysfunction(CD)encompasses a complex group of diseases and has frequently been described in the field of autoimmune diseases,especially in multiple non-CNS-related autoimmune diseases.Recent studies have provided various hypotheses regarding the occurrence of cognitive impairment in autoimmune diseases,including that abnormally activated immune cells can disrupt the integrity of the blood-brain barrier(BBB)to trigger a central neuroinflammatory response.When the BBB is intact,autoantibodies and pro-inflammatory molecules in peripheral circulation can enter the brain to activate microglia,inducing CNS inflammation and CD.However,the mechanisms explaining the association between the immune system and neural function and their contribution to diseases are uncertain.In this review,we used clinical statistics to illustrate the correlation between CD and autoimmune diseases that do not directly affect the CNS,summarized the clinical features and mechanisms by which autoimmune diseases trigger cognitive impairment,and explored existing knowledge regarding the link between CD and autoimmune diseases from the perspective of the field of neuroimmunology.

关键词： Autoimmune diseases Neuroinflammation Central nervous system dysfunction Autoantibodies Inflammatory cytokines

The dysfunctional Wnt pathway down-regulates MLH1/SET expression and promotes microsatellite instability and immunotherapy response in colorectal cancer

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Genes & Diseases 2024年第2期11卷 542-545页

作者： Jiyan Wang Tao He Qingle Gao Hongkai Chang Xintong Dai Juze Yang Shuangping Liu Shuai Zhang Changliang Shan Chunze Zhang State Key Laboratory of Medicinal Chemical Biology College of Pharmacy and Tianjin Key Laboratory of Molecular Drug ResearchNankai UniversityTianjin 300350China Departments of Pathology Characteristic Medical Center of The Chinese People's Armed Police ForceTianjin 300162China Department of Respiratory Medicine Sir Run Run Shaw Hospital and Institute of Translational MedicineZhejiang University School of MedicineHangzhouZhejiang 310016China Department of Pathology Medical SchoolDalian UniversityDalianLiaoning 116622China School of Integrative Medicine Tianjin University of Traditional Chinese MedicineTianjin 301617China Department of Colorectal Surgery Tianjin Union Medical CenterNankai UniversityTianjin 300121China

The tumor heterogeneity results in different clinical characteristics of tumor patients,so precise therapy is a popular treatment strategy clinically.Microsatellite instability(MSI)is found in 10%-15%of colorectal cancer(CRC)patients and exhibits different clinical outcomes than microsatellite stable(MSS)patients.Surprisingly,MSI patients have a better prognosis than patients with stable microsatellites.Msl patients exhibit clinical features that are not responsive to chemotherapy,however,Msl patients showed excellent responses to immunotherapy.'Although the subtype classification of MSI is beneficial to the clinical treatment of CRC patients,the mechanism of MSl remains unclear.

关键词： immunotherapy colorectal clinical

Neddylation is a novel therapeutic target for lupus by regulating double negative T cell homeostasis

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Signal Transduction and Targeted Therapy 2024年第2期9卷 738-750页

作者： Yun Zhang Lijun Du Chenxi Wang Zhangsheng Jiang Qingchi Duan Yiping Li Zhijun Xie Zhixing He Yi Sun Lin Huang Liwei Lu Chengping Wen Key Laboratory of Chinese medicine rheumatology of Zhejiang Province Research Institute of Chinese Medical Clinical Foundation and ImmunologyCollege of Basic Medical ScienceZhejiang Chinese Medical UniversityHangzhou 310053China Department of General Surgery Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhou 310016China Cancer Institute(Key Laboratory of Cancer Prevention and Intervention China National Ministry of Education)of the Second Affiliated Hospital and Institute of Translational MedicineZhejiang University School of MedicineHangzhou 310029China Cancer Center of Zhejiang University Hangzhou 310029China Department of Pathology and Shenzhen Institute of Research and Innovation The University of Hong KongHong KongChina Chongqing International Institute for Immunology Chongqing 400038China

Systemic lupus erythematosus(SLE),a severe autoimmune disorder,is characterized by systemic inflammatory response,autoantibody accumulation and damage to organs.The dysregulation of double-negative(DN)T cells is considered as a crucial commander during SLE.Neddylation,a significant type of protein post-translational modification(PTM),has been well-proved to regulate T cell-mediated immune response.However,the function of neddylation in SLE is still unknown.Here,we reported that neddylation inactivation with MLN4924,a specific inhibitor of NEDD8-activating enzyme E1(NAE1),or genetic abrogation of Ube2m in T cells decreased DN T cell accumulation and attenuated murine lupus development.Further investigations revealed that inactivation of neddylation blocked Bim ubiquitination degradation and maintained Bim level in DN T cells,contributing to the apoptosis of the accumulated DN T cells in lupus mice.Then double knockout(KO)lupus-prone mice(Ube2m-/-Bim-/-lpr)were generated and results showed that loss of Bim reduced Ube2m deficiency-induced apoptosis in DN T cells and reversed the alleviated lupus progression.Our findings identified that neddylation inactivation promoted Bim-mediated DN T cell apoptosis and attenuated lupus progression.Clinically,we also found that in SLE patients,the proportion of DN T cells was raised and their apoptosis was reduced.Moreover,compared to healthy groups,SLE patients exhibited decreased Bim levels and elevated Cullin1 neddylation levels.Meantime,the inhibition of neddylation induced Bim-dependent apoptosis of DN T cells isolated from SLE patients.Altogether,our findings provide the direct evidence about the function of neddylation during lupus,suggesting a promising therapeutic approach for this disease.

关键词： inactivation double finding

Advances of nanoparticles in transmucosal drug delivery

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Nano Research 2024年第4期17卷 2874-2885页

作者： Li Zhang Changwei Yang Yingxiang Song Tao Sheng Junyan Li Jicheng Yu Xiaohong Wu Xiao Ye Geriatric Medicine Center Department of EndocrinologyZhejiang Provincial People’s Hospital(Affiliated People’s HospitalHangzhou Medical College)Hangzhou 310014China Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Jinhua Institute of Zhejiang University Jinhua 321299China Liangzhu Laboratory Zhejiang University Medical CenterHangzhou 311121China Department of General Surgery Sir Run Run Shaw HospitalSchool of MedicineZhejiang UniversityHangzhou 310016China National Key Laboratory of Advanced Drug Delivery and Release Systems Zhejiang UniversityHangzhou 310058China Key Laboratory for Diagnosis and Treatment of Endocrine Gland Diseases of Zhejiang Province Hangzhou 310014China

Transmucosal drug administration represents a potential strategy for enhancing treatment efficacy and reducing side effects by avoiding the first-pass effect into the systemic circulation and delivering therapeutics directly to the target disease site.However,many challenges still remain in its clinical application,including low drug availability and limited retention time in the mucosa.The burgeoning advancement of nanotechnologies offers great potential to overcome the above limitations,leveraging their distinct advantages of high drug-loading capacity and strong permeability.In this review,the latest developments of nanoparticles(NPs)in transmucosal drug delivery as well as their clinical applications are discussed.

关键词： nanoparticles(NPs) transmucosal drug delivery mucosal barriers biomaterials