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Targets of immunotherapy for hepatocellular carcinoma: An update

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World Journal of Hepatology 2022年第1期14卷 140-157页

作者： Vikrant Rai sandeep mukherjee Department of Translational Research Western University of Health SciencesPomonaCA 91766United States Department of Medicine Creighton University School of MedicineOmahaNE 68124United States

Hepatocellular carcinoma,the most common primary liver cancer,in an immunogenic tumor with a poor prognosis because these tumors are diagnosed at late ***,surgical resection,ablation,liver transplant,and locoregional therapies are available for early stages;however,there are yet no effective treatment for advanced and recurrent *** checkpoint inhibitor therapy and adoptive cell transfer therapy has gained the popularity with some positive results because these therapies overcome anergy and systemic immune ***,still there is a lack of an effective treatment and thus there is an unmet need of a novel *** present,the focus of the research is on oncolytic viral therapy and combination therapy where therapies including radiotherapy,immune checkpoint therapy,adoptive cell transfer therapy,and vaccines are combined to get an additive or synergistic effect enhancing the immune response of the liver with a cytotoxic effect on tumor *** review discusses the recent key development,the basis of drug resistance,immune evasion,immune tolerance,the available therapies based on stage of the tumor,and the ongoing clinical trials on immune checkpoint inhibitor therapy,adoptive cell transfer therapy,oncolytic viral vaccine therapy,and combination therapy.

关键词： Hepatocellular carcinoma Immunotherapy Immune checkpoint inhibitors Adoptive cell therapy Oncolytic vaccines Combination therapy

Current status of liver transplantation for cholangiocarcinoma

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World Journal of Gastrointestinal Surgery 2022年第1期14卷 1-11页

作者： Patrick Twohig Thoetchai Bee Peeraphatdit sandeep mukherjee Department of Internal Medicine Division of Gastroenterology and Transplant HepatologyUniversity of Nebraska Medical CenterOmahaNE 68198United States Department of Internal Medicine Division of GastroenterologyCreighton UniversityOmahaNE 68124United States

Cholangiocarcinoma(CCA)is the second most common liver cancer with a median survival of 12-24 mo without *** is further classified based on its location into intrahepatic CCA(iCCA),perihilar CCA(pCCA),and distal *** resection is the mainstay of treatment,but up to 70%of these tumors are inoperable at the time of *** was previously an absolute contraindication for liver transplantation(LT)due to poor outcomes primary due to early recurrent ***,improvement in patient selection criteria and neoadjuvant treatment protocols have improved outcomes for inoperable pCCA patients with recent studies reporting LT may improve survival in *** advances in the treatment of CCA should include refining patient selection criteria and organ allocation for all subtypes of CCA,determining effective immunotherapies and the evolving role of personalized medicine in patients ineligible for surgical resection or *** article reviews the current status of LT in CCA,along with future directions in managing patients with CCA.

关键词： Intrahepatic cholangiocarcinoma Perihilar cholangiocarcinoma Liver transplantation Immunotherapy Chemotherapy Transplant

Betaine and nonalcoholic steatohepatitis: Back to the future?

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World Journal of Gastroenterology 2011年第32期17卷 3663-3664页

作者： sandeep mukherjee Section of Gastroenterology and Hepatology Nebraska Medical Center Omaha Nebraska NE 68198-3285 United States

Nonalcoholic steatohepatitis (NASH) is an important indication for liver transplantation in many Western countries. Obesity and insulin resistance are the two most common risk factors for NASH, which can lead to recurrent NASH after liver transplantation. There is currently no approved therapy for NASH, and treatment is directed at risk factor modification and lifestyle changes. Betaine has been used for NASH, with mixed results, and may show promise in conjunction with other agents in clinical trials.

关键词：酒精性甜菜碱肝炎脂肪胰岛素抵抗西方国家 NASH 危险因素

Role of betaine in liver disease-worth revisiting or has the die been cast?

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World Journal of Gastroenterology 2020年第38期26卷 5745-5748页

作者： sandeep mukherjee Department of Medicine Creighton University Medical CenterDivision of GastroenterologyOmahaNE 68124United States

Nonalcoholic steatohepatitis(NASH)is an important indication for liver transplantation in many Western countries due to the epidemic of obesity and insulin ***,no medication is approved for NASH and risk factor modification is often *** the last decade,several clinical trials on NASH have been conducted with several ongoing and the future looks *** betaine(trimethyl glycine)was evaluated for NASH,results were mixed in the clinical trials in large part due to the quality of the *** seems reasonable to re-evaluate betaine in clinical trials for NASH and alcoholic liver disease due to its low cost,tolerability and mechanism of action.

关键词： Betaine Obesity Insulin resistance Nonalcoholic steatohepatitis Cirrhosis S-adenosyl homocysteine S-adenosyl methionine

Spontaneous bacterial empyema in cirrhosis:A systematic review and meta-analysis

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World Journal of Hepatology 2022年第6期14卷 1258-1268页

作者： William Reiche Smit Deliwala Saurabh Chandan Babu P Mohan Banreet Dhindsa Daryl Ramai Abhilash Perisetti Rajani Rangray sandeep mukherjee Department of Internal Medicine CHI Creighton University Medical CenterOmahaNE 68124United States Department of Internal Medicine Michigan State University at Hurley Medical CenterFlintMI 48503United States Division of Gastroenterology and Hepatology CHI Creighton University Medical CenterOmahaNE 68124United States Department of Gastroenterology University of UtahSalt Lake CityUT 84132United States Division of Gastroenterology and Hepatology University of Nebraska Medical CenterOmahaNE 68198United States Division of Gastroenterology Parkview HealthFort WayneIN 46845United States

BACKGROUND Spontaneous bacterial empyema(SBE)occurs when a hepatic hydrothorax becomes infected and runs a course similar to spontaneous bacterial peritonitis(SBP).It remains underdiagnosed as patients with cirrhosis do not routinely undergo diagnostic *** understanding is limited by small cohorts,while studies reporting its association with ascites/SBP are *** To explore the incidence of SBE,to determine its association with ascites,and to summarize what is known regarding treatment and outcomes for patients with *** Major databases were searched until June *** include the incidence of SBE in pleural effusions,SBP in peritoneal fluid,and SBE in patients without ascites within our cohort of patients with *** performed a meta-analysis using a randomeffects model with pooled proportions and 95%confidence intervals(CI).We assessed heterogeneity using I^(2)and classic fail-safe to determine *** Eight studies with 8899 cirrhosis patients were *** median age ranged between 41.2 to 69.7 *** majority of the patients were Child-Pugh B and *** MELD score was 18.6±8.09.A total of 1334 patients had pleural effusions and the pooled incidence of SBE was 15.6%(CI 12.6-19;I^(2)50).Amongst patients diagnosed with SBE,the most common locations included right(202),left(64),and bilateral(8).Amongst our cohort,a total of 2636 patients had ascites with a pooled incidence of SBP of 22.2%(CI 9.9-42.7;I^(2)97.8).The pooled incidence of SBE in patients with cirrhosis but without concomitant ascites was 9.5%(CI 3.6-22.8;I^(2)82.5).CONCLUSION SBE frequently occurs with concurrent ascites/SBP;our results suggest high incidence rates of SBE even in the absence of *** pleura can be an unrecognized nidus and our findings support the use of diagnostic thoracentesis in patients with decompensated cirrhosis after exclusion of other causes of pleural *** should be considered particularly in p

关键词： Spontaneous bacterial peritonitis Spontaneous bacterial peritonitis Postparacentesis circulatory dysfunction Refractory ascites Hepatic hydrothorax

2P3FL:A Novel Approach for Privacy Preserving in Financial Sectors Using Flower Federated Learning

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Computer Modeling in Engineering & Sciences 2024年第8期140卷 2035-2051页

作者： sandeep Dasari Rajesh Kaluri School of Computer Science Engineering and Information Systems Vellore Institute of TechnologyVellore632014India

The increasing data pool in finance sectors forces machine learning(ML)to step into new *** data has significant financial implications and is *** users data from several organizations for various banking services may result in various intrusions and privacy *** a result,this study employs federated learning(FL)using a flower paradigm to preserve each organization’s privacy while collaborating to build a robust shared global ***,diverse data distributions in the collaborative training process might result in inadequate model learning and a lack of *** address this issue,the present paper proposes the imple-mentation of Federated Averaging(FedAvg)and Federated Proximal(FedProx)methods in the flower framework,which take advantage of the data locality while training and guaranteeing global *** improves the privacy of the local *** analysis used the credit card and Canadian Institute for Cybersecurity Intrusion Detection Evaluation(CICIDS)***,recall,and accuracy as performance indicators to show the efficacy of the proposed strategy using FedAvg and *** experimental findings suggest that the proposed approach helps to safely use banking data from diverse sources to enhance customer banking services by obtaining accuracy of 99.55%and 83.72%for FedAvg and 99.57%,and 84.63%for FedProx.

关键词： Federated learning FedAvg FedProx flower framework privacy preservation financial sectors

Bile acid indices as biomarkers for liver diseases Ⅱ: The bile acid score survival prognostic model

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World Journal of Hepatology 2021年第5期13卷 543-556页

作者： Jawaher Abdullah Alamoudi Wenkuan Li Nagsen Gautam Marco Olivera Jane Meza sandeep mukherjee Yazen Alnouti Department of Pharmaceutical Sciences University of Nebraska Medical CenterOmahaNE 68198-6025United States Department of Pharmaceutical Sciences Princess Nourah Bint Abdulrahman UniversityRiyadh 11564Saudi Arabia Department of Internal Medicine University of Nebraska Medical CenterOmahaNE 68105United States Department of Biostatistics University of Nebraska Medical CenterOmahaNE 68198-4375United States Department of Internal Medicine Creighton University Medical CenterOmahaNE 68124United States

BACKGROUND Cholestatic liver diseases are characterized by an accumulation of toxic bile acids(BA)in the liver,blood and other tissues which lead to progressive liver injury and poor prognosis in *** To discover and validate prognostic biomarkers of cholestatic liver diseases based on the urinary BA *** We analyzed urine samples by liquid chromatography-tandem mass spectrometry and investigated the use of the urinary BA profile to develop survival models that can predict the prognosis of hepatobiliary *** urinary BA profile,a set of non-BA parameters,and the adverse events of liver transplant and/or death were monitored in 257 patients with cholestatic liver diseases for up to 7 *** BA profile was characterized by calculating BA indices,which quantify the composition,metabolism,hydrophilicity,formation of secondary BA,and toxicity of the BA *** have developed and validated the bile-acid score(BAS)model(a survival model based on BA indices)to predict the prognosis of cholestatic liver *** We have developed and validated a survival model based on BA(the BAS model)indices to predict the prognosis of cholestatic liver *** results demonstrate that the BAS model is more accurate and results in higher truepositive and true-negative prediction of death compared to both non-BAS and model for end-stage liver disease(MELD)*** 5-and 3-year survival probabilities markedly decreased as a function of ***,patients with high BAS had a 4-fold higher rate of death and lived for an average of 11 mo shorter than subjects with low *** increased risk of death with high vs low BAS was also 2-4-fold higher and the shortening of lifespan was 6-7-mo lower compared to MELD or ***,we have shown the use of BAS to predict the survival of patients with and without liver transplant(LT).Therefore,BAS could be used to define the most seriously ill patients,who need earlier intervention such as ***

关键词： Hepatobiliary diseases Bile acid indices Death Liver transplant Survival model Prognosis

Early Paleozoic basement diorite of arc-magmatism from Kutch basin, Western India

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Acta Geochimica 2024年第2期43卷 296-307页

作者： Piyush Gupta sandeep Singh Shakti Singh Rathore Argha Narayan Sarkar Geochronology Laboratory KDMIPEOil and Natural Gas Corporation Ltd.9Kaulagarh RoadDehradun 248195India Department of Earth Sciences Indian Institute of TechnologyRoorkee 247667India

In this study,we report for theﬁrst time an Early Palaeozoic basement diorite from the drilled well Nirona-A in the Banni Half-Graben of the Kutch basin,western *** 40Ar–39Ar dates provided a plateau age of 441.84±2.66 Ma and another pseudo plateau of 441.28±5.82 to 388.08±16.65 Ma for the basement *** ages constrain the basement formation age to the Late Ordovician-Early Silurian *** obtained basement ages are correlatable with the later part of Cambro-Ordovician alkaline magmatism that has been reported from the Huqf area in Central Oman,whereas their lithological and petrographic correlativity with base-ment diorites occurring in the Dinsi Body of Nagar Parkar igneous complex in Pakistan can also be *** geochemical studies characterized the diorite with enrich-ment of LILE(Rb,Ba,and K)and LREE(La,Ce,Nd),strong depletion of HFSE(Nb,Sr,P,and Ti),along with weakly negative Eu *** geochemical signatures indicate their petrogenetic afﬁliation with mantle-derived magmas,as well as their tectonic setting to be arc-related,having post-collisional continental-arc type afﬁ****440 Ma basement of Kutch,therefore,appears to rep-resent the later thermal event associated with the reworked Neoproterozoic subduction-related suite from Greater India’s northwest edge,which has implications for Gond-wana assembly in the northwest Indian subcontinent.

关键词： Kutch basin 40Ar–39Ar ages Early palaeozoic basement Continental-arc magmatism Calc-alkaline magmatism

On the Enhanced Power Graph of a Semigroup

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Algebra Colloquium 2024年第1期31卷 83-96页

作者： sandeep Dalal Jitender Kumart Siddharth Singh Department of Mathematics Birla Institute of Technology and Science Pilani PilaniIndia

The enhanced power graph P_(E)(S)of a semigroup S is a simple graph whose vertex set is S and two vertices a,y∈S are adjacent if and only if c,y∈(z)for some z∈S,where(z)is the subsemigroup generated by *** this paper,we first describe the structure of P_(E)(S)for an arbitrary semigroup S,and then discuss the connectedness of P_(E)(S).Further,we characterize the semigroup S in the cases when P_(E)(S)is separately a complete,bipartite,regular,tree and null *** planarity,together with the minimum degree and independence number,of P_(E)(S)is also *** chromatic number of a spanning subgraph,i.e.,the cyclic graph,of P_(E)(S)is proved to be *** the final part of this paper,we construct an example of a semigroup S such that the chromatic number of P_(E)(S)need not be countable.

关键词： monogenic semigroup completely regular semigroup planar graph enhanced powergraph