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Advances in discovery of novel investigational agents for functional cure of chronic hepatitis B:A comprehensive review of phases II and III therapeutic agents

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World Journal of Hepatology 2024年第3期16卷 331-343页

作者： Robert Lam joseph k Lim Section of Digestive Diseases Yale University School of MedicineNew HavenCT 06520United States

Chronic hepatitis B virus(HBV)infection affects over 295 million people globally and an estimated 1.6 million people in the United *** is associated with significant morbidity and mortality due to cirrhosis,liver failure,and liver *** therapy with oral nucleos(t)ide analogues is associated with high rates of virologic suppression,which in turn has been associated with a decreased risk of liver ***,current antiviral regimens are limited by concerns with adverse effects,adherence,resistance,long-term treatment,and ongoing risk for liver *** investigational agents are currently in development and are targeted at achieving functional cure with sustained hepatitis B surface antigen(HBsAg)loss and suppression of HBV *** we review key evidence from phases II and III trials defining the efficacy and safety profiles for key investigational agents for functional cure of chronic hepatitis B,including core/capsid inhibitors,entry inhibitors,RNA interference(siRNA/ASO),HBsAg inhibitors,toll-like receptor agonists,checkpoint inhibitors,and therapeutic vaccines.

关键词： Hepatitis B virus treatment Clinical trials RNA interference Entry inhibitors Core inhibitors Immunomodulators

Evaluation of slope stability through rock mass classification and kinematic analysis of some major slopes along NH-1A from Ramban to Banihal, North Western Himalayas

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Journal of Rock Mechanics and Geotechnical Engineering 2024年第1期16卷 167-182页

作者： Amit Jaiswal A.k.Verma t.N.Singh Department of Civil and Environmental Engineering Indian Institute of Technology PatnaPatna801106India

the network of Himalayan roadways and highways connects some remote regions of valleys or hill slopes,which is vital for India’s socio-economic *** to natural and artificial factors,frequency of slope instabilities along the networks has been increasing over last few *** of stability of natural and artificial slopes due to construction of these connecting road networks is significant in safely executing these roads throughout the *** rock mass classification methods are generally used to assess the strength and deformability of rock *** study assesses slope stability along the NH-1A of Ramban district of North Western *** structurally and non-structurally controlled rock mass classification systems have been applied to assess the stability conditions of 14 *** evaluating the stability of these slopes,kinematic analysis was performed along with geological strength index(GSI),rock mass rating(RMR),continuous slope mass rating(CoSMR),slope mass rating(SMR),and Q-slope in the present *** SMR gives three slopes as completely unstable while CoSMR suggests four slopes as completely *** stability of all slopes was also analyzed using a design chart under dynamic and static conditions by slope stability rating(SSR)for the factor of safety(FoS)of 1.2 and 1 respectively.Q-slope with probability of failure(PoF)1%gives two slopes as stable *** slope angle has been determined based on the Q-slope safe angle equation and SSR design chart based on the *** value ranges given by different empirical classifications were RMR(37-74),GSI(27.3-58.5),SMR(11-59),and CoSMR(3.39-74.56).Good relationship was found among RMR&SSR and RMR&GSI with correlation coefficient(R 2)value of 0.815 and 0.6866,***,a comparative stability of all these slopes based on the above classification has been performed to identify the most critical slope along this road.

关键词： Rock mass classification kinematic analysis Slope stability Himalayan road Static and dynamic conditions

Near resonance vibration isolation on a levered-dual response(LEDAR)Coulomb-damped system by differential preloads/offsets in linear springs

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Applied Mathematics and Mechanics(English Edition) 2024年第6期45卷 1033-1050页

作者： t.I.tOLUWALOJU C.k.t.EIN D.HALIM Department of Mechanical Materials and Manufacturing EngineeringUniversity of Nottingham Ningbo ChinaNingbo 315100Zhejiang ProvinceChina Nottingham Ningbo China Beacons of Excellence Research and Innovation Institute University of Nottingham Ningbo ChinaNingbo 315048Zhejiang ProvinceChina

the levered-dual response(LEDAR)Coulomb-damped system attains near resonant vibration isolation by differential preloads/offsets in linear *** takes the advantages of both the preloads/offsets in linear springs and the guiderail friction for realizing different levels of vibration *** isolation capacities are investigated on the strategies with both the horizontal and vertical guiderails,with the horizontal rail only,and without *** compressive preloads generally result in the consumption of most of the initial excitation energy so as to overcome the potential *** isolation onsets at the frequency ratio of 1∓0.095 on the left-hand side(LHS)and the right-hand side(RHS)of the lever are relative to the load plate *** observed near resonant isolation thus makes the LEDAR system a candidate for the isolation of the mechanical systems about resonance while opening a path for simultaneous harvesterisolation functions and passive functions at extreme frequencies.

关键词： lever ratio Coulomb damping preload tension/compression isolation band/depth offset potential

Management of male obesity-related secondary hypogonadism:A clinical update

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World Journal of Experimental Medicine 2024年第2期14卷 11-28页

作者： Mohan t Shenoy Sunetra Mondal Cornelius James Fernandez joseph M Pappachan Department of Endocrinology Sree Gokulam Medical Collegeand Research FoundationTrivandrum 695607KeralaIndia Department of Endocrinology NRS Medical College and HospitalKolkata 700014West BengalIndia Department of Endocrinology&Metabolism Pilgrim HospitalUnited Lincolnshire Hospitals NHS TrustBoston PE219QSUnited Kingdom Department of Endocrinology and Metabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology Medicine&HealthThe University of ManchesterManchester M139PLUnited Kingdom

the global obesity pandemic has resulted in a rise in the prevalence of male obesity-related secondary hypogonadism(MOSH)with emerging evidence on the role of testosterone *** aim to provide an updated and practical approach towards its *** did a comprehensive literature search across MEDLINE(via PubMed),Scopus,and Google Scholar databases using the keywords“MOSH”OR“Obesity-related hypogonadism”OR“testosterone replacement therapy”OR“Selective estrogen receptor modulator”OR“SERM”OR“Guidelines on male hypogonadism”as well as a manual search of references within the articles.A narrative review based on available evidence,recommendations and their practical implications was *** weight loss is the ideal therapeutic strategy for patients with MOSH,achievement of significant weight reduction is usually difficult with lifestyle changes alone in real-world ***,androgen administration is often necessary in the management of hypogonadism in patients with MOSH which also improves many other comorbidities related to ***,there is conflicting evidence for the appropriate use of testosterone replacement therapy(tRt),and it can also be associated with *** evidence-based review updates the available evidence including the very recently published results of the tRAVERSE trial and provides comprehensive clinical practice pearls for the management of patients with *** starting testosterone replacement in functional hypogonadism of obesity,it would be desirable to initiate lifestyle modification to ensure weight *** should be coupled with the management of other comorbidities related to obesity in MOSH *** the risks and benefits of tRt should be considered in every patient before and during longterm management.

关键词： Male obesity-related secondary hypogonadism Androgen therapy testosterone replacement therapy Obesity Cardiovascular benefits

SARS-CoV-2 and innate immunity:the good,the bad,and the"goldilocks"

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Cellular & Molecular Immunology 2024年第2期21卷 171-183页

作者： Benjamin L.Sievers Mark.t.k.Cheng k.t. Csiba Bo Meng Ravindra k.Gupta Department of Medicine University of CambridgeCambridgeUK Cambridge Institute of therapeutic Immunology&Infectious Disease(CItID) Department of MedicineUniversity of CambridgeCambridgeUk

An ancient conflict between hosts and pathogens has driven the innate and adaptive arms of *** about this interplay can not only help us identify biological mechanisms but also reveal pathogen vulnerabilities that can be leveraged *** humoral response to SARS-CoV-2 infection has been the focus of intense research,and the role of the innate immune system has received significantly less ***,we review current knowledge of the innate immune response to SARS-CoV-2 infection and the various means SARS-CoV-2 employs to evade innate defense *** also consider the role of innate immunity in SARS-CoV-2 vaccines and in the phenomenon of long COVID.

关键词： SARS-CoV-2 Innate immune response Interferon Cytokines Inflammation Antiviral targets

Supposition of graphene stacks to estimate the contact resistance and conductivity of nanocomposites

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Applied Mathematics and Mechanics(English Edition) 2024年第4期45卷 663-676页

作者： Y.ZARE M.t.MUNIR G.J.WENG k.Y.RHEE Biomaterials and tissue Engineering Research Group Department of Interdisciplinary TechnologiesBreast Cancer Research CenterMotamed Cancer InstituteTehran ***Iran College of Engineering and technology American University of the Middle EastEgaila 54200Kuwait Department of Mechanical and Aerospace Engineering Rutgers UniversityNew BrunswickNJ 08903U.S.A. Department of Mechanical Engineering(Bk21 Four) College of EngineeringKyung Hee UniversityYongin 446701Republic of Korea

In this study,the effects of stacked nanosheets and the surrounding interphase zone on the resistance of the contact region between nanosheets and the tunneling conductivity of samples are evaluated with developed equations superior to those previously *** contact resistance and nanocomposite conductivity are modeled by several influencing factors,including stack properties,interphase depth,tunneling size,and contact *** developed model's accuracy is verified through numerous experimental *** further validate the models and establish correlations between parameters,the effects of all the variables on contact resistance and nanocomposite conductivity are ***,the contact resistance is primarily dependent on the polymer tunnel resistivity,contact area,and tunneling *** dimensions of the graphene nanosheets significantly influence the conductivity,which ranges from 0 S/m to90 S/*** increased number of nanosheets in stacks and a larger gap between them enhance the nanocomposite's ***,the thicker interphase and smaller tunneling size can lead to higher sample conductivity due to their optimistic effects on the percolation threshold and network efficacy.

关键词： graphene polymer composite stacked nanosheet tunneling conductivity contact resistance interphase

Marine yeast Rhodotorula paludigena VA 242 a pigment enhancing feed additive for the Ornamental Fish koi Carp

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Aquaculture and Fisheries 2024年第1期9卷 66-70页

作者： R.Rekha k.A.Nimsi k.Manjusha t.k.Sirajudheen Faculty of Ocean Science&technology Kerala University of Fisheries and Ocean Studies(KUFOS)CochinKerala682506India

Skin colour is an important criterion in determining the aesthetic appeal of ornamental fishes,and thus their mark.t.*** the pigment enhancement in ornamental fishes has been the subject of extensive research by using various synthetic as well as natural pigment *** composition is one of the most important elements that influence the development of pigmentation in *** study is an attempt to assess the possibility of using carotenogenic marine yeast as pigment enhancer in fish diet for koi carp,Cyprinus *** 60 days feeding experiment was done by using feed incorporated with mangrove associated marine yeast Rhodotorula paludigena *** pigmentation in the scales of fishes fed with experimental feed was observed than that fed with the control diet(normal pellet feed).Furthermore the improved growth rate and general wellbeing in fishes fed with experimental feed provides scope for further studies in this field with respect to the growth and survival of fishes.

关键词： Marine yeasts Carotenoids Ornamental fishes Pigment enhancer Feed additive Rhodotorula sp

Approach to traumatic cardiac arrest in the emergency department: a narrative literature review for emergency providers

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World Journal of Emergency Medicine 2024年第1期15卷 3-9页

作者： Rashed Alremeithi Quincy k.t.an Megan t.Quintana Soroush Shahamatdar Ali Pourmand Department of Emergency Medicine George Washington University School of Medicine and Health SciencesWashington DC 20037USA Department of Emergency Medicine University of Maryland School of MedicineBaltimore 21201USA Program in trauma the R Adams Cowley Shock Trauma CenterUniversity of Maryland School of MedicineBaltimore 21201USA Center for trauma and Critical Care Department of Surgerythe George Washington University School of Medicine&Health SciencesWashington DC 20037USA

BACkGROUND:traumatic cardiac arrest(tCA)is a major contributor to mortality and morbidity in all age groups and poses a significant burden on the healthcare *** there have been advances in treatment modalities,survival rates for tCA patients remain *** narrative literature review critically examines the indications and eff ectiveness of current therapeutic approaches in treating ***:We performed a literature search in the PubMed and Scopus databases for studies published before December 31,*** search was refi ned by combining search terms,examining relevant study references,and restricting publications to the English *** the search,943 articles were retrieved,and two independent reviewers conducted a screening ***:A review of various studies on pre-and intra-arrest prognostic factors showed that survival rates were higher when patients had an initial shockable *** were conflicting results regarding other prognostic factors,such as witnessed arrest,bystander cardiopulmonary resuscitation(CPR),and the use of prehospital or in-hospital *** thoracotomy was found to result in more favorable outcomes in cases of penetrating trauma than in those with blunt *** endovascular balloon occlusion of the aorta(REBOA)provides an advantage to emergency thoracotomy in terms of occupational safety for the operator as an alternative in managing hemorrhagic *** implemented in the setting of aortic occlusion,emergency thoracotomy and REBOA resulted in comparable mortality ***-venous extracorporeal life support(V-V ECLS)and veno-arterial extracorporeal life support(V-A ECLS)are viable options for treating respiratory failure and cardiogenic shock,*** the context of traumatic injuries,V-V ECLS has been associated with higher rates of survival to discharge than V-A ***:tCA remains a signifi cant challenge for emergency medical services due to its high m

关键词： traumatic cardiac arrest Emergency thoracotomy Resuscitative endovascular balloon occlusion of the aorta

Dynamic Forecasting of traffic Event Duration in Istanbul:A Classification Approach with Real-time Data Integration

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Computers, Materials & Continua 2024年第8期80卷 2259-2281页

作者： Mesut Ulu Yusuf Sait türkan kenan Menguc Ersin Namlı tarık kucukdeniz Occupational Health and Safety Department Bandirma Onyedi Eylul UniversityBalikesir10200Türkiye Department of Industrial Engineering Istanbul University-CerrahpasaIstanbul34320Türkiye Department of Industrial Engineering Istanbul Technical UniversityIstanbul34467Türkiye

today,urban traffic,growing populations,and dense transportation networks are contributing to an increase in traffic *** incidents include traffic accidents,vehicle breakdowns,fires,and traffic disputes,resulting in long waiting times,high carbon emissions,and other undesirable *** is vital to estimate incident response times quickly and accurately after traffic incidents occur for the success of incident-related planning and response *** study presents a model for forecasting the traffic incident duration of traffic events with high *** proposed model goes through a 4-stage process using various features to predict the duration of four different traffic events and presents a feature reduction approach to enable real-time data collection and *** the first stage,the dataset consisting of 24,431 data points and 75 variables is prepared by data collection,merging,missing data processing and data *** the second stage,models such as Decision trees(Dt),k-Nearest Neighbour(kNN),Random Forest(RF)and Support Vector Machines(SVM)are used and hyperparameter optimisation is performed with *** the third stage,feature selection and reduction are performed and real-time data are *** the last stage,model performance with 14 variables is evaluated with metrics such as accuracy,precision,recall,F1-score,MCC,confusion matrix and *** RF model outperforms other models with an accuracy of 98.5%.the study’s prediction results demonstrate that the proposed dynamic prediction model can achieve a high level of success.

关键词： traffic event duration forecasting machine learning feature reduction shapley additive explanations(SHAP)