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High Frequency of Antiviral Resistance Mutations in HBV Genotypes A2 and H: Multidrug Resistance Strains in Mexico

Journal of Clinical and Translational Hepatology 2023年第5期11卷 1023-1034页

作者： Alexis Jose-Abrego Sonia Roman João Renato Rebello Pinho Michele Soares gomes-Gouvêa Arturo Panduro Department of Genomic Medicine in Hepatology Civil Hospital of Guadalajara“Fray Antonio Alcalde”GuadalajaraJaliscoMexico Health Sciences Center University of GuadalajaraGuadalajaraJaliscoMexico LIM07 Department of GastroenterologyUniversity of São PauloSão PauloBrazil Hospital Israelita Albert Einstein São PauloBrazil

Background and Aims:Lamivudine(3TC),telbivudine(LdT),entecavir(ETV),adefovir(ADF),and tenofovir(TFV)are drugs used to treat hepatitis B virus(HBV)infection,but specific mutations allow some viruses to become resistant to antiviral drugs or to acquire immune escape capacities.These mutations have not been thoroughly investigated in Mexico.This study aimed to estimate the prevalence of HBV antiviral resistance and escape mutations.Methods:This cross-sectional study analyzed 158 samples.HBV DNA was extracted,amplified,and sequenced in serum samples using the spin column method,PCR assay,and Sanger’s sequencing,respectively.HBV genotypes were determined,and HBV mutations were tested using the Geno2pheno tool.Results:Overall,68.4%(108/158)of HBV patients were infected with genotype H,followed by G(11.4%,18/158),A2(10.8%,17/158),F1b(6.9.0%,11/158),D(1.9%,3/158),and E(0.6%,1/158),and 5.1%(8/158)had evidence of recombination.The prevalence of resistance mutations was 8.2%(13/158)and the most common combined mutation was rt180M+rt204V.Notably,we found the combinations rt180M+rt204V+rt173L(n=2)and rt180M+rt204V+rt202G(n=1)that confer multidrug resistance to 3TC,LdT,and ETV.Resistance mutations were found in genotypes A2(11.8%,2/17),and H(10.2%,11/108),and escape mutations were detected in HBV genotypes A2(11.8%,2/17),H(10.2%,11/108),F1b(9.1%,1/11)and G(5.6%,1/18).Conclusions:The highest prevalence of antiviral resistance mutations or escape mutations was detected in HBV genotypes A2 and H.The earliest cases of HBV multidrug resistance were detected in Mexico.

关键词： Hepatitis B virus Drug resistance mutations Multidrug resistance strain Immune escape

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Molecular mechanisms underlying the neuroprotection of environmental enrichment in Parkinson’s disease

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Neural Regeneration Research 2023年第7期18卷 1450-1456页

作者： Tamara Andrea Alarcón Sarah Martins Presti-Silva Ana Paula Toniato Simões Fabiola Mara Ribeiro Rita gomes Wanderley Pires Department of Physiological Sciences Health Science CenterUniversidade Federal do Espirito SantoVitoriaBrazil Laboratory of Molecular and Behavioral Neurobiology Health Science CenterUniversidade Federal do Espirito SantoVitoriaBrazil Department of Biochemistry and Immunology Institute o Biological SciencesUniversidade Federal de Minas GeraisAvenida Antônio CarlosBelo HorizonteBrazil

Parkinson’s disease is the most common movement disorder,affecting about 1%of the population over the age of 60 years.Parkinson’s disease is characterized clinically by resting tremor,bradykinesia,rigidity and postural instability,as a result of the progressive loss of nigrostriatal dopaminergic neurons.In addition to this neuronal cell loss,Parkinson’s disease is characterized by the accumulation of intracellular protein aggregates,Lewy bodies and Lewy neurites,composed primarily of the proteinα-synuclein.Although it was first described almost 200 years ago,there are no disease-modifying drugs to treat patients with Parkinson’s disease.In addition to conventional therapies,non-pharmacological treatment strategies are under investigation in patients and animal models of neurodegenerative disorders.Among such strategies,environmental enrichment,comprising physical exercise,cognitive stimulus,and social interactions,has been assessed in preclinical models of Parkinson’s disease.Environmental enrichment can cause structural and functional changes in the brain and promote neurogenesis and dendritic growth by modifying gene expression,enhancing the expression of neurotrophic factors and modulating neurotransmission.In this review article,we focus on the current knowledge about the molecular mechanisms underlying environmental enrichment neuroprotection in Parkinson’s disease,highlighting its influence on the dopaminergic,cholinergic,glutamatergic and GABAergic systems,as well as the involvement of neurotrophic factors.We describe experimental pre-clinical data showing how environmental enrichment can act as a modulator in a neurochemical and behavioral context in different animal models of Parkinson’s disease,highlighting the potential of environmental enrichment as an additional strategy in the management and prevention of this complex disease.

关键词： acetylcholine brain-derived neurotrophic factor dopamine environment enrichment gamma-aminobutyric acid glial cell line-derived neurotrophic factor glutamate molecular mechanisms Parkinson’s disease

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Origami-Based Design for 4D Printing of 3D Support-Free Hollow Structures

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Engineering 2022年第5期8卷 70-82页

作者： Bingcong Jian Frederic Demoly Yicha Zhang H.Jerry Qi Jean-Claude Andre Samuel gomes Laboratoire Interdisciplinaire Carnot de Bourgogne UMR 6303 Centre National de la Recherche Scientifique&Universitede Technologie de Belfort-MontbeliardUniversite Bourgogne Franche-ComteBelfort 90400France George W.Woodruff School of Mechanical Engineering Georgia Institute of TechnologyAtlantaGA 30332USA Laboratoire Reactions et Genie des Procedes UMR 7274 Centre National de la Recherche Scientifique-Universitede LorraineNancy 54001France

The integration of additive manufacturing(AM)in design and engineering has prompted a wide spectrum of research efforts,involving topologically optimized solid/lattice structures,multimaterial structures,bioinspired organic structures,and multiscale structures,to name a few.However,except for obvious cases,very little attention has been given to the design and printing of more complex three-dimensional(3D)hollow structures or folded/creased structures.One of the main reasons is that such complex open or closed 3D cavities and regular/freeform folds generally lead to printing difficulties from support-structure-related issues.To address this barrier,this paper aims to investigate four-dimensional(4D)printing as well as origami-based design as an original research direction to design and build 3D support-free hollow structures.This work consists of describing the rough 3D hollow structures in terms of two-dimensional(2D)printed origami precursor layouts without any support structure.Such origami-based definitions are then embodied with folding functions that can be actuated and fulfilled by 3D printed smart materials.The desired 3D shape is then built once an external stimulus is applied to the active materials,therefore ensuring the transformation of the 2D origami layout to 3D structures.To demonstrate the relevance of the proposal,some illustrative cases are introduced.

关键词： Origami-based design 4D printing Smart material Hollow 3D structures Additive manufacturing

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^(222)Rn calibration procedure for water analyses by liquid scintillation counting

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辐射探测技术与方法(英文) 2023年第2期7卷 311-319页

作者： Ana Rita gomes Sérgio Dias Anabela Mourato Joao Abrantes Mário Reis Laboratório de Protecao e Seguranca Radiológica Instituto Superior TécnicoUniversidade de LisboaEstrada Nacional 10km 13972695‑066 Bobadela LRSPortugal Laboratórios de Massa e Massa Volúmica de Sólidos Instituto Portugues da QualidadeRua António Giao22829‑513 CaparicaPortugal Centro de Ciências e Tecnologias Nucleares Instituto Superior TécnicoUniversidade de LisboaEstrada Nacional 10km 13972695‑066 Bobadela LRSPortugal

Purpose Among the several methods to measure ^(222)Rn in water,the liquid scintillation counting(LSC)technique is one of the most sensitive and widely used when analysing non-saline waters by liquid extraction,providing excellent accuracy,precision and low-level detection limits.When using the liquid scintillation counter Tri-Carb 3170 TR/SL(Perkin-Elmer)it is not possible to make an automatic determination of the alpha/beta discrimination parameter,being necessary to evaluate the pulse decay discriminator(PDD)value manually to the ^(222)Rn determination.In this work,we describe the steps to perform the calibration of that type of equipment.Methods The method consists in the preparation of standard samples from a ^(226)Ra certified standard solution and the adjustment of the PDD value by hand until the percentage of alpha events reaches a plateau of a near-constant fraction of total events.The process consists in taking several measures between PDD 80 and 200 with 15 min counting time each.Within the plateau,the alpha/beta ratio was used to determine the plateau final range as well as the optimum PDD value.After that,the calibration standards and blanks were measured and the region of interest(ROI)was established by finding the maximum value for the figure of merit(FOM)in the upper and lower limits.Results The optimal PDD value of 148 was established by the alpha/beta ratio,and after that,it was possible to measure ^(226)Ra standards to perform the calibration.An efficiency of(9.758±0.035)×1^(0-1) was obtained.In routine measurements,a detection limit of about 0.50 Bq L^(-1) is achieved for a 120 min counting time.To evaluate the uncertainty budget,the uncertainties of the net count rate,the efficiency,the sample amount and the decay correction factor were considered.Conclusions A method was developed for the calibration of LSC Tri-Carb 3170 TR/SL with the optimization of the PDD using a ^(226)Ra standard solution.The acquisition to obtain the plot of the variation of the events fraction in each window(alpha and

关键词： Radon Waters Pulse decay discriminator Liquid scintillation counting Calibration

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Traumatic brain injury and sight loss in military and veteran populations–a review

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Military Medical Research 2022年第1期9卷 71-85页

作者： Syeda F.Hussain Zara Raza Andrew T.G.Cash Thomas Zampieri Robert A.Mazzoli Randy H.Kardon Renata S.M.gomes Research&Innovation Blind Veterans UK12-14 Harcourt StreetLondon W1H 4HDUK. Bravo Victor Research12-14 Harcourt StreetLondon W1H 4HDUK Blinded Veterans Association 1101 King StreetSuite 300AlexandriaVirginia 22314USA Department of Ophthalmology Madigan Army Medical Center9040 Jackson AvenueTacomaWashington 98431USA lowa City VA Health Care System and Iowa City VA Center for the Prevention and Treatment of Visual Loss Iowa CityIowa 52246USA department of Ophthalmology and Visual Sciences The University of IowaIowa CityIowa 52242USA Northern Hub for Veterans and Military Families Research Department of NursingMidwifery and HealthFaculty of Health and Life SciencesNorthumbria UniversityNewcastle NE77XAUK.

War and combat exposure pose great risks to the vision system.More recently,vision related deficiencies and impairments have become common with the increased use of powerful explosive devices and the subsequent rise in incidence of traumatic brain injury(TBI).Studies have looked at the effects of injury severity,aetiology of injury and the stage at which visual problems become apparent.There was little discrepancy found between the frequencies or types of visual dysfunctions across blast and non-blast related groups,however complete sight loss appeared to occur only in those who had a blast-related injury.Generally,the more severe the injury,the greater the likelihood of specific visual disturbances occurring,and a study found total sight loss to only occur in cases with greater severity.Diagnosis of mild TBI(mTBI)is challenging.Being able to identify a potential TBI via visual symptoms may offer a new avenue for diagnosis.

关键词： Traumatic brain injury Visual impairment Military Veteran

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Combined Effect of Concept Drift and Class Imbalance on Model Performance During Stream Classification

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Computers, Materials & Continua 2023年第4期75卷 1827-1845页

作者： Abdul Sattar Palli Jafreezal Jaafar Manzoor Ahmed Hashmani Heitor Murilo gomes Aeshah Alsughayyir Abdul Rehman Gilal Department of Computer and Information Sciences Universiti Teknologi PETRONAS(UTP)Seri Iskandar32610Malaysia Centre for Research in Data Science UTPPerak32610Malaysia High Performance Cloud Computing Centre(HPC3) UTPPerak32610Malaysia School of Engineering and Computer Science Victoria University of WellingtonWellington6012New Zealand AI Institute University of Waikato WellingtonHamilton3240New Zealand Anti-Narcotics Force Ministry of Narcotics ControlIslamabad46000Pakistan College of Computer Science and Engineering Taibah UniversityMadinah42353Saudi Arabia

Every application in a smart city environment like the smart grid,health monitoring, security, and surveillance generates non-stationary datastreams. Due to such nature, the statistical properties of data changes overtime, leading to class imbalance and concept drift issues. Both these issuescause model performance degradation. Most of the current work has beenfocused on developing an ensemble strategy by training a new classifier on thelatest data to resolve the issue. These techniques suffer while training the newclassifier if the data is imbalanced. Also, the class imbalance ratio may changegreatly from one input stream to another, making the problem more complex.The existing solutions proposed for addressing the combined issue of classimbalance and concept drift are lacking in understating of correlation of oneproblem with the other. This work studies the association between conceptdrift and class imbalance ratio and then demonstrates how changes in classimbalance ratio along with concept drift affect the classifier’s performance.We analyzed the effect of both the issues on minority and majority classesindividually. To do this, we conducted experiments on benchmark datasetsusing state-of-the-art classifiers especially designed for data stream classification.Precision, recall, F1 score, and geometric mean were used to measure theperformance. Our findings show that when both class imbalance and conceptdrift problems occur together the performance can decrease up to 15%. Ourresults also show that the increase in the imbalance ratio can cause a 10% to15% decrease in the precision scores of both minority and majority classes.The study findings may help in designing intelligent and adaptive solutionsthat can cope with the challenges of non-stationary data streams like conceptdrift and class imbalance.

关键词： Classification data streams class imbalance concept drift class imbalance ratio

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The Relationship Between Training Volume and BMI in the Expression of Running Performance in Runners: A Mediation Model

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Journal of Science in Sport and Exercise 2023年第2期5卷 142-148页

作者： Mabliny Thuany Lee Hill JoséRamón Alvero‑Cruz Beat Knechtle Thayse Natacha gomes CIFI²D Faculty of SportUniversity of PortoPortoPortugal Division of Gastroenterology and Nutrition Department of PediatricsMcMaster UniversityHamiltonON L8N 3Z5Canada Dpto de Fisiología Humana HistologíaAnatomia Patológica y Educación Física y DeportivaUniversidad de MálagaMálagaSpain Medbase St.Gallen Am Vadianplatz Vadianstrasse 269001 St.GallenSwitzerland Department of Physical Education Federal University of SergipeSão CristóvãoSEBrazil

Purpose The relationships between anthropometric and training variables with running performance were previously investi-gated.However,it is possible that through the moderating role of anthropometric variables,the magnitude of the relationship between training and performance may be changed.The purpose of this study was to estimate the mediation role of body mass index(BMI)in the relationship between training volume and running performance among non-professional runners,taking into account sex and age category.Methods The sample comprised 1151 non-professional road runners(61.8%male),aged 18–72 years.Information about sex,age,body mass(kg),body height(cm),running pace,motivation for running,training volume and frequency were obtained through an online questionnaire.Taking into account athletes’age,they were split into two age categories:“until 34 years”(adult runners)and“≥35 years”(master athletes).A mediation analysis was computed in Macro Process(SPSS 26),considering sex and age category.BMI was the mediating variable,while training volume/week was used as independ-ent variable,and running pace was considered as dependent variable.Results For both sexes and age categories,a significant association between training volume on running pace was observed[male adult:β=-0.67;95%CI(-1.04 to-0.53);male master:β=-0.241;95%CI(-0.44 to-0.26);female adult:-0.83;95%CI(-1.25 to-0.41);female master:-0.76;95%CI(-1.09 to-0.44)],as well the association between training volume and BMI;and running BMI and running pace.Except for female adult runners,a mediation effect of BMI was observed.Conclusion The present study showed that BMI mediated the association between training volume and running pace in non-professional runners of different sexes and age categories.On the other hand,a small influence of training volume on the expression of BMI was found.

关键词： Body mass index Running Mediation model

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Prevalence,phenotype and medication for the pediatric inflammatory bowel disease population of a state in Southeastern Brazil

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World Journal of Clinical Pediatrics 2022年第4期11卷 341-350页

作者： Adalberta Lima Martins Renata de SáBrito Fróes Maria da Penha Zago-gomes Pharmaceutical Assistance Health Department of Espírito SantoVitoria 29052-210Espírito SantoBrazil Department of Gastroenterology GastromedRio de Janeiro 22640-100Rio de JaneiroBrazil Departament of Medical Clinical Hospital Universitário Cassiano Antonio MoraesVitoria 29042-755Espírito SantoBrazil

BACKGROUND Inflammatory bowel disease(IBD)can lead to social and economic impacts worldwide.In Brazil,where its adult prevalence is increasing,the epidemiology of the pediatric population is not well known,although there is a documented increase in pediatric IBD incidence worldwide.Brazil has continental dimensions,and Espírito Santo is a state of southeastern Brazil,the region with the highest demographic densities and is the economically most important in the country.AIM To assess the prevalence,incidence,phenotype and medications in a Southeastern Brazilian pediatric population.METHODS Data were retrieved from the Public Medication-Dispensing System of the Department of Health in Espírito Santo state from documentation required to have access to highly expensive medication from August 1,2012 to July 31,2014.There were 1048 registered patients with IBD of all ages,and of these patients,the cases≤17 years were selected.The data were obtained through the analysis of administrative requests for these medications and included medical reports,endoscopy exams,histopathology and imaging tests,which followed the Clinical Protocols and Therapeutic Guidelines of the Brazilian Government.Only confirmed cases of IBD were included in the study.RESULTS There were 55 pediatric patients/1048 registered patients(5.34%),with Crohn's disease(CD)representing 30/55(55%),ulcerative colitis(UC)24/55(43.6%)and 1 unclassified IBD,a significant difference from adult patients(P=0.004).The prevalence of IBD in pediatric patients was 5.02 cases/100.000 inhabitants;the incidence in 2014 was 1.36 cases/100.000 inhabitants.The mean age at diagnosis was 12.2 years(±4.2).There were 7 children diagnosed up to 6 years old,7 between 7 to 10 years old and 41 between 11 and≤17 years old.There was no difference in the distribution of UC and CD between these age categories(P=0.743).There was no difference in gender distribution in relation to adults.Children and adolescents with UC had a predominance of pancolitis,unlike adults(P=0.001),and used amino

关键词： Inflammatory bowel disease Pediatric Prevalence Phenotype Brazil

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Intimate partner violence against women. Does violence decrease after the entry of the alleged offender into the criminal justice system?

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Forensic Sciences Research 2022年第1期7卷 53-60页

作者： Paulo Vieira-Pinto JoséIgnacio Muñoz-Barús Tiago Taveira-gomes Maria João Vidal-Alves Teresa Magalhães Department of Forensic Sciences PathologyGynaecology and ObstetricsPaediatricsInstitute of Forensic SciencesUniversity of Santiago de CompostelaSantiago de CompostelaSpain IINFAC TS-Institute of Research and Advanced Training in Health Sciences Department of SciencesCESPUUniversity Institute of Health Sciences(IUCS)GandraPortugal cFaculty of Medicine University of PortoPortoPortugal CINTESIS-Centre of Health Technology and Service Research University of PortoPortoPortugal Fernando Pessoa University PortoPortugal

Intimate partner violence(IPV)is simultaneously assumed as a serious crime and a major public health issue,having recurrences as one of its main characteristics and,consequently,re-entries of some alleged offenders in the criminal justice system(CJS).The main goal of this study is to assess if in cases of female victims of IPV,violence decreases after the first entry of the alleged offender in the CJS.A retrospective study was performed based on the analysis of police reports of alleged cases of IPV during a 4-year period.The final sample(n=1488)was divided into two groups according to the number of entries in the CJS(single or multiple)followed by a comparative approach.Results suggest that violence decreases after the first entry of alleged offenders in the CJS.Re-entries were found in only 15.5%of the cases but they were accountable for 3.3 times more crimes on average.Besides,victims of recidivism presented more injuries and required more medical care.Thus,a small group of alleged offenders seems to be more violent and accountable for most of the IPV crimes registered in the CJS suggesting that regardless of legal sanctions aiming to deter violence,these measures may not be enough for a certain group of offenders.This study sustains the need for a predictive model to quantify the risk of repeated IPV cases within the Portuguese population.

关键词： Forensic sciences intimate partner violence women re-entry recidivism criminal justice system

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Doubling down with CAR-T cell cancer immunotherapy:a two-step recognition circuit enables discrimination between target antigen high and low cancer cells

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Signal Transduction and Targeted Therapy 2021年第8期6卷 2280-2281页

作者： Jehad Charo Bruno gomes hoffmann-la roche ag pharmaceutical research and early development oncologyroche innovation center zurichzurichswitzerland hoffmann-la roche ag pharmaceutical research and early development oncologyroche innovation center baselbaselswitzerland

In a recent article published in Science by Hernandez-Lopez et al.chimeric antigen receptor(CAR)expressing T(CAR-T)cells with a two-step recognition system successfully discriminated between target cells expressing hi... 详细信息

关键词： CAR cancer

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