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New avenues for the treatment of immunotherapy-resistant pancreatic cancer

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1134-1153页

作者： luis Guilherme de Oliveira Silva Fabian Fellipe Bueno Lemos Marcel Silva Luz Samuel Luca Rocha Pinheiro Mariana dos Santos Calmon gabriel Lima Correa Santos gabriel Reis Rocha Fabrício Freire de Melo Instituto Multidisciplinar em Saúde Universidade Federal da BahiaVitória da Conquista 45029-094BahiaBrazil

Pancreatic cancer(PC)is characterized by its extremely aggressive nature and ranks 14th in the number of new cancer cases ***,due to its complexity,it ranks 7th in the list of the most lethal cancers *** pathogenesis of PC involves several complex processes,including familial genetic factors associated with risk factors such as obesity,diabetes mellitus,chronic pancreatitis,and *** in genes such as KRAS,TP53,and SMAD4 are linked to the appearance of malignant cells that generate pancreatic lesions and,consequently,*** this context,some therapies are used for PC,one of which is immunotherapy,which is extremely promising in various other types of cancer but has shown little response in the treatment of PC due to various resistance mechanisms that contribute to a drop in immunotherapy *** is therefore clear that the tumor microenvironment(TME)has a huge impact on the resistance process,since cellular and non-cellular elements create an immunosuppressive environment,characterized by a dense desmoplastic stroma with cancerassociated fibroblasts,pancreatic stellate cells,extracellular matrix,and immunosuppressive *** to this are genetic mutations in TP53 and immunosuppressive factors that act on T cells,resulting in a shortage of CD8+T cells and limited expression of activation markers such as *** this way,finding new strategies that make it possible to manipulate resistance mechanisms is ***,techniques such as the use of TME modulators that block receptors and stromal molecules that generate resistance,the use of genetic manipulation in specific regions,such as microRNAs,the modulation of extrinsic and intrinsic factors associated with T cells,and,above all,therapeutic models that combine these modulation techniques constitute the promising future of PC ***,this study aims to elucidate the main mechanisms of resistance to immunotherapy in PC and new ways of manipulating thi

关键词： Pancreatic cancer Immunotherapy Resistance Tumor microenvironment manipulation Combined immunotherapy

Woody plant taxonomic,functional,and phylogenetic diversity decrease along elevational gradients in Andean tropical montane forests:Environmental filtering and arrival of temperate taxa

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Plant Diversity 2024年第4期46卷 491-501页

作者： Guillermo Bañares-de-Dios Manuel J.Macía gabriel Arellano Íñigo Granzow-de la Cerda Julia Vega-álvarez Itziar Arnelas Carlos I.Espinosa Norma Salinas luis Cayuela Departamento de Biología y Geología Física y Química InorgánicaUniversidad Rey Juan CarlosCalle Tulipán s/nMóstolesMadridES-28933Spain Departamento de Biología Área de BotánicaUniversidad Autónoma de MadridCalle Darwin 2MadridES-28049Spain Centro de Investigación en Biodiversidad y Cambio Global(CIBC-UAM) Universidad Autónoma de MadridCalle Darwin 2MadridES-28049Spain Ecology and Evolutionary Biology University of MichiganAnn ArborMI 48109USA Oikobit LLC ***AlbuquerqueNM87120USA Real Jardín Botánico–CSIC Plaza Murillo 2MadridES-28014Spain Departamento de Biología Animal EcologíaParasitologíaEdafología y Química AgrícolaUniversidad de SalamancaCalle Donantes de Sangre s/nSalamancaES-37007Spain Departamento de Biodiversidad Ecología y EvoluciónUniversidad Complutense de MadridCalle JoséAntonio Nováis 12Ciudad UniversitariaES-28040Spain Departamento de Ciencias Biológicas y Agropecuarias Universidad Técnica Particular de LojaA.P.11-01-608 LojaEcuador Sección Química Pontificia Universidad Católica del PerúA.P.Lima 32LimaPeru ECI School of Geography and EnvironmentUniversity of OxfordOX13QYOxfordshireUnited Kingdom Instituto de Investigación en Cambio Global(IICG-URJC) Universidad Rey Juan CarlosCalle Tulipán s/nMóstolesMadridES-28933Spain

Mountains are paramount for exploring biodiversity patterns due to the mosaic of topographies and climates encompassed over short *** research has traditionally focused on taxonomic diversity when investigating changes along elevational gradients,but other facets should be *** first time,we simultaneously assessed elevational trends in taxonomic,functional,and phylogenetic diversity of woody plants in Andean tropical montane forests and explored their underlying ecological and evolutionary *** investigation covered four transects(traversing ca.2200 m a.s.l.) encompassing 114 plots of 0.1 ha across a broad latitudinal range(ca.10°).Using Hill numbers to quantify abundance-based diversity among 37,869 individuals we observed a consistent decrease in taxonomic,functional,and phylogenetic diversity as elevation increased,although the decrease was less pronounced for higher Hill *** exception was a slight increase in phylogenetic diversity when dominant species were *** decrease in taxonomic and functional diversity might be attributed to an environmental filtering process towards highlands,where the increasingly harsher conditions exclude species and functional ***,the differences in steepness decrease between Hill orders suggest that rare species disproportionately contribute to functional *** phylogenetic diversity the shifting elevational trend between Hill orders indicates a greater than previously considered influence in central Andean highlands of tropical lowlands originated species with strong niche conservatism relative to distantly related temperate *** could be explained by a decreasing presence and abundance of temperate,extratropical taxa towards the central Andes relative to northern or southern Andes,where they are more prevalent.

关键词： Altitudinal gradients Andes Environmentalﬁltering Out of the Tropical Lowlands Functional rarity Tropical Niche Conservatism

The biosynthetic pathway of the hallucinogen mescaline and its heterologous reconstruction

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Molecular Plant 2024年第7期17卷 1129-1150页

作者： Paula Berman luis Alejandro de Haro Ana-Rita Cavaco Sayantan Panda Younghui Dong Nikolay Kuzmich gabriel Lichtenstein Yoav Peleg Hila Harat Adam Jozwiaki Jianghua Cai Uwe Heinig Sagit Meir Ilana Rogachev Asaph Aharoni Department of Plant and Environmental Sciences Weizmann Institute of ScienceRehovot 7610001Israel Life Sciences Core Facilities Weizmann Institute of ScienceRehovot 7610001Israel The Maurice and Vivienne Wohl Institute for Drug Discovery Weizmann Institute of ScienceRehovot 7610001Israel Present address:Department of Cell and Metabolic Biology Leibniz Institute of Plant BiochemistryWeinberg 306120 Halle(Saale)Germany Department of Molecular&Cellular Pharmacology University of Miami Miler School of MedicineMiamiFL 33136USA Department of Botany and Plant Sciences University of California RiversideRiversideCA 92521USA Laboratory of Plant Hormones and Development Regulation of Chongqing School of Life SciencesChongqing UniversityChongqing 401331China

Mescaline,among the earliest identified natural hallucinogens,holds great potential in psychotherapy ***,despite the existence of a postulated biosynthetic pathway for more than half a century,the specific enzymes involved in this process are yet to be *** this study,we investigated the cactus Lophophora williamsii(Peyote),the largest known natural producer of the phenethylamine *** employed a multi-faceted approach,combining de novo whole-genome and transcriptome sequencing with comprehensive chemical profiling,enzymatic assays,molecular modeling,and pathway engineering for pathway *** identified four groups of enzymes responsible for the six catalytic steps in the mescaline biosynthetic pathway,and an N-methyltransferase enzyme that N-methylates all phenethylamine intermediates,likely modulating mescaline levels in ***,we reconstructed the mescaline biosynthetic pathway in both Nicotiana benthamiana plants and yeast cells,providing novel insights into several challenges hindering complete heterologous mescaline *** together,our study opens up avenues for exploration of sustainable production approaches and responsible utilization of mescaline,safeguarding this valuable natural resource for future generations.

关键词： mescaline Lophophora williamsi Peyote biosynthetic pathway de novo genome sequencing mo-lecular modeling

Immune pathway through endometriosis to ovarian cancer

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World Journal of Clinical Oncology 2024年第4期15卷 496-522页

作者： Mariana Santos Calmon Fabian Fellipe Bueno Lemos Marcel Silva Luz Samuel Luca Rocha Pinheiro luis Guilherme de Oliveira Silva gabriel Lima Correa Santos gabriel Reis Rocha Fabrício Freire de Melo Instituto Multidisciplinar em Saúde Universidade Federal da BahiaVitória da Conquista 45029-094BahiaBrazil

Endometriosis is an estrogen-dependent inflammatory disease,defined by the presence of functional endometrial tissue outside of the uterine *** disease is one of the main gynecological diseases,affecting around 10%-15%women and girls of reproductive age,being a common gynecologic *** endometriosis is a benign disease,it shares several characteristics with invasive *** support that it has been linked with an increased chance of developing endometrial ovarian cancer,representing an earlier stage of neoplastic *** is particularly true for women with clear cell carcinoma,low-grade serous carcinoma and ***,the carcinogenic pathways between both pathologies remain poorly *** studies suggest a connection between endometriosis and endometriosis-associated ovarian cancers(EAOCs)via pathways associated with oxidative stress,inflammation,and *** article aims to review current data on the molecular events linked to the development of EAOCs from endometriosis,specifically focusing on the complex relationship between the immune response to endometriosis and cancer,including the molecular mechanisms and their *** recent developments in immunotherapy and their potential to boost the effectiveness of future treatments.

关键词： Ovarian neoplasms Endometriosis Endometriosis-associated ovarian cancers Immune response Immunotherapy

From liver to hormones:The endocrine consequences of cirrhosis

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World Journal of Gastroenterology 2024年第9期30卷 1073-1095页

作者： Juan Eduardo Quiroz-Aldave Elman Rolando Gamarra-Osorio María del Carmen Durand-Vásquez Luciana del Pilar Rafael-Robles Jhean gabriel Gonzáles-Yovera María Alejandra Quispe-Flores luis Alberto Concepción-Urteaga Alejandro Román-González José Paz-Ibarra Marcio José Concepción-Zavaleta Non-communicable Diseases Endocrinology Research LineHospital de Apoyo ChepénChepén 13871Peru Department of Endocrinology Hospital Víctor Lazarte EchegarayTrujillo 13006Peru Department of Endocrinology Clínica Javier PradoLima 15046Peru Department of Gastroenterology Hospital Nacional Guillermo Almenara IrigoyénLima 15018Peru Department of Endocrinology Hospital de Emergencias GrauLima 15001Peru Internal Medicine Hospital Regional Docente de TrujilloTrujillo 13011Peru Department of Endocrinology Hospital Universitario de San Vicente FundaciónMedellin 050010Colombia Internal Medicine Universidad de AntioquiaMedellín 050010Colombia School of Medicine Universidad Nacional Mayor de San MarcosLima 15081Peru Department of Endocrinology Hospital Nacional Edgardo Rebagliati MartinsLima 15072Peru Carrera de Medicina Humana Universidad Científica del SurLima 15067Peru

Hepatocrinology explores the intricate relationship between liver function and the endocrine *** liver diseases such as liver cirrhosis can cause endocrine disorders due to toxin accumulation and protein synthesis *** its importance,assessing endocrine issues in cirrhotic patients is frequently *** article provides a comprehensive review of the epidemiology,pathophysiology,diagnosis,and treatment of endocrine disturbances in liver *** review was conducted using the PubMed/Medline,EMBASE,and Scielo databases,encompassing 172 *** cirrhosis is associated with endocrine disturbances,including diabetes,hypoglycemia,sarcopenia,thyroid dysfunction,hypogonadotropic hypogonadism,bone disease,adrenal insufficiency,growth hormone dysfunction,and secondary *** optimal tools for diagnosing diabetes and detecting hypoglycemia are the oral glucose tolerance test and continuous glucose monitoring system,*** can be assessed through imaging and functional tests,while other endocrine disorders are evaluated using hormonal assays and imaging *** options include metformin,glucagon-like peptide-1 analogs,sodium-glucose co-transporter-2 inhibitors,and insulin,which are effective and safe for diabetes *** standards are followed for managing hypoglycemia,and hormone replacement therapy is often necessary for other endocrine *** transplantation can address some of these problems.

关键词： Diabetes mellitus Hypoglycemia Thyroid diseases Hypogonadism Metabolic bone diseases Liver cirrhosis

Epidemiology of work-related hand and wrist injuries in a referral center: A descriptive study

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World Journal of Orthopedics 2024年第7期15卷 650-659页

作者： Angélica M Rodríguez Ginna P Tocanchón Jessica T Villalba luis M Pombo Aníbal A Teherán gabriel Camero-Ramos Karen P Ayala Gerhard M Acero Research Center Fundación Universitaria Juan N.CorpasBogotá111321Colombia Red Cross Cruz Roja Colombiana-Seccional Cundinamarca BogotáBogotá111221Colombia Vigilancia Epidemiológica Instituto Nacional de SaludBogotá111321Colombia

BACKGROUND Occupational hand and wrist injuries(OHWIs)account for 25%of work-related accidents in low-and middle-income *** Colombia,more than 500000 occupational accidents occurred in 2021,and although the rate declined to less than 5%in 2020 and 2021,at least one in four accidents involved a hand or wrist *** To describe the OHWIs in workers seen at the emergency room at a second-level hospital in *** An observational study was performed using data from workers who experienced OHWIs and attended a second-level hospital,between June,2020 and May,*** overall frequency of OHWIs,as well as their distribution by sociodemo-graphic,clinical,and occupational variables,are ***,association patterns between sex,anatomical area(fingers,hand,wrist),and type of job were analyzed by correspondence analysis(CA).RESULTS There were 2.101 workers treated for occupational accidents,423(20.3%)were cases of OHWIs,which mainly affected men(93.9%)with a median age of 31 years and who worked mainly in mining(75.9%).OHWIs were more common in the right upper extremity(55.3%)and comprised different types of injuries,such as contusion(42.1%),laceration(27.9%),fracture(18.7%),and crush injury(15.6%).They primarily affected the phalanges(95.2%),especially those of the first finger(25.7%).The CAs showed associations between the injured anatomical area and the worker’s job that differed in men and women(explained variance>90%).CONCLUSION One out of five workers who suffered occupational accidents in Cundinamarca,Columbia had an OHWI,affecting mainly males employed in *** occupational profile is likely to lead to prolonged rehabilitation,and permanent functional *** results might be useful for adjusting preventive measures in cluster risk groups.

关键词： Accidents Occupational Epidemiology Hand injuries Wrist injuries Occupational health

Sarcopenia and Anemia Are Predictors of Poor Prognostic in Cervical Cancer Patients

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Open Journal of Obstetrics and Gynecology 2024年第5期14卷 693-704页

作者： Leandro Santos de Araujo Resende Francine Vilela de Amorim Miguel Soares Conceição Rodrigo Menezes Jales Patrick Nunes pereira luis Otávio Sarian Glauco Baiocchi Sophie Derchain Agnaldo Lopes da Silva Filho Department of Gynecology and Obstetrics Botucatu Medical School S&#227o Paulo State University UNESP S&#227o Paulo Brazil Department of Health Sciences University of Sao Francisco S&#227o Paulo Brazil Department of Obstetrics and Gynecology School of Medical Science State University of Campinas (UNICAMP) Campinas Brazil Department of Gynecologic Oncology AC Camargo Cancer Center Sao Paulo Brazil Department of Gynecology and Obstetrics School of Medicine of the Federal University of Minas Gerais Belo Horizonte Brazil

Objective: Evaluate pretreatment sarcopenia and anemia as prognostic factors in women undergoing treatment for cervical cancer (CC) with concurrent chemoradiotherapy (CCRT). Methods: 151 women with CC were analysed in this cohort study. Pretreatment computed tomography (CT) images were analysed to assess skeletal muscle index (SMI). Hazard ratios (HR) and multivariate Cox proportional HR were used to analyse association between low SMI, age, body mass index (BMI), haemoglobin levels, histological type, and International Federation of Gynaecology and Obstetrics (FIGO) stage with PFS and OS. Results: A total of 151 patients were included, 53 (35.1%) presented pretreatment sarcopenia;51 (34%) stage I/II and 100 (66%) stage III/IV. Among those patients in advanced stage (III/IV) 37 (70%) (p = 0.28) were sarcopenic at the beginning of treatment. Sarcopenia was associated with worse progression-free survival (PFS) and overall survival (OS) in our cohort [HR 0.97 (p = 0.01)] [HR 0.73 (p = 0.001)], as well as anemia [HR 0.73 (p = 0.001)] [HR 0.78 (p = 0.001)]. Linear regression models indicated that despite showing no association with age, neutrophil or platelet counts, sarcopenia was associated with pretreatment anemia levels (p = 0.01). After a multivariate analysis, only haemoglobin (anemia) and complete CCRT remained associated with PFS and OS. Sarcopenia and anemia were associated with worse PFS and OS in FIGO stage I/II. Conclusion: Pretreatment sarcopenia was significantly associated with low haemoglobin levels. Anemia and incomplete CCRT were independently associated with poor prognosis in women with CC. Pretreatment sarcopenia, as low SMI, was a predictor of poor prognostic in early stages of CC.

关键词： Cervical Cancer Sarcopenia Anemia Chemoradiotherapy

Clinical/Behavioral Monitoring of Rodents and Rabbits Undergoing Scientific Experiments

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Open Journal of Veterinary Medicine 2024年第5期14卷 91-109页

作者： Luiz Cesar Cavalcanti pereira Jhônata Willy Rocha Coelho Hyago da Silva Medeiros Elidio Rita de Cássia dos Passos Ferraz Da Silva João gabriel Regis Sobral Bárbara Alves de Brito Soledade Leandro Thomaz Vilela Isabele Barbieri Dos Santos Institute of Science and Technology in Biomodels (ICTB) Oswaldo Cruz Foundation (FIOCRUZ) Rio de Janeiro Brazil Laboratory Animal Facility of the Carlos Chagas Pavilion of the Animal Experimentation Center (CEA) Oswaldo Cruz Institute (IOC) Oswaldo Cruz Foundation (FIOCRUZ) Rio de Janeiro Brazil

Background: We currently have international and national guidelines regarding the assessment and monitoring of clinical signs and humane endpoints in animals used in teaching and research, which make the performance of these activities mandatory for any experiment and professional working in this area. Assigning the severity of a research experiment is the result of an analysis of records of observations of the animal’s behavior, and clinical signs. The aim of this study was to describe the importance of carrying out a severity assessment associated with clinical and behavioral monitoring of rodents and rabbits during experimentation to maintain the welfare of these animals undergoing scientific research. Methods: The literature search was carried out using the following terms: “Monitoring”;“Humane endpoints”;“Animal welfare”, “Rodents”;“Rabbits”, and as connectors “and”;“or”, in the following databases: PubMed;LILACS/BIREME and SciELO. Results: A total of 987 articles were identified in the databases, and 20 of these studies were included in this review. Conclusions: Humane endpoint protocols and procedure severity tables are of the utmost importance, both from an ethical point and to refine the results of research conducted on laboratory animals. They should be drawn up jointly by the teams responsible for the project and the maintenance of the animals during the research period, and the data obtained should be published so that the scientific community can have access to it, helping to disseminate these practices, as well as helping to draw up new procedures. Monitoring and evaluating the welfare and clinical condition of animals undergoing scientific research procedures is the responsibility of the professors, researchers, veterinarians, and animal facility coordinators. The Ethics Committee on the Use of Animals must monitor all the activities conducted with the animals, by inspecting the experimental procedures and the physical environment of the laboratory an

关键词： Monitoring Humane Endpoints Animal Welfare Experimental Design Laboratory Animals’ Investigations

Disaster Journalism in Print Media:Analysis of the Top 10 Hydrogeomorphological Disaster Events in Portugal,1865–2015

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International Journal of Disaster Risk Science 2022年第4期13卷 521-535页

作者： Michele Nacif Antunes Susana da Silva pereira Joséluis Zêzere Adauto Emmerich Oliveira Postgraduate Program in Public Health(PPGSC) Federal University of Espírito SantoVitoriaEspírito Santo 29047-105Brazil Centre for Geographical Studies Institute of Geography and Spatial PlanningUniversidade de Lisboa1600-276 LisbonPortugal Associate Laboratory TERRA 1349-017 LisbonPortugal

Disaster communication guidelines emphasize that journalists should be aware of past major disasters and draw lessons from the coverage of those *** press is an important source for the evolution of historical disaster and risk research paradigms over *** study explored the top 10 damaging hydrogeomorphological events in Portugal selected from the disaster database,which includes events that caused human damages(fatalities,injured,missing,evacuated,and displaced)reported over a period of 151years(1865–2015)by the Portuguese newspaper Diário de Notícias(DN).News analysis was guided by the news *** analysis of the news published in DN enabled us to identify textual marks that present interconnections in the journalistic coverage and produce discursive standards for these *** textual marks were associated with the hazard and risk *** discursive standards of DN did not clearly reflect the ruptures in the hazard *** a rule,the journalistic reports contributed to the naturalization of disasters and the gap in public understanding of risks,by presenting an approach focused on relief actions—ignoring social issues,vulnerability,and population resilience—reducing the discourse of preparedness for future disasters.

关键词： Disaster journalism Hydrogeomorphological events News protocol Portugal Print media