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A comprehensive review of genetic causes of obesity

World Journal of Pediatrics 2024年第1期20卷 26-39页

作者： Marcio Jose Concepcion-Zavaleta Juan Eduardo Quiroz-Aldave Maria del Carmen Durand-Vasquez Elman Rolando Gamarra-Osorio Juan del Carmen Valencia de la Cruz Claudia Mercedes Barrueto-Callirgos Susan Luciana Puelles-Leon Elena de Jesus Alvarado-Leon Frans Leiva-Cabrera Francisca Elena Zavaleta-Gutierrez Luis Alberto Concepcion-Urteaga Jose Paz-Ibarra Universidad Cientifica del Sur Bolivar 2150 AvenuePueblo Libre15084LimaPeru Division of Medicine Hospital de Apoyo ChepénChepenPeru Division of Family Medicine Hospital de Apoyo ChepénChepenPeru Division of Endocrinology Hospital Victor Lazarte EchegarayTrujilloPeru Division of Pediatrics Hospital de Apoyo ChepenChepenPeru Division of Internal Medicine Hospital de Apoyo ChepenChepenPeru Division of Genetics Universidad Nacional de TrujilloTrujilloPeru Division of Neonatology Hospital Belen de TrujilloTrujilloPeru Division of Internal Medicine Universidad Nacional de TrujilloTrujilloPeru department of Medicine School of MedicineUniversidad Nacional Mayor de San MarcosLimaPeru

Background Obesity is a multifactorial chronic disease with a high,increasing worldwide *** causes account for 7%of the cases in children with extreme *** sources This narrative review was conducted by searching for papers published in the PubMed/MEDLINE,Embase and SciELO databases and included 161 *** search used the following search terms:"obesity","obesity and genetics","leptin","Prader-Willi syndrome",and"melanocortins".The types of studies included were systematic reviews,clinical trials,prospective cohort studies,cross-sectional and prospective studies,narrative reviews,and case *** The leptin-melanocortin pathway is primarily responsible for the regulation of appetite and body ***,several important aspects of the pathophysiology of obesity remain *** causes of obesity can be grouped into syndromic,monogenic,and polygenic causes and should be assessed in children with extreme obesity before the age of 5 years,hyperphagia,or a family history of extreme obesity.A microarray study,an analysis of the melanocortin type 4 receptor gene mutations and leptin levels should be performed for this *** are three therapeutic levels:lifestyle modifications,pharmacological treatment,and bariatric *** Genetic study technologies are in constant development;however,we are still far from having a personalized approach to genetic causes of obesity.A significant proportion of the affected individuals are associated with genetic causes;however,there are still barriers to its approach,as it continues to be underdiagnosed.

关键词： Leptin Melanocortin Obesity Prader-Willi syndrome Precision medicine

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Presynaptic endoplasmic reticulum architecture and hereditary spastic paraplegia

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Neural Regeneration Research 2024年第3期19卷 485-486页

作者： Juan JoséPérez-Moreno Instituto de Biomedicina de Sevilla(IBiS) Hospital Universitario Virgen Del Rocío/CSIC/Universidad de Sevillaand Departamento de Biología CelularFacultad de BiologíaUniversidad de SevillaSevilleSpain

Hereditary spastic paraplegia(HSP)is a clinically and genetically heterogeneous neurodegenerative disorder,characterized primarily by progressive spasticity and weakness in the lower *** ients can also experience peripheral neuropathy,cognitive impairment,and other neurological *** date,more than 80 genes have been implicated in HSP,encompassing various cellular components,although mutations in genes encoding endoplasmic reticulum(ER)-shaping proteins are the most prevalent(Parodi et al.,2017).ER-shaping proteins are generally known for regulating the tubulation and curvation of the ER,but most of them show additional functions,including fusion of ER tubules,microtubule-severing,ER autophagy,lipid droplet synthesis,contact sites with other organelles(Öztürk et al.,2020).This highlights the complexity of studying the role of these proteins and the link between ER function and HSP.

关键词： reticulum endoplasmic

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Multi-tissue transcriptomics of a unique monozygotic discordant twin case of severe progressive osseous heteroplasia

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Genes & Diseases 2024年第3期11卷 22-25页

作者： Alberto Gomez-Carballa Maria Jose Curras-Tuala Sara Pischedda Miriam Cebey-Lopez Jose Gomez-Rial Irene Rivero-Cale Jacobo Pardo-seco Xabier Bello Sandra Viz-Lasheras Antonio Justicia-Grande Julian Montoto-Louzao Alba Camino-Mera Isabel Ferreiros-Vidal Maximo Fraga Jose RAntunez Rodolfo Gomez Federico Martinon-Torres Antonio Salas Genetics Vaccines and Infections Research Group(GENVIP)Instituto de Investigacion Sanitaria de SantiagoSantiagode CompostelaGalicia 15706Spain Translational Pediatrics and Infectious Diseases Department of PediatricsHospital Clinico Universitario de Santiago de CompostelaServicio Galego de Saude(SERGAS)Galicia 15706Spain Laboratorio de Inmunologia Servicio de Andlisis ClinicosHospital Clinico Universitario de Santiago de CompostelaServicio Galego de Saude(SERGAS)Galicia 15706Spain Unidade de Xenetica Instituto de Ciencias Forenses(INCIFOR)Facultade de MedicinaUniversidade de Santiago de Compostelaand GenPoB Research GroupInstituto de Investigacion SanitariaHospital Clinico Universitario de Santiago de CompostelaServicio Galego de Saude(SERGAS)Galicia 15706Spain Musculoskeletal Pathology Group Instituto de Investigacion Sanitaria de SantiagoServicio Galego de Saude(SERGAS)Santiago de CompostelaGalicia 15706Spain department of Pathology Hospital Clinico Universitario de Santiago de Compostela(SERGAS)Galicia 15706Spain Unidad Integrada de BiobancosBiomodelos 3D y Modelos Animales IDIS(lnstituto de Investigacion Sanitaria de Santiagode Compostela)Galicia15706Spain Centro de Investigacion Biomedica en Red de Enfermedades Respiratorias(CIBER-ES) MadridSpain

Progressive osseous heteroplasia(POH)is an ultra-rare autosomal dominant disabling disorder characterized by heterotopic ossification(HO).It is caused by heterozygous inactivating mutations in the GNAS(guanine nucleotide-binding protein alpha-stimulating activity polypeptide)***,the molecular mechanisms underlying HO remain poorly *** a treatment for POH is not yet available,the identification of the mechanisms driving POH in affected tissues using gene expression may be of great help to underestand the molecular basis of POH and develop new therapeutic approaches.

关键词： stimulating driving asi

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Systemic Inflammation Response Index and weight loss as prognostic factors in metastatic pancreatic cancer: A concept study from the PANTHEIA-SEOM trial

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 386-397页

作者： Vilma Pacheco-Barcia Sara Custodio-Cabello Fatima Carrasco-Valero Magda Palka-Kotlowska Axel Mariño-Mendez Alberto Carmona-Bayonas Javier Gallego A J Muñoz Martín Paula Jimenez-Fonseca Luis Cabezon-Gutierrez department of Medical Oncology Hospital Universitario de TorrejonMadrid 28850Spain department of Internal Medicine Hospital Universitario de TorrejonMadrid 28850Spain department of Medical Oncology Hospital Universitario Central de AsturiasOviedo 33011Spain department of Medical Oncology Hospital Universitario Morales MeseguerUniversity of MurciaMurcia 30001Spain department of Medical Oncology Hospital General Universitario de ElcheElche 03202Spain department of Medical Oncology Hospital General Universitario Gregorio MarañónUniversidad Complutense MadridMadrid 28007Spain Universidad Francisco de Vitoria Madrid 28223Spain

BACKGROUND The prognostic value of the Systemic Inflammation Response Index(SIRI)in advanced pancreatic cancer is recognized,but its correlation with patients´nutritional status and outcomes remains *** To study the prognostic significance of SIRI and weight loss in metastatic pancreatic *** The PANTHEIA-Spanish Society of Medical Oncology(SEOM)study is a multicentric(16 Spanish hospitals),observational,longitudinal,non-interventional initiative,promoted by the SEOM Real World-Evidence work *** pilot study sought to analyze the association between weight loss and inflammatory status as defined by *** cohort stems from a proof-of-concept pilot study conducted at one of the coordinating *** with pathologically confirmed metastatic pancreatic adenocarcinoma,treated from January 2020 to January 2023,were *** index was calculated using the product of neutrophil and monocyte counts,divided by lymphocyte counts,obtained within 15 days before initiation *** study evaluated associations between overall survival(OS),SIRI and weight *** A total of 50 patients were included.66%of these patients were male and the median age was 66 *** sites:36%liver,12%peritoneal carcinomatosis,10%lung,and 42%multiple *** the first line palliative chemotherapy treatments:50%received gemcitabine plus nab-paclitaxel;28%,modified fluorouracil,leucovorin,irinotecan and oxaliplatin,and 16%were administered gemcitabine.42%had a weight loss>5%in the three months(mo)preceding diagnosis.21 patients with a SIRI≥2.3×10^(3)/L exhibited a trend towards a lower median OS compared to those with a SIRI5%weight loss before diagnosis,the median OS was 6 mo,in contrast to 19 mo for those who did not experience such weight loss(P=0.003).Patients with a weight loss>5%showed higher SIRI *** difference was statistically significant(P<0.000).For pat

关键词： Pancreatic cancer Nutrition Prognostic factor Inflammation Advanced cancer Systemic inflammatory response index Weight loss

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Omics-based biomarkers as useful tools in metabolic dysfunctionassociated steatotic liver disease clinical practice:How far are we?

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World Journal of Gastroenterology 2024年第14期30卷 1982-1989页

作者： Julieta Trinks María F Mascardi Adrián Gadano Sebastián Marciano Instituto de Medicina Traslacional e Ingeniería Biomédica-Consejo Nacional de Investigaciones Científicas y Técnicas-Instituto Universitario del hospital Italiano-hospital Italiano de Buenos Aires Ciudad Autónoma de Buenos Aires C1199ACLArgentina Consejo Nacional de Investigaciones Científicas y Técnicas Ciudad Autónoma de Buenos Aires C1425FQBArgentina Liver Unit Hospital Italiano de Buenos AiresCiudad Autónoma de Buenos Aires C1199DFArgentina department of Research Hospital Italiano de Buenos AiresCiudad Autónoma de Buenos Aires C1199DFArgentina

Unmet needs exist in metabolic dysfunction-associated steatotic liver disease(MASLD)risk *** ability to identify patients with MASLD with advanced fibrosis and at higher risk for adverse outcomes is still *** novel biomarkers could represent a meaningful improvement to current risk *** this aim,omics technologies have revolutionized the process of MASLD biomarker discovery over the past *** the research in this field is thriving,much of the publication has been haphazard,often using single-omics data and specimen sets of convenience,with many identified candidate biomarkers but lacking clinical validation and *** we incorporate these biomarkers to direct patients’management,it should be considered that the roadmap for translating a newly discovered omics-based signature to an actual,analytically valid test useful in MASLD clinical practice is rigorous and,therefore,not easily *** article presents an overview of this area’s current state,the conceivable opportunities and challenges of omics-based laboratory diagnostics,and a roadmap for improving MASLD biomarker research.

关键词： Metabolic dysfunction-associated steatotic liver disease Non-alcoholic steatohepatitis Biomarker Risk stratification Omics

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Real-world clinical efficacy of tofacitinib in moderate-to-severe ulcerative colitis

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World Journal of Gastroenterology 2024年第34期30卷 3929-3931页

作者： Sara R Lopes Claudio Martins Madalena Teixeira David Tomás department of Gastroenterology Unidade Local de Saúde da Arrábida-Hospital de São BernardoSetúbal 2910-446Portugal

Tofacitinib is an oral small-molecule Janus kinase(JAK)inhibitor that preferentially inhibits JAK1 and *** efficacy in inducing and maintaining remission in ulcerative colitis(UC)as well as its safety profile has been demonstrated in multicenter,randomized,double-blind,placebo-controlled ***,real-world studies evaluating the effectiveness and adverse effects of tofacitinib have been conducted,affirming its clinical efficacy in moderate-to-severe UC.

关键词： Ulcerative colitis Tofacitinib Real-world studies Inflammatory bowel disease Janus kinase inhibitor

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Clinical profile and outcomes in very elderly patients with atrial fibrillation anticoagulated with rivaroxaban: data from the EMIR study

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Journal of Geriatric Cardiology 2024年第7期21卷 723-732页

作者： Francisco Marín Manuel Anguita Sánchez Iñaki Lekuona Marcelo Sanmartín Fernán-dez Vivencio Barrios Carlos Perez Muñoz Juan Cosín-Sales Alejandro IPérez Cabeza Vanesa Roldán Schilling Carles Rafols Priu Esteban Orenes-Piñero María Asunción Es-teve-Pastor department of Cardiology Hospital Clínico Universitario Virgen de la ArrixacaIMIB-ArrixacaUniversity of MurciaCIBERCVMurciaSpain department of Cardiology Hospital Reina Sofía CórdobaIMIBICUniversity of CordobaCIBERCVCórdobaSpain hospital Galdakao-Usansolo BizkaiaSpain department of Cardiology Hospital Uni-versitario Ramony CajalCIBERCVMadridSpain department of Cardiology University Hospital Ramóny CajalAl-caláUniversityMadridSpain Medical Center La Capillita Sanlúcar de Barrameda.Private cardiology clinicJerez de la FronteraSpain department of Cardiology Hospital Arnau de VilanovaValenciaSpain department of Car-diology Virgen de la Victoria University HospitalCIBERCV.MalagaSpain department of Haematology Hospital Clínico Universitario Virgen de la ArrixacaUniversity of MurciaMurciaSpain department of Medical Affairs Bayer HispaniaBarcelonaSpain department of Biochemistry and Molecular Biology-A University of MurciaMurciaSpain

Objectives To analyze the clinical profile,adequacy of treatment with rivaroxaban and outcomes in octogenarians with atrial fibrillation(AF),taking rivaroxaban in clinical *** Observational and non-interventional study that included AF adults recruited from 79 Spanish centers,anticoagulated with rivaroxaban ≥ 6 months before being *** were analyzed according to age(≥ 80 vs.dequately prescribed in 83.4% of patients,but more frequently in the younger population(71.1% vs.89.1%;P = 0.039).After a mean follow-up of 2.2 ± 0.6 years,annual rates of stroke + systemic embolism + transient ischemic attack,MACE,cardiovascular death and major bleeding were 1.03%,1.24%,1.03% and 1.75%,respectively,in octogenarian *** for progressive heart failure death and major bleeding,rates of outcomes in octogenarians were similar compared to younger *** octogenarians,the concomitant use of antiplatelet agents and non-severe dementia were independently associated with the development of ischemic stroke,whereas previous coronary revascularization and heart failure with MACE,and higher HAS-BLED score with major *** In clinical practice,around one third of patients taking rivaroxaban are *** patients have many comorbidities and a high thromboembolic *** that,rates of adverse events remain *** is adequately prescribed in the majority of octogenarians.

关键词： patients atrial bleeding

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The Iberian Roma Population Variant Server(IRPVS)

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Journal of Genetics and Genomics 2024年第7期51卷 769-773页

作者： Fabiola Mavillard Javier Perez-Florido Francisco M.Ortuño Amador Valladares Miren L.Álvarez-Villegas Gema Roldán Rosario Carmona Manuel Soriano Santiago Susarte Pilar Fuentes Daniel López-López Ana María Nuñez-Negrillo Alejandra Carvajal Yolanda Morgado Daniel Arteaga Rosa Ufano Pablo Mir Juan F.Gamella Joaquín Dopazo Carmen Paradas Macarena Cabrera-Serrano Instituto de Biomedicina de Sevilla(IBiS) Hospital Universitario Virgen del Rocío/CSIC/Universidad de SevillaSevillaSpain Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas(CIBERNED) Instituto de Salud CarlosⅢSevillaSpain Plataforma Andaluza de Medicina Computacional Fundación Progreso y Salud(FPS)Hospital Virgen del RocíoSevillaSpain Grupo de medicina computacional de sistemas Instituto de Biomedicina de Sevilla(IBiS)Hospital Virgen del RocíoSevillaSpain Nodo de Genómica Funcional (INB-ELIXIR-es)Fundación Progreso y Salud(FPS)Hospital Virgen del RocíoSevilla 41013Spain Bioinformática en Enfermedades raras(BiER) Centro de Investigación Biomédica en Red de Enfermedades Raras(CIBERER)Instituto de salud CarlosⅢSevillaSpain departamento de Ingeniería de Computadores Automática y RobóticaUniversidad de GranadaGranadaSpain Servicio de Urgencias de Atención Primaria Distrito SevillaSevillaSpain Centro de Servicios Sociales Negociado de Servicios EspecializadosAyuntamiento de SevillaSevillaSpain departamento de Enfermería Facultad de Ciencias de la SaludUniversidad de GranadaGranadaSpain departamento de Neurología Hospital Virgen de las NievesGranadaSpain departamento de Neurología Hospital Virgen de ValmeSevillaSpain Centro de Salud Utrera Sur SevillaSpain Centro de Salud Polígono Sur SevillaSpain Unidad de Trastornos del Movimiento Servicio de Neurología y Neurofisiología ClínicaHospital Universitario Virgen del RocíoSevillaSpain departamento de Medicina Facultad de MedicinaUniversidad de SevillaSevilleSpain departamento de Antropología Social Universidad de GranadaSpain Unidad Enfermedades Neuromusculares Servicio de Neurología y Neurofisiología ClínicaHospital Universitario Virgen del RocíoSevillaSpain

In recent years,the number of known disease genes has exponentially grown due to the widespread adoption of cost-effective massive parallel *** identify new disease variants,especially in monogenic disorders,a frequen... 详细信息

关键词： Server filtering massive

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Prevalence of Helicobacter pylori infection among patients with esophageal carcinoma

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World Journal of Gastroenterology 2024年第29期30卷 3479-3487页

作者： Miriam López-Gómez Maria Morales Rebeca Fuerte Marta Muñoz Pedro-David delgado-López Jorge Francisco Gómez-Cerezo Enrique Casado department of Medical Oncology Precision Oncology LaboratoryInfanta Sofía University HospitalSan Sebastián de los Reyes 28231MadridSpain department of Medical Oncology Infanta Sofía University HospitalSan Sebastián de los Reyes 28702Spain department of Internal Medicine Infanta Sofía University HospitalSan Sebastián de los Reyes 28703MadridSpain department of Pathology Infanta Sofía University HospitalSan Sebastián de los Reyes 28702Spain department of Neurosurgery Burgos University HospitalBurgos 09006Spain department of Internal Medicine Infanta Sofía University Hospital and Henares University Hospital Foundation for Biomedical Research and InnovationSan Sebastian de los Reyes 28702MadridSpain department of Medical Oncology Infanta Sofia University Hospital and Henares University Hospital Foundation for Biomedical Research and InnovationSan Sebastian de los Reyes 28702MadridSpain

BACKGROUND Helicobacter pylori(***)is a widespread microorganism related to gastric adenocarcinoma(AC).In contrast,it has been reported that an inverse association exists between *** infection and esophageal *** mechanisms underlying this supposedly protective effect remain *** To determine the prevalence of *** infection in esophageal carcinoma patients,we performed a retrospective observational study of esophageal tumors diagnosed in our *** We retrospectively reviewed the prevalence of *** infection in a cohort of patients diagnosed with esophageal *** or previous proton pump inhibitor(PPI)usage was also *** A total of 89 patients with esophageal carcinoma(69 males,77.5%),with a mean age of 66 years(range,26-93 years)were *** was the most frequent pathological variant(n=47,52.8%),followed by squamous cell carcinoma(n=37,41.6%).Fourteen ACs(29.8%)originated in the gastroesophageal junction and 33(70.2%)in the esophageal ***,54 patients(60.7%)presented at stages III and *** *** infection occurred only in 4 patients(4.5%),3 with AC(6.3%of all ACs)and 1 with squamous cell carcinoma(2.7%of all squamous cell tumors).All patients with previous *** infection had stage *** one patient had received prior *** eradication therapy,whereas 86(96.6%)had received previous or concomitant PPI *** In our cohort of patients,and after histologic evaluation of paraffin-embedded primary tumors,we found a very low prevalence of previous *** *** also reviewed the medical history of the patients,concluding that the majority had received or were on PPI *** minimal prevalence of *** infection found in this cohort of patients with esophageal carcinoma suggests a protective role.

关键词： Helicobacter pylori Eradication Esophageal tumor Dysbiosis Proton pump inhibitors Carcinogenesis Microbiota Incidence

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Metastatic pancreatic and lung cancer patient in complete remission following immunotherapy: A case report and review of literature

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2233-2240页

作者： Joaquina Martínez-Galán Cristina Jiménez-Luna Isabel Rodriguez Elisabeth Maza Carlos García-Collado Antonio Rodríguez-Fernández Javier Luis López-Hidalgo Octavio Caba department of Medical Oncology Virgen de las Nieves University HospitalGranada 18014Spain Instituto de Investigación Biosanitaria Ibs.GranadaGranada 18012Spain Institute of Biopathology and Regenerative Medicine(IBIMER) University of GranadaGranada 18016Spain Pharmacogenetics Unit Virgen de las Nieves University HospitalGranada 18014Spain department of Medicina Nuclear Virgen de las Nieves University HospitalGranada 18014Spain department of Anatomía Patológica Virgen de las Nieves University HospitalGranada 18014Spain

BACKGROUND Metastatic pancreatic ductal adenocarcinoma(PDAC)is a lethal malignancy with dispiriting survival *** is a promising approach to many cancer types,but achieves poor outcomes in advanced PDAC due to its immunosuppressive tumor *** describe a case of metastatic PDAC effectively treated with *** SUMMARY We report the case of a 67-year-old woman with unresectable locally advanced PDAC,treated with gemcitabine plus nab-paclitaxel followed by radiotherapy plus *** nine months,pancreatic tumor progression was observed at the level of the hepatic hilum with the appearance of a new pulmonary nodule suggestive of a second primary,confirmed by left lung *** immunotherapy was then initiated with pembrolizumab,an immune checkpoint inhibitor targeting programmed cell death protein-1 that covers the two tumor *** patient showed a complete metabolic response that was maintained throughout the *** patient continues to be disease-free at 5.6 years since the start of *** These results suggest that the administration of pembrolizumab after chemoradiotherapy has a beneficial effect in patients with metastatic *** our knowledge,this is the first reported case of a patient with metastatic PDAC and metastatic lung cancer showing such a long-lasting complete response after pembrolizumab treatment without curative *** studies are required to determine biomarkers that identify PDAC patients most likely to benefit from this immunotherapy.

关键词： Pancreatic ductal adenocarcinoma Lung cancer Immunotherapy Pembrolizumab Programmed cell death protein-1 Case report

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