Base de dados : MEDLINE
Pesquisa : I03.784 [Categoria DeCS]
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[PMID]:29363500
[Au] Autor:Blomstedt Y; Bhutta ZA; Dahlstrand J; Friberg P; Gostin LO; Nilsson M; Sewankambo NK; Tomson G; Alfvén T
[Ad] Endereço:Epidemiology and Global Health Unit, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
[Ti] Título:Partnerships for child health: capitalising on links between the sustainable development goals.
[So] Source:BMJ;360:k125, 2018 01 23.
[Is] ISSN:1756-1833
[Cp] País de publicação:England
[La] Idioma:eng
[Mh] Termos MeSH primário: Saúde da Criança/normas
Conservação dos Recursos Naturais/métodos
Prática Associada/organização & administração
[Mh] Termos MeSH secundário: Adolescente
Criança
Saúde da Criança/legislação & jurisprudência
Pré-Escolar
Tomada de Decisões/ética
Feminino
Saúde Global/legislação & jurisprudência
Saúde Global/normas
Política de Saúde/legislação & jurisprudência
Seres Humanos
Lactente
Recém-Nascido
Cooperação Internacional
Masculino
Sobrevida
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180125
[St] Status:MEDLINE
[do] DOI:10.1136/bmj.k125


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[PMID]:28906153
[Au] Autor:Amoroso L; Haupt R; Garaventa A; Ponzoni M
[Ad] Endereço:a Department of Pediatric Oncology , Istituto G.Gaslini , Genova , Italy.
[Ti] Título:Investigational drugs in phase II clinical trials for the treatment of neuroblastoma.
[So] Source:Expert Opin Investig Drugs;26(11):1281-1293, 2017 Nov.
[Is] ISSN:1744-7658
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Neuroblastoma (NB) is an embryonal tumor originating from undifferentiated neural crest cell, highly heterogeneous ranging from spontaneous regression to progression despite multimodal treatments. Approximately, 20% of patients are refractory to frontline therapy and 50% will relapse/progress after an initial response. The overall five year survival for high-risk neuroblastoma ranges from 35-45%. Despite enhanced understanding of NB biology and the addition of myeloablative chemotherapy, isotretinoin and immunotherapy, survival for high risk NB remains less than 50%. Areas covered: This review summarizes and gives a critical overview of phase II trials investigating therapies for relapsed-refractory and high risk neuroblastoma. Expert opinion: Several novel molecules have been developed and are currently under investigation for the treatment of NB. The trend of novel targeted agents is one towards individualized, tailored therapy, based on the molecular and biological differences that characterize tumors that seem similar based solely on histological analysis. The task of developing new molecules is particularly difficult for NB, given the recurrent development of new patterns of drug resistance. However, even if current research is focused towards identifying the best treatments for each children and young adult with a NB defined disease, a deeper knowledge of the molecular biology and genetics is needed.
[Mh] Termos MeSH primário: Antineoplásicos/uso terapêutico
Drogas em Investigação/uso terapêutico
Neuroblastoma/tratamento farmacológico
[Mh] Termos MeSH secundário: Antineoplásicos/farmacologia
Criança
Ensaios Clínicos Fase II como Assunto
Desenho de Drogas
Resistência a Medicamentos Antineoplásicos
Drogas em Investigação/farmacologia
Seres Humanos
Terapia de Alvo Molecular
Recidiva Local de Neoplasia
Neuroblastoma/patologia
Sobrevida
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Drugs, Investigational)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170915
[St] Status:MEDLINE
[do] DOI:10.1080/13543784.2017.1380625


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[PMID]:28864675
[Au] Autor:McDonnell E; Schoenfeld D; Paganoni S; Atassi N
[Ad] Endereço:From the Biostatistics Center (E.M., D.S.) and Neurological Clinical Research Institute (S.P., N.A.), Massachusetts General Hospital; and Harvard Medical School (D.S., S.P., N.A.), Boston, MA. EIM726@mail.harvard.edu NAtassi@mgh.harvard.edu.
[Ti] Título:Causal inference methods to study gastric tube use in amyotrophic lateral sclerosis.
[So] Source:Neurology;89(14):1483-1489, 2017 Oct 03.
[Is] ISSN:1526-632X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: To estimate effects of gastric tube (G-tube) on survival and quality of life (QOL) in people with amyotrophic lateral sclerosis (ALS) correcting for confounding by indication inherent in nonrandomized observational data. METHODS: To complement a recent causal inference analysis, which concluded that G-tube placement increases the hazard of death, permanent assisted ventilation, or tracheostomy by 28%, we fit causal inference models on a different sample of 481 patients with ALS enrolled in a recent clinical trial of ceftriaxone. Forward selection identified predictors of G-tube placement. Effects of G-tube on survival and QOL were estimated using structural nested models and marginal structural models, accounting for predictors of G-tube treatment. RESULTS: Forced vital capacity and the total score and bulbar subscale of the revised ALS Functional Rating Scale best predicted G-tube placement. Correcting for these confounders, G-tube placement decreased survival time by 46% ( < 0.001) and had no effect on QOL ( = 0.078). Sensitivity survival analyses varied in significance, but none revealed a survival benefit. CONCLUSIONS: In the absence of randomization, causal inference methods are necessary to correct for time-varying confounding. G-tube placement may have a negative effect on survival with no QOL-related benefit for people with ALS. A randomized controlled trial is warranted to further evaluate the efficacy of this widely used intervention. CLINICALTRIALSGOV IDENTIFIER: NCT00349622. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with ALS, G-tube placement decreases survival time and does not affect QOL.
[Mh] Termos MeSH primário: Esclerose Amiotrófica Lateral/psicologia
Esclerose Amiotrófica Lateral/terapia
Nutrição Enteral/métodos
Qualidade de Vida
Sobrevida
[Mh] Termos MeSH secundário: Adulto
Idoso
Esclerose Amiotrófica Lateral/epidemiologia
Progressão da Doença
Feminino
Seguimentos
Seres Humanos
Masculino
Meia-Idade
Respiração Artificial/métodos
Sobrevida/psicologia
Análise de Sobrevida
Capacidade Vital
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171013
[Lr] Data última revisão:
171013
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170903
[St] Status:MEDLINE
[do] DOI:10.1212/WNL.0000000000004534


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[PMID]:28719604
[Au] Autor:Lockey DJ
[Ad] Endereço:Blizard Institute, Queen Mary University, London, United Kingdom.
[Ti] Título:Research questions in pre-hospital trauma care.
[So] Source:PLoS Med;14(7):e1002345, 2017 Jul.
[Is] ISSN:1549-1676
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Noting that a variety of pre-hospital interventions can now be applied to treat traumatic injury, David J Lockey calls for research to determine which of these actually improve survival and reduce morbidity.
[Mh] Termos MeSH primário: Pesquisa
Ferimentos e Lesões/terapia
[Mh] Termos MeSH secundário: Seres Humanos
Tempo de Internação
Morbidade
Sobrevida
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170719
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pmed.1002345


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[PMID]:28719316
[Au] Autor:Samayoa B; Roy M; Cleveland AA; Medina N; Lau-Bonilla D; Scheel CM; Gomez BL; Chiller T; Arathoon E
[Ad] Endereço:Facultad de Ciencias Químicas y Farmacia, Universidad de San Carlos de Guatemala, Guatemala, Guatemala.
[Ti] Título:High Mortality and Coinfection in a Prospective Cohort of Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome Patients with Histoplasmosis in Guatemala.
[So] Source:Am J Trop Med Hyg;97(1):42-48, 2017 Jul.
[Is] ISSN:1476-1645
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Histoplasmosis is one of the most common and deadly opportunistic infections among persons living with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome in Latin America, but due to limited diagnostic capacity in this region, few data on the burden and clinical characteristics of this disease exist. Between 2005 and 2009, we enrolled patients ≥ 18 years of age with suspected histoplasmosis at a hospital-based HIV clinic in Guatemala City. A case of suspected histoplasmosis was defined as a person presenting with at least three of five clinical or radiologic criteria. A confirmed case of histoplasmosis was defined as a person with a positive culture or urine antigen test for . Demographic and clinical data were also collected and analyzed. Of 263 enrolled as suspected cases of histoplasmosis, 101 (38.4%) were confirmed cases. Median time to diagnosis was 15 days after presentation (interquartile range [IQR] = 5-23). Crude overall mortality was 43.6%; median survival time was 19 days (IQR = 4-69). Mycobacterial infection was diagnosed in 70 (26.6%) cases; 26 (25.7%) histoplasmosis cases were coinfected with mycobacteria. High mortality and short survival time after initial symptoms were observed in patients with histoplasmosis. Mycobacterial coinfection diagnoses were frequent, highlighting the importance of pursuing diagnoses for both diseases.
[Mh] Termos MeSH primário: Infecções Oportunistas Relacionadas com a AIDS/mortalidade
Síndrome de Imunodeficiência Adquirida/mortalidade
Coinfecção/mortalidade
Infecções por HIV/mortalidade
Histoplasmose/complicações
Histoplasmose/mortalidade
[Mh] Termos MeSH secundário: Infecções Oportunistas Relacionadas com a AIDS/complicações
Síndrome de Imunodeficiência Adquirida/complicações
Adulto
Idoso
Idoso de 80 Anos ou mais
Causas de Morte
Estudos de Coortes
Coinfecção/complicações
Feminino
Guatemala
Infecções por HIV/complicações
Histoplasma/isolamento & purificação
Seres Humanos
Masculino
Meia-Idade
Mortalidade
Estudos Prospectivos
Sobrevida
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170821
[Lr] Data última revisão:
170821
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170719
[St] Status:MEDLINE
[do] DOI:10.4269/ajtmh.16-0009


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[PMID]:28692670
[Au] Autor:Raffel J; Wallace A; Gveric D; Reynolds R; Friede T; Nicholas R
[Ad] Endereço:Division of Brain Sciences, Faculty of Medicine, Imperial College London, London, United Kingdom.
[Ti] Título:Patient-reported outcomes and survival in multiple sclerosis: A 10-year retrospective cohort study using the Multiple Sclerosis Impact Scale-29.
[So] Source:PLoS Med;14(7):e1002346, 2017 Jul.
[Is] ISSN:1549-1676
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: There is increasing emphasis on using patient-reported outcomes (PROs) to complement traditional clinical outcomes in medical research, including in multiple sclerosis (MS). Research, particularly in oncology and heart failure, has shown that PROs can be prognostic of hard clinical endpoints such as survival time (time from study entry until death). However, unlike in oncology or cardiology, it is unknown whether PROs are associated with survival time in neurological diseases. The Multiple Sclerosis Impact Scale-29 (MSIS-29) is a PRO sensitive to short-term change in MS, with questions covering both physical and psychological quality of life. This study aimed to investigate whether MSIS-29 scores can be prognostic for survival time in MS, using a large observational cohort of people with MS. METHODS AND FINDINGS: From 15 July 2004 onwards, MSIS-29 questionnaires were completed by people with MS registered with the MS Society Tissue Bank (n = 2,126, repeated 1 year later with n = 872 of the original respondents). By 2014, 264 participants (12.4%) had died. Higher baseline MSIS-29 physical (MSIS-29-PHYS) score was associated with reduced survival time (subgroup with highest scores versus subgroup with lowest scores: hazard ratio [HR] 5.7, 95% CI 3.1-10.5, p < 0.001). Higher baseline MSIS-29 psychological score was also associated with reduced survival time (subgroup with highest scores versus subgroup with lowest scores: HR 2.8, 95% CI 1.8-4.4, p < 0.001). In those with high baseline MSIS-29 scores, mortality risk was even greater if the MSIS-29 score worsened over 1 year (HR 2.3, 95% CI 1.2-4.4, p = 0.02). MSIS-29-PHYS scores were associated with survival time independent of age, sex, and patient-reported Expanded Disability Status Scale score in a Cox regression analysis (per 1-SD increase in MSIS-29-PHYS score: HR 1.8, 95% CI 1.1-2.9, p = 0.03). A limitation of the study is that this cohort had high baseline age and disability levels; the prognostic value of MSIS-29 for survival time at earlier disease stages requires further investigation. CONCLUSIONS: This study reports that PROs can be prognostic for hard clinical outcomes in neurological disease, and supports PROs as a meaningful clinical outcome for use in research and clinical settings.
[Mh] Termos MeSH primário: Esclerose Múltipla/etiologia
Medidas de Resultados Relatados pelo Paciente
[Mh] Termos MeSH secundário: Adulto
Idoso
Estudos de Coortes
Feminino
Seres Humanos
Masculino
Meia-Idade
Esclerose Múltipla/diagnóstico
Prognóstico
Estudos Retrospectivos
Inquéritos e Questionários
Sobrevida
Reino Unido
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170726
[Lr] Data última revisão:
170726
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170711
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pmed.1002346


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[PMID]:28515105
[Au] Autor:Schröck A; Leisse A; de Vos L; Gevensleben H; Dröge F; Franzen A; Wachendörfer M; Schröck F; Ellinger J; Teschke M; Wilhelm-Buchstab T; Landsberg J; Holdenrieder S; Hartmann G; Field JK; Bootz F; Kristiansen G; Dietrich D
[Ad] Endereço:Department of Otolaryngology, Head and Neck Surgery, University Hospital Bonn, Bonn, Germany.
[Ti] Título:Free-Circulating Methylated DNA in Blood for Diagnosis, Staging, Prognosis, and Monitoring of Head and Neck Squamous Cell Carcinoma Patients: An Observational Prospective Cohort Study.
[So] Source:Clin Chem;63(7):1288-1296, 2017 Jul.
[Is] ISSN:1530-8561
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Circulating cell-free DNA methylation testing in blood has recently received regulatory approval for screening of colorectal cancer. Its application in other clinical settings, including staging, prognosis, prediction, and recurrence monitoring is highly promising, and of particular interest in head and neck squamous cell carcinomas (HNSCCs) that represent a heterogeneous group of cancers with unsatisfactory treatment guidelines. METHODS: Short stature homeobox 2 ( ) and septin 9 ( ) DNA methylation in plasma from 649 prospectively enrolled patients (training study: 284 HNSCC/122 control patients; testing study: 141 HNSCC/102 control patients) was quantified before treatment and longitudinally during surveillance. RESULTS: In the training study, 59% of HNSCC patients were methylation-positive at 96% specificity. Methylation levels correlated with tumor and nodal category ( < 0.001). Initially increased methylation levels were associated with a higher risk of death [ : hazard ratio (HR) = 5.27, = 0.001; : HR = 2.32, = 0.024]. Disease recurrence/metastases were detected in 47% of patients up to 377 days earlier compared to current clinical practice. The onset of second cancers was detected up to 343 days earlier. In the testing study, sensitivity (52%), specificity (95%), prediction of overall survival ( : HR = 2.78, = 0.022; : HR = 2.50, = 0.026), and correlation with tumor and nodal category ( <0.001) were successfully validated. CONCLUSIONS: Methylation testing in plasma is a powerful diagnostic tool for molecular disease staging, risk stratification, and disease monitoring. Patients with initially high biomarker levels might benefit from intensified treatment and posttherapeutic surveillance. The early detection of a recurrent/metastatic disease or a second malignancy could lead to an earlier consecutive treatment, thereby improving patients' outcomes.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/sangue
Carcinoma de Células Escamosas/diagnóstico
Metilação de DNA
Neoplasias de Cabeça e Pescoço/diagnóstico
[Mh] Termos MeSH secundário: Carcinoma de Células Escamosas/sangue
Estudos de Coortes
Neoplasias de Cabeça e Pescoço/sangue
Proteínas de Homeodomínio/sangue
Proteínas de Homeodomínio/genética
Seres Humanos
Estadiamento de Neoplasias
Valor Preditivo dos Testes
Prognóstico
Septinas/sangue
Septinas/genética
Sobrevida
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (Homeodomain Proteins); 0 (SHOX2 protein, human); EC 3.6.1.- (SEPT9 protein, human); EC 3.6.1.- (Septins)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170713
[Lr] Data última revisão:
170713
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170519
[St] Status:MEDLINE
[do] DOI:10.1373/clinchem.2016.270207


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[PMID]:28399822
[Au] Autor:De Mandal S; Chatterjee R; Kumar NS
[Ad] Endereço:Department of Biotechnology, Mizoram University, Aizawl, Mizoram, 796004, India.
[Ti] Título:Dominant bacterial phyla in caves and their predicted functional roles in C and N cycle.
[So] Source:BMC Microbiol;17(1):90, 2017 Apr 11.
[Is] ISSN:1471-2180
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Bacteria present in cave often survive by modifying their metabolic pathway or other mechanism. Understanding these adopted bacteria and their survival strategy inside the cave is an important aspect of microbial ecology. Present study focuses on the bacterial community and geochemistry in five caves of Mizoram, Northeast India. The objective of this study was to explore the taxonomic composition and presumed functional diversity of cave sediment metagenomes using paired end Illumina sequencing using V3 region of 16S rRNA gene and bioinformatics pipeline. RESULTS: Actinobacteria, Proteobacteria, Verrucomicrobia and Acidobacteria were the major phyla in all the five cave sediment samples. Among the five caves the highest diversity is found in Lamsialpuk with a Shannon index 12.5 and the lowest in Bukpuk (Shannon index 8.22). In addition, imputed metagenomic approach was used to predict the functional role of microbial community in biogeochemical cycling in the cave environments. Functional module showed high representation of genes involved in Amino Acid Metabolism in (20.9%) and Carbohydrate Metabolism (20.4%) in the KEGG pathways. Genes responsible for carbon degradation, carbon fixation, methane metabolism, nitrification, nitrate reduction and ammonia assimilation were also predicted in the present study. CONCLUSION: The cave sediments of the biodiversity hotspot region possessing a oligotrophic environment harbours high phylogenetic diversity dominated by Actinobacteria and Proteobacteria. Among the geochemical factors, ferric oxide was correlated with increased microbial diversity. In-silico analysis detected genes involved in carbon, nitrogen, methane metabolism and complex metabolic pathways responsible for the survival of the bacterial community in nutrient limited cave environments. Present study with Paired end Illumina sequencing along with bioinformatics analysis revealed the essential ecological role of the cave bacterial communities. These results will be useful in documenting the biospeleology of this region and systematic understanding of bacterial communities in natural sediment environments as well.
[Mh] Termos MeSH primário: Bactérias/classificação
Bactérias/isolamento & purificação
Bactérias/metabolismo
Ciclo do Carbono/fisiologia
Cavernas/microbiologia
Ciclo do Nitrogênio/fisiologia
Filogenia
[Mh] Termos MeSH secundário: Aminoácidos/metabolismo
Amônia/metabolismo
Bactérias/genética
Sequência de Bases
Biodiversidade
Metabolismo dos Carboidratos
Carbono/metabolismo
Classificação
DNA Bacteriano
Ecologia
Compostos Férricos/metabolismo
Sedimentos Geológicos/química
Sedimentos Geológicos/microbiologia
Índia
Redes e Vias Metabólicas/fisiologia
Metagenoma
Metagenômica
Nitratos/metabolismo
Nitrificação
Nitrogênio/metabolismo
RNA Ribossômico 16S/genética
Análise de Sequência
Microbiologia do Solo
Sobrevida
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amino Acids); 0 (DNA, Bacterial); 0 (Ferric Compounds); 0 (Nitrates); 0 (RNA, Ribosomal, 16S); 1K09F3G675 (ferric oxide); 7440-44-0 (Carbon); 7664-41-7 (Ammonia); N762921K75 (Nitrogen)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170831
[Lr] Data última revisão:
170831
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170413
[St] Status:MEDLINE
[do] DOI:10.1186/s12866-017-1002-x


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[PMID]:28360419
[Au] Autor:Bach DR; Dayan P
[Ad] Endereço:Division for Clinical Psychiatry Research, Psychiatric Hospital, University of Zurich; at the Neuroscience Centre Zurich, University of Zurich, 8032 Zurich, Switzerland; and at the Wellcome Trust Centre for Neuroimaging, University College London, London WC1N 3BG, UK.
[Ti] Título:Algorithms for survival: a comparative perspective on emotions.
[So] Source:Nat Rev Neurosci;18(5):311-319, 2017 May.
[Is] ISSN:1471-0048
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The nature and neural implementation of emotions is the subject of vigorous debate. Here, we use Bayesian decision theory to address key complexities in this field and conceptualize emotions in terms of their relationship to survival-relevant behavioural choices. Decision theory indicates which behaviours are optimal in a given situation; however, the calculations required are radically intractable. We therefore conjecture that the brain uses a range of pre-programmed algorithms that provide approximate solutions. These solutions seem to produce specific behavioural manifestations of emotions and can also be associated with core affective dimensions. We identify principles according to which these algorithms are implemented in the brain and illustrate our approach by considering decision making in the face of proximal threat.
[Mh] Termos MeSH primário: Algoritmos
Encéfalo/fisiologia
Emoções/fisiologia
Sobrevida/psicologia
[Mh] Termos MeSH secundário: Animais
Teorema de Bayes
Tomada de Decisões
Seres Humanos
Sobrevida/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170420
[Lr] Data última revisão:
170420
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170401
[St] Status:MEDLINE
[do] DOI:10.1038/nrn.2017.35


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[PMID]:28323497
[Au] Autor:Bao HX; Bi Q; Han Y; Zhao C; Zou H
[Ad] Endereço:a Department of Orthopedics , the First Clinical Medical College of Zhejiang Chinese Medical University , Hangzhou , PR China.
[Ti] Título:Potential mechanisms underlying CDK5 related Osteosarcoma progression.
[So] Source:Expert Opin Ther Targets;21(5):455-460, 2017 May.
[Is] ISSN:1744-7631
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: Identification of new prognostic biomarkers and therapeutic targets is of crucial importance for patients with osteosarcoma. Cyclin-dependent kinase 5 (CDK5) is overexpressed in several tumor types. However, the exact role CDK5 plays in osteosarcoma is still unknown. METHODS: In this study, we explored the association between CDK5 expression and the prognosis of osteosarcoma patients using publicly available gene expression datasets. Potential molecular mechanisms underlying its pro-malignant role in cancer progression were also discussed. RESULTS: We demonstrated that tricarboxylic acid (TCA) cycle is activated while antigen presentation is repressed in patients with CDK5 overexpression and poor survival. This results indicated that sufficient energy production and tumor immune escape are important characteristics and potential therapeutic targets for this subgroup of osteosarcoma patients. Furthermore, several critical hub genes that are associated with CDK5 related osteosarcoma progression such as MELK were identified. CONCLUSION: This study discussed the pro-malignant role of CDK5 and potential mechanisms involved. Further preclinical and clinical studies to develop CDK5 based treatments are warranted.
[Mh] Termos MeSH primário: Neoplasias Ósseas/patologia
Quinase 5 Dependente de Ciclina/genética
Osteossarcoma/patologia
[Mh] Termos MeSH secundário: Neoplasias Ósseas/genética
Ciclo do Ácido Cítrico/genética
Bases de Dados Genéticas
Progressão da Doença
Regulação Neoplásica da Expressão Gênica
Seres Humanos
Osteossarcoma/genética
Proteínas Serina-Treonina Quinases/genética
Sobrevida
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 2.7.1.- (MELK protein, human); EC 2.7.11.1 (Cyclin-Dependent Kinase 5); EC 2.7.11.1 (Protein-Serine-Threonine Kinases); EC 2.7.11.22 (CDK5 protein, human)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170605
[Lr] Data última revisão:
170605
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170322
[St] Status:MEDLINE
[do] DOI:10.1080/14728222.2017.1310194



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