RESUMO
The lack of comprehensive diagnostics and consensus analytical models for evaluating the status of a patient's immune system has hindered a wider adoption of immunoprofiling for treatment monitoring and response prediction in cancer patients. To address this unmet need, we developed an immunoprofiling platform that uses multiparameter flow cytometry to characterize immune cell heterogeneity in the peripheral blood of healthy donors and patients with advanced cancers. Using unsupervised clustering, we identified five immunotypes with unique distributions of different cell types and gene expression profiles. An independent analysis of 17,800 open-source transcriptomes with the same approach corroborated these findings. Continuous immunotype-based signature scores were developed to correlate systemic immunity with patient responses to different cancer treatments, including immunotherapy, prognostically and predictively. Our approach and findings illustrate the potential utility of a simple blood test as a flexible tool for stratifying cancer patients into therapy response groups based on systemic immunoprofiling.
Assuntos
Imunoterapia , Neoplasias , Humanos , Neoplasias/imunologia , Neoplasias/terapia , Neoplasias/sangue , Imunoterapia/métodos , Citometria de Fluxo/métodos , Transcriptoma , Prognóstico , Perfilação da Expressão Gênica/métodos , Feminino , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/imunologiaRESUMO
Aim of the study was assessment of executive functions and quality of life (QoL) among scientists aged 22-80 years working in state research centers. The screening test included several questionnairs: "Cognitive screening", "Age is not a barrier", "Geriatric Depression Scale" (GDS) and Social Functioning 36 (SF-36) survey. According to the assessment, the group of scientists showed problems related to physical health disorders and presence of numerous risk factors for professional efficiency decline. High rate of preasthenia (39.62%) and asthenia syndrome (11.32%) was identified. This might be due to high level of stress and informational load that causes depletion of functional organism reserves. The rate of cognitive executive functions decline was low (3.77%), stated in young age and possibly associated with depression and asthenia. In comparison to general population, Russian scientists showed a generally high level of quality of life (more than 70% in all domains), best indicators on the scales of "Body Pain" and "Vitality", but lower indicators of "Role functioning" due to the emotional state. In general, scientists' quality of life decreased with age, especially "Physical Functioning" and "Body Pain" scales. Social skills such as "Role functioning due to emotional state" increased with age. In the scientists group, connection between cognitive functions and the quality of life was observed. Specifically, between "Physical Functioning", "General Health", "Vitality", "Social Functioning" and "Mental Health".
RESUMO
A reaction of 4-(2-mercaptophenyl)-1,2,3-thiadiazoles with an oxidant in the presence of 1.1 equiv of base afforded good yields of benzo[4,5]thieno[3,2-d][1,2,3]thiadiazoles via the intramolecular oxidative nucleophilic substitution of a hydrogen (ONHS) pathway. The reaction of 4-(2-mercaptophenyl)-1,2,3-thiadiazoles in the presence of ≥2 equiv of base gave 2-mercaptobenzo[b]thiophenes via an anionic ring-opening/ring-closure pathway.