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Investigational New Drugs - Although many cancer drugs are clinically approved, they still suffer from no adequate efficiency or drug resistance, or bad side effects. Therefore, developing safer...  相似文献   
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Microsatellite instability-high (MSI-H) and tumor mutational burden (TMB) are predictive biomarkers for immune-checkpoint inhibitors (ICIs). Still, the relationship between the underlying cause(s) of MSI and TMB in tumors remains poorly defined. We investigated associations of TMB to mismatch repair (MMR) protein expression patterns by immunohistochemistry (IHC) and MMR mutations in a diverse sample of tumors. Hypothesized differences were identified by the protein/gene affected/mutated and the tumor histology/primary site. Overall, 1057 MSI-H tumors were identified from the 32 932 tested. MSI was examined by NGS using 7000+ target microsatellite loci. TMB was calculated using only nonsynonymous missense mutations sequenced with a 592-gene panel; a subset of MSI-H tumors also had MMR IHC performed. Analyses examined TMB by MMR protein heterodimer impacted (loss of MLH1/PMS2 vs. MSH2/MSH6 expression) and gene-specific mutations. The sample was 54.6% female; mean age was 63.5 years. Among IHC tested tumors, loss of co-expression of MLH1/PMS2 was more common (n = 544/705, 77.2%) than loss of MSH2/MSH6 (n = 81/705, 11.5%; P < .0001), and was associated with lower mean TMB (MLH1/PMS2: 25.03 mut/Mb vs MSH2/MSH6 46.83 mut/Mb; P < .0001). TMB also varied by tumor histology: colorectal cancers demonstrating MLH1/PMS2 loss had higher TMBs (33.14 mut/Mb) than endometrial cancers (20.60 mut/Mb) and other tumors (25.59 mut/Mb; P < .0001). MMR gene mutations were detected in 42.0% of tumors; among these, MSH6 mutations were most common (25.7%). MSH6 mutation patterns showed variability by tumor histology and TMB. TMB varies by underlying cause(s) of MSI and tumor histology; this heterogeneity may contribute to differences in response to ICI.  相似文献   
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Purpose

To describe the relationship between psychosocial factors and mental health among housekeepers.

Methods

A cross-sectional study was conducted nearby all the housekeepers of Farhat-Hached teaching hospital of Sousse (Tunisia). After their oral consent, employees completed a self-administrated questionnaire including socio-demographic and lifestyle data, the Job Content Questionnaire (JCQ) evaluating psychological stress at work and the Hopkins Symptoms Checklist (HSCL-25) studying mental health.

Results

Overall, 136 cleaners were enrolled in the study, corresponding to a response rate of 89.5%. The mean age was 41.9 ± 7.7 years. According to the demand control model, 26.5% of the participants were in the situation of job-strain. The study of HSCL-25 scales revealed a positive mental health disorders in 50% of cases. The study of the psychosocial factors revealed a correlation between job-strain and urban origin (P = 0.007), high psychological demand and seniority in the cleaning sector (P = 0.030) and low decision latitude and the night work (P = 0.015). The mental health association were associated with unmarried status (P = 0.006), high psychological demand (P < 0.001), active employees (P = 0.037), and iso-strain (P = 0.013). Mental disorders were associated with a high psychological demand in the presence of a high decision latitude (OR = 9.2 [2.8–30.8]) and a job-strain in the presence of low social support (OR = 3.5 [1.2–10.4]).

Conclusion

Psychosocial factors can deteriorate seriously the mental health of workers. Their identification is the most important step in any efficient preventive strategy.  相似文献   
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Clear‐cell carcinoma (CCC) is an uncommon malignant tumor of minor salivary glands. It characteristically has a low‐grade morphology and a favorable outcome by most reports. An EWSR1‐ATF1 fusion can be detected in the majority of cases. We present a rare case of CCC, which had an aggressive course with the development of cutaneous metastases. Practicing dermatopathologists should be aware of this tumor given its low‐grade appearance and histopathologic resemblance to other primary cutaneous adnexal and metastatic neoplasms.  相似文献   
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Lasers in Medical Science - Vitiligo is a chronic acquired disease. Various therapeutic strategies are available but with variable degrees of success. Fractional CO2 laser is claimed to be...  相似文献   
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