The buffering effect of spirituality at work on the mediated relationship between job demands and turnover intention among teachers

The purpose of this study was to examine whether spirituality at work moderates the direct and indirect (through burnout) effects of quantitative and emotional job demands on turnover intention among teachers. The sample consisted of 952 Polish primary and secondary school teachers. Burnout mediated the relationship between both types of job demands and turnover intention. In the model with quantitative job demands as an independent variable, spirituality at work moderated the second stage path of the indirect effect, i.e., the relationship between burnout and turnover intention (b = −0.022; SE = 0.004; p < 0.001; β = −0.14). In the model with emotional job demands as an independent variable, spirituality at work moderated the first and second stage paths of the indirect effect, i.e., the relationship between emotional job demands and burnout (b = −0.001; SE = 0.001; p = 0.032; β = −0.05) and the relationship between burnout and turnover intention (b = −0.020; SE = 0.004; p < 0.001; β = −0.14). In both models, the indirect effect of job demands on turnover intention through burnout weakened as spirituality at work increased. The results of the study support the inclusion of spirituality at work as a subcategory of personal resources in studies using the job demands-resources model

The intratumour microbiota and neutrophilic inflammation in squamous cell vulvar carcinoma microenvironment

Abstract Background A causal link between microbiota composition (dysbiosis) and oncogenesis has been demonstrated for several types of cancer. Neutrophils play a role in both immune protection against bacterial threats and carcinogenesis. This study aimed to characterise intratumoral bacteria in vulvar squamous cell carcinoma (VSCC) and their putative effect on neutrophil recruitment and cancer progression. Methods Clinical material was obtained from 89 patients with VSCC. Next-generation sequencing (NGS) of 16S rRNA and quantitative polymerase chain reaction (qPCR) were used to detect bacterial species in VSCC. To verify neutrophil activation, CD66b expression in tumour specimens was analysed by immunohistochemistry (IHC). Subsequently, IHC was applied to detect the main neutrophil serine proteases (NSPs), cathepsin G (CTSG), neutrophil elastase (ELANE), and proteinase 3 (PRTN3) in VSCC. Results Fusobacterium nucleatum and Pseudomonas aeruginosa were identified as tumour-promoting bacteria, and their presence was found to be associated with a shorter time to progression in VSCC patients. Furthermore, high abundance of CD66b, the neutrophil activation marker, in VSCC samples, was found to relate to poor survival of patients with VSCC. The selected NSPs were shown to be expressed in vulvar tumours, also within microabscess. The increased numbers of microabscesess were correlated with poor survival in VSCC patients. Conclusions Our results show that neutrophilic inflammation seem to be permissive for tumour-promoting bacteria growth in VSCC. The findings provide new therapeutic opportunities, such as based on shifting the balance of neutrophil populations to those with antitumorigenic activity and on targeting NSPs produced by activated neutrophils at the inflammation sites

Tumor location matters, next generation sequencing mutation profiling of left-sided, rectal, and right-sided colorectal tumors in 552 patients

Abstract Despite the introduction of new molecular classifications, advanced colorectal cancer (CRC) is treated with chemotherapy supplemented with anti-EGFR and anti-VEGF targeted therapy. In this study, 552 CRC cases with different primary tumor locations (250 left side, 190 rectum, and 112 right side) were retrospectively analyzed by next generation sequencing for mutations in 50 genes. The most frequently mutated genes were TP53 in left-sided tumors compared to right-sided tumors and BRAF in right-sided tumors compared to left-sided tumors. Mutations in KRAS, NRAS, and BRAF were not detected in 45% of patients with left-sided tumors and in 28.6% of patients with right-sided tumors. Liver metastases were more common in patients with left-sided tumors. Tumors on the right side were larger at diagnosis and had a higher grade (G3) than tumors on the left. Rectal tumors exhibit distinctive biological characteristics when compared to left-sided tumors, including a higher absence rate of KRAS, NRAS, and BRAF mutations (47.4% in rectal versus 42.8% in left-sided tumors). These rectal tumors are also unique in their primary metastasis site, which is predominantly the lungs, and they have varying mutation rates, particularly in genes such as BRAF, FBXW7, and TP53, that distinguish them from tumors found in other locations. Primary tumor location has implications for the potential treatment of CRC with anti-EGFR therapy

CD276 as a Candidate Target for Immunotherapy in Medullary Thyroid Cancer

Medullary thyroid cancer (MTC) is a rare malignancy, and the treatment of metastatic MTC is challenging. In previous work, immune profiling (RNA-Seq) of MTC identified CD276 as a potential target for immunotherapy. CD276 expression was 3-fold higher in MTC cells than in normal tissues. Paraffin blocks from patients with MTC were analyzed by immunohistochemistry to confirm the results of RNA-Seq. Serial sections were incubated with anti-CD276 antibody, and scored according to staining intensity and the percentage of immunoreactive cells. The results showed that CD276 expression was higher in MTC tissues than in controls. A lower percentage of immunoreactive cells correlated with the absence of lateral node metastasis, lower levels of calcitonin after surgery, no additional treatments, and remission. There were statistically significant associations of intensity of immunostaining and percentage of CD276 immunoreactive cells with clinical factors and the course of the disease. These results suggest that targeting this immune checkpoint molecule CD276 could be a promising strategy for the treatment of MTC

Incidence of the CHEK2 Germline Mutation and Its Impact on Clinicopathological Features, Treatment Responses, and Disease Course in Patients with Papillary Thyroid Carcinoma

The CHEK2 gene is involved in the repair of damaged DNA. CHEK2 germline mutations impair this repair mechanism, causing genomic instability and increasing the risk of various cancers, including papillary thyroid carcinoma (PTC). Here, we asked whether CHEK2 germline mutations predict a worse clinical course for PTC. The study included 1547 unselected PTC patients (1358 women and 189 men) treated at a single center. The relationship between mutation status and clinicopathological characteristics, treatment responses, and disease outcome was assessed. CHEK2 mutations were found in 240 (15.5%) of patients. A CHEK2 I157T missense mutation was found in 12.3%, and CHEK2 truncating mutations (IVS2 + 1G &gt; A, del5395, 1100delC) were found in 2.8%. The truncating mutations were more common in women (p = 0.038), and were associated with vascular invasion (OR, 6.91; p &lt; 0.0001) and intermediate or high initial risk (OR, 1.92; p = 0.0481) in multivariate analysis. No significant differences in these parameters were observed in patients with the I157T missense mutation. In conclusion, the CHEK2 truncating mutations were associated with vascular invasion and with intermediate and high initial risk of recurrence/persistence. Neither the truncating nor the missense mutations were associated with worse primary treatment response and outcome of the disease

Genotyping results according to tumor size (PTMiC or PTMaC) and diagnostic method (S, Seq; A, ASA-PCR; q, qPCR).

<p>Genotyping results according to tumor size (PTMiC or PTMaC) and diagnostic method (S, Seq; A, ASA-PCR; q, qPCR).</p

<i>BRAF</i> c.1799T>A (p.V600E) mutation genotyping results using the ASA-PCR method visualized by MultiNA chip electrophoresis (Shimadzu, Japan).

<p>X1, molecular weight marker; A1, no template control; A2, negative control (sample without the BRAF p.V600E mutation; WT); A3, negative control sample without mutation (K-); A4, control sample with BRAF p.V600E mutation (K+); A5–A7 and C1, tested samples. 224pz, reaction control band; 126pz, band indicating the presence of the p.V600E mutation.</p

Evaluation of molecular diagnostic approaches for the detection of BRAF p.V600E mutations in papillary thyroid cancer: Clinical implications - Fig 1

<p><b>Sequencing chromatograms representing three different types of results:</b> a) mutation <i>BRAF</i> c.1799T>A (p.V600E) present; b) ambiguous result; c) wild-type.</p