Gingivo-buccal oral squamous cell carcinoma (OSCC-GB), an anatomical and clinical subtype of head and neck squamous cell carcinoma (HNSCC), is prevalent in regions where tobacco-chewing is common. ...Exome sequencing (n=50) and recurrence testing (n=60) reveals that some significantly and frequently altered genes are specific to OSCC-GB (USP9X, MLL4, ARID2, UNC13C and TRPM3), while some others are shared with HNSCC (for example, TP53, FAT1, CASP8, HRAS and NOTCH1). We also find new genes with recurrent amplifications (for example, DROSHA, YAP1) or homozygous deletions (for example, DDX3X) in OSCC-GB. We find a high proportion of C>G transversions among tobacco users with high numbers of mutations. Many pathways that are enriched for genomic alterations are specific to OSCC-GB. Our work reveals molecular subtypes with distinctive mutational profiles such as patients predominantly harbouring mutations in CASP8 with or without mutations in FAT1. Mean duration of disease-free survival is significantly elevated in some molecular subgroups. These findings open new avenues for biological characterization and exploration of therapies.
Lymph node density (LND) has previously been reported to reliably predict recurrence risk and survival in oral cavity squamous cell carcinoma (OSCC). This multicenter international study was designed ...to validate the concept of LND in OSCC.
The study included 4254 patients diagnosed as having OSCC. The median follow-up was 41 months. Five-year overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), locoregional control and distant metastasis rates were calculated using the Kaplan-Meier method. Lymph node density (number of positive lymph nodes/total number of excised lymph nodes) was subjected to multivariate analysis.
The OS was 49% for patients with LND0.07 compared with 35% for patients with LND>0.07 (P<0.001). Similarly, the DSS was 60% for patients with LND0.07 compared with 41% for those with LND>0.07 (P<0.001). Lymph node density reliably stratified patients according to their risk of failure within the individual N subgroups (P=0.03). A modified TNM staging system based on LND ratio was consistently superior to the traditional system in estimating survival measures.
This multi-institutional study validates the reliability and applicability of LND as a predictor of outcomes in OSCC. Lymph node density can potentially assist in identifying patients with poor outcomes and therefore for whom more aggressive adjuvant treatment is needed.
Environmental toxicants viz lead or cadmium and phthalate esters (di(2-ethylhexyl) phthalate DEHP, dibutyl phthalate DBP, and diethyl phthalate DEP) widely found in different environmental strata are ...linked to deteriorating male reproductive health. The objective was to assess the relationships between the seminal lead, cadmium, and phthalate (DEHP, DBP, DEP) concentrations at environmental level and serum hormone levels and semen quality in non-occupationally exposed men and specify the effect of individual and combined exposure of toxicants on semen quality. A study of 60 male partners of couples attending the Andrology Laboratory of the Reproductive Biology Department, All India Institute of Medical Sciences (AIIMS), New Delhi, India for semen analysis to assess their inability to achieve a pregnancy was selected for the study. The results of univariate and stepwise multiple regression analysis in the unadjusted model showed a significant correlation between lead or cadmium and phthalates DEHP/DBP/DEP and sperm motility, sperm concentration, and DNA damage. After adjusting for potential confounders, an association with lead or DEHP was only observed. The present data shows that lead (Pb) or cadmium (Cd) or phthalates might independently contribute to decline in semen quality and induce DNA damage. Phthalates might influence reproductive hormone testosterone. These findings are significant in light of the fact that men are exposed to a volley of chemicals; however, due to the small sample size, our finding needs to be confirmed in a larger population.
ABSTRACT
Flares are known to play an important role for the evolution of the atmospheres of young planets. In order to understand the evolution of planets, it is thus important to study the ...flare-activity of young stars. This is particularly the case for young M‐stars, because they are very active. We study photometrically and spectroscopically the highly active M‐star 2MASS J16111534–1757214. We show that it is a member of the Upper Sco OB association, which has an age of 5–10 Myrs. We also re-evaluate the status of other bona-fide M‐stars in this region and identify 42 members. Analyzing the K2-light curves, we find that 2MASS J16111534–1757214 has, on average, one super-flare with $\rm E\ge 10^{35}$ erg every 620 h, and one with $\rm E\ge 10^{34}$ erg every 52 h. Although this is the most active M‐star in the Upper Sco association, the power-law index of its flare-distribution is similar to that of other M‐stars in this region. 2MASS J16111534–1757214 as well as other M‐stars in this region show a broken power-law distribution in the flare-frequency diagram. Flares larger than $\rm E \ge 3\, 10^{34}$ erg have a power-law index $\rm \beta =-1.3\pm 0.1$ and flares smaller than that $\rm \beta =-0.8\pm 0.1$. We furthermore conclude that the flare-energy distribution for young M‐stars is not that different from solar-like stars.
Several methodological tests are available to detect SARS-CoV-2 antibody. Tests are mostly used in the aid of diagnosis or for serological assessment. No tests are fully confirmatory and have ...variable level of diagnostic ability. We aimed at assessing agreement with three serological tests: quantitative anti receptor binding domain ELISA (Q-RBD), qualitative ELISA (WANTAI SARS-CoV-2 Ab) and qualitative chemiluminescence assay (CLIA).
This study was a part of a large population based sero-epidemiological cohort study. Participants aged 1 year or older were included from 25 randomly selected clusters each in Delhi urban (urban resettlement colony of South Delhi district) and Delhi rural (villages in Faridabad district, Haryana). Three type of tests were applied to all the baseline blood samples. Result of the three tests were evaluated by estimating the total agreement and kappa value.
Total 3491 blood samples collected from March to September, 2021, out of which 1700 (48.7%) from urban and 1791 (51.3%) from rural. Overall 44.1% of participants were male. The proportion of sero-positivity were 78.1%, 75.2% and 31.8% by Wantai, QRBD and CLIA tests respectively. The total agreement between Wantai and QRBD was 94.5%, 53.1% between Wantai and CLIA, and 56.8% between QRBD and CLIA. The kappa value between these three tests were 0.84 (95% CI 0.80-0.87), 0.22 (95% CI 0.19-0.24) and 0.26 (95% CI 0.23-0.28).
There was strong concordance between Wantai and QRBD test. Agreement between CLIA with other two tests was low. Wantai and QRBD tests measuring the antibody to same S protein can be used with high agreement based on the relevant scenario.
Previous studies have identified the odd-skipped related 2 (Osr2) transcription factor as a key intrinsic regulator of palatal shelf growth and morphogenesis. However, little is known about the ...molecular program acting downstream of Osr2 in the regulation of palatogenesis. In this study, we isolated palatal mesenchyme cells from embryonic day 12.5 (E12.5) and E13.5 Osr2RFP/+ and Osr2RFP/- mutant mouse embryos and performed whole transcriptome RNA sequencing analyses. Differential expression analysis of the RNA sequencing datasets revealed that expression of 70 genes was upregulated and expression of 61 genes was downregulated by >1.5-fold at both E12.5 and E13.5 in the Osr2RFP/- palatal mesenchyme cells, in comparison with Osr2RFP/+ littermates. Gene ontology analysis revealed enrichment of signaling molecules and transcription factors crucial for skeletal development and osteoblast differentiation among those significantly upregulated in the Osr2 mutant palatal mesenchyme. Using quantitative real-time polymerase chain reaction (RT-PCR)and in situ hybridization assays, we validated that the Osr2-/- embryos exhibit significantly increased and expanded expression of many osteogenic pathway genes, including Bmp3, Bmp5, Bmp7, Mef2c, Sox6, and Sp7 in the developing palatal mesenchyme. Furthermore, we demonstrate that expression of Sema3a, Sema3d, and Sema3e, is ectopically activated in the developing palatal mesenchyme in Osr2-/- embryos. Through chromatin immunoprecipitation, followed by RT-PCR analysis, we demonstrate that endogenous Osr2 protein binds to the promoter regions of the Sema3a and Sema3d genes in the embryonic palatal mesenchyme. Moreover, Osr2 expression repressed the transcription from the Sema3a and Sema3d promoters in cotransfected cells. Since the Sema3 subfamily of signaling molecules plays diverse roles in the regulation of cell proliferation, migration, and differentiation, these data reveal a novel role for Osr2 in regulation of palatal morphogenesis through preventing aberrant activation of Sema3 signaling. Together, these data indicate that Osr2 controls multiple molecular pathways, including BMP and Sema3 signaling, in palate development.
Labile soil organic matter pools (LSOMs) are the fine indicators of soil quality which are influenced by changes in management practices. The suitability of forest tree species is essential for soil ...quality improvement of a nutrient deficient calciorthent with very high percentage of free CaCO
3 (34%). Six multipurpose tree species were selected to investigate the effect of afforestation after 18 years of plantations on size and dynamics of LSOMs, e.g. dissolved organic carbon (DOC), microbial biomass carbon (MBC) and light fraction carbon (LFC) and also on soil respiration. LSOMs were estimated during four seasons: summer (June), autumn (September), winter (December) and spring (March) in 0–15
cm and 15–30
cm soil depths and
in situ soil respiration was also measured during the corresponding periods. Afforestation by
Eucalyptus tereticornis (Smith) increased soil organic carbon (SOC) of the surface 30
cm soil layer by 142% which was at par with
Terminalia arjuna Bedd. and
Albizia procera (Roxb.) Benth while 63% increase was found by
Pongamia pinnata (Linn.) over control plot (3.10
kg
ha
−1 SOC). Soil under
T. arjuna had the highest increase in the mean annual concentration of DOC (by 201%), MBC (by 413%) and LFC (by 263%) over control in the 30
cm soil layer followed by
E. tereticornis. Among the LSOMs, LFC had the maximum contribution to SOC (9.61–11.71%) in the afforested plots up to 30
cm soil layer. The relationships among the three labile pools were highly significant. Mean annual soil respiration was highest in
E. tereticornis plot which was at par with
Acacia lenticularis (L.) Willd and
A. procera, while it was lowest in
T. arjuna plot. Thus, MBC was the most sensitive to afforestation and LFC was the largest reservoir of carbon among the three LSOMs. The results suggest that afforestation by the six multipurpose tree species had increased the LSOMs and soil respiration to different magnitudes.
T. arjuna was found to be the most suitable plantation with highest increase in LSOMs and lowest respiration among the different plantations.
Ocular tear film and the ocular surface together represent a dynamic playground of various protective factors against environmental influencers. Surrounding environment and geoclimatic milieu are the ...pertinent and continuous influencing factors. Prevalence study of Dry eye disease (DED) in various climatic conditions and professions provides an insight into this peculiar aspect of DED and human geography.
This was a hospital based, cross-sectional, comparative, analytical observational study. 1840 young soldiers between 25 and 45 years of age were studied. Divided in five climate groups based on Köppen-Geiger climate classification system the subjects were sub-grouped into professions exposed to known aggravating environmental factors. The ocular surface was examined for signs and symptoms of DED and its prevalence and risk ratio for different climates and professions were calculated.
Highest prevalence of DED was found in cold desert climate and among visual display unit (VDU) users. Least prevalence was seen in highland type of climate and among people involved in professional exposed to high temperature. Prevalence of DED based upon the signs and ocular surface disease index (OSDI) was calculated and stratified with risk ratio for climatic conditions and professions.
Different climatic conditions and professions had different prevalence of signs, symptoms of OSD and DED which indicated its influence on prevalence of the disease.
Most cases of breast cancer (BrCa) mortality are due to vascular metastasis. BrCa cells must intravasate through endothelial cells (ECs) to enter a blood vessel in the primary tumor and then adhere ...to ECs and extravasate at the metastatic site. In this study we demonstrate that inhibition of hypoxia-inducible factor (HIF) activity in BrCa cells by RNA interference or digoxin treatment inhibits primary tumor growth and also inhibits the metastasis of BrCa cells to the lungs by blocking the expression of angiopoietin-like 4 (ANGPTL4) and L1 cell adhesion molecule (L1CAM). ANGPTL4 is a secreted factor that inhibits EC-EC interaction, whereas L1CAM increases the adherence of BrCa cells to ECs. Interference with HIF, ANGPTL4 or L1CAM expression inhibits vascular metastasis of BrCa cells to the lungs.
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