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Skills development is imperative to sustaining traditional growth and development in a country like India which is experiencing a demographic dividend. It is a huge challenge not only for the government, but also for the private sector and educational institutions to rise up and specialize to make the country’s youth employable and ensure that there is no mismatch between demand and the offer. This study examines the role of Deen Dayal Upadhyay Grameen Kaushalya Vikas Yojana (DDU-GKY) in the development of rural youth in the Haryana State. Secondary data (2015-2021) were used for the study. The results show that the interest of the population towards DDU-GKY and the interns recruited has greatly diminished, which is a matter of concern. Key Words: Demographic Dividend, Inclusive Growth, Smart Cities, Skill India

Background: Circulating cell-free tumor DNA (ctDNA) analysis for minimal residual disease (MRD) detection is transforming cancer care. However, the sensitivity of these approaches remains subpar and there is significant risk of false negative results. We analyzed the most proximal biofluid (urine) in localized muscle-invasive bladder cancer (MIBC) patients, and performed two orthogonal ctDNA analytical techniques, one focusing on driver mutation detection, and another focusing on genome-wide copy number alterations. The primary objective of this combinatorial approach was to sensitively detect ctDNA MRD, predict pathologic complete response (pCR), and improve patient risk-stratification. Methods: Urine samples from 74 localized bladder cancer patients were collected preoperatively on the day of curative-intent radical cystectomy (RC) to assess urine tumor DNA (utDNA). We performed ultra-low pass whole genome sequencing (ULP-WGS) of urine cfDNA from all 74 patients as well as 15 healthy adults. Tumor fraction (TFx) level based on genome-wide copy number alterations was estimated using ichorCNA. Variant allele frequency (VAF) based on single-nucleotide variants (SNVs) was estimated by uCAPP-Seq. We also noninvasively inferred tumor mutation burden (iTMB). pCR was determined by surgical pathology. A random forest (RF) model with leave-one-out cross-validation (LOOCV) was utilized to predict disease status. Kaplan-Meier (KM) and Cox proportional hazards model survival analyses were performed to assess overall survival (OS) and progression-free survival (PFS). Results: Our study cohort consisted of 74 patients, of which 58 (78%) harbored localized MIBC, and 16 (22%) harbored treatment-refractory high-risk localized NMIBC. Among MIBC patients, 64% (37/58) received neo-adjuvant chemotherapy. VAF, iTMB and TFx levels significantly predicted pCR status. Our RF model incorporating these three utDNA parameters achieved a sensitivity of 87%, a negative predictive value of 77%, and a positive predictive value of 65% for predicting residual disease. AUC for the model was 0.80 (p Conclusions: Integration of ULP-WGS with uCAPP-Seq enabled robust detection of residual urine tumor DNA with high sensitivity and predicted survival in localized bladder cancer patients. In the future, this type of multimodal urine-based genomic analysis may lead to more precise risk stratification and nonoperative clinical decision-making for bladder cancer patients. Citation Format: Pradeep Singh Chauhan, Alexander L. Shiang, Irfan Alahi, R. Taylor Sundby, Wenjia Feng, Bilge Gungoren, Cayce Nawaf, Kevin Chen, Ramandeep K. Babbra, Peter K. Harris, Faridi Qaium, Casey Hatscher, Anna Antiporda, Lindsey Brunt, Lindsey R. Mayer, Jack F. Shern, Brian C. Baumann, Eric H. Kim, Melissa A. Reimers, Zachary L. Smith, Aadel A. Chaudhuri. Urine cell-free DNA multi-omics to detect molecular residual disease and predict survival in bladder cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2219.

Background: Electronic equipment manufacturing units are among the most common industries all over the world. It involves a large amount of employees required for processing, manufacturing, building and setting up electronic equipments. Workers are usually sedentary and involve very less physical movement. Chronic illnesses are common among these sedentary workers of which most important are cardiovascular diseases, hypertension, obesity and diabetes. Considering the importance of the subject and the lack of published evidence on health status of electronic manufacturing workers, our study was done with an aim of assessing selected morbidities among electronic equipment manufacturing units in Goa.Methods: Our retrospective record based cross-sectional study was conducted over a period of one month in March 2019. The study was done in electronic equipment manufacturing workers. Data included sociodemographic details of the workers and details of periodic medical check-up. The data analysis was done using and analyzed using SPSS version 22. Chi square test was used to assess association between qualitative variables.Results: Among the 109 electronic manufacturing workers, it was observed that 10.1% (11) had obesity with a BMI >30, 24.8% (27) had hypertension (>140/90) and 31.2% (34) had diabetes mellitus with HbA1c >6.5. In addition, 24.8% (27) had far vision defect and 39.4% (43) had near vision defect. 42.2% (46) had abnormal lung function tests, 0.9% (1) had hearing disability and 4.6% (5) had abnormal ECG findings. Among male workers 0.9% (1) had elevated PSA levels, whereas all PAPs smear reports were normal among female workers.Conclusions: This study highlights the need of periodic medical check-up of the electronic manufacturing workers for timely detection and early management of their health problems.

High incidence of nasopharyngeal carcinoma (NPC) has been reported from China, Southeast Asia and Northeast (NE) region of India. Populations at geographic regions having higher incidence of NPC display human leukocyte antigen (HLA) distribution patterns different from areas having low incidence. The current study has investigated the contribution of environmental risk factors and ethnic variation of microsatellite markers in HLA region for the high incidence of NPC in NE India. Genotyping of HLA region using 33 microsatellite markers by fragment length analysis was done in 220 study subjects (120 NPC patients and 100 healthy controls). Association analysis showed two adjacent microsatellite markers HL003 (allele 121) and D6S2704 (allele 218) in the HLA class I region having association with high risk of NPC while allele 127 of HL003 and allele 255 of D6S2678 conferred a protective effect. The environmental factors mainly use of firewood (odds ratio (OR) = 3.797385, confidence interval (CI) = 1.97-7.30, P

Targeting breast cancer stem cells (BCSCs) offers a promising strategy for breast cancer treatment. We examined the plant alkaloid ellipticine for its efficacy to inhibit the expression of aldehyde dehydrogenase 1 class A1 (ALDH1A1)-positive BCSCs by in vitro and in silico methods. At 3 mM concentration, ellipticine decreased the expression of ALDH1A1-positive BCSCs by 62 % (p = 0.073) in the MCF7 cell line and by 53 % (p = 0.024) in the SUM159 cell line compared to vehicle-treated cultures. Ellipticine significantly reduced the formation of mammospheres, whereas paclitaxel enhanced mammosphere formation in both the treated cell lines. Interestingly, when treated with a combination of ellipticine and paclitaxel, the percentage of ALDH1A1-positive BCSCs dropped by several fold in vitro. A homology model of Homo sapiens ALDH1A1 was built using the crystal structure of NAD-bound sheep liver class I aldehyde dehydrogenase [PDB ID: 1BXS] as a template. Molecular simulation and docking studies revealed that the amino acids Asn-117 and Asn-121, Glu-249, Cys-302, and Gln-350, present in the active site of human ALDH1A1, played a vital role in interacting with the drug. The present study suggests that ellipticine reduces the proliferation and self-renewal ability of ALDH1A1-positive BCSCs and can be used in combination with a cytotoxic drug like paclitaxel for potential targeting of BCSCs.

Background.Mutations in NPM1 and FLT3 genes represent the most frequent genetic alterations and important diagnostic and prognostic indicators in patients with acute myeloid leukemia (AML).Objective.We investigated the prevalence and clinical characteristics of NPM1 and FLT3 mutations in 161 patients of de novo AML including adults and children.Results.NPM1 mutation was found in 21% and FLT3 mutation in 25% of the AML patients. Thirteen (8%) samples were positive for both NPM1 and FLT3/ITD mutations. Adult patients had significantly higher frequency of NPM1 mutation than children (25.8% versus 8.8%;P=0.02). Further, NPM1 mutation was found to be more frequent in patients above 45 years of age (P=0.02). NPM1 mutation was significantly associated with higher platelet count (P=0.05) and absence of hepatosplenomegaly (P=0.01), while FLT3/ITD mutation was associated with higher white blood count (P=0.01). Immunophenotypically, NPM1 mutation was associated with the lack of CD34 (P<0.001) and HLD-DR expression (P<0.001), while FLT3/ITD mutation was positively associated with the expression of CD7 (P=0.04). No correlation was found between NPM1 mutation and fusion gene. Interestingly, FLT3/ITD mutation was found to be inversely associated with AML/ETO fusion gene (P=0.04).Conclusions.The results suggest that distinct clinical and immunophenotypic characteristics of NPM1 and FLT3/ITD mutations present further insight into the molecular mechanism of leukemogenesis.

Polymorphisms in DNA repair and cell cycle genes contribute to increased breast cancer (BC) risk. Their association and interaction in relation to betel quid and tobacco chewing habits need exhaustive multi-analytical investigation to explain BC predisposition due to DNA damage. Polymorphism in TP53-72Arg>Pro, RAD51-135G>C, BRCA2, and CCND1-G870A were examined in 204 BC cases and 217 controls from Northeast Indian population. Multifaceted analytic approaches were used to explore relationships between polymorphisms, tobacco history, and BC susceptibility. Betel quid chewing was identified as the predominant risk factor. CCND-AA and dominant model showed protection towards BC in betel quid chewer (BQC) [(0.28 (0.10–0.77), 0.01 and 0.32 (0.12–0.81), 0.01)] and non-betel quid chewers (NBQC) [(0.26 (0.09–0.78), 0.01 and 0.37 (0.16–0.87), 0.02)]. TP53-Pro/Pro genotype showed protection towards BC in NBQC (0.29 (0.10–0.81), p = 0.01) and (0.51 (0.32–0.80), p = 0.003, respectively). RAD51-C allele was associated with BC risk (2.03 (1.26–3.30) 0.002) in BQC. Two BQC cases had BRCA2 8415G>T:K2729N mutation in Exon18. MDR analysis showed best four locus model with TBA 0.6765 (0.005) and CVC of 10/10 in NBQC. Interaction diagram concurred the interactions between TP53 and RAD51 (1.32 %) with independent effect (1.89 %) of CCND1in NBQC. In CART analysis, BQC with CCND1 GG genotype were at risk (OR = 33.0; 95 % CI = 6.08–179.07), p

Complex disease such as cancer results from interactions of multiple genetic and environmental factors. Studying these factors singularly cannot explain the underlying pathogenetic mechanism of the disease. Multi-analytical approach, including logistic regression (LR), classification and regression tree (CART) and multifactor dimensionality reduction (MDR), was applied in 188 lung cancer cases and 290 controls to explore high order interactions among xenobiotic metabolizing genes and environmental risk factors. Smoking was identified as the predominant risk factor by all three analytical approaches. Individually, CYP1A1*2A polymorphism was significantly associated with increased lung cancer risk (OR = 1.69;95%CI = 1.11–2.59,p = 0.01), whereas EPHX1 Tyr113His and SULT1A1 Arg213His conferred reduced risk (OR = 0.40;95%CI = 0.25–0.65,p