Multi-class waste segregation using computer vision and robotic arm.

Waste segregation is an essential aspect of a smoothly functioning waste management system. Usually, various recyclable waste types are disposed of together at the source, and this brings in the necessity to segregate them into their categories. Dry waste needs to be separated into its own categories to ensure that the proper procedures are implemented to treat and process it, which leads to an overall increased recycling rate and reduced landfill impact. Paper, plastics, metals, and glass are just a few examples of the many dry waste materials that can be recycled or recovered to create new goods or energy. Over the past years, much research has been conducted to devise effective and productive ways to achieve proper segregation for the waste that is being produced at an ever-increasing rate. This article introduces a multi-class garbage segregation system employing the YOLOv5 object detection model. Our final prototype demonstrates the capability of classifying dry waste categories and segregating them into their respective bins using a 3D-printed robotic arm. Within our controlled test environment, the system correctly segregated waste classes, mainly paper, plastic, metal, and glass, eight out of 10 times successfully. By integrating the principles of artificial intelligence and robotics, our approach simplifies and optimizes the traditional waste segregation process.

Highlighting the role of long non-coding RNA (LncRNA) in multiple myeloma (MM) pathogenesis and response to therapy.

Transcripts longer than 200 nucleotides that are not translated into proteins are known as long non-coding RNAs, or lncRNAs. Now, they are becoming more significant as important regulators of gene expression, and as a result, of many biological processes in both healthy and pathological circumstances, such as blood malignancies. Through controlling alternative splicing, transcription, and translation at the post-transcriptional level, lncRNAs have an impact on the expression of genes. In multiple myeloma (MM), the majority of lncRNAs is elevated and promotes the proliferation, adhesion, drug resistance and invasion of MM cells by blocking apoptosis and altering the tumor microenvironment (TME). To control mRNA splicing, stability, and translation, they either directly attach to the target mRNA or transfer RNA-binding proteins (RBPs). By expressing certain miRNA-binding sites that function as competitive endogenous RNAs (ceRNAs), most lncRNAs mimic the actions of miRNAs. Here, we highlight lncRNAs role in the MM pathogenesis with emphasize on their capacity to control the molecular mechanisms known as "hallmarks of cancer," which permit earlier tumor initiation and progression and malignant cell transformation.

New Therapeutic Strategies for the Inflammatory Rheumatoid Arthritis Disease: Emphasizing Mesenchymal Stem Cells and Associated exo-miRNA or exo-lncRNA.

The most prevalent inflammatory arthritis and a leading contributor to disability is rheumatoid arthritis (RA). Although it may not have arrived in Europe until the 17th century, it was present in early Native American communities several thousand years ago. Exosomes released by mesenchymal stem cells (MSCs) are highly immunomodulatory due to the origin of the cell. As a cell-free therapy, MSCs-exosomes are less toxic and elicit a weakened immune response than cell-based therapies. Exosomal noncoding RNAs (ncRNAs) are closely associated with a number of biological and functional facets of human health, especially microRNAs (miRNAs) and long noncoding RNAs (lncRNAs). Various exo-miRNAs and lncRNAs such as HAND2-AS1, miR-150-5p, miRNA-124a, and miR-320a lodged with MSC could be appropriate therapeutic ways for RA treatment. These MSC-derived exosomes affect RA disorders via different molecular pathways such as NFK-ß, MAPK, and Wnt. The purpose of this review is to review the research that has been conducted since 2020 so far in the field of RA disease treatment with MSC-loaded exo-miRNAs and exo-lncRNAs.

Elucidating the Role of MicroRNA-18a in Propelling a Hybrid Epithelial-Mesenchymal Phenotype and Driving Malignant Progression in ER-Negative Breast Cancer.

Epigenetic alterations that lead to differential expression of microRNAs (miRNAs/miR) are known to regulate tumour cell states, epithelial-mesenchymal transition (EMT) and the progression to metastasis in breast cancer. This study explores the key contribution of miRNA-18a in mediating a hybrid E/M cell state that is pivotal to the malignant transformation and tumour progression in the aggressive ER-negative subtype of breast cancer. The expression status and associated effects of miR-18a were evaluated in patient-derived breast tumour samples in combination with gene expression data from public datasets, and further validated in in vitro and in vivo breast cancer model systems. The clinical relevance of the study findings was corroborated against human breast tumour specimens (n = 446 patients). The down-regulated expression of miR-18a observed in ER-negative tumours was found to drive the enrichment of hybrid epithelial/mesenchymal (E/M) cells with luminal attributes, enhanced traits of migration, stemness, drug-resistance and immunosuppression. Further analysis of the miR-18a targets highlighted possible hypoxia-inducible factor 1-alpha (HIF-1α)-mediated signalling in these tumours. This is a foremost report that validates the dual role of miR-18a in breast cancer that is subtype-specific based on hormone receptor expression. The study also features a novel association of low miR-18a levels and subsequent enrichment of hybrid E/M cells, increased migration and stemness in a subgroup of ER-negative tumours that may be attributed to HIF-1α mediated signalling. The results highlight the possibility of stratifying the ER-negative disease into clinically relevant groups by analysing miRNA signatures.

Therapeutic vulnerabilities in triple negative breast cancer: Stem-like traits explored within molecular classification.

Triple Negative Breast Cancer (TNBC) is the most aggressive type of breast cancer (BC). Despite advances in the clinical management of TNBC, recurrence-related mortality remains a challenge. The stem-like phenotype of TNBC plays a significant role in the persistence of minimal disease residue after therapy. Individuals exhibiting stem-like characteristics are particularly prone to inducing malignant relapse accompanied by strong resistance. Therefore, stem-like traits have been broadly proposed as therapeutic vulnerabilities to treat TNBC and reduce recurrence. However, heterogeneity within TNBC often generally restricts the stability of the therapeutic efficacy. To understand the heterogeneity and manage TNBC more precisely, multiple TNBC subtyping categories have been reported, providing the basis for profile-according therapeutic regimens. To provide more insight into targeting stem-like traits to ablate TNBC and reduce recurrence in the context of heterogeneity, this paper reviewed the molecular subtyping of TNBC, identified the consensus subtypes with distinct stem-like phenotypes, characterized the stemness hierarchy of TNBC, outlined the biological models for stem-like TNBC subtypes, summarized the therapeutic vulnerabilities in stem-like traits of the subtypes, and proposed potential therapeutic regimens targeting stem-like characteristics to improve TNBC prognosis.

Differential role of glucocorticoid receptor based on its cell type specific expression on tumor cells and infiltrating lymphocytes.

BACKGROUND: The glucocorticoid receptor (GR) is frequently expressed in breast cancer (BC), and its prognostic implications are contingent on estrogen receptor (ER) status. To address conflicting reports and explore therapeutic potential, a GR signature (GRsig) independent of ER status was developed. We also investigated cell type-specific GR protein expression in BC tumor epithelial cells and infiltrating lymphocytes. METHODS: GRsig was derived from Dexamethasone treated cell lines through a bioinformatic pipeline. Immunohistochemistry assessed GR protein expression. Associations between GRsig and tumor phenotypes (proliferation, cytolytic activity (CYT), immune cell distribution, and epithelial-to-mesenchymal transition (EMT) were explored in public datasets. Single-cell RNA sequencing data evaluated context-dependent GR roles, and a cell type-specific prognostic role was assessed in an independent BC cohort. RESULTS: High GRsig levels were associated with a favorable prognosis across BC subtypes. Tumor-specific high GRsig correlated with lower proliferation, increased CYT, and anti-tumorigenic immune cells. Single-cell data analysis revealed higher GRsig expression in immune cells, negatively correlating with EMT while a positive correlation was observed with EMT primarily in tumor and stromal cells. Univariate and multivariate analyses demonstrated the robust and independent predictive capability of GRsig for favorable prognosis. GR protein expression on immune cells in triple-negative tumors indicated a favorable prognosis. CONCLUSION: This study underscores the cell type-specific role of GR, where its expression on tumor cells is associated with aggressive features like EMT, while in infiltrating lymphocytes, it predicts a better prognosis, particularly within TNBC tumors. The GRsig emerges as a promising independent prognostic indicator across diverse BC subtypes.

Longitudinal associations between ambient PM2.5 exposure and lipid levels in two Indian cities.

Background: Exposure to ambient PM2.5 is known to affect lipid metabolism through systemic inflammation and oxidative stress. Evidence from developing countries, such as India with high levels of ambient PM2.5 and distinct lipid profiles, is sparse. Methods: Longitudinal nonlinear mixed-effects analysis was conducted on >10,000 participants of Centre for cArdiometabolic Risk Reduction in South Asia (CARRS) cohort in Chennai and Delhi, India. We examined associations between 1-month and 1-year average ambient PM2.5 exposure derived from the spatiotemporal model and lipid levels (total cholesterol [TC], triglycerides [TRIG], high-density lipoprotein cholesterol [HDL-C], and low-density lipoprotein cholesterol [LDL-C]) measured longitudinally, adjusting for residential and neighborhood-level confounders. Results: The mean annual exposure in Chennai and Delhi was 40 and 102 µg/m3 respectively. Elevated ambient PM2.5 levels were associated with an increase in LDL-C and TC at levels up to 100 µg/m3 in both cities and beyond 125 µg/m3 in Delhi. TRIG levels in Chennai increased until 40 µg/m3 for both short- and long-term exposures, then stabilized or declined, while in Delhi, there was a consistent rise with increasing annual exposures. HDL-C showed an increase in both cities against monthly average exposure. HDL-C decreased slightly in Chennai with an increase in long-term exposure, whereas it decreased beyond 130 µg/m3 in Delhi. Conclusion: These findings demonstrate diverse associations between a wide range of ambient PM2.5 and lipid levels in an understudied South Asian population. Further research is needed to establish causality and develop targeted interventions to mitigate the impact of air pollution on lipid metabolism and cardiovascular health.

Nationwide estimation of daily ambient PM2.5 from 2008 to 2020 at 1 km2 in India using an ensemble approach.

High-resolution assessment of historical levels is essential for assessing the health effects of ambient air pollution in the large Indian population. The diversity of geography, weather patterns, and progressive urbanization, combined with a sparse ground monitoring network makes it challenging to accurately capture the spatiotemporal patterns of ambient fine particulate matter (PM2.5) pollution in India. We developed a model for daily average ambient PM2.5 between 2008 and 2020 based on monitoring data, meteorology, land use, satellite observations, and emissions inventories. Daily average predictions at each 1 km × 1 km grid from each learner were ensembled using a Gaussian process regression with anisotropic smoothing over spatial coordinates, and regression calibration was used to account for exposure error. Cross-validating by leaving monitors out, the ensemble model had an R2 of 0.86 at the daily level in the validation data and outperformed each component learner (by 5-18%). Annual average levels in different zones ranged between 39.7 µg/m3 (interquartile range: 29.8-46.8) in 2008 and 30.4 µg/m3 (interquartile range: 22.7-37.2) in 2020, with a cross-validated (CV)-R2 of 0.94 at the annual level. Overall mean absolute daily errors (MAE) across the 13 years were between 14.4 and 25.4 µg/m3. We obtained high spatial accuracy with spatial R2 greater than 90% and spatial MAE ranging between 7.3-16.5 µg/m3 with relatively better performance in urban areas at low and moderate elevation. We have developed an important validated resource for studying PM2.5 at a very fine spatiotemporal resolution, which allows us to study the health effects of PM2.5 across India and to identify areas with exceedingly high levels.

Telomerase inhibitors induce mitochondrial oxidation and DNA damage-dependent cell death rescued by Bcl-2/Bcl-xL.

BACKGROUND: Reactivation of telomerase is a hallmark of cancer and the majority of cancers over-express telomerase. Telomerase-dependent telomere length maintenance confers immortality to cancer cells. However, telomere length-independent cell survival functions of telomerase also play a critical role in tumorigenesis. Multiple telomerase inhibitors have been developed as therapeutics and include anti-sense oligonucleotides, telomerase RNA component targeting agents, chemical inhibitors of telomerase, small molecule inhibitors of hTERT, and telomerase vaccine. In general, telomerase inhibitors affect cell proliferation and survival of cells depending on the telomere length reduction, culminating in replicative senescence or cell death by crisis. However, most telomerase inhibitors kill cancer cells prior to significant reduction in telomere length, suggesting telomere length independent role of telomerase in early telomere dysfunction-dependent cell death. METHODS: In this study, we explored the mechanism of cell death induced by three prominent telomerase inhibitors utilizing a series of genetically encoded sensor cells including redox and DNA damage sensor cells. RESULTS: We report that telomerase inhibitors induce early cell cycle inhibition, followed by redox alterations at cytosol and mitochondria. Massive mitochondrial oxidation and DNA damage induce classical cell death involving mitochondrial transmembrane potential loss and mitochondrial permeabilization. Real-time imaging of the progression of mitochondrial oxidation revealed that treated cells undergo a biphasic mitochondrial redox alteration during telomerase inhibition, emphasizing the potential role of telomerase in the redox regulation at mitochondria. Additionally, silencing of hTERT confirmed its predominant role in maintaining mitochondrial redox homeostasis. Interestingly, the study also demonstrated that anti-apoptotic Bcl-2 family proteins still confer protection against cell death induced by telomerase inhibitors. CONCLUSION: The study demonstrates that redox alterations and DNA damage contribute to early cell death by telomerase inhibitors and anti-apoptotic Bcl-2 family proteins confer protection from cell death by their ability to safeguard mitochondria from oxidation damage.

A multiplex immunoprofiling approach for detecting the co-localization of breast cancer biomarkers using a combination of Alexafluor - Quantum dot conjugates and a panel of chromogenic dyes.

There is a plethora of information embedded in a tissue section that the conventional IHC understands only partially. Predictive biomarkers for precision immuno-oncology heavily dependent on the spatial arrangement of cells and the co-expression patterns in the tissue sections. Here we have explored the versatility of indirect multiplex immunofluorescence (mIF) and indirect multiplex immunohistochemistry (mIHC) for the labeling of breast cancer prognostic markers in routinely processed, formalin-fixed paraffin-embedded (FFPE) tissues at high resolution. The multiplex immunohistochemistry protocol utilized sequential staining for the chromogenic immunolabelling of Estrogen Receptor α (ERα) or Progesterone Receptor (PR), Human Epidermal Growth Factor Receptor 2 (HER2), and Nucleoside diphosphate kinase 1 (NM23) by multicolor chromogens in different combinations. A feasible workflow for multiplex immunofluorescence was also effectively standardized for ERα, PR, and HER2 using combinations of commercially available Alexa Fluor and Quantum dots semiconductor nanocrystal conjugated secondary antibodies. Multiplex chromogenic immunolabeling revealed differential expression of the markers on the same slide. Kappa statistics revealed perfect agreement with uniplex immunohistochemistry. For multiplex fluorescence approach, surface receptor detection using Quantum dots and Alexa fluor dyes for cytoplasmic or nuclear markers performed well for profiling multiple co-localized biomarkers on a single paraffin tissue section. The technique developed reveals additional information such as co-expression, spatial relationships, and tumor heterogeneity, providing a deeper insight into developing combinatorial therapeutic strategies in clinical care. This high throughput workflow complements the outcomes of traditional IHC while saving tissue, time, labour, and reagents.

Mechanical thrombectomy for AIS from large vessel occlusion - current trends and future perspectives.

Stroke is found to be one of the global top causes of mortality and the major factor in years of life with a handicap (DALYs). Ischemic strokes contributed to nearly 70% of all strokes worldwide. For endovascular thrombectomy in acute ischemic stroke with large vessel obstruction (AIS-LVO), using stent retrievers and/or reperfusion catheters has become the gold standard of therapy. The methodology involved keyword-based search in databases like PubMed, Embase, and Google Scholar for recent publications on mechanical thrombectomy (MT), AIS, large vessel occlusion (Large Vessel Occlusion (LVO)), screening relevant articles, retrieving full texts, and synthesizing key findings on procedural advancements, patient selection, COVID-19 (coronavirus disease 2019) impact, delay effects, effectiveness, clinical outcomes, and future perspectives. Only people with substantial cerebral artery obstruction may do well from MT. This includes the distal carotid artery and the proximal middle cerebral artery (segment M1). The size of a blocked vessel and NIHSS (National Institute of Health Stroke Scale) score are directly connected. Both the 2018 and 2019 versions of the AHA/ASA (American Heart Association/American Stroke Association) Guidelines for the Early Management of Patients with Acute Ischemic Stroke contained the recommendations that cases with AIS-LVO get endovascular therapy when administered during the time frame of 0-6 h after onset (Grade IA evidence). It is questionable whether this group of patients can be managed without the need for intravenous tissue plasminogen activator at the onset. When functional independence [modified Rankin Scale (mRS) score 2] was present at long-term follow-up, the endovascular intervention was favored. Tenecteplase, which differs from alteplase in terms of genetic variation, has a greater half-life and a higher level of fibrin selectivity, enabling bolus infusion. Studies have also demonstrated its efficacy and safety, as well as its long-term cost-effectiveness.

Multi-modal transcriptomic analysis unravels enrichment of hybrid epithelial/mesenchymal state and enhanced phenotypic heterogeneity in basal breast cancer.

Intra-tumoral phenotypic heterogeneity promotes tumor relapse and therapeutic resistance and remains an unsolved clinical challenge. It manifests along multiple phenotypic axes and decoding the interconnections among these different axes is crucial to understand its molecular origins and to develop novel therapeutic strategies to control it. Here, we use multi-modal transcriptomic data analysis - bulk, single-cell and spatial transcriptomics - from breast cancer cell lines and primary tumor samples, to identify associations between epithelial-mesenchymal transition (EMT) and luminal-basal plasticity - two key processes that enable heterogeneity. We show that luminal breast cancer strongly associates with an epithelial cell state, but basal breast cancer is associated with hybrid epithelial/mesenchymal phenotype(s) and higher phenotypic heterogeneity. These patterns were inherent in methylation profiles, suggesting an epigenetic crosstalk between EMT and lineage plasticity in breast cancer. Mathematical modelling of core underlying gene regulatory networks representative of the crosstalk between the luminal-basal and epithelial-mesenchymal axes recapitulate and thus elucidate mechanistic underpinnings of the observed associations from transcriptomic data. Our systems-based approach integrating multi-modal data analysis with mechanism-based modeling offers a predictive framework to characterize intra-tumor heterogeneity and to identify possible interventions to restrict it.

BRCA1 expression, its correlation with clinicopathological features, and response to neoadjuvant chemotherapy in high-grade serous ovarian cancer.

AIM: In high-grade serous ovarian cancers (HG-SOC), BRCA1 mutation is one of the predominant mutations reported by various studies. However, the non-mutational mechanisms of BRCA pathway inactivation in HG-SOC are unclear. We evaluated BRCA1 inactivation by estimating its expression with its repressor, ID4, in primary and neoadjuvant chemotherapy (NACT)-treated HG-SOC tumors with known therapeutic responses. METHODS: We evaluated the expression pattern of BRCA1 protein by immunohistochemistry in 119 cases of HG-SOC from a hospital cohort consisting of primary (N = 69) and NACT-treated (N = 50) tumors. Histological patterns (SET), stromal infiltration by lymphocytes (sTILs), and chemotherapy response score (CRS) were estimated by microscopic examination. Gene expression levels of BRCA1, and its repressor ID4, were estimated by qPCR. The association of BRCA1 protein and mRNA with clinicopathological features was studied. The relevance of the BRCA1/ID4 ratio was evaluated in tumors with different CRS. RESULTS: BRCA1 protein expression was observed in 12% of primary and 19% of NACT-treated HG-SOC tumors. We observed moderate concordance between BRCA1 protein and mRNA expression (AUC = 0.677). High BRCA1 mRNA expression was significantly associated with a more frequent SET pattern (p = 0.024), higher sTILs density (p = 0.042), and increased mitosis (p = 0.028). BRCA1-negative tumors showed higher expression of ID4 though not statistically significant. A higher BRCA1/ID4 ratio was associated with high sTILs density in primary (p = 0.042) and NACT-treated tumors (p = 0.040). CONCLUSION: Our findings show the utility of the BRCA1/ID4 ratio in predicting neoadjuvant therapy response, which needs further evaluation in larger cohorts with long-term outcomes.

PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer.

The PI3K/AKT/mTOR (PAM) signaling pathway is a highly conserved signal transduction network in eukaryotic cells that promotes cell survival, cell growth, and cell cycle progression. Growth factor signalling to transcription factors in the PAM axis is highly regulated by multiple cross-interactions with several other signaling pathways, and dysregulation of signal transduction can predispose to cancer development. The PAM axis is the most frequently activated signaling pathway in human cancer and is often implicated in resistance to anticancer therapies. Dysfunction of components of this pathway such as hyperactivity of PI3K, loss of function of PTEN, and gain-of-function of AKT, are notorious drivers of treatment resistance and disease progression in cancer. In this review we highlight the major dysregulations in the PAM signaling pathway in cancer, and discuss the results of PI3K, AKT and mTOR inhibitors as monotherapy and in co-administation with other antineoplastic agents in clinical trials as a strategy for overcoming treatment resistance. Finally, the major mechanisms of resistance to PAM signaling targeted therapies, including PAM signaling in immunology and immunotherapies are also discussed.

An androgen receptor regulated gene score is associated with epithelial to mesenchymal transition features in triple negative breast cancers.

BACKGROUND: Androgen receptor (AR) is considered a marker of better prognosis in hormone receptor positive breast cancers (BC), however, its role in triple negative breast cancer (TNBC) is controversial. This may be attributed to intrinsic molecular differences or scoring methods for AR positivity. We derived AR regulated gene score and examined its utility in BC subtypes. METHODS: AR regulated genes were derived by applying a bioinformatic pipeline on publicly available microarray data sets of AR+ BC cell lines and gene score was calculated as average expression of six AR regulated genes. Tumors were divided into AR high and low based on gene score and associations with clinical parameters, circulating androgens, survival and epithelial to mesenchymal transition (EMT) markers were examined, further evaluated in invitro models and public datasets. RESULTS: 53% (133/249) tumors were classified as AR gene score high and were associated with significantly better clinical parameters, disease-free survival (86.13 vs 72.69 months, log rank p = 0.032) when compared to AR low tumors. 36% of TNBC (N = 66) were AR gene score high with higher expression of EMT markers (p = 0.024) and had high intratumoral levels of 5α-reductase, enzyme involved in intracrine androgen metabolism. In MDA-MB-453 treated with dihydrotestosterone, SLUG expression increased, E-cadherin decreased with increase in migration and these changes were reversed with bicalutamide. Similar results were obtained in public datasets. CONCLUSION: Deciphering the role of AR in BC is difficult based on AR protein levels alone. Our results support the context dependent function of AR in driving better prognosis in ER positive tumors and EMT features in TNBC tumors.

Premenopausal women with breast cancer in the early post-partum period show molecular profiles of invasion and are associated with poor prognosis.

PURPOSE: Young premenopausal women develop breast cancer (BC) within 5-10 years of the last childbirth, known as post-partum breast cancers (PPBC), often present with aggressive disease. The exact mechanisms that lead to poor prognosis in these patients are largely unknown. METHODS: We have evaluated the association of clinical and reproductive factors with BC in a cohort of women ≤ 45 years (N = 155) with long-term follow-up. Based on duration since last childbirth (LCB), grouped patients into PPBC1 (LCB ≤ 5 years), PPBC2 (LCB between 6 and 10 years), PPBC3 (LCB > 10 years), and NPBC (age-matched nulliparous BC patients). We compared disease-free survival and hazard associated with recurrence/metastasis between the groups. RNA sequencing of tumor samples was performed from three parous groups (n = 10), and transcriptomic data were analyzed for differentially expressed genes and altered pathways. RESULTS: Women in the PPBC1 group had an early menarche and late age at first and last childbirth compared to other groups. Survival analysis within lymph node-positive tumors showed that PPBC1 tumors had a worse prognosis than PPBC2 and NPBC tumors (p = 0.015 and p = 0.026, respectively). Clustering of the differentially expressed genes between the groups showed distinct expression in early PPBC (E-PPBC) tumors. Pathway analysis revealed upregulation of invasive-related pathways along with T cell exhaustion, extracellular matrix remodeling, angiogenesis, and epithelial-to-mesenchymal transition in E-PPBC tumors. CONCLUSION: Early PPBC is a unique subtype with aggressive clinical features and distinct biology. Further research is needed to accurately project the risk of recurrence and optimal treatment strategies in these young patients.

The dynamic tumor-stromal crosstalk: implications of 'stromal-hot' tumors in the process of epithelial-mesenchymal transition in breast cancer.

BACKGROUND: Breast cancer metastatic programming involves an intricate process by which the tumor cell coevolves with the surrounding extracellular niche. The supporting cells from the local host stroma get transformed into cancer-associated stromal cells. This complex crosstalk leads to extracellular matrix remodeling, invasion, and eventually distant metastasis. METHODS: In this review, we examine the protein-miRNA secretome that is crucial for this crosstalk. We also provide evidence from the literature for the pivotal role played by the various stromal cells like fibroblasts, adipocytes, and immune cells in promoting the process of EMT in breast cancer. Through in-silico analysis, we have also attempted to establish that stromal presence is integral to the process of EMT. RESULTS AND CONCLUSION: The in-silico analysis delineates the persuasive role of the stroma in mediating epithelial-to-mesenchymal transition. This review elucidates the importance of examining the role of the stromal niche that can yield promising diagnostic markers and pave avenues for formulating tailored anti-cancer therapy. Process of EMT as driven by 'stroma-hot' tumors: The process of EMT is driven by the stromal cells. The stromal cells in the form of  fibroblasts, adipocytes, endothelial cells, mesenchymal stromal cells and tissue associated macrophages secrete the miRNA-protein secretome that modulates the stromal niche and the tumor cells to be become 'tumor associated'. This drives tumor progression and invasion. The 'stromal-hot' tumors eventually get the benefit of the surplus nurturing from the stroma that facilitates EMT leading to distant organ seeding and metastasis.

Determination of Microhardness of Remineralized Bleached Surface Subjected to Erosion-An In Vitro Study.

Objectives: The aim of this study is to evaluate the microhardness of remineralized bleached surface subjected to erosion. Materials and methods: Fifteen samples were divided into three groups and subjected to bleaching and erosion treatment. Group I-treated with 30% hydrogen peroxide then treated with 1% citric acid solution; group II-treated with 30% hydrogen peroxide and a remineralizing agent followed by 1% citric acid solution; group III-without bleaching with 1% citric acid solution. Five samples per group, GI, GII, and GIII were subjected to the Vickers microhardness analysis. Loss of surface hardness loss (% SHL) was analyzed followed by one-way ANOVA test, post hoc multiple comparison test, Bonferroni test to compare the various group. Result: Group II showed the lowest % SHL after the erosive phase when compared with group I. Conclusion: Erosion which usually occurs as a consequence of bleaching can be minimized by the application of remineralizing agents after bleaching. How to cite this article: Chandrashekhar S, Mithare SS, Bharath M, et al. Determination of Microhardness of Remineralized Bleached Surface Subjected to Erosion-An In Vitro Study. Int J Clin Pediatr Dent 2023;16(1):97-100.

A comparative analysis of clinicopathological features and survival between pre and postmenopausal breast cancer from an Indian cohort.

Breast cancer (BC) among premenopausal women is an aggressive disease associated with poor outcome despite intensive treatment. Higher burden is observed in southeast Asian countries attributed to younger population structure. We compared the reproductive and clinicopathological characteristics, distribution of subtypes and survival between pre and postmenopausal women from a retrospective cohort of BC patients with median follow up over 6 years to examine the differences. In our cohort of 446 BC patients, 162/446 (36.3%) were premenopausal. Parity and age at last childbirth were significantly different between pre and postmenopausal women. Premenopausal BC had a higher proportion of HER2 amplified and triple negative breast cancer (TNBC) tumors (p = 0.012). Stratified analysis by molecular subtypes showed TNBC had significantly better disease free (DFS) and overall survival (OS) among premenopausal group (mean survival, pre vs. post, DFS = 79.2 vs. 54.0 months, OS = 72.5 vs. 49.5 months, p = 0.002 for both). Analysis on external datasets (SCAN-B, METABRIC) confirmed this finding for overall survival. Our data confirmed the previously observed association of clinical and pathological features between pre and postmenopausal BC. Exploration of better survival among premenopausal TNBC tumors is warranted in larger cohorts with long term follow up.