Unveiling the Role of Artificial Intelligence (AI) in Polycystic Ovary Syndrome (PCOS) Diagnosis: A Comprehensive Review.

Polycystic Ovary Syndrome (PCOS) is one of the most widespread endocrine and metabolic disorders affecting women of reproductive age. Major symptoms include hyperandrogenism, polycystic ovary, irregular menstruation cycle, excessive hair growth, etc., which sometimes may lead to more severe complications like infertility, pregnancy complications and other co-morbidities such as diabetes, hypertension, sleep apnea, etc. Early detection and effective management of PCOS are essential to enhance patients' quality of life and reduce the chances of associated health complications. Artificial intelligence (AI) techniques have recently emerged as a popular methodology in the healthcare industry for diagnosing and managing complex diseases such as PCOS. AI utilizes machine learning algorithms to analyze ultrasound images and anthropometric and biochemical test result data to diagnose PCOS quickly and accurately. AI can assist in integrating different data sources, such as patient histories, lab findings, and medical records, to present a clear and complete picture of an individual's health. This information can help the physician make more informed and efficient diagnostic decisions. This review article provides a comprehensive analysis of the evolving role of AI in various aspects of the management of PCOS, with a major focus on AI-based diagnosis tools.

Worst Pattern of Invasion as a Predictor of Nodal Metastasis in Early-Stage Oral Squamous Cell Carcinoma.

About one-third of early stage oral cancer patients have occult nodal metastasis. High grade worst pattern of invasion (WPOI) is associated with an increased risk of nodal metastasis and poor prognosis. However, it still remains unanswered whether to perform an elective neck dissection for clinically node-negative disease or not. This study aims to evaluate the role of histological parameters including WPOI in predicting nodal metastasis in early-stage oral cancers. This analytical observational study comprised 100 patients of early-stage, node-negative, oral squamous cell carcinoma, admitted in the Surgical Oncology Department from April, 2018 till the sample size was reached. The socio-demographic data, clinical history, and findings of clinical and radiological examination were noted. The association of nodal metastasis with various histological parameters like tumour size, degree of differentiation, depth of invasion (DOI), WPOI, perineural invasion (PNI), lymphovascular invasion (LVI) and lymphocytic response was determined. SPSS 20.0 statistical tool; student's 't' test and chi-square tests were applied. While the buccal mucosa was the commonest site, the rate of occult metastasis was highest in the tongue. Nodal metastasis was not significantly associated with age, sex, smoking and primary site. While the nodal positivity was not significantly associated with tumour size, pathological stage, DOI, PNI and lymphocytic response, it was associated with LVI, degree of differentiation and WPOI. Increasing WPOI grade correlated significantly with the nodal stage, LVI and PNI, but not with DOI. WPOI is not only a significant predictor of occult nodal metastasis but can also be a novel therapeutic tool in the management of early-stage oral cancers. In patients with an aggressive WPOI pattern or other high-risk histological parameters, the neck can be addressed with either elective neck dissection or radiotherapy after wide excision of the primary tumor; otherwise, an active surveillance approach can be followed.

Role of a Disease-associated ST3Gal-4 in Non-small Cell Lung Cancer.

Sialylation promotes tumorigenesis by affecting various cancer-related events, including apoptosis inhibition, cell growth, invasion, migration, metastasis, chemo-resistance, and immunomodulation in favor of tumor progression. An altered expression of sialyltransferase enzymes is responsible for synthesizing various tumor-associated sialylated structures. In the present study, our findings have revealed a significant up-regulation of ST3Gal-4 transcript in the two major subtypes of NSCLC cell lines [squamous cell carcinoma cell line (NCI-H520) and adenocarcinoma cell line (A549)]. Thus, the role of the ST3Gal-4 gene was assessed on cancer-associated signal transduction pathways in these cells in view of proliferation, invasion, and migration. ST3Gal-4 was silenced by transfection of both the cell lines with esi-ST3Gal-4-RNA, which RT-PCR and western immunoblotting confirmed. Silencing of ST3Gal-4 resulted in a decreased expression of MAL-I interacting membrane-HSP60, identified earlier as an α2,3-sialylated glycoprotein, thus pointing towards the possible role of ST3Gal-4 in its sialylation. The proliferation, invasion, and migration of both types of NSCLC cells were reduced significantly in the ST3Gal-4 silenced cells. Our findings were substantiated by the down-regulation of ß-catenin and E-cadherin, a reduced expression of activated AKT1, ERK1/2, and NF-ƙB in these cells. We propose that ST3Gal-4 may be the disease-associated sialyltransferase involved in α2,3 sialylation of the membrane proteins, including HSP60 of the NSCLC cells. This may lead to the conformational alteration of these proteins, required for the activation of E-cadherin/ß-catenin, AKT, and ERK/NF-ƙB mediated signal transduction pathways in these cells, resulting in their proliferation, invasion, and migration.

The lipolytic activity of LipJ, a stress-induced enzyme, is regulated by its C-terminal adenylate cyclase domain.

Aim: The confirmation of lipolytic activity and role of Rv1900c in the Mycobacterium physiology Methods:rv1900c/N-terminus domain (rv1900NT) were cloned in pET28a/Escherichia coli, purified by affinity chromatography and characterized. Results: A zone of clearance on tributyrin-agar and activity with pNP-decanoate confirmed the lipolytic activity of Rv1900c. The Rv1900NT demonstrated higher enzyme specific activity, Vmax and kcat, but Rv1900c was more thermostable. The lipolytic activity of Rv1900c decreased in presence of ATP. Mycobacterium smegmatis expressed rv1900c/rv1900NT-altered colony morphology, growth, cell surface properties and survival under stress conditions. The effect was more prominent with Rv1900NT as compared with Rv1900c. Conclusion: The study confirmed the lipolytic activity of Rv1900c and suggested its regulation by the adenylate cyclase domain and role in the intracellular survival of bacteria.

Lay abstract Tuberculosis (TB) remains the top contagious/infectious killer in the world. It is caused by the bacteria Mycobacterium tuberculosis. The bacteria resides/replicates in the immune cell that normally has to eradicate infectious microorganisms. Though the treatment of TB is available, the emergence of drug-resistant bacteria is of major concern. The treatment of drug-resistant TB has been reported to be more difficult due to lengthy and complex treatment regimens. Therefore, there is an urgent need for new and better drugs to treat TB/drug-resistant TB. For this purpose understanding the role of each protein in the physiology of mycobacteria is required. Lipids play a critical role in the intracellular survival of this pathogen in the host. Our study demonstrated that LipJ supported the intracellular survival of bacteria. Therefore, it could be a potential drug target.

Adrenal histoplasmosis in immunocompetent individuals a case series from the North-Western part of India, Rajasthan province: An emerging endemic focus.

Histoplasmosis is a fungal infection caused by Histoplasma capsulatum and very few cases reported from North-West India. Adrenal histoplasmosis is an even more uncommon mycotic disease. We describe five immunocompetent men with adrenal histoplasmosis presenting with constitutional symptoms. Four patients had bilateral adrenal involvement, whereas one had unilateral adrenal mass. Three patients had adrenal insufficiency at presentation and the other two developed adrenal insufficiencies during follow-up. All the patients received amphotericin B and itraconazole treatment which led to symptomatic improvement but adrenal insufficiency persisted in all patients at the end of the follow-up.

Rv2223c, an acid inducible carboxyl-esterase of Mycobacterium tuberculosis enhanced the growth and survival of Mycobacterium smegmatis.

Aim: To elucidate the role of Rv2223c in Mycobacterium tuberculosis. Methods: Purified recombinant Rv2223c protein was characterized. Expression of rv2223c in the presence of different stress environment and subcellular localization were performed in M. tuberculosis H37Ra and Mycobacterium smegmatis (MS_2223c). Effect of its overexpression on growth rate, infection and intracellular survival in THP-1/PBMC cells were studied. Results: rRv2223c demonstrated esterase activity with preference for pNP-octanoate and hydrolyzed trioctanoate to di- and mono-octanoate. Expression of rv2223c was upregulated in acidic and nutritive stress conditions. rRv2223c was identified in extracellular and cell wall fractions. MS_2223c exhibited enhanced growth, survival during in vitro stress, infection and intracellular survival. Conclusions: Rv2223c is a secretary, carboxyl-esterase, with enhanced expression under acidic and nutritive stress condition and might help in intracellular survival of bacteria.

Molecular characterization and immunogenic function of ML1899 (LipG) of Mycobacterium leprae.

Introduction. ML1899 is conserved in all mycobacterium sp. and is a middle member of mle-ML1898 operon involved in mycolic acid modification.Aim. In the present study attempts were made to characterize ML1899 in detail.Methodology. Bioinformatics tools were used for prediction of active-site residues, antigenic epitopes and a three-dimensional model of protein. The gene was cloned, expressed and purified as His-tagged protein in Escherichia coli for biophysical/biochemical characterization. Recombinant protein was used to treat THP-1 cells to study change in production of nitric oxide (NO), reactive oxygen species (ROS), cytokines and chemokines using flowcytometry/ELISA.Results. In silico analysis predicted ML1899 as a member of α/ß hydrolase family with GXSXG-motif and Ser126, His282, Asp254 as active-site residues that were confirmed by site-directed mutagensis. ML1899 exhibited esterase activity. It hydrolysed pNP-butyrate as optimum substrate at pH 8.0 and 50 °C with 5.56 µM-1 min-1 catalytic efficiency. The enzyme exhibited stability up to 60 °C temperature and between pH 6.0 to 9.0. K m, V max and specific activity of ML1899 were calculated to be 400 µM, 40 µmoles min-1 ml-1 and 27 U mg- 1, respectively. ML1899 also exhibited phospholipase activity. The protein affected the survival of macrophages when treated at higher concentration. ML1899 enhanced ROS/NO production and up-regulated pro-inflammatory cytokines and chemokine including TNF-α, IFN-γ, IL-6 and IL-8 in macrophages. ML1899 was also observed to elicit humoral response in 69 % of leprosy patients.Conclusion. These results suggested that ML1899, an esterase could up-regulate the immune responses in favour of macrophages at a low concentration but kills the THP-1 macrophages cells at a higher concentration.

Rv1288, a Two Domain, Cell Wall Anchored, Nutrient Stress Inducible Carboxyl-Esterase of Mycobacterium tuberculosis, Modulates Cell Wall Lipid.

Rv1288, a conserved hypothetical protein of M. tuberculosis (M.tb), was recently characterized as two-domain esterase enzyme by in silico study. In the present study, Rv1288 and its domains (Est and Lyt) were cloned individually from M.tb into E. coli for expression and purification. The purified rRv1288 and rEst proteins exhibited lipolytic activity with medium chain length esters as optimum substrates, while Lyt domain did not show enzymatic activity. However, presence of Lyt domain resulted in enhanced rate of protein aggregation at higher temperature. Both rRv1288 and rEst followed the similar patterns of substrate specificity, temperature and pH activity. Site directed mutagenesis confirmed the Ser-294, Asp-391 and His-425 as catalytic site residues. Rv1288 was found to be present in cell wall fraction of M.tb H37Ra. Peptidoglycan binding activity of Rv1288 and its domains demonstrated that the Lyt domain is essential for anchoring protein to the cell wall. Expression of rv1288 was up regulated in M.tb under nutrient starved condition. Over expression of rv1288 in surrogate host M. smegmatis led to change in colony morphology, enhanced pellicle and aggregate formation that might be linked with the changed lipid composition of bacterial cell wall. Cell wall of M. smegmatis expressing rv1288 had higher amount of lipids, with a significant increase in trehalose dimycolate content. Rv1288 also leads to increase in drug resistance of M. smegmatis. Rv1288 also enhanced the intracellular survival of M. smegmatis in Raw264.7 cell line. Overall, this study suggested that Rv1288, a cell wall localized carboxyl hydrolase with mycolyl-transferase activity, modulated the cell wall lipids to favor the survival of bacteria under stress condition.

Invasive Ductal Carcinoma Breast: How Neoadjuvant Chemotherapy Affects the Status of Estrogen Receptor, Progesterone Receptor and HER2/Neu-A Tertiary Care Centre Study.

INTRODUCTION: Determination of Estrogen Receptor (ER), Progesterone Receptor (PR) and HER2/neu in primary Invasive Ductal Carcinoma (IDC) breast is the standard of care parameter for determining treatment options. Whether or not Neoadjuvant Chemotherapy (NAC) affects the receptor status is still an unanswered question. AIM: To compare immunohistochemical (IHC) profiles of ER, PR and HER2/neu in primary IDC breast before and after NAC to assess the subsequent effects on receptor status. MATERIALS AND METHODS: Thirty two patients diagnosed with primary IDC breast who had a previous breast core biopsy with complete IHC profile followed by NAC and Modified Radical Mastectomy (MRM) were included. For each case demographic and histologic data was collected, including age, grade, amount of necrosis post NAC and IHC panel for ER, PR and HER2/neu in core biopsies. The same IHC panel was applied on Post NAC MRM specimen. Pre- and post NAC IHC expression was compared. RESULTS: Patients ranged from 30 years to 75 years in range. ER, PR and HER2/neu status of core biopsies and MRM specimen were compared and overall agreement was noted. Comparison for each receptor was done using McNemar's test and significance was calculated. There was no statistically significant difference in ER and Her2/neu expression between pre- and post-NAC specimens. However, a statistically significant loss of PR expression was noted between the two groups. CONCLUSION: Accurate determination of ER, PR and Her2/neu status in primary IDC breast is important to guide further treatment. Change in receptor status post NAC may warrant corresponding change in hormonal therapy.

Cell Wall Associated Factors of Mycobacterium tuberculosis as Major Virulence Determinants: Current Perspectives in Drugs Discovery and Design.

BACKGROUND: Mycobacteria genus is responsible for deadly diseases like tuberculosis and leprosy. Cell wall of bacteria belonging to this genus is unique in many ways. It plays a major role in the pathogenesis and intracellular survival inside the host. In intracellular pathogens, their cell wall acts as molecular shield and interacts with host cell milieu to modulate host defense responses. OBJECTIVES: In this review, we summarize the factors that participate in the biosynthesis of unique mycobacterial cell wall, understand their potential as drug targets and the recent developments where they have been evaluated as possible drug targets. RESULTS: Several cell wall associated factors that play crucial roles in the synthesis of cell wall components like Antigen 85 complex, Glycosyltransferases (GTs), LM (lipomannan) and LAM (lipoarabinomannan), mAGP Complex, lipolytic enzyme have been categorically documented. Most of the presently used anti TB regimens interrupted cell wall synthesis, but the emergence of drug resistant strains made it mandatory to identify new drug targets. Novel drug candidates which could inhibit the synthesis of cell wall components have been thoroughly studied worldwide. CONCLUSION: Studies demonstrated that the cell wall components are unique in terms of their contribution in mycobacterium pathogenesis. Targeting these can hamper the growth of M. tuberculosis. In this study, we scrutinize the drugs under trials and the potential candidates screened through in silico findings.

Malignant Granular Cell Tumour Presenting as a Paravertebral Mass in an Adolescent Male- A Rare Presentation of an Uncommon Tumour.

Granular Cell Tumour (GCT), also known as Abrikossoff's tumour is a rare neural tumour, mostly benign and solitary but rare malignant and multifocal occurrence are also reported. Location of tumour varies widely within body with tongue, skin and subcutaneous tissue being the most common sites. We report a case of malignant GCT in a 17-year-old male presented with a paravertebral swelling. Radiological and histopathological findings along with immunohistochemistry were of malignant GCT. We emphasize this case for its uncommon age and site of presentation in addition to invasive nature.

In-Silico Characterization of a Hypothetical Protein, Rv1288 of Mycobacterium tuberculosis Containing an Esterase Signature and an Uncommon LytE Domain.

BACKGROUND: Death toll due to tuberculosis is still rising day by day. Whole genome sequence of Mycobacterium tuberculosis has provided a platform to conduct research in order to identify the probable drug target. OBJECTIVES: Out of 4000 gene products of M. tuberculosis, approximately 40% of proteins are annotated as hypothetical. Identifying and characterizing these proteins could provide a new prescriptive for developing new TB drugs. Rv1288, a protein of M. tuberculosis H37Rv has been annotated as a hypothetical protein in database. Attempt has been made to assign a meaningful role to rv1288 gene product in M. tuberculosis life cycle. METHODS: A homology 3D structure of both domains was separately generated and assigned as Rv1288LytE and Rv1288est. Molecular simulation of Rv1288est was carried out for proper structure analysis. To further confirm the predictive role of Rv1288 in mycobacterium life cycle, molecular docking was performed. N-acetyl glucosamine, a major constituent of cell wall was docked with LytE domain, whereas, esterase domain was docked with lipolytic substrate, pNP-ester derivatives and inhibitors THL/PMSF. RESULTS: In-silico analysis revealed that Rv1288 is a two domain protein, an N-terminal LytE domain containing three consecutive LysM motifs and a C-terminal esterase domain of esterase D family. LytE domain has the property to bind N-acetyl glucosamine moieties of peptidoglycan, a major component of cell wall. Detailed in-silico sequence analysis revealed that this LytE domain may help in positioning the esterase domain to the cell wall of mycobacterium. Esterase domain comprised a tetrapeptide motif HGGG, a pentapeptide sequence motif GxSxG and conserved amino acid residues Ser-141, Asp-238 and His-272 which constitute a catalytic triad characteristic of other hormone sensitive lipases/ esterases. Docking studies suggested that THL and PMSF could be the potent inhibitors for Rv1288 protein. CONCLUSION: In the present investigation, we bioinformatically confirmed that Rv1288 is most likely a LytE domain containing lipolytic enzyme showing similarity to hormone sensitive lipases/esterases.

Biocatalytic potential of lipase from Staphylococcus sp. MS1 for transesterification of jatropha oil into fatty acid methyl esters.

An extracellular lipase producing isolate Staphylococcus sp. MS1 was optimized for lipase production and its biocatalytic potential was assessed. Medium with tributyrin (0.25 %) and without any exogenous inorganic nitrogen source was found to be optimum for lipase production from Staphylococcus sp. MS1. The optimum pH and temperature for lipase production were found to be pH 7 and 37 °C respectively, showing lipase activity of 37.91 U. It showed good lipase production at pH 6-8. The lipase was found to be stable in organic solvents like hexane and petroleum ether, showing 98 and 88 % residual activity respectively. The biotransformation using the concentrated enzyme in petroleum ether resulted in the synthesis of fatty acid methyl esters like methyl oleate, methyl palmitate and methyl stearate. Thus, the lipase under study has got the potential to bring about transesterification of oils into methyl esters which can be exploited for various biotechnological applications.