MicroRNA signature of stromal-epithelial interactions in prostate and breast cancers.

Stromal-epithelial communication is an absolute necessity when it comes to the morphogenesis and pathogenesis of solid tissues, including the prostate and breast. So far, signalling pathways of several growth factors have been investigated. Besides such chemical factors, non-coding RNAs such as miRNAs have recently gained much interest because of their variety and complexity of action. Prostate and breast tissues being highly responsive to steroid hormones such as androgen and estrogen, respectively, it is not surprising that a huge set of available literature critically investigated the interplay between such hormones and miRNAs, especially in carcinogenesis. This review showcases our effort to highlight hormonally-related miRNAs that also somehow perturb the regular stromal-epithelial interactions during carcinogenesis in the prostate and breast. In future, we look forward to exploring how hormonal changes in the tissue microenvironment bring about miRNA-mediated changes in stromal-epithelial interactome in carcinogenesis and cancer progression.

Effect of Transcutaneous Electrical Nerve Stimulation of T6 Dermatome on Appetite and Weight Reduction in Obese Individuals: A Pilot Study.

BACKGROUND: Previous work demonstrated the beneficial effect of T6 dermatomal stimulation by the percutaneous method in managing obesity. However, a simple, cost-effective, and feasible intervention stimulating the dermatome can be a potential solution for obesity care. OBJECTIVE: The objective of this study was to find the effect of transcutaneous electrical nerve stimulation (TENS) of T6 dermatome on appetite and weight loss in obese individuals. MATERIAL AND METHODS: In this prospective single-arm experimental study, 20 obese patients received TENS treatment of T6 dermatome for 30 min, once a week and for 12 weeks. Outcome measures such as appetite level in the visual analog scale (VAS), weight in kg, and basal metabolic index (BMI) in kg/m2 were assessed at baseline, 12 weeks -post-intervention, and at 8 weeks of follow-up. RESULTS: A statistically significant difference in all the variables was found from baseline to 12 weeks of intervention (P < 0.001) and maintained till 8 weeks of follow-up. From pre- to post-treatment, the effect size for appetite reduction was large (>1) while for weight and BMI loss was (0.14, 0.16), respectively small. Additionally, a weak correlation was found between pre- and follow-up appetite and weight loss (r = 0.25, P = 0.294). CONCLUSIONS: Twelve weeks of TENS treatment of T6 dermatome showed a positive effect in reducing appetite with sustained reduction up to 8 weeks of follow-up even after completion of the intervention. However, in the absence of dietary modification, TENS treatment was associated with low effect sizes weight and BMI loss.

Discovering hidden patterns: Association rules for cardiovascular diseases in type 2 diabetes mellitus.

BACKGROUND: It is increasingly common to find patients affected by a combination of type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD), and studies are able to correlate their relationships with available biological and clinical evidence. The aim of the current study was to apply association rule mining (ARM) to discover whether there are consistent patterns of clinical features relevant to these diseases. ARM leverages clinical and laboratory data to the meaningful patterns for diabetic CAD by harnessing the power help of data-driven algorithms to optimise the decision-making in patient care. AIM: To reinforce the evidence of the T2DM-CAD interplay and demonstrate the ability of ARM to provide new insights into multivariate pattern discovery. METHODS: This cross-sectional study was conducted at the Department of Biochemistry in a specialized tertiary care centre in Delhi, involving a total of 300 consented subjects categorized into three groups: CAD with diabetes, CAD without diabetes, and healthy controls, with 100 subjects in each group. The participants were enrolled from the Cardiology IPD & OPD for the sample collection. The study employed ARM technique to extract the meaningful patterns and relationships from the clinical data with its original value. RESULTS: The clinical dataset comprised 35 attributes from enrolled subjects. The analysis produced rules with a maximum branching factor of 4 and a rule length of 5, necessitating a 1% probability increase for enhancement. Prominent patterns emerged, highlighting strong links between health indicators and diabetes likelihood, particularly elevated HbA1C and random blood sugar levels. The ARM technique identified individuals with a random blood sugar level > 175 and HbA1C > 6.6 are likely in the "CAD-with-diabetes" group, offering valuable insights into health indicators and influencing factors on disease outcomes. CONCLUSION: The application of this method holds promise for healthcare practitioners to offer valuable insights for enhancing patient treatment targeting specific subtypes of CAD with diabetes. Implying artificial intelligence techniques with medical data, we have shown the potential for personalized healthcare and the development of user-friendly applications aimed at improving cardiovascular health outcomes for this high-risk population to optimise the decision-making in patient care.

A Review on Functionalization of Benzo-5,6-Fused Bicyclic Heteroaromatic Compounds.

Over the decades, functionalized heteroaromatic compounds and their scaffolds have drawn the significant attention in synthetic organic chemistry as well as in interdisciplinary sciences due to their prevalence in natural products, hormones, vitamins, and their applications in pharmaceuticals, agrochemicals, veterinary products, dyes and pigments, bio-imaging, semiconductors, and optoelectronics, etc. This review explores various synthetic strategies for functionalization of numerous 5,6 benzo-fused heteroaromatic derivatives such as indole, aza-indole, benzofuran, benzothiophene, benzimidazole, benzoxazole, benzothiazole and benzotriazole through various methods including C-H activation, cross-coupling, metal catalysis, photo-catalysis, electrocatalysis and organocatalysis in recent years (2019-2023). Highly functionalized heterocyclic scaffolds are the important precursors for synthesizing many bioactive drugs like fenbendazole, viozan, Griseofulvin, zileuton, flunoxaprofen, natural products, and optoelectronic materials, etc.

AI-based 3D-QSAR model of FDA-approved repurposed drugs for inhibiting sclerostin.

BACKGROUND: Wnt activation promotes bone formation and prevents bone loss. The Wnt pathway antagonist sclerostin and additional anti-sclerostin antibodies were discovered as a result of the development of the monoclonal antibody romosozumab. These monoclonal antibodies greatly increase the risk of cardiac arrest. Three-dimensional quantitative structure-activity relationships (3D-QSAR) predicts biological activities of ligands based on their three-dimensional features by employing powerful chemometric investigations such as artificial neural networks (ANNs) and partial least squares (PLS). OBJECTIVE: In this study, ligand-receptor interactions were investigated using 3D-QSAR Comparative molecular field analysis (CoMFA). Estimates of steric and electrostatic characteristics in CoMFA are made using Lennard-Jones and Coulomb potentials. METHODS: To identify the conditions necessary for the activity of these molecules, fifty Food and Drug Administration (FDA)-approved medications were chosen for 3D-QSAR investigations and done by CoMFA. For QSAR analysis, there are numerous tools available. This study employed Open 3D-QSAR for analysis due to its simplicity of use and capacity to produce trustworthy results. Four tools were used for the analysis on this platform: Py-MolEdit, Py-ConfSearch, and Py-CoMFA. RESULTS: Maps that were generated were used to determine the screen's r2 (Coefficient of Multiple Determinations) value and q2 (correlation coefficient). These numbers must be fewer than 1, suggesting a good, trustworthy model. Cross-validated (q2) 0.532 and conventional (r2) correlation values of 0.969 made the CoMFA model statistically significant. The model showed that hydroxamic acid inhibitors are significantly more sensitive to the steric field than the electrostatic field (70%) (30%). This hypothesis states that steric (43.1%), electrostatic (26.4%), and hydrophobic (20.3%) qualities were important in the design of sclerostin inhibitors. CONCLUSION: With 3D-QSAR and CoMFA, statistically meaningful models were constructed to predict ligand inhibitory effects. The test set demonstrated the model's robustness. This research may aid in the development of more effective sclerostin inhibitors that are synthesised using FDA-approved medications.

PMTPred: machine-learning-based prediction of protein methyltransferases using the composition of k-spaced amino acid pairs.

Protein methyltransferases (PMTs) are a group of enzymes that help catalyze the transfer of a methyl group to its substrates. These enzymes play an important role in epigenetic regulation and can methylate various substrates with DNA, RNA, protein, and small-molecule secondary metabolites. Dysregulation of methyltransferases is implicated in various human cancers. However, in light of the well-recognized significance of PMTs, reliable and efficient identification methods are essential. In the present work, we propose a machine-learning-based method for the identification of PMTs. Various sequence-based features were calculated, and prediction models were trained using various machine-learning algorithms using a tenfold cross-validation technique. After evaluating each model on the dataset, the SVM-based CKSAAP model achieved the highest prediction accuracy with balanced sensitivity and specificity. Also, this SVM model outperformed deep-learning algorithms for the prediction of PMTs. In addition, cross-database validation was performed to ensure the robustness of the model. Feature importance was assessed using shapley additive explanations (SHAP) values, providing insights into the contributions of different features to the model's predictions. Finally, the SVM-based CKSAAP model was implemented in a standalone tool, PMTPred, due to its consistent performance during independent testing and cross-database evaluation. We believe that PMTPred will be a useful and efficient tool for the identification of PMTs. The PMTPred is freely available for download at https://github.com/ArvindYadav7/PMTPred and http://www.bioinfoindia.org/PMTPred/home.html for research and academic use.

Effect of Padina gymnospora biowaste inclusion on in vitro methane production, feed fermentation, and microbial diversity.

In vitro studies were undertaken aiming to study the methane (CH4) mitigation potential of biowaste (BW) of Padina gymnospora at the graded inclusion of 0% (C), 2% (A2), 5% (A5), and 10% (A10) of the diet composed of straw and concentrate in 40:60 ratio. The chemical composition analysis revealed that the BW contained higher crude protein (CP), neutral detergent fiber (NDF), acid detergent fiber (ADF), and ether extract (EE) than the PF (fresh seaweed, P. gymnospora). The concentration of cinnamic acid, sinapic acid, kaempferol, fisetin p-coumaric acid, ellagic acid, and luteolin in BW was 1.5-6-folds less than the PF. Inclusion of BW decreased (P < 0.0001) CH4 production by 34%, 38%, and 45% in A2, A5, and A10 treatments, respectively. A decrease (P < 0.0001) of 7.5%-8% in dry matter (DM) and organic matter (OM) digestibility was also recorded with the BW supplementation. The BW inclusion also decreased the numbers of total (P = 0.007), Entodinomorphs (P = 0.011), and Holotrichs (P = 0.004) protozoa. Metagenome data revealed the dominance of Bacteroidetes, Proteobacteria, Firmicutes, Actinobacteria, and Fibrobacter microbial phyla. At the phylum level, Euryarchaeota dominated the archaeal community, whereas Methanobrevibacter was most abundant at the genus level. It can be concluded that the inclusion of BW in straw and concentrate based diet by affecting rumen fermentation, protozoal numbers, and compositional shift in the archaeal community significantly decreased CH4 production. Utilization of biowaste of P. gymnospora as a CH4 mitigating agent will ensure its efficient utilization rather than dumping, which shall cause environmental pollution and health hazards.

Impacts of industrial actions, protests, strikes and lockouts by health and care workers during COVID-19 and other pandemic contexts: a systematic review.

BACKGROUND: Public health emergencies of international concern (PHEICs) as the COVID-19 pandemic and others that have occurred since the early 2000s put enormous pressure on health and care systems. This is being a context for protests by health and care workers (HCWs) because of additional workload, working conditions and effects on mental and physical health. In this paper, we intended to analyze the demands of HCWs associated with industrial actions, protests, strikes and lockouts (IAPSLs) which occurred during COVID-19 pandemic and other PHEICs; to identify the impact of these grievances; and describe the relevant interventions to address these IAPSLs. METHODS: We included studies published between January 2000 and March 2022 in PubMed, Embase, Scopus, BVS/LILACS, WHO's COVID-19 Research Database, ILO, OECD, HSRM, and Google Scholar for grey literature. Eligibility criteria were HCWs as participants, IAPSLs as phenomenon of interest occurring in the context of COVID-19 and other PHEICs. GRADE CERQual was used to assess risk of bias and confidence of evidence. RESULTS: 1656 records were retrieved, and 91 were selected for full-text screening. We included 18 publications. A system-wide approach, rather than a limited approach to institutions on strike, makes it possible to understand the full impact of the strike on health and care services. PHEICs tend to aggravate already adverse working conditions of HCWs, acting as drivers for HCWs strikes, leading to staff shortages, and financial issues, both in the North and in the Global South, particularly evident in Asia and Africa. In addition, issues related to deficiencies in leadership and governance in heath sector and lack of medical products and technologies (e.g., lack of personal protective equipment) were the main drivers of strikes, each contributing 25% of the total drivers identified. CONCLUSIONS: It is necessary to focus on the preparedness of health and care systems to respond adequately to PHEICs, and this includes being prepared for HCWs' IAPSLs, talked much in the context of COVID-19 pandemic. Evidence to assist policymakers in defining strategies to respond adequately to the health and care needs of the population during IAPSLs is crucial. The main impact of strikes is on the disruption of health care services' provision. Gender inequality being a major issue among HCWs, a proper understanding of the full impact of the strike on health and care services will only be possible if gender lens is combined with a systemic approach, rather than gender-undifferentiated approaches limited to the institutions on strike.

Tofacitinib Treatment Suppresses CD4+ T-Cell Activation and Th1 Response, Contributing to Protection against Staphylococcal Toxic Shock.

Staphylococcal toxic shock syndrome (STSS) is a rare, yet potentially fatal disease caused by Staphylococcus aureus (S. aureus) enterotoxins, known as superantigens, which trigger an intense immune response. Our previous study demonstrated the protective effect of tofacitinib against murine toxin-induced shock and a beneficial effect against S. aureus sepsis. In the current study, we examined the effects of tofacitinib on T-cell response in peripheral blood using a mouse model of enterotoxin-induced shock. Our data revealed that tofacitinib suppresses the activation of both CD4+ and CD8+ T cells in peripheral blood. Furthermore, both gene and protein levels of Th1 cytokines were downregulated by tofacitinib treatment in mice with enterotoxin-induced shock. Importantly, we demonstrated that CD4+ cells, but not CD8+ cells, are pathogenic in mice with enterotoxin-induced shock. In conclusion, our findings suggest that tofacitinib treatment suppresses CD4+ T-cell activation and Th1 response, thereby aiding in protection against staphylococcal toxic shock in mice. This insight may guide the future development of novel therapies for STSS.

Lead and calcium crosstalk tempted acrosome damage and hyperpolarization of spermatozoa: signaling and ultra-structural evidences.

BACKGROUND: Exposure of humans and animals to heavy metals is increasing day-by-day; thus, lead even today remains of significant public health concern. According to CDC, blood lead reference value (BLRV) ranges from 3.5 µg/dl to 5 µg/dl in adults. Recently, almost 2.6% decline in male fertility per year has been reported but the cause is not well established. Lead (Pb2+) affects the size of testis, semen quality, and secretory functions of prostate. But the molecular mechanism(s) of lead toxicity in sperm cells is not clear. Thus, present study was undertaken to evaluate the adverse effects of lead acetate at environmentally relevant exposure levels (0.5, 5, 10 and 20 ppm) on functional and molecular dynamics of spermatozoa of bucks following in vitro exposure for 15 min and 3 h. RESULTS: Lead significantly decreased motility, viable count, and motion kinematic patterns of spermatozoa like curvilinear velocity, straight-line velocity, average path velocity, beat cross frequency and maximum amplitude of head lateral displacement even at 5 ppm concentration. Pb2+ modulated intracellular cAMP and Ca2+ levels in sperm cells through L-type calcium channels and induced spontaneous or premature acrosome reaction (AR) by increasing tyrosine phosphorylation of sperm proteins and downregulated mitochondrial transmembrane potential. Lead significantly increased DNA damage and apoptosis as well. Electron microscopy studies revealed Pb2+ -induced deleterious effects on plasma membrane of head and acrosome including collapsed cristae in mitochondria. CONCLUSIONS: Pb2+ not only mimics Ca2+ but also affects cellular targets involved in generation of cAMP, mitochondrial transmembrane potential, and ionic exchange. Lead seems to interact with Ca2+ channels because of charge similarity and probably enters the sperm cell through these channels and results in hyperpolarization. Our findings also indicate lead-induced TP and intracellular Ca2+ release in spermatozoa which in turn may be responsible for premature acrosome exocytosis which is essential feature of capacitation for fertilization. Thus, lead seems to reduce the fertilizing capacity of spermatozoa even at 0.5 ppm concentrations.

A Case Report Highlighting the Significance of COVID-19 Unveiling Megaloblastic Anemia and Worsening Dementia in the Elderly.

The COVID-19 pandemic has resulted in substantial lifestyle changes with significant implications for nutritional health. Factors such as movement restrictions and disruptions in food supply chains led to the restricted availability of primary sources of essential micronutrients. To highlight this, we present the case of an elderly woman with an underlying subclinical cobalamin deficiency who developed symptomatic megaloblastic anemia, requiring hospital admission under lockdown conditions. This exemplifies how changes in diet during the COVID-19 lockdown have hastened the onset of B12 deficiency symptoms. Adverse outcomes can be avoided by identifying people at high risk of poor nutritional status and implementing policy initiatives that enhance their nutritional condition. This case report showed how important the B12 shortage was during the COVID-19 lockdown, especially for older people. They are more likely to be malnourished during COVID-19 for several reasons.

Artificial Intelligence (AI)-Based Detection of Anaemia Using the Clinical Appearance of the Gingiva.

Background and aim Millions suffer from anaemia worldwide, and systemic disorders like anaemia harm oral health. Anaemia is linked to periodontitis as certain inflammatory cytokines produced during periodontal inflammation can depress erythropoietin production leading to the development of anemia. Thus, detecting and treating it is crucial to tooth health. Hence, this study aimed to evaluate three different machine-learning approaches for the automated detection of anaemia using clinical intraoral pictures of a patient's gingiva. Methodology Orange was employed with squeeze net embedding models for machine learning. Using 300 intraoral clinical photographs of patients' gingiva, logistic regression, neural network, and naive Bayes were trained and tested for prediction and detection. Accuracy was measured using a confusion matrix and receiver operating characteristic (ROC) curve. Results In the present study, three convolutional neural network (CNN)-embedded machine-learning algorithms detected and predicted anaemia. For anaemia identification, naive Bayes had an area under curve (AUC) of 0.77, random forest plot had an AUV of 0.78, and logistic regression had 0.85. Thus, the three machine learning methods detected anaemia with 77%, 78%, and 85% accuracy, respectively. Conclusion Using artificial intelligence (AI) with clinical intraoral gingiva images can accurately predict and detect anaemia. These findings need to be confirmed with larger samples and additional imaging modalities.

Case Report: Scorpion Envenomation with Delayed Ischemic Priapism in a Preadolescent-An Unusual Presentation.

Priapism as a complication of scorpionism in children is rare and is categorized as grade II of severity. The pathogenesis is the activation of parasympathetic pathways that stimulate the release of acetylcholine. An 8-year-old boy, a known case of steroid-dependent nephrotic syndrome, presented with a history of persistent penile erection for the previous 12 hours. He had a history of a black scorpion (Heterometrus swammerdami) sting on his right leg 4 days earlier. He was given adequate analgesia, and prazosin was started at 30 µg/kg/dose because of the parasympathetic overactivity. Doppler ultrasonography of the penile shaft showed a bilateral thickened, bulky, and edematous corpus cavernosa and no arterial flow due to venous congestion, suggesting ischemic (low-flow) priapism. Detumescence was not accomplished with saline irrigation and aspiration or with intracorporeal irrigation with phenylephrine. Thus, a distal T-shunt was done. We illustrate an interesting case of scorpion envenomation with delayed ischemic priapism.

Legionella-Induced Rhabdomyolysis and Acute Kidney Injury: A Case Report.

Legionella pneumonia is a severe form of pneumonia caused by the bacterium Legionella pneumophila. It often presents with atypical symptoms and can lead to complications such as rhabdomyolysis and acute kidney injury (AKI). Here, we report a case of Legionella pneumonia-induced rhabdomyolysis and AKI in a 32-year-old male. Laboratory investigations revealed elevated creatinine kinase levels and acute kidney injury. Further investigation confirmed Legionella pneumonia. The patient was promptly treated with appropriate antibiotics and supportive care, resulting in clinical improvement and resolution of rhabdomyolysis and AKI. This case underscores the importance of considering Legionella pneumonia as a potential cause of rhabdomyolysis and AKI, especially in patients with atypical pneumonia presentations.

1H and 31P Magnetic Resonance Spectroscopic Metabolomic Imaging: Assessing Mitogen-Activated Protein Kinase Inhibition in Melanoma.

The MAPK signaling pathway with BRAF mutations has been shown to drive the pathogenesis of 40-60% of melanomas. Inhibitors of this pathway's BRAF and MEK components are currently used to treat these malignancies. However, responses to these treatments are not always successful. Therefore, identifying noninvasive biomarkers to predict treatment responses is essential for personalized medicine in melanoma. Using noninvasive 1H magnetic resonance spectroscopy (1H MRS), we previously showed that BRAF inhibition reduces lactate and alanine tumor levels in the early stages of effective therapy and could be considered as metabolic imaging biomarkers for drug response. The present work demonstrates that these metabolic changes observed by 1H MRS and those assessed by 31P MRS are also found in preclinical human melanoma models treated with MEK inhibitors. Apart from 1H and 31P MRS, additional supporting in vitro biochemical analyses are described. Our results indicate significant early metabolic correlations with response levels to MEK inhibition in the melanoma models and are consistent with our previous study of BRAF inhibition. Given these results, our study supports the potential clinical utility of noninvasive MRS to objectively image metabolic biomarkers for the early prediction of melanoma's response to MEK inhibition.

Enhancing the properties of swelling soils with lime, fly ash, and expanded polystyrene -A review.

This paper discusses efforts made by past researchers to steady the expansive (problematic) soils using mechanical and chemical techniques - specifically with EPS beads, lime and fly ash. Administering swelling of problematic soils is critical for civil engineers to prevent structural distress. This paper summarizes studies on reduction of swelling potential using EPS, lime and fly ash individually. Chemical stabilization with lime and fly ash are conventional methods for expansive soil stabilization, with known merits and demerits. This paper explores the suitability of different materials under various conditions and stabilization mechanisms, including cation exchange, flocculation, and pozzolanic reactions. The degree of stabilization is influenced by various factors such as the type and amount of additives, soil mineralogy, curing temperature, moisture content during molding, and the presence of nano-silica, organic matter, and sulfates. Additionally, expanded polystyrene (EPS) improves structural integrity by compressing when surrounded clay swells, reducing overall swelling. Thus, EPS addresses limitations of chemicals by mechanical means. Combining EPS, lime and fly ash creates a customized system promoting efficient, long-lasting, cost-effective and eco-friendly soil stabilization. Chemicals address EPS limitations like poor stabilization. This paper benefits civil engineers seeking to control expansive soil swelling and prevent structural distress. It indicates potential of an EPS-lime-fly ash system and concludes by identifying research gaps for further work on such combinatorial stabilizer systems.

Escherichia coli infected scalp abscess with osteomyelitis following a cephalhaematoma in a neonate.

We discuss an illustrative case of Escherichia coli infected scalp abscess with osteomyelitis following a cephalhaematoma in a 19-day-old neonate. Cephalhaematoma is a common occurrence in neonates after prolonged labour, instrument-assisted, and traumatic deliveries and resolves spontaneously in the majority of cases. Infection may follow haematogenous dissemination or direct inoculation via a skin breach. Complications such as scalp abscess, sepsis, and osteomyelitis of the skull present with local signs, including increasing size, local erythema and tenderness, and fluctuant swelling.