AttGRU-HMSI: enhancing heart disease diagnosis using hybrid deep learning approach.

Heart disease is a major global cause of mortality and a major public health problem for a large number of individuals. A major issue raised by regular clinical data analysis is the recognition of cardiovascular illnesses, including heart attacks and coronary artery disease, even though early identification of heart disease can save many lives. Accurate forecasting and decision assistance may be achieved in an effective manner with machine learning (ML). Big Data, or the vast amounts of data generated by the health sector, may assist models used to make diagnostic choices by revealing hidden information or intricate patterns. This paper uses a hybrid deep learning algorithm to describe a large data analysis and visualization approach for heart disease detection. The proposed approach is intended for use with big data systems, such as Apache Hadoop. An extensive medical data collection is first subjected to an improved k-means clustering (IKC) method to remove outliers, and the remaining class distribution is then balanced using the synthetic minority over-sampling technique (SMOTE). The next step is to forecast the disease using a bio-inspired hybrid mutation-based swarm intelligence (HMSI) with an attention-based gated recurrent unit network (AttGRU) model after recursive feature elimination (RFE) has determined which features are most important. In our implementation, we compare four machine learning algorithms: SAE + ANN (sparse autoencoder + artificial neural network), LR (logistic regression), KNN (K-nearest neighbour), and naïve Bayes. The experiment results indicate that a 95.42% accuracy rate for the hybrid model's suggested heart disease prediction is attained, which effectively outperforms and overcomes the prescribed research gap in mentioned related work.

The Ribosome Hypothesis: Decoding Mood Disorder Complexity.

Several types of mood disorders lie along a continuum, with nebulous boundaries between them. Understanding the mechanisms that contribute to mood disorder complexity is critical for effective treatment. However, present treatments are largely centered around neurotransmission and receptor-based hypotheses, which, given the high instance of treatment resistance, fail to adequately explain the complexities of mood disorders. In this opinion piece, based on our recent results, we propose a ribosome hypothesis of mood disorders. We suggest that any hypothesis seeking to explain the diverse nature of mood disorders must incorporate infrastructure diversity that results in a wide range of effects. Ribosomes, with their mobility across neurites and complex composition, have the potential to become specialized during stress; thus, ribosome diversity and dysregulation are well suited to explaining mood disorder complexity. Here, we first establish a framework connecting ribosomes to the current state of knowledge associated with mood disorders. Then, we describe the potential mechanisms through which ribosomes could homeostatically regulate systems to manifest diverse mood disorder phenotypes and discuss approaches for substantiating the ribosome hypothesis. Investigating these mechanisms as therapeutic targets holds promise for transdiagnostic avenues targeting mood disorders.

Reprogramming of breast tumor-associated macrophages with modulation of arginine metabolism.

HER2+ breast tumors have abundant immune-suppressive cells, including M2-type tumor associated macrophages (TAMs). While TAMs consist of the immune-stimulatory M1-type and immune-suppressive M2-type, M1/M2-TAM ratio is reduced in immune-suppressive tumors, contributing to their immunotherapy refractoriness. M1 vs. M2-TAM formation depends on differential arginine metabolism, where M1-TAMs convert arginine to nitric oxide (NO) and M2-TAMs convert arginine to polyamines (PAs). We hypothesize that such distinct arginine metabolism in M1- vs M2-TAMs is attributed to different availability of BH4 (NO synthase cofactor) and that its replenishment would reprogram M2-TAMs to M1-TAMs. Recently, we reported that sepiapterin (SEP), the endogenous BH4 precursor, elevates the expression of M1-TAM markers within HER2+ tumors. Here, we show that SEP restores BH4 levels in M2-TAMs, which then redirects arginine metabolism to NO synthesis and converts M2-TAMs to M1-TAMs. The reprogrammed TAMs exhibit full-fledged capabilities of antigen presentation and induction of effector T cells to trigger immunogenic cell death of HER2+ cancer cells. This study substantiates the utility of SEP in metabolic shift of HER2+ breast tumor microenvironment as a novel immunotherapeutic strategy.

Design, Synthesis, ADME, and Anticancer Studies of Newer N-Aryl-5-(3,4,5-Trifluorophenyl)-1,3,4-Oxadiazol-2-Amines: An Insight into Experimental and Theoretical Investigations.

In continuance of our investigation into the anticancer activity of oxadiazoles, we report here the preparation of 10 new 1,3,4-oxadiazole analogues using the scaffold hopping technique. We have prepared the oxadiazoles having a common pharmacophoric structure (oxadiazole linked aryl nucleus) as seen in the reported anticancer agents IMC-038525 (tubulin inhibitor), IMC-094332 (tubulin inhibitor), and FATB (isosteric replacement of the S of thiadiazole with the O of oxadiazole). All of the oxadiazole analogues were predicted for their absorption, distribution, metabolism, and excretion (ADME) profiles and toxicity studies. All of the compounds were found to follow Lipinski's rule of 5 with a safe toxicity profile (Class IV compound) against immunotoxicity, mutagenicity, and toxicity. All of the compounds were synthesized and characterized using spectral data, followed by their anticancer activity tested in a single-dose assay at 10 µM as reported by the National Cancer Institute (NCI US) Protocol against nearly 59 cancer cell lines obtained from nine panels, including non-small-cell lung, ovarian, breast, central nervous system (CNS), colon, leukemia, prostate, and cancer melanoma. N-(2,4-Dimethylphenyl)-5-(3,4,5-trifluorophenyl)-1,3,4-oxadiazol-2-amine (6h) displayed significant anticancer activity against SNB-19, OVCAR-8, and NCI-H40 with percent growth inhibitions (PGIs) of 86.61, 85.26, and 75.99 and moderate anticancer activity against HOP-92, SNB-75, ACHN, NCI/ADR-RES, 786-O, A549/ATCC, HCT-116, MDA-MB-231, and SF-295 with PGIs of 67.55, 65.46, 59.09, 59.02, 57.88, 56.88, 56.53, 56.4, and 51.88, respectively. The compound 6h also registered better anticancer activity than Imatinib against CNS, ovarian, renal, breast, prostate, and melanoma cancers with average PGIs of 56.18, 40.41, 36.36, 27.61, 22.61, and 10.33, respectively. Molecular docking against tubulin, one of the appealing cancer targets, demonstrated an efficient binding within the binding site of combretastatin A4. The ligand 6h (docking score = -8.144 kcal/mol) interacted π-cationically with the residue Lys352 (with the oxadiazole ring). Furthermore, molecular dynamic (MD) simulation studies in complex with the tubulin-combretastatin A4 protein and ligand 6h were performed to examine the dynamic stability and conformational behavior.

A robust NIfTI image authentication framework to ensure reliable and safe diagnosis.

Advancements in digital medical imaging technologies have significantly impacted the healthcare system. It enables the diagnosis of various diseases through the interpretation of medical images. In addition, telemedicine, including teleradiology, has been a crucial impact on remote medical consultation, especially during the COVID-19 pandemic. However, with the increasing reliance on digital medical images comes the risk of digital media attacks that can compromise the authenticity and ownership of these images. Therefore, it is crucial to develop reliable and secure methods to authenticate these images that are in NIfTI image format. The proposed method in this research involves meticulously integrating a watermark into the slice of the NIfTI image. The Slantlet transform allows modification during insertion, while the Hessenberg matrix decomposition is applied to the LL subband, which retains the most energy of the image. The Affine transform scrambles the watermark before embedding it in the slice. The hybrid combination of these functions has outperformed previous methods, with good trade-offs between security, imperceptibility, and robustness. The performance measures used, such as NC, PSNR, SNR, and SSIM, indicate good results, with PSNR ranging from 60 to 61 dB, image quality index, and NC all close to one. Furthermore, the simulation results have been tested against image processing threats, demonstrating the effectiveness of this method in ensuring the authenticity and ownership of NIfTI images. Thus, the proposed method in this research provides a reliable and secure solution for the authentication of NIfTI images, which can have significant implications in the healthcare industry.

GC-MS based untargeted metabolomics reveals the metabolic response of earthworm (Eudrilus eugeniae) after chronic combinatorial exposure to three different pesticides.

In this study GC-MS-based untargeted metabolomics was used to identify the metabolic response of earthworm; Eudrilus eugeniae exposed to sub-lethal concentrations of chlorpyrifos-CHL, cypermethrin-CYP, Glyphosate-GLY, and Combined-C (all three pesticides) at the concentrations of 3, 6, and 12 mg/kg. Principal component analysis of the obtained datasets revealed a clear distinction between the control and treatment groups. The mean weight of the worms in the treated groups decreased significantly (p < 0.05). Among the identified metabolites, oleic acid (~ 93.47%), lysine (~ 92.20%), glutamic acid (~ 91.81%), leucine (~ 90.20%), asparagine (~ 94.20%), methionine (~ 92.27%), malic acid (~ 93.37%), turanose (~ 95.04%), maltose (~ 92.36%), cholesta-3,5-diene (~ 86.11%), galactose (~ 93.20%), cholesterol (~ 91.56%), tocopherol (~ 85.09%), decreased significantly (p < 0.05), whereas myoinositol (~ 83%) and isoleucine (78.09%) increased significantly (p < 0.05) upon exposure to the CHL, CYP, GLY, and C. Overall, the findings suggest that earthworms might be a new entry point for the pesticides into the food chain. The present study highlights that metabolomics can be a reliable approach to understand the effect of different xenobiotics including pesticides on the metabolic response of earthworms.

Optimizing the Construction of Outcome Measures for Impact Evaluations of Intimate Partner Violence Prevention Interventions.

Most impact evaluations of intimate partner violence (IPV) prevention interventions use binary measures of "any" versus "no" physical and/or sexual IPV as their primary outcome measure, missing opportunities to capture nuance. In this study, we reanalyzed secondary data from six randomized controlled trials conducted in low- and middle-income countries-Bandebereho (Rwanda), Becoming One (Uganda), Indashyikirwa (Rwanda), MAISHA CRT01, MAISHA CRT02 (Tanzania), Stepping Stones Creating Futures (South Africa), and Unite for a Better Life (Ethiopia), to assess how different conceptualizations and coding of IPV variables can influence interpretations of the impact of an intervention. We compared the standard outcome measures to new measures that reflect the severity and intensity of violence and whether interventions prevent new cases of IPV or reduce or stop ongoing violence. Results indicate that traditional binary indicators masked some of the more subtle intervention effects, and the use of the new indicators allowed for a better understanding of the impacts of the interventions. Conclusions on whether a program is perceived "to work" are highly influenced by the IPV outcomes that the investigators choose to report, and how they are measured and coded. Lack of attention to outcome choice and measurement could lead to prematurely abandoning strategies useful for violence reduction or missing essential insights into how programs may or may not affect IPV. While these results must be interpreted cautiously, given differences in intervention types, the underlying prevalence of violence, sociodemographic factors, sample sizes, and other contextual differences across the trial sites, they can help us move toward a new approach to reporting multiple outcomes that allow us to unpack the "impact" of an intervention by assessing intervention effect by the severity of violence and type of prevention, whether primary and secondary.

Novel 3D Flipwell system that models gut mucosal microenvironment for studying interactions between gut microbiota, epithelia and immunity.

Gut mucosa consists of stratified layers of microbes, semi-permeable mucus, epithelium and stroma abundant in immune cells. Although tightly regulated, interactions between gut commensals and immune cells play indispensable roles in homeostasis and cancer pathogenesis in the body. Thus, there is a critical need to develop a robust model for the gut mucosal microenvironment. Here, we report our novel co-culture utilizing 3D Flipwell system for establishing the stratified layers of discrete mucosal components. This method allows for analyzing synchronous effects of test stimuli on gut bacteria, mucus, epithelium and immune cells, as well as their crosstalks. In the present report, we tested the immuno-stimulatory effects of sepiapterin (SEP, the precursor of the cofactor of nitric oxide synthase (NOS)-BH4) on the gut mucosal community. We previously reported that SEP effectively reprogrammed tumor-associated macrophages and inhibited breast tumor cell growth. In our co-cultures, SEP largely promoted mucus integrity, bacterial binding, and M1-like polarization of macrophages. Conversely, these phenomena were absent in control-treated cultures. Our results demonstrate that this novel co-culture may serve as a robust in vitro system to recapitulate the effects of pharmacological agents on the gut mucosal microenvironment, and could potentially be expanded to test the effects outside the gut.

"Belief of Splitting of Clitoris": A Case Report of an Adolescent Girl with Body Dysmorphic Disorder.

Body dysmorphic disorder (BDD) was first described centuries ago, but it is still unknown to many clinicians. Although onset of body dysmorphic disorder occurs in adolescent age, BDD has received very little attention in adolescent psychiatry literature. Here, we are discussing a case report of 14-year girl suffering from belief of splitting of her clitoris. She would watch it in mirror multiple times and feel disgust due to her malformed genital part. She would often become very distressed and force her family member for genital surgery. She was taken to gynaecologist. She was referred and treated successfully with the use of SSRI and cognitive behaviour therapy.

Clinical Profile of Pediatric Neurology Disorders: A Study From a Semi-Urban Medical College in Northwestern India.

INTRODUCTION: Neurological disorders are characterized by dysfunction in any part of the nervous system and are a major cause of disability among children and adolescents in developing countries, just as it is in India. There is a lack of information on the prevalence of neurological disorders in developing countries due to the lack of quality health information and a lack of awareness of these disorders. This local study aims to provide an understanding of the profile and characteristics of neurological disorders in children that will aid in the development and implementation of preventive healthcare strategies. METHODS: A retrospective observational study was conducted in the Department of Pediatrics. All pediatric neurology patients' data were retrieved from January 2020 to December 2020. RESULTS: Of the 12,782 children seen in the pediatric outpatient department (OPD), 133 (1.04%) had neurological disorders and about 65% were male. Childhood seizures 92 (69%) and developmental delay 13 (9.7%) were the most common neurological conditions, although there was an overlap of the conditions. CONCLUSION: This study provides some valuable information about common neurological disorders in children. Seizures, cerebral palsy, and developmental delay were the most common neurological disorders in children.

Identification of Suitable Reference Genes for Lowlanders Exposed to High Altitude and Ladakhi Highlanders.

Sharma, Vandana, Rajeev Varshney, and Niroj Kumar Sethy. Identification of suitable reference genes for lowlanders exposed to high altitude and Ladakhi highlanders. High Alt Med Biol. 23:319-329, 2022. Background: Identifying a stable and reliable reference gene (RG) is a prerequisite for the unbiased and unambiguous analysis of gene expression data. It has become evident that conventionally used housekeeping genes such as beta-actin (ACTB), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and peptidylprolyl Isomerase A (PPIA) exhibit varied expression patterns under hypoxia. Hence, the identification of stable RGs for humans exposed to hypobaric hypoxia can enhance the accuracy of gene expression studies by limiting the negligent use of random housekeeping genes. Methods: Using TaqMan™ array-based quantitative real-time quantitative polymerase chain reaction, we evaluated the expression of 32 commonly used human RGs among lowlanders at Delhi (altitude 216 m, SL), lowlanders at Leh (altitude 3,524 m) after 1 day (HA-D1) and 7 days (HA-D7), as well as indigenous Ladakhi highlanders at the same altitude. The expression stability of the RGs was evaluated using geNorm, NormFinder, BestKeeper, Delta CT method, and RefFinder algorithms. Results: Our studies identify TATA-box binding protein (TBP), proteasome 26S subunit, ATPase 4 (PSMC4), and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ) as the most stable human RGs for normalizing human gene expression under hypobaric hypoxia. In addition, we report the combination of TBP and cyclin-dependent kinase inhibitor 1B (CDKN1B) as the most stable RG for studying lowlander gene expression during high-altitude exposure. In contrast, RPL30 and 18S exhibited maximum variation across study groups and were identified as the least stable RGs.

Human adaptation to high altitude: a review of convergence between genomic and proteomic signatures.

Both genomics- and proteomics-based investigations have identified several essential genes, proteins, and pathways that may facilitate human adaptive genotype/phenotype in a population-specific manner. This comprehensive review provides an up-to-date list of genes and proteins identified for human adaptive responses to high altitudes. Genomics studies for indigenous high-altitude populations like Tibetans, Andeans, Ethiopians, and Sherpas have identified 169 genes under positive natural selection. Similarly, global proteomics studies have identified 258 proteins (± 1.2-fold or more) for Tibetan, Sherpa, and Ladakhi highlanders. The primary biological processes identified for genetic signatures include hypoxia-inducible factor (HIF)-mediated oxygen sensing, angiogenesis, and erythropoiesis. In contrast, major biological processes identified for proteomics signatures include 14-3-3 mediated sirtuin signaling, integrin-linked kinase (ILK), phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT), and integrin signaling. Comparing genetic and protein signatures, we identified 7 common genes/proteins (HBB/hemoglobin subunit beta, TF/serotransferrin, ANGPTL4/angiopoietin-related protein 4, CDC42/cell division control protein 42 homolog, GC/vitamin D-binding protein, IGFBP1/insulin-like growth factor-binding protein 1, and IGFBP2/insulin-like growth factor-binding protein 2) involved in crucial molecular functions like IGF-1 signaling, LXR/RXR activation, ferroptosis signaling, iron homeostasis signaling and regulation of cell cycle. Our combined multi-omics analysis identifies common molecular targets and pathways for human adaptation to high altitude. These observations further corroborate convergent positive selection of hypoxia-responsive molecular pathways in humans and advocate using multi-omics techniques for deciphering human adaptive responses to high altitude.

Displacement, Polygyny, Romantic Jealousy, and Intimate Partner Violence: A Qualitative Study among Somali Refugees in Ethiopia.

Romantic jealousy is a well-known relational driver of intimate partner violence (IPV), but is under-studied among displaced and polygynous populations. This study aimed to explore factors that elicit jealousy among Somali refugees in the Bokolmayo Refugee camp in Ethiopia, and the pathways leading from jealousy to IPV against women and men, to inform interventions. We conducted an exploratory, thematic analysis of 30 in-depth interviews with both women and men who were Somali refugees, as well as elders and religious leaders, organizational and service providers, policy makers, and host community members. We found that jealousy experienced by women was elicited by an unequal distribution of money and affection between co-wives, which was exacerbated by displacement-related economic hardship, and women in monogamous partnerships suspecting their husband of having other relationships. The jealousy experienced by men was elicited by their wives' increased financial independence and interactions with other men when working outside of the home, which became more common because of displacement-related economic hardship and relaxed patriarchal gender norms. IPV interventions should address jealousy and controlling behaviors in all relationship types. Addressing conflict and relationship dynamics in polygynous households and in humanitarian settings may require specialized content, acknowledging the complex interactions and resource allocation between co-wives. Gender-transformative interventions that move away from masculinities that are built on the provider role and the introduction of alternative masculinities could also be effective in reducing IPV in this and other similar contexts.

Interferon-gamma and perforin-positive T cells in acquired aplastic anemia: implication in therapeutic response.

Acquired aplastic anemia (aAA) is an autoimmune disease, characterized by infiltration of T lymphocytes in the bone marrow with destruction of hematopoietic stem cells by the effector cells. Interferon-gamma (IFN-γ) and perforin are important mediators of cell destruction. In this flow cytometry-based study, we have investigated the percentage of intracellular IFN-γ+ and perforin+ CD5+ T cells in peripheral blood of newly diagnosed aAA patients before and after immunosuppressive therapy (IST). Patients were categorized as per standard disease severity and response to IST. The median percentage of IFN-γ+ and perforin+ CD5+ T cells was higher in untreated patients compared to healthy controls. The percentage of these cells was also increased in untreated severe and very severe aplastic anemia when compared with non-severe aplastic anemia patients. In patients before and after IST the median percentage of T cells producing IFN-γ and perforin was elevated in non-responders as compared to partial plus complete responders. The higher percentage of IFN-γ+ and perforin+ CD5+ T cells may be useful as an early diagnostic marker for aberrant activation of immune system and predict poor response to IST in aAA patients, who will benefit from alternative therapy.

Predictors of Discordance and Concordance in Reporting of Intimate Partner Violence: Evidence From a Large Sample of Rural Ethiopian Couples.

Intimate partner violence (IPV) is a major worldwide health challenge, and addressing this challenge requires high-quality data. This analysis uses a large-scale survey of 5033 households in rural Ethiopia in which both men and women were surveyed about past-year IPV in order to quantify the degree of discordance, including both husband only reporting and wife only reporting, for multiple forms of IPV (emotional, physical, and sexual). In addition, logistic regression is employed to analyze the effects of demographic characteristics and individual norms and behaviors on the probability of discordant reporting. The results suggest that almost half of households (44%) are characterized by discordant reporting in at least one dimension of IPV. Given the high level of discordance, 61.4% of households report any physical and/or sexual IPV using the household-level measure, compared to a rate of 41.9% from the women's data only. In addition, men who report more gender-equitable attitudes and behaviors (failing to concur with justifications for IPV, reporting higher support for gender equitable norms, and reporting a higher level of female engagement in decision-making and intrahousehold task-sharing) are more likely to be members of wife only reporting households: that is, they are less likely to report perpetration of IPV. Women who report more gender-equitable attitudes and behaviors, by contrast, are more likely to be members of husband only reporting households.

Drosophila ecdysone receptor activity-based ex vivo assay to assess the endocrine disruption potential of environmental chemicals.

Insect pollinators, critical for both agricultural output and the ecosystem, are declining at an alarming levels partly due to human-made chemicals. Majority of environmental chemicals hamper the endocrine function and studies on the same in insects remain neglected. Here, we report a Drosophila-based ex vivo assay system that employs a reproductive tissue from transgenic males carrying a reporter gene (lacZ) downstream of ecdysone receptor response element (EcRE) and permits the evaluation of chemical-mediated activity modulation of all three isoforms of ecdysone receptor, which are critical for male fertility. We show agonistic [plasticizers, cypermethrin, atrazine, methyl parathion, imidacloprid, cadmium chloride, mercuric chloride or 3-(4-methylbenzylidene) camphor] or antagonistic (apigenin, tributyltin chloride) effects or lack of effect thereof (rutin hydrate, dichlorvos, lead acetate, parabens) for seven different classes of environmental chemicals on ecdysone receptor activity reflecting the specificity and sensitivity of the developed ex vivo assay. Exposure to a few of these chemicals in vivo hampers the fertility of Drosophila males, thus linking the observed endocrine disruption to a quantifiable reproductive phenotype. The developed ex vivo assay offers a quick Drosophila-based screening tool for throughput monitoring of environmental chemicals for their ability to hamper the endocrine function of insect pollinators and other invertebrates.