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Background: Craniopharyngiomas are rare benign tumors located in the sellar and suprasellar region, with an incidence of 0.5–2 cases per million as reported in Western studies. Post-treatment, including surgery and/or radiotherapy, many patients develop significant obesity, primarily due to hypothalamic damage and associated complications such as hypopituitarism. In the South Asian population, genetic predisposition to obesity at lower BMIs, coupled with a carbohydrate-rich diet, may exacerbate obesity in craniopharyngioma patients, presenting a unique challenge. Methods: This submission is a commentary based on a comprehensive literature review. The authors conducted the review using PubMed to focus on English-language articles covering hypothalamic obesity, craniopharyngioma and obesity in the South Asian population from 1939 to the present. Results: The literature review revealed that 50–60 % of patients treated for craniopharyngioma develop obesity, predominantly linked to hypothalamic damage, although these data are mainly derived from Western studies. Hypopituitarism was frequently observed, further contributing to the obesity. Despite a caloric intake appropriate for the age and gender, these patients exhibited reduced physical activity as measured by wrist accelerometers. Patients with hypothalamic obesity due to craniopharyngioma are at risk for metabolic syndrome and cardiovascular morbidity. Additionally, visual impairment was common, leading to a decreased quality of life. The South Asian population, genetically predisposed to visceral obesity and a carbohydrate-rich diet, may display a distinct phenotype. Although multiple treatment modalities have been tried, there is no definite treatment modality available to counteract this condition at present. Conclusion: South Asian phenotype of craniopharyngioma-related obesity is characterized by significant metabolic and hormonal dysregulation, influenced by both dietary and genetic factors. Nevertheless, there may be a lot to be still understood about this devastating, rapid, relentless hypothalamic obesity syndrome. Also, a higher morbidity rate within this population, underscores the need for further research to develop targeted interventions.

Substantial advancements have been made in applying fractional calculus to understanding the epidemiology of viral diseases. However, it remains troubling that over 2,000,000 children, particularly those under the age of 5 and elderly individuals over 65, succumb to pneumonia annually in developing nations. This paper uses a deterministic SVEIR (susceptible, vaccinated, exposed, infected, and recovered) model to investigate pneumonia disease dynamics from a mathematical perspective. The governing model has been generalized from Caputo fractional derivatives, and the generalized Euler’s method has been used to calculate the approximate solution of the governing model. The dynamical systems theory examines the model’s stability analysis, basic reproduction number, and equilibrium points. The linearization method for spatial equilibrium and the Lyapunov functional method demonstrate that the model is locally asymptotic stable for disease-free equilibrium. Graphical results are showcased through MATLAB21 to illustrate the resolution of the problem. The research findings suggest that the disease will eventually disappear from the population if vaccination coverage rises over the necessary vaccination threshold. According to sensitivity analysis, the most sensitive factors are the transmission rate and the pace at which exposed individuals become contagious. According to the study, we must strengthen treatment effectiveness to prevent disease spreading.

In this paper, we delve into the realm of mathematical modeling as a powerful theoretical tool to understand essential aspects of medical-biological phenomena. This study focuses on developing a mathematical model incorporating the incomplete I-function (IIF) and estimating glucose supply in the human bloodstream. The results of our investigations are far-reaching, revealing many exciting scenarios across the various parameters under investigation. These results are not only practical but can also play an essential role in the contexts of medical and biological fields.

In order to understand and manage infectious illnesses, mathematical models are extremely important. They support decision making by researchers and public health workers in predicting the spread of diseases, evaluate the results of interventions, and gathering data. This study considers a fractionalized hepatitis B virus (HBV) infection model with cell cure. The Atangana Baleanu fractional model was initially established for the epidemic issue. This paper analyses the fractional form that makes up the HBV infection model utilizing the numerical methodology, homotopy analysis transform method (HATM). The suggested technique is created with the use of the homotopy analysis method (HAM), the homotopy polynomial, and the Laplace transformation. Additionally, the existence and uniqueness of the solution are considered, and stability analysis is given by the fixed-point theory (FPT) of the HBV model. Through MATLAB21, the obtained solutions are graphically simulated. The graphical solutions demonstrated that the peak of viral propagation is reduced when a fractional-order derivative is included to the model, and cell damage is minimized by starting treatment early on; however, the disease takes longer to be completely eradicated. The outcomes will be beneficial in the medical field. The fractional model lets us draw significant information essential for predicting disease outcomes and planning appropriate clinical management for patients.

Background: Skeletal fluorosis is a metabolic bone disease that results from the chronic ingestion of fluoride. Although there are national programs in place to raise awareness and curtail this disease condition, skeletal fluorosis continues to cause crippling deformities in areas where it continues to be endemic. Method: ology: An observational study was undertaken at a university-affiliated teaching hospital in southern India. Clinical, biochemical features and densitometric variables including bone mineral density (BMD) and trabecular bone score (TBS) were assessed. Results: All patients (n = 9) hailed from fluorosis-endemic Indian states and the source of drinking water was from a bore-well in all cases. The mean (±SD) age and BMI were 45.6(±11.0) years and 25.6 (±8.4) kg/m2 respectively. Dental mottling was present in five subjects. Five subjects each had vitamin D deficiency with osteomalacia. The mean (±SD) urine fluoride was 2.9(±1.4) ppm. The bone mineral density showed a sclerotic pattern, with the mean (±SD) TBS being 1.607 (±0.160). All patients were initiated on calcium and cholecalciferol supplements and those with osteomalacia were treated with calcitriol. Conclusion: While fluorosis continues to be a challenge in endemic regions, the presence of osteomalacia proves to be a treatable component of the disease condition. There seems to be an unmet need for more aggressive defluoridation techniques and the provision of safe drinking water in susceptible individuals.

Rotavirus is the most common cause of acute gastroenteritis in infants and children worldwide. The functional correlation of B- and T-cells to long-lasting immunity against rotavirus infection in the literature is limited. In this work, a series of computational immuno-informatics approaches were applied and identified 28 linear B-cells, 26 conformational B-cell, 44 TC cell and 40 TH cell binding epitopes for structural and non-structural proteins of rotavirus. Further selection of putative B and T cell epitopes in the multi-epitope vaccine construct was carried out based on immunogenicity, conservancy, allergenicity and the helical content of predicted epitopes. An in-silico vaccine constructs was developed using an N-terminal adjuvant (RGD motif) followed by TC and TH cell epitopes and B-cell epitope with an appropriate linker. Multi-threading models of multi-epitope vaccine construct with B- and T-cell epitopes were generated and molecular dynamics simulation was performed to determine the stability of designed vaccine. Codon optimized multi-epitope vaccine antigens was expressed and affinity purified using the E. coli expression system. Further the T cell epitope presentation assay using the recombinant multi-epitope constructs and the T cell epitope predicted and identified in this study have not been investigated. Multi-epitope vaccine construct encompassing predicted B- and T-cell epitopes may help to generate long-term immune responses against rotavirus. The computational findings reported in this study may provide information in developing epitope-based vaccine and diagnostic assay for rotavirus-led diarrhea in children's.

Liposarcoma, the most common soft tissue sarcoma, is a group of fat cell mesenchymal tumors with different histological subtypes. The dysregulation of long non-coding RNAs (lncRNAs) has been observed in human cancers including a few studies in sarcoma. However, the global transcriptome analysis and potential role of lncRNAs remain unexplored in liposarcoma. The present investigation uncovers the transcriptomic profile of liposarcoma by RNA sequencing to gain insight into the global transcriptional changes in liposarcoma. Our RNA sequencing analysis has identified that many oncogenic lncRNAs are differentially expressed in different subtypes of liposarcoma including MALAT1, PVT1, SNHG15, LINC00152, and MIR210HG. Importantly, we identified a highly overexpressed, unannotated, and novel lncRNA in dedifferentiated liposarcomas. We have named it TODL, transcript overexpressed in dedifferentiated liposarcoma. TODL lncRNA displayed significantly higher expression in dedifferentiated liposarcoma cell lines and patient samples. Interestingly, functional studies revealed that TODL lncRNA has an oncogenic function in liposarcoma cells by regulating proliferation, cell cycle, apoptosis, differentiation, and tumorigenesis in the murine model. Silencing of TODL lncRNA highlighted the enrichment of several key oncogenic signaling pathways including cell cycle, transcriptional misregulation, FOXM1 network, p53 signaling, PLK1 signaling, FoxO, and signaling Aurora signaling pathways. RNA pull-down assay revealed the binding of TODL lncRNA with FOXM1, an oncogenic transcription factor, and the key regulator of the cell cycle. Silencing of TODL lncRNA also induces adipogenesis in dedifferentiated liposarcomas. Altogether, our finding indicates that TODL could be utilized as a novel, specific diagnostic biomarker, and a pharmacological target for therapeutic development in controlling aggressive and metastatic dedifferentiated liposarcomas., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

CCAAT/enhancer binding protein ε (CEBPE) is an essential transcription factor for granulocytic differentiation. Mutations of CEBPE occur in individuals with neutrophil-specific granule deficiency (SGD), which is characterized by defects in neutrophil maturation. Cebpe -knockout mice also exhibit defects in terminal differentiation of granulocytes, a phenotype reminiscent of SGD. Analysis of DNase I hypersensitive sites sequencing data revealed an open chromatin region 6 kb downstream of the transcriptional start site of Cebpe in murine myeloid cells. We identified an interaction between this +6-kb region and the core promoter of Cebpe using circular chromosome conformation capture sequencing (4C-seq). To understand the role of this putative enhancer in transcriptional regulation of Cebpe , we targeted it using catalytically inactive Cas9 fused to Krüppel-associated box (KRAB) domain and observed a significant downregulation of transcript and protein levels of CEBPE in cells expressing guide RNA targeting the +6-kb region. To further investigate the role of this novel enhancer further in myelopoiesis, we generated mice with deletion of this region using CRISPR/Cas9 technology. Germline deletion of the +6-kb enhancer resulted in reduced levels of CEBPE and its target genes and caused a severe block in granulocytic differentiation. We also identified binding of CEBPA and CEBPE to the +6-kb enhancer, which suggests their role in regulating the expression of Cebpe In summary, we have identified a novel enhancer crucial for regulating expression of Cebpe and required for normal granulocytic differentiation., (© 2019 by The American Society of Hematology.)

The neonatal heart is a very useful tool for the study of biochemical pathways and properties of cardiomyocytes and as it has the potential to regenerate for a brief period of time from birth; it is also useful to study cardiac regeneration. However, as the heart matures, this proficiency for regeneration is reduced. This regenerative potential may be influenced by the microenvironment of the heart in the early stages of postnatal development and therefore, cell cultures derived at this stage may contain functional cardiomyocytes and progenitor cells. The aim of this study was to identify key steps in the isolation and culture of such early stage-neonatal mouse hearts to allow maximum migration of cardiomyocytes from the explant and their maintenance as functional, long term cultures. Explant cultures of mouse ventricles preserved 3-dimensional structure and generated migrating layers of cardiomyocytes that expressed alpha sarcomeric actin which could be further sub-cultured by enzymatic dissociation. Western blotting demonstrated expression of c-KIT, GATA4, alpha sarcomeric actin and connexin43 proteins after 20 days of explant culture. ACTA1, GATA4, and CX43 continued to express in five weeks old explant cultures while the c-KIT protein was expressed up to two passages during sub-culture. Real time PCR and SQRT PCR also demonstrated gene expression of cardiomyocyte markers in long term cultures. Migrating cells from the explants assembled into contracting spheroids after subculture and expressed the c-KIT protein. Progenitor markers CD44, CD90, and extracellular proteins, periostin and vimentin demonstrated the preservation of cellular heterogeneity in such cultures. Supplementation with Hydrocortisone maintained a cardioprotective environment and reduced the non-myocyte population. This is an optimized and efficient method for the generation of neonatal heart cultures that is not labor intensive and does not require supplementation with cytokines., (Copyright © 2015 Elsevier GmbH. All rights reserved.)