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Melanoma is a fatal type of skin cancer; the fury spread results in a high fatality rate when the malignancy is not treated at an initial stage. The patients’ lives can be saved by accurately detecting skin cancer at an initial stage. A quick and precise diagnosis might help increase the patient’s survival rate. It necessitates the development of a computer-assisted diagnostic support system. This research proposes a novel deep transfer learning model for melanoma classification using MobileNetV2. The MobileNetV2 is a deep convolutional neural network that classifies the sample skin lesions as malignant or benign. The performance of the proposed deep learning model is evaluated using the ISIC 2020 dataset. The dataset contains less than 2% malignant samples, raising the class imbalance. Various data augmentation techniques were applied to tackle the class imbalance issue and add diversity to the dataset. The experimental results demonstrate that the proposed deep learning technique outperforms state-of-the-art deep learning techniques in terms of accuracy and computational cost.

Cancer is one of the most common malignancies and the leading cause of death worldwide. As a member of the transmembrane emp24 domain (Tmed)/p24 family of proteins, TMED2 expression variations have been documented earlier in only a few subtypes of human cancers, and the multi-omics profiling of TMED2 as a shared biomarker in different other subtypes of human cancers remains to be uncovered. In the current study, TMED2 multi-omics analysis in 24 major subtypes of human cancer was performed using different authentic online databases and bioinformatics analysis including UALCAN, Kaplan-Meier (KM) plotter, Human Protein Atlas (HPA), GENT2, MEXPRESS, cBioportal, STRING, DAVID, TIMER, and CTD. In general, the TMED2 expression in 24 major subtypes of human cancers was higher relative to normal controls and was also strongly associated with the lower overall survival (OS) and relapse-free survival (RFS) duration of CESC, ESCA, HNSC, KIRC, LIHC, and LUAD patients. This implies that TMED2 plays a significant role in the development and progression of these cancers. Furthermore, the TMED2 overexpression was also correlated with different clinicopathological features of CESC, ESCA, HNSC, KIRC, LIHC, and LUAD patients. TMED2-associated genes network was involved in 3 diverse pathways, and finally, few stronger correlations were also explored between TMED2 expression and its promoter methylation level, genetic alterations, and CD8+ T immune cells level. In conclusion, via this in silico study, we have elucidated that TMED2 can serve as a shared diagnostic and prognostic biomarker in CESC, ESCA, HNSC, KIRC, LIHC, and LUAD patients of different clinicopathological features but, further in vitro and in vivo research should be carried out to confirm these findings.

The current study was designed to synthesize derivatives of succinimide and compare their biological potency in anticholinesterase, alpha-glucosidase inhibition, and antioxidant assays. In this research, two succinimide derivatives including ( )-1-(2,5-dioxo-1-phenylpyrrolidin-3-yl) cyclohexanecarbaldehyde (Compound ) and ( )-2-(( )-2,5-dioxo-1-phenylpyrrolidin-3-yl)-2-phenylpropanal (Compound ) were synthesized using Michael addition. Both the compounds, ie, and were evaluated for in-vitro acetylcholinesterase (AChE), butyrylctcholinesterase (BChE), antioxidant, and α-glucosidase inhibitory potentials. Furthermore, molecular docking was performed using Molecular Operating Environment (MOE) to explore the binding mode of both the compounds against different enzymes. Lineweaver-Burk plots of enzyme inhibitions representing the reciprocal of initial enzyme velocity versus the reciprocal of substrate concentration in the presence of synthesized compounds and standard drugs were constructed using Michaelis-Menten kinetics. In AChE inhibitory assay, compounds and exhibited IC of 343.45 and 422.98 µM, respectively, against AChE enzyme. Similarly, both the compounds showed IC of 276.86 and 357.91 µM, respectively, against BChE enzyme. Compounds and displayed IC of 157.71 and 471.79 µM against α-glucosidase enzyme, respectively. In a similar pattern, compound exhibited to be more potent as compared to compound in all the three antioxidant assays. Compound exhibited IC values of 297.98, 332.94, and 825.92 µM against DPPH, ABTS, and H O free radicals, respectively. Molecular docking showed a triple fold in the AChE and BChE activity for compound compared with compound . The compound 1 revealed good interaction against both the AChE and BChE enzymes which revealed the high potency of this compound compared to compound  . Both succinimide derivatives exhibited considerable inhibitory activities against cholinesterases and α-glucosidase enzymes. Of these two, compound revealed to be more potent against all the in-vitro targets which was supported by molecular docking with the lowest binding energies. Moreover, compound also proved to have antiradical properties.

Study of monogenic forms of obesity has demonstrated the pivotal role of the central leptin–melanocortin pathway in controlling energy balance, appetite and body weight 1 . The majority of loss-of-function mutations (mostly recessive or co-dominant) have been identified in genes that are directly involved in leptin–melanocortin signaling. These genes, however, only explain obesity in <5% of cases, predominantly from outbred populations 2 . We previously showed that, in a consanguineous population in Pakistan, recessive mutations in known obesity-related genes explain ~30% of cases with severe obesity 3 , 4 – 5 . These data suggested that new monogenic forms of obesity could also be identified in this population. Here we identify and functionally characterize homozygous mutations in the ADCY3 gene encoding adenylate cyclase 3 in children with severe obesity from consanguineous Pakistani families, as well as compound heterozygous mutations in a severely obese child of European-American descent. These findings highlight ADCY3 as an important mediator of energy homeostasis and an attractive pharmacological target in the treatment of obesity. Genetic analysis of children with severe obesity identifies mutations in the ADCY3 gene (encoding adenylate cyclase 3). These variants are rare in public databases and affect the functional activity of the protein, indicating that ADCY3 is a potential pharmacological target for obesity treatment.

Alzheimer's disease (AD) is a neurodegenerative illness described predominantly by dementia. Even though Alzheimer's disease has been known for over a century, its origin remains a mystery, and researchers are exploring many therapy options, including the cholinesterase technique. A decreased acetylcholine ACh neurotransmitter level is believed to be among the important factors in the progression of Alzheimer's disease. In continuation of synthesizing potential anti-Alzheimer agents and known appreciative pharmacological potential of amide-containing compounds, this study presents the synthesis of two novel amide-based transition metal zinc (II) complexes, AAZ7 and AAZ8, attached with a heterocyclic pyridine ring, which was synthesized and characterized by Fourier transform infrared spectroscopy (FT-IR), elemental analysis, H_NMR, and C_NMR. FT-IR spectroscopic records showed the development of bidentate ligand as Δν value was decreased in both complexes when compared with the free ligand. Both of the synthesized complexes were analyzed for acetylcholinesterase and butyrylcholinesterase inhibitory potential along with the antioxidizing activity. Importantly, the complex of AAZ8 exhibited more potent activity giving IC values of 14 µg/mL and 18µg/mL as AChE and BChE cholinesterase inhibitors, respectively, when compared with standard positive control galantamine. Interestingly, AAZ8 also displayed promising antioxidant potential by showing IC values of 35 µg/mL for DPPH and 29 µg/mL for ABTS in comparison with positive control ascorbic acid. Herein, we report two new amide carboxylate zinc (II) complexes which were potentially analyzed for various biological applications like acetylcholinesterase (AChE), butyrylcholinesterase (BChE) inhibitory potentials, and antioxidant assays. Computational docking studies also simulated results to understand the interactions. Additionally, thermodynamic parameters utilizing molecular dynamic simulation were performed to determine the ligand protein stability and flexibility that supported the results. Studies have shown that these compounds have the potential to be good anti-Alzheimer candidates for future studies due to inhibition of cholinesterase enzymes and display of free radical scavenging potential against DPPH as well as ABTS free radicals.

Introduction: In light of the increased demand for reliable cancer-associated biomarkers and ANLN oncogenic potential, the present study aimed to investigate ANLN's role in 24 human cancers. Methods: The UALCAN, Kaplan--Meier (KM) plotter, TNM Plot, GENT2, GEPIA, HPA, cBioPortal, STRING, Enrichr, TIMER, Cytoscape, DAVID, MuTarget, and CTD online databases and bioinformatic tools were used in this study. Results: In three of the cancers analyzed, ANLN expression was downregulated in tumor tissue, while it was overexpressed in the 21 other types of tumor tissue relative to controls. In CESC, ESCA, HNSC, and KIRC patients, ANLN overexpression was correlated with shorter overall survival, relapse-free survival, and metastasis. This suggests that ANLN is significantly involved in the development and progression of these four cancers. Further expression analysis revealed upregulation of ANLN in CESC, ESCA, HNSC, and KIRC patients with different clinical characteristics, regardless of the heterogeneity barrier. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that ANLN-associated genes were coexpressed with ANLN and were included in diverse BP, MF, and KEGG terms. Moreover, some interesting correlations were also documented between ANLN expression and its promoter-methylation level, genetic alterations, other mutant genes, and CD[8.sup.+] T- and CD[4.sup.+] T-cell infiltration. Moreover, we also identified ANLN-associated transcription factors, miRNAs, and chemotherapeutic drugs. Conclusion: This pan-cancer study revealed the novel diagnostic and prognostic role of ANLN across four cancers, regardless of heterogeneity. Keywords: cancer, ANLN, diagnostic, prognostic, biomarker

In the current study, unexplored type IV halogen⋯halogen interaction was thoroughly elucidated, for the first time, and compared to the well-established types I–III interactions by means of the second-order Møller–Plesset (MP2) method. For this aim, the halobenzene⋯halobenzene homodimers (where halogen = Cl, Br, and I) were designed into four different types, parodying the considered interactions. From the energetic perspective, the preference of scouted homodimers was ascribed to type II interactions (i.e., highest binding energy), whereas the lowest binding energies were discerned in type III interactions. Generally, binding energies of the studied interactions were observed to decline with the decrease in the σ-hole size in the order, C6H5I⋯IC6H5 > C6H5Br⋯BrC6H5 > C6H5Cl⋯ClC6H5 homodimers and the reverse was noticed in the case of type IV interactions. Such peculiar observations were relevant to the ample contributions of negative-belt⋯negative-belt interactions within the C6H5Cl⋯ClC6H5 homodimer. Further, type IV torsional trans → cis interconversion of C6H5X⋯XC6H5 homodimers was investigated to quantify the π⋯π contributions into the total binding energies. Evidently, the energetic features illustrated the amelioration of the considered homodimers (i.e., more negative binding energy) along the prolonged scope of torsional trans → cis interconversion. In turn, these findings outlined the efficiency of the cis configuration over the trans analog. Generally, symmetry-adapted perturbation theory-based energy decomposition analysis (SAPT-EDA) demonstrated the predominance of all the scouted homodimers by the dispersion forces. The obtained results would be beneficial for the omnipresent studies relevant to the applications of halogen bonds in the fields of materials science and crystal engineering.

Background Coronary artery disease (CAD) significantly contributes to morbidity and mortality globally, particularly in individuals with diabetes mellitus, who are at a heightened risk for cardiovascular complications. The complexity of coronary lesions and diffuse atherosclerosis in diabetic patients presents challenges in their treatment and prognosis. Coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) are primary revascularization strategies for managing multi-vessel CAD in diabetic patients. Despite advancements in both techniques, their relative efficacy and safety remain debated, especially in the diabetic population. Objective This multicenter study aims to compare the long-term outcomes of CABG and PCI in diabetic patients with multi-vessel CAD. The primary endpoints include overall survival and the incidence of major adverse cardiac events (MACE). Secondary endpoints encompass revascularization success and procedural complication rates. Methods This retrospective cohort study was conducted across multiple centers, and the research spanned from January 2020 to December 2021. A total of 500 diabetic patients with multi-vessel CAD were included: 250 underwent CABG and 250 received PCI. Data were collected from electronic health records, capturing demographic details, clinical characteristics, procedural specifics, and follow-up outcomes over 24 months. Statistical analyses were performed using SPSS version 25 (IBM Corp., Armonk, NY), including Kaplan-Meier survival curves and Cox proportional hazards regression. Results The mean age of participants was 60.3 ± 10.5 years, with males constituting 52% of each group. Both groups achieved a high revascularization success rate of 90%. The CABG group treated more vessels on average (2.3 ± 0.7) compared to the PCI group (1.9 ± 0.8) (p < 0.001). Survival rates were higher in the CABG group (88%) compared to the PCI group (82%) (p = 0.08). MACE incidence was lower in the CABG group (22%) compared to the PCI group (28%) (p = 0.10). Procedural complications were marginally higher in the CABG group (16%) than in the PCI group (14%) (p = 0.60). Conclusion Both CABG and PCI are effective revascularization options for diabetic patients with multi-vessel CAD. CABG may offer a slight advantage in long-term survival and reduction in MACE, although the differences were not statistically significant. These findings suggest that individualized treatment strategies should be considered to optimize patient outcomes.

Anemia has been a growing concern for the pediatric population in sub-Saharan Africa. Emerging risk factors for anemia under five years of age in low-income countries are multifaceted, including infectious diseases, nutritional deficiencies, hidden hunger, and various economic determinants, and its health burdens include childhood stunting and reduced cognitive function diminished school performance in children. However, the influence of climatic factors, particularly ambient temperatures, on pediatric anemia remains understudied. In this population-based study, we assess the region-specific associations between pediatric anemia and ambient temperatures in 43 countries in Africa from 2000 to 2019. Using generalized linear regression models (upon adjusting for covariates), we found that the risk of temperatures on pediatric anemia varies across four African regions, whereby the Central and Southern African regions have a positive association between pediatric anemia and ambient temperatures, and Western and Eastern regions are negatively affected. The study aims to provide evidence to stakeholders to curtail the onset of pediatric anemia in high-risk African regions to set up key interventions based on the sustainability goals set by the World Health Organization.