Computational exploration and molecular dynamic simulation for the discovery of antiviral agents targeting Newcastle disease virus.

Newcastle disease virus (NDV) is a highly infectious viral disease that impacts birds globally, especially domestic poultry. NDV is a type of avian paramyxovirus which poses a major threat to the poultry industry due to its ability to inflict significant economic damage. The membrane protein, Hemagglutinin-Neuraminidase (HN) of NDV is an attractive therapeutic candidate. It contributes to pathogenicity through various functions, such as promoting fusion and preventing viral self-agglutination, which allows for viral spread. In this study, we used pharmacophore modeling to identify natural molecules that can inhibit the HN protein of NDV. Physicochemical characteristics and phylogenetic analysis were determined to elucidate structural information and phylogeny of target protein across different species as well as members of the virus family. For structural analysis, the missing residues of HN target protein were filled and the structure was evaluated by PROCHECK and VERIFY 3D. Moreover, shape and feature-based pharmacophore model was employed to screen natural compounds' library through numerous scoring schemes. Top 48 hits with 0.8860 pharmacophore fit score were subjected towards structure-based molecular docking. Top 9 compounds were observed witihin the range of -8.9 to -7.5 kcal/mol binding score. Five best-fitting compounds in complex with HN receptor were subjected to predict biological activity and further analysis. Top two hits were selected for MD simulations to validate binding modes and structural stability. Finally, upon scrutinization, A1 (ZINC05223166) emerges as potential HN inhibitor to treat NDV, necessitating further validation via clinical trials.

Deciphering host-pathogen interaction during Streptomyces spp. infestation of potato.

Potato crop, currently, is the staple food crop of about 1.3 billion global population. Potato is attaining even more admiration globally day by day owing to its public acceptability. However, potato sustainable production is distinctly challenged by multiple factors like diseases, pests and climate change etc. Among diseases, common scab is one of the prime threats to potato crop due to its soil-borne nature and versatility in phytotoxins' secretion. Common scab is caused multiple number of phytopathogenic streptomyces strains. Despite extensive research programs, researchers are still unable to identify a significant solution to this threat that is proliferating exceptional rate across the globe. To develop feasible remedies, adequate information regarding host-pathogen interaction should be available. This review possesses insights on existing pathogenic species, the evolution of novel pathogenic streptomyces spp. and phytotoxins produced by the pathogenic strains. Furthermore, which type of physiological, biochemical and genetic activities occur during pathogen's infestation of the host are also canvassed.

Identification of Small Molecule Inhibitors of Human Cytomegalovirus pUL89 Endonuclease Using Integrated Computational Approaches.

Replication of Human Cytomegalovirus (HCMV) requires the presence of a metal-dependent endonuclease at the C-terminus of pUL89, in order to properly pack and cleave the viral genome. Therefore, pUL89 is an attractive target to design anti-CMV intervention. Herein, we used integrated structure-based and ligand-based virtual screening approaches in combination with MD simulation for the identification of potential metal binding small molecule antagonist of pUL89. In this regard, the essential chemical features needed for the inhibition of pUL89 endonuclease domain were defined and used as a 3D query to search chemical compounds from ZINC and ChEMBL database. Thereafter, the molecular docking and ligand-based shape screening were used to narrow down the compounds based on previously identified pUL89 antagonists. The selected virtual hits were further subjected to MD simulation to determine the intrinsic and ligand-induced flexibility of pUL89. The predicted binding modes showed that the compounds reside well in the binding site of endonuclease domain by chelating with the metal ions and crucial residues. Taken in concert, the in silico investigation led to the identification of potential pUL89 antagonists. This study provided promising starting point for further in vitro and in vivo studies.

Recent Progress on Synthesis, Characterization, and Performance of Energetic Cocrystals: A Review.

In the niche area of energetic materials, a balance between energy and safety is extremely important. To address this "energy-safety contradiction", energetic cocrystals have been introduced. The investigation of the synthesis methods, characteristics, and efficacy of energetic cocrystals is of the utmost importance for optimizing their design and development. This review covers (i) various synthesis methods for energetic cocrystals; (ii) discusses their characteristics such as structural properties, detonation performance, sensitivity analysis, thermal properties, and morphology mapping, along with other properties such as oxygen balance, solubility, and fluorescence; and (iii) performance with respect to energy contents (detonation velocity and pressure) and sensitivity. This is followed by concluding remarks together with future perspectives.

Monitoring land use land cover changes and its impacts on land surface temperature over Mardan and Charsadda Districts, Khyber Pakhtunkhwa (KP), Pakistan.

Land use/land cover (LULC) changes due to urban growth on the regional scale affect land surface temperature (LST). The present study aims to assess the LULC changes and their impact on LST over Mardan and Charsadda districts of Khyber Pakhtunkhwa (KP), Pakistan, in the period from 1990 to 2019. Landsat satellite (TM& ETM +) datasets in the period from 1990 to 2010 and Sentinel-2 images from 2016 to 2019 were used in this study. All the datasets were pre-processed and the LULC types were classified by maximum likelihood classification algorithm. The vegetation degradation was computed from normalized difference vegetation index (NDVI), and the LST was derived based on the LULC changes. The results showed that the overall accuracy of LULC classification was 87.84%. Dramatic LULC changes were observed during the last three decades, where the vegetation degradation area was decreased from 1307.8 (59.27%) to 1147.6 km2 (52.1%) and the barren land area increased from 816.6 (37.07%) to 961.4 km2 (42.64%). Similarly, the built-up area has also increased from 57.2 (2.5%) to 104.3 km2 (4.73%) in the years 1990 and 2019, respectively. These variations in LULC types have significantly influenced the LST from 1990 to 2019; specifically, the LST of built-up area, barren land, and vegetation cover increased from 20.1 to 32.1 °C, 21.5 to 35.5 °C, and 17.1 to 28.2 °C, respectively. The regression line plotted defines that the LST has a negative correlation with NDVI and a positive correlation with normalized difference of built-up index (NDBI). In particular, the vegetation and land covers dramatically transformed to barren land and/or to urban development over the study area in the period from 1990 to2019, which has severely affected the LST and the natural resources of the study area. Therefore, our study will be very helpful for managing the rapid environmental changes and urban planning.

Pancreaticoduodenectomy: Outcomes of a complex surgical procedure from a developing country.

BACKGROUND: Pancreaticoduodenectomy (PD) plays an integral part in the management of pancreatic, periampullary and duodenal cancers, along with a few other pathologies of this region. Despite advances in surgery PD continues to have significant morbidity and noteworthy mortality. The aim of this study is to provide an in-depth report on the patient characteristics, indications and the outcomes of PD) in a tertiary cancer hospital in Pakistan. MATERIALS AND METHODS: The study population included patients who underwent PD between January 1, 2014 and march 31, 2019, at Shaukat Khanum Memorial Cancer Hospital and Research Center (SKMCH&RC) in Pakistan. The data was retrospectively analyzed from the Hospital Information System (HIS), which is a prospectively maintained patient electronic database of SKMCH&RC. Patient characteristics, procedural details and post-operative outcomes according to internationally accepted definitions were reported. RESULTS: A total of 161 patients underwent PD at our hospital in the study period at a median age of 53 years, ranging from 19 to 78 years. 62% of the patients were males while 37% were females. Jaundice was the most common presenting symptom (64.6%), followed by abdominal pain (26.7%). PD with pancreaticogastrostomy was performed in 110 patients (68.3%), while pancreaticojejunostomy was performed in the rest of the cohort. Surgical site infection (SSI) was observed in 64 patients (40%). The incidence of Pancreatic Fistula grade C based on the International Study Group on Pancreatic Fistula (ISGPF) definition was 7.45% (n = 12). The 30 days mortality rate was 3.1%. Median survival of the cohort was 21 ±1.13 months and disease-free survival was 16±2.62 months. CONCLUSION: PD can be performed with acceptable morbidity and mortality in a resource constrained country, as long as it is undertaken in a high-volume center. This is in keeping with data published from other well-reputed international centers.

Angiofibroma In A 50-Year-Old Patient.

Juvenile Angiofibroma (JNA) is a benign tumour that tends to bleed and occur in the nasopharynx with most cases occurring in pre-pubertal and adolescent males 10-20 years. We present the case of a 50-year-old male shopkeeper who consulted the ENT out patients' department (OPD) of Khyber Teaching Hospital (KTH) with the chief complaint of right sided nasal obstruction for the last 2.5 months which was associated with two episodes of epistaxis and diplopia which started 2 months back. He complained of right sided frontal and periorbital pain for the last 15 days. Past medical and surgical history was insignificant. Computerized Tomography (CT) scan without contrast and magnetic resonance imaging (MRI) showed finding consistent with a pedunculated tumour like growth. After baseline investigations, surgery was done and a Wilson's incision was given and the mass was excised and sent to the lab for histopathological report which showed angiofibroma. The age of the patient shows that this is a very rare case of angiofibroma. Dissection of such tumours is important as they have propensity to bleed. Excision along with biopsy is the method of choice. Proper surgical techniques and use of better medical technology are required to make and early diagnosis. Further studies/case reports around the world would assert our findings that a nasopharyngeal angiofibroma can also be found in middle aged men.

Pleomorphic Adenoma Of Minor Salivary Glands.

Pleomorphic adenoma is the most common benign tumour of salivary glands which is Known for its wide pleomorphic architecture. It accounts for 45-75% of all salivary gland neoplasm. It can involve major as well as minor salivary glands. Among minor salivary glands (5-10% of cases) the palate lip, nasal cavity, pharynx, larynx and trachea are the most common sites. Diagnosis is made with biopsy along with histopathology. Wide excision with biopsy and removal of underlying extension of tumour is the treatment of choice. Sixty years old farmer presented with painless swelling in the upper lip for the last 8 years. History revealed recurrent mass in the midline of upper lip with no other complaints. He was operated 3 times for this complaint in the past. Belonging to poor socioeconomic status no biopsy records were found. On examination 3×4 cm hard and mobile mass was found. Lymph nodes of head and neck and parotid gland revealed no enlargement. Surgery by wide excision was planned. After baseline investigation surgery was done and the mass sent for histopathology. Biopsy reports showed pleomorphic adenoma on unusual site. Dissection of salivary gland tumour is important as they have propensity to metastasize. Wide local excision along with biopsy is the method of choice. Proper surgical techniques are required to avoid recurrence.

Exploring the historical roots, advantages and efficacy of phage therapy in plant diseases management.

In the drug-resistance era, phage therapy has received considerable attention from worldwide researchers. Phage therapy has been given much attention in public health but is rarely applied to control plant diseases. Herein, we discuss phage therapy as a biocontrol approach against several plant diseases. The emergence of antibiotic resistance in agriculturally important pathogenic bacteria and the toxic nature of different synthetic compounds used to control microbes has driven researchers to rethink the century-old strategy of phage therapy''. Compared to other treatment strategies, phage therapy offers remarkable advantages such as high specificity, less chances of drug resistance, non-harmful nature, and benefit to soil microbial flora. The optimizations and protective formulations of phages are significant accomplishments; however, steps towards a better understanding of the physiologic characteristics of phages need to be preceded to commercialize their use. The future of phage therapy in the context of plant disease management is promising and could play a significant role in sustainable agriculture. Ongoing research will likely affirm the safety of phage therapy, ensuring that it does not harm non-target organisms, including beneficial soil microbes. Phage therapy could become vital in addressing global food security challenges, particularly in regions heavily impacted by plant bacterial diseases. Efforts to create formulations that enhance the stability and shelf-life of phages will be crucial, especially for their use in varied environmental conditions.

Tympanic Cavity Packing in Tympanoplasty Type 1: A Meta-Analysis.

Packing of tympanic cavity is generally considered an essential step in myringoplasty. However, each packing material comes with one or another side effect. The objective of this meta-analysis was to compare the results of Type 1 myringoplasty with or without packing. Pubmed, Cochrane database, Embase, Google Scholar, and clinicaltrials.gov were searched using 'tympanoplasty or myringoplasty and packing' as the search query. All RCTs / quasi-RCTs comparing tympanoplasty Type 1 with packing (control) versus without packing (intervention) of tympanic cavity in the human population were included. For dichotomous and continuous outcomes, relative risks (RR) and mean differences (MD) were calculated with 95% confidence interval, respectively. Heterogeneity was assessed using I2 statistics. Publication bias was checked using funnel plot and Egger's test, if applicable. Quality of evidence was assessed for each outcome using GRADE approach. Eleven studies were deemed eligible. For graft uptake and functional success rate, RR of 1.01 and 1.05 were obtained, respectively, showing no significant differences between the intervention and control groups. At 1st and 3rd postoperative month, no-packing group showed 3.86 dB and 2.08 dB better air-bone gap (ABG) closure than the packing group, respectively. Also, intervention with no-packing was 9.28-minute shorter procedure. With RR 0.35, no-packing had significantly lesser postoperative aural fullness. Type 1 tympanoplasty performed with or without packing show comparable results in terms of graft uptake and functional success rate. However, if performed without packing, it takes shorter time, provides early hearing improvement and causes less aural fullness. Key Words: Tympanoplasty Type 1, Packing, Gelfoam, No-packing, Meta-analysis, Endoscopic myringoplasty.

Global research trends on gut microbiota and metabolic dysfunction-associated steatohepatitis: Insights from bibliometric and scientometric analysis.

Background: Metabolic dysfunction-associated steatohepatitis (MASH) is an inflammatory subtype of metabolic dysfunction-associated steatotic liver disease (MASLD) has recently been proposed as a replacement term for NAFLD, a common, multifactorial and poorly understood liver disease whose incidence is increasing worldwide. In recent years, there has been increasing scientific interest in exploring the relationship between gut microbiota and MASH. To learn more about the gut microbiota in MASH, this study aims to provide a comprehensive analysis of the knowledge structure and research hotspots from a bibliometric perspective. Methods: We searched the Web of Science Core Collection for articles and reviews that covered the connections between gut microbiota and MASH over the last decade. The Online Analysis Platforms, VOSviewer, CiteSpace, the R tool "bibliometrix" were used to analyzed existing publications trends and hotspots. Results: A total of 4,069 documents related to the interaction between gut microbiota and MASH were retrieved from 2014 to 2023. The number of annual publications increased significantly over the last decade, particularly in the United States and China. The University of California-San Diego was the most productive institution, while researcher Rohit Loomba published the most papers in the field. Younossi ZM was ranked as the first co-cited author and largest contributor of highly cited articles in the field. Gastroenterology and hepatology were the most common specialty category. The most cited journal in the last decade was Hepatology. The Keyword Bursts analysis highlighted the importance of studying the association between gut microbiota and MASH, as well as related factors such as metabolic syndrome, insulin resistance, endotoxemia and overgrowth of gut bacteria. Keyword clusters with co-citation were used to illustrate important topics including intestinal permeability, insulin sensitivity and liver immunology. The most common keywords include insulin resistance, obesity, dysbiosis, inflammation and oxidative stress, which are current hotspots. Conclusion: Our analysis highlights key aspects of this field and emphasizes multiorgan crosstalk in MASLD/MASH pathogenesis. In particular, the central role of the gut-liver axis and the significant influence of gut microbiota dysbiosis on disease progression are highlighted. Furthermore, our results highlight the transformative potential of microbiota-specific therapies and cover the way for innovative healthcare and pharmaceutical strategies.

On discovery of novel hub genes for ER+ and TN breast cancer types through RNA seq data analyses and classification models.

Breast cancer (BC) is a malignant neoplasm which is classified into various types defined by underlying molecular factors such as estrogen receptor positive (ER+), progesterone receptor positive (PR+), human epidermal growth factor positive (HER2+) and triple negative (TNBC). Early detection of ER+ and TNBC is crucial in the choice of diagnosis and appropriate treatment strategy. Here we report the key genes associated to ER+ and TNBC using RNA-Seq analysis and machine learning models. Three ER+ and TNBC RNA seq datasets comprising 164 patients in-toto were selected for standard NGS hierarchical data processing and data analyses protocols. Enrichment pathway analysis and network analysis was done and finally top hub genes were identified. To come with a reliable classifier which could distinguish the distinct transcriptome patterns associated to ER+ and TNBC, ML models were built employing Naïve Bayes, SVM and kNN. 1730 common DEG's exhibiting significant logFC values with 0.05 p-value threshold were identified. A list of top ten hub genes were screened on the basis of maximal clique centrality (MCC) which included CDC20, CDK1, BUB1, AURKA, CDCA8, RRM2, TTK, CENPF, CEP55 and NDC80.These genes were found to be involved in crucial cell cycle pathways. k-Nearest Neighbor (kNN) model was observed to be best classifier with accuracy 84%, specificity 66% and sensitivity 95% to differentiate between ER+ and TNBC RNA-Seq transcriptomes. Our screened list of 10 hub genes can thus help unearth novel molecular signatures implicated in ER+ and TNBC onset, prognosis and design of novel protocols for breast cancer diagnostics and therapeutics.

Impact of Serum Triglyceride Levels on Severity and Outcomes in Acute Biliary Pancreatitis: A Retrospective Cohort Study.

Background Acute biliary pancreatitis (ABP), a major inflammatory illness, is primarily caused by gallstone blockage of the common bile duct. The pathophysiology of ABP has been linked to serum triglyceride (TG) levels, suggesting a potential role for TG in predicting disease severity. Objective The research objective was to investigate the association between serum TG levels and the severity of ABP. Methodology This retrospective cohort study sought to determine the relationship between blood TG levels and the severity of ABP. It was conducted at Lady Reading Hospital in Peshawar, Pakistan, from September 2023 to March 2024. A total of 530 ABP patients were divided into two groups based on their TG levels: normal (<150 mg/dl) and elevated (≥150 mg/dl). Clinical data were gathered, including demographics, comorbidities, laboratory results, severity ratings (APACHE II and Ranson's criteria), and clinical outcomes. Descriptive statistics, Chi-square tests, and multivariate logistic regression were used in the statistical analysis. Results Patients with elevated TG levels (n=130) demonstrated higher median Ranson's criteria (3.24 vs. 2.53, p<0.001) and APACHE II scores (10.53 vs. 8.73, p<0.001) compared to those with normal TG levels (n=400). Elevated TG levels were associated with increased severity of ABP, with ORs of 2.41 (95% CI: 1.23-4.74) for mild vs. severe ABP. Clinical outcomes such as ICU admission (21.54% vs. 3.25%, p<0.001), mortality (6.15% vs. 0.50%, p<0.001), and pancreatic necrosis (10.77% vs. 1.25%, p<0.001) were significantly worse in the elevated TG group. Conclusion Elevated serum TG levels (≥150 mg/dl) are independently associated with increased severity of ABP, as indicated by higher severity scores and poorer clinical outcomes.

Exploring the Antimicrobial Resistance Profile of Salmonella typhi and Its Clinical Burden.

Background: Typhoid fever caused by Salmonella enterica serovar Typhi (S. typhi) continues to pose a significant risk to public health in developing countries, including Pakistan. This study investigated the epidemiological factors linked to suspected and confirmed S. typhi infections in Peshawar's hospital population. Methodology: A total of 5735 blood samples of patients with suspected enteric fever were collected from September 2022 to November 2023. S. typhi infection was confirmed using microbiological culture of blood samples, biochemical-based tests, and DNA-sequencing methods. Drug sensitivity testing on cultures was conducted as per the CLSI guidelines. Chi-square tests were used to analyze the clinical and epidemiologic characteristics of 5735 samples stratified by S. typhi infection status, and risk factors were assessed by applying logistic regression models to estimate odds ratios (ORs). Results: The number of confirmed typhoid fever cases in this hospital-based study population was 691 (/5735, 12.0%), more prevalent in males (447/3235 13.8%) and children (0-11 years) (429/2747, 15.6%). Compared to children, the risk of S. typhi infection was lower in adolescence (adjusted OR = 0.52; 95% CI: 0.42-0.66), adulthood (19-59 years; aOR = 0.30; 95% CI: 0.25-0.38), and older adulthood (aOR = 0.08; 95% CI: 0.04-0.18) (p < 0.001). Compared to males, the risk of S. typhi infection was lower in females (aOR = 0.67; 95% CI = 0.56-0.80; p = 0.002). Living in a rural residence (compared to urban) was associated with a higher risk of infection (aOR = 1.38; 95% CI: 1.16-1.63; p = 0.001), while access to a groundwater source (compared to municipal water supply) led to a lower risk (aOR = 0.56; 95% CI: 0.43-0.73; p = 0.002). Vaccination demonstrated a robust protective effect (aOR = 0.069; 95% CI = 0.04-0.11, p = 0.002). For those with typhoid infections, clinical biomarker analysis revealed the presence of leucopenia (65/691, 9.4%), thrombocytopenia (130/691, 18.8%), and elevated alanine aminotransferase (ALT) (402/691, 58.2%) and C-reactive protein (CRP) (690/691, 99.9%) levels. Worryingly, among the positive S. typhi isolates, there was a high prevalence of drug resistance (653/691), including multidrug-resistant (MDR 82/691, 11.9%) and extensively drug-resistant types (XDR, 571/691, 82.6%). Conclusions: This study highlights the importance of age, sex, locality, water source, and vaccination status in shaping the epidemiological landscape of S. typhi in the Peshawar district. It implies that expanding vaccination coverage to the broader population of Khyber Pakhtunkhwa province, particularly in the district of Peshawar, would be beneficial.

Audiological Outcomes of Type 1 Tympanoplasty Using Conchal Cartilage and Temporalis Fascia.

OBJECTIVE: To compare the efficacy of conchal cartilage graft and temporalis fascia graft in Type 1 tympanoplasty in terms of graft uptake and hearing improvement. STUDY DESIGN: Descriptive study. Place and Duration of the Study: Department of Otolaryngology, Khyber Teaching Hospital, Peshawar, Pakistan, from January 2020 till December 2022. METHODOLOGY: Using quota sampling, 2 groups were made i.e. conchal cartilage group (Group A) and temporalis fascia group (Group B). Total of 124 records were selected with 62 records from each group. Graft uptake rate and audiological outcomes were compared between the groups. Moreover, postoperative complication rate was also noted for each group. RESULTS: The graft uptake rates between Group A and B at 3rd month were compared postoperatively (98.39%, 93.55%, p=0.36). The difference between preoperative mean air-bone gap (ABG, 28.05 ± 2.19dB, 28.68 ± 2.38 dB, p=0.12) and postoperative mean ABG (13.35 ± 3.45, 14.47 ± 3.29, p=0.69) was also statistically not significant. However, the differences regarding audiological success rate between cartilage and fascia groups (96.77%, 82.25%, p=0.01) and average operating time (51.8 ± 2.1 vs. 43.5 ± 3.2 minutes, p=0.009) were significantly different. CONCLUSION: In chronic otitis media (COM) patients with subtotal perforations, endoscopic tympanoplasty using conchal cartilage or temporalis fascia as graft yielded comparable outcomes in terms of graft uptake, hearing improvement, and postoperative complications. However, using conchal cartilage, the procedure showed better audiological success rate. With temporalis fascia as graft, the procedure was performed in a shorter time. KEY WORDS: Chronic otitis media, Tympanoplasty, Temporalis fascia, Conchal cartilage, Subtotal perforation.

Computational exploration of novel ROCK2 inhibitors for cardiovascular disease management; insights from high-throughput virtual screening, molecular docking, DFT and MD simulation.

Cardiovascular disorders are the world's major cause of death nowadays. To treat cardiovascular diseases especially coronary artery diseases and hypertension, researchers found potential ROCK2 (Rho-associated coiled-coil-containing protein kinase 2) target due to its substantial role in NO-cGMP and RhoA/ROCK pathway. Available drugs for ROCK2 are less effective and some of them depict side effects. Therefore, a set of novel compounds were screened that can potentially inhibit the activity of ROCK2 and help to treat cardiovascular diseases by employing In-silico techniques. In this study, we undertook ligand based virtual screening of 50 million compound's library, to that purpose shape and features (contain functional groups) based pharmacophore query was modelled and validated by Area Under Curve graph (AUC). 2000 best hits were screened for Lipinski's rule of 5 compliance. Subsequently, these selected compounds were docked into the binding site of ROCK2 to gain insights into the interactions between hit compounds and the target protein. Based on binding affinity and RMSD scores, a final cohort of 15 compounds were chosen which were further refined by pharmacokinetics, ADMET and bioactivity scores. 2 potential hits were screened using density functional theory, revealing remarkable biological and chemical activity. Potential inhibitors (F847-0007 and 9543495) underwent rigorous examination through MD Simulations and MMGBSA analysis, elucidating their stability and strong binding affinities. Results of current study unveil the potential of identified novel hits as promising lead compounds for ROCK2 associated with cardiovascular diseases. These findings will further investigate via In-vitro and In-vivo studies to develop novel druglike molecules against ROCK2.

Energy, environmental degradation, and health status: evidence from South Asia.

Energy is considered a vital factor of economic growth that contributes to improve quality of life and health status. However, global warming, climate change, and environmental degradation are due primarily because of energy emissions, whereas environmental degradation is detrimental to health. Since one-fifth of the population lives in South Asia, it is necessary to analyze the impact of energy and environmental degradation on health status in this region. For this purpose, health status in South Asia is proxy with health expenditure, life expectancy, and infant mortality, and this study investigates the effect of energy intensity, income, and carbon emissions on health status, whereas urbanization is considered a control variable. The cointegration test indicates South Asia's long-term health status factors are energy intensity, income, carbon emissions, and urbanization. Long-run results suggest that energy intensity and income improve health status as these factors reduce health expenditure, improve life expectancy, and decrease infant mortality. Environmental degradation not only increases health expenditure but also hinders life expectancy and increases mortality. Moreover, an increase in income diminishes health expenditure and is responsible for high life expectancy and low mortality in South Asia.

Interleukins (Cytokines) as Biomarkers in Colorectal Cancer: Progression, Detection, and Monitoring.

Cancer is the primary cause of death in economically developed countries and the second leading cause in developing countries. Colorectal cancer (CRC) is the third most common cause of cancer-related deaths worldwide. Risk factors for CRC include obesity, a diet low in fruits and vegetables, physical inactivity, and smoking. CRC has a poor prognosis, and there is a critical need for new diagnostic and prognostic biomarkers to reduce related deaths. Recently, studies have focused more on molecular testing to guide targeted treatments for CRC patients. The most crucial feature of activated immune cells is the production and release of growth factors and cytokines that modulate the inflammatory conditions in tumor tissues. The cytokine network is valuable for the prognosis and pathogenesis of colorectal cancer as they can aid in the cost-effective and non-invasive detection of cancer. A large number of interleukins (IL) released by the immune system at various stages of CRC can act as "biomarkers". They play diverse functions in colorectal cancer, and include IL-4, IL-6, IL-8, IL-11, IL-17A, IL-22, IL-23, IL-33, TNF, TGF-ß, and vascular endothelial growth factor (VEGF), which are pro-tumorigenic genes. However, there are an inadequate number of studies in this area considering its correlation with cytokine profiles that are clinically useful in diagnosing cancer. A better understanding of cytokine levels to establish diagnostic pathways entails an understanding of cytokine interactions and the regulation of their various biochemical signaling pathways in healthy individuals. This review provides a comprehensive summary of some interleukins as immunological biomarkers of CRC.

Molecular Understanding of ACE-2 and HLA-Conferred Differential Susceptibility to COVID-19: Host-Directed Insights Opening New Windows in COVID-19 Therapeutics.

The genetic variants of HLAs (human leukocyte antigens) play a crucial role in the virus-host interaction and pathology of COVID-19. The genetic variants of HLAs not only influence T cell immune responses but also B cell immune responses by presenting a variety of peptide fragments of invading pathogens. Peptide cocktail vaccines produced by using various conserved HLA-A2 epitopes provoke substantial specific CD8+ T cell responses in experimental animals. The HLA profiles vary among individuals and trigger different T cell-mediated immune responses in COVID-19 infections. Those with HLA-C*01 and HLA-B*44 are highly susceptible to the disease. However, HLA-A*02:01, HLA-DR*03:01, and HLA-Cw*15:02 alleles show resistance to SARS infection. Understanding the genetic association of HLA with COVID-19 susceptibility and severity is important because it can help in studying the transmission of COVID-19 and its physiopathogenesis. The HLA-C*01 and B*44 allele pathways can be studied to gain insight into disease transmission and physiopathogenesis. Therefore, integrating HLA testing is suggested in the ongoing pandemic, which will help in the rapid identification of highly susceptible populations worldwide and possibly acclimate vaccine development. Therefore, understanding the correlation between HLA and SARS-CoV-2 is critical in opening new insights into COVID-19 therapeutics, based on previous studies conducted.

Revolutionizing Diabetes Diagnosis: Machine Learning Techniques Unleashed.

The intricate and multifaceted nature of diabetes disrupts the body's crucial glucose processing mechanism, which serves as a fundamental energy source for the cells. This research aims to predict the occurrence of diabetes in individuals by harnessing the power of machine learning algorithms, utilizing the PIMA diabetes dataset. The selected algorithms employed in this study encompass Decision Tree, K-Nearest Neighbor, Random Forest, Logistic Regression, and Support Vector Machine. To execute the experiments, two software tools, namely Waikato Environment for Knowledge Analysis (WEKA) version 3.8.1 and Python version 3.10, were utilized. To evaluate the performance of the algorithms, several metrics were employed, including true positive rate, false positive rate, precision, recall, F-measure, Matthew's correlation coefficient, receiver operating characteristic area, and precision-recall curves area. Furthermore, various errors such as Mean Absolute Error, Root Mean Squared Error, Relative Absolute Error, and Root Relative Squared Error were examined to assess the accuracy of the models. Upon conducting the experiments, it was observed that Logistic Regression outperformed the other techniques, exhibiting the highest precision of 81 percent using Python and 80.43 percent using WEKA. These findings shed light on the efficacy of machine learning in predicting diabetes and highlight the potential of Logistic Regression as a valuable tool in this domain.