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.

The activity of hydrolytic enzymes and antibiotics against biofilms of bacteria isolated from industrial-scale cooling towers.

BACKGROUND: Cooling towers (CTs) are crucial to myriad industrial processes, supporting thermal exchange between fluids in heat exchangers using water from lakes and rivers as coolant. However, CT water can sometimes introduce microbial contaminants that adhere to and colonize various surfaces within the CT system. These microorganisms can form biofilms, significantly hindering the system's thermal exchange efficiency. Current treatment strategies employ oxidizing biocides to prevent microbial growth. However, despite their affordability, they do not eliminate biofilms effectively and can lead to corrosive damage within the system. Herein, we aim to devise an anti-biofilm strategy utilizing hydrolytic enzymes (such as α-amylase, glucoamylase, pectin-lyase, cellulase, protease, and DNase) alongside antibiotics (including meropenem, ciprofloxacin, gentamicin, erythromycin, chloramphenicol, and ceftriaxone) to combat microbial growth and biofilm formation in cooling systems. RESULTS: All enzymes reduced the development of the biofilms significantly compared to controls (p < 0.05). The polysaccharidases exhibited biomass reduction of 90%, except for pectin-lyase (80%), followed by DNAse and protease at 43% and 49%, respectively. The antibiotics reduced the biofilms of 70% of isolates in concentration of > 2 mg/mL. The minimal biofilm eradication concentration (MBEC) lower than 1 mg/mL was detected for some 7-day-old sessile isolates. The enzymes and antibiotics were also used in combination against biofilms using the modified Chequerboard method. We found six synergistic combinations, with Fractional inhibitory concentrations (FIC) < 0.5, out of the ten tested. In the presence of the enzymatic mixture, MBECs presented a significant decrease (p < 0.05), at least 4-fold for antibiotics and 32-fold for enzymes. Moreover, we characterized high molecular weight (> 12 kDa) exopolysaccharides (EPS) from biofilms of ten isolates, and glycosyl composition analysis indicated a high frequency of glucose, mannose, erythrose, arabinose, and idose across isolates EPS contrasting with rhamnose, allose, and those carbohydrates, which were detected in only one isolate. CONCLUSION: The synergistic approach of combining enzymes with antibiotics emerges as a highly effective and innovative strategy for anti-biofilm intervention, highlighting its potential to enhance biofilm management practices.

Phytopathological management through bacteriophages: enhancing food security amidst climate change.

The increasing global population and climate change pose significant challenges to agriculture, particularly in managing plant diseases caused by phytopathogens. Traditional methods, including chemical pesticides and antibiotics, have become less effective due to pathogen resistance and environmental concerns. Phage therapy emerges as a promising alternative, offering a sustainable and precise approach to controlling plant bacterial diseases without harming beneficial soil microorganisms. This review explores the potential of bacteriophages as biocontrol agents, highlighting their specificity, rapid multiplication, and minimal environmental impact. We discuss the historical context, current applications, and prospects of phage therapy in agriculture, emphasizing its role in enhancing crop yield and quality. Additionally, the paper examines the integration of phage therapy with modern agricultural practices and the development phage cocktails and genetically engineered phages to combat resistant pathogens. The findings suggest that phage therapy could revolutionize phytopathological management, contributing to global food security and sustainable agricultural practices. ONE-SENTENCE SUMMARY: The burden of plant diseases and phage-based phytopathological treatment.

Exploring the frontiers of therapeutic breadth of antifungal peptides: A new avenue in antifungal drugs.

The growing prevalence of fungal infections alongside rising resistance to antifungal drugs poses a significant challenge to public health safety. At the close of the 2000s, major pharmaceutical firms began to scale back on antimicrobial research due to repeated setbacks and diminished economic gains, leaving only smaller companies and research labs to pursue new antifungal solutions. Among various natural sources explored for novel antifungal compounds, antifungal peptides (AFPs) emerge as particularly promising. Despite their potential, AFPs receive less focus than their antibacterial counterparts. These peptides have been sourced extensively from nature, including plants, animals, insects, and especially bacteria and fungi. Furthermore, with advancements in recombinant biotechnology and computational biology, AFPs can also be synthesized in lab settings, facilitating peptide production. AFPs are noted for their wide-ranging efficacy, in vitro and in vivo safety, and ability to combat biofilms. They are distinguished by their high specificity, minimal toxicity to cells, and reduced likelihood of resistance development. This review aims to comprehensively cover AFPs, including their sources-both natural and synthetic-their antifungal and biofilm-fighting capabilities in laboratory and real-world settings, their action mechanisms, and the current status of AFP research. ONE-SENTENCE SUMMARY: This comprehensive review of AFPs will be helpful for further research in antifungal research.

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.

The Breadth of Bacteriophages Contributing to the Development of the Phage-Based Vaccines for COVID-19: An Ideal Platform to Design the Multiplex Vaccine.

Phages are highly ubiquitous biological agents, which means they are ideal tools for molecular biology and recombinant DNA technology. The development of a phage display technology was a turning point in the design of phage-based vaccines. Phages are now recognized as universal adjuvant-free nanovaccine platforms. Phages are well-suited for vaccine design owing to their high stability in harsh conditions and simple and inexpensive large-scale production. The aim of this review is to summarize the overall breadth of the antiviral therapeutic perspective of phages contributing to the development of phage-based vaccines for COVID-19. We show that phage vaccines induce a strong and specific humoral response by targeted phage particles carrying the epitopes of SARS-CoV-2. Further, the engineering of the T4 bacteriophage by CRISPR (clustered regularly interspaced short palindromic repeats) presents phage vaccines as a valuable platform with potential capabilities of genetic plasticity, intrinsic immunogenicity, and stability.

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.

Etiology, pathology, and host-impaired immunity in medical implant-associated infections.

Host impaired immunity and pathogens adhesion factors are the key elements in analyzing medical implant-associated infections (MIAI). The infection chances are further influenced by surface properties of implants. This review addresses the medical implant-associated pathogens and summarizes the etiology, pathology, and host-impaired immunity in MIAI. Several bacterial and fungal pathogens have been isolated from MIAI; together, they form cross-kingdom species biofilms and support each other in different ways. The adhesion factors initiate the pathogen's adherence on the implant's surface; however, implant-induced impaired immunity promotes the pathogen's colonization and biofilm formation. Depending on the implant's surface properties, immune cell functions get slow or get exaggerated and cause immunity-induced secondary complications resulting in resistant depression and immuno-incompetent fibro-inflammatory zone that compromise implant's performance. Such consequences lead to the unavoidable and straightforward conclusion for the downstream transformation of new ideas, such as the development of multifunctional implant coatings.

Eco-smart biocontrol strategies utilizing potent microbes for sustainable management of phytopathogenic diseases.

Plants have an impact on the economy because they are used in the food and medical industries. Plants are a source of macro- and micronutrients for the health of humans and animals; however, the rise in microbial diseases has put plant health and yield at risk. Because there are insufficient controls, microbial infections annually impact approximately 25 % of the world's plant crops. Alternative strategies, such as biocontrol, are required to fight these illnesses. This review discusses the potential uses of recently discovered microorganisms because they are safe, effective, and unlikely to cause drug resistance. They have no negative effects on soil microbiology or the environment because they are environmentally benign. Biological control enhances indigenous microbiomes by reducing bacterial wilt, brown blotch, fire blight, and crown gall. More research is required to make these biocontrol agents more stable, effective, and less toxic before they can be used in commercial settings.

Total Endoscopic or Endoscope-Assisted Excision of Non-embolized Advanced Juvenile Nasopharyngeal Angiofibroma: A Clinical Case Series.

Background Surgical excision is the primary treatment for juvenile nasopharyngeal angiofibroma (JNA), but this procedure is challenging due to its high vascularity and local aggressiveness. Moreover, preoperative embolization is a subject of debate. Objective The objective of this study is to assess the efficacy, safety, and feasibility of endoscope-assisted excision as a surgical intervention for non-embolized advanced JNA. Materials and methods This case series involved six male patients (mean age: 16 years) with JNA, classified as stages Ⅱc to Ⅲb according to the Radkowski classification. None underwent preoperative embolization. Results Two stage Ⅱc cases underwent total endoscopic endonasal excision. One patient with stage Ⅲa and another with stage Ⅲb underwent surgery via an endoscope-assisted sublabial approach. Two patients, one with stage Ⅱc JNA and another with Ⅲb, underwent a two-stage procedure. Postoperative CT scans showed no residual disease at the six-month mark. On average, each procedure required 1.5 units of blood transfusion. One patient experienced intraoperative bleeding, whereas the remaining patients were free of any major complications. The mean operation duration was 175 minutes per procedure. The mean length of stay at the hospital was 3.75 days per procedure. Conclusion Endoscope-assisted or purely endoscopic approaches can be safely and effectively employed for the complete excision of non-embolized advanced JNAs.

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.

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.

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.