Integrated virtual screening and compound generation targeting H275Y mutation in the neuraminidase gene of oseltamivir-resistant influenza strains.

Neuraminidase (NA) is an essential enzyme located at the outer layer of the influenza virus and plays a key role in the release of virions from infected cells. The rising incidence of global epidemics has made the urgent need for effective antiviral medications an urgent public health priority. Furthermore, the emergence of resistance caused by specific mutations in the influenza viral genome exacerbates the challenges of antiviral therapy.

Pathological interplay of NF-κB and M1 macrophages in chronic inflammatory lung diseases.

Inflammatory lung diseases such as asthma, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis depend on the pathology of the nuclear factor kappa B (NF-κB) signalling pathway and M1 macrophage polarization. This review discusses the intimate molecular interactions and processes that modulate NF-κB's promotion of M1 macrophages and chronic inflammation/tissue damage within the confines of this review. NF-κB activation in macrophages produces pro-inflammatory mediators (cytokines - TNFα, IL6, IL1β, and reactive oxygen species (ROS), further increasing airway remodeling and fibrosis.

A Young Male With SCAD: Challenging Conventional Risk Factors and Insights.

Spontaneous coronary artery dissection (SCAD) is a relatively rare and underdiagnosed condition that can lead to acute coronary syndrome (ACS), with a notable incidence in young female patients without traditional cardiovascular risk factors. We present an unusual case of SCAD in a young male patient in the absence of common predisposing factors such as fibromuscular dysplasia (FMD), connective tissue disorders, and systemic inflammatory conditions. A 29-year-old man presenting with chest pain was diagnosed with SCAD involving the left anterior descending artery (LAD), resulting in an acute myocardial infarction (MI).

Effects of disability on early childhood development in 3 to 4-year-old children in three South Asian countries: evidence from multiple indicators cluster surveys.

Background: The Sustainable Development Goals (SDGs) prioritize optimal early childhood development (ECD) for all children, emphasizing the principle of leaving no one behind. Despite this focus, the association between disability and ECD remains largely unknown in low- and middle-income countries. This study aims to investigate the impact of disability on ECD among 3 to 4-year-old children in three South Asian countries.

Assessment of the prognostic performance of TIMI, PAMI, CADILLAC and GRACE scores for short-term major adverse cardiovascular events in patients undergoing emergent percutaneous revascularisation: a prospective observational study.

Objectives: Accurately predicting short-term MACE (major adverse cardiac events) following primary percutaneous coronary intervention (PCI) remains a clinical challenge. This study aims to assess the effectiveness of four established risk scores in predicting short-term MACE after primary PCI.

Design: Prospective observational study.

The influence of RAD51 (rs1801320) on breast cancer risk: an updated meta-analysis.

Background: DNA repair mechanisms, particularly RAD51-mediated homologous recombination repair, play a crucial role in breast cancer development, with the rs1801320 (135G > C) polymorphism showing conflicting associations across studies. This meta-analysis aimed to assess the relationship between RAD51 rs1801320 polymorphism and breast cancer susceptibility.

Method: We systematically searched PubMed and Web of Science databases through August 15, 2024, and included 16 case-control studies comprising 4743 breast cancer cases and 4448 controls, analyzing various genetic models using R Studio.

Optimizing Biotinidase Activity Assays: Insights From Clinical and Laboratory Evaluation From a Low-Middle Income Country.

Objective This study aimed to verify the methods used for biotinidase deficiency (BTD) assays, including fluorometric and colorimetric techniques, measure biotinidase (BT) activity in dried blood spots (DBS) and serum samples, and explore the clinical spectrum of patients with BTD based on low serum BT activity. Methods A cross-sectional study was conducted at the Newborn Screening Lab, Aga Khan University, Karachi, following ethical approval from August 2021 to December 2024. The study was conducted in three phases.

Environmental implications of improving global value chain participation via trade diversification: Offsetting the effects of resource rents.

This study explores the moderating effect of trade diversification on the relationship between global value-chain participation and natural resource rents for 106 nations from 2005 to 2018. The study employs an extended system Generalized Method of Moments (GMM) model to address potential challenges related to endogeneity and serial correlation. The results demonstrate how natural resource rents inhibit global value-chain participation by multinational firms, deterring them from investing in resource-dependent economies and restricting their integration into global trade networks.

The vaccine dosing effect overcomes the reduced immunogenic potential and in vivo efficacy of 33F pneumococcal serotype.

Serotype 33F is an emerging Streptococcus pneumoniae (Spn) serotype associated with asymptomatic nasopharyngeal (NP) colonization and invasive pneumococcal disease (IPD). Serotype 33F is a component in the advanced version of the pneumococcal conjugate vaccine 15 (PCV 15) formulation. However, in the murine vaccination model, serotype 33F exhibits reduced immunogenicity, correlating with reduced protection against 33F.

Risk Factors Contributing to 30 Day and One Year Mortality Event Scores Following Major Lower Extremity Amputation for Limb Ischemia.

Objective: The purpose of this study is to create a risk score for 30-day and one year mortality following major lower extremity amputation to facilitate clinical expectations and the identification of patients in need of heightened vigilance in longitudinal care.

Methods: In the Vascular Quality Initiative, 25,150 patients were identified who underwent lower extremity amputation. Two primary outcomes were investigated : 30 day mortality following major lower extremity amputation; and, 1 year mortality following amputation.

Sexually dimorphic cardiovascular impacts of prenatal exposure to a real-life environmental chemical mixture in adult offspring.

Cardiovascular disease (CVD) is a leading cause of death that is sexually dimorphic. This study used an ovine model to investigate whether maternal exposure to an environmental chemical (EC) mixture (biosolids) prior to and throughout pregnancy, affected offspring cardiovascular (CV) structure and function in adulthood. CV function of male and female offspring from ewes grazed on either conventionally fertilised (control, C) or biosolids-treated pasture (B) was assessed.

Structure Preserving Cycle-Gan for Unsupervised Medical Image Domain Adaptation.

The presence of domain shift in medical imaging is a common issue, which can greatly impact the performance of segmentation models when dealing with unseen image domains. This work introduces the Structure Preserving Cycle-GAN (SP Cycle-GAN) for unsupervised domain adaptation (DA) of segmentation datasets, which promotes medical structure preservation during image translation through the enforcement of a segmentation loss term in the overall Cycle-GAN training process. We demonstrate the structure preserving capability of the SP Cycle-GAN both visually and through comparison of Dice score segmentation performance for the un-supervised domain adaptation models.

Automated Abnormality Detection in Patient Retinal Function: A Deep Learning-Powered Electroretinogram Analysis System.

The electroretinogram (ERG) is an ophthalmic electrophysiology test designed to objectively measure the electrical response of the photoreceptor cells in the human retina. The analysis of the ERG is highly useful in evaluating various retinal diseases arising from both inherited and acquired disorders. However, analyzing ERG test results can be a time-intensive process for electrophysiologists, requiring meticulous examination of recorded ERG waveforms for accurate diagnosis and assessment.

Hemodynamics comparison of an hour-long rest and activity state data in a human coronary digital twin.

Although it is well established that hemodynamics can significantly influence the location and progression of cardiovascular disease (CVD), and 3D blood flow metrics are recognized as potential diagnostic indicators of these diseases, the dynamics of these metrics over time and their variation at different activity levels are not well understood. A relevant example is the impact of exercise on the vascular system over extended periods. Although exercise is widely recognized as a preventive measure of heart disease, the specifics of how activity levels and subsequent alterations in blood flow contribute to the mechanisms that drive CVD remain unclear.

Multi-Modal Emotion Recognition Using EEG and Eye Tracking Features.

Multi-modal emotion recognition from various human physiological indicators has emerged as a large topic of interest, including the use of EEG, ECG, GSR and Eye Tracking features. This work introduced a simple CNN based multi-modal EEG and Eye Tracking emotion recognition model for the SEED V dataset. In contrast to other works on the SEED V dataset, different Differential Entropy time windows were tested for EEG feature extraction.

EEG Signal Denoising Using Beta-Variational Autoencoder.

Electroencephalography (EEG) signals are a valuable source of information for investigating brain activity and different types of brain-related disease diagnoses. However, EEG signals are often contaminated by various kinds of noises/artifacts. Several methods have been proposed for EEG reconstruction/denoising to facilitate signal analysis, but such algorithms often fail when the EEG contains extreme artifacts.

Global mental health commentary: using innovation to create a workforce to deliver and implement culturally adapted CBT in Pakistan.

Most low- and middle-income countries (LMICs) have poor or non-existent mental healthcare. Many of LMIC countries allocate less than 1% of their health budgets to addressing mental illness, making large-scale public health interventions not a practical option, at least for the foreseeable future. Psychiatric services are limited to large urban centres, and mental health literacy is low.

Effect of biological lignin depolymerization on rice straw enzymatic hydrolysis, anerobic fermentation characteristics and in vitro ruminal digestibility.

This study investigated the effects of lignin depolymerization using laccase on rice straw silage fermentation characteristics, lignocellulose biodegradation and in vitro digestibility. Rice straw was ensiled for 120 days, either without additives (control), or pretreated with Lactobacillus plantarum and cellulases (LPC), cellulases and laccase (CL), and L. plantarum, cellulases and laccase (LPCL).

Transformer-Based Approach for Predicting Transactive Energy in Neurorehabilitation.

Advancements in robotic neurorehabilitation have made it imperative to enhance the safety and personalization of physical human-robot interactions (pHRI). Estimation and management of energy transfer between humans and robots is essential for enhancing safety during the rehabilitation. Traditional control methods, which rely on coordinate-based monitoring of robot velocity and external forces, often fail in unstructured environments due to their susceptibility to sensor noise and limited adaptability to individual patient needs.

Tailored therapies for triple-negative breast cancer: current landscape and future perceptions.

Triple-negative breast cancer (TNBC) has become one of the most challenging cancers to date due to its great variability in biological features, high growth rate, and rare options for treatment. This review examines several innovative strategies for tailored treatment of TNBC, focusing mainly on the most recent developments and potential directions. The molecular landscape of TNBC is covered in the first section, which keeps the focus on transcriptome and genomic profiling while highlighting key molecular targets like mutations in the BRCA1/2, PIK3CA, androgen receptors (AR), epidermal growth factor receptors (EGFR), and immunological checkpoint molecules.

Nanoemulgel mediated enhanced skin curcumin penetration/retention for local treatment of cutaneous leishmaniasis: and assessment.

Background: Skin delivery of a therapeutically effective drug is imperative for local cutaneous leishmaniasis (CL) treatment.

Objective: This study aimed to formulate, optimize, and characterize curcumin-loaded nanoemulgel for enhanced skin drug retention to treat CL locally.

Methods: Nanoemulsions were prepared by high-speed homogenization, characterized, and optimized for size, PDI, zeta potential, stability, morphology, drug contents, encapsulation efficiency, drug release, antileishmanial activity, and cell viability.

Seroprevalence of measles antibodies in women born between 1985 and 1999 in metropolitan city in India: a cross-sectional study.

Introduction: The Universal Immunisation Programme of India recommends first dose of measles vaccine in children at 9 months as the infant is protected by the maternal antibodies till then, and the vaccine provides optimal protection. However, during the recent outbreaks in 2023, in Mumbai, India, 31% of the measles cases reported till March end were infants below 9 months of age. The study was undertaken in view of increased vulnerability of infants below 9 months of age which might possibly indicate insufficient maternal antibodies against measles.

Exploring the Patterns of Gallbladder Diseases and Associated Risk Factors in a Tertiary Care Hospital of Mardan, Khyber Pakhtunkhwa Province, Pakistan.

Background Gallbladder diseases represent a significant contributor to global morbidity. The most common pathological conditions affecting the gallbladder include cholelithiasis, calculous and acalculous cholecystitis, gallbladder gangrene, and perforation. Gallbladder diseases are a common health concern in European and American societies, with a significant number of new cases diagnosed annually and a substantial number of surgical procedures performed each year to address the condition.