The current standard of care (SOC) for hepatitis C virus (HCV) infection is the combination of pegylated interferon (PEG-IFN), Ribavirin and protease inhibitor for HCV genotype 1. Nevertheless, this treatment is successful only in 70-80% of the patients. In addition, the treatment is not economical and is of immense physical burden for the subject. It has been established now, that virus-host interactions play a significant role in determining treatment outcomes. Therefore identifying biological markers that may predict the treatment response and hence treatment outcome would be useful. Both IFN and Ribavirin mainly act by modulating the immune system of the patient. Therefore, the treatment response is influenced by genetic variations of the human as well as the HCV genome. The goal of this review article is to summarize the impact of recent scientific advances in this area regarding the understanding of human and HCV genetic variations and their effect on treatment outcomes. Google scholar and PubMed have been used for literature research. Among the host factors, the most prominent associations are polymorphisms within the region of the interleukin 28B (IL28B) gene, but variations in other cytokine genes have also been linked with the treatment outcome. Among the viral factors, HCV genotypes are noteworthy. Moreover, for sustained virological responses (SVR), variations in core, p7, non-structural 2 (NS2), NS3 and NS5A genes are also important. However, all considered single nucleotide polymorphisms (SNPs) of IL28B and viral genotypes are the most important predictors for interferon based therapy of HCV infection.

Hepatitis C virus (HCV) is a major health problem in developing countries including Pakistan. Chronic HCV infection results in progressive liver disease including fibrosis, cirrhosis, insulin resistance and eventually hepatocellular carcinoma (HCC). Ionotrophic purinergic (P2X) receptors are identified to involve in a spectrum of physiological and pathophysiological processes. However, the role of P2X receptors in HCV liver associated diseases still remains to be investigated. The current study was designed to identify the presence of P2X receptors in human liver cells. Furthermore, it investigates the response of P2X receptors towards HCV structural proteins (E1E2). To determine that how many isoforms of P2X receptors are expressed in human liver cells, human hepatoma cell line (Huh-7) was used. Transcripts (mRNA) of five different isoforms of P2X receptors were identified in Huh-7 cells. To examine the gene expression of identified isoforms of P2X receptors in presence of HCV structural proteins E1E2, Huh-7/E1E2 cell line (stably expressing HCV structural proteins E1E2) was used. The results showed significant increase (6.2 fold) in gene expression of P2X4 receptors in Huh-7/E1E2 cells as compared to control Huh-7 cells. The findings of present study confirmed the presence of transcripts of five different isoforms of P2X receptors in human liver cells and suggest that P2X4 receptors could be represented an important component of the purinergic signaling complex in HCV induced liver pathogenesis.

Background: There is a dire need for the establishment of active dengue surveillance to continuously detect cases, circulating serotypes, and determine the disease burden of dengue fever (DF) in the country and region. Predicting dengue PCR results using machine learning (ML) models represents a significant advancement in pre‐emptive healthcare measures. This study outlines the comprehensive process of data preprocessing, model selection, and the underlying mechanisms of each algorithm employed to accurately predict dengue PCR outcomes.Methods: We analyzed data from 300 suspected dengue patients in Islamabad and Rawalpindi, Pakistan, from August to October 2023. NS1 antigen ELISA, IgM and IgG antibody tests, and serotype‐specific real‐time polymerase chain reaction (RT‐PCR) were used to detect the dengue virus (DENV). Representative PCR‐positive samples were sequenced by Sanger sequencing to confirm the circulation of various dengue serotypes. Demographic information, serological test results, and hematological parameters were used as inputs to the ML models, with the dengue PCR result serving as the output to be predicted. The models used were logistic regression, XGBoost, LightGBM, random forest, support vector machine (SVM), and CatBoost.Results: Of the 300 patients, 184 (61.33%) were PCR positive. Among the total positive cases detected by PCR, 9 (4.89%), 171 (92.93%), and 4 (2.17%) were infected with serotypes 1, 2, and 3, respectively. A total of 147 (79.89%) males and 37 (20.11%) females were infected, with a mean age of 33 ± 16 years. In addition, the mean platelet and leukocyte counts and the hematocrit percentages were 75,447%, 4189.02%, and 46.05%, respectively. The SVM was the best‐performing ML model for predicting RT‐PCR results, with 71.4% accuracy, 97.4% recall, and 71.6% precision. Hyperparameter tuning improved the recall to 100%.Conclusion: Our study documents three circulating serotypes in the capital territory of Pakistan and highlights that the SVM outperformed other models, potentially serving as a valuable tool in clinical settings to aid in the rapid diagnosis of DF.

Objectives: The study aimed to assess the effectiveness of anxiety reduction protocol using auditory distraction in alleviating dental anxiety among patients undergoing tooth extraction.Materials and Methods: A randomized controlled trial was conducted at the Oral Surgery Department at Islamabad Dental Hospital from July to December 2022, involving 50 patients scheduled for tooth extraction. Participants were randomly divided into two groups: an interventional group, exposed to auditory distraction, and a noninterventional group, without exposure to auditory distraction before the dental extraction. Dental anxiety was measured using the modified dental anxiety scale (MDAS) questionnaire, which scores anxiety levels on a range from 5 (not anxious) to 25 (extremely anxious). Anxiety levels were assessed in the waiting room and just before extraction, and the results were compared across both groups to evaluate the effectiveness of auditory distraction in reducing dental anxiety.Results: The sample size of 50 was randomly and equally allocated to the interventional and noninterventional groups. The study population consisted of 28 (56%) female and 22 (44%) male participants. No significant difference was observed between the anxiety scores of interventional and noninterventional groups at baseline. A significant reduction in anxiety scores was observed in the intervention group during postintervention assessment, while no significant difference was seen in the noninterventional group's anxiety scores.Conclusions: The study supports the efficacy of anxiety reduction protocol using auditory distraction as a practical tool for reducing dental anxiety among patients undergoing tooth extraction.