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Pulmonary arterial hypertension (PAH) is a serious, progressive, and potentially fatal lung disease characterized by a gradual increase in mean pulmonary arterial pressure to over 20 mmHg at rest. The pathogenesis of PAH is multifactorial. It involves dynamic obstruction of the pulmonary vasculature through vasoconstriction, structural obstruction due to adverse vascular remodeling, and pathological obstruction caused by vascular fibrosis and stiffening, which reduces compliance. PAH often presents with vague initial symptoms and is frequently diagnosed at an advanced stage. The increased pulmonary arterial pressure leads to vascular remodeling, eventually resulting in right ventricular hypertrophy and failure. PAH is a rare condition with a median life expectancy of three years, underscoring the need for effective treatment alternatives. Several FDA-approved therapeutic options are available, including prostacyclin analogs (epoprostenol, iloprost, and treprostinil), the non-prostanoid IP receptor agonist selexipag, selective endothelin receptor antagonists (ERA) (ambrisentan, bosentan, and macitentan), phosphodiesterase 5 inhibitors (sildenafil and tadalafil), and the soluble guanylate cyclase (sGC) stimulator riociguat. Despite these advancements, current medications do not provide a permanent cure. This study presents an overview of current and emerging PAH therapies through a systematic literature review. It involved an analysis of nine studies and a review of 800 papers from reputable journals published between 2013 and June 2023. The research focused on drug effects on the six-minute walk distance (6-MWD) and associated side effects in randomized controlled trials. The review found that while udenafil, imatinib, racecadotril, sotatercept, anastrozole, riociguat, tacrolimus, and ralinepag were evaluated, imatinib was notably associated with adverse side effects. Conversely, udenafil, racecadotril, sotatercept, anastrozole, riociguat, tacrolimus, and ralinepag were found to be safe, well-tolerated, and effective in improving hemodynamic measures and 6-MWDs. This study aims to summarize the developing treatment options currently under clinical trials, highlighting the need for further trials before their application in clinical practice., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Rasheed et al.)

Since two-dimensionalal (2D) materials have distinct chemical and physical properties, they are widely used in various sectors of modern technologies. In the domain of diagnostic biodevices, particularly for point-of-care (PoC) biomedical diagnostics, 2D-based field-effect transistor biosensors (bio-FETs) demonstrate substantial potential. Here, in this review article, the operational mechanisms and detection capabilities of biosensing devices utilizing graphene, transition metal dichalcogenides (TMDCs), black phosphorus, and other 2D materials are addressed in detail. The incorporation of these materials into FET-based biosensors offers significant advantages, including low detection limits (LOD), real-time monitoring, label-free diagnosis, and exceptional selectivity. The review also highlights the diverse applications of these biosensors, ranging from conventional to wearable devices, underscoring the versatility of 2D material-based FET devices. Additionally, the review provides a comprehensive assessment of the limitations and challenges faced by these devices, along with insights into future prospects and advancements. Notably, a detailed comparison of FET-based biosensors is tabulated along with various other biosensing platforms and their working mechanisms. Ultimately, this review aims to stimulate further research and innovation in this field while educating the scientific community about the latest advancements in 2D materials-based biosensors., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background/aims: Hepatitis C virus infects more than 3% of the world's population and 4% of Pakistan's population. The virus multiplies in the host using novel methods, defending itself from the host's immune response, ultimately leading to liver cirrhosis and hepatocellular carcinoma. The approved therapy for the disease is interferon alpha combined with ribavirin. The disease is incurable, and often resistant, due to multiple viral and cellular factors. However, a strong host system can minimize the viral count to zero. This study was designed to detect the functional interferon alpha receptor 2 in liver biopsies of interferon resistant hepatitis C virus patients., Methodology: Total messenger ribonucleic acid was isolated from the liver biopsies of the interferon resistant hepatitis C virus patients and subjected to complementary deoxyribonucleic acid synthesis. Primers specific to interferon alpha receptor 2 were designed and used in polymerase chain reaction to detect interferon alpha receptor 2., Results: Interferon alpha receptor 2 was detected in 90% of interferon resistant hepatitis C virus patients., Conclusion: Lack of expression of functional Interferon Alpha Receptor 2 does not seem to be the major cause of interferon resistance in hepatitis C virus patients receiving standard interferon therapy.

Objective: To describe the methodology used to conduct a scoping review of spinal cord injury (SCI) rehabilitation service delivery in Canada, and to explain the reporting process intended to advance future service delivery., Evidence Acquisition: A SCI rehabilitation framework derived from the International Classification of Function, Disability and Health was developed to describe the goals and interprofessional processes of rehabilitation. An adapted Arksey and O'Malley (2005) methodological framework was used to conduct a scoping review of SCI rehabilitation services in Canada. Data were obtained from multiple relevant sources via survey (N = 3572 data fields) from 13 of 15 Canadian tertiary SCI rehabilitation sites, systematic reviews, white papers, literature reviews, clinical practice resources, and clinicians. Multidisciplinary teams of content experts (N = 17), assisted with data interpretation and validation by articulating practice trends, gaps, and priorities., Evidence Synthesis: The findings will be presented in an atlas, which includes aggregate national data regarding impairment and demographic characteristics, service utilization, available resources (staff and capital equipment), specialized services, local expertise, and current best practice indicators, outcome measures, and clinical guidelines. Data were collated and synthesized relative to specific rehabilitation goals. The current state of SCI rehabilitation service delivery (specific to each rehabilitation goal) is summarized in a report card within three domains, knowledge generation, clinical application, and policy change, and specifies key 2020 priorities., Conclusion: These findings should prompt critical evaluation of current Canadian SCI rehabilitation service delivery while specifying enhancements in knowledge generation, clinical application and policy change domains likely to assist with achievement of best practices by 2020.