The long-term impact of vaccine clinical research on national stakeholders involved: Experience from a low-income Country.

Clinical trials are the most rigorous scientific and regulated method to investigate the safety and efficacy of vaccines or drugs in pre-licensure stage. Clinical trial design and implementation are complex, time-consuming and involves close engagement with country's regulatory authority, clinical trial sites, investigators, and the healthcare system. Over the past few decades, a significant number of clinical trials have been conducted in low- and middle-income countries (LMICs), particularly in resource-limited settings.

Parental motivations and perceived barriers to participating in pediatric vaccine clinical trials: Findings from the OCV-S trial in Nepal.

Background: Pediatric vaccine clinical trials are crucial for evaluating and ensuring the safety and efficacy of new vaccines for children. However, in low-resource settings like Nepal, where clinical trials are relatively new, recruitment and retention of participants are challenging particularly due to diverse parental backgrounds, motivations and concerns. As such, parental motivations, perceived barriers, and experiences of participating in pediatric vaccine trial in Nepal, which hasn't previously been explored, needs to be understood.

Safety and immunogenicity of the Euvichol-S oral cholera vaccine for prevention of Vibrio cholerae O1 infection in Nepal: an observer-blind, active-controlled, randomised, non-inferiority, phase 3 trial.

Background: In October, 2017, WHO launched a strategy to eliminate cholera by 2030. A primary challenge in meeting this goal is the limited global supply capacity of oral cholera vaccine and the worsening of cholera outbreaks since 2021. To help address the current shortage of oral cholera vaccine, a WHO prequalified oral cholera vaccine, Euvichol-Plus was reformulated by reducing the number of components and inactivation methods.

Safety and immunogenicity of conjugate vaccine for typhoid (Vi-DT): Finding from an observer-blind, active-controlled, randomized, non-inferiority, phase III clinical trial among healthy volunteers.

Typhoid fever is a significant public health concern with most of the sufferers between 15 and 25 y of age in Nepal. We undertook this study to demonstrate Vi polysaccharide conjugated with diphtheria toxoid (Vi-DT) conjugate vaccine which is non-inferior to Typbar typhoid conjugate vaccine, a Vi polysaccharide vaccine conjugated with tetanus toxoid (Vi-TT) with a focus on the adult population from Dhulikhel Hospital which was one of the total four sites in Nepal. In this study, we assigned the eligible participants in 1:1:1:1 ratio by block randomization, and stratified into three age groups (6 months to less than 2 y, 2 y to less than 18 y, and 18 y to 45 y), allotted to Group A, B, C, and D.

Antitumor efficacy of synthesized Ag-Au nanocomposite loaded with PEG and ascorbic acid in human lung cancer stem cells.

Lung cancer is the leading cause of mortality worldwide of which non-small cell lung carcinoma constitutes majority of the cases. High mortality is attributed to early metastasis, late diagnosis, ineffective treatment and tumor relapse. Chemotherapy and radiotherapy form the mainstay of its treatment.

Effect of short-term exposure to air pollution on daily cardio- and cerebrovascular hospitalisations in areas with a low level of air pollution.

Exposure to air pollution is associated with increased cardio- and cerebrovascular diseases. However, the evidence regarding the short-term effect of air pollution on cardio- and cerebrovascular hospitalisations in areas with relatively low air pollution levels is limited. This study aims to examine the effect of short-term exposure to different air pollutants on hospital admissions due to cardio- and cerebrovascular diseases in rural and regional Australia with low air pollution.

Conducting a phase III clinical trial in children during the COVID- 19 pandemic: Experience and lessons learnt from a clinical research facility of Nepal.

Clinical trials in humans are vital to test safety and efficacy of new interventions and are accompanied with the complexity of related regulatory guidelines, stringent time frame and financial burden particularly when participants are children. Conducting clinical trials in low and middle income countries, where 90% of global diseases occur, increases the complexity as resources, infrastructures, and experience related to clinical trials may be limited in some countries. During the COVID-19 pandemic, due to multiple infection control measures such as social distancing, lock-down of the societies, and increased work load of hospital workers, conducting clinical trials seemed very challenging.

Evaluating the cost implications of integrating SARS-CoV-2 genome sequencing for infection prevention and control investigation of nosocomial transmission within hospitals.

Background: The COG-UK hospital-onset COVID-19 infection (HOCI) trial evaluated the impact of SARS-CoV-2 whole-genome sequencing (WGS) on acute infection, prevention, and control (IPC) investigation of nosocomial transmission within hospitals.

Aim: To estimate the cost implications of using the information from the sequencing reporting tool (SRT), used to determine likelihood of nosocomial infection in IPC practice.

Methods: A micro-costing approach for SARS-CoV-2 WGS was conducted.

A randomized, observer-blind, controlled phase III clinical trial assessing safety and immunological non-inferiority of Vi-diphtheria toxoid versus Vi-tetanus toxoid typhoid conjugate vaccine in healthy volunteers in eastern Nepal.

Typhoid remains one of the major serious health concerns for children in developing countries. With extremely drug-resistant cases emerging, preventative measures like sanitation and vaccination, including typhoid conjugate vaccines (TCV) remain the mainstay in its prevention and control. Different types of TCVs are being developed to meet the global demand.

Effectiveness of rapid SARS-CoV-2 genome sequencing in supporting infection control for hospital-onset COVID-19 infection: Multicentre, prospective study.

Background: Viral sequencing of SARS-CoV-2 has been used for outbreak investigation, but there is limited evidence supporting routine use for infection prevention and control (IPC) within hospital settings.

Methods: We conducted a prospective non-randomised trial of sequencing at 14 acute UK hospital trusts. Sites each had a 4-week baseline data collection period, followed by intervention periods comprising 8 weeks of 'rapid' (<48 hr) and 4 weeks of 'longer-turnaround' (5-10 days) sequencing using a sequence reporting tool (SRT).

Immune non-interference and safety study of Vi-DT typhoid conjugate vaccine with a measles, mumps and rubella containing vaccine in 9-15 months old Nepalese infants.

Background: Typhoid fever is a common disease in developing countries especially in the Indian subcontinent and Africa. The available typhoid conjugate vaccines (TCV) have been found to be highly immunogenic in infants and children less than 2 years of age. Many countries are planning to adopt TCV in their routine EPI programs around 9 months of age when measles containing vaccines are given.

Under-mask beard covers achieve an adequate seal with tight-fitting disposable respirators using quantitative fit testing.

Background: Tight-fitting respirators are a critical component of respiratory protection against airborne diseases for health workers. However, they are not recommended for health workers with facial hair. Some health workers are unable to shave for religious or medical reasons.

Detection of differential expression of miRNAs in computerized tomography-guided lung biopsy.

Aims: Nonsmall-cell lung carcinoma comprises 85% of lung malignancies and is usually associated with a poor prognosis due to diagnosis at advanced stages. Molecular diagnosis of computerized tomography (CT)-guided biopsy has the potential to identify subtypes of lung carcinoma like adenocarcinoma (AC) and squamous cell carcinoma (SCC) along with its molecular stratification. This approach will help predict the genetic signature of lung cancer in individual patients.

Factors affecting willingness to participate in vaccine clinical trials in an underdeveloped country: perspective from Nepal.

Due to the inherent complex nature of clinical trials, individual's willingness to participate and hence, enrollment in a clinical trial maybe challenging. When it comes to vaccine clinical trial in children, informed consent needs to be secured from the parents or legally acceptable representatives (LARs). Some of the factors which contribute to hesitancy in taking part in clinical trials are based on the level of education, living standards, part of the world they live, associated burden of disease, fear of different procedures in clinical trial, side effects, limited understanding, limited time, and mistrust with Investigational product.

Oral Cholera Vaccine Efficacy and Effectiveness.

Although measuring vaccine efficacy through the conventional phase III study design, randomized, double-blinded controlled trial serves as the "gold standard", effectiveness studies, conducted in the context of a public health program, seek to broaden the understanding of the impact of a vaccine in a real world setting including both individual and population level impacts. Cholera is an acute diarrheal infection caused by the ingestion of food or water contaminated with the bacterium . Since the 1980s, either killed or live oral cholera vaccines (OCVs) have been developed and efficacy and effectiveness studies have been conducted on OCV.

Safety and immunogenicity of the Vi-DT typhoid conjugate vaccine in healthy volunteers in Nepal: an observer-blind, active-controlled, randomised, non-inferiority, phase 3 trial.

Background: Typhoid fever is an endemic disease in many low-income and middle-income countries. The 2018 WHO position paper recommends that countries should consider typhoid vaccination in high-risk groups and for outbreak control. To address the typhoid vaccine supply and demand gap, a typhoid Vi polysaccharide-diphtheria toxoid (Vi-DT) conjugate vaccine development effort was undertaken to achieve WHO prequalification and contribute to the global supply of typhoid conjugate vaccine.

Challenges and opportunities in setting up a phase III vaccine clinical trial in resource limited settings: Experience from Nepal.

Clinical trials are complicated, time-consuming and costly. From the initial screening, informed consent and recruitment of the participants' to study completion, the sponsor must undertake a wide array of complex and closely monitored operations, complying with international standards for human subject research and local requirements. Conducting these studies in an underdeveloped country, with limited resources, infrastructure, and experience with regulated clinical trials adds to this complexity.

Safety and immunogenicity of Vi-DT conjugate vaccine among 6-23-month-old children: Phase II, randomized, dose-scheduling, observer-blind Study.

Background: Typhoid causes significant mortality among young children in resource-limited settings. Conjugate typhoid vaccines could significantly reduce typhoid-related child deaths, but only one WHO-prequalified typhoid conjugate vaccine exists for young children. To address this gap, we investigated the safety, immunogenicity and dose-scheduling of Vi-DT typhoid conjugate vaccine among children aged 6-23 months.

Review on the Recent Advances on Typhoid Vaccine Development and Challenges Ahead.

Control of Salmonella enterica serovar typhi (S. typhi), the agent of typhoid fever, continues to be a challenge in many low- and middle-income countries. The major transmission route of S.

Prognostic evaluation of metastasizing ameloblastoma: A systematic review of reported cases in literature.

Ameloblastoma is a benign odontogenic tumor which undergoes malignant transformation to ameloblastic carcinoma. However, rarely it metastasizes without undergoing cytological malignant changes, an entity referred to as Metastasizing Ameloblastoma (MA). Through this study, we aimed to review cases of MA reported since 2000 to explore the impact of clinico-demographic variables on its prognosis.

Mitochondrial Stress-Mediated Targeting of Quiescent Cancer Stem Cells in Oral Squamous Cell Carcinoma.

Introduction: Despite improved therapeutics in oral squamous cell carcinoma (OSCC), tumor cells that are either quiescent and/or endowed with stem cell-like attributes usually survive treatment and recreate tumor load at relapse. Through this study, we aimed strategically to eliminate these stem cell-like cancer cells using a combination drug approach.

Methods: Primary cultures from 15 well-moderately differentiated OSCC were established, and the existence of cancer cells with stem cell-like characteristics using five cancer stem cell (CSC) specific markers - CD44, CD133, CD147, C166, SOX2 and spheroid assay was ascertained.

A quantitative method to determine osteogenic differentiation aptness of scaffold.

Osteogenic differentiation of Mesenchymal stem cells (MSCs) on scaffold is crucial for bone tissue engineering. Alkaline phosphatase (ALP) assay is an important method of assessing osteogenesis. Here, a very simple and innovative procedure is being described for quantification of osteogenic differentiation of MSCs in presence of scaffold using ALP assay.

Differential diagnosis of non-small cell lung carcinoma by circulating microRNA.

Introduction: More than 70% of lung cancer comprises nonsmall-cell lung carcinoma and is associated with poor survival outcome owing to late diagnosis. Identification of lung cancer in early stages when no clinical signs or symptoms are evident, can drastically improve the prognosis. To this end, we aimed to evaluate the changes occurring at tissue level by assessing the expression of six microRNAs (miRNAs) in lung adenocarcinoma (AC) and squamous cell carcinoma (SCC).