Publications by authors named "Niraj Shrestha"

To comply with regulatory guidelines and ensure that biopharmaceutical agents meet safety and efficacy, we developed an analytical method to detect anti-drug antibodies (ADAs) generated in response to HCW9218, a fusion molecule containing the human soluble TGF-β RII and IL-15/IL-15 Rα sushi domains. The method demonstrated a sensitivity of 34.6 ng/mL with a suitably high degree of specificity, selectivity, and precision.

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  • Adoptive cellular therapy (ACT) using memory-like natural killer (NK) cells activated with specific cytokines shows promise in treating blood cancers, especially when combined with new fusion molecules.
  • The multifunctional fusion molecule HCW9206 improves the expansion of NK cells that have been primed with another molecule (HCW9201), leading to a significant increase in their quantity and activity.
  • The "Prime and Expand" strategy enhances NK cell metabolism and durability, making it a more efficient method for preparing clinical-grade NK cells for future cancer treatments.
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Chronic kidney disease (CKD) has emerged as one of the major public health concerns. The increasing prevalence of its correlates such as obesity, diabetes, and hypertension has been, due in part responsible for the increased burden. However, very few studies have presented the comprehensive data on burden of disease particularly in developing countries like Nepal.

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Cardiovascular diseases (CVDs) have emerged as the leading cause of deaths worldwide in 2019. Globally, more than three-quarters of the total deaths due to CVDs occur in low- and middle-income countries like Nepal. Although increasing number of studies is available on the prevalence of CVDs, there is limited evidence presenting a complete picture on the burden of CVDs in Nepal.

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  • The accumulation of senescent cells (SNCs) contributes to chronic inflammation and age-related diseases, but the bifunctional immunotherapeutic HCW9218 can reduce these cells and their harmful effects.
  • In diabetic mice, HCW9218 improved glucose metabolism and insulin resistance by decreasing senescent pancreatic beta cells and related inflammation.
  • Additionally, in aged mice, HCW9218 not only lowered senescent cells but also improved gene expression linked to metabolism and longevity, enhancing physical performance without harming their overall health.
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Women's autonomy on sexual and reproductive health issues is critical to women's health and well-being. Women have the right to decide on their fertility and sexuality, be free from coercion and violence, and achieve well-being. This study has identified women's autonomy regarding decision and exercise of their sexual reproductive health and rights and its association with determining factors in Nepal.

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Atherosclerosis is a chronic inflammatory disease caused by deposition of oxidative low-density lipoprotein (LDL) in the arterial intima which triggers the innate immune response through myeloid cells such as macrophages. Regulatory T cells (Tregs) play an important role in controlling the progression or regression of atherosclerosis by resolving macrophage-mediated inflammatory functions. Interleukin-2 (IL-2) signaling is essential for homeostasis of Tregs.

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Globally, the number of people living with diabetes mellitus (DM) increased by 62% between 1990 and 2019, affecting 463 million people in 2019, and is projected to increase further by 51% by 2045. The increasing burden of DM that requires chronic care could have a considerable cost implication in the health system, particularly in resource constraint settings like Nepal. In this context, this study attempts to present the burden of DM in terms of prevalence, mortality, and disability adjusted life years (DALYs).

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  • Therapy induced senescence (TIS) in tumors leads to cancer cells producing proinflammatory substances known as SASP factors, which can cause treatment resistance and cancer relapse.
  • The immunotherapeutic agent HCW9218 enhances the ability of immune cells to target and eliminate TIS tumor cells, improving the effectiveness of standard chemotherapy drugs like docetaxel and gemcitabine.
  • HCW9218 works by breaking down the immunosuppressive tumor environment, boosting immune cell activity, and reducing harmful SASP factors in both tumors and surrounding healthy tissues.
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Copper (Cu) incorporation is a key process for fabricating efficient CdTe-based thin-film solar cells and has been used in CdTe-based solar cell module manufacturing. Here, we investigate the effects of different Cu precursors on the performance of CdTe-based thin-film solar cells by incorporating Cu using a metallic Cu source (evaporated Cu) and ionic Cu sources (solution-processed cuprous chloride (CuCl) and copper chloride (CuCl)). We find that ionic Cu precursors offer much better control in Cu diffusion than the metallic Cu precursor, producing better front junction quality, lower back-barrier heights, and better bulk defect property.

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  • Natural killer (NK) cells show promise as a cancer treatment but face issues such as persistence and tumor recognition; priming them with specific interleukins (rhIL-12, rhIL-15, rhIL-18) enhances their effectiveness.
  • A new platform using inert tissue factor scaffolds was created to produce heteromeric fusion protein complexes, enabling scalable production of these interleukins (HCW9201) and additional CD16 engagement (HCW9207).
  • Studies show that HCW9201 improves NK cell function and memory-like characteristics, making it a potential solution for producing effective NK cells in a clinical setting for cancer therapies.
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Background: Equity has emerged as a cross-cutting theme in the health sector, and countries across the world are striving to ensure that all people have access to the health services they need without undue financial hardship and educational, social, cultural and geographical barriers. In this context, this analysis has attempted to analyse Nepal's progress in reducing inequalities in reproductive, maternal, newborn and child health services based on economic status and place of residence.

Methods: In this analysis, we have used data available from the web version of the Health Equity Assessment Toolkit, a data visualisation tool developed by the World Health Organisation.

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  • - The study highlights violence among adolescents as a significant public health issue in Nepal, with findings indicating high rates of physical and sexual violence experienced by school-going youths.
  • - Using data from the Global School-based Student Health Survey, the researchers identified factors linked to violence, such as age, parental supervision, feelings of safety in school, bullying, and corporal punishment.
  • - The results suggest that addressing these factors could inform better interventions by school administrations, parents, and policymakers to reduce violence among adolescents.
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Background: Between 1990 and 2017, Nepal experienced a shift in the burden of disease from communicable, maternal, neonatal and nutritional (CMNN) diseases to non-communicable diseases (NCDs). With an increasing ageing population and life-style changes including tobacco use, harmful alcohol consumption, unhealthy diets, and insufficient physical activity, the proportion of total deaths from NCDs will continue to increase. An analysis of current diseases pattern and projections of the trends informs planning of health interventions.

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Background: Injury-related mortality and morbidity, a leading cause of death and disability worldwide, is common among adolescents.  However, there is insufficient information on the status and factors responsible for injury among adolescents in Nepal. Hence, the paper estimates the injury prevalence and identify the factors associated with it among adolescent Nepalese students.

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Management of COVID-19 in Nepal will certainly benefit from the experiences of other countries. However, they are less likely to be suitable for Nepal both in terms of context and resource availability. Social contact pattern studies have shown that understanding the nature of human-to-human contacts can help describe the dynamics of infectious disease transmission.

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The replacement of traditional CdS with zinc magnesium oxide (ZMO) has been demonstrated as being helpful to boost power conversion efficiency of cadmium telluride (CdTe) solar cells to over 18%, due to the reduced interface recombination and parasitic light absorption by the buffer layer. However, due to the atmosphere sensitivity of ZMO film, the post treatments of ZMO/CdTe stacks, including CdCl treatment, back contact deposition, etc., which are critical for high-performance CdTe solar cells became crucial challenges.

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Background: The purpose of this study is to compare the clinical and radiological outcome of medial versus posterior triceps splitting approach in open reduction internal fixation of displaced supracondylar fracture of humerus in children.

Methods: A retrospective review of total 70 children with medial approach (n=30) and posterior triceps splitting approach (n=40) children was made. Time to radiological union, postoperative Bauman's angle and Lateral humerocapitellar angle was compared for radiological outcome.

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Temperature-dependent photoluminescence (PL) spectroscopy measurements have been performed over a range from 9 K to room temperature on polycrystalline methylammonium (MA)/formamidinium (FA) lead iodide (MAFAPbI) perovskite thin films. Our low-temperature PL analysis reveals the existence of charge compensating defects in MAPbI, which may explain the lower net free carrier concentration in MAPbI perovskite. More interestingly, we observe the suppression of the PL emission associated with the charged defects by appropriate FA inclusion.

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Organic p-type semiconductors with tunable structures offer great opportunities for hybrid perovskite solar cells (PVSCs). We report herein two dithieno[3,2-b:2',3'-d]pyrrole (DTP) cored molecular semiconductors prepared through π-conjugation extension and an N-alkylation strategy. The as-prepared conjugated molecules exhibit a highest occupied molecular orbital (HOMO) level of -4.

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Organic-inorganic metal halide perovskites are notoriously unstable in humid environments. While many studies have revealed the morphology and crystal structure changes that accompany exposure to humidity, little is known about changes to the photophysics that accompany the degradation process. By combining in situ steady-state and time-resolved photoluminescence with Hall effect measurements, we examined the changes in the photoexcited carrier dynamics for methylammonium lead iodide (MAPbI) and bromide (MAPbBr) films exposed to nitrogen gas containing water vapor at 80% relative humidity.

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The host employs both cell-autonomous and system-level responses to limit pathogen replication in the initial stages of infection. Previously, we reported that the eukaryotic initiation factor 2α (eIF2α) kinases heme-regulated inhibitor (HRI) and protein kinase R (PKR) control distinct cellular and immune-related activities in response to diverse bacterial pathogens. Specifically for , there was reduced translocation of the pathogen to the cytosolic compartment in HRI-deficient cells and consequently reduced loading of pathogen-derived antigens on major histocompatibility complex class I (MHC-I) complexes.

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Background: Models of infectious disease are increasingly utilising empirical contact data to quantify the number of potentially infectious contacts between age groups. While a growing body of data is being collected on contact patterns across many populations, less attention has been paid to the social contacts of young infants. We collected information on the social contacts of primary carers of young infants and investigated their potential for use as a proxy for contacts made by their infant.

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Control over grain size and crystallinity is important for preparation of methylammonium lead iodide (MAPbI) solar cells. We explore the effects of using small concentrations of Cd and unusually high concentrations of methylammonium iodide during the growth of MAPbI in the two-step solution process. In addition to improved crystallinity and an enhancement in the size of the grains, time-resolved photoluminescence measurements indicated a dramatic increase in the carrier lifetime.

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Perovskite/silicon tandem solar cells with high power conversion efficiencies have the potential to become a commercially viable photovoltaic option in the near future. However, device design and optimization is challenging because conventional characterization methods do not give clear feedback on the localized chemical and physical factors that limit performance within individual subcells, especially when stability and degradation is a concern. In this study, we use light beam induced current (LBIC) to probe photocurrent collection nonuniformities in the individual subcells of perovskite/silicon tandems.

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