Search results for: Lok Bahadur Shrestha

Authors: Sachin Mulmi Shrestha, Xin Fang, Hui Ye, Lihua Ren, Qinghua Ji, Ruihua Shi

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Background: Esophageal squamous cell carcinoma (ESCC) is a tumor arising from esophageal epithelial cells and is one of the major disease subtype in Asian countries, including China. Esophageal cancer is the 7th highest incidence based on the 2020 data of GLOBOCAN. The pathogenesis of cancer is still not well understood as many molecular and genetic basis of esophageal carcinogenesis has yet to be clearly elucidated. Circular RNAs are RNA molecules that are formed by back-splicing covalently joined 3′- and 5′-endsrather than canonical splicing, and recent data suggest circular RNAs could sponge miRNAs and are enriched with functional miRNA binding sites. Hence, we studied the mechanism of circular RNA, its biological function, and the relationship between microRNA in the carcinogenesis of ESCC. Methods: 4 pairs of normal and esophageal cancer tissues were collected in Zhongda hospital, affiliated to Southeast University, and high-throughput RNA sequencing was done. The result revealed that circ_0032746 was upregulated, and thus we selected circ_0032746 for further study. The backsplice junction of circRNA was validated by sanger sequence, and stability was determined by RNASE R assay. The binding site of circRNA and microRNA was predicted by circinteractome,mirandaand RNAhybrid database. Furthermore, circRNA was silenced by siRNA and then by lentivirus. The regulatory axis of circ0032746/miR4270 was validated by shRNA, mimic, and inhibitor transfection. Then, in vitro experiments were performed to assess the role of circ0032746 on proliferation (CCK-8 assay and colon formation assay), migration and invasion (Transewell assay), and apoptosis of ESCC. Results: The upregulated circ0032746 was validated in 9 pairs of tissues and 5 types of cell lines by qPCR, which showed high expression and was statistically significant (P<0.005) ). Upregulated circ0032746 was silenced by shRNA, which showed significant knockdown in KYSE 30 and TE-1 cell lines expression compared to control. Nuclear and cytoplasmic mRNA fraction experiment displayed the cytoplasmic location of circ0032746. The sponging of miR4270 was validated by co-transfection of sh-circ0032746 and mimic or inhibitor. Transfection with mimic showed the decreased expression of circ_0032746, whereas inhibitor inhibited the result. In vitro experiments showed that silencing of circ_0032746 inhibited the proliferation, migration, and invasion compared to the negative control group. The apoptosis was seen higher in a knockdown group than in the control group. Furthermore, 11 common mircoRNA target mRNAs were predicted by Targetscan, MirTarbase, and miRanda database, which may further play role in the pathogenesis. Conclusion: Our results showed that novel circ_0032746 is upregulated in ESCC and plays role in itsoncogenicity. Silencing of circ_0032746 inhibits the proliferation and migration of ESCC whereas increases the apoptosis of cancer cells. Hence, circ0032746 acts as an oncogene in ESCC by sponging with miR4270 and could be a potential biomarker in the diagnosis of ESCC in the future.

Keywords: circRNA, esophageal squamous cell carcinoma, microRNA, upregulated

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Authors: Purna Bahadur Lamichhane

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Education planning and management are foundational pillars for developing effective educational systems. However, in many educational contexts, especially in developing nations, technology-enabled management is still emerging. In such settings, manual-based systems, where instructions and guidelines are physically documented, remain central to educational planning and management. This paper examines the effectiveness, challenges, and potential of manual-based education planning systems in fostering structured, reliable, and adaptable management frameworks. The objective of this study is to explore how a manual-based approach can successfully guide administrators, educators, and policymakers in delivering high-quality education. By using structured, accessible instructions, this approach serves as a blueprint for educational governance, offering clear, actionable steps to achieve institutional goals. Through an analysis of case studies from various regions, the paper identifies key strategies for planning school schedules, managing resources, and monitoring academic and administrative performance without relying on automated systems. The findings underscore the significance of organized documentation, standard operating procedures, and comprehensive manuals that establish uniformity and maintain educational standards across institutions. With a manual-based approach, management can remain flexible, responsive, and user-friendly, especially in environments where internet access and digital literacy are limited. Moreover, it allows for localization, where instructions can be tailored to the unique cultural and socio-economic contexts of the community, thereby increasing relevancy and ownership among local stakeholders. This paper also highlights several challenges associated with manual-based education management. Manual systems often require significant time and human resources for maintenance and updating, potentially leading to inefficiencies and inconsistencies over time. Furthermore, manual records can be susceptible to loss, damage, and limited accessibility, which may affect decision-making and institutional memory. There is also the risk of siloed information, where crucial data resides with specific individuals rather than being accessible across the organization. However, with proper training and regular oversight, many of these limitations can be mitigated. The study further explores the potential for hybrid approaches, combining manual planning with selected digital tools for record-keeping, reporting, and analytics. This transitional strategy can enable schools and educational institutions to gradually embrace digital solutions without discarding the familiarity and reliability of manual instructions. In conclusion, this paper advocates for a balanced, context-sensitive approach to education planning and management. While digital systems hold the potential to streamline processes, manual-based systems offer resilience, inclusivity, and adaptability for institutions where technology adoption may be constrained. Ultimately, by reinforcing the importance of structured, detailed manuals and instructional guides, educational institutions can build robust management frameworks that facilitate both short-term successes and long-term growth in their educational mission. This research aims to provide a reference for policymakers, educators, and administrators seeking practical, low-cost, and adaptable solutions for sustainable educational planning and management.

Keywords: educatoin, planning, management, manual

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Authors: Kuo Chieh Chao, Thishani Amarathunga, Sangam Shrestha

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Rainfall induced slope failures are one of the most damaging and disastrous natural hazards which occur frequently in the world. This type of sliding mainly occurs in the zone above the groundwater level in silty/sandy soils. When the rainwater begins to infiltrate into the vadose zone of the soil, the negative pore-water pressure tends to decrease and reduce the shear strength of soil material. Climate change has resulted in excessive and unpredictable rainfall in all around the world, resulting in landslides with dire consequences to human lives and infrastructure. Such problems could be overcome by examining in detail the causes for such slope failures and recommending effective repair plans for vulnerable locations by considering future climatic change. The selected area for this study is located in the road rehabilitation section from Maubara to Mota Ain road in Timor-Leste. Slope failures and cracks have occurred in 2013 and after repairs reoccurred again in 2017 subsequent to heavy rains. Both observed and future predicted climate data analyses were conducted to understand the severe precipitation conditions in past and future. Observed climate data were collected from NOAA global climate data portal. CORDEX data portal was used to collect Regional Climate Model (RCM) future predicted climate data. Both observed and RCM data were extracted to location-based data using ArcGIS Software. Linear scaling method was used for the bias correction of future data and bias corrected climate data were assigned to GeoStudio Software. Precipitations of wet seasons (December to March ) in 2007 to 2013 is higher than 2001-2006 period and it is more than nearly 40% higher precipitation than usual monthly average precipitation of 160mm.The results of seepage analyses which were carried out using SEEP/W model with observed climate, clearly demonstrated that the pore water pressure within the fill slope was significantly increased due to the increase of the infiltration during the wet season of 2013.One main Regional Climate Models (RCM) was analyzed in order to predict future climate variation under two Representative Concentration Pathways (RCPs).In the projected period of 76 years ahead from 2014, shows that the amount of precipitation is considerably getting higher in the future in both RCP 4.5 and RCP 8.5 emission scenarios. Critical pore water pressure conditions during 2014-2090 were used in order to recommend appropriate remediation methods. Results of slope stability analyses indicated that the factor of safety of the fill slopes was reduced from 1.226 to 0.793 during the dry season to wet season in 2013.Results of future slope stability which were obtained using SLOPE/W model for the RCP emissions scenarios depict that, the use of tieback anchors and geogrids in slope protection could be effective in increasing the stability of slopes to an acceptable level during the wet seasons. Moreover, methods and procedures like monitoring of slopes showing signs or susceptible for movement and installing surface protections could be used to increase the stability of slopes.

Keywords: climate change, precipitation, SEEP/W, SLOPE/W, unsaturated soil

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Authors: Nirajan Shrestha

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Karnali is one of the most vulnerable provinces in Nepal, facing challenges from climate change, poverty, and natural calamities across different regions. In recent years, the province has been severely impacted by climate change stress such as temperature rises in glacier lake of mountainous region and spring source water shortages, particularly in hilly areas where settlements are located, and water sources have depleted from their original ground levels. As a result, Karnali could face a future without enough water for all. Deep causes of sustainable safe water supply have always been neglected in rural areas of Nepal, and communities are unfairly burdened with a challenge of keeping water facilities functioning in areas affected by frequent natural disasters where there is a substantial, well-documented funding gap between the revenues from user payments and the full cost of sustained services. The key importance of a permanent system to support communities in service delivery has been always underrated so far. The complexity of water service sustainability as a topic should be simplified to one clear indicator: the functionality rate, which can be expressed as uptime or the percentage of time that the service is delivered over the total time. For example, a functionality rate of 80% means that the water service is operational 80% of the time, while 20% of the time the system is not functioning. This represents 0.2 multiplied by 365, which equals 73 days every year, or roughly two and a half months without water. This percentage should be widely understood and used in Karnali. All local governments should report their targets and performance in improving it, and there should be a broader discussion about what target is acceptable and what can be realistically achieved. In response to these challenges, the Sustainable WASH for All (SUSWA) project has introduced innovative models and policy formulation strategies in various working local government. SUSWA’s approach, which delegates rural water supply and sanitation responsibilities to local governments, has been instrumental in addressing these issues. To keep pace with the growing demand, the province has adopted a service support center model, linking local governments with federal authorities to ensure effective service delivery to the communities By enhancing WASH governance through local governments engagement, capacity building and inclusive WASH policy frameworks, there is potential to address WASH gaps while fostering a circular economy. This strategy emphasizes resource recovery, waste minimization and the creation of local employment generation opportunities. The research highlights key governance mechanisms, innovative practices and policy interventions that can be scaled up across other regions. It also provides recommendations on how to leverage Karnali’s unique socio-economic and environmental context nature-based solutions to inspire innovation and drive sustainable WASH solutions. Key findings suggest that with strong ownership and leadership of local governments, community engagement and appropriate technology, Karnali Province can become a model for integrating WASH governance with circular economy concept, providing broader lessons for other regions in Nepal.

Keywords: vulnerable provinces, natural calamities, climate change stres, spring source depletion, resources recovery, governance mechanisms, appropriate technology, community engagement, innovation

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Authors: Keshari Shrestha, Philip Vatterott

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Introduction: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare and potentially fatal drug-related syndrome. DRESS classically presents with a diffuse maculopapular rash, fevers, and eosinophilia more than three weeks after drug exposure. DRESS can present with multi-organ involvement, with liver damage being the most common and severe. Pulmonary involvement is a less common manifestation and is associated with poor clinical outcomes. Chest imaging is often nonspecific, and symptoms can range from mild cough to acute respiratory distress syndrome (ARDS) . This is a case of a 49-year-old female with a history of recent clostridium difficile colitis status post treatment with oral vancomycin who presented with rash, acute liver and kidney failure, as well as diffuse nodular alveolar lung opacities concerning for DRESS syndrome with multi-organ involvement. Clinical Course: This patient initially presented to an outside hospital with clostridium difficile colitis, acute liver injury, and acute kidney injury. She developed a desquamating maculopapular rash in the setting of recent oral vancomycin, meloxicam, and furosemide initiation. She was hospitalized on two additional occasions with worsening altered mental status, liver injury, and acute kidney injury and was initiated on intermittent hemodialysis. Notably, she was found to have systemic eosinophilia (4100 cells/microliter) several weeks prior. She was transferred to this institution for further management where she was found to have encephalopathy, jaundice, lower extremity edema, and diffuse bilateral rhonchorous breath sounds on pulmonary examination. The patient was started on methylprednisolone for suspected DRESS syndrome. She underwent an evaluation for alternative causes of her organ failure. Her workup included a negative infectious, autoimmune, metabolic, toxic, and malignant work-up. Abdominal computed tomography (CT) and ultrasound were remarkable for evidence of hepatic steatosis and possible cirrhotic morphology. Additionally, a chest CT demonstrated diffuse and symmetric nodular alveolar lung opacities with peripheral sparing not consistent with acute respiratory distress syndrome or edema. Ultimately, her condition continued to decline, and she required intubation on several occasions. On hospital day 25 she succumbed to distributive shock in the setting of probable sepsis and multi-organ failure. Discussion: DRESS syndrome occurs in 1 in 1,000 to 10,000 patients with a mortality rate of around 10%. Anti-convulsant, anti-bacterial, anti-viral, and sulfonamide drugs are the most common drugs implicated in the development of DRESS syndrome; however, the list of offending agents is extensive . The diagnosis of DRESS syndrome is made after excluding other causes of disease such as infectious and autoimmune etiologies. The RegiSCAR scoring system is used to diagnose DRESS syndrome with 2-3 points indicating possible disease, 4-5 probable disease, and >5 definite disease. This patient scored a 7 on the RegiSCAR scale for eosinophilia, rash, organ involvement, and exclusion of other causes (infectious and autoimmune). While the pharmacologic trigger in this case is unknown, it is speculated to be caused by vancomycin, meloxicam, or furosemide due to the favorable timeline of initiation. Despite aggressive treatment, DRESS syndrome can often be fatal. Because of this, early diagnosis and treatment of patients with suspected DRESS syndrome is imperative.

Keywords: drug reaction with eosinophilia and systemic symptoms, multi-organ failure, pulmonary involvement, renal failure

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