Publications by authors named "Dhakal A"

Paediatric dialysis services have been available in Nepal for three decades but are limited to a few tertiary referral centres in major cities. The availability of a small number of paediatric nephrologists, an increasing number of adult nephrologists, and a modest increase in dialysis facilities have contributed to the gradual expansion of paediatric nephrology and kidney replacement therapy services in Nepal over the last decade. These services have grown steadily and will continue to grow because of the positive impact of government support for kidney replacement therapy and various public health initiatives to promote kidney health.

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Cryo-electron microscopy (cryo-EM) has revolutionized structural biology by enabling the determination of high-resolution 3-Dimensional (3D) structures of large biological macromolecules. Protein particle picking, the process of identifying individual protein particles in cryo-EM micrographs for building protein structures, has progressed from manual and template-based methods to sophisticated artificial intelligence (AI)-driven approaches in recent years. This review critically examines the evolution and current state of cryo-EM particle picking methods, with an emphasis on the impact of AI.

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  • Researchers sequenced 470 genomes of domesticated river and swamp buffaloes and their wild ancestors to investigate the genetic factors influencing domestication and productivity in Asian water buffaloes.* -
  • Wild swamp buffaloes maintain ancestral morphology, while river buffaloes show distinct traits, yet both have genomes that align closely with wild counterparts; genetic diversity varies significantly across regions.* -
  • Key findings indicate that artificial selection has led to significant genetic adaptations in traits like reproduction, milk production, and coat color, highlighting how domestication affects evolutionary changes in these animals.*
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  • * A qualitative study involving 35 patients with non-communicable diseases revealed that facilitators for using healthcare services included free medicines, accessibility, and positive interactions with providers, while barriers included insufficient services, high costs, and lack of information.
  • * The study concludes that improving the utilization of NCD services can be achieved by enhancing patient knowledge, motivation, and addressing misconceptions, along with strengthening healthcare accessibility and provider-patient communication.
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We report the efficacy of trastuzumab deruxtecan (T-DXd) in treating human epidermal growth factor receptor 2 (HER2) low, type ID leptomeningeal breast cancer (LMD) (with positive cerebrospinal fluid [CSF] cytology and hydrocephalus as the only abnormal imaging finding) and the diagnostic and monitoring utilization of a novel microfluidic platform called CNSide™. Breast cancer LMD is associated with poor prognosis, and effective treatments are lacking. Our case highlights two crucial aspects related to the treatment and monitoring of breast cancer LMD.

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Background: Indigenous buffaloes, as the important livestock species contributing to economy of the country, are the lifeline of livelihood in Nepal. They are distributed across diverse geographical regions of the country and have adapted to various feeding, breeding, and management conditions. The larger group of these native buffalo breeds are present in narrow and stiff hilly terrains.

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  • The study examines the connection between breast cancer subtypes and CSF cytology results with overall survival among patients with leptomeningeal disease.
  • Out of 69 participants, triple-negative breast cancer was linked to significantly shorter survival compared to ER+/HER2- subtype, while CSF- patients had better overall survival compared to those with positive or not tested CSF results.
  • The findings highlight the importance of breast cancer subtypes and CSF cytology in determining patient prognosis, suggesting that specific subtypes could influence survival outcomes.
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Catalytic DNA has gained significant attention in recent decades as a highly efficient and tunable catalyst, thanks to its flexible structures, exceptional specificity, and ease of optimization. Despite being composed of just four monomers, DNA's complex conformational intricacies enable a wide range of nuanced functions, including scaffolding, electrocatalysis, enantioselectivity, and mechano-electro spin coupling. DNA catalysts, ranging from traditional DNAzymes to innovative DNAzyme hybrids, highlight the remarkable potential of DNA in catalysis.

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  • The study explores how different polymers affect the formation of metal-organic framework (MOF) composites and how these MOFs influence the polymer gelation process, with implications for drug delivery and environmental applications.
  • Polymers with high-density carboxylic acids hinder MOF formation, while using fewer carboxylic acids or substituting with hydroxyls allows both MOF creation and polymer gelation, demonstrated with poly(ethylene glycol) (PEG) and poly(vinyl alcohol) (PVA) composites.
  • The resulting PVA-MOF composites show significantly improved properties, like enhanced drug loading and release capabilities, highlighting their potential in advanced materials design.
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Purpose: Imlunestrant is a next-generation oral selective estrogen receptor (ER) degrader designed to deliver continuous ER target inhibition, including in mutant breast cancer. This phase Ia/b trial determined the recommended phase II dose (RP2D), safety, pharmacokinetics, and efficacy of imlunestrant, as monotherapy and in combination with targeted therapy, in ER-positive (ER+) advanced breast cancer (ABC) and endometrial endometrioid cancer. The ER+/human epidermal growth factor receptor 2-negative (HER2-) ABC experience is reported here.

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The objective of the study is to assess impact of systemic disease (SD) status on overall survival and brain metastasis (BM) control, adopting a novel landmark approach to categorize SD among breast cancer (BC) patients. This single institution retrospective study included BCBM patients who have received stereotactic radiosurgery (SRS) to brain. Separate endpoints [CNS failure-free survival (cFFS), overall survival (OS)] were analyzed from each Landmark (LM): LM1 (3-months), LM2 (6-months).

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In this work, carbonization and subsequent activation procedures were adopted to synthesize waste shea butter shells into oxygen-rich interconnected porous activated carbon (SAC_x, x is the mass ratio of KOH used for activation). The SAC_1.5 electrode material showed outstanding electrochemical performance with high specific capacitance (286.

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Ethnomedicinally, more than 2000 plants were found to be used in Nepal. Among them, the red colored rhizome of and the bark of have been used widely to treat muscle fatigue, bone pain, fever, postpartum hemorrhage, and thirst by healers in Kaski and Tanahun districts, Nepal. However, scientific evidence towards their traditional uses is lacking till December, 2023.

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Picking protein particles in cryo-electron microscopy (cryo-EM) micrographs is a crucial step in the cryo-EM-based structure determination. However, existing methods trained on a limited amount of cryo-EM data still cannot accurately pick protein particles from noisy cryo-EM images. The general foundational artificial intelligence-based image segmentation model such as Meta's Segment Anything Model (SAM) cannot segment protein particles well because their training data do not include cryo-EM images.

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Breast cancer (BC) with average human epidermal growth factor receptor 2 (HER2) signals/cell ≥6 and HER2/chromosome enumeration probe 17 (CEP17) ratio <2 (in situ hybridization [ISH] group 3) is very rare, accounting for 0.4% to 3.0% of cases sent for the dual-probe ISH assay.

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Oats (Avena sativa L.) provide unique nutritional benefits and contribute to sustainable agricultural systems. Breeding high-value oat varieties that meet milling industry standards is crucial for satisfying the demand for oat-based food products.

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  • Head and Neck Squamous Cell Carcinoma (HNSCC) is a complex group of tumors influenced by the tumor microenvironment (TME), which includes microorganisms and immune cells, affecting treatment response and survival rates.
  • Researchers analyzed RNA sequencing data from The Cancer Genome Atlas (TCGA) to link specific microbes and gene expression patterns to overall survival (OS), finding that the presence of the Alphapapillomavirus 9 virus was associated with better survival outcomes.
  • The study revealed that HPV-negative tumors had a higher presence of certain harmful microbes and macrophages linked to tumor progression, suggesting the TME's potential role in predicting patient outcomes and understanding resistance to therapies.
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Household buffalo dairy farming is gaining popularity nowadays in Bangladesh because of the outstanding food value of buffalo milk as well as the lower production cost of buffalo compared to cattle. An initiative has recently been taken for the genetic improvement of indigenous dairy buffaloes. The present study was carried out to determine the influence of some environmental factors like age, parity, season of calving, calving interval, dry period on the lactation yield, and lactation curve of indigenous dairy buffaloes of Bangladesh.

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Background The tonsillectomy is the most common Ear, Nose, and Throat (ENT) surgical procedure. Different methods have been used to improve the outcome of the surgery. One such method is tonsillectomy performed with bipolar scissors.

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Introduction: Urinary tract infections are the most common infections encountered in clinical practice. Treatment needs to take into account the likely organism, comorbidities and local antibiotic sensitivity pattern. This study aimed to find the prevalence of positive bacterial culture among adults with suspected urinary tract infections presenting to the department of medicine of a tertiary care centre.

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Motivation: Cryo-electron microscopy (cryo-EM) is a powerful technique for determining the structures of large protein complexes. Picking single protein particles from cryo-EM micrographs (images) is a crucial step in reconstructing protein structures from them. However, the widely used template-based particle picking process requires some manual particle picking and is labor-intensive and time-consuming.

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Background: In all organisms, the innate immune system defends against pathogens through basal expression of molecules that provide critical barriers to invasion and inducible expression of effectors that combat infection. The adenosine deaminase that act on RNA (ADAR) family of RNA-binding proteins has been reported to influence innate immunity in metazoans. However, studies on the susceptibility of ADAR mutant animals to infection are largely lacking.

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Background: Breast cancer has an unacceptably high recurrence rate when any residual disease is found following neoadjuvant treatment of high-risk disease. Based on clinical data suggesting an adjuvant role for epigenetic modifying agents in breast cancer and preclinical data suggesting synergistic activity of entinostat combined with capecitabine, we conducted a phase I, open-label study of these agents in metastatic breast cancer (MBC). Both agents have published doses for use in combination therapy, but the agents had not previously been combined with each other in a human trial.

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Breast cancer is the most common cancer among women worldwide, and estrogen receptor-positive (ER+) breast cancer accounts for a significant proportion of cases. While various treatments are available, endocrine therapies are often the first-line treatment for this type of breast cancer. However, the development of drug resistance poses a significant challenge in managing this disease.

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Introduction: Stunting refers to low height for age, resulting from chronic undernutrition, often linked to poor socio-economic conditions, maternal health, infant care, and nutrition. It hinders children's physical and cognitive development. In Nepal, over half of children under five suffer from malnutrition.

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