Effect of Clinical, Biochemical, and Genetic Variations on Medical Management in Filarial Chyluria: A Prospective Study at a Tertiary Care Centre in North India.

Objective To analyze the effect of clinical, biochemical factors, and Mannose Binding Lectin 2 () gene variations on medical management in filarial chyluria (FC) patients. Material and methods We conducted a study between March 2013 and April 2016. polymorphisms were genotyped in confirmed 101 medically-treated cases of FC.

A Phase 1b Trial of Prexasertib in Combination with Standard-of-Care Agents in Advanced or Metastatic Cancer.

Background: The checkpoint kinase 1 (CHK1) inhibitor prexasertib exhibited modest monotherapy antitumor activity in prior trials, suggesting that combination with chemotherapy or other targeted agents may be needed to maximize efficacy.

Objectives: The aim of this study was to determine the recommended phase II dose and schedule of prexasertib in combination with either cisplatin, cetuximab, pemetrexed, or 5-fluorouracil in patients with advanced and/or metastatic cancer, and to summarize preliminary antitumor activity of these combinations.

Patients And Methods: This phase Ib, nonrandomized, open-label study comprised dose-escalation phase(s) with multiple sub-arms evaluating different prexasertib-drug combinations: Part A, prexasertib + cisplatin (n = 63); Part B, prexasertib + cetuximab (n = 41); Part C, prexasertib + pemetrexed (n = 3); Part D, prexasertib + 5-fluorouracil (n =8).

Inhibition of the RNA-dependent RNA Polymerase of the SARS-CoV-2 by Short Peptide Inhibitors.

The rapid proliferation of SARS-CoV-2 in COVID-19 patients has become detrimental to their lives. However, blocking the replication cycle of SARS-CoV-2 will help in suppressing the viral loads in patients, which would ultimately help in the early recovery. To discover such drugs, molecular docking, MD-simulations, and MM/GBSA approaches have been used herein to examine the role of several short ionic peptides in inhibiting the RNA binding site of the RNA-dependent RNA polymerase (RdRp).

Hepsin regulates TGFβ signaling via fibronectin proteolysis.

Transforming growth factor-beta (TGFβ) is a multifunctional cytokine with a well-established role in mammary gland development and both oncogenic and tumor-suppressive functions. The extracellular matrix (ECM) indirectly regulates TGFβ activity by acting as a storage compartment of latent-TGFβ, but how TGFβ is released from the ECM via proteolytic mechanisms remains largely unknown. In this study, we demonstrate that hepsin, a type II transmembrane protease overexpressed in 70% of breast tumors, promotes canonical TGFβ signaling through the release of latent-TGFβ from the ECM storage compartment.

Johne's Disease in Dairy Cattle: An Immunogenetic Perspective.

Johne's disease (JD), also known as paratuberculosis, is a severe production-limiting disease with significant economic and welfare implications for the global cattle industry. Caused by infection with subspecies (MAP), JD manifests as chronic enteritis in infected cattle. In addition to the economic losses and animal welfare issues associated with JD, MAP has attracted public health concerns with potential association with Crohn's disease, a human inflammatory bowel disease.

Anxiety among Patients Visiting for Periodontal Therapy in a Tertiary Care Dental Hospital: A Descriptive Cross-sectional Study.

Introduction: The aetiological factors of dental fear include negative information, witnessing or having a bad experience, and negative conditions related to periodontal treatment. Modified Dental Anxiety Scale Nepali version, is one of the tools used in epidemiological studies to measure dental anxiety in adults. The objective was to find out the prevalence of anxiety among dental patients visiting for periodontal therapy in a tertiary care hospital.

Perception towards Online Teaching-learning in Medical Education among Medical Students during COVID-19 Outbreak in Nepal: A Descriptive Cross-sectional Study.

Introduction: The outbreak of coronavirus disease in Nepal led medical colleges to suspend in person teaching-learning activities and ultimately online platform was introduced to deliver the contents of medical education. The objective of this study was to describe the perception of medical students towards online teaching-learning introduced during the COVID-19 outbreak in Nepal.

Methods: An online survey using a descriptive cross-sectional study design was carried out among 515 undergraduate medical students currently enrolled in medical colleges in Nepal.

Fluorescence Spectral Properties of Methyl Orange in Homogeneous Media.

The methyl orange [CHNSONa], an azo dye exhibited strong emission and large Stokes shift in various solvents, and the largest shift (Δλ = 125.51nm or Δν = 9297cm) was obtained in the water. The UV-visible spectra of the dye showed the absorption in the range (33,333 - 20,000) cm.

A proof of concept study for machine learning application to stenosis detection.

This proof of concept (PoC) assesses the ability of machine learning (ML) classifiers to predict the presence of a stenosis in a three vessel arterial system consisting of the abdominal aorta bifurcating into the two common iliacs. A virtual patient database (VPD) is created using one-dimensional pulse wave propagation model of haemodynamics. Four different machine learning (ML) methods are used to train and test a series of classifiers-both binary and multiclass-to distinguish between healthy and unhealthy virtual patients (VPs) using different combinations of pressure and flow-rate measurements.

Experience of Treating COVID-19 With Remdesivir and Convalescent Plasma in a Resource-Limited Setting: A Prospective, Observational Study.

Background: Convalescent plasma therapy (CPT) and remdesivir (REM) have been approved for investigational use to treat coronavirus disease 2019 (COVID-19) in Nepal.

Methods: In this prospective, multicentered study, we evaluated the safety and outcomes of treatment with CPT and/or REM in 1315 hospitalized COVID-19 patients over 18 years in 31 hospitals across Nepal. REM was administered to patients with moderate, severe, or life-threatening infection.

Structural, Electronic and NLO Properties of 6-aminoquinoline: A DFT/TD-DFT Study.

A computational study based on the DFT/TD-DFT approach was performed to explore various properties of 6-aminoquinoline (6AQ). The geometrical parameters, molecular orbitals (MOs), electronic spectra, electrostatic potential, molecular surface, reactivity parameters and thermodynamic properties of 6AQ were explored. The absorption and emission spectra of 6AQ in solvents have been estimated by TD-DFT coupled with the PCM model and correlated with the available experimental results.

Validation of Prognostic Scores in Patients With Metastatic Urothelial Cancer Enrolling in Phase I Targeted Therapy or Next Generation Immunotherapy Trials.

Introduction: Enrolling patients with metastatic urothelial carcinoma (mUC) in phase I trials provides an opportunity to identify biological drug activity. Developing prognostic scores may aid in patient selection for phase 1 trials.

Patients And Methods: We analyzed records of patients with mUC who participated in targeted therapy and immunotherapy phase I clinical trials at MD Anderson Cancer Center (MDACC).

Hypothermia for moderate or severe neonatal encephalopathy in low-income and middle-income countries (HELIX): a randomised controlled trial in India, Sri Lanka, and Bangladesh.

Background: Although therapeutic hypothermia reduces death or disability after neonatal encephalopathy in high-income countries, its safety and efficacy in low-income and middle-income countries is unclear. We aimed to examine whether therapeutic hypothermia alongside optimal supportive intensive care reduces death or moderate or severe disability after neonatal encephalopathy in south Asia.

Methods: We did a multicountry open-label, randomised controlled trial in seven tertiary neonatal intensive care units in India, Sri Lanka, and Bangladesh.

Machine learning for detection of stenoses and aneurysms: application in a physiologically realistic virtual patient database.

This study presents an application of machine learning (ML) methods for detecting the presence of stenoses and aneurysms in the human arterial system. Four major forms of arterial disease-carotid artery stenosis (CAS), subclavian artery stenosis (SAS), peripheral arterial disease (PAD), and abdominal aortic aneurysms (AAA)-are considered. The ML methods are trained and tested on a physiologically realistic virtual patient database (VPD) containing 28,868 healthy subjects, adapted from the authors previous work and augmented to include disease.

Antibiotic use influences outcomes in advanced pancreatic adenocarcinoma patients.

Recent studies defined a potentially important role of the microbiome in modulating pancreatic ductal adenocarcinoma (PDAC) and responses to therapies. We hypothesized that antibiotic usage may predict outcomes in patients with PDAC. We retrospectively analyzed clinical data of patients with resectable or metastatic PDAC seen at MD Anderson Cancer from 2003 to 2017.

Comprehensive Clinical and Molecular Characterization of -Mutant Colorectal Cancer.

Purpose: p.G12C mutations occur in approximately 3% of metastatic colorectal cancers (mCRC). Recently, two allosteric inhibitors of p.

Pembrolizumab in Patients with Refractory Cutaneous Squamous Cell Carcinoma: A Phase II Trial.

Introduction: Patients with advanced cutaneous squamous cell carcinoma (CSCC) have a poor prognosis. Blocking the PD-1-PD-L1 axis has shown promising activity in this patient population. We assessed the safety and antitumor activity of PD-1 inhibitor pembrolizumab in patients with refractory advanced CSCC.

Development and Performance of a CD8 Gene Signature for Characterizing Inflammation in the Tumor Microenvironment across Multiple Tumor Types.

Across multiple tumor types, immune checkpoint inhibitors (ICIs) have demonstrated clinical benefit to patients with cancer, yet there is a need to identify predictive biomarkers of response to these therapies. A multiparameter gene expression profiling-based tumor inflammation assay may offer robust characterization of the tumor microenvironment, thereby extending the utility of single-gene analysis or immunohistochemistry (IHC) in predicting response to ICIs. The authors interrogated 1778 commercially procured, formalin-fixed, paraffin-embedded samples using gene expression profiling and pathology-assisted digital CD8 IHC.

Sex Disparity in the Effect of Obesity in Hospitalized COVID-19 Patients: A Retrospective Cohort Study From the New York City Metropolitan Area.

Introduction:  Obesity has been recognized as a risk factor for poor outcomes in coronavirus disease 2019 (COVID-19) illness. We analyzed the impact of patient characteristics including obesity on hospital mortality and specifically analyzed the effect of obesity by body mass index (BMI) class and by sex.

Methods:  This retrospective case series included adult patients consecutively hospitalized with confirmed COVID-19 illness between March 12, 2020 and May 13, 2020, at a teaching hospital in the New York City (NYC) metropolitan area.

Erythropoietin monotherapy for neuroprotection after neonatal encephalopathy in low-to-middle income countries: a systematic review and meta-analysis.

Objective: We examined whether erythropoietin monotherapy improves neurodevelopmental outcomes in near-term and term infants with neonatal encephalopathy (NE) in low-middle income countries (LMICs).

Methods: We searched Pubmed, Embase, and Web of Science databases to identify studies that used erythropoietin (1500-12,500 units/kg/dose) or a derivative to treat NE.

Results: Five studies, with a total of 348 infants in LMICs, were retrieved.

Management of Different Types of Pneumothorax at Dhulikhel Hospital, Kathmandu University Hospital.

Background Pneumothorax is defined as the presence of air in the pleural cavity. Pneumothorax can be classified as Spontaneous and Traumatic according to the etiology. Spontaneous pneumothorax is further classified as Primary and Secondary.

Regarding HER2-Amplified Biliary Tract Cancer.

This letter to the editor focuses on promising data that led to a phase II study in HER2‐amplified biliary tract cancer that is now open globally for enrollment (NCT04466891).

Ethical Issues around Death and Withdrawal of Life Support in Neonatal Intensive Care.

Amongst all the traumatic experiences in a human life, death of child is considered the most painful, and has profound and lasting impact on the life of parents. The experience is even more complex when the death occurs within a neonatal intensive care unit, particularly in situations where there have been conflicts associated with decisions regarding the redirection of life-sustaining treatments. In the absence of national guidelines and legal backing, clinicians are faced with a dilemma of whether to prolong life-sustaining therapy even in the most brain-injured infants or allow a discharge against medical advice.