Golden eagle optimized fractional-order PI controller design for a PFC SEPIC converter in EV charging.

The power factor correction converter is the function of the front-end converter, followed by the DC-DC converter of the electric vehicle charger. It improves the power factor and regulates the output voltage and current. This research article proposes the Golden Eagle optimization for fractional order PI (FOPI) controller for Single Ended Primary Inductor Converter (SEPIC) power factor correction.

The SOS1 Inhibitor MRTX0902 Blocks KRAS Activation and Demonstrates Antitumor Activity in Cancers Dependent on KRAS Nucleotide Loading.

KRAS is the most frequently mutated oncogene in human cancer and facilitates uncontrolled growth through hyperactivation of the receptor tyrosine kinase (RTK)/mitogen-activated protein kinase (MAPK) pathway. The Son of Sevenless homolog 1 (SOS1) protein functions as a guanine nucleotide exchange factor (GEF) for the RAS subfamily of small GTPases and represents a druggable target in the pathway. Using a structure-based drug discovery approach, MRTX0902 was identified as a selective and potent SOS1 inhibitor that disrupts the KRAS:SOS1 protein-protein interaction to prevent SOS1-mediated nucleotide exchange on KRAS and translates into an anti-proliferative effect in cancer cell lines with genetic alterations of the KRAS-MAPK pathway.

Ancient and modern mechanisms compete in progesterone receptor activation.

The progesterone receptor (PR) belongs to the steroid receptor family of ligand-regulated transcription factors, controlling genes important for development, metabolism, and reproduction. Understanding how diverse ligands bind and modulate PR activity will illuminate the design of ligands that control PR-driven signaling pathways. Here, we use molecular dynamics simulations to investigate how PR dynamics are altered by functionally diverse ligands.

Digital Survey Assessment of Individual and Occupational Factors Associated with Musculoskeletal Disorders among Indian Ophthalmologists.

Purpose: To study the prevalence of musculoskeletal disorder (MSD) and the associated occupational risk factors among Indian ophthalmologists, including residents and fellows.

Methods: A cross-sectional survey was conducted among ophthalmologists in India using a semi-structured questionnaire in a web-based survey. The questionnaire was prepared in English after extensive literature research and consulting with subject experts.

Illuminating ligand-induced dynamics in nuclear receptors through MD simulations.

Nuclear receptors (NRs) regulate gene expression in critical physiological processes, with their functionality finely tuned by ligand-induced conformational changes. While NRs may sometimes undergo significant conformational motions in response to ligand-binding, these effects are more commonly subtle and challenging to study by traditional structural or biophysical methods. Molecular dynamics (MD) simulations are a powerful tool to bridge the gap between static protein-ligand structures and dynamical changes that govern NR function.

TEAD Inhibition Overcomes YAP1/TAZ-Driven Primary and Acquired Resistance to KRASG12C Inhibitors.

Unlabelled: Primary/intrinsic and treatment-induced acquired resistance limit the initial response rate to and long-term efficacy of direct inhibitors of the KRASG12C mutant in cancer. To identify potential mechanisms of resistance, we applied a CRISPR/Cas9 loss-of-function screen and observed loss of multiple components of the Hippo tumor suppressor pathway, which acts to suppress YAP1/TAZ-regulated gene transcription. YAP1/TAZ activation impaired the antiproliferative and proapoptotic effects of KRASG12C inhibitor (G12Ci) treatment in KRASG12C-mutant cancer cell lines.

Study of retinal nerve fiber layer thickness in diabetic patients using optical coherence tomography.

Purpose: This study aimed to assess and compare the changes in peripapillary retinal nerve fiber layer (RNFL) thickness in nondiabetics and diabetics with various stages of diabetic retinopathy (DR).

Methods: The study subjects were divided into four groups based on their diabetic status and findings, namely, controls (normal subjects without diabetes [NDM]), diabetics without retinopathy (NDR), nonproliferative DR (NPDR), and proliferative DR (PDR). Peripapillary RNFL thickness was assessed using optical coherence tomography.

A study on the perception, knowledge, attitude, and practices of eye donation among fresh medical graduates in India.

Objective: The objective of the study was to assess the perception, knowledge, attitude, and practices of eye donation among fresh medical graduates in India.

Materials And Methods: Responses to a semi-structured questionnaire were collected from 410 respondents using an online Google Form which were analyzed using IBM SPSS software version 21.

Results: First information source about eye donation was textbooks (31%), while ophthalmologists accounted for 10.

Prevalence of overlap syndrome in patients with obstructive sleep apnea in a quaternary care center of Kerala.

Background: The coexistence of obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) is termed "Overlap syndrome (OS)."

Objectives: The present study aimed at estimating the prevalence of OS among patients diagnosed with OSA.

Methods: It was a prospective observational study conducted on patients presenting to respiratory medicine outpatient department (sleep clinic) with symptoms of sleep-disordered breathing and was found to have OSA by overnight polysomnography.

Study on factors associated with post bronchodilator reversibility among patients presenting with dyspnea: An experience at a tertiary care academic hospital in Kerala.

Background: The change in FEV after administration of a short-acting bronchodilator has been widely used for diagnosis of obstructive airway diseases. Many factors can influence the post bronchodilator reversibility.

Aim: The aim of the present study was to estimate the presence of reversibility among the patients of obstructive airway disease and to identify the factors affecting it.

Design and Discovery of MRTX0902, a Potent, Selective, Brain-Penetrant, and Orally Bioavailable Inhibitor of the SOS1:KRAS Protein-Protein Interaction.

SOS1 is one of the major guanine nucleotide exchange factors that regulates the ability of KRAS to cycle through its "on" and "off" states. Disrupting the SOS1:KRAS protein-protein interaction (PPI) can increase the proportion of GDP-loaded KRAS, providing a strong mechanistic rationale for combining inhibitors of the SOS1:KRAS complex with inhibitors like MRTX849 that target GDP-loaded KRAS. In this report, we detail the design and discovery of MRTX0902─a potent, selective, brain-penetrant, and orally bioavailable SOS1 binder that disrupts the SOS1:KRAS PPI.

Comparison of smartphone application-based visual acuity with traditional visual acuity chart for use in tele-ophthalmology.

Purpose: The aim of this study was to compare the visual acuity (VA) by smartphone-based applications - EyeChart and the Peek Acuity to the standard Snellen chart to explore the possibility of using them as an alternative in tele-ophthalmology in the current COVID-19 pandemic.

Materials And Methods: An analytical type of observational study was done on 360 eyes of 184 patients above 18 years of age. Patients with VA <6/60 and gross ocular pathology were excluded from the study.

Case series of concurrent occurrence of sarcoidosis and breast cancer - A diagnostic dilemma.

Sarcoidosis is a multi-system granulomatous disorder characterized by involvement of multiple systems with or without lymphadenitis. Pulmonary complications are common and may lead to morbidity. Breast cancer is one of the commonest malignancy among women across the world.

Fluorescein Based Fluorescence Sensors for the Selective Sensing of Various Analytes.

Fluorescein molecules are extensively used to develop fluorescent probes for various analytes due to their excellent photophysical properties and the spirocyclic structure. The main structural modification of fluorescein occurs at the carboxyl group where different groups can be easily introduced to produce the spirolactam structure which is non-fluorescent. The spirolactam ring opening accounts for the fluorescence and the dual sensing of analytes using fluorescent sensors is still a topic of high interest.

The KRAS Inhibitor MRTX849 Reconditions the Tumor Immune Microenvironment and Sensitizes Tumors to Checkpoint Inhibitor Therapy.

KRAS inhibitors, including MRTX849, are promising treatment options for KRAS-mutant non-small cell lung cancer (NSCLC). PD-1 inhibitors are approved in NSCLC; however, strategies to enhance checkpoint inhibitor therapy (CIT) are needed. mutations are smoking-associated transversion mutations associated with high tumor mutation burden, PD-L1 positivity, and an immunosuppressive tumor microenvironment.

Identification of the Clinical Development Candidate , a Covalent KRAS Inhibitor for the Treatment of Cancer.

Capping off an era marred by drug development failures and punctuated by waning interest and presumed intractability toward direct targeting of KRAS, new technologies and strategies are aiding in the target's resurgence. As previously reported, the tetrahydropyridopyrimidines were identified as irreversible covalent inhibitors of KRAS that bind in the switch-II pocket of KRAS and make a covalent bond to cysteine 12. Using structure-based drug design in conjunction with a focused in vitro absorption, distribution, metabolism and excretion screening approach, analogues were synthesized to increase the potency and reduce metabolic liabilities of this series.

Evaluation of the Immunoprotective Potential of Recombinant Paraflagellar Rod Proteins of in Mice.

Trypanosomosis, caused by , is an economically significant disease of livestock. Systematic antigenic variation by the parasite has undermined prospects for the development of a protective vaccine that targets the immunodominant surface antigens, encouraging exploration of alternatives. The paraflagellar rod (PFR), constituent proteins of the flagellum, are prominent non-variable vaccine candidates for owing to their strategic location.

The KRAS Inhibitor MRTX849 Provides Insight toward Therapeutic Susceptibility of KRAS-Mutant Cancers in Mouse Models and Patients.

Despite decades of research, efforts to directly target KRAS have been challenging. MRTX849 was identified as a potent, selective, and covalent KRAS inhibitor that exhibits favorable drug-like properties, selectively modifies mutant cysteine 12 in GDP-bound KRAS, and inhibits KRAS-dependent signaling. MRTX849 demonstrated pronounced tumor regression in 17 of 26 (65%) KRAS-positive cell line- and patient-derived xenograft models from multiple tumor types, and objective responses have been observed in patients with KRAS-positive lung and colon adenocarcinomas.

High seroprevalence of Toxoplasma gondii in goats in Jharkhand state of India.

Toxoplasmosis, caused by Toxoplasma gondii, is an important food borne zoonosis worldwide. Although goat meat constitutes an important dietary protein source, improperly cooked meat is a potential source of infection to humans. Data on prevalence of toxoplasma in goat is scanty from India.

AQUEOUS HUMOR CYTOKINES AND THERAPEUTIC CUSTOMIZATION IN NONRESPONDING MACULAR EDEMA SECONDARY TO RETINAL VEIN OCCLUSION.

Aim: To report an alternative cytokine-based customized therapeutic approach of macular edema secondary to retinal vein occlusion.

Methods: A 64-year-old male patient presented with left eye macular edema secondary to central retinal vein occlusion, status after three consecutive anti-vascular endothelial growth factor injections. He was subsequently subjected to aqueous humor cytokine analysis.

Discovery of Tetrahydropyridopyrimidines as Irreversible Covalent Inhibitors of KRAS-G12C with In Vivo Activity.

is the most frequently mutated driver oncogene in human cancer, and KRAS mutations are commonly associated with poor prognosis and resistance to standard treatment. The ability to effectively target and block the function of mutated KRAS has remained elusive despite decades of research. Recent findings have demonstrated that directly targeting KRAS-G12C with electrophilic small molecules that covalently modify the mutated codon 12 cysteine is feasible.

Cytotoxicity and Apoptotic Assay in HT-29 Cell Line Using Linn: Leaves Extract.

Background: Linn. (Family ), well-known beneficial medicinal shrub, has been traditionally used for the treatment of various diseases such as leukoderma.

Objective: The aim of the present study is to investigate the efficacy of ethanolic leaves extract for antiproliferative, apoptotic, cell cycle blockade, and wound healing.

The class I/IV HDAC inhibitor mocetinostat increases tumor antigen presentation, decreases immune suppressive cell types and augments checkpoint inhibitor therapy.

Checkpoint inhibitor therapy has led to major treatment advances for several cancers including non-small cell lung cancer (NSCLC). Despite this, a significant percentage of patients do not respond or develop resistance. Potential mechanisms of resistance include lack of expression of programmed death ligand 1 (PD-L1), decreased capacity to present tumor antigens, and the presence of an immunosuppressive tumor microenvironment.