The Complex Energy Landscape of miRFP709, a 4-Knotted Protein, Results in Its Irreversible Denaturation.

Knotted proteins have a unique topological feature with an open knot, and the physiological significance of these knots remains elusive. In addition, these proteins challenge our understanding of the protein folding process, and whether they retain their native state during unfolding/refolding cycles like other proteins is debated. Most folding studies on knotted proteins have been performed on 3 and 5 knots, monitoring the tryptophan fluorescence.

Relationship Between Pituitary Gland and Stem Cell in the Aspect of Hormone Production and Disease Prevention: A Narrative Review.

Objectives: In the last two decades, scientists have gained a better understanding of several aspects of pituitary development. The signaling pathways that govern pituitary morphology and development have been identified, and the compensatory relationships among them are now known.

Aims: This paper aims to emphasize the wide variety of relationships between Pituitary Gland and Stem cells in hormone Production and disease prevention.

A deoxyfluoroalkylation-aromatization strategy to access fluoroalkyl arenes.

Fluoroalkyl arenes (Ar-R) are valuable substructures present in several FDA-approved drugs, patents, agrochemicals, and materials, and complementary strategies that enable access to a broad spectrum of Ar-R compounds benefit these applied fields. Herein, we report a deoxyfluoroalkylation-aromatization strategy to convert cyclohexanones into broad-spectrum Ar-R containing compounds. Generally, the fluoroalkyl sources were activated to participate in a 1,2-addition reaction followed by aromatization in a sequence that contrasts more common preparations of these Ar-R compounds, such as (i) transition-metal catalyzed cross-coupling reactions of aryl electrophiles and nucleophiles, and (ii) radical fluoroalkylation reactions of C-H bonds of arenes.

Outcomes following resective and disconnective strategies in the treatment of epileptic spasms: a systematic review of the literature and individual patient data meta-analysis.

Epileptic spasms (ES) are a unique seizure type typically presenting in the form of infantile epileptic spasms syndrome (IESS) with characteristic hypsarrhythmia on scalp EEG and a preponderance with developmental delay or regression. While pharmacotherapy is the mainstay of treatment, surgical options, including disconnective or resective procedures, are increasingly recognized as viable therapeutic options for recurrent or persistent ES. However, limited data on safety, effectiveness, and prognostic factors hinder informed decision-making regarding surgery indications, timing, and intervention type.

Microwave-Assisted Palladium-Catalyzed Crossover-Annulation: Access to Fused Polycyclic Benzofuran Scaffolds.

This study demonstrates quick access to heteroatom-embodied complex fused polycyclic frameworks through a palladium-catalyzed domino process facilitated by microwave-assisted crossover annulation of -alkynylarylhalides and dihydrobenzofurans derivatives. The overall success of this process lies in the careful design of dihydrobenzofuran precursors that direct the initial palladium-mediated annulation step to proceed in a highly regioselective manner to furnish a single regioisomeric product. Notably, this one-pot method has witnessed good substrate scope and has furnished products with excellent yields.

Harnessing RNA-Protein Interactions for Therapeutic Interventions.

Interactions between RNAs and proteins play a crucial role in various diseases, including viral infections and cancer. Hence, understanding and inhibiting these interactions are important for the development of novel therapeutics. However, the identification of drugs targeting RNA-protein interactions with high specificity and affinity is challenged by our limited molecular understanding of these interactions.

A rapid pathway to molecular complexity: a palladium-catalyzed six-fold domino process to access polycyclic frameworks.

Herein, we present a hitherto unexplored efficient strategy for rapidly constructing structurally constrained and intriguing polycyclic frameworks with two adjacent quaternary centers. Remarkably, this becomes possible through palladium-catalyzed six-fold domino crossover annulations of simple 1,2-bis(2-bromoaryl)ethynes and 1,2-diarylethynes. Notably, this approach demonstrates the synthesis of both C-symmetric and unsymmetric polycyclic products.

Outcome of Surgery for Hypothalamic Hamartoma-Related Epilepsy: A Systematic Review and Individual Participant Data Meta-Analysis.

Background And Objectives: There is a paucity of data directly comparing the outcome of surgical techniques available for the treatment of hypothalamic hamartomas (HHs). This study aims to evaluate the safety and efficacy of commonly used surgical approaches in the treatment of HH-related epilepsy.

Methods: A systematic review and individual participant data (IPD) meta-analysis was conducted.

Effect of the COVID-19 vaccination on feto-maternal outcomes: A prospective cohort study among Indian pregnant women.

Background & objectives Studies on the effects of COVID-19 vaccination among pregnant women in Asian settings, more specifically in India, are scarce. The present study evaluated the feto-maternal outcomes among Indian pregnant women who received the COVID-19 vaccine. Methods A prospective cohort study was undertaken among 430 pregnant women from two primary health centres (PHC) in Chandigarh, India during 2021-2022.

Medicinal chemistry-based perspectives on thiophene and its derivatives: exploring structural insights to discover plausible druggable leads.

Thiophene is a privileged pharmacophore in medicinal chemistry owing to its diversified biological attributes. The thiophene moiety has been ranked 4th in the US FDA drug approval of small drug molecules, with around 7 drug approvals over the last decade. The present review covers USFDA-approved drugs possessing a thiophene ring system.

Behavioural economics to improve and motivate vaccination in primary care using nudges through the electronic health record: rationale and design of the BE IMMUNE randomised clinical trial.

Introduction: Annual influenza vaccination reduces disease burden but vaccination rates are suboptimal, with persistent disparities among subpopulations. The purpose of this trial is to evaluate multicomponent behavioural economic nudge interventions to clinicians and patients to increase influenza vaccination. This trial also includes an intensification nudge to reduce disparities in vaccination among older adult, primary care patients.

Transcatheter Aortic-Valve Replacement for Asymptomatic Severe Aortic Stenosis.

Background: For patients with asymptomatic severe aortic stenosis and preserved left ventricular ejection fraction, current guidelines recommend routine clinical surveillance every 6 to 12 months. Data from randomized trials examining whether early intervention with transcatheter aortic-valve replacement (TAVR) will improve outcomes in these patients are lacking.

Methods: At 75 centers in the United States and Canada, we randomly assigned, in a 1:1 ratio, patients with asymptomatic severe aortic stenosis to undergo early TAVR with transfemoral placement of a balloon-expandable valve or clinical surveillance.

Is Transcutaneous Electrical Nerve Stimulation Therapy the Answer for Tinnitus: A Prospective Study.

The study was aimed at determining the effectiveness of transcutaneous electrical nerve stimulation in treatment of tinnitus using Tinnitus handicap inventory (THI) and Visual analogue scale (VAS). 60 patients with bilateral, non-pulsatile, chronic subjective tinnitus; aged 18-65 years were subjected to 8 sessions (2 sessions/week) of TENS therapy given over a total period of 4 weeks. Pre-treatment and Post-treatment VAS, THI scores were compiled and analyzed statistically.

Repurposing of USFDA-approved drugs to identify leads for inhibition of acetylcholinesterase enzyme: a plausible utility as an anti-Alzheimer agent.

In the quest to identify new anti-Alzheimer agents, we employed drug repositioning or drug repositioning techniques on approved USFDA small molecules. Herein, we report the structure-based virtual screening (SBVS) of 1880 USFDA-approved drugs. The -based identification was followed by calculating Prime MMGB-SA binding energy and molecular dynamics simulation studies.

Prevalence of HIV Self-Testing Among Men Who Have Sex With Men: Evidence Synthesis by Systematic Review and Meta-Analysis.

HIV self-testing (HIVST) plays a significant role in addressing the health care needs of high-risk populations, particularly men who have sex with men (MSM). The present systematic review and meta-analysis provide an assessment of the prevalence of HIVST among MSM within the last 5 years. Seven databases (PubMed, Web of Science, Cochrane, Scopus, EMBASE, ProQuest, and EBSCOhost) were searched systematically from January 1, 2018 to March 10, 2023.

A comprehensive analysis of SOX17 expression by immunohistochemistry in human epithelial tumors, with an emphasis on gynecologic tumors.

Objectives: The objective of this study was to evaluate SOX17, a transcription factor from the Sry high-mobility group-related box superfamily, as a diagnostic marker to determine site of origin using both whole-tissue sections and tissue microarrays (TMAs).

Methods: SOX17 immunohistochemistry was performed on gynecologic and nongynecologic tissues (N = 1004) using whole-tissue sections and both internally constructed and commercially available TMAs. SOX17 nuclear reactivity was scored as positive or negative on the whole-tissue sections and using the semiquantitative H score method on TMAs.

Real-world outcomes of atypical EGFR-mutated metastatic non-small cell lung cancer (mNSCLC)treated with osimertinib (osi) vs. Afatinib or erlotinib.

Objectives: Limited data are available comparing the efficacy of osi versus earlier generation TKIs for mNSCLC with atypical EGFR mutations (AMs) such as L861Q, G719X, S768I and exon20.

Methods: We performed a single-institution retrospective analysis of patients with EGFR-mutated mNSCLC treated from 2007 to 2023 with 1L TKIs, comparing outcomes for AM patients treated with osi, afatinib, and erlotinib. Baseline demographics, disease characteristics, treatment history, toxicity, and clinical outcomes were abstracted from the electronic medical record and compared between TKIs using independent sample t-tests and chi-square analyses.

Concussions in ice hockey: mixed methods study including assessment of concussions on games missed and cap hit among National Hockey League players, systematic review, and concussion protocol analysis.

Objective: Concussions can occur at any level of ice hockey. Incidence estimates of concussions in ice hockey vary, and optimal prevention strategies and return-to-play (RTP) considerations have remained in evolution. The authors performed a mixed-methods study with the aim of elucidating the landscape of concussion in ice hockey and catalyzing initiatives to standardize preventative mechanisms and RTP considerations.

Exploring anticancer properties of the phytoconstituents and comparative analysis of their chemical space parameters with USFDA-approved synthetic anticancer agents.

The present review article thoroughly analyses natural products and their derived phytoconstituents as a rich source of plausible anticancer drugs. The study thoroughly explores the chemical components derived from various natural sources, thus emphasizing their unique structural characteristics and therapeutic potential as an anticancer agent. The review contains the critical chemical constituents' in-depth molecular mechanisms, their source's chemical structures and the categories.

National Implementation of an Artificial Intelligence-Based Virtual Dietitian for Patients With Cancer.

Purpose: Nutritional status is an established driver of cancer outcomes, but there is an insufficient workforce of registered dietitians to meet patient needs for nutritional counseling. Artificial intelligence (AI) and machine learning (ML) afford the opportunity to expand access to guideline-based nutritional support.

Methods: An AI-based nutrition assistant called Ina was developed on the basis of a learning data set of >100,000 expert-curated interventions, peer-reviewed literature, and clinical guidelines, and provides a conversational text message-based patient interface to guide dietary habits and answer questions.