Computer-Aided Retrosynthesis for Greener and Optimal Total Synthesis of a Helicase-Primase Inhibitor Active Pharmaceutical Ingredient.

This study leverages and upgrades the capabilities of computer-aided retrosynthesis (CAR) in the systematic development of greener and more efficient total synthetic routes for the active pharmaceutical ingredient (API) IM-204, a helicase-primase inhibitor that demonstrated enhanced efficacy against Herpes simplex virus (HSV) infections. Using various CAR tools, several total synthetic routes were uncovered, evaluated, and experimentally validated, with the goal to maximize selectivity and yield and minimize the environmental impact. The CAR tools revealed several synthetic options under different constraints, which can overperform the patented synthetic route used as a reference.

Corrigendum to "A customizable digital holographic microscope" [HardwareX 19 (2024) e00569].

[This corrects the article DOI: 10.1016/j.ohx.

Anterior Cruciate Ligament Revision Using Bone-Patellar Tendon-Bone Autograft and Lateral Extra-articular Tenodesis.

Revision of anterior cruciate ligament reconstruction presents various challenges not encountered in the primary settings, including malpositioned tunnels, tunnel widening, and the lack of consensus on the ideal graft to be used. This Technical Note describes a one-stage anterior cruciate ligament reconstruction revision using a bone-patellar tendon-bone autograft combined with lateral extra-articular tenodesis. This technique represents the ideal approach to tackle complex revision cases primarily characterized by tibial and femoral tunnel osteolysis and rotational knee instability.

In-silico-based lead optimization of hit compounds targeting mitotic kinesin Eg5 for cancer management.

Unlabelled: Lead optimization is vital for turning hit compounds into therapeutic drugs. This study builds upon a prior in silico research, where the hit compounds had better binding affinity and stability compared to a reference drug. Using a genetic algorithm, 12,500 analogs of the top compounds from the prior study were generated.

Cardiovascular toxicity induced by TKIs in patients with chronic myeloid leukaemia: Are women and men different?

Aims: Knowledge of the effects of sex in cardio-oncology is limited, particularly in patients treated with tyrosine kinase inhibitors (TKIs) for chronic myeloid leukaemia (CML). This study aims to evaluate the influence of gender differences on the incidence of cardiovascular toxicity in patients with CML.

Methods: The study population consisted of 148 patients (45% women, mean age: 58 ± 14.

On-treatment dynamics of circulating extracellular vesicles in the first-line setting of patients with advanced non-small cell lung cancer: the LEXOVE prospective study.

Extracellular vesicle (EV) monitoring can complement clinical assessment of cancer response. In this study, patients with advanced non-small cell lung cancer (NSCLC) undergoing osimertinib, alectinib, pembrolizumab or platinum-based chemotherapy ± pembrolizumab were enrolled. EVs were characterized using Bradford assay to quantify the circulating cell-free EV protein content (cfEV), and dynamic light scattering to assess Rayleigh ratio excess at 90°, z-averaged hydrodynamic diameter and polydispersity index.

Resolving the Nanostructure of Carbon Nitride-Supported Single-Atom Catalysts.

Single-atom catalysts (SACs) are gathering significant attention in chemistry due to their unique properties, offering uniform active site distribution and enhanced selectivity. However, their precise structure often remains unclear, with multiple models proposed in the literature. Understanding the coordination environment of the active site at the atomic level is crucial for explaining catalytic activity.

Correction: Selective binding and fluorescence sensing of Zn(II)/Cd(II) using macrocyclic tetra-amines with different fluorophores: insights into the design of selective chemosensors for transition metals.

Correction for 'Selective binding and fluorescence sensing of Zn(II)/Cd(II) using macrocyclic tetra-amines with different fluorophores: insights into the design of selective chemosensors for transition metals' by Giammarco Maria Romano , , 2025, https://doi.org/10.1039/d4dt02415j.

The Complex Epigenetic Panorama in the Multipartite Genome of the Nitrogen-Fixing Bacterium Sinorhizobium meliloti.

In prokaryotes, DNA methylation plays roles in DNA repair, gene expression, cell cycle progression, and immune recognition of foreign DNA. Genome-wide methylation patterns can vary between strains, influencing phenotype, and gene transfer. However, broader evolutionary studies on bacterial epigenomic variation remain limited.

Measuring trends in extinction risk: a review of two decades of development and application of the Red List Index.

The Red List Index (RLI) is an indicator of the average extinction risk of groups of species and reflects trends in this through time. It is calculated from the number of species in each category on the IUCN Red List of Threatened Species, with trends influenced by the number moving between categories when reassessed owing to genuine improvement or deterioration in status. The global RLI is aggregated across multiple taxonomic groups and can be disaggregated to show trends for subsets of species (e.

LIFE: A metric for mapping the impact of land-cover change on global extinctions.

Human-driven habitat loss is recognized as the greatest cause of the biodiversity crisis, yet to date we lack robust, spatially explicit metrics quantifying the impacts of anthropogenic changes in habitat extent on species' extinctions. Existing metrics either fail to consider species identity or focus solely on recent habitat losses. The persistence score approach developed by Durán .

Unraveling the Atomistic Mechanism of Electrostatic Lateral Association of Peptide β-Sheet Structures and Its Role in Nanofiber Growth and Hydrogelation.

Guiding molecular assembly of peptides into rationally engineered nanostructures remains a major hurdle against the development of functional peptide-based nanomaterials. Various non-covalent interactions come into play to drive the formation and stabilization of these assemblies, of which electrostatic interactions are key. Here, the atomistic mechanisms by which electrostatic interactions contribute toward controlling self-assembly and lateral association of ultrashort β-sheet forming peptides are deciphered.

Psychotic-Like Experiences in Young Recreational Users of Ketamine: A Case Study.

This study explores the psychotic-like experiences (PLEs) associated with recreational ketamine use among young adults. Ketamine, initially introduced as an anesthetic, is now widely used recreationally for its dissociative effects, raising concerns about its impact on mental health. Ten participants aged 18-24, who used ketamine recreationally multiple times a week, were assessed using the Community Assessment of Psychic Experiences (CAPE-42).

Pseudomorphic Transformation in Nanostructured Thiophene-Based Materials.

This study reveals the capability of nanostructured organic materials to undergo pseudomorphic transformations, a ubiquitous phenomenon occurring in the mineral kingdom that involves the replacement of a mineral phase with a new one while retaining the original shape and volume. Specifically, it is demonstrated that the postoxidation process induced by HOF·CHCN on preformed thiophene-based 1D nanostructures preserves their macro/microscopic morphology while remarkably altering their electro-optical properties by forming a new oxygenated phase. Experimental evidence proves that this transformation proceeds via an interface-coupled dissolution-precipitation mechanism, leading to the growth of a porous oxidized shell that varies in thickness with exposure time, enveloping the pristine smooth core.

Analysis of different strains of the turquoise killifish identify transcriptomic signatures associated with heritable lifespan differences.

The African turquoise killifish Nothobranchius furzeri represents an emerging short-lived model for aging research. Captive strains of this species are characterized by large differences in lifespan. To identify the gene expression correlates of this lifespan differences, we analyzed a public transcriptomic dataset consisting of four different tissues in addition to embryos.

The Venus score for the assessment of the quality and trustworthiness of biomedical datasets.

Biomedical datasets are the mainstays of computational biology and health informatics projects, and can be found on multiple data platforms online or obtained from wet-lab biologists and physicians. The quality and the trustworthiness of these datasets, however, can sometimes be poor, producing bad results in turn, which can harm patients and data subjects. To address this problem, policy-makers, researchers, and consortia have proposed diverse regulations, guidelines, and scores to assess the quality and increase the reliability of datasets.

Airway pressures generated by high flow nasal cannula in patients with acute hypoxemic respiratory failure: a computational study.

Introduction And Objectives: High flow nasal cannula (HFNC) therapy is an increasingly popular mode of non-invasive respiratory support for the treatment of patients with acute hypoxemic respiratory failure (AHRF). Previous experimental studies in healthy subjects have established that HFNC generates flow-dependent positive airway pressures, but no data is available on the levels of mean airway pressure (mP) or positive end-expiratory pressure (PEEP) generated by HFNC therapy in AHRF patients. We aimed to estimate the airway pressures generated by HFNC at different flow rates in patients with AHRF, whose functional lung volume may be significantly reduced compared to healthy subjects due to alveolar consolidation and/or collapse.

A blended learning approach for capacity strengthening to improve the quality of integrated HIV, TB, and malaria services during antenatal and postnatal care in LMICs: a feasibility study.

Background: The blended learning (BL) approach to training health care professionals is increasingly adopted in many countries because of high costs and disruption to service delivery in the light of severe human resource shortage in low resource settings. The Covid-19 pandemic increased the urgency to identify alternatives to traditional face-to-face (f2f) education approach. A four-day f2f antenatal care (ANC) and postnatal care (PNC) continuous professional development course (CPD) was repackaged into a 3-part BL course; (1) self-directed learning (16 h) (2) facilitated virtual sessions (2.

A systematic realist synthesis of digital interventions for enhancing mental health at work: contexts, mechanisms, and outcomes.

Background: Digital interventions (DIs) have emerged as promising tools for promoting mental health in the workplace. However, evidence on if, how, and under what circumstances they affect positive outcomes requires elucidation. This systematic realist review aimed to synthesize current knowledge on contexts, mechanisms, and outcomes of workplace DIs to enhance mental health at work.

Dynamic supramolecular snub cubes.

Mimicking the superstructures and properties of spherical biological encapsulants such as viral capsids and ferritin offers viable pathways to understand their chiral assemblies and functional roles in living systems. However, stereospecific assembly of artificial polyhedra with mechanical properties and guest-binding attributes akin to biological encapsulants remains a formidable challenge. Here we report the stereospecific assembly of dynamic supramolecular snub cubes from 12 helical macrocycles, which are held together by 144 weak C-H hydrogen bonds.