Resistance mechanisms to immune checkpoint inhibitors: updated insights.

The last decade has witnessed unprecedented succusses with the use of immune checkpoint inhibitors in treating cancer. Nevertheless, the proportion of patients who respond favorably to the treatment remained rather modest, partially due to treatment resistance. This has fueled a wave of research into potential mechanisms of resistance to immune checkpoint inhibitors which can be classified into primary resistance or acquired resistance after an initial response.

Transducing chemical energy through catalysis by an artificial molecular motor.

Cells display a range of mechanical activities generated by motor proteins powered through catalysis. This raises the fundamental question of how the acceleration of a chemical reaction can enable the energy released from that reaction to be transduced (and, consequently, work to be done) by a molecular catalyst. Here we demonstrate the molecular-level transduction of chemical energy to mechanical force in the form of the powered contraction and powered re-expansion of a cross-linked polymer gel driven by the directional rotation of artificial catalysis-driven molecular motors.

Deciphering the safeguarding role of cysteine residues in p53 against HO-induced oxidation using high-resolution native mass spectrometry.

The transcription factor p53 is exquisitely sensitive and selective to a broad variety of cellular environments. Several studies have reported that oxidative stress weakens the p53-DNA binding affinity for certain promoters depending on the oxidation mechanism. Despite this body of work, the precise mechanisms by which the physiologically relevant DNA-p53 tetramer complex senses cellular stresses caused by HO are still unknown.

Multiplex lateral flow test sensitivity and specificity in detecting influenza A, B and SARS-CoV-2 in adult patients in a UK emergency department.

Background: Rapid identification of individuals with acute respiratory infections is crucial for preventing nosocomial infections. For rapid diagnosis, especially in EDs, lateral flow devices (LFDs) are a convenient, inexpensive option with a rapid turnaround. Several 'multiplex' LFDs (M-LFDs) now exist, testing for multiple pathogens from a single swab sample.

Larger sample sizes are needed when developing a clinical prediction model using machine learning in oncology: methodological systematic review.

Background: Having a sufficient sample size is crucial when developing a clinical prediction model. We reviewed details of sample size in studies developing prediction models for binary outcomes using machine learning (ML) methods within oncology and compared the sample size used to develop the models with the minimum required sample size needed when developing a regression-based model (N).

Methods: We searched the Medline (via OVID) database for studies developing a prediction model using ML methods published in December 2022.

The structural organisation of pentraxin-3 and its interactions with heavy chains of inter-α-inhibitor regulate crosslinking of the hyaluronan matrix.

Pentraxin-3 (PTX3) is an octameric protein, comprised of eight identical protomers, that has diverse functions in reproductive biology, innate immunity and cancer. PTX3 interacts with the large polysaccharide hyaluronan (HA) to which heavy chains (HCs) of the inter-α-inhibitor (IαI) family of proteoglycans are covalently attached, playing a key role in the (non-covalent) crosslinking of HC•HA complexes. These interactions stabilise the cumulus matrix, essential for ovulation and fertilisation in mammals, and are also implicated in the formation of pathogenic matrices in the context of viral lung infections.

A randomised phase III study of bevacizumab and carboplatin-pemetrexed chemotherapy with or without atezolizumab, as first-line treatment for advanced pleural mesothelioma: results of the ETOP 13 18 BEAT-meso trial.

Background: The currently approved frontline treatments for diffuse pleural mesothelioma (DPM) are ipilimumab-nivolumab or platinum-pemetrexed. The addition of bevacizumab to chemotherapy improves overall survival (OS). While single-agent immunotherapy or chemotherapy-immunotherapy combinations are superior to chemotherapy monotherapy, there is a potential for synergistic triple combination of chemotherapy, bevacizumab, and immunotherapy.

Engineered enzymes for enantioselective nucleophilic aromatic substitutions.

Nucleophilic aromatic substitutions (SAr) are amongst the most widely used processes in the pharmaceutical and agrochemical industries, allowing convergent assembly of complex molecules through C-C and C-X (X = O, N, S) bond formation. SAr reactions are typically carried out using forcing conditions, involving polar aprotic solvents, stoichiometric bases and elevated temperatures, which do not allow for control over reaction selectivity. Despite the importance of SAr chemistry, there are only a handful of selective catalytic methods reported that rely on small organic hydrogen-bonding or phase-transfer catalysts.

Interleukin-17 and fat: Timing is everything.

Interleukin-17 plays a major role in controlling adipose tissue homeostasis. In a recent study published in Nature, Douglas et al. demonstrate that time-of-day-dependent expression of interleukin-17 by tissue-resident innate lymphocytes in the adipose tissue drives circadian regulation of adipose tissue homeostasis and function.

Cu-EAB zeolite catalyst: A promising candidate with excellent SO poisoning resistance for NH-SCR reaction.

In this work, we synthesized Cu-EAB catalysts with an EAB topology for the NH-SCR of NO and evaluated their resistance to SO poisoning for the first time. The Cu-EAB catalyst showed superior NO conversion and selectivity for N, along with a notable tolerance to high space velocities and SO, outperforming the commercial Cu-CHA catalyst. This enhanced resistance was attributed to the Cu species formation at the 2.

Hydrophilic interaction liquid chromatography-tandem mass spectrometry analysis of oligosaccharides and iridoid glycosides in rat plasma: Pharmacokinetic characterization of previously overlooked oligosaccharides from Radix Rehmanniae.

Radix Rehmanniae (RR) is a widely used herb in traditional Chinese Medicine with properties of tonifying the kidneys and nourishing the blood. Both raw and processed RR are effective for the treatment of diabetes in clinical practice. Oligosaccharides and iridoid glycosides are the primary active components responsible for the anti-diabetic effects of RR.

From Taxus to paclitaxel: Opportunities and challenges for urban agriculture to promote human health.

Conifers of the genus Taxus are environmentally friendly plants with significant medicinal and ecological value, contributing to the enhancement of urban living environments. Paclitaxel, a compound found in Taxus, has garnered particular research interest owing to its potent anti-cancer effects. However, traditional methods of extracting paclitaxel from Taxus are not only inefficient, but also destructive and unsustainable, posing the major risk of Taxus extinction.

Comparison of Outcomes of Deep Sclerectomy, Canaloplasty, and Viscocanaloplasty: A Multi-Centred Study.

Prcis: Deep sclerectomy (DS) and canaloplasty provide better intraocular pressure (IOP) control than viscocanalostomy. DS required less glaucoma medications but more interventions to reach target IOP.

Purpose: To compare real-world outcomes of three non-penetrating glaucoma surgery (NPGS) techniques.

Estimating the burden of underdiagnosis within England: A modelling study of linked primary care data.

Introduction: Undiagnosed chronic disease has serious health consequences, and variation in rates of underdiagnosis between populations can contribute to health inequalities. We aimed to estimate the level of undiagnosed disease of 11 common conditions and its variation across sociodemographic characteristics and regions in England.

Methods: We used linked primary care, hospital and mortality data on approximately 1.

Qualitative methods: the missing link in orthopaedic research.

Cite this article:  2025;14(1):16–19.

Translation, cross-cultural adaptation and psychometric evaluation of the Serbian Ankylosing Spondylitis Quality of Life (ASQoL) Questionnaire (refers to r-axSpA) and its relations with disease activity and functional status indices.

Objectives: To translate, cross-culturally adapt and validate the Serbian Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire, e.g. according to the new nomenclature Radiographic-Axial Spondyloarthritis (r-axSpA), and to relate it to disease activity and functional status domains.

Ablation of satellite cell-specific clock gene, Bmal1, alters force production, muscle damage, and repair following contractile-induced injury.

Following injury, skeletal muscle undergoes repair via satellite cell (SC)-mediated myogenic progression. In SCs, the circadian molecular clock gene, Bmal1, is necessary for appropriate myogenic progression and repair with evidence that muscle molecular clocks can also affect force production. Utilizing a mouse model allowing for inducible depletion of Bmal1 within SCs, we determined contractile function, SC myogenic progression and muscle damage and repair following eccentric contractile-induced injury.

Endocytic recycling is central to circadian collagen fibrillogenesis and disrupted in fibrosis.

Collagen-I fibrillogenesis is crucial to health and development, where dysregulation is a hallmark of fibroproliferative diseases. Here, we show that collagen-I fibril assembly required a functional endocytic system that recycles collagen-I to assemble new fibrils. Endogenous collagen production was not required for fibrillogenesis if exogenous collagen was available, but the circadian-regulated vacuolar protein sorting (VPS) 33b and collagen-binding integrin α11 subunit were crucial to fibrillogenesis.

Transferability of Single- and Cross-Tissue Transcriptome Imputation Models Across Ancestry Groups.

Transcriptome-wide association studies (TWAS) investigate the links between genetically regulated gene expression and complex traits. TWAS involves imputing gene expression using expression quantitative trait loci (eQTL) as predictors and testing the association between the imputed expression and the trait. The effectiveness of TWAS depends on the accuracy of these imputation models, which require genotype and gene expression data from the same samples.

Success Rates of Assisted Reproduction for Men With Cystic Fibrosis.

Background: The vast majority of men with CF (mwCF) are infertile. Improvements in assisted reproductive technology (ART) have made it possible for these patients to become biological fathers.

Methods: Data were examined for all male CF patients attending a large adult CF center over a 23-year period.

Safety Assessment of Graphene-Based Materials.

Graphene is the first 2D atomic crystal, and its isolation heralded a new era in materials science with the emergence of several other atomically thin materials displaying multifunctional properties. The safety assessment of new materials is often something of an afterthought, but in the case of graphene, the initial isolation and characterization of the material was soon followed by the assessment of its potential impact on living systems. The Graphene Flagship project addressed the health and environmental aspects of graphene and other 2D materials, providing an instructive lesson in interdisciplinarity - from materials science to biology.

Joint modeling of correlated binary outcomes using multivariate logistic regression: contraception and HIV knowledge in Sri Lanka.

Reproductive health significantly contributes to the overall well-being and social welfare of women. Within the spectrum of modern and traditional contraceptive methods in use, condoms have been strongly advocated by numerous HIV programs as a primary means of preventing HIV infection in Sri Lanka. Given the intrinsic relationship between contraceptive utilization and HIV awareness, our study aims to concurrently analyze the patterns of contraceptive usage and HIV knowledge, while accounting for their potential correlation.