Comparison of two strategies of glucocorticoid withdrawal in patients with rheumatoid arthritis in low disease activity (STAR): a randomised, placebo- controlled, double-blind trial.

Objectives: To compare two strategies-a hydrocortisone replacement strategy and a prednisone tapering strategy-for their success in glucocorticoid discontinuation in patients with rheumatoid arthritis (RA) with low disease activity (LDA).

Methods: The Strategies for glucocorticoid TApering in Rheumatoid arthritis (STAR) study was a double- blind, double-placebo randomised controlled trial including patients with RA receiving a stable dose of glucocorticoid 5 mg/day for ≥3 months and were in LDA for ≥3 months. Patients were randomly assigned in a 1:1 ratio to either replace prednisone with 20 mg/day of hydrocortisone for 3 months, then reduce to 10 mg/day for 3 months before discontinuation or to taper prednisone by 1 mg/day every month until complete discontinuation, contingent on maintaining LDA.

Association of methotrexate polyglutamates concentration with methotrexate efficacy and safety in patients with rheumatoid arthritis treated with predefined dose: results from the MIRACLE trial.

Objectives: The usefulness of methotrexate-polyglutamates (MTX-PGs) concentration for management of rheumatoid arthritis has been debated. We aimed to clarify the association of MTX-PGs concentration with efficacy and safety in MTX-naïve patients initiating MTX in a prospective interventional clinical trial.

Methods: The MIRACLE trial enrolled 300 MTX-naïve patients.

EULAR recommendations for the treatment of systemic sclerosis: 2023 update.

Objectives: To update the 2017 European Alliance of Associations for Rheumatology (EULAR) recommendations for treatment of systemic sclerosis (SSc), incorporating new evidence and therapies.

Methods: An international task force was convened in line with EULAR standard operating procedures. A nominal group technique exercise was performed in two rounds to define questions underpinning a subsequent systematic literature review.

Assessing the performance of AI chatbots in answering patients' common questions about low back pain.

Objectives: The aim of this study was to assess the accuracy and readability of the answers generated by large language model (LLM)-chatbots to common patient questions about low back pain (LBP).

Methods: This cross-sectional study analysed responses to 30 LBP-related questions, covering self-management, risk factors and treatment. The questions were developed by experienced clinicians and researchers and were piloted with a group of consumer representatives with lived experience of LBP.

Therapeutic interception in individuals at risk of rheumatoid arthritis to prevent clinically impactful disease.

Multiple clinical trials for rheumatoid arthritis (RA) prevention have been completed. Here, we set out to report on the lessons learnt from these studies. Researchers who conducted RA prevention trials shared the background, rationale, approach and outcomes and evaluated the lessons learnt to inform the next generation of RA prevention trials.

Relationship between serum urate and changes in dual-energy CT monosodium urate crystal volume over 1 year in people with gout: an individual participant data analysis.

Objectives: The dynamics of monosodium urate (MSU) crystal changes across a range of serum urate concentrations in people with gout are unknown. This study aimed to systematically examine the relationship between serum urate and changes in dual-energy CT (DECT) urate volume in people with gout and stable serum urate concentrations.

Methods: Individual participant data were analysed from three studies of people with gout.

Predicting rapid progression in knee osteoarthritis: a novel and interpretable automated machine learning approach, with specific focus on young patients and early disease.

Objectives: To facilitate the stratification of patients with osteoarthritis (OA) for new treatment development and clinical trial recruitment, we created an automated machine learning (autoML) tool predicting the rapid progression of knee OA over a 2-year period.

Methods: We developed autoML models integrating clinical, biochemical, X-ray and MRI data. Using two data sets within the OA Initiative-the Foundation for the National Institutes of Health OA Biomarker Consortium for training and hold-out validation, and the Pivotal Osteoarthritis Initiative MRI Analyses study for external validation-we employed two distinct definitions of clinical outcomes: Multiclass (categorising OA progression into pain and/or radiographic) and binary.

Comparison of definitions of early knee osteoarthritis for likelihood of progression at 2-year and 5-year follow-up: the Multicenter Osteoarthritis Study.

Background: Preventing worsening osteoarthritis (OA) in persons with early OA is a major treatment goal. We evaluated if different early OA definitions yielded enough cases of worsening OA within 2-5 years to make trial testing treatments feasible.

Methods: We assessed different definitions of early OA using data from Multicenter Osteoarthritis (MOST) Study participants who were followed up longitudinally.

The Effectiveness of Nonpharmacological Interventions to Reduce Procedural Pain of Pediatric Oncology Patients: A Systematic Review and Meta-analysis.

Background: Relieving procedural pain in pediatric oncology is an important facilitator of the cancer treatment process.

Objective: To synthesize the effect of nonpharmacological interventions on reducing the procedural pain of pediatric oncology patients in randomized controlled trials.

Methods: A meta-analysis and systematic review for randomized controlled trials.

Deciphering the interplay between SETD2 mediated H3K36me3 and RNA N6-methyladenosine in clear cell renal cell carcinoma (ccRCC).

RNA N6-methyladenosine (m6A) plays diverse roles in RNA metabolism and its deregulation contributes to tumor initiation and progression. Clear cell renal cell carcinoma (ccRCC) is characterized by near ubiquitous loss of followed by mutations in epigenetic regulators , , and . Mutations in , a histone H3 lysine 36 trimethylase (H3K36me3), are associated with reduced survival, greater metastatic propensity, and metabolic reprogramming.

Lobaric acid suppresses the stemness potential of colorectal cancer cells through mTOR/AKT.

Stereocaulon alpinum has been found to have potential pharmaceutical properties due to the presence of secondary metabolites such as usnic acid, atranorin, and lobaric acid (LA) which have anticancer activity. On the other hand, the effect of LA on the stemness potential of colorectal cancer (CRC) cells remains unexplored, and has not yet been thoroughly investigated. In this study, we examined the inhibitory activity of LA from Stereocaulon alpinum against the stemness potential of CRC cells and investigated the possible underlying mechanisms.

Cyclo-N : a Novel 5/6 Fused Polynitrogen Anion for High Energy Density Materials.

After cyclo-pentazolate anion, a 5/6 fused structure of N is constructed, and four novel nitrogen-rich ionic compounds are assembled on its basis. The results of the quantum calculations revealed an uneven distribution of electrons on cyclo-N , with significant charge density near the N5/N9 atoms and an ADCH charge of -0.425.

Transition-Metal-Free Radical Approach for the Synthesis of Isothiocyanates by Pyridinium 1,4-Zwitterionic Thiolates as a Sulfur Source.

Herein, we disclose a novel, mild, transition-metal-free approach to synthesizing diversely functionalized isothiocyanates from the corresponding isocyanide precursors, achieving high to excellent yields (up to 97%). The current method sheds light on the reactivity of pyridinium 1,4-zwitterionic thiolates as an unprecedented sulfur source strikingly distinct from their previously known reactivity in ionic annulation reactions, showcasing an innovative approach to organic synthesis.

High-Conductivity, Self-Healing, and Adhesive Ionic Hydrogels for Health Monitoring and Human-Machine Interactions Under Extreme Cold Conditions.

Ionic conductive hydrogels (ICHs) are emerging as key materials for advanced human-machine interactions and health monitoring systems due to their unique combination of flexibility, biocompatibility, and electrical conductivity. However, a major challenge remains in developing ICHs that simultaneously exhibit high ionic conductivity, self-healing, and strong adhesion, particularly under extreme low-temperature conditions. In this study, a novel ICH composed of sulfobetaine methacrylate, methacrylic acid, TEMPO-oxidized cellulose nanofibers, sodium alginate, and lithium chloride is presented.

Toughening Poly(lactic acid) without Compromise - Statistical Copolymerization with a Bioderived Bicyclic Lactone.

Poly(lactic acid) (PLA) offers a renewable and degradable alternative to petroleum-based plastic, but its mechanical properties are not ideal for many applications. Herein, we describe the synthesis and polymerization of 2-oxo-3,8-dioxabicyclo[3.2.

Improving Bond Dissociations of Reactive Machine Learning Potentials through Physics-Constrained Data Augmentation.

In the field of computational chemistry, predicting bond dissociation energies (BDEs) presents well-known challenges, particularly due to the multireference character of reactive systems. Many chemical reactions involve configurations where single-reference methods fall short, as the electronic structure can significantly change during bond breaking. As generating training data for partially broken bonds is a challenging task, even state-of-the-art reactive machine learning interatomic potentials (MLIPs) often fail to predict reliable BDEs and smooth dissociation curves.

A Biomimetic Passive Mechanotransduction Mechanism Based on Interfacial Regulation of Ionic p-n Junctions.

Natural skin receptors use ions as signal carriers, while most of the developed artificial tactile sensors utilize electrons as information carriers. To imitate the biological ionic sensing behavior, here, we present a kind of biomimetic, ionic, and fully passive mechanotransduction mechanism leveraging mechanical modulation of interfacial ionic p-n junction (IPNJ) through microchannels. Sensors based on this mechanism do not rely on an external power supply and can encode external tactile stimuli into highly analogous signal outputs to those of natural skin receptors, in terms of both signal type (i.

Plant Diversity Reduces the Risk of Antibiotic Resistance Genes in Agroecosystems.

Despite advances in dispersal mechanisms and risk assessment of antibiotic resistance genes (ARGs), how plants influence ARG contamination in agricultural soils remains underexplored. Here, the impacts of plant species and diversity on ARGs and mobile genetic elements (MGEs) in three agricultural soils are comprehensively investigated in a pot experiment. The results indicate that increased plant diversity reduces ARGs and MGEs abundance by 19.

Insight into the Mechanism of d-Glucose Accelerated Exchange in GLUT1 from Molecular Dynamics Simulations.

Transmembrane glucose transport, facilitated by glucose transporters (GLUTs), is commonly understood through the simple mobile carrier model (SMCM), which suggests that the central binding site alternates exposure between the inside and outside of the cell, facilitating glucose exchange. An alternative "multisite model" posits that glucose transport is a stochastic diffusion process between ligand-operated gates within the transporter's central channel. This study aims to test these models by conducting atomistic molecular dynamics simulations of multiple glucose molecules docked along the central cleft of GLUT1 at temperatures both above and below the lipid bilayer melting point.

Functional Characterization of an Aldol Condensation Synthase PheG for the Formation of Hispidin from Phellinus Igniarius.

Hispidin (1) is a polyphenolic compound with a wide range of pharmacological activities that is distributed in both plants and fungi. In addition to natural extraction, hispidin can be obtained by chemical or enzymatic synthesis. In this study, the identification and characterization of an undescribed enzyme, PheG, from Phellinus igniarius (P.

Large-Area Conductor-Loaded PDMS Flexible Composites for Wireless and Chipless Electromagnetic Multiplexed Temperature Sensors.

Capacitive dielectric temperature sensors based on polydimethylsiloxane (PDMS) loaded with 10 vol% of inexpensive, commercially-available conductive fillers including copper, graphite, and milled carbon fiber (PDMS-CF) powders are reported. The sensors are tested in the range of 20-110 °C and from 0.5 to 200 MHz, with enhanced sensitivity from 20 to 60 °C, and a relative response of 85.

Ruthenium-Catalyzed Remote Trifunctionalization of Non-Activated Alkenes via Cyano Migration and -C(sp)-H Functionalization.

A novel Ru-catalyzed radical-triggered trifunctionalization of hexenenitriles is presented, employing a strategy of remote cyano group migration and -C(sp)-H functionalization. Through remote cyano migration, the alkenyl moiety undergoes difunctionalization to the formation of a benzylic radical intermediate. This intermediate facilitates -selective C-H bond addition relative to the C-Ru bond within the Ru(III) complex, ultimately enabling trifunctionalization.

Promiscuity Guided Evolution of Decarboxylative Aldolases for Synthesis of Tertiary γ-Hydroxy Amino Acids.

Many applications of enzymes benefit from activity on structurally diverse substrates. Here, we sought to engineer the decarboxylative aldolase UstD to perform a challenging C-C bond forming reaction with ketone electrophiles. The parent enzyme had only low levels of activity, portending multiple rounds of directed evolution and a possibility that mutations may inadvertently increase the specificity of the enzyme for a single model screening substrate.