Effect of weight loss and liraglutide on neutrophil gelatinase-associated lipocalin levels among individuals with overweight and knee osteoarthritis: Exploratory analyses of a randomized controlled trial.

Objective: Obesity is a major risk factor for osteoarthritis (OA). Adipose tissues may be linked to OA development through secretion of potential proinflammatory cytokines including neutrophil gelatinase-associated lipocalin (NGAL). Our objective was to assess changes in serum NGAL after a low-calorie diet (LCD) and subsequent glucagon-like peptide 1 receptor agonist (GLP-1 RA) treatment.

Towards Solid-State Batteries Using a Calcium Hydridoborate Electrolyte.

Solid-state batteries created from abundant elements, such as calcium, may pave the way for cheaper and safer electrical energy storage. Here we report a new type of solid calcium hydridoborate electrolyte, Ca(BH4)2·2NH2CH3, with a high ionic conductivity of σ(Ca2+) ~ 10-5 S cm-1 at T = 70 °C, which is assigned to a relatively open and flexible structure with apolar moieties and weak dihydrogen bonds that facilitate migration of Ca2+ ions in the solid state. The compound display a low electronic conductivity, providing an ionic transport number close to unity (tion = 0.

The therapeutic potential of circular RNAs.

Over the past decade, research into circular RNA (circRNA) has increased rapidly, and over the past few years, circRNA has emerged as a promising therapeutic platform. The regulatory functions of circRNAs, including their roles in templating protein translation and regulating protein and RNA functions, as well as their unique characteristics, such as increased stability and a favourable immunological profile compared with mRNAs, make them attractive candidates for RNA-based therapies. Here, we describe the properties of circRNAs, their therapeutic potential and technologies for their synthesis.

Enabling simultaneous photoluminescence spectroscopy and X-ray footprinting mass spectrometry to study protein conformation and interactions.

X-ray footprinting mass spectrometry (XFMS) is a structural biology method that uses broadband X-rays for hydroxyl radical labeling to map protein interactions and conformation in solution. However, while XFMS alone provides important structural information on biomolecules, as we move into the era of the interactome, hybrid methods are becoming increasingly necessary to gain a comprehensive understanding of protein complexes and interactions. Toward this end, we report the development of the first synergetic application of inline and real-time fluorescent spectroscopy at the Advanced Light Source's XFMS facility to study local protein interactions and global conformational changes simultaneously.

Terbinafine Resistance in Trichophyton Species From Patients With Recalcitrant Infections Detected by the EUCAST Broth Microdilution Method and DermaGenius Resistance Multiplex PCR Kit.

Background: Emerging terbinafine resistance in Trichophyton species has been reported globally. The prevalence in clinical samples from patients with treatment failure is unknown in Denmark.

Objectives: Prospective study of terbinafine resistance in Trichophyton isolates from patients with recalcitrant skin or nail infections.

The Prognostic Potential of circRNAs in Multiple Myeloma: Insights From Whole Bone Marrow and Purified Plasma Cells.

Multiple myeloma (MM) is a haematological malignancy with abnormal proliferation of plasma cells in the bone marrow (BM), and MM patients with highly proliferative plasma cells have reduced overall survival. Circular RNAs (circRNAs) are endogenous, non-coding molecules that are promising biomarkers in cancer. Here, we present the largest study of circRNAs in MM to date and explore the prognostic potential of circRNAs and the link between proliferation and circRNA expression in MM.

Association of achieving clinical disease control criteria and patient-reported outcomes in bimekizumab-treated patients with active psoriatic arthritis: results from two phase III studies.

Background: Psoriatic arthritis (PsA) is a chronic inflammatory disease that causes pain and fatigue, reduces physical function, and negatively impacts health-related quality of life (HRQoL). In the phase III BE OPTIMAL and BE COMPLETE studies, bimekizumab demonstrated clinical efficacy and meaningful improvements in patient-reported outcome (PRO) measures in biologic disease-modifying antirheumatic drug (bDMARD)-naïve patients, and those who had prior inadequate response/intolerance to tumor necrosis factor inhibitors (TNFi-IR).

Objectives: To examine the association between achieving increasingly stringent clinical disease control criteria and improvements in PRO measures in patients with active PsA receiving bimekizumab.

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Cardiac arrest (CA) survivorship is associated with risk of cognitive deficits, emotional and social consequences. Early recognition of these symptoms and referral to rehabilitation is considered to be the fifth link in the chain of survival. This review highlights the need for a national standardized care plan for CA survivors based on a multidisciplinary approach.

Influence of study characteristics on harm estimates from randomised controlled trials in patients with inflammatory arthritis receiving biological or synthetic antirheumatic drugs: a meta-epidemiological study.

Objective: To examine the association between study characteristics and the harms reported in randomised controlled trials (RCTs) on biological and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in patients with inflammatory arthritis (IA).

Methods: We searched MEDLINE for all Cochrane reviews and for systematic reviews published since April 2015. RCTs were eligible if they included patients with IA receiving b/tsDMARD, compared with any comparator arm.

Automated acute skin toxicity scoring in a mouse model through deep learning.

This study presents a novel approach to skin toxicity assessment in preclinical radiotherapy trials through an advanced imaging setup and deep learning. Skin reactions, commonly associated with undesirable side effects in radiotherapy, were meticulously evaluated in 160 mice across four studies. A comprehensive dataset containing 7542 images was derived from proton/electron trials with matched manual scoring of the acute toxicity on the right hind leg, which was the target area irradiated in the trials.

Once-Weekly Semaglutide in Persons with Obesity and Knee Osteoarthritis.

Background: Weight reduction has been shown to alleviate symptoms of osteoarthritis of the knee, including pain. The effect of glucagon-like peptide-1 receptor agonists on outcomes in knee osteoarthritis among persons with obesity has not been well studied.

Methods: We conducted a 68-week, double-blind, randomized, placebo-controlled trial at 61 sites in 11 countries.

A Modular Smart Ocean Observatory for Development of Sensors, Underwater Communication and Surveillance of Environmental Parameters.

The rapid growth of marine industries has emphasized the focus on environmental impacts for all industries, as well as the influence of key environmental parameters on, for instance, offshore wind or aquaculture performance, animal welfare and structural integrity of different constructions. Development of automatized sensors together with efficient communication and information systems will enhance surveillance and monitoring of environmental processes and impact. We have developed a modular Smart Ocean observatory, in this case connected to a large-scale marine aquaculture research facility.

Efficacy and Safety of Tofacitinib in Patients with Psoriatic Arthritis or Ankylosing Spondylitis by Cigarette Smoking Status.

Introduction: Routine care studies of psoriatic arthritis (PsA) and ankylosing spondylitis (AS) demonstrated attenuated responses to tumor necrosis factor inhibitors in current/past versus never smokers. This post hoc analysis assessed tofacitinib efficacy and safety in patients with PsA or AS by cigarette smoking status at trial screening.

Methods: Pooled data from phase 3 and long-term extension (safety only) PsA trials and phase 2 and 3 AS trials were assessed by current/past versus never smoker status.

Residue-Specific Epitope Mapping of the PD-1/Nivolumab Interaction Using X-ray Footprinting Mass Spectrometry.

X-ray footprinting coupled with mass spectrometry (XFMS) presents a novel approach in structural biology, offering insights into protein conformation and dynamics in the solution state. The interaction of the cancer-immunotherapy monoclonal antibody nivolumab with its antigen target PD-1 was used to showcase the utility of XFMS against the previously published crystal structure of the complex. Changes in side-chain solvent accessibility, as determined by the oxidative footprint of free PD-1 versus PD-1 bound to nivolumab, agree with the binding interface side-chain interactions reported from the crystal structure of the complex.

Comparative early effectiveness across 14 PsA drugs and 5 classes of PsA treatment: 3-month results from the PRO-SPIRIT study.

Background: The psoriatic arthritis (PsA) Observational Study of Persistence of Treatment (PRO-SPIRIT) assesses effectiveness and persistence of real-world PsA treatments. Ixekizumab (IXE) is an interleukin (IL)-17A inhibitor (i) (IL-17Ai), approved for the treatment of adult PsA.

Methods: The aim of this predefined interim analysis was to report baseline characteristics along with early (3-month) descriptive and comparative real-world effectiveness in patients with PsA prescribed with advanced treatment including IL-17Ai; IXE or secukinumab (SEC), IL-12/23i, IL-23i, tumour necrosis factor (TNFi) or Janus kinase (JAKi).

Correlation between local instantaneous dose rate and oxygen pressure reduction during proton pencil beam scanning irradiation.

Background And Purpose: Oxygen dynamics may be important for the tissue-sparing effect observed at ultra-high dose rates (FLASH sparing effect). This study investigated the correlation between local instantaneous dose rate and radiation-induced oxygen pressure reduction during proton pencil beam scanning (PBS) irradiations of a sample and quantified the oxygen consumption g-value.

Materials And Methods: A 0.

circHIPK3 nucleates IGF2BP2 and functions as a competing endogenous RNA.

Circular RNAs represent a class of endogenous RNAs that regulate gene expression and influence cell biological decisions with implications for the pathogenesis of several diseases. Here, we disclose a novel gene-regulatory role of circHIPK3 by combining analyses of large genomics datasets and mechanistic cell biological follow-up experiments. Using time-course depletion of circHIPK3 and specific candidate RNA-binding proteins, we identify several perturbed genes by RNA sequencing analyses.

Spread-out Bragg peak FLASH: quantifying normal tissue toxicity in a murine model.

Objective: A favorable effect of ultra-high dose rate (FLASH) radiation on normal tissue-sparing has been indicated in several preclinical studies. In these studies, the adverse effects of radiation damage were reduced without compromising tumor control. Most studies of proton FLASH investigate these effects within the entrance of a proton beam.

Minimal dose CT for left ventricular ejection fraction and combination with chest-abdomen-pelvis CT.

Objectives: This prospective study tested the diagnostic accuracy, and absolute agreement with MRI of a low-dose CT protocol for left ventricular ejection fraction (LVEF) measurement. Furthermore we assessed its potential for combining it with Chest-Abdomen-Pelvis CT (CAP-CT) for a one-stop examination.

Materials & Methods: Eighty-two patients underwent helical low-dose CT.

Retention rate of a novel autoinjector e-Device introduced to patients with chronic arthritis treated with certolizumab pegol in clinical practice: an observational implementation study.

Objectives: The objectives were to explore the clinical retention rate of an e-Device aimed at empowering chronic arthritis patients using certolizumab pegol (CZP) and to analyse beliefs about medication in the Danish population.

Method: Patients treated with CZP were recruited from the Netherlands, Denmark, and Sweden through rheumatology clinics at initiation of, or switching to, the e-Device. Patients were adults (aged 18-85 years) diagnosed with rheumatoid arthritis, axial spondyloarthritis, or psoriatic arthritis.

Structure and Interactions of HIV-1 gp41 CHR-NHR Reverse Hairpin Constructs Reveal Molecular Determinants of Antiviral Activity.

Engineered reverse hairpin constructs containing a partial C-heptad repeat (CHR) sequence followed by a short loop and full-length N-heptad repeat (NHR) were previously shown to form trimers in solution and to be nanomolar inhibitors of HIV-1 Env mediated fusion. Their target is the in situ gp41 fusion intermediate, and they have similar potency to other previously reported NHR trimers. However, their design implies that the NHR is partially covered by CHR, which would be expected to limit potency.

Proton FLASH: Impact of Dose Rate and Split Dose on Acute Skin Toxicity in a Murine Model.

Purpose: Preclinical studies have shown a preferential normal tissue sparing effect of FLASH radiation therapy with ultra-high dose rates. The aim of the present study was to use a murine model of acute skin toxicity to investigate the biologic effect of varying dose rates, time structure, and introducing pauses in the dose delivery.

Methods And Materials: The right hind limbs of nonanaesthetized mice were irradiated in the entrance plateau of a pencil beam scanning proton beam with 39.