A randomized phase 2 study of efmarodocokin alfa, an IL-22 agonist, versus vedolizumab in patients with ulcerative colitis.

Background And Aims: Efmarodocokin alfa is an interleukin (IL)-22 agonist, with favorable pharmacokinetic (PK) properties and an acceptable safety profile. This study further explored the therapeutic potential of efmarodocokin alfa compared to vedolizumab in patients with ulcerative colitis (UC).

Methods: This randomized phase 2 trial evaluated the efficacy, safety, PK, and pharmacodynamics of 3 doses of efmarodocokin alfa administered intravenously every 4 weeks (30 μg/kg [n=43], 60 μg/kg [n=44], and 90 μg/kg [n=43]) compared with placebo (n=22) and with vedolizumab (n=43) in the treatment of moderate to severe UC.

Multimodal Profiling of Peripheral Blood Identifies Proliferating Circulating Effector CD4 T Cells as Predictors for Response to Integrin α4β7-Blocking Therapy in Inflammatory Bowel Disease.

Background & Aims: Despite the success of biological therapies in treating inflammatory bowel disease, managing patients remains challenging due to the absence of reliable predictors of therapy response.

Methods: In this study, we prospectively sampled 2 cohorts of patients with inflammatory bowel disease receiving the anti-integrin α4β7 antibody vedolizumab. Samples were subjected to mass cytometry; single-cell RNA sequencing; single-cell B and T cell receptor sequencing (BCR/TCR-seq); serum proteomics; and multiparametric flow cytometry to comprehensively assess vedolizumab-induced immunologic changes in the peripheral blood and their potential associations with treatment response.

Safety, tolerability, and efficacy of subcutaneous efgartigimod in patients with chronic inflammatory demyelinating polyradiculoneuropathy (ADHERE): a multicentre, randomised-withdrawal, double-blind, placebo-controlled, phase 2 trial.

Background: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an autoimmune disease of the peripheral nervous system that can lead to severe disability from muscle weakness and sensory disturbances. Around a third of patients do not respond to currently available treatments, and many patients with a partial response have residual neurological impairment, highlighting the need for effective alternatives. Efgartigimod alfa, a human IgG1 antibody Fc fragment, has demonstrated efficacy and safety in patients with generalised myasthenia gravis.

European Academy of Neurology: First 10 years.

The European Academy of Neurology (EAN) was founded in May 2014 as the scientific society of all neurologists and all national neurological societies in Europe. The creation of EAN was based on the conscious decision of two predecessor societies (the European Federation of Neurological Societies and the European Neurological Society) to have a unique society for this continent with its 53 countries according to the World Health Organization and with the EU as the most important continental political decision level. In this report, the important milestones and the motivations of the decision-makers during the first 10 years are described.

Mental effort during mindless reading? Pupil fluctuations indicate internal processing during levels of inattention.

Mind wandering, an experience characterized by a reduced external focus of attention and an increased internal focus, has seen significant theoretical advancement in understanding its underlying cognitive processes. The levels-of-inattention hypothesis posits that in mind wandering, external attention is reduced in a graded fashion, reflecting different levels of weak versus deep attentional decoupling. However, it has remained unclear whether internal processing during mind wandering, and mindless reading in particular, requires effort and, if so, whether it is graded or distinct.

Inflammation promotes stomach epithelial defense by stimulating the secretion of antimicrobial peptides in the mucus.

The mucus serves as a protective barrier in the gastrointestinal tract against microbial attacks. While its role extends beyond merely being a physical barrier, the extent of its active bactericidal properties remains unclear, and the mechanisms regulating these properties are not yet understood. We propose that inflammation induces epithelial cells to secrete antimicrobial peptides, transforming mucus into an active bactericidal agent.

Curvature analysis of CI electrode arrays: a novel approach to categorize perimodiolar positions without anatomical landmarks.

Purpose: Perimodiolar electrode arrays may be positioned regular, over-inserted or under-inserted into the cochlea depending on the cochlear size and shape. The study aimed to examine whether there are differences between these groups in the local curvature along the intracochlear array. Individual curvature variables were developed to categorize the groups and the relationship between the curvature and the angular insertion depth at the electrode tip was analyzed.

Marine particle size-fractionation indicates organic matter is processed by differing microbial communities on depth-specific particles.

Passive sinking flux of particulate organic matter in the ocean plays a central role in the biological carbon pump and carbon export to the ocean's interior. Particle-associated microbes colonize particulate organic matter, producing "hotspots" of microbial activity. We evaluated variation in particle-associated microbial communities to 500 m depth across four different particle size fractions (0.

Anti-TNF therapy impairs both short- and long-term IgG responses after repeated vaccination.

Background: Recently, it has been questioned whether vaccination of patients with inflammatory (auto)immune diseases under anti-tumor necrosis factor (TNF) treatment leads to impaired vaccine-induced immune responses and protection against breakthrough infections. However, the effects of TNF blockade on short- and long-term immune responses after repeated vaccination remain unclear. Vaccination studies have shown that initial short-term IgG antibodies (Abs) carry highly galactosylated and sialylated Fc glycans, whilst long-term IgG Abs have low levels of galactosylation and sialylation and are most likely generated by long-lived plasma cells (PCs) derived primarily from the germinal center (GC) response.

Risankizumab for Ulcerative Colitis: Two Randomized Clinical Trials.

Importance: The clinical effects of risankizumab (a monoclonal antibody that selectively targets the p19 subunit of IL-23) for the treatment of ulcerative colitis are unknown.

Objective: To evaluate the efficacy and safety of risankizumab when administered as an induction and a maintenance therapy for patients with ulcerative colitis.

Design, Setting, And Participants: Two phase 3 randomized clinical trials were conducted.

Contrast enhanced photoacoustic detection of fibrillar collagen in the near infrared region-I.

Fibrillar collagen accumulation emerges as a promising biomarker in several diseases, such as desmoplastic tumors and unstable atherosclerotic plaque. Gold nanorods (GNRs) hold great potential as contrast agents in high-resolution, biomedically safe, and non-invasive photoacoustic imaging (PAI). This study presents the design and characterization of a specialized imaging tool which exploits GNR assisted targeted photoacoustic imaging that is tailored for the identification of fibrillar collagen.

Role of Interfacial Morphology in CuO/TiO and Band Bending: Insights from Density Functional Theory.

Photocatalysis, a promising solution to environmental challenges, relies on the generation and utilization of photogenerated charge carriers within photocatalysts. However, the recombination of these carriers often limits efficiency. Heterostructures, especially CuO/TiO, have emerged as effective solutions to enhance charge separation.

A spatio-temporal analysis of environmental fate and transport processes of pesticides and their transformation products in agricultural landscapes dominated by subsurface drainage with SWAT.

Pesticides are detected in surface water and groundwater, endangering the environment. In lowland regions with subsurface drainage systems, drained depressions become hotspots for transport of pesticides and their transformation products (TPs). This study focuses on detailed modelling of the degradation and transport of pesticides with different physico-chemical properties.

Mitochondrial DNA variants and microbiota: An experimental strategy to identify novel therapeutic potential in chronic inflammatory diseases.

We previously demonstrated that mice carrying natural mtDNA variants of the FVB/NJ strain (m.7778 G>T in the mt-Atp8 gene in mitochondrial complex V), namely C57BL/6 J-mt (B6-mtFVB), exhibited (i) partial protection from experimental skin inflammatory diseases in an anti-murine type VII collagen antibody-induced skin inflammation model and psoriasiform dermatitis model; (ii) significantly altered metabolites, including short-chain fatty acids, according to targeted metabolomics of liver, skin and lymph node samples; and (iii) a differential composition of the gut microbiota according to bacterial 16 S rRNA gene sequencing of stool samples compared to wild-type C57BL/6 J (B6) mice. To further dissect these disease-contributing factors, we induced an experimental antibody-induced skin inflammatory disease in gnotobiotic mice.

Revealing the pathogenesis of gastric intestinal metaplasia based on the mucosoid air-liquid interface.

Background: Gastric intestinal metaplasia (GIM) is an essential precancerous lesion. Although the reversal of GIM is challenging, it potentially brings a state-to-art strategy for gastric cancer therapeutics (GC). The lack of the appropriate in vitro model limits studies of GIM pathogenesis, which is the issue this work aims to address for further studies.

Human resource management to assist infection prevention and control professionals: a scoping review.

Infection prevention and control (IPC) professionals are key intermediaries between hospital managers and frontline staff. During the novel coronavirus disease pandemic, IPC professionals faced new challenges. Unfortunately, research on human resource management (HRM) to support IPC during and between pandemics is lacking.

Synthesis, Structure and (Photo)Catalytic Behavior of Ce-MOFs Containing Perfluoroalkylcarboxylate Linkers: Experimental and Theoretical Insights.

Cerium-based Metal-Organic frameworks (Ce-MOFs) are attracting increasing interest due to their similar structural features to zirconium MOFs. The redox behavior of Ce(III/IV) adds a range of properties to the compounds. Recently, perfluorinated linkers have been used in the synthesis of MOFs to introduce new characteristic into the structure.

Tumor associated microglia/macrophages utilize GPNMB to promote tumor growth and alter immune cell infiltration in glioma.

Tumor-associated microglia and blood-derived macrophages (TAMs) play a central role in modulating the immune suppressive microenvironment in glioma. Here, we show that GPNMB is predominantly expressed by TAMs in human glioblastoma multiforme and the murine RCAS-PDGFb high grade glioma model. Loss of GPNMB in the in vivo tumor microenvironment results in significantly smaller tumor volumes and generates a pro-inflammatory innate and adaptive immune cell microenvironment.

Clinical validation of RCSMS: A rapid and sensitive CRISPR-Cas12a test for the molecular detection of SARS-CoV-2 from saliva.

Peru's holds the highest COVID death rate per capita worldwide. Key to this outcome is the lack of robust, rapid, and accurate molecular tests to circumvent the elevated costs and logistics of SARS-CoV-2 detection via RT-qPCR. To facilitate massive and timely COVID-19 testing in rural and socioeconomically deprived contexts, we implemented and validated RCSMS, a rapid and sensitive CRISPR-Cas12a test for the molecular detection of SARS-CoV-2 from saliva.