Usability, efficacy, and safety of candidate tocilizumab biosimilar CT-P47 self-administration via auto-injector and pre-filled syringe in patients with rheumatoid arthritis: a single-arm, open-label, phase 3 study.

Background: CT-P47 is a candidate tocilizumab biosimilar that is currently in clinical development. We assessed the usability of CT-P47 self-administration via auto-injector (AI) in patients with rheumatoid arthritis (RA).

Research Design And Methods: This was a 12-week, single-arm, open-label, multiple-dose, Phase 3 study.

Identifying a Genetic Link Between Lung Function and Psoriasis.

Introduction: The common genetic underpinnings of psoriasis and pulmonary comorbidities have yet to be explored.

Material And Methods: In this cross-sectional study, we investigated the single-nucleotide polymorphisms (SNPs) associated with psoriasis and their relationship with pulmonary function using data from the UK Biobank (UKBB) and the Vanderbilt University Medical Center Biobank (BioVU).

Results: Out of the 63 psoriasis-associated SNPs identified in previous genome-wide association studies within the European population, we successfully identified 53 SNPs, including proxy SNPs in UKBB database.

Distinct virologic trajectories in chronic hepatitis B identify heterogeneity in response to nucleos(t)ide analogue therapy.

Background & Aims: The dynamics of HBV viral load (VL) in patients with chronic hepatitis B (CHB) on nucleos(t)ide analogue (NA) treatment and its relationship with liver disease are poorly understood. We aimed to study longitudinal VL patterns and their associations with CHB clinical outcomes.

Methods: Utilising large scale, routinely collected electronic health records from six centres in England, collated by the National Institute for Health and Care Research Health Informatics Collaborative (NIHR HIC), we applied latent class mixed models to investigate VL trajectory patterns in adults receiving NA treatment.

Characterization of Human CD8αβ Interaction With Classical and Unconventional MHC Molecules.

The CD8 co-receptor exists as both an αα homodimer, expressed on subsets of specialized lymphoid cells, and as an αβ heterodimer, which is the canonical co-receptor on cytotoxic T-cells, tuning TCR thymic selection and antigen-reactivity in the periphery. However, the biophysical parameters governing human CD8αβ interactions with classical MHC class I (MHCI) and unconventional MHC-like molecules have not been determined. Using hetero-dimerized Fc-fusions to generate soluble human CD8αβ, we demonstrate similar weak binding affinity to multiple different MHCI alleles compared with CD8αα.

Turncoat antibodies unmasked in a model of autoimmune demyelination: from biology to therapy.

Autoantibodies contribute to many autoimmune diseases, yet there is no approved therapy to neutralize them selectively. A popular mouse model, experimental autoimmune encephalomyelitis (EAE), could serve to develop such a therapy, provided we can better understand the nature and importance of the autoantibodies involved. Here we report the discovery of autoantibody-secreting extrafollicular plasmablasts in EAE induced with specific myelin oligodendrocyte glycoprotein (MOG) antigens.

Treatment of patellar luxation with polyethylene sulcal ridge prostheses in 44 feline stifles: a retrospective study.

Objectives: The aim of this study was to assess the complication rates and long-term outcomes, as well as to refine case selection criteria for cats undergoing trochlear ridge augmentation (TRA) using an ultra-high molecular weight polyethylene implant (UHMWPEI) for the treatment of patellar luxation (PL).

Methods: The clinical records from two referral veterinary hospitals were searched for cases that fitted defined inclusion criteria. A short-term assessment was based on examination and radiography at 8 weeks postoperatively.

Expanding the genetic landscape of endometriosis: Integrative -omics analyses uncover key pathways from a multi-ancestry study of over 900,000 women.

We report the findings of a genome-wide association study (GWAS) meta-analysis of endometriosis consisting of a large portion (31%) of non-European samples across 14 biobanks worldwide as part of the Global Biobank Meta-Analysis Initiative (GBMI). We identified 45 significant loci using a wide phenotype definition, seven of which are previously unreported and detected first genome-wide significant locus ( ) among only African-ancestry. Our narrow phenotypes and surgically confirmed case definitions for endometriosis analyses replicated the known loci near , , and .

Assessing Wear Characteristics of Sprayable, Diacetylene-Containing Sensor Formulations.

This work extends recent developments in diacetylene-based, sprayable sensors by identification and assessment of formulations which facilitate their use for wearable sensing. Diacetylene-based spray-on sensors have the potential to be a widely deployed sensing technology, as they require no power and can be applied as thin coatings onto surfaces to provide a colorimetric response to target exposure. In responding to radiation, liquid-phase targets, or gas-phase targets specifically determined by the formulation of the sprayable sensor used, this technology is amenable to wearable sensors for measuring exposure to different environmental risks.

Pharmacogenetics of tuberculosis treatment toxicity and effectiveness in a large Brazilian cohort.

Background: Genetic polymorphisms have been associated with risk of antituberculosis treatment toxicity. We characterized associations with adverse events and treatment failure/recurrence among adults treated for tuberculosis in Brazil.

Methods: Participants were followed in Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil.

Enhancing genetic association power in endometriosis through unsupervised clustering of clinical subtypes identified from electronic health records.

Endometriosis is a complex and heterogeneous condition affecting 10% of reproductive-age women, and yet, it often goes undiagnosed for several years. Limited observed heritability (7%) of large genetic association studies may be attributable to underlying heterogeneity of disease mechanisms. Therefore, we conducted this study to investigate genetic associations across sub-phenotypes of endometriosis.

Metabolic dysfunction-associated steatotic liver disease - A new indication for sodium-glucose Co-transporter-2 inhibitors.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has been proposed as a new name for the previous non-alcoholic fatty liver disease (NAFLD). There are some differences between MASLD and NAFLD, e.g.

Steel ribbed dome structural performance with different node connections and bracing system.

The conventional design of steel structure objects relies on a first-order elastic analysis, where the entire object is treated as a set of individual structural elements requiring time-consuming, semi-empirical design calculations. Such an approach leads to inefficient design time and excessive material consumption and may additionally result in designing on the verge of structural safety. The AEC sector's technological and digitization advancement process forces designers to use advanced design methods.

The challenge of diagnosing and classifying eosinophilia and eosinophil disorders: A review.

Eosinophilia is a feature of multiple conditions, both hematologic and non-hematologic, and may be associated with organ damage. The pathogenesis of eosinophilia can follow two distinct pathways. Primary eosinophilia is caused by a cell-intrinsic mechanism originating from clonal expansion of eosinophils through acquisition of a somatic mutation, such as FIP1L1-PDGFRA.

Autophagy initiation triggers p150-AP-2β interaction on the lysosomes and facilitates their transport.

The endocytic adaptor protein 2 (AP-2) complex binds dynactin as part of its noncanonical function, which is necessary for dynein-driven autophagosome transport along microtubules in neuronal axons. The absence of this AP-2-dependent transport causes neuronal morphology simplification and neurodegeneration. The mechanisms that lead to formation of the AP-2-dynactin complex have not been studied to date.

Targeting the EGFR pathway: An alternative strategy for the treatment of tuberous sclerosis complex?

Introduction: Tuberous sclerosis complex (TSC) is caused by variants in TSC1/TSC2, leading to constitutive activation of the mammalian target of rapamycin (mTOR) complex 1. Therapy with everolimus has been approved for TSC, but variations in success are frequent. Recently, caudal late interneuron progenitor (CLIP) cells were identified as a common origin of the TSC brain pathologies such as subependymal giant cell astrocytomas (SEGA) and cortical tubers (CT).

Evaluation of measurement reliability for selected indices of postural stability based on data from the GYKO Inertial Sensor System.

The main aim of this study is to use comprehensive statistical analyses to evaluate measurement reliability of selected variables that characterize postural stability. The study examined twenty-nine healthy non-athlete students. The examinations were performed twice, with a one-week interval.

Reliability of Domestic Gas Flow Sensors with Hydrogen Admixtures.

Static flow sensors (e.g., thermal gas micro electro-mechanical sensors-MEMS-and ultrasonic time of flight) are becoming the prevailing technology for domestic gas metering and billing since they show advantages in respect to the traditional volumetric ones.

Spray-On Colorimetric Sensors for Distinguishing the Presence of Lead Ions.

Sprayable stimuli-responsive material coatings represent a new class of detection system which can be quickly implemented to transform a surface into a color-responsive sensor. In this work, we describe a dipicolylamine-terminated diacetylene-containing amphiphile formulation for spray coating on to a simple paper substrate to yield disposable test strips that can be used to detect the presence of lead ions in solution. We find the response to be very selective to only lead ions and that the sensitivity can be modulated by altering the UV curing time after spraying.

Implementation of an Experiential Service-Learning Course in Biomedical Engineering Design for Undergraduate Students.

The unique characteristics of the training needed for today's biomedical engineers can represent a challenge in curriculum design. Practical experiential learning for biomedical engineering undergraduates is important to prevent under-developed professional skills. In this teaching tips article, we provide an example of how to incorporate experiential learning into the biomedical engineering curriculum to address the need for undergraduates to gain the desired skillsets to serve as the next generation of leaders in engineering, medicine, and business all through the lens of civic engagement.

Cadaveric comparison of two techniques for intraoperative placement of tibial plateau levelling osteotomies in dogs.

Background: Both tibial tuberosity fractures and deviation from the planned postoperative tibial plateau angle have been associated with poor centring of tibial plateau levelling osteotomies (TPLOs). The aim of this cadaveric study was to compare two techniques for centring the osteotomy and preserving the tibial tuberosity width (TTW).

Methods: Stifle radiographs were obtained from 20 limbs of 10 dogs.

Rab11 regulates autophagy at dendritic spines in an mTOR- and NMDA-dependent manner.

Synaptic plasticity is a process that shapes neuronal connections during neurodevelopment and learning and memory. Autophagy is a mechanism that allows the cell to degrade its unnecessary or dysfunctional components. Autophagosomes appear at dendritic spines in response to plasticity-inducing stimuli.

Interaction between Continuous Pack-Years Smoked and Polygenic Risk Score on Lung Cancer Risk: Prospective Results from the Framingham Heart Study.

Background: Lung cancer risk attributable to smoking is dose dependent, yet few studies examining a polygenic risk score (PRS) by smoking interaction have included comprehensive lifetime pack-years smoked.

Methods: We analyzed data from participants of European ancestry in the Framingham Heart Study Original (n = 454) and Offspring (n = 2,470) cohorts enrolled in 1954 and 1971, respectively, and followed through 2018. We built a PRS for lung cancer using participant genotyping data and genome-wide association study summary statistics from a recent study in the OncoArray Consortium.

Dendritic arbor dynamics and stability in health and disease.

Dendritogenesis, a process of dendritic arbor development, is essential for the formation of functional neuronal networks, and in mammals, it begins in early life and continues into adulthood. It is a highly dynamic process in which dendritic branches form and regress until mature connectivity is achieved. Thereafter, dendritic branches are considered stable and do not undergo substantial rearrangements, although several exceptions have been described in the literature.