EEFSEC deficiency: A selenopathy with early-onset neurodegeneration.

Inborn errors of selenoprotein expression arise from deleterious variants in genes encoding selenoproteins or selenoprotein biosynthetic factors, some of which are associated with neurodegenerative disorders. This study shows that bi-allelic selenocysteine tRNA-specific eukaryotic elongation factor (EEFSEC) variants cause selenoprotein deficiency, leading to progressive neurodegeneration. EEFSEC deficiency, an autosomal recessive disorder, manifests with global developmental delay, progressive spasticity, ataxia, and seizures.

Experimental medicine study with stabilised native-like HIV-1 Env immunogens drives long-term antibody responses, but lacks neutralising breadth.

Background: We report findings from an experimental medicine study of rationally designed prefusion stabilised native-like HIV envelope glycoprotein (Env) immunogens, representative of global circulating strains, delivered by sequential intramuscular injection.

Methods: Healthy adult volunteers were enrolled into one of five groups (A to E) each receiving a different schedule of one of two consensus Env immunogens (ConM SOSIP, ConS UFO, either unmodified or stabilised by chemical cross-linking, followed by a boost with two mosaic Env immunogens (Mos3.1 and Mos3.

Visceral Pain in Preterm Infants with Necrotizing Enterocolitis: Underlying Mechanisms and Implications for Treatment.

Necrotizing enterocolitis (NEC) is a relatively rare but very severe gastrointestinal disease primarily affecting very preterm infants. NEC is characterized by excessive inflammation and ischemia in the intestines, and is associated with prolonged, severe visceral pain. Despite its recognition as a highly painful disease, current pain management for NEC is often inadequate, and research on optimal analgesic therapy for these patients is lacking.

Salivary microbiota dysbiosis and elevated polyamine levels contribute to the severity of periodontal disease.

Background: The oral cavity is a complex environment which harbours the second largest and most diverse microflora after the gastrointestinal tract. The bacteriome in the oral cavity plays a pivotal role in promoting the health and well-being of human beings. Gingivitis, an inflammation of the gingival tissue, arises due to plaque accumulation on the teeth, often leads to periodontitis.

Molecular and spatial analysis of tertiary lymphoid structures in Sjogren's syndrome.

Tertiary lymphoid structures play important roles in autoimmune and non-autoimmune conditions. While many of the molecular mechanisms involved in tertiary lymphoid structure formation have been identified, the cellular sources and temporal and spatial relationship remain unknown. Here we use combine single-cell RNA-sequencing, spatial transcriptomics and proteomics of minor salivary glands of patients with Sjogren's disease and Sicca Syndrome, with ex-vivo functional studies to construct a cellular and spatial map of key components involved in the formation and function of tertiary lymphoid structures.

ATRX silences Cartpt expression in osteoblastic cells during skeletal development.

ATP-dependent chromatin remodeling protein ATRX is an essential regulator involved in maintenance of DNA structure and chromatin state and regulation of gene expression during development. ATRX was originally identified as the monogenic cause of X-linked α-thalassemia mental retardation (ATR-X) syndrome. Affected individuals display a variety of developmental abnormalities and skeletal deformities.

MHC-related protein 1-restricted recognition of cancer via a semi-invariant TCR-α chain.

The T cell antigen presentation platform MR1 consists of 6 allomorphs in humans that differ by no more than 5 amino acids. The principal function of this highly conserved molecule involves presenting microbial metabolites to the abundant mucosal-associated invariant T (MAIT) cell subset. Recent developments suggest that the role of MR1 extends to presenting antigens from cancer cells, a function dependent on the K43 residue in the MR1 antigen binding cleft.

More Than the Sum of Its Parts: Disrupted Core Periphery of Multiplex Brain Networks in Multiple Sclerosis.

Disruptions to brain networks, measured using structural (sMRI), diffusion (dMRI), or functional (fMRI) MRI, have been shown in people with multiple sclerosis (PwMS), highlighting the relevance of regions in the core of the connectome but yielding mixed results depending on the studied connectivity domain. Using a multilayer network approach, we integrated these three modalities to portray an enriched representation of the brain's core-periphery organization and explore its alterations in PwMS. In this retrospective cross-sectional study, we selected PwMS and healthy controls with complete multimodal brain MRI acquisitions from 13 European centers within the MAGNIMS network.

Separating dementia with Lewy bodies from Alzheimer's disease dementia using a volumetric MRI classifier.

Objectives: Distinguishing dementia with Lewy bodies (DLB) from Alzheimer's disease (AD) dementia, particularly in patients with DLB and concomitant AD pathology (DLB/AD+), can be challenging and there is no specific MRI signature for DLB. The aim of this study is to examine the additional value of MRI-based brain volumetry in separating patients with DLB (AD+/-) from patients with AD and controls.

Methods: We included 1518 participants from four cohorts (ADC, ADNI, PDBP and PredictND); 147 were patients with DLB (n = 76, DLB/AD+; n = 71, DLB/AD-), 668 patients with AD dementia, and 703 controls.

An antibody cocktail targeting two different CD73 epitopes enhances enzyme inhibition and tumor control.

CD73, an ectoenzyme responsible for adenosine production, is often elevated in immuno-suppressive tumor environments. Inhibition of CD73 activity holds great promise as a therapeutic strategy for CD73-expressing cancers. In this study, we have developed a therapeutic anti-human CD73 antibody cocktail, HB0045.

Comparison of models to predict incident chronic liver disease: a systematic review and external validation in Chinese adults.

Background: Risk prediction models can identify individuals at high risk of chronic liver disease (CLD), but there is limited evidence on the performance of various models in diverse populations. We aimed to systematically review CLD prediction models, meta-analyze their performance, and externally validate them in 0.5 million Chinese adults in the China Kadoorie Biobank (CKB).

G-cleave LC3B biosensor: monitoring autophagy and assessing resveratrol's synergistic impact on doxorubicin-induced apoptosis in breast cancer cells.

Autophagy, a crucial process in cancer, is closely intertwined with both tumor progression and drug resistance development. However, existing methods used to assess autophagy activity often pose invasiveness and time-related constraints, limiting their applicability in preclinical drug investigations. In this study, we developed a non-invasive autophagy detection system (NIADS-autophagy, also called G-cleave LC3B biosensor) by integrating a split-luciferase-based biosensor with an LC3B cleavage sequence, which swiftly identified classic autophagic triggers, such as Earle's Balanced Salt Solution and serum deprivation, through protease-mediated degradation pathways.

Examining the effects of psychological resilience and wellbeing on perceived stress and depressive symptoms among undergraduate nursing interns: testing a moderated mediation model.

Background: Perceived stress is recognized as a significant risk factor for depressive symptoms, while psychological resilience and wellbeing are considered crucial protective factors. However, the intricate relationships among these variables in undergraduate nursing interns remain largely unexplored. This study aims to investigate the mediating role of psychological resilience in the relationship between perceived stress and depressive symptoms, as well as the moderating influence of wellbeing on this mediation.

Nutraceuticals silybin B, resveratrol, and epigallocatechin-3 gallate-bind to cardiac muscle troponin to restore the loss of lusitropy caused by cardiomyopathy mutations , , and .

Introduction: Adrenergic activation of protein kinase A (PKA) in cardiac muscle targets the sarcolemma, sarcoplasmic reticulum, and contractile apparatus to increase contractile force and heart rate. In the thin filaments of the contractile apparatus, cardiac troponin I (cTnI) Ser22 and Ser23 in the cardiac-specific N-terminal peptide (NcTnI: residues 1 to 32) are the targets for PKA phosphorylation. Phosphorylation causes a 2-3 fold decrease of affinity of cTn for Ca associated with a higher rate of Ca dissociation from cTnC leading to a faster relaxation rate of the cardiac muscle (lusitropy).

Camouflaging in neurodivergent and neurotypical girls at the transition to adolescence and its relationship to mental health: A participatory methods research study.

Background: Adolescent girls with diagnoses of autism, ADHD and/or developmental coordination disorder (DCD) are at higher risk for mental health problems than boys with the same diagnoses and neurotypical girls. These girls are called neurodivergent here, though neurodivergence includes a broader range of diagnoses. One possible reason for this mental health disparity could be camouflaging, a coping strategy used more by girls.

Evaluation of population immunity against SARS-CoV-2 variants, EG.5.1, FY.4, BA.2.86, JN.1, JN.1.4, and KP.3.1.1 using samples from two health demographic surveillance systems in Kenya.

Increased immune evasion by emerging and highly mutated SARS-CoV-2 variants is a key challenge to the control of COVID-19. The majority of these mutations mainly target the spike protein, allowing the new variants to escape the immunity previously raised by vaccination and/or infection by earlier variants of SARS-CoV-2. In this study, we investigated the neutralizing capacity of antibodies against emerging variants of interest circulating between May 2023 and October 2024 using sera from representative samples of the Kenyan population.

Regulatory T cell therapy is associated with distinct immune regulatory lymphocytic infiltrates in kidney transplants.

Background: Adoptive transfer of autologous regulatory T cells (Tregs) is a promising therapeutic strategy aimed at enabling immunosuppression minimization following kidney transplantation. In our phase 1 clinical trial of Treg therapy in living donor renal transplantation, the ONE Study (ClinicalTrials.gov: NCT02129881), we observed focal lymphocytic infiltrates in protocol kidney transplant biopsies that are not regularly seen in biopsies of patients receiving standard immunosuppression.

An Exploratory Analysis of Child Characteristics Predicting Clinical Outcomes in Parent-Led Cognitive Behavioral Teletherapy for Anxiety in Autistic Children.

Parent-led cognitive behavioral therapy (CBT) is an efficient, promising form of therapy that may be well suited for autistic youth with anxiety disorders. A recent clinical trial found that parent-led CBT - in which parents led their child through a guided CBT workbook with varying degrees of therapist support - was efficacious for reducing anxiety and associated functional impairment. While such findings demonstrate promise for future intervention development and dissemination efforts with this population, more work is needed to elucidate clinical factors that impact response to treatment as well as drop-out.

Discovery, Characterization, and Application of Broad-Spectrum Antimicrobial Peptide AtR905 from as a Biocontrol Agent.

This study investigates a novel antimicrobial peptide AtR905 derived from the endophytic fungus , which was successfully expressed in , purified, and characterized, and highlighted as a promising potential biocontrol agent against various plant pathogens. The results indicated AtR905 exhibited broad-spectrum antimicrobial activities against key pathogens such as and with very low minimal inhibitory concentrations (MICs). Stability tests confirmed that AtR905 retains its antimicrobial properties under varying thermal, pH, and UV conditions.

H and P MR Spectroscopy to Assess Muscle Mitochondrial Dysfunction in Long COVID.

Background Emerging evidence suggests mitochondrial dysfunction may play a role in the fatigue experienced by individuals with post-COVID-19 condition (PCC), commonly called long COVID, which can be assessed using MR spectroscopy. Purpose To compare mitochondrial function between participants with fatigue-predominant PCC and healthy control participants using MR spectroscopy, and to investigate the relationship between MR spectroscopic parameters and fatigue using the 11-item Chalder fatigue questionnaire. Materials and Methods This prospective, observational, single-center study (June 2021 to January 2024) included participants with PCC who reported moderate to severe fatigue, with normal blood test and echocardiographic results, alongside control participants without fatigue symptoms.

The impact of psoriatic arthritis on quality of life: a systematic review.

Background: Psoriatic arthritis (PsA) is a chronic inflammatory condition that can affect individuals of all ages. Patients may experience a range of physical and psychological issues.

Objective: To examine the impact of PsA on an individual's quality of life (QoL) and physical function.

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.