DNA methylation analysis on anal swabs for anal cancer screening in people living with HIV.

Introduction: High-resolution anoscopy (HRA) to prevent anal cancer is complex and screening capacity is limited. Previously, we showed that DNA methylation analysis of anal high-grade squamous intraepithelial lesions (HSIL) biopsies can distinguish between HSIL with an increased cancer risk, and HSIL with a low cancer risk, in which treatment may be safely withheld. Here, we assessed the performance of methylation analysis in anal swabs to identify patients with underlying HSIL with an increased cancer risk.

Liver abscesses secondary to a non-O1/non-O139 Vibrio cholerae bacteremia acquired in a non-coastal area: a case report.

Non-O1/non-O139 Vibrio cholerae (NOVC) strains are a distinct group of Vibrio cholerae that do not cause epidemic cholera. NOVC infections usually cause mild forms of gastroenteritis, and rarely severe (extra)intestinal infections, mostly affecting immunocompromised patients. Here, we describe the clinical course of a patient with NOVC bacteremia causing multiple liver abscesses, after drinking from a freshwater well in a non-coastal area.

Infiltrative classical monocyte-derived and SPP1 lipid-associated macrophages mediate inflammation and fibrosis in ANCA-associated glomerulonephritis.

Background And Hypothesis: Kidney macrophage infiltration is a histological hallmark of vasculitic lesions and is strongly linked to disease activity in anti-neutrophil cytoplasmic antibodies (ANCA)-associated glomerulonephritis (AGN). The precise mechanisms by which kidney macrophages influence local inflammation and long-term damage remain largely unknown.

Methods: Here, we investigate kidney macrophage diversity using single-cell transcriptome analysis of 25 485 freshly retrieved unfrozen, high-quality kidney CD45+ immune cells from five AGN patients during active disease, a lupus nephritis and nephrectomy control.

Skeletal muscle adaptations and post-exertional malaise in long COVID.

When acute SARS-CoV-2 infections cause symptoms that persist longer than 3 months, this condition is termed long COVID. Symptoms experienced by patients often include myalgia, fatigue, brain fog, cognitive impairments, and post-exertional malaise (PEM), which is the worsening of symptoms following mental or physical exertion. There is little consensus on the pathophysiology of exercise-induced PEM and skeletal-muscle-related symptoms.

Association of blood inflammatory phenotypes and asthma burden in children with moderate-to-severe asthma.

Background: Underlying immunological mechanisms in children with moderate-to-severe asthma are complex and unclear. We aimed to investigate the association between blood inflammatory parameters and asthma burden in children with moderate-to-severe asthma.

Methods: Blood inflammatory parameters (eosinophil and neutrophil counts and inflammatory mediators using multiplex immunoassay technology) were measured in children (6-17 years) with moderate-to-severe asthma from the SysPharmPediA cohort across four European countries.

Evaluation of Spliceosome Protein SmD2 as a Potential Target for Cancer Therapy.

The core spliceosome Sm proteins are gaining attention as potential targets for cancer treatment. Here, we evaluate this, with focus on SmD2. A pan-cancer analysis including 26 solid tumor types revealed that the SmD2-encoding gene was overexpressed in almost all cancers.

De-implementation strategy to reduce overtreatment of asymptomatic bacteriuria in the emergency department: a stepped-wedge cluster randomised trial.

Background: Asymptomatic bacteriuria (ASB) is the presence of bacteria in the urine of patients without symptoms of a urinary tract infection. Generally, treating ASB is not beneficial.

Objective: We aimed to reduce overtreatment of ASB in the emergency department (ED) through a multifaceted de-implementation strategy.

Defective proviruses significantly impact viral transcription and immune activation in men and women with HIV-1 subtype C in rural South Africa.

Introduction: The main obstacle to achieving an HIV-1 cure is the proviral reservoir. To promote equity in HIV cure strategies, it is crucial to study the viral reservoir of the predominant HIV-1 subtype C in both women and men. Therefore, we investigated the dynamics of the (intact) viral reservoir in relation to plasma viral load (VL), CD4 T cell count, and immune activation before and during 96 weeks of successful antiretroviral therapy (ART).

Skeletal muscle mitochondrial fragmentation predicts age-associated decline in physical capacity.

Ageing substantially impairs skeletal muscle metabolic and physical function. Skeletal muscle mitochondrial health is also impaired with ageing, but the role of skeletal muscle mitochondrial fragmentation in age-related functional decline remains imprecisely characterized. Here, using a cross-sectional study design, we performed a detailed comparison of skeletal muscle mitochondrial characteristics in relation to in vivo markers of exercise capacity between young and middle-aged individuals.

Leveraging Vγ9Vδ2 T cells against prostate cancer through a VHH-based PSMA-Vδ2 bispecific T cell engager.

Vγ9Vδ2 T cells constitute a homogeneous effector T cell population that lyses tumors of different origin, including the prostate. We generated a bispecific T cell engager (bsTCE) to direct Vγ9Vδ2 T cells to PSMA prostate cancer (PCa) cells. The PSMA-Vδ2 bsTCE triggered healthy donor and PCa patient-derived Vγ9Vδ2 T cells to lyse PSMA PCa cell lines and patient-derived tumor cells while sparing normal prostate cells and enhanced Vγ9Vδ2 T cell antigen cross-presentation to CD8 T cells.

Long-term sequelae of SARS-CoV-2 two years following infection: exploring the interplay of biological, psychological, and social factors.

Background: Severe fatigue and cognitive complaints are frequently reported after SARS-CoV-2 infection and may be accompanied by depressive symptoms and/or limitations in physical functioning. The long-term sequelae of COVID-19 may be influenced by biomedical, psychological, and social factors, the interplay of which is largely understudied over time. We aimed to investigate how the interplay of these factors contribute to the persistence of symptoms after COVID-19.

The tissue glycome as regulator of immune activation and tolerance mediated by C-type lectins and Siglecs.

The immune system is a complex network of highly specialized microenvironments, denominated niches, which arise from dynamic interactions between immune and parenchymal cells as well as acellular components such as structural elements and local molecular signals. A critical, yet underexplored, layer shaping these niches is the glycome, the complete repertoire of glycans and glycoconjugates produced by cells. The glycome is prevalent in the outer membrane of cells and their secreted components, and can be sensed by glycan binding receptors on immune cells.

The Progression of Symptoms in Post COVID-19 Patients: A Multicentre, Prospective, Observational Cohort Study.

Background: Although the coronavirus disease 2019 (COVID-19) pandemic is no longer a public health emergency of international concern, 30% of COVID-19 patients still have long-term complaints. A better understanding of the progression of symptoms after COVID-19 is needed to reduce the burden of the post COVID-19 condition.

Objective: This study aims to investigate the progression of symptoms, identify patterns of symptom progression, and assess their associations with patient characteristics.

Heterozygous BTNL8 variants in individuals with multisystem inflammatory syndrome in children (MIS-C).

Multisystem inflammatory syndrome in children (MIS-C) is a rare condition following SARS-CoV-2 infection associated with intestinal manifestations. Genetic predisposition, including inborn errors of the OAS-RNAseL pathway, has been reported. We sequenced 154 MIS-C patients and utilized a novel statistical framework of gene burden analysis, "burdenMC," which identified an enrichment for rare predicted-deleterious variants in BTNL8 (OR = 4.

Clinical Subtype Trajectories in Sepsis Patients Admitted to the ICU: A Secondary Analysis of an Observational Study.

Objectives: Sepsis is an evolving process and proposed subtypes may change over time. We hypothesized that previously established sepsis subtypes are dynamic, prognostic of outcome, and trajectories are associated with host response alterations.

Design: A secondary analysis of two observational critically ill sepsis cohorts: the Molecular diAgnosis and Risk stratification of Sepsis (MARS) and the Medical Information Mart for Intensive Care-IV (MIMIC-IV).

Precision Dosing of Intravenous Tocilizumab: Development of Pharmacokinetic Model-Derived Tapering Strategies for Patients With Rheumatoid Arthritis.

Background: Tocilizumab targets the interleukin-6 receptor, and dosing is complex owing to its nonlinear clearance related to target binding. Therefore, tapering tocilizumab requires a different approach than that of tumor necrosis factor inhibitors (TNFi). This study aimed to identify these differences and enable personalized treatment of rheumatoid arthritis (RA) beyond TNFi therapy.

Effects of gestational age on blood cortisol and prolactin levels during pregnancy in malaria endemic area.

Background: The hormonal shift occurring in pregnant women is crucial for the outcome of pregnancy. We conducted a study in pregnant women living in a malaria endemic area to determine the potential effect of gestational age on the modulation of the endocrine system by cortisol and prolactin production during pregnancy.

Methods: Primigravidae and multigravidae with a gestational age between 16-20 weeks were included in the study and followed up to delivery and 6-7 weeks thereafter.

Vδ2 T-cell engagers bivalent for Vδ2-TCR binding provide anti-tumor immunity and support robust Vγ9Vδ2 T-cell expansion.

Background: Vγ9Vδ2 T-cells are antitumor immune effector cells that can detect metabolic dysregulation in cancer cells through phosphoantigen-induced conformational changes in the butyrophilin (BTN) 2A1/3A1 complex. In order to clinically exploit the anticancer properties of Vγ9Vδ2 T-cells, various approaches have been studied including phosphoantigen stimulation, agonistic BTN3A-specific antibodies, adoptive transfer of expanded Vγ9Vδ2 T-cells, and more recently bispecific antibodies. While Vγ9Vδ2 T-cells constitute a sizeable population, typically making up ~1-10% of the total T cell population, lower numbers have been observed with increasing age and in the context of disease.

Intrathecal IgG and IgM synthesis correlates with neurodegeneration markers and corresponds to meningeal B cell presence in MS.

Intrathecal synthesis of immunoglobulins (Igs) is a key hallmark of multiple sclerosis (MS). B cells are known to accumulate in the leptomeninges of MS patients and associate with pathology in the underlying cortex and a more severe disease course. However, the role of locally produced antibodies in MS brain pathology is poorly understood.

9-HODE associates with thalamic atrophy and predicts white matter damage in multiple sclerosis.

Background: Multiple sclerosis (MS) is characterized by extensive tissue damage leading to a range of complex symptoms, including physical disability and cognitive dysfunction. Recent work has indicated the clinical relevance of bioactive lipid mediators (LMs), which are known to orchestrate inflammation and its resolution and are deregulated in MS. However, it is unknown whether LM profiles relate to white matter (WM) damage.