Identification of red flags for IgG4-related disease: an international European Reference Network for Rare Connective Tissue Diseases framework.

IgG4-related disease is a rare fibroinflammatory condition. Prompt recognition is fundamental to initiate treatment and to prevent organ damage. Diagnostic and classification criteria are primarily intended for use by clinicians with established expertise in IgG4-related disease.

Clinical prognosticators and targets in the immune microenvironment of intrahepatic cholangiocarcinoma.

Background: Intrahepatic cholangiocarcinoma (ICC) is a disease with poor prognosis and limited therapeutic options. We investigated the tumor immune microenvironment (TIME) to identify predictors of disease outcome and to explore targets for therapeutic modulation.

Methods: Liver tissue samples were collected during 2008-2019 from patients ( = 139) diagnosed with ICC who underwent curative intent surgery without neoadjuvant chemotherapy.

Stress in pregnancy - Implications for fetal BDNF in amniotic fluid at birth.

Introduction: At the maternal-fetal interface in pregnancy, stress during pregnancy can lead to an increased vulnerability to later psychopathology of the fetus. Potential mediators of this association have scarcely been studied and may include early alterations of fetal brain-derived neurotrophic factor (BDNF). Amniotic fluid is of particular interest for effects on fetal endocrine alterations, as the assessment in amniotic fluid allows for measurements over a time integral.

The Role of Chimeric Antigen Receptor T-Cell Therapy in Immune-Mediated Neurological Diseases.

Despite the use of 'high efficacy' disease-modifying therapies, disease activity and clinical progression of different immune-mediated neurological diseases continue for some patients, resulting in accumulating disability, deteriorating social and mental health, and high economic cost to patients and society. Although autologous hematopoietic stem cell transplant is an effective treatment modality, it is an intensive chemotherapy-based therapy with a range of short- and long-term side-effects. Chimeric antigen receptor T-cell therapy (CAR-T) has revolutionized the treatment of B-cell and other hematological malignancies, conferring long-term remission for otherwise refractory diseases.

Missense variants in ANO4 cause sporadic encephalopathic or familial epilepsy with evidence for a dominant-negative effect.

Anoctamins are a family of Ca-activated proteins that may act as ion channels and/or phospholipid scramblases with limited understanding of function and disease association. Here, we identified five de novo and two inherited missense variants in ANO4 (alias TMEM16D) as a cause of fever-sensitive developmental and epileptic or epileptic encephalopathy (DEE/EE) and generalized epilepsy with febrile seizures plus (GEFS+) or temporal lobe epilepsy. In silico modeling of the ANO4 structure predicted that all identified variants lead to destabilization of the ANO4 structure.

Stress during pregnancy and fetal serum BDNF in cord blood at birth.

Introduction: Adverse environments during pregnancy impact neurodevelopment including cognitive abilities of the developing children. The mediating biological alterations are not fully understood. Maternal stress may impact the neurotrophic regulation of the offspring as early as in utero and at birth.

Unraveling the mechanisms and evolution of a two-domain module in IQGAP proteins for controlling eukaryotic cytokinesis.

The IQGAP family of proteins plays a crucial role in cytokinesis across diverse organisms, but the underlying mechanisms are not fully understood. In this study, we demonstrate that IQGAPs in budding yeast, fission yeast, and human cells use a two-domain module to regulate their localization as well as the assembly and disassembly of the actomyosin ring during cytokinesis. Strikingly, the calponin homology domains (CHDs) in these IQGAPs bind to distinct cellular F-actin structures with varying specificity, whereas the non-conserved domains immediately downstream of the CHDs in these IQGAPs all target the division site, but differ in timing, localization strength, and binding partners.

Evidence of Cytolysin A nanopore incorporation in mammalian cells assessed by a graphical user interface.

Technologies capable of assessing cellular metabolites with high precision and temporal resolution are currently limited. Recent developments in the field of nanopore sensors allow the non-stochastic quantification of metabolites, where a nanopore is acting as an electrical transducer for selective substrate binding proteins (SBPs). Here we show that incorporation of the pore-forming toxin Cytolysin A (ClyA) into the plasma membrane of Chinese hamster ovary cells (CHO-K1) results in the appearance of single-channel conductance amenable to multiplexed automated patch-clamp (APC) electrophysiology.

Protein Sizing with 15 nm Conical Biological Nanopore YaxAB.

Nanopores are promising single-molecule tools for the electrical identification and sequencing of biomolecules. However, the characterization of proteins, especially in real-time and in complex biological samples, is complicated by the sheer variety of sizes and shapes in the proteome. Here, we introduce a large biological nanopore, YaxAB for folded protein analysis.

Exercise elevates serum brain-derived neurotrophic factor in partially remitted depression.

Brain-derived neurotrophic factor (BDNF) is a pleiotropic cytokine implicated in the pathogenesis of major depressive disorder (MDD). In MDD, serum BDNF levels are attenuated. Healthy adults show BDNF elevation after exercise.

Regulation of tumor angiogenesis by the crosstalk between innate immunity and endothelial cells.

Endothelial cells and immune cells are major regulators of cancer progression and prognosis. Endothelial cell proliferation and angiogenesis are required for providing nutrients and oxygen to the nascent tumor and infiltration of immune cells to the tumor is dependent on endothelial cell activation. Myeloid cells and innate lymphocytes have an important role in shaping the tumor microenvironment by crosstalking with cancer cells and structural cells, including endothelial cells.

Increased levels of immature and activated low density granulocytes and altered degradation of neutrophil extracellular traps in granulomatosis with polyangiitis.

Granulomatosis with Polyangiitis (GPA) is a small vessel vasculitis typically associated with release of neutrophil extracellular traps (NETs) by activated neutrophils. In this study, we further aimed to investigate the contributions of neutrophils and NETs to the complex disease pathogenesis. We characterized the phenotype of neutrophils and their capacity to induce NETs.

A more novel and robust gene signature predicts outcome in patients with esophageal squamous cell carcinoma.

Background: Esophageal squamous cell carcinoma (ESCC) is a life-threatening thoracic tumor with a poor prognosis. The tumor microenvironment (TME) mainly comprises tumor cells and tumor-infiltrating immune cells mixed with stromal components. The latest research has displayed that tumor immune cell infiltration (ICI) is closely connected with the ESCC patients' clinical prognosis.

Retinal TRP channels: Cell-type-specific regulators of retinal homeostasis and multimodal integration.

Transient receptor potential (TRP) channels are a widely expressed family of 28 evolutionarily conserved cationic ion channels that operate as primary detectors of chemical and physical stimuli and secondary effectors of metabotropic and ionotropic receptors. In vertebrates, the channels are grouped into six related families: TRPC, TRPV, TRPM, TRPA, TRPML, and TRPP. As sensory transducers, TRP channels are ubiquitously expressed across the body and the CNS, mediating critical functions in mechanosensation, nociception, chemosensing, thermosensing, and phototransduction.

German Cardiac Arrest Registry: rationale and design of G-CAR.

Background: In Germany, 70,000-100,000 persons per year suffer from out-of-hospital cardiac arrest (OHCA). Despite medical progress, survival rates with good neurological outcome remain low. For many important clinical issues, no or only insufficient evidence from randomised trials is available.

Prognostic Implications of N-Terminal Pro-B-Type Natriuretic Peptide and High-Sensitivity Cardiac Troponin T in EMPEROR-Preserved.

Background: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) are associated with disease severity and outcomes among patients with heart failure (HF) with preserved ejection fraction.

Objectives: The authors evaluated associations between both biomarkers and clinical outcomes in the EMPEROR-Preserved (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Preserved Ejection Fraction) trial.

Methods: Of 5,988 study participants, 5,986 (99.

A Novel Immune-Related Gene Signature Predicts Prognosis of Lung Adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) is the most common form of lung cancer, accounting for 30% of all cases and 40% of all non-small-cell lung cancer cases. Immune-related genes play a significant role in predicting the overall survival and monitoring the status of the cancer immune microenvironment. The present study was aimed at finding an immune-related gene signature for predicting LUAD patient outcomes.

Blood biomarkers recommended for diagnosing and monitoring IgG4-related disease. Considerations from the ERN ReCONNET and collaborating partners.

Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is a chronic, clinically heterogenous fibroinflammatory condition, characterised by an accumulation of IgG4 secreting plasma cells in affected tissues and associated with increased serum IgG4 concentrations. Despite a growing recognition of the disease among clinicians from different specialties worldwide, its indolent nature, lack of a single diagnostic test and ability to mimic other malignant, infective and inflammatory conditions, makes the diagnosis challenging. As treatment options evolve, biomarkers correlating with disease activity, predicting prognosis and response to treatment are deemed required.

Construction and validation of a novel gene signature for predicting the prognosis of osteosarcoma.

Osteosarcoma (OS) is the most common type of primary malignant bone tumor. The high-throughput sequencing technology has shown potential abilities to illuminate the pathogenic genes in OS. This study was designed to find a powerful gene signature that can predict clinical outcomes.

B cells in systemic lupus erythematosus.

Purpose Of Review: New insight into altered B cell distribution including newly identified subsets and abnormalities in systemic lupus erythematosus (SLE) as well as their role in immune protection are summarized in this review.

Recent Findings: SLE carries characteristic B cell abnormalities, which offer new insights into B cell differentiation and their disturbances including discoveries of pathogenic B cell subsets and intrinsic B cell abnormalities. A recent study in SLE found that antigen-experienced B cell subsets lacking expression of CD27 and IgD defined by their lack of CXCR5 and CD19low expression are expanded in SLE and represent plasmablasts likely escaping proper selection.

Systemic lupus erythematosus - Are children miniature adults?

Systemic lupus erythematosus (SLE) is a systemic autoimmune/inflammatory disease that can affect any organ system and cause significant damage and organ failure. Disease-onset during childhood (juvenile-onset SLE) is associated with less typical autoantibody patterns, diffuse organ involvement, more damage already at diagnoses, and a higher need of immunomodulating treatment, including corticosteroids, when compared to adult-onset SLE. Differences in the molecular pathophysiology within SLE, and over-representation of patients with "genetic SLE" contribute to differences in clinical presentation and treatment responses between children and adults.