Method for Quantitative HDV RNA Detection: I, Manual Workflow (Serum and Liver Tissue) and II, Fully Automated High Throughput Workflow for Diagnostic Use.

The hepatitis delta virus (HDV) is a small RNA virus (1700 base pairs), which uses the surface proteins of the hepatitis B virus (HBV) as an envelope. Accurate and reliable quantitative detection of HDV RNA is central for scientific and translational clinical research or diagnostic purposes. However, HDV poses challenges for nucleic acid amplification techniques: (1) the circular genome displays high intramolecular base pairing; (2) high content of cytosine and guanine; and (3) enormous genomic diversity among the eight known HDV genotypes (GTs).

Rapid and Reliable Protein-Free HBV DNA Extraction and Sensitive Branched DNA Southern Blot Assay.

HBV covalently closed circular DNA (cccDNA) plays an important role in the persistence of hepatitis B virus (HBV) infection by serving as the template for transcription of viral RNAs. To cure HBV infection, it is expected that cccDNA needs either to be eliminated or silenced. Hence, precise cccDNA quantification is essential.

Building a Better Defense: Expanding and Improving Natural Killer Cells for Adoptive Cell Therapy.

Natural killer (NK) cells have gained attention as a promising adoptive cell therapy platform for their potential to improve cancer treatments. NK cells offer distinct advantages over T-cells, including major histocompatibility complex class I (MHC-I)-independent tumor recognition and low risk of toxicity, even in an allogeneic setting. Despite this tremendous potential, challenges persist, such as limited persistence, reduced tumor infiltration, and low absolute NK cell numbers.

Intestinal Epithelia and Myeloid Immune Cells Shape Colitis Severity and Colorectal Carcinogenesis via High-mobility Group Box Protein 1.

Background: High-mobility group box protein 1 [HMGB1] is a ubiquitous nucleoprotein with immune-regulatory properties following cellular secretion or release in sterile and in infectious inflammation. Stool and serum HMGB1 levels correlate with colitis severity and colorectal cancer [CRC] progression, yet recent reports indicate that HMGB1 mainly operates as an intracellular determinant of enterocyte fate during colitis, and investigations into the roles of HMGB1 in CRC are lacking.

Methods: Using mice with conditional HMGB1-knockout in enterocytes [Hmgb1ΔIEC] and myeloid cells [Hmgb1ΔLysM], respectively, we explored functions of HMGB1 in pathogenetically diverse contexts of colitis and colitis-associated CRC.

Vitamin D resolved human and experimental asthma via B lymphocyte-induced maturation protein 1 in T cells and innate lymphoid cells.

Background: Vitamin D (VitD) is known to have immunomodulatory functions, and VitD deficiency is associated with more severe asthma.

Objective: We aimed to assess the immunoregulatory effects of VitD food supplementation on asthma manifestation, with particular focus on T cells and type 2 innate lymphoid cells.

Methods: Preschool children and adult asthmatic cohorts were analyzed in the context of VitD supplementation and serum levels.

Building smart CAR T cell therapies: The path to overcome current challenges.

Successful implementation of adoptive cell therapy (ACT) of cancer requires comprehensively addressing biological and practical challenges. This approach has been largely overlooked, resulting in a gap between the potential of ACT and its actual effectiveness. We summarize the most promising technical strategies in creating an "ideal" ACT product, focusing on chimeric antigen receptor (CAR)-engineered cells.

Subannular repair in secondary mitral regurgitation with restricted leaflet motion during systole.

Objective: Ventricular secondary mitral regurgitation (SMR) (Carpentier type IIIb) results from left ventricular (LV) remodelling, displacement of papillary muscles and tethering of mitral leaflets. The most appropriate treatment approach remains controversial. We aimed to assess the safety and efficacy of standardised relocation of both papillary muscles (subannular repair) at 1-year follow-up (FU).

Endogenous myoglobin expression in mouse models of mammary carcinoma reduces hypoxia and metastasis in PyMT mice.

Myoglobin (MB) is expressed in different cancer types and may act as a tumor suppressor in breast cancer. The mechanisms by which basal MB expression level impacts murine mammary tumorigenesis are unclear. We investigated how MB expression in breast cancer influences proliferation, metastasis, tumor hypoxia, and chemotherapy treatment in vivo.

Quantification of the hepatitis B virus cccDNA: evidence-based guidelines for monitoring the key obstacle of HBV cure.

Objectives: A major goal of curative hepatitis B virus (HBV) treatments is the reduction or inactivation of intrahepatic viral covalently closed circular DNA (cccDNA). Hence, precise cccDNA quantification is essential in preclinical and clinical studies. Southern blot (SB) permits cccDNA visualisation but lacks sensitivity and is very laborious.

The Prevalence of Hearing Loss and Provision With Hearing Aids in the Gutenberg Health Study.

Background: Hearing is a basic ability that is needed for participation in daily life. Hearing loss often greatly reduces a person's quality of life. Nevertheless, epidemiological data on the prevalence of hearing disorders in Germany are sparse.

SARS-CoV-2 Specific Immune Response and Inflammatory Profile in Advanced HIV-Infected Persons during a COVID-19 Outbreak.

The main aim of this study was to describe the clinical and immunological outcomes, as well as the inflammatory profile, of patients with advanced HIV in an assisted-living facility in which an outbreak of SARS-CoV-2 occurred. SARS-CoV-2 humoral and specific T-cell response were analyzed in patients with HIV infection and COVID-19; as a secondary objective of the analysis, levels of the inflammatory markers (IL-1β, IL-6, IL-8, and TNFα) were tested in the HIV/COVID-19 group, in HIV-positive patients without COVID-19, and in HIV-negative patients with mild/moderate COVID-19. Antibody kinetics and ability to neutralize SARS-CoV-2 were evaluated by ELISA assay, as well as the inflammatory cytokines; SARS-CoV-2 specific T-cell response was quantified by ELISpot assay.

Whom Should We Screen for Cushing Syndrome? The Endocrine Society Practice Guideline Recommendations 2008 Revisited.

Context: Cushing syndrome (CS) is a rare and serious disease with high mortality. Patients are often diagnosed late in the course of the disease.

Objective: This work investigated whether defined patient populations should be screened outside the at-risk populations defined in current guidelines.

High risk of complications and acute-on-chronic liver failure in cirrhosis patients with acute pancreatitis.

Background & Aims: Acute pancreatitis (AP) is a frequent indication for hospitalization and may present with varying degrees of severity. AP often coincides with hepatic disease, yet the impact of liver cirrhosis (LC) on the course of AP is uncertain, and early identification of patients at risk for complications remains challenging. We aimed to assess the impact of LC on the development of pancreatic and extra-pancreatic complications of AP, and to identify predictors of adverse outcomes in cirrhotic patients.

Assessing immunological and virological responses in the liver: Implications for the cure of chronic hepatitis B virus infection.

Cure from chronic HBV infection is rare with current therapies. Basic research has helped to fundamentally improve our knowledge of the viral life cycle and virus-host interactions, and provided the basis for several novel drug classes that are currently being developed or are being tested in clinical trials. While these novel compounds targeting the viral life cycle or antiviral immune responses hold great promise, we are still lacking a comprehensive understanding of the immunological and virological processes that occur at the site of infection, the liver.

Second MAFA Variant Causing a Phosphorylation Defect in the Transactivation Domain and Familial Insulinomatosis.

Adult-onset familial insulinomatosis is a rare disorder with recurrent, severe hypoglycemia caused by multiple insulin-secreting pancreatic tumors. The etiology was unclear until the variant p.Ser64Phe in the transcription factor MAFA, a key coordinator of β-cell insulin secretion, was defined as the cause in two families.

Quantitative Analysis of Plasma Cell-Free DNA and Its DNA Integrity and Hypomethylation Status as Biomarkers for Tumor Burden and Disease Progression in Patients with Metastatic Neuroendocrine Neoplasias.

Background: Neuroendocrine neoplasia (NEN) encompasses a diverse group of malignancies marked by histological heterogeneity and highly variable clinical outcomes. Apart from Chromogranin A, specific biomarkers predicting residual tumor disease, tumor burden, and disease progression in NEN are scant. Thus, there is a strong clinical need for new and minimally invasive biomarkers that allow for an evaluation of the prognosis, clinical course, and response to treatment of NEN patients, thereby helping implement individualized treatment decisions in this heterogeneous group of patients.

Targeting Neoepitopes to Treat Solid Malignancies: Immunosurgery.

Successful outcome of immune checkpoint blockade in patients with solid cancers is in part associated with a high tumor mutational burden (TMB) and the recognition of private neoantigens by T-cells. The quality and quantity of target recognition is determined by the repertoire of 'neoepitope'-specific T-cell receptors (TCRs) in tumor-infiltrating lymphocytes (TIL), or peripheral T-cells. Interferon gamma (IFN-γ), produced by T-cells and other immune cells, is essential for controlling proliferation of transformed cells, induction of apoptosis and enhancing human leukocyte antigen (HLA) expression, thereby increasing immunogenicity of cancer cells.

A simple, sensitive, and low-cost FACS assay for detecting antibodies against the native SARS-CoV-2 spike protein.

Background: Hamburg is a city state of approximately 1.9 Mio inhabitants in Northern Germany. Currently, the COVID-19 epidemic that had largely subsided during last summer is resurging in Hamburg and in other parts of the world, underlining the need for additional tools to monitor SARS-CoV-2 antibody responses.