Decreased Oligodendrocyte Number in Hippocampal Subfield CA4 in Schizophrenia: A Replication Study.

Hippocampus-related cognitive deficits in working and verbal memory are frequent in schizophrenia, and hippocampal volume loss, particularly in the cornu ammonis (CA) subregions, was shown by magnetic resonance imaging studies. However, the underlying cellular alterations remain elusive. By using unbiased design-based stereology, we reported a reduction in oligodendrocyte number in CA4 in schizophrenia and of granular neurons in the dentate gyrus (DG).

CD8 T cells induce interferon-responsive oligodendrocytes and microglia in white matter aging.

A hallmark of nervous system aging is a decline of white matter volume and function, but the underlying mechanisms leading to white matter pathology are unknown. In the present study, we found age-related alterations of oligodendrocyte cell state with a reduction in total oligodendrocyte density in aging murine white matter. Using single-cell RNA-sequencing, we identified interferon (IFN)-responsive oligodendrocytes, which localize in proximity to CD8 T cells in aging white matter.

D-dopachrome tautomerase in cardiovascular and inflammatory diseases-A new kid on the block or just another MIF?

Macrophage migration inhibitory factor (MIF) as well as its more recently described structural homolog D-dopachrome tautomerase (D-DT), now also termed MIF-2, are atypical cytokines and chemokines with key roles in host immunity. They also have an important pathogenic role in acute and chronic inflammatory conditions, cardiovascular diseases, lung diseases, adipose tissue inflammation, and cancer. Although our mechanistic understanding of MIF-2 is relatively limited compared to the extensive body of evidence available for MIF, emerging data suggests that MIF-2 is not only a functional phenocopy of MIF, but may have differential or even oppositional activities, depending on the disease and context.

Determinants of anti-S immune response at 6 months after COVID-19 vaccination in a multicentric European cohort of healthcare workers - ORCHESTRA project.

Background: The duration of immune response to COVID-19 vaccination is of major interest. Our aim was to analyze the determinants of anti-SARS-CoV-2 IgG titer at 6 months after 2-dose vaccination in an international cohort of vaccinated healthcare workers (HCWs).

Methods: We analyzed data on levels of anti-SARS-CoV-2 Spike antibodies and sociodemographic and clinical characteristics of 6,327 vaccinated HCWs from 8 centers from Germany, Italy, Romania and Slovakia.

Timing of Blood Sample Processing Affects the Transcriptomic and Epigenomic Profiles in CD4 T-cells of Atopic Subjects.

Optimal pre-analytical conditions for blood sample processing and isolation of selected cell populations for subsequent transcriptomic and epigenomic studies are required to obtain robust and reproducible results. This pilot study was conducted to investigate the potential effects of timing of CD4 T-cell processing from peripheral blood of atopic and non-atopic adults on their transcriptomic and epigenetic profiles. Two heparinized blood samples were drawn from each of three atopic and three healthy individuals.

Comprehensive analysis of immune responses in CLL patients after heterologous COVID-19 vaccination.

Patients with chronic lymphocytic leukemia (CLL) treated with B-cell pathway inhibitors and anti-CD20 antibodies exhibit low humoral response rate (RR) following SARS-CoV-2 vaccination. To investigate the relationship between the initial transcriptional response to vaccination with ensuing B and T cell immune responses, we performed a comprehensive immune transcriptome analysis flanked by antibody and T cell assays in peripheral blood prospectively collected from 15 CLL/SLL patients vaccinated with heterologous BNT162b2/ChAdOx1 with follow up at a single institution. The two-dose antibody RR was 40% increasing to 53% after booster.

Lymphoma tumor burden before chimeric antigen receptor T-Cell treatment: RECIL vs. Lugano vs. metabolic tumor assessment.

Purpose: High tumor burden has emerged as a negative predictor of efficacy in chimeric antigen receptor T-cell therapy (CART) in patients with refractory or relapsed large B-cell lymphoma. This study analyzed the deviation among imaging-based tumor burden (TB) metrics and their association with progression-free (PFS) and overall survival (OS).

Materials And Methods: In this single-center observational study, we included all consecutively treated patients receiving CD19 CART with available baseline PET-CT imaging.

Effects of knockout and overexpression on local cortisol production and differentiation of mesenchymal stem cells.

Exogenous glucocorticoids increase the risk for osteoporosis, but the role of endogenous glucocorticoids remains elusive. Here, we describe the generation and validation of a loss- and a gain-of-function model of the cortisol producing enzyme 11β-HSD1 () to modulate the endogenous glucocorticoid conversion in SCP-1 cells - a model for human mesenchymal stem cells capable of adipogenic and osteogenic differentiation. CRISPR-Cas9 was successfully used to generate a cell line carrying a single base duplication and a 5 bp deletion in exon 5, leading to missense amino acid sequences after codon 146.

Cholinergic signaling impairs cardiomyocyte cohesion.

Aim: Cardiac autonomic nervous system (ANS) dysregulation is a hallmark of several cardiovascular diseases. Adrenergic signaling enhanced cardiomyocyte cohesion via PKA-mediated plakoglobin phosphorylation at serine 665, referred to as positive adhesiotropy. This study investigated cholinergic regulation of cardiomyocyte cohesion using muscarinic receptor agonist carbachol (CCH).

Designed peptides as nanomolar cross-amyloid inhibitors acting via supramolecular nanofiber co-assembly.

Amyloid self-assembly is linked to numerous devastating cell-degenerative diseases. However, designing inhibitors of this pathogenic process remains a major challenge. Cross-interactions between amyloid-β peptide (Aβ) and islet amyloid polypeptide (IAPP), key polypeptides of Alzheimer's disease (AD) and type 2 diabetes (T2D), have been suggested to link AD with T2D pathogenesis.

Diagnosis of paediatric TB using Xpert MTB/RIF Ultra on fresh respiratory samples.

To evaluate the diagnostic accuracy of Xpert MTB/RIF Ultra (Ultra) on fresh respiratory samples for the diagnosis of pulmonary TB (PTB) in children. Between July 2017 and December 2019, children with presumed TB were prospectively enrolled at clinical sites in three African countries. Children were assessed using history, physical examination and chest X-ray.

Middle Cerebral Artery M2 Thrombectomy: Safety and Technical Considerations in the German Stroke Registry (GSR).

There is ongoing debate concerning the safety and efficacy of various mechanical thrombectomy (MT) approaches for M2 occlusions. We compared these for MT in M2 versus M1 occlusions. Subgroup analyses of different technical approaches within the M2 MT cohort were also performed.

Molecular Subtyping of Invasive Breast Cancer Using a PAM50-Based Multigene Expression Test-Comparison with Molecular-Like Subtyping by Tumor Grade/Immunohistochemistry and Influence on Oncologist's Decision on Systemic Therapy in a Real-World Setting.

In intermediate risk hormone receptor (HR) positive, HER2 negative breast cancer (BC), the decision regarding adjuvant chemotherapy might be facilitated by multigene expression tests. In all, 142 intermediate risk BCs were investigated using the PAM50-based multigene expression test Prosigna® in a prospective multicentric study. In 119/142 cases, Prosigna® molecular subtyping was compared with local and two central (C1 and C6) molecular-like subtypes relying on both immunohistochemistry (IHC; HRs, HER2, Ki-67) and IHC + tumor grade (IHC+G) subtyping.

Vitamin B12 in Leber hereditary optic neuropathy mutation carriers: a prospective cohort study.

Background: Leber hereditary optic neuropathy (LHON) is the most common mitochondrial disorder, frequently resulting in acute or subacute severe bilateral central vision loss. Vitamin B12 deficiency is also a known cause of optic neuropathy through mitochondrial dysfunction. Here we evaluated the prevalence and clinical significance of vitamin B12 deficiency in a large cohort of LHON patients and asymptomatic mutation carriers from a tertiary referral center.

Evidence of a role for cAMP in mitochondrial regulation in ovarian granulosa cells.

In the ovary, proliferation and differentiation of granulosa cells (GCs) drive follicular growth. Our immunohistochemical study in a non-human primate, the Rhesus monkey, showed that the mitochondrial activity marker protein cytochrome c oxidase subunit 4 (COX4) increases in GCs in parallel to follicle size, and furthermore, its intracellular localization changes. This suggested that there is mitochondrial biogenesis and trafficking, and implicates the actions of gonadotropins, which regulate follicular growth and ovulation.

Chimeric antigen receptor T cells engineered to recognize the P329G-mutated Fc part of effector-silenced tumor antigen-targeting human IgG1 antibodies enable modular targeting of solid tumors.

Background: Chimeric antigen receptor (CAR) T cell therapy has proven its clinical utility in hematological malignancies. Optimization is still required for its application in solid tumors. Here, the lack of cancer-specific structures along with tumor heterogeneity represent a critical barrier to safety and efficacy.

T-cell exhaustion induced by continuous bispecific molecule exposure is ameliorated by treatment-free intervals.

T-cell-recruiting bispecific molecule therapy has yielded promising results in patients with hematologic malignancies; however, resistance and subsequent relapse remains a major challenge. T-cell exhaustion induced by persistent antigen stimulation or tonic receptor signaling has been reported to compromise outcomes of T-cell-based immunotherapies. The impact of continuous exposure to bispecifics on T-cell function, however, remains poorly understood.

pT3 colorectal cancer revisited: a multicentric study on the histological depth of invasion in more than 1000 pT3 carcinomas-proposal for a new pT3a/pT3b subclassification.

Background: Pathological TNM staging (pTNM) is the strongest prognosticator in colorectal carcinoma (CRC) and the foundation of its post-operative clinical management. Tumours that invade pericolic/perirectal adipose tissue generally fall into the pT3 category without further subdivision.

Methods: The histological depth of invasion into the pericolic/perirectal fat was digitally and conventionally measured in a training cohort of 950 CRCs (Munich).

Clinical and virological features of first human monkeypox cases in Germany.

Background: Monkeypox is a zoonotic orthopoxvirus infection endemic in central and western Africa. In May 2022, human monkeypox infections including human-to-human transmission were reported in a multi-country outbreak in Europe and North America.

Case Presentations: Here we present the first two cases of monkeypox infection in humans diagnosed in Germany.

Direct addition of poly-lysine or poly-ethylenimine to the medium: A simple alternative to plate pre-coating.

For most cell culture experiments, it is indispensable that the cells are firmly anchored to culture plates, withstanding rinsing steps that can create shear forces and tolerating temperature changes without detaching. For semi-adherent cells such as the common HEK 293 or PC-12 cells, this could so far be obtained by time-consuming plate pre-coating with cationic polymer solutions. We report here, that i) pre-coating with the cheaper poly-ethylenimine (PEI) works as well as the commonly used poly-D-lysine (PDL), but more importantly and novel ii) that simple direct addition of either PEI (1.

Type-1 Grade 2 Multi-Focal Gastric Neuroendocrine Tumors Secondary to Chronic Autoimmune Gastritis.

Background: Chronic autoimmune gastritis (CAG) refers to chronic atrophic gastritis due to autoimmunity. Loss of gastric glands in CAG results in hypergastrinemia and achlorhydria leading to Vitamin B deficiency and hyperplasia of G cells and enterochromaffin-like (ECL) cells. Vitamin B deficiency could cause pernicious anemia and subacute combined degeneration, while G cells and ECL cells hyperplasia might develop gastric neuroendocrine tumor (G-NET).

Definition, diagnosis and clinical management of non-obstructive kidney dysplasia: a consensus statement by the ERKNet Working Group on Kidney Malformations.

Kidney dysplasia is one of the most frequent causes of chronic kidney failure in children. While dysplasia is a histological diagnosis, the term 'kidney dysplasia' is frequently used in daily clinical life without histopathological confirmation. Clinical parameters of kidney dysplasia have not been clearly defined, leading to imprecise communication amongst healthcare professionals and patients.

Pleiotropic actions of melatonin in testicular peritubular myoid cells of immature Syrian hamsters.

Background: Peritubular myoid cells are emerging as key regulators of testicular function in adulthood. However, little is known about the role of testicular peritubular myoid cells (TPMCs) in the development of the male gonad. We found that, compared to testes of young adult hamsters, gonads of 21 day-old animals show increased melatonin concentration, seminiferous tubular wall thickening and a heterogeneous packaging of its collagen fibers thus raising the question whether melatonin may be involved in the regulation of TPMCs.