Recanalization Therapies for Large Vessel Occlusion Due to Cervical Artery Dissection: A Cohort Study of the EVA-TRISP Collaboration.

Background And Purpose: This study aimed to investigate the effect of endovascular treatment (EVT, with or without intravenous thrombolysis [IVT]) versus IVT alone on outcomes in patients with acute ischemic stroke (AIS) and intracranial large vessel occlusion (LVO) attributable to cervical artery dissection (CeAD).

Methods: This multinational cohort study was conducted based on prospectively collected data from the EVA-TRISP (EndoVAscular treatment and ThRombolysis for Ischemic Stroke Patients) collaboration. Consecutive patients (2015-2019) with AIS-LVO attributable to CeAD treated with EVT and/or IVT were included.

True-to-scale DNA-density maps correlate with major accessibility differences between active and inactive chromatin.

Chromatin compaction differences may have a strong impact on accessibility of individual macromolecules and macromolecular assemblies to their DNA target sites. Estimates based on fluorescence microscopy with conventional resolution, however, suggest only modest compaction differences (∼2-10×) between the active nuclear compartment (ANC) and inactive nuclear compartment (INC). Here, we present maps of nuclear landscapes with true-to-scale DNA densities, ranging from <5 to >300 Mbp/μm.

Corrigendum: Monocyte signature as a predictor of chronic lung disease in the preterm infant.

[This corrects the article DOI: 10.3389/fimmu.2023.

Surgical site infection in skin surgery-An observational study.

Background: Surgical site infection (SSI) has a significant impact on patients' morbidity and aesthetic results.

Objective: To identify risk factors for SSI in dermatologic surgery.

Patients And Methods: This prospective, single-centre, observational study was performed between August 2020 and May 2021.

Recombinant Modified Vaccinia Virus Ankara Expressing a Glycosylation Mutant of Dengue Virus NS1 Induces Specific Antibody and T-Cell Responses in Mice.

The four serotypes of dengue virus (DENV1-4) continue to pose a major public health threat. The first licenced dengue vaccine, which expresses the surface proteins of DENV1-4, has performed poorly in immunologically naïve individuals, sensitising them to antibody-enhanced dengue disease. DENV non-structural protein 1 (NS1) can directly induce vascular leakage, the hallmark of severe dengue disease, which is blocked by NS1-specific antibodies, making it an attractive target for vaccine development.

The small molecule inhibitor BX-795 uncouples IL-2 production from inhibition of Th2 inflammation and induces CD4 T cells resembling iTreg.

Background: Treg cells have been shown to be an important part of immune-homeostasis and IL-2 which is produced upon T cell receptor (TCR)-dependent activation of T lymphocytes has been demonstrated to critically participate in Treg development.

Objective: To evaluate small molecule inhibitors (SMI) for the identification of novel IL-2/Treg enhancing compounds.

Materials And Methods: We used TCR-dependent and allergen-specific cytokine secretion of human and mouse T cells, next generation messenger ribonucleic acid sequencing (RNA-Seq) and two different models of allergic airway inflammation to examine lead SMI-compounds.

Monocyte signature as a predictor of chronic lung disease in the preterm infant.

Introduction: Inflammation is a key driver of morbidity in the vulnerable preterm infant exposed to pre- and postnatal hazards and significantly contributes to chronic lung disease, bronchopulmonary dysplasia (BPD). However, the early changes in innate immunity associated with BPD development are incompletely understood.

Methods: In very immature preterm infants below 32 weeks gestational age (GA; n=30 infants), monocyte subtypes were identified by Flow Cytometry at birth and throughout the postnatal course including intracellular TNF expression upon LPS stimulation.

Brain metastases in the elderly - Impact of residual tumor volume on overall survival.

Background: Due to demographic changes and an increased incidence of cancer with age, the number of patients with brain metastases (BMs) constantly increases, especially among the elderly. Novel systemic therapies, such as immunotherapy, have led to improved survival in recent years, but intracranial tumor progression may occur independently of a systemically effective therapy. Despite the growing number of geriatric patients, they are often overlooked in clinical trials, and there is no consensus on the impact of BM resection on survival.

Recent advances in understanding neuronal diversity and neural circuit complexity across different brain regions using single-cell sequencing.

Neural circuits are characterized as interconnecting neuron networks connected by synapses. Some kinds of gene expression and/or functional changes of neurons and synaptic connections may result in aberrant neural circuits, which has been recognized as one crucial pathological mechanism for the onset of many neurological diseases. Gradual advances in single-cell sequencing approaches with strong technological advantages, as exemplified by high throughput and increased resolution for live cells, have enabled it to assist us in understanding neuronal diversity across diverse brain regions and further transformed our knowledge of cellular building blocks of neural circuits through revealing numerous molecular signatures.

Influence of Adipose Tissue Distribution, Sarcopenia, and Nutritional Status on Clinical Outcomes After CD19 CAR T-cell Therapy.

Although CD19-directed chimeric antigen receptor T-cell therapy (CD19.CAR-T) has proven clinical efficacy for multiple refractory B-cell malignancies, over 50% of patients ultimately relapse. Recent evidence has underlined the critical role of the host in determining treatment responses.

Glucocorticoid activation by HSD11B1 limits T cell-driven interferon signaling and response to PD-1 blockade in melanoma.

Background: Immune responses against tumors are subject to negative feedback regulation. Immune checkpoint inhibitors (ICIs) blocking Programmed cell death protein 1 (PD-1), a receptor expressed on T cells, or its ligand PD-L1 have significantly improved the treatment of cancer, in particular malignant melanoma. Nevertheless, responses and durability are variables, suggesting that additional critical negative feedback mechanisms exist and need to be targeted to improve therapeutic efficacy.

Chitinase A, a tightly regulated virulence factor of Salmonella enterica serovar Typhimurium, is actively secreted by a Type 10 Secretion System.

As a facultative intracellular pathogen, Salmonella enterica serovar Typhimurium is one of the leading causes of food-borne diseases in humans. With the ingestion of fecal contaminated food or water, S. Typhimurium reaches the intestine.

Ninety-six-hour starved peripheral blood mononuclear cell supernatant inhibited LA7 breast cancer stem cells induced tumor reduction in angiogenesis and alternations in and expressions.

Introduction: The microenvironment of solid tumors such as breast cancer is heterogeneous and complex, containing different types of cell, namely, cancer stem cells and immune cells. We previously reported the immunoregulatory behavior of the human immune cell in a solid tumor microenvironment-like culture under serum starvation stress for 96 h. Here, we examined the effect of this culture-derived solution on breast cancer development in rats.

EGFR inhibition leads to enhanced desmosome assembly and cardiomyocyte cohesion via ROCK activation.

Arrhythmogenic cardiomyopathy (AC) is a familial heart disease partly caused by impaired desmosome turnover. Thus, stabilization of desmosome integrity may provide new treatment options. Desmosomes, apart from cellular cohesion, provide the structural framework of a signaling hub.

Cardiomyocyte cohesion is increased after ADAM17 inhibition.

A Disintegrin And Metalloprotease (ADAM) family proteins are involved in several cardiac diseases, and some ADAMs have been associated with cardiomyopathies. ADAM17 is known to cleave desmoglein 2 (DSG2), one of the proteins involved in the pathogenesis of arrhythmogenic cardiomyopathy (AC). Desmosomal stability is impaired in AC, an inheritable genetic disease, the underlying causes of which can be mutations in genes coding for proteins of the desmosome, such as DSG2, desmoplakin (DP), plakoglobin (PG), plakophilin 2 or desmocollin 2.

Quantitative proteomics of differentiated primary bronchial epithelial cells from chronic obstructive pulmonary disease and control identifies potential novel host factors post-influenza A virus infection.

Background: Chronic obstructive pulmonary disease (COPD) collectively refers to chronic and progressive lung diseases that cause irreversible limitations in airflow. Patients with COPD are at high risk for severe respiratory symptoms upon influenza virus infection. Airway epithelial cells provide the first-line antiviral defense, but whether or not their susceptibility and response to influenza virus infection changes in COPD have not been elucidated.

Extracellular CahB1 from Sodalinema gerasimenkoae IPPAS B-353 Acts as a Functional Carboxysomal β-Carbonic Anhydrase in Synechocystis sp. PCC6803.

Cyanobacteria mostly rely on the active uptake of hydrated CO (i.e., bicarbonate ions) from the surrounding media to fuel their inorganic carbon assimilation.

Lower HLA-G levels in extravillous trophoblasts of human term placenta in gestational diabetes mellitus than in normal controls.

The non-classical human leucocyte antigen (HLA) class I molecule HLA-G is widely known to play a major role in feto-maternal tolerance. We tested the hypothesis that HLA-G expression is altered in placentas of women with gestational diabetes mellitus (GDM) in a specific pattern that depends on fetal sex. HLA-G expression was analysed in a total of 80 placentas (40 placentas from women with GDM and 40 healthy controls) by immunohistochemistry using the semi-quantitative immunoreactive score (IRS).

A FHIR has been lit on gICS: facilitating the standardised exchange of informed consent in a large network of university medicine.

Background: The Federal Ministry of Education and Research of Germany (BMBF) funds a network of university medicines (NUM) to support COVID-19 and pandemic research at national level. The "COVID-19 Data Exchange Platform" (CODEX) as part of NUM establishes a harmonised infrastructure that supports research use of COVID-19 datasets. The broad consent (BC) of the Medical Informatics Initiative (MII) is agreed by all German federal states and forms the legal base for data processing.

Pharmacology of orismilast, a potent and selective PDE4 inhibitor.

Background: There remains an unmet need for oral medications that are safe and efficacious for long-term management of chronic inflammatory skin diseases (CISD). Inhibition of phosphodiesterase 4 (PDE4) can modulate a broad range of pro-inflammatory cytokines that play a major role in CISD pathogenesis. Orismilast is a second generation PDE4 inhibitor in clinical development for CISD treatment.

Spontaneous healing of acute ACL ruptures: rate, prognostic factors and short-term outcome.

Introduction: Anterior cruciate ligament (ACL) reconstruction is considered the first line treatment in ACL rupture. However, some patients return to high intensity sport activities and show a normal knee function without ACL reconstruction. Therefore, aim of this study was to evaluate the rate and prognostic factors of spontaneous healing in patients with ACL rupture and the short-term functional outcome.

Oral orismilast: Efficacy and safety in moderate-to-severe psoriasis and development of modified release tablets.

Background: Orismilast is a high-potency phosphodiesterase 4 (PDE4) inhibitor with enhanced selectivity for the PDE4B and PDE4D subtypes.

Objectives: The objective of this phase 2a trial was to examine the efficacy and safety of orismilast for psoriasis using a first-generation immediate-release (IR) formulation. The objective of the subsequent phase 1 trial was to test new formulations designed to minimize the gastrointestinal (GI)-related adverse events (AEs) observed with the first-generation IR formulation.