Cardiac-specific BACH1 ablation attenuates pathological cardiac hypertrophy by inhibiting the Ang II type 1 receptor expression and the Ca2+/CaMKII pathway.

Aims: BACH1 is up-regulated in hypertrophic hearts, but its function in cardiac hypertrophy remains largely unknown. This research investigates the function and mechanisms of BACH1 in the regulation of cardiac hypertrophy.

Methods And Results: Male cardiac-specific BACH1 knockout mice or cardiac-specific BACH1 transgenic (BACH1-Tg) mice and their respective wild-type littermates developed cardiac hypertrophy induced by angiotensin II (Ang II) or transverse aortic constriction (TAC).

Intestinal B cells license metabolic T-cell activation in NASH microbiota/antigen-independently and contribute to fibrosis by IgA-FcR signalling.

Background & Aims: The progression of non-alcoholic steatohepatitis (NASH) to fibrosis and hepatocellular carcinoma (HCC) is aggravated by auto-aggressive T cells. The gut-liver axis contributes to NASH, but the mechanisms involved and the consequences for NASH-induced fibrosis and liver cancer remain unknown. We investigated the role of gastrointestinal B cells in the development of NASH, fibrosis and NASH-induced HCC.

Human memory B cells show plasticity and adopt multiple fates upon recall response to SARS-CoV-2.

The B cell response to different pathogens uses tailored effector mechanisms and results in functionally specialized memory B (B) cell subsets, including CD21 resting, CD21CD27 activated and CD21CD27 B cells. The interrelatedness between these B cell subsets remains unknown. Here we showed that single severe acute respiratory syndrome coronavirus 2-specific B cell clones showed plasticity upon antigen rechallenge in previously exposed individuals.

Shaping the brain vasculature in development and disease in the single-cell era.

The CNS critically relies on the formation and proper function of its vasculature during development, adult homeostasis and disease. Angiogenesis - the formation of new blood vessels - is highly active during brain development, enters almost complete quiescence in the healthy adult brain and is reactivated in vascular-dependent brain pathologies such as brain vascular malformations and brain tumours. Despite major advances in the understanding of the cellular and molecular mechanisms driving angiogenesis in peripheral tissues, developmental signalling pathways orchestrating angiogenic processes in the healthy and the diseased CNS remain incompletely understood.

The vascular gene Apold1 is dispensable for normal development but controls angiogenesis under pathological conditions.

The molecular mechanisms of angiogenesis have been intensely studied, but many genes that control endothelial behavior and fate still need to be described. Here, we characterize the role of Apold1 (Apolipoprotein L domain containing 1) in angiogenesis in vivo and in vitro. Single-cell analyses reveal that - across tissues - the expression of Apold1 is restricted to the vasculature and that Apold1 expression in endothelial cells (ECs) is highly sensitive to environmental factors.

Multiplex imaging of breast cancer lymph node metastases identifies prognostic single-cell populations independent of clinical classifiers.

Although breast cancer mortality is largely caused by metastasis, clinical decisions are based on analysis of the primary tumor and on lymph node involvement but not on the phenotype of disseminated cells. Here, we use multiplex imaging mass cytometry to compare single-cell phenotypes of primary breast tumors and matched lymph node metastases in 205 patients. We observe extensive phenotypic variability between primary and metastatic sites and that disseminated cell phenotypes frequently deviate from the clinical disease subtype.

Nucleolin promotes angiogenesis and endothelial metabolism along the oncofetal axis in the human brain vasculature.

Glioblastomas are among the deadliest human cancers and are highly vascularized. Angiogenesis is dynamic during brain development, almost quiescent in the adult brain but reactivated in vascular-dependent CNS pathologies, including brain tumors. The oncofetal axis describes the reactivation of fetal programs in tumors, but its relevance in endothelial and perivascular cells of the human brain vasculature in glial brain tumors is unexplored.

A multicenter phase II trial of anti-EGFR-immunoliposomes loaded with doxorubicin in patients with advanced triple negative breast cancer.

Advanced triple negative breast cancer (TNBC) is an aggressive, but initially chemo-sensitive disease. The prognosis is poor and more than three quarters of patients experience progression 12 months after the initiation of conventional first-line chemotherapy. Approximately two thirds of TNBC express epidermal growth factor receptor 1 (EGFR).

Discharge Age and Weight for Very Preterm Infants in Six Countries: 2012-2020.

Background: Postmenstrual age for surviving infants without congenital anomalies born at 24-29 weeks' gestational age from 2005 to 2018 in the USA increased 8 days, discharge weight increased 316 grams, and median discharge weight z-score increased 0.19 standard units. We asked whether increases were observed in other countries.

Radiomics for the detection of diffusely impaired myocardial perfusion: A proof-of-concept study using 13N-ammonia positron emission tomography.

Aim: The current proof-of-concept study investigates the value of radiomic features from normal 13N-ammonia positron emission tomography (PET) myocardial retention images to identify patients with reduced global myocardial flow reserve (MFR).

Methods: Data from 100 patients with normal retention 13N-ammonia PET scans were divided into two groups, according to global MFR (i.e.

Single-cell resolved ploidy and chromosomal aberrations in nonalcoholic steatohepatitis-(NASH) induced hepatocellular carcinoma and its precursor lesions.

Nonalcoholic steatohepatitis (NASH)-induced hepatocellular carcinoma (HCC) and its precursor, nonalcoholic fatty liver disease (NAFLD) are an unmet health issue due to widespread obesity. We assessed copy number changes of genes associated with hepatocarcinogenesis and oxidative pathways at a single-cell level. Eleven patients with NASH-HCC and 11 patients with NAFLD were included.

Genetic and epigenetic analysis of hepatocellular adenomas with atypical morphological features.

Background: Hepatocellular adenoma (HCA) is a rare liver tumour, which can have atypical morphological features such as cytological atypia, pseudoglandular architecture, and altered reticulin framework. Little is known about the genetic and epigenetic alterations of such HCAs and whether they show the alterations classically found in hepatocellular carcinoma (HCC) or in HCA without atypical morphology.

Methods: We analysed five HCAs with atypical morphological features and one HCA with transition to HCC.

Central versus Peripheral Postcardiotomy Veno-Arterial Extracorporeal Membrane Oxygenation: Systematic Review and Individual Patient Data Meta-Analysis.

Background: It is unclear whether peripheral arterial cannulation is superior to central arterial cannulation for postcardiotomy veno-arterial extracorporeal membrane oxygenation (VA-ECMO).

Methods: A systematic review was conducted using PubMed, Scopus, and Google Scholar to identify studies on postcardiotomy VA-ECMO for the present individual patient data (IPD) meta-analysis. Analysis was performed according to the intention-to-treat principle.

The impact of direct oral anticoagulants on viscoelastic testing - A systematic review.

Background: In case of bleeding patients and in acute care, the assessment of residual direct oral anticoagulant (DOAC) activity is essential for evaluating the potential impact on hemostasis, especially when a timely decision on urgent surgery or intervention is required. Viscoelastic tests are crucial in a modern goal-directed coagulation management to assess patients' coagulation status. However, the role of viscoelastic test to detect and quantify residual DOAC plasma levels is controversially discussed.

Dynamics of T cell repertoire renewal following autologous hematopoietic stem cell transplantation in multiple sclerosis.

Autologous hematopoietic stem cell transplantation (aHSCT) is a highly effective treatment of multiple sclerosis (MS). It depletes autoreactive cells and subsequently renews adaptive immune cells. The possible proinflammatory potential of surviving T cells early after aHSCT has not been studied.

Molecular and genetic mechanisms in brain arteriovenous malformations: new insights and future perspectives.

Brain arteriovenous malformations (bAVMs) are rare vascular lesions made of shunts between cerebral arteries and veins without the interposition of a capillary bed. The majority of bAVMs are asymptomatic, but some may be revealed by seizures and potentially life-threatening brain hemorrhage. The management of unruptured bAVMs remains a matter of debate.

Sequencing of Ipilimumab Plus Nivolumab and Encorafenib Plus Binimetinib for Untreated -Mutated Metastatic Melanoma (SECOMBIT): A Randomized, Three-Arm, Open-Label Phase II Trial.

Purpose: Limited prospective data are available on sequential immunotherapy and BRAF/MEK inhibition for -mutant metastatic melanoma.

Methods: SECOMBIT is a randomized, three-arm, noncomparative phase II trial (ClinicalTrials.gov identifier: NCT02631447).

Epigenetics in the primary and secondary prevention of cardiovascular disease: influence of exercise and nutrition.

Increasing evidence links changes in epigenetic systems, such as DNA methylation, histone modification, and non-coding RNA expression, to the occurrence of cardiovascular disease (CVD). These epigenetic modifications can change genetic function under influence of exogenous stimuli and can be transferred to next generations, providing a potential mechanism for inheritance of behavioural intervention effects. The benefits of exercise and nutritional interventions in the primary and secondary prevention of CVD are well established, but the mechanisms are not completely understood.