Regulation of Clusterin in the Heart and Plasma of Mice After Transverse Aortic Constriction.

Chronic pressure overload induces adverse cardiac remodelling characterised by left ventricular (LV) hypertrophy and fibrosis, leading to heart failure (HF). Identification of new biomarkers for adverse cardiac remodelling enables us to better understand this process and, consequently, to prevent HF. We recently identified clusterin (CLU) as a biomarker of cardiac remodelling and HF after myocardial infarction.

Impact of the 2022 pulmonary hypertension definition on haemodynamic classification and mortality in patients with aortic stenosis undergoing valve replacement.

Aims: With the 2022 pulmonary hypertension (PH) definition, the mean pulmonary artery pressure (mPAP) threshold for any PH was lowered from ≥25 to >20 mmHg, and the pulmonary vascular resistance (PVR) value to differentiate between isolated post-capillary PH (IpcPH) and combined pre- and post-capillary PH (CpcPH) was reduced from >3 Wood units (WU) to >2 WU. We assessed the impact of this change in the PH definition in aortic stenosis (AS) patients undergoing aortic valve replacement (AVR).

Methods And Results: Severe AS patients ( = 503) undergoing pre-AVR cardiac heart catheterization were classified according to both the 2015 and 2022 definitions.

: Processing utilities for high-resolution images for spatially resolved transcriptomics data.

Spatially resolved transcriptomics (SRT) is a growing field that links gene expression to anatomical context. SRT approaches that use next-generation sequencing (NGS) combine RNA sequencing with histological or fluorescent imaging to generate spatial maps of gene expression in intact tissue sections. These technologies directly couple gene expression measurements with high-resolution histological or immunofluorescent images that contain rich morphological information about the tissue under study.

The gene expression landscape of the human locus coeruleus revealed by single-nucleus and spatially-resolved transcriptomics.

Norepinephrine (NE) neurons in the locus coeruleus (LC) make long-range projections throughout the central nervous system, playing critical roles in arousal and mood, as well as various components of cognition including attention, learning, and memory. The LC-NE system is also implicated in multiple neurological and neuropsychiatric disorders. Importantly, LC-NE neurons are highly sensitive to degeneration in both Alzheimer's and Parkinson's disease.

Pulmonary Congestion by Conventional Chest Radiography: Relationship With Hemodynamics and Mortality in Patients With Severe Aortic Stenosis.

Background: The relationship between chest radiograph (CXR) findings of pulmonary congestion and invasive hemodynamics and clinical outcomes in patients with cardiac diseases is unclear. We assessed the correlation between a CXR-based congestion score (RxCS) and the mean pulmonary artery wedge pressure (mPAWP) and the prognostic impact of RxCS and mPAWP in severe aortic stenosis (AS).

Methods: In 471 patients with severe AS undergoing right heart catheterization and upright CXR, the RxCS was calculated (6 items, maximum score: 10 points) independently by 2 radiologists (average value taken) blinded to clinical data.

Pleural effusion in severe aortic stenosis: marker of an adverse haemodynamic constellation and poor prognosis.

Aim: Pleural effusion (PE) is a common chest radiography (CXR) finding in patients with advanced cardiac disease. The pathophysiology and clinical value of PE in this setting are incompletely defined. We aimed to assess the haemodynamic correlates and prognostic impact of PE in patients with severe aortic stenosis (AS).

Performance of computational algorithms to deconvolve heterogeneous bulk ovarian tumor tissue depends on experimental factors.

Background: Single-cell gene expression profiling provides unique opportunities to understand tumor heterogeneity and the tumor microenvironment. Because of cost and feasibility, profiling bulk tumors remains the primary population-scale analytical strategy. Many algorithms can deconvolve these tumors using single-cell profiles to infer their composition.

ECG left ventricular hypertrophy in aortic stenosis: Relationship with cardiac structure, invasive hemodynamics, and long-term mortality.

Background: In aortic stenosis (AS), left ventricular hypertrophy (LVH) is the response to pressure overload and represents the substrate for a maladaptive cascade, the so-called AS-related cardiac damage. We hypothesized that in AS patients electrocardiogram (ECG) LVH not only predicts echocardiography LVH but also other noninvasive and invasive markers of cardiac damage and prognosis after aortic valve replacement (AVR).

Methods: In 279 patients with severe AS undergoing ECG, echocardiography, and cardiac catheterization before AVR, the Sokolow-Lyon index, the Cornell product, the Romhilt-Estes score, and the Peguero-Lo Presti score were assessed.

[Evaluating the introduction of HIV pre-exposure prophylaxis as a benefit of statutory health insurance (EvE-PrEP) : Highly effective protection against HIV without an increase in sexually transmitted infections].

Background: We investigated the impact of HIV pre-exposure prophylaxis (PrEP) as a new service of the statutory health insurance (SHI) on the incidence of HIV and other sexually transmitted infections (STIs) in Germany. In addition, PrEP needs and access barriers were analyzed.

Methods: The following data were evaluated as part of the evaluation project: HIV and syphilis notification data and extended surveillance by the Robert Koch Institute (RKI), pharmacy prescription data, SHI routine data, PrEP use in HIV-specialty care centers, Checkpoint, the BRAHMS and PrApp studies, as well as a community board.

nnSVG for the scalable identification of spatially variable genes using nearest-neighbor Gaussian processes.

Feature selection to identify spatially variable genes or other biologically informative genes is a key step during analyses of spatially-resolved transcriptomics data. Here, we propose nnSVG, a scalable approach to identify spatially variable genes based on nearest-neighbor Gaussian processes. Our method (i) identifies genes that vary in expression continuously across the entire tissue or within a priori defined spatial domains, (ii) uses gene-specific estimates of length scale parameters within the Gaussian process models, and (iii) scales linearly with the number of spatial locations.

Estimated glomerular filtration rate, haemodynamics, and mortality in patients with aortic stenosis.

Background: In aortic stenosis (AS), estimated glomerular filtration rate (eGFR) is an important prognostic marker but its haemodynamic determinants are unknown. We investigated the correlation between eGFR and invasive haemodynamics and long-term mortality in AS patients undergoing aortic valve replacement (AVR).

Methods: We studied 503 patients [median (interquartile range) age 76 (69-81) years] with AS [indexed aortic valve area .

Systemic blood pressure in severe aortic stenosis: Haemodynamic correlates and long-term prognostic impact.

Aims: Blood pressure (BP) targets in patients with aortic stenosis (AS) are controversial. This study sought to describe the haemodynamic profile and the clinical outcome of severe AS patients with low versus high central meaarterial pressure (MAP).

Methods And Results: Patients with severe AS (n = 477) underwent right and left heart catheterization prior to aortic valve replacement (AVR).

Complement downregulation promotes an inflammatory signature that renders colorectal cancer susceptible to immunotherapy.

Background And Aims: The role of inflammatory immune responses in colorectal cancer (CRC) development and response to therapy is a matter of intense debate. While inflammation is a known driver of CRC, inflammatory immune infiltrates are a positive prognostic factor in CRC and predispose to response to immune checkpoint blockade (ICB) therapy. Unfortunately, over 85% of CRC cases are primarily unresponsive to ICB due to the absence of an immune infiltrate, and even the cases that show an initial immune infiltration can become refractory to ICB.

Sympathetic nerve innervation and metabolism in ischemic myocardium in response to remote ischemic perconditioning.

Sympathetic nerve denervation after myocardial infarction (MI) predicts risk of sudden cardiac death. Therefore, therapeutic approaches limit infarct size, improving adverse remodeling and restores sympathetic innervation have a great clinical potential. Remote ischemic perconditioning (RIPerc) could markedly attenuate MI-reperfusion (MIR) injury.

Methylation of the Hippo effector YAP by the methyltransferase SETD7 drives myocardial ischaemic injury: a translational study.

Aims: Methylation of non-histone proteins is emerging as a central regulatory mechanism in health and disease. The methyltransferase SETD7 has shown to methylate and alter the function of a variety of proteins in vitro; however, its function in the heart is poorly understood. The present study investigates the role of SETD7 in myocardial ischaemic injury.

spatialLIBD: an R/Bioconductor package to visualize spatially-resolved transcriptomics data.

Background: Spatially-resolved transcriptomics has now enabled the quantification of high-throughput and transcriptome-wide gene expression in intact tissue while also retaining the spatial coordinates. Incorporating the precise spatial mapping of gene activity advances our understanding of intact tissue-specific biological processes. In order to interpret these novel spatial data types, interactive visualization tools are necessary.

SpatialExperiment: infrastructure for spatially-resolved transcriptomics data in R using Bioconductor.

Summary: SpatialExperiment is a new data infrastructure for storing and accessing spatially-resolved transcriptomics data, implemented within the R/Bioconductor framework, which provides advantages of modularity, interoperability, standardized operations and comprehensive documentation. Here, we demonstrate the structure and user interface with examples from the 10x Genomics Visium and seqFISH platforms, and provide access to example datasets and visualization tools in the STexampleData, TENxVisiumData and ggspavis packages.

Availability And Implementation: The SpatialExperiment, STexampleData, TENxVisiumData and ggspavis packages are available from Bioconductor.

Wedge Pressure vs Left Ventricular End-Diastolic Pressure for Pulmonary Hypertension Classification and Prognostication in Severe Aortic Stenosis.

Background: Differentiation between precapillary and postcapillary pulmonary hypertension (PH) classically relies on mean pulmonary artery wedge pressure (mPAWP). The left ventricular end-diastolic pressure (LVEDP) is proposed as an equivalent alternative. However, mPAWP and LVEDP may differ substantially.

Hemodynamics Prior to Valve Replacement for Severe Aortic Stenosis and Pulmonary Hypertension during Long-Term Follow-Up.

(1) Background: Pulmonary hypertension after aortic valve replacement (AVR; post-AVR PH) carries a poor prognosis. We assessed the pre-AVR hemodynamic characteristics of patients with versus without post-AVR PH. (2) Methods: We studied 205 patients (mean age 75 ± 10 years) with severe AS (indexed aortic valve area 0.

miQC: An adaptive probabilistic framework for quality control of single-cell RNA-sequencing data.

Single-cell RNA-sequencing (scRNA-seq) has made it possible to profile gene expression in tissues at high resolution. An important preprocessing step prior to performing downstream analyses is to identify and remove cells with poor or degraded sample quality using quality control (QC) metrics. Two widely used QC metrics to identify a 'low-quality' cell are (i) if the cell includes a high proportion of reads that map to mitochondrial DNA (mtDNA) encoded genes and (ii) if a small number of genes are detected.

Pulmonary Hypertension in Patients With Heart Failure With Mid-Range Ejection Fraction.

Pulmonary hypertension (PH) is common in patients with heart failure (HF). The role of PH in patients with HF with reduced (HFrEF) and preserved (HFpEF) left ventricular ejection fraction (LVEF) has been extensively characterized during the last years. In contrast, the pathophysiology of HF with mid-range LVEF (HFmrEF), and in particular the role of PH in this context, are largely unknown.

Impact of the new pulmonary hypertension definition on long-term mortality in patients with severe aortic stenosis undergoing valve replacement.

Background: The new 2018 pulmonary hypertension (PH) definition includes a lower mean pulmonary artery pressure (mPAP) cut-off (>20 mmHg rather than ≥25 mmHg) and the compulsory requirement of a pulmonary vascular resistance (PVR) ≥3 Wood units (WU) to define precapillary PH. We assessed the clinical impact of the 2018 compared to the 2015 PH definition in aortic stenosis (AS) patients undergoing aortic valve replacement (AVR).

Methods: Severe AS patients (n = 487) undergoing pre-AVR right heart catheterization were classified according to the 2015 and 2018 definitions.

The Role of Tenascin C in Cardiac Reverse Remodeling Following Banding-Debanding of the Ascending Aorta.

Background: Tenascin-C (TN-C) plays a maladaptive role in left ventricular (LV) hypertrophy following pressure overload. However, the role of TN-C in LV regression following mechanical unloading is unknown.

Methods: LV hypertrophy was induced by transverse aortic constriction for 10 weeks followed by debanding for 2 weeks in wild type (Wt) and TN-C knockout (TN-C KO) mice.