The age pigment lipofuscin causes oxidative stress, lysosomal dysfunction, and pyroptotic cell death.

Accumulation of the age pigment lipofuscin represents a ubiquitous hallmark of the aging process. However, our knowledge about cellular effects of lipofuscin accumulation is potentially flawed, because previous research mainly utilized highly artificial methods of lipofuscin generation. In order to address this tremendous problem, we developed a convenient protocol for isolation of authentic lipofuscin from human and equine cardiac tissue in high purity and quantity.

In vitro testing of drug response in primary multiple myeloma cells using a microwell-based technology.

Multiple myeloma is an aggressive neoplasm of plasma cells. While numerous drugs have gained approval, the absence of established predictive markers for individual drug responses poses a challenge. In this study, we explored the microwell- and fluorescence-based Cellply CC-Array® technology for high-throughput analysis of in vitro drug responses as a potential predictive marker for patient treatment outcomes.

Radiation Therapy for Meningiomas - Where Do We Stand and What's on the Horizon?

Radiation therapy, including conventionally fractionated external beam radiation therapy, stereotactic radiosurgery, and fractionated stereotactic radiation therapy, is a cornerstone in the interdisciplinary management of meningiomas. Recent advances in radiation oncology and also in other fields, such as neuropathology and imaging, have various implications for meningioma radiation therapy. This review aims to summarize current and anticipated developments, as well as active clinical trials related to the use of radiation therapy for meningiomas.

Feasibility analysis of using patient-derived tumour organoids for treatment decision guidance in locally advanced head and neck squamous cell carcinoma.

Background: Current treatment for head and neck squamous cell carcinoma (HNSCC) involves surgery, radiotherapy, and chemotherapy. Despite aggressive multimodal approaches, tumour recurrence occurs in 40-60 % of cases, leading to poor survival outcomes. HNSCC lacks common genetic drivers for tailored therapies, and reliable biomarkers for treatment selection are scarce.

Reduced GABA Levels in the ACC of Actively Drinking High Risk Individuals Compared to Recently Detoxified Alcohol-Dependent Patients.

Background: Acute gamma-aminobutyric acid (GABAergic) effects of alcohol consumption are well-known, whereas prior research has yielded inconsistent findings regarding on adaptations of the GABAergic neurotransmitter system to chronic alcohol use. Previous studies indicate either elevated or reduced GABA levels in cortical regions such as the anterior cingulate cortex (ACC) in persons with alcohol use disorder (AUD). We tested the hypothesis that active alcohol consumption compared to abstinence contributes to GABA levels as observed in prior research on chronic alcohol use.

GPA33 expression in colorectal cancer can be induced by WNT inhibition and targeted by cellular therapy.

GPA33 is a promising surface antigen for targeted therapy in colorectal cancer (CRC). It is expressed almost exclusively in CRC and intestinal epithelia. However, previous clinical studies have not achieved expected response rates.

Pre-assembled ECMO: Enhancing efficiency and reducing stress in refractory cardiac arrest care.

Aim: Extracorporeal cardiopulmonary resuscitation (ECPR) by veno-arterial extracorporeal membrane oxygenation (VA-ECMO) during refractory cardiac arrest presents significant medical and psychological challenges for healthcare providers. Beyond managing cardiac arrest and preparing for potential coronary angiography, the ECMO circuit must be assembled and primed under strictly sterile conditions, contributing to additional psychological stress and potential delays in ECMO cannulation. This pragmatic study thought to evaluate whether pre-assembled and pre-primed ECMO circuits (pre-primed group) maintain sterility over a 21-day period, expedite ECMO initiation in ECPR patients and alleviate the psychological burden on the ECPR team, compared to newly assembled and primed ECMO circuits (on-demand group).

Targeting neutrophil serine proteases in bronchiectasis.

Persistent neutrophilic inflammation is a central feature in both the pathogenesis and progression of bronchiectasis. Neutrophils release neutrophil serine proteases (NSPs), such as neutrophil elastase (NE), cathepsin G and proteinase 3. When chronically high levels of free NSP activity exceed those of protective antiproteases, structural lung destruction, mucosal-related defects, further susceptibility to infection and worsening of clinical outcomes can occur.

Physiologists as medical scientists: An early warning from the German academic system.

"Medical scientists" are postgraduate investigators who are engaged in biomedical research, and either hold a biomedical PhD or are qualified in medicine but do not participate in patient care. Medical scientists constitute ~40% of staff at medical faculties and >90% at nonuniversity medical research institutions in Germany. However, medical scientists in Germany face limited long-term career prospects and a lack of dedicated training and support programmes.

Deep learning-based whole-brain B -mapping at 7T.

Purpose: This study investigates the feasibility of using complex-valued neural networks (NNs) to estimate quantitative transmit magnetic RF field (B ) maps from multi-slice localizer scans with different slice orientations in the human head at 7T, aiming to accelerate subject-specific B -calibration using parallel transmission (pTx).

Methods: Datasets containing channel-wise B -maps and corresponding multi-slice localizers were acquired in axial, sagittal, and coronal orientation in 15 healthy subjects utilizing an eight-channel pTx transceiver head coil. Training included five-fold cross-validation for four network configurations: used transversal, sagittal, coronal data, and was trained on all slice orientations.

Prognostic Value of Speckle Tracking Echocardiography-Derived Strain in Unmasking Risk for Arrhythmias in Children with Myocarditis.

Risk assessment in pediatric myocarditis is challenging, particularly when left ventricular ejection fraction (LVEF) is preserved. This study aimed to evaluate LV myocardial deformation using speckle-tracking echocardiography (STE)-derived longitudinal +strain (LS) and assessed its diagnostic and prognostic value in children with myocarditis. Retrospective STE-derived layer-specific LV LS analysis was performed on echocardiograms from patients within the multicenter, prospective registry for pediatric myocarditis "MYKKE".

Real-world federated learning in radiology: hurdles to overcome and benefits to gain.

Objective: Federated Learning (FL) enables collaborative model training while keeping data locally. Currently, most FL studies in radiology are conducted in simulated environments due to numerous hurdles impeding its translation into practice. The few existing real-world FL initiatives rarely communicate specific measures taken to overcome these hurdles.

Comparison of exercise training modalities and change in peak oxygen consumption in heart failure with preserved ejection fraction: a secondary analysis of the OptimEx-Clin trial.

Aims: Exercise training (ET) is an effective therapy in heart failure with preserved ejection fraction (HFpEF), but the influence of different ET characteristics is unclear. We aimed to evaluate the associations between ET frequency, duration, intensity [% heart rate reserve (%HRR)] and estimated energy expenditure (EEE) with the change in peak oxygen consumption (V̇O2) over 3 months of moderate continuous training (MCT, 5×/week) or high-intensity interval training (HIIT, 3×/week) in HFpEF.

Methods And Results: ET duration and heart rate (HR) were recorded with a smartphone application.

Applicability of heart failure clinical practice guidelines in low- and middle-income countries.

Aims: Clinical practice guidelines are commonly written by professional societies in high-income countries (HIC) with limited anticipation of implementation obstacles in other environments. We used heart failure (HF) guidelines as a paradigm to examine this concern, by conducting a survey to understand clinicians' ability to implement HF guidelines and their perceptions of the current HF guideline applicability in low- and middle-income countries (LMIC).

Methods And Results: An online survey of physicians in the database of the Translational Medicine Academy who treat HF patients was offered by email from 5 October to 27 November 2023, inquiring of participants' demographic information, experience, and views of HF guidelines as related to their practice.

Effects of separate and combined estradiol and progesterone administration on fear extinction in healthy pre-menopausal women.

Altered fear conditioning and extinction learning are discussed as key etiological features in anxiety disorders. Women have an increased risk for anxiety disorders and fear conditioning has been shown to be influenced by the menstrual cycle phase and circulating gonadal hormones. The objective of our study was to investigate the effects of separate and combined estradiol and progesterone administration on fear extinction in healthy women.

Timing of veno-arterial extracorporeal membrane oxygenation support in patients with cardiogenic shock.

Aims: The optimal timing for implementing mechanical circulatory support (MCS) in cardiogenic shock (CS) remains indeterminate. This study aims to evaluate patient characteristics and outcome associated with the time interval between CS onset and veno-arterial extracorporeal membrane oxygenation (VA-ECMO) implementation.

Methods And Results: In this study, patients with CS treated with MCS at 15 tertiary care centres in three countries were enrolled.

Leveraging weak complementary labels enhances semantic segmentation of hepatocellular carcinoma and intrahepatic cholangiocarcinoma.

In this paper we present a deep learning segmentation approach to classify and quantify the two most prevalent primary liver cancers - hepatocellular carcinoma and intrahepatic cholangiocarcinoma - from hematoxylin and eosin (H&E) stained whole slide images. While semantic segmentation of medical images typically requires costly pixel-level annotations by domain experts, there often exists additional information which is routinely obtained in clinical diagnostics but rarely utilized for model training. We propose to leverage such weak information from patient diagnoses by deriving complementary labels that indicate to which class a sample cannot belong to.