Low income, being without employment, and living alone: how they are associated with cognitive functioning-Results from the German national cohort (NAKO).

Aim was to investigate to what extent cognitive functioning differs by three socioeconomic conditions: low income, being without employment, and living alone. A total of N = 158,144 participants of the population-based German National Cohort (NAKO) provided data on socioeconomic conditions and completed cognitive tests. Multivariable confounder-adjusted regression analyses indicated that cognitive functioning was lower in those with low income (b = -0.

Mixed- and multi-relative biological effectiveness model simultaneous optimization in carbon ion radiotherapy: A proof-of-concept.

Background And Purpose: In carbon ion radiotherapy (CIRT), different relative biological effectiveness (RBE) models have been used for calculating RBE-weighted dose (D). Conversion between current RBE predictions and introduction of novel approaches remains a challenging task. Our aim is to introduce a framework considering multiple RBE models simultaneously during CIRT plan optimization, easing the translation between D prescriptions.

Risk-Adapted Starting Ages of Colorectal Cancer Screening for People With Diabetes or Metabolic Syndrome.

Background: Individuals with diabetes and metabolic syndrome have an increased risk of colorectal cancer (CRC), suggesting earlier screening than the average-risk population may be warranted.

Aims: To derive risk-adapted starting ages of CRC screening for people with diabetes or metabolic syndrome.

Methods: We determined 5-year cumulative risks of CRC at individual ages between 30 and 50 across Europe (overall and individually for Germany, France, the UK and Italy) and North America (the United States and Canada) based on the GLOBOCAN 2022 database.

Rapid Stiffness Mapping in Soft Biologic Tissues With Micrometer Resolution Using Optical Multifrequency Time-Harmonic Elastography.

Rapid mapping of the mechanical properties of soft biological tissues from light microscopy to macroscopic imaging can transform fundamental biophysical research by providing clinical biomarkers to complement in vivo elastography. This work introduces superfast optical multifrequency time-harmonic elastography (OMTHE) to remotely encode surface and subsurface shear wave fields for generating maps of tissue stiffness with unprecedented detail resolution. OMTHE rigorously exploits the space-time propagation characteristics of multifrequency time-harmonic waves to address current limitations of biomechanical imaging and elastography.

Prediagnostic Plasma Nutrimetabolomics and Prostate Cancer Risk: A Nested Case-Control Analysis Within the EPIC Study.

: Nutrimetabolomics may reveal novel insights into early metabolic alterations and the role of dietary exposures on prostate cancer (PCa) risk. We aimed to prospectively investigate the associations between plasma metabolite concentrations and PCa risk, including clinically relevant tumor subtypes. : We used a targeted and large-scale metabolomics approach to analyze plasma samples of 851 matched PCa case-control pairs from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

Hematologic Toxicity Profiles and the Impact of Hemoglobin Nadir and Transfusion on Oncologic Outcome in Definitive Radiochemotherapy for Cervical Cancer.

: Definitive radiochemotherapy with concomitant cisplatin 40 mg/m weekly represents the standard of care for locally advanced cervical cancer. Current studies (KEYNOTE-A18 and INTERLACE) are intensifying this regimen at the cost of increased hematologic toxicity. We aimed to evaluate influencing factors on hematotoxicity to ensure the safe application of radiochemotherapy.

Design, Synthesis, and Biochemical Evaluation of Novel MLK3 Inhibitors: A Target Hopping Example.

The human kinome has tremendous medical potential. In the past decade, mixed-lineage protein kinase 3 (MLK3) has emerged as an interesting and druggable target in oncogenic signaling. The important role of MLK3 has been demonstrated in several types of cancer.

The prognostic influence of hospital type, method of first histological confirmation and time to chemotherapy in patients with advanced primary ovarian cancer.

Purpose: Ovarian cancer is the fifth most common cancer in women and the leading cause of death of all gynecological malignancies. Prognosis is determined by optimal surgical outcome (macroscopic complete resection) most commonly achieved in tertiary hospitals. We investigated whether tertiary versus non-tertiary hospital as the location of an initial diagnostic intervention for histological confirmation before cytoreductive surgery versus immediate primary debulking surgery impacts outcome in patients with advanced ovarian cancer.

Golgi pH elevation due to loss of V-ATPase subunit V0a2 function correlates with tissue-specific glycosylation changes and globozoospermia.

Loss-of-function variants in ATP6V0A2, encoding the trans Golgi V-ATPase subunit V0a2, cause wrinkly skin syndrome (WSS), a connective tissue disorder with glycosylation defects and aberrant cortical neuron migration. We used knock-out (Atp6v0a2) and knock-in (Atp6v0a2) mice harboring the R755Q missense mutation selectively abolishing V0a2-mediated proton transport to investigate the WSS pathomechanism. Homozygous mutants from both strains displayed a reduction of growth, dermis thickness, and elastic fiber formation compatible with WSS.

Radiomics and Artificial Intelligence Landscape for [F]FDG PET/CT in Multiple Myeloma.

[F]FDG PET/CT is a powerful imaging modality of high performance in multiple myeloma (MM) and is considered the appropriate method for assessing treatment response in this disease. On the other hand, due to the heterogeneous and sometimes complex patterns of bone marrow infiltration in MM, the interpretation of PET/CT can be particularly challenging, hampering interobserver reproducibility and limiting the diagnostic and prognostic ability of the modality. Although many approaches have been developed to address the issue of standardization, none can yet be considered a standard method for interpretation or objective quantification of PET/CT.

Second Comment on 'Modeling for predicting survival fraction of cells after ultra-high dose rate irradiation'.

We comment on the reply by Shiraishito our comments regarding their recently published study 'Modeling for Predicting Survival Fraction of Cells after Ultra-High Dose Rate Irradiation'. While we appreciate the effort of the authors to consider our comments, we see ourselves compelled to add another short comment as we believe that some of our suggestions have been misrepresented. This may have resulted in a misguiding re-evaluation of the model.

Mass-Guided Single-Cell MALDI Imaging of Low-Mass Metabolites Reveals Cellular Activation Markers.

Single-cell MALDI mass spectrometry imaging (MSI) of lipids and metabolites >200 Da has recently come to the forefront of biomedical research and chemical biology. However, cell-targeting and metabolome-preserving methods for analysis of low mass, hydrophilic metabolites (<200 Da) in large cell populations are lacking. Here, the PRISM-MS (PRescan Imaging for Small Molecule - Mass Spectrometry) mass-guided MSI workflow is presented, which enables space-efficient single cell lipid and metabolite analysis.

DNA methylation-based analysis reveals accelerated epigenetic aging in giant cell-enriched adult-type glioblastoma.

Background: Giant cell (gc)-enriched glioblastoma (gcGB) represents a distinct histological variant of isocitrate dehydrogenase wild-type adult-type glioblastoma with notable enlarged mono- or multinuclear tumor cells. While some studies suggest a survival advantage for gcGB patients, the underlying causes remain elusive. GcGBs are associated with TP53 mutations, and gcs were shown to accumulate DNA double-strand breaks and show deficient mitosis, potentially triggering cellular senescence programs.

EOMES establishes mesoderm and endoderm differentiation potential through SWI/SNF-mediated global enhancer remodeling.

Mammalian pluripotent cells first segregate into neuroectoderm (NE), or mesoderm and endoderm (ME), characterized by lineage-specific transcriptional programs and chromatin states. To date, the relationship between transcription factor activities and dynamic chromatin changes that guide cell specification remains ill-defined. In this study, we employ mouse embryonic stem cell differentiation toward ME lineages to reveal crucial roles of the Tbx factor Eomes to globally establish ME enhancer accessibility as the prerequisite for ME lineage competence and ME-specific gene expression.

Beyond classical immunity: Mast cells as signal converters between tissues and neurons.

Mast cells are regarded as effectors in immune defense against parasites and venoms and play an essential role in the pathology of allergic diseases. More recently, mast cells have been shown to receive stimuli derived from type 2 immunity, tissue damage, stress, and inflammation. Mast cells then rapidly convert these diverse signals into appropriate, organ-specific protective reflexes that can limit inflammation or reduce tissue damage.

MRgRT real-time target localization using foundation models for contour point tracking and promptable mask refinement.

. This study aimed to evaluate two real-time target tracking approaches for magnetic resonance imaging (MRI) guided radiotherapy (MRgRT) based on foundation artificial intelligence models..

Warehouse-based, immunopeptidome-guided design of personalised peptide vaccines shows feasibility in clinical trial evaluation in CLL patients.

Unlabelled: Cancer peptide vaccination represents a promising therapeutic approach, but has been hampered by lack of suitable antigens and restricted applicability due to different HLA backgrounds of individual patients. We here introduce a novel warehouse-based concept for composition of personalized peptide vaccines and report on its successful application in a Phase II clinical trial in patients with chronic lymphocytic leukemia (CLL) after first-line therapy. 26 CLL patients in at least partial remission (PR) after 6 months of immuno-chemotherapy were vaccinated with a personalized vaccine compiled from a premanufactured peptide warehouse comprising immunopeptidome-defined CLL-associated peptides.

Enhancing clinical decision-making: An externally validated machine learning model for predicting isocitrate dehydrogenase mutation in gliomas using radiomics from presurgical magnetic resonance imaging.

Background: Glioma, the most prevalent primary brain tumor, poses challenges in prognosis, particularly in the high-grade subclass, despite advanced treatments. The recent shift in tumor classification underscores the crucial role of isocitrate dehydrogenase (IDH) mutation status in the clinical care of glioma patients. However, conventional methods for determining IDH status, including biopsy, have limitations.

Heterogeneity-driven phenotypic plasticity and treatment response in branched-organoid models of pancreatic ductal adenocarcinoma.

In patients with pancreatic ductal adenocarcinoma (PDAC), intratumoural and intertumoural heterogeneity increases chemoresistance and mortality rates. However, such morphological and phenotypic diversities are not typically captured by organoid models of PDAC. Here we show that branched organoids embedded in collagen gels can recapitulate the phenotypic landscape seen in murine and human PDAC, that the pronounced molecular and morphological intratumoural and intertumoural heterogeneity of organoids is governed by defined transcriptional programmes (notably, epithelial-to-mesenchymal plasticity), and that different organoid phenotypes represent distinct tumour-cell states with unique biological features in vivo.

Comparative benchmarking of failure detection methods in medical image segmentation: Unveiling the role of confidence aggregation.

Semantic segmentation is an essential component of medical image analysis research, with recent deep learning algorithms offering out-of-the-box applicability across diverse datasets. Despite these advancements, segmentation failures remain a significant concern for real-world clinical applications, necessitating reliable detection mechanisms. This paper introduces a comprehensive benchmarking framework aimed at evaluating failure detection methodologies within medical image segmentation.

Variability in resistance training trajectories of breast cancer patients undergoing therapy.

Purpose: In resistance training (RT), the change in volume-load from training sessions (TS) to TS is an indicator of training progress. Resulting growth trajectories are likely to differ between individuals. Understanding this variation is important for exercise planning in general, but even more for clinical populations.