The sarcoma ring trial: a case-based analysis of inter-center agreement across 21 German-speaking sarcoma centers.

Purpose: The management of soft tissue sarcoma (STS) at reference centers with specialized multidisciplinary tumor boards (MTB) improves patient survival. The German Cancer Society (DKG) certifies sarcoma centers in German-speaking countries, promoting high standards of care. This study investigated the variability in treatment recommendations for localized STS across different German-speaking tertiary sarcoma centers.

Simulator training in focus assessed transthoracic echocardiography (FATE) for undergraduate medical students: results from the FateSim randomized controlled trial.

Introduction: Ultrasound is important in heart diagnostics, yet implementing effective cardiac ultrasound requires training. While current strategies incorporate digital learning and ultrasound simulators, the effectiveness of these simulators for learning remains uncertain. This study evaluates the effectiveness of simulator-based versus human-based training in Focused Assessed with Transthoracic Echocardiography (FATE).

Perioperative outcomes in an age-adapted analysis of the German StuDoQ|Pancreas registry for PDAC.

Background: Pancreatic ductal adenocarcinoma (PDAC) typically occurs in an older patient population. Yet, early-onset pancreatic cancer (EOPC) has one of the fastest growing incidence rates. This study investigated the influence of age and tumor location on postoperative morbidity and mortality in a large, real-world dataset.

Altered thrombin generation with prothrombin complex concentrate is not detected by viscoelastic testing: an in vitro study.

Background: Bleeding guidelines currently recommend use of viscoelastic testing (VET) to direct haemostatic resuscitation in severe haemorrhage. However, VET-derived parameters of clot initiation, such as clotting time (CT) and activated clotting time (ACT), might not adequately reflect a clinically relevant interaction of procoagulant and anticoagulant activity, as revealed by thrombin generation assays. The aim of this study was to evaluate the ability of CT and ACT to indicate thrombin generation activity.

Novel, standardized sample collection from the brain-nose interface.

Background: Diagnostics for neurodegenerative diseases lack non-invasive approaches suitable for early-stage biochemical screening and routine examination of neuropathology. Biomarkers of neurodegenerative diseases pass through the brain-nose interface (BNI) and accumulate in nasal secretion. Sample collection from the brain-nose interface presents a compelling prospect as basis for a non-invasive molecular diagnosis of neuropathologies.

Ethnic origin in cancer clinical trials: overrated or understated? A comprehensive analysis of cancer clinical trials leading to FDA and EMA approvals between 2020 and 2022.

Background: Ethnic diversity in cancer clinical trials is essential to ensure that therapeutic advances are equitable and broadly applicable in multicultural societies. Yet, missing consensus on the documentation of ethnic origin, partially based on the complexity of the terminology and fear of discrimination, leads to suboptimal patient management of minority populations. Additionally, eligibility criteria, such as stringent laboratory cut-offs, often fail to account for variations across ethnic groups, potentially excluding patients without evidence-based justification.

Translation, adaptation, and validation of the Care Coordination Instrument for cancer patients.

Background: Cancer requires interdisciplinary intersectoral care. The Care Coordination Instrument (CCI) captures patients' perspectives on cancer care coordination. We aimed to translate, adapt, and validate the CCI for Germany (CCI German version).

Interfacial water confers transcription factors with dinucleotide specificity.

Transcription factors (TFs) recognize specific bases within their DNA-binding motifs, with each base contributing nearly independently to total binding energy. However, the energetic contributions of particular dinucleotides can deviate strongly from the additive approximation, indicating that some TFs can specifically recognize DNA dinucleotides. Here we solved high-resolution (<1 Å) structures of MYF5 and BARHL2 bound to DNAs containing sets of dinucleotides that have different affinities to the proteins.

Analysis of multi-condition single-cell data with latent embedding multivariate regression.

Identifying gene expression differences in heterogeneous tissues across conditions is a fundamental biological task, enabled by multi-condition single-cell RNA sequencing (RNA-seq). Current data analysis approaches divide the constituent cells into clusters meant to represent cell types, but such discrete categorization tends to be an unsatisfactory model of the underlying biology. Here, we introduce latent embedding multivariate regression (LEMUR), a model that operates without, or before, commitment to discrete categorization.

ZIC1 is a context-dependent medulloblastoma driver in the rhombic lip.

Transcription factors are frequent cancer driver genes, exhibiting noted specificity based on the precise cell of origin. We demonstrate that ZIC1 exhibits loss-of-function (LOF) somatic events in group 4 (G4) medulloblastoma through recurrent point mutations, subchromosomal deletions and mono-allelic epigenetic repression (60% of G4 medulloblastoma). In contrast, highly similar SHH medulloblastoma exhibits distinct and diametrically opposed gain-of-function mutations and copy number gains (20% of SHH medulloblastoma).

Circulating tumor cell plasticity determines breast cancer therapy resistance via neuregulin 1-HER3 signaling.

Circulating tumor cells (CTCs) drive metastasis, the leading cause of death in individuals with breast cancer. Due to their low abundance in the circulation, robust CTC expansion protocols are urgently needed to effectively study disease progression and therapy responses. Here we present the establishment of long-term CTC-derived organoids from female individuals with metastatic breast cancer.

Perennial disaster patterns in Central Europe since 2000 and implications for hospital preparedness planning - a cross-sectional analysis.

The goal of this analysis is to describe seasonal disaster patterns in Central Europe in order to raise awareness and improve hospital disaster planning and resilience, particularly during peak events. Hospitals are essential pillars of a country's critical infrastructure, vital for sustaining healthcare services and supporting public well-being-a key issue of national security. Disaster planning for hospitals is crucial to ensure their functionality under special circumstances.

Genomic and phenotypic stability of fusion-driven pediatric sarcoma cell lines.

Human cancer cell lines are the mainstay of cancer research. Recent reports showed that highly mutated adult carcinoma cell lines (mainly HeLa and MCF-7) present striking diversity across laboratories and that long-term continuous culturing results in genomic/transcriptomic heterogeneity with strong phenotypical implications. Here, we hypothesize that oligomutated pediatric sarcoma cell lines mainly driven by a fusion transcription factor, such as Ewing sarcoma (EwS), are genetically and phenotypically more stable than the previously investigated adult carcinoma cell lines.

Evolving concepts in intracranial pressure monitoring - from traditional monitoring to precision medicine.

A wide range of acute brain injuries, including both traumatic and non-traumatic causes, can result in elevated intracranial pressure (ICP), which in turn can cause further secondary injury to the brain, initiating a vicious cascade of propagating injury. Elevated ICP is therefore a neurological injury that requires intensive monitoring and time-sensitive interventions. Patients at high risk for developing elevated ICP undergo placement of invasive ICP monitors including external ventricular drains, intraparenchymal ICP monitors, and lumbar drains.

Compromising tyrosine hydroxylase function extends and blunts the temporal profile of reinforcement by dopamine neurons in .

For a proper representation of the causal structure of the world, it is adaptive to consider both evidence for and evidence against causality. To take punishment as an example, the causality of a stimulus is unlikely if there is a temporal gap before punishment is received, but causality is credible if the stimulus immediately precedes punishment. In contrast, causality can be ruled out if the punishment occurred first.

Functional Characterization of Pathway Inhibitors for the Ubiquitin-Proteasome System (UPS) as Tool Compounds for CRBN and VHL-Mediated Targeted Protein Degradation.

Small molecule degraders such as PROteolysis TArgeting Chimeras (PROTACs) and molecular glues are new modalities for drug development and important tools for target validation. When appropriately optimized, both modalities lead to proteasomal degradation of the protein of interest (POI). Due to the complexity of the induced multistep degradation process, controls for degrader evaluation are critical and commonly used in the literature.

mRNA export factors store nascent transcripts within nuclear speckles as an adaptive response to transient global inhibition of transcription.

Several transcription inhibitors have been developed as cancer therapies. However, they show modest clinical activity, highlighting that our understanding of the cellular response to transcriptional inhibition remains incomplete. Here we report that potent inhibitors of transcription not only impact mRNA output but also markedly impair mRNA transcript localization and nuclear export.

4D structural biology-The 9 Murnau Conference on structural biology.

The data presented at the 9 International Murnau Conference on September 18-21, 2024, the largest recurring structural biology meeting in Central Europe, illustrated the thriving state of the structural biology community. This is largely attributed to the ground-breaking developments over the last decade, which were intensely discussed during the meeting.

Preliminary findings on the association between maternal salivary and hair cortisol and the mother-infant-interaction during the early postpartum period.

Maternal capabilities to engage in sensitive caregiving are important for infant development and mother-infant-interaction, however, can be negatively affected by cortisol due to a stress response. Previous research suggested that cortisol possibly impairs cognitive functions important for caregiving behavior, which potentially leads to less maternal sensitivity. However, studies investigating the influence of cortisol using endocrine parameters on the mother-infant-interaction during the early postpartum are lacking.

Realization of a Laughlin State of Two Rapidly Rotating Fermions.

We realize a Laughlin state of two rapidly rotating fermionic atoms in an optical tweezer. By utilizing a single atom and spin resolved imaging technique, we sample the Laughlin wave function thereby revealing its distinctive features, including a vortex distribution in the relative motion, correlations in the particles' relative angle, and suppression of the interparticle interactions. Our Letter lays the foundation for atom-by-atom assembly of fractional quantum Hall states in rotating atomic gases.

Disentangling Sources of Momentum Fluctuations in Xe+Xe and Pb+Pb Collisions with the ATLAS Detector.

High-energy nuclear collisions create a quark-gluon plasma, whose initial condition and subsequent expansion vary from event to event, impacting the distribution of the eventwise average transverse momentum [P([p_{T}])]. Disentangling the contributions from fluctuations in the nuclear overlap size (geometrical component) and other sources at a fixed size (intrinsic component) remains a challenge. This problem is addressed by measuring the mean, variance, and skewness of P([p_{T}]) in ^{208}Pb+^{208}Pb and ^{129}Xe+^{129}Xe collisions at sqrt[s_{NN}]=5.

Two-Loop Electron Self-Energy for Low Nuclear Charges.

Calculations of the two-loop electron self-energy for the 1S Lamb shift are reported, performed to all orders in the nuclear binding strength parameter Zα (where Z is the nuclear charge number and α is the fine structure constant). Our approach allows calculations to be extended to nuclear charges lower than previously possible and improves the numerical accuracy by more than an order of magnitude. Extrapolation of our all-order results to hydrogen yields a result twice as precise as the previously accepted value [E.

Final CONUS Results on Coherent Elastic Neutrino-Nucleus Scattering at the Brokdorf Reactor.

The CONUS experiment studies coherent elastic neutrino-nucleus scattering in four 1 kg germanium spectrometers. Low ionization energy thresholds of 210 eV were achieved. The detectors were operated inside an optimized shield at the Brokdorf nuclear power plant which provided a reactor antineutrino flux of up to 2.