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).

Weight cycling exacerbates glucose intolerance and hepatic triglyceride storage in mice with a history of chronic high fat diet exposure.

Background: Obese subjects undergoing weight loss often fear the Yoyo dieting effect, which involves regaining or even surpassing their initial weight. To date, our understanding of such long-term obesity and weight cycling effects is still limited and often based on only short-term murine weight gain and loss studies. This study aimed to investigate the long-term impacts of weight cycling on glycemic control and metabolic health, focusing on adipose tissue, liver, and hypothalamus.

Liquid biopsy in organ damage: introduction of an innovative tool for assessing the complexity of blunt splenic injury.

Liquid biomarkers are essential in trauma cases and critical care and offer valuable insights into the extent of injury, prognostic predictions, and treatment guidance. They can help assess the severity of organ damage (OD), assist in treatment decisions and forecast patient outcomes. Notably, small extracellular vesicles, particularly those involved in splenic trauma, have been overlooked.

Modulating delirium through stimulation (MoDeSt): study protocol for a randomized, double-blind, sham-controlled trial assessing the effect of postoperative transcranial electrical stimulation on delirium incidence.

Background: Postoperative delirium (POD) is the most common neurological adverse event among elderly patients undergoing surgery. POD is associated with an increased risk for postoperative complications, long-term cognitive decline, an increase in morbidity and mortality as well as extended hospital stays. Delirium prevention and treatment options are currently limited.

Surveillance of drug prescribing: why outliers miss their targets - a qualitative study.

Background: Rising costs are a challenge for healthcare systems. To keep expenditure for drugs under control, in many healthcare systems, drug prescribing is continuously monitored. The Bavarian Drug Agreement (German: Wirkstoffvereinbarung or WSV) for the ambulatory sector in Bavaria (the federal state of Germany) was developed for this purpose.

Meta-analysis of MitraClip and PASCAL for transcatheter mitral edge-to-edge repair.

Background: Despite the promising results of both MitraClip and PASCAL systems for the treatment of mitral regurgitation (MR), there is limited data on the comparison of both systems regarding their safety and efficacy. We aim to compare both systems for MR.

Materials And Methods: Five databases were searched until October 2024.

Transcriptome and DNA methylation profiling during the NSN to SN transition in mouse oocytes.

Background: During the latter stages of their development, mammalian oocytes under dramatic chromatin reconfiguration, transitioning from a non-surrounded nucleolus (NSN) to a surrounded nucleolus (SN) stage, and concomitant transcriptional silencing. Although the NSN-SN transition is known to be essential for developmental competence of the oocyte, less is known about the accompanying molecular changes. Here we examine the changes in the transcriptome and DNA methylation during the NSN to SN transition in mouse oocytes.

Migraine in men.

Background: Migraine is a common primary headache disorder, less frequently affecting men than women, and often regarded as predominantly a "women's disease." Despite this, migraine in men presents with unique characteristics in terms of symptoms, treatment responses, comorbidities, and pain perception. Historically, research has focused more on migraine in women, overlooking critical male-specific aspects.

Genome-wide development of simple sequence repeat (SSR) markers at 2-Mb intervals in lotus (Nelumbo Adans.).

Background: Despite the rapid advancement of high-throughput sequencing, simple sequence repeats (SSRs) remain indispensable molecular markers for various applied and research tasks owing to their cost-effectiveness and ease of use. However, existing SSR markers cannot meet the growing demand for research on lotus (Nelumbo Adans.) given their scarcity and weak connections to the lotus genome.

Personalized, autologous neoantigen-specific T cell therapy in metastatic melanoma: a phase 1 trial.

New treatment approaches are warranted for patients with advanced melanoma refractory to immune checkpoint blockade (ICB) or BRAF-targeted therapy. We designed BNT221, a personalized, neoantigen-specific autologous T cell product derived from peripheral blood, and tested this in a 3 + 3 dose-finding study with two dose levels (DLs) in patients with locally advanced or metastatic melanoma, disease progression after ICB, measurable disease (Response Evaluation Criteria in Solid Tumors version 1.1) and, where appropriate, BRAF-targeted therapy.

Establishing bio-logging data collections as dynamic archives of animal life on Earth.

Rapid growth in bio-logging-the use of animal-borne electronic tags to document the movements, behaviour, physiology and environments of wildlife-offers opportunities to mitigate biodiversity threats and expand digital natural history archives. Here we present a vision to achieve such benefits by accounting for the heterogeneity inherent to bio-logging data and the concerns of those who collect and use them. First, we can enable data integration through standard vocabularies, transfer protocols and aggregation protocols, and drive their wide adoption.

Pharmacological targeting of caspase-8/c-FLIP heterodimer enhances complex II assembly and elimination of pancreatic cancer cells.

Extrinsic apoptotic network is driven by Death Ligand (DL)-mediated activation of procaspase-8. Recently, we have developed the first-in class small molecule, FLIPinB, which specifically targets the key regulator of extrinsic apoptosis, the protein c-FLIP, in the caspase-8/c-FLIP heterodimer. We have shown that FLIPinB enhances DL-induced caspase-8 activity and apoptosis.

Pro-inflammatory macrophage activation does not require inhibition of oxidative phosphorylation.

Pro-inflammatory macrophage activation is a hallmark example of how mitochondria serve as signaling organelles. Oxidative phosphorylation sharply decreases upon classical macrophage activation, as mitochondria are thought to shift from ATP production towards accumulating signals that amplify effector function. However, evidence is conflicting regarding whether this collapse in respiration is essential or dispensable.

The proximity-based protein interactome and regulatory logics of the transcription factor p65 NF-κB/RELA.

The protein interactome of p65/RELA, the most active subunit of the transcription factor (TF) NF-κB, has not been previously determined in living cells. Using p65-miniTurbo fusion proteins and biotin tagging, we identify >350 RELA interactors from untreated and IL-1α-stimulated cells, including many TFs (47% of all interactors) and >50 epigenetic regulators belonging to different classes of chromatin remodeling complexes. A comparison with the interactomes of two point mutants of p65 reveals that the interactions primarily require intact dimerization rather than DNA-binding properties.

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.

Comprehensive genomic characterization of early-stage bladder cancer.

Understanding the molecular landscape of nonmuscle-invasive bladder cancer (NMIBC) is essential to improve risk assessment and treatment regimens. We performed a comprehensive genomic analysis of patients with NMIBC using whole-exome sequencing (n = 438), shallow whole-genome sequencing (n = 362) and total RNA sequencing (n = 414). A large genomic variation within NMIBC was observed and correlated with different molecular subtypes.

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).

Future food prices will become less sensitive to agricultural market prices and mitigation costs.

Agricultural production costs represent less than half of total food prices for higher-income countries and will likely further decrease globally. Added-value components such as transport, processing, marketing and catering show increasing importance in food value chains, especially as countries undergo a nutrition transition towards more complex and industrial food systems. Here, using a combined statistical and process-based modelling framework, we derive and project the value-added component of food prices for 136 countries and 11 different food groups, for food-at-home and food-away-from-home.

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.

Two decades of bacterial ecology and evolution in a freshwater lake.

Ecology and evolution are considered distinct processes that interact on contemporary time scales in microbiomes. Here, to observe these processes in a natural system, we collected a two-decade, 471-metagenome time series from Lake Mendota (Wisconsin, USA). We assembled 2,855 species-representative genomes and found that genomic change was common and frequent.

Addressing inter individual variability in CSF levels of brain derived proteins across neurodegenerative diseases.

Accurate diagnosis and monitoring of neurodegenerative diseases require reliable biomarkers. Cerebrospinal fluid (CSF) proteins are promising candidates for reflecting brain pathology; however, their diagnostic utility may be compromised by natural variability between individuals, weakening their association with disease. Here, we measured the levels of 69 pre-selected proteins in cerebrospinal fluid using antibody-based suspension bead array technology in a multi-disease cohort of 499 individuals with neurodegenerative disorders including Alzheimer's disease (AD), behavioral variant frontotemporal dementia, primary progressive aphasias, amyotrophic lateral sclerosis (ALS), corticobasal syndrome, primary supranuclear palsy, along with healthy controls.

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.

"We are doing it together, don't worry" - A qualitative study on the implementation of electronic medical records in German hospitals.

Background: The ongoing implementation of electronic medical records (EMRs) in German hospitals is currently slow. Implementation science widely acknowledges the barriers and facilitators to implementation. Thus, specific preconditions are necessary to address the former and to support an effective EMR implementation.

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.

Behind the scenes of EQA - characteristics, capabilities, benefits and assets of external quality assessment (EQA).

This is the first in a series of five papers that detail the role and substantial impact that external quality assessment (EQA) and their providers' services play in ensuring diagnostic (IVD) performance quality. The aim is to give readers and users of EQA services an insight into the processes in EQA, explain to them what happens before EQA samples are delivered and after examination results are submitted to the provider, how they are assessed, what benefits participants can expect, but also who are stakeholders other than participants and what significance do EQA data and assessment results have for them. This first paper presents the history of EQA, insights into legal, financing and ethical matters, information technology used in EQA, structure and lifecycle of EQA programs, frequency and intensity of challenges, and unique requirements of extra-examination and educational EQA programs.