Cancer risk in carriers of TP53 germline variants grouped into different functional categories.

Li-Fraumeni syndrome is a cancer predisposition syndrome caused by pathogenic TP53 germline variants and associated with a high lifelong cancer risk. We analysed the German LFS registry that contains data on 304 individuals. Cancer phenotypes were correlated with variants grouped according to their ability to transactivate target genes in a yeast assay using a traditional (non-functional, partially-functional) and a novel (clusters A, B, C) classification of variants into different groups.

Nebulized aminoglycosides for ventilator-associated pneumonia: Methodological considerations and lessons from experimental studies.

Aminoglycosides are concentration-dependent antibiotics exerting a bactericidal effect when concentrations at the site of infection are equal to or greater than 5 times the minimum inhibitory concentrations (MIC). When administered intravenously, they exhibit poor lung penetration and high systemic renal and ototoxicity, imposing to restrict their administration to 5 days. Experimental studies conducted in anesthetized and mechanically ventilated sheep and pigs provide evidence that high doses of nebulized aminoglycosides induce a rapid and potent bacterial killing in the infected lung parenchyma.

PEARL: Protein Eluting Alginate with Recombinant Lactobacilli.

Engineered living materials (ELMs) made of bacteria in hydrogels have shown considerable promise for therapeutic applications through controlled and sustained release of complex biopharmaceuticals at low costs and with reduced wastage. While most therapeutic ELMs use E. coli due to its large genetic toolbox, most live biotherapeutic bacteria in development are lactic acid bacteria due to native health benefits they offer.

Gender-specific outcomes in pilonidal sinus disease: Female outcomes after cleft lift surgery in a large prospective Danish cohort.

Aim: Pilonidal sinus disease (PSD) is a common condition particularly affecting young men. Females affected by the condition account for about 20% of patients and are rarely mentioned, much less studied specifically. In this study we evaluate the surgical outcomes in a female population following Bascom's cleft lift (BCL) surgery in primary extensive disease, non-healing wounds after previous surgery and recurrent disease in a large Danish cohort from a high-volume centre.

Model-based perfusion reconstruction with time separation technique in cone-beam CT dynamic liver perfusion imaging.

Background: The success of embolization, a minimally invasive treatment of liver cancer, could be evaluated in the operational room with cone-beam CT by acquiring a dynamic perfusion scan to inspect the contrast agent flow.

Purpose: The reconstruction algorithm must address the issues of low temporal sampling and higher noise levels inherent in cone-beam CT systems, compared to conventional CT.

Methods: Therefore, a model-based perfusion reconstruction based on the time separation technique (TST) was applied.

Determining the QRS axis: visual estimation is equal to calculation.

Background: The QRS axis of the electrocardiogram (ECG) is often considered in clinical practice, but its determination is frequently limited to a rough estimation, such as "normal", with left or right deviation, and superior or inferior in the case of premature ventricular complexes (PVCs). However, a more exact determination of the QRS axis may be warranted in certain scenarios, such as to determine the origin of PVCs more precisely, and is attainable by visual estimation using the hexaxial reference system.

Objectives: The aim of this study was to determine how well such an estimation of the QRS axis would correlate with the axis calculated by formulas.

Oral Tributyrin Treatment affects Short-Chain Fatty Acid Transport, Mucosal Health, and Microbiome in a Mouse Model of Inflammatory Diarrhea.

Butyrate may decrease intestinal inflammation and diarrhea. This study investigates the impact of oral application of sodium butyrate (NaB) and tributyrin (TB) on colonic butyrate concentration, SCFA transporter expression, colonic absorptive function, barrier properties, inflammation, and microbial composition in the colon of slc26a3 mice, a mouse model for inflammatory diarrhea. In vivo fluid absorption and bicarbonate secretory rates were evaluated in the cecum and mid-colon of slc26a3 and slc26a3 mice before and during luminal perfusion of NaB-containing saline and were significantly stimulated in both slc26a3 and slc26a3 colon by NaB.

Acute respiratory tract infections during the first six years of life - results from the German birth cohort study LoewenKIDS.

Objectives: Acute respiratory infections (ARI) often occur in early childhood and are mostly self-limited. However, they impose a high socioeconomic burden and can be associated with chronic diseases later in life. To date, data on self-reported ARI beyond infancy are limited.

Attention-deficit/hyperactivity disorder-related psychomotor activity and altered neuronal activity in the medial prefrontal cortex and striatum in the A53T mouse model of Parkinson's disease and other synucleinopathies: Findings from an "endophenotype" approach.

Attention-Deficit/Hyperactivity Disorder (ADHD) is associated with an increased risk of Parkinson's disease (PD) and other synucleinopathies later in life. The severity of the ADHD phenotype may play a significant role in this association. There is no indication that any of the existing animal models can unify these disorders.

Artificial intelligence-enabled obesity prediction: A systematic review of cohort data analysis.

Background: Obesity, now the fifth leading global cause of death, has seen a dramatic rise in prevalence over the last forty years. It significantly increases the risk of diseases such as type 2 diabetes and cardiovascular disease. Early identification of obesity risk allows for preventative actions against obesity-related factors.

Variable treatment response to lumasiran in pediatric patients with primary hyperoxaluria type 1.

Background: Primary hyperoxaluria type 1 (PH 1) is a rare genetic condition due to mutations in the AGXT gene. This leads to an overproduction of oxalate in the liver. Hyperoxaluria often causes kidney stones, nephrocalcinosis, and chronic kidney disease.

Occurrence and clinical correlates of SARS-CoV-2 viremia in two German patient cohorts.

Viremia defined as detectable SARS-CoV-2 RNA in the blood is a potential marker of disease severity and prognosis in COVID-19 patients. Here, we determined the frequency of viremia in serum of two independent COVID-19 patient cohorts within the German National Pandemic Cohort Network (German: tionales andemie horten etzwerk, NAPKON) with diagnostic RT-PCR against SARS-CoV-2. A cross-sectional cohort with 1,122 COVID-19 patients (German: , SUEP) and 299 patients recruited in a high-resolution platform with patients at high risk to develop severe courses (German: , HAP) were tested for viremia.

Highly pathogenic avian influenza virus (H5N5) detected in an Atlantic walrus () in the Svalbard Archipelago, Norway, 2023.

We present the first documented case of highly pathogenic avian influenza virus (HPAIV) subtype H5N5 in an Atlantic walrus (). The animal was found dead in Svalbard, Norway, in 2023. Sequence analysis revealed the highest genetic similarity with virus isolates from different avian hosts.

A Short Cognitive and Neuropsychiatric Assessment Scale for Progressive Supranuclear Palsy.

Background: Patients with Progressive Supranuclear Palsy (PSP) suffer from several neuropsychological impairments. These mainly affect the frontal lobe and subcortical brain structures. However, a scale for the assessment of cognitive and neuropsychiatric disability in PSP is still missing.

Roads to remission: evolving treatment concepts in type 2 inflammatory diseases.

Unlabelled: Non-communicable diseases (NCDs) characterised by type 2 inflammation, including asthma, allergic rhinitis, chronic rhinosinusitis with nasal polyps, atopic dermatitis, food allergies and eosinophilic esophagitis, are increasing in prevalence worldwide. Currently, there is a major paradigm shift in the management of these diseases, towards the concept of disease modification and the treatment goal remission, regardless of severity and age. Remission as a treatment goal in chronic inflammatory NCDs was first introduced in rheumatoid arthritis, and then adopted in other non-type 2 inflammatory diseases.

Rab10-associated tubulation as an early marker for biogenesis of the assembly compartment in cytomegalovirus-infected cells.

Introduction: Cytomegalovirus (CMV) infection reorganizes early endosomes (EE), recycling endosome (RE), and trans-Golgi network (TGN) and expands their intermediates into a large perinuclear structure that forms the inner part of the cytoplasmic assembly complex (AC). The reorganization begins and results with the basic configuration (known as pre-AC) in the early (E) phase of infection, but the sequence of developmental steps is not yet well understood. One of the first signs of the establishment of the inner pre-AC, which can be observed by immunofluorescence, is the accumulation of Rab10.

A conceptual framework for the ethical analysis of moral conflicts in migrant live-in care.

In many industrialized countries, hiring a migrant live-in carer represents a promising solution to support families caring for an older person at home and to avoid institutionalization. Migrant live-in carers live in the household of the person in need of care and provide extensive care and social support. They usually come from geographic areas such as Eastern Europe or Southeast Asia.

Heat stress induces oxidative stress and activates the KEAP1-NFE2L2-ARE pathway in reproduction-related cells.

Heat stress negatively affects the reproductive function of in animals and humans. Although a relationship between heat and oxidative stress has been suggested, the underlying mechanism has not been sufficiently examined in reproduction-related cells. Therefore, we aimed to investigate whether heat stress induces oxidative stress using a variety of reproduction-related cells including bovine placental and cumulus-granulosa cells, human cell lines derived from cervical and endometrial cancers, and fibroblasts derived from endometrium.

Characterization of Hospital Admissions During Immune Checkpoint Inhibitor Therapy: Insights From the ICOG Study.

Introduction: Immune checkpoint inhibitors (ICI) have improved the therapeutic arsenal in outpatient oncology care; however, data on necessity of hospitalizations associated with immune-related adverse events (irAEs) are scarce. Here, we characterized hospitalizations of patients undergoing ICI, from the prospective cohort study of the immune cooperative oncology group (ICOG) Hannover.

Methods: Between 12/2019 and 06/2022, 237 patients were included.

Factors associated with statural growth in pediatric kidney transplant recipients with focus on metabolic acidosis.

Background: We investigated factors associated with post-transplant growth in pediatric kidney transplant (KTx) recipients with a focus on plasma bicarbonate (HCO3) and estimated the effect of alkali treatment on growth.

Methods: In this study of the CERTAIN Registry, data were collected up to 5 years post-transplant. Generalized Additive Mixed Models were applied to assess the association between post-transplant growth and covariates.

Soft tissue-like coupling materials for in vitro acoustic emission studies in total hip arthroplasty.

In hip arthroplasty, relative movements between the femoral stem and bone can lead to implant loosening, resulting in extensive bone loss. Acoustic emission (AE) analysis is a promising technique for a nondestructive and noninvasive detection of these relative movements. To develop such a detection method, in vitro investigations using piezoelectric AE sensors on implant stems in artificial or human femora are required to characterize the AE signals induced by loosening.