Aging platelets shift their hemostatic properties to inflammatory functions.

Platelets are crucial players in hemostasis and thrombosis, but also contribute to immune regulation and host defense, using different receptors, signaling pathways and effector functions, respectively. Whether distinct subsets of platelets specialize in these diverse tasks is insufficiently understood. Here, we employed an in vivo pulse-labelling method in Mus musculus models for tracking in vivo platelet ageing and its functional implications.

A novel micelleplex for tumour-targeted delivery of CRISPR-Cas9 against KRAS-mutated lung cancer.

CRISPR-Cas9 has emerged as a highly effective and customizable genome editing tool, holding significant promise for the treatment of KRAS mutations in lung cancer. In this study, we introduce a novel micelleplex, named C14-PEI, designed to co-deliver Cas9 mRNA and sgRNA efficiently to excise the mutated KRAS allele in lung cancer cells. C14-PEI is synthesised from 1,2-epoxytetradecane and branched PEI 600 Da a ring-opening reaction.

Symptom and problem burden, performance status and palliative care phases in specialist palliative care: cross-sectional analysis of care episodes.

Objectives: Palliative care phases (stable, unstable, deteriorating, terminal and bereavement) are useful in describing the palliative care situation of patients/relatives and their care needs as well as the suitability of care plans. Little is known about care setting-specific differences of the phases and their association with burden of symptoms/problems and functional status. We aimed to describe the presence and association of symptom/problem burden and functional status with the palliative care phase at the beginning of care episodes in specialist palliative care units, specialist home care teams and advisory services.

An atlas of transcription initiation reveals regulatory principles of gene and transposable element expression in early mammalian development.

Transcriptional activation of the embryonic genome (EGA) is a major developmental landmark enabling the embryo to become independent from maternal control. The magnitude and control of transcriptional reprogramming during this event across mammals remains poorly understood. Here, we developed Smart-seq+5' for high sensitivity, full-length transcript coverage and simultaneous capture of 5' transcript information from single cells and single embryos.

Direct-acting oral anticoagulant removal by intraoperative hemoadsorption in CABG and/or single valve surgery: interim analysis of the International Safe and Timely Antithrombotic Removal (STAR) registry.

Objective: Patients on direct-acting oral anticoagulants (DOACs) are at high risk of perioperative bleeding complications. Intraoperative hemoadsorption is a novel strategy to reduce perioperative bleeding in patients on DOACs undergoing non-deferable cardiac surgery. The international STAR-registry reports real-world clinical outcomes associated with this application.

From the last 100 to the first 100-outcome after a manufacturer change in reverse fracture arthroplasty.

Purpose: If surgery is indicated for elderly patients suffering a proximal humerus fracture, reverse fracture arthroplasty became the preferred type of treatment due to its good and reliable outcomes over the last decade. Surgeons could choose from a wide range of implants and up to now there was no evaluation, if a change of the manufacturer affects patients` outcome.

Methods: The last 100 patients before and the first 100 after manufacturer change in reverse fracture arthroplasty were evaluated at a level one trauma center, all treated by only 3 senior shoulder surgeons.

[Celiac disease: an update].

Celiac disease is one of the most common lifelong autoimmune disorders and is currently understood as a genetically determined immune intolerance to gluten. In genetically predisposed individuals, the consumption of gluten, along with additional environmental factors, triggers an immunological reaction in the small intestinal epithelium, leading to the destruction of the mucosal architecture with villous atrophy. This can be asymptomatic, but may also cause a wide range of symptoms and lead to systemic complications, such as osteoporosis or infertility.

Chronic intermittent fasting impairs β cell maturation and function in adolescent mice.

Intermittent fasting (IF) is a nutritional lifestyle intervention with broad metabolic benefits, but whether the impact of IF depends on the individual's age is unclear. Here, we investigated the effects of IF on systemic metabolism and β cell function in old, middle-aged, and young mice. Short-term IF improves glucose homeostasis across all age groups without altering islet function and morphology.

EGR1 regulates oxidative stress and aldosterone production in adrenal cells and aldosterone-producing adenomas.

Aldosterone-producing adenomas (APAs) are a major cause of primary aldosteronism, a common form of endocrine hypertension. Here, we demonstrate that Early Growth Response 1 (EGR1) plays a dual role in adrenal cell biology, regulating both oxidative stress and aldosterone production. Using RNA sequencing of RSL3-treated human adrenal cells and spatial transcriptomics of adrenal glands from patients with primary aldosteronism, we identify EGR1 as a key gene associated with RSL3-related oxidative stress and APAs.

Multinational retrospective analysis of bridging therapy prior to chimeric antigen receptor t cells for relapsed/refractory acute lymphoblastic leukemia in children and young adults.

Anti-CD19 chimeric antigen receptor T cells (CAR) are a well-established treatment option for children and young adults suffering from relapsed/refractory B-lineage acute lymphoblastic leukemia. Bridging therapy is used to control disease prior to start of lymphodepletion before CAR infusion and thereby improve efficacy of CAR therapy. However, the effect of different bridging strategies on outcome, side effects and response to CAR therapy is still poorly understood.

Retrovirus-based manufacturing of chimeric antigen receptor-modified T cells for cancer therapy research.

Treatment with autologous chimeric antigen receptor (CAR)-modified T cells can achieve outstanding clinical response rates in heavily pretreated patients with B and plasma cell malignancies. However, relapses occur, and they limit the efficacy of this promising treatment approach. The complex GMP-compliant production and high treatment costs cause that CAR T cells cannot yet be used in a broad population.

[Diagnostic algorithm and key differential diagnoses of hematuria].

The different causes of hematuria depend largely on age, gender and clinical context. Macrohematuria should always be investigated using cystoscopy and advanced imaging (CT/MRI with urographic phase). The most common differential diagnoses of macrohematuria include urinary tract infection, stones and urothelial carcinoma.

Predicting work ability impairment in post COVID-19 patients: a machine learning model based on clinical parameters.

The Post COVID-19 condition (PCC) is a complex disease affecting health and everyday functioning. This is well reflected by a patient's inability to work (ITW). In this study, we aimed to investigate factors associated with ITW (1) and to design a machine learning-based model for predicting ITW (2) twelve months after baseline.

Establishment of the complete life cycle of Calicophoron daubneyi under experimental conditions.

The complex life cycle of the rumen fluke Calicophoron daubneyi is similar to that of the liver fluke Fasciola hepatica. Interestingly, C. daubneyi and F.

Patient perspectives on stress after ICU and a short primary care based psychological intervention - results from a qualitative sub‑study of the PICTURE trial.

Background: Approximately 20-25% of patients who survive medical treatment at an intensive care unit (ICU) develop post-traumatic stress symptoms. There is currently a gap in follow-up care for them. As part of the PICTURE study, general practitioners (GPs) carried out a brief interview-based intervention.

Maintenance treatment with trofosfamide in patients with advanced soft tissue sarcoma - a retrospective single-centre analysis.

Background: The prognosis of patients with advanced soft tissue sarcoma (STS) remains dismal. Trofosfamide (TRO) has been proposed as a well-tolerated oral maintenance therapy. This retrospective analysis aims to determine the value of this therapy.

[Patient safety in palliative surgery].

Palliative surgery aims to improve the quality of life for patients with incurable diseases. This patient group is vulnerable due to the underlying illness, prior treatment and comorbidities, which increase the risk of complications that can negatively impact the course of the disease and quality of life. Palliative surgical interventions often provide effective long-term symptom control but are more invasive than conservative, interventional endoscopic or interventional radiological alternatives.

[Influencing fracture healing by specific osteoporosis medications].

Background: Osteoporosis is a widespread disease defined by a reduction in bone mass and structure, thereby increasing the risk of fragility fractures. Treatment typically involves specific medications, which either inhibit bone resorption (antiresorptive) or stimulate bone formation (anabolic) and may potentially influence the healing of osteoporotic fractures. On the other hand, metabolic disorders, immune system dysfunctions or circulatory problems can impair fracture healing.