Development of a StIW111C-based bioresponsive pore-forming conjugate for permeabilizing the endosomal membrane.

Gene expression manipulation is pivotal in therapeutic approaches for various diseases. Non-viral delivery systems present a safer alternative to viral vectors, with reduced immunogenicity and toxicity. However, their effectiveness in promoting endosomal escape, a crucial step in gene transfer, remains limited.

Gene expression dynamics in fibroblasts during early-stage murine pancreatic carcinogenesis.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by aggressive growth and metastasis, partly driven by fibroblast-mediated stromal interactions. Using RNA sequencing of fibroblasts from early-stage KPC mouse models, we identified significant upregulation of genes involved in adipogenesis, fatty acid metabolism, and the ROS pathway. ANGPTL4, a key adipogenesis regulator, was highly expressed in fibroblasts and promoted pancreatic cancer cell proliferation and migration through paracrine signaling.

Nerve transfer of the median flexor pollicis brevis branch to the deep branch of the ulnar nerve for ulnar nerve palsy: a cadaveric feasibility study.

An ulnar nerve (UN) palsy is devastating for hand function, resulting in an intrinsic minus position or claw hand with a loss of pinch grip. Distal nerve transfers facilitate faster reinnervation of hand intrinsic muscles in cases of proximal ulnar nerve lesions. The traditional anterior interosseous nerve (AIN) to UN motor transfer is commonly used, however, this still leads to long reinnervation times for the distal intrinsic muscles, important for the thumb to index pinch grip.

Informal care for people with dementia in Europe.

Introduction: Informal care estimates for use in health-economic models are lacking. We aimed to estimate the association between informal care time and dementia symptoms across Europe.

Methods: A secondary analysis was performed on 13,529 observations in 5,369 persons from 9 European pooled cohort or trial studies in community-dwelling persons with dementia.

Skin Physiological Parameters and Their Association with Severe Atopic Dermatitis in Mongolian Children.

: Atopic dermatitis (AD) is a chronic skin condition that weakens the skin barrier, leading to increased trans-epidermal water loss and reduced skin moisture. Understanding how these changes in the skin barrier relate to AD severity in Mongolian children may offer insights that could apply to other regions facing similar environmental challenges. : A cross-sectional study was conducted at the National Dermatology Center of Mongolia, involving 103 children with AD.

Robot-assisted Kidney Transplantation: The 8-year European Experience.

Background And Objective: Evidence regarding perioperative results and long-term functional outcomes of robotic-assisted kidney transplantation (RAKT) is limited. We evaluated perioperative surgical results and long-term functional outcomes of RAKT in patients receiving kidney transplants from living donors.

Methods: This retrospective analysis is based on a prospective multicenter cohort study conducted from July 2015 to October 2023 across ten European centers.

Management of acute myocardial infarction in chronic kidney disease in Germany: an observational study.

Background: Managing acute myocardial infarction (AMI) in patients with chronic kidney disease (CKD) or end-stage renal disease on dialysis (renal replacement therapy, RRT) presents challenges due to elevated complication risks. Concerns about contrast-related kidney damage may lead to the omission of guideline-directed therapies like percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) in this population.

Methods: We analysed German-DRG data of 2016 provided by the German Federal Bureau of Statistics (DESTATIS).

Neural network surrogate and projected gradient descent for fast and reliable finite element model calibration: A case study on an intervertebral disc.

Accurate calibration of finite element (FE) models is essential across various biomechanical applications, including human intervertebral discs (IVDs), to ensure their reliability and use in diagnosing and planning treatments. However, traditional calibration methods are computationally intensive, requiring iterative, derivative-free optimization algorithms that often take days to converge. This study addresses these challenges by introducing a novel, efficient, and effective calibration method demonstrated on a human L4-L5 IVD FE model as a case study using a neural network (NN) surrogate.

Activity and safety of avelumab in high-grade neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas progressive after chemotherapy (AveNEC trial).

Background: Neuroendocrine neoplasias grade 3 (NEN G3) are rare tumors with poor prognosis and no established second-line therapy. The role of immune checkpoint blockade in these aggressive tumors remains unclear.

Methods: The phase II AVENEC study evaluated the effect of avelumab (AVE, 10 mg/kg IV Q2W) in 60 patients with well-differentiated high-grade neuroendocrine tumors (NET G3, N=22) or poorly differentiated neuroendocrine carcinomas (NEC, N=38) progressing after ≥ one prior chemotherapy (excluding Merkel cell and small-cell lung cancer).

A novel prognostic risk model for patients with refractory/relapsed acute myeloid leukemia receiving venetoclax plus hypomethylating agents.

Off-label hypomethylating agents and venetoclax (HMA/VEN) are often used for relapsed and refractory (R/R) AML patients. However, predictors of outcome are elusive. The objective of the current retrospective observational multicenter study of 240 adult patients (median age 68.

Isolation of anti-inflammatory and cytotoxic secondary metabolites from Valeriana phu and evaluation of their mechanisms of action.

As a result of anti-inflammatory activity-guided fractionation, 16 secondary metabolites from the underground parts of Valeriana phu L. were obtained, including five new ones belonging to iridoid (1, 2, and 5), phenylpropanoid (6) and neolignan (7) chemical classes. Their structures were elucidated by 1D and 2D NMR analyses as well as HRESIMS.

Monitoring and modelling landscape structure, land use intensity and landscape change as drivers of water quality using remote sensing.

The interactions between landscape structure, land use intensity (LUI), climate change, and ecological processes significantly impact hydrological processes, affecting water quality. Monitoring these factors is crucial for understanding their influence on water quality. Remote sensing (RS) provides a continuous, standardized approach to capture landscape structures, LUI, and landscape changes over long-term time series.

Predicting fiber content in herbivore fecal samples using a multispecies NIRS model.

Fiber is essential for rumen health, microbial fermentation, and the energy supply of herbivores. Even though the study of fecal fiber contents (neutral detergent fiber NDF, acid detergent fiber ADF, and acid detergent lignin ADL) using near-infrared reflectance spectroscopy (NIRS) has allowed investigating nutritional ecology of different herbivore species, NIRS calibrations are species-specific and require a large number of samples for predictions. A multispecies calibration would be an advantage since samples from different herbivores could be used to calibrate a model capable of predicting the fecal fiber content of other herbivores.

Study protocol for key interventions to improve the follow-up adherence postcervical precancerous lesion treatment in Ethiopia: a pragmatic randomised controlled trial.

Introduction: The follow-up adherence after treatment for a positive screening test is critical for preventing the development of screen-detected abnormalities in cervical cancer. Yet, this poses a major challenge in developing countries like Ethiopia, emphasising the urgency for intervention strategies. Our trial aims to assess which strategies would be effective in improving adherence to follow-up after suspicious cervical lesion treatment in Ethiopia.

The magnitude of legal wildlife trade and implications for species survival.

The unsustainable use of wildlife is a primary driver of global biodiversity loss. No comprehensive global dataset exists on what species are in trade, their geographic origins, and trade's ultimate impacts, which limits our ability to sustainably manage trade. The United States is one of the world's largest importers of wildlife, with trade data compiled in the US Law Enforcement Management Information System (LEMIS).

Individual Pharmacotherapy Management (IPM-II) for Patient and Drug Safety in Polypharmacy via Clinical Electronic Health Record Is Associated with Significant Fall Prevention.

Background/objectives: Falls and fractures are emerging as a near-pandemic and major global health concern, placing an enormous burden on ageing patients and public health economies. Despite the high risk of polypharmacy in the elderly patients, falls are usually attributed to age-related changes. For the "Individual Pharmacotherapy Management (IPM)" established at the University Hospital Halle, the IPM medication adjustments and their association with in-hospital fall prevention were analysed.

Functional and Biological Characterization of the LGR5Δ5 Splice Variant in HEK293T Cells.

The regulator of the canonical Wnt pathway, leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), is expressed in the stem cell compartment of several tissues and overexpressed in different human carcinomas. The isoform of the stem cell marker LGR5, named LGR5Δ5 and first described by our group, is associated with prognosis and metastasis in oral squamous cell carcinoma (OSCC) and soft tissue sarcoma (STS). In a proof-of-principle analysis, the function of LGR5Δ5 was investigated in HEK293T cells, a model cell line of the Wnt pathway, compared to full-length LGR5 (FL) expression.

Oncological resection and perioperative outcomes of robotic, laparoscopic and open pancreatoduodenectomy for ampullary adenocarcinoma: a propensity score matched international multicenter cohort study.

Background: Ampullary adenocarcinoma (AAC) typically presents at an early stage due to biliary obstruction and therefore might be specifically suitable for minimally invasive pancreatoduodenectomy (MIPD). However, studies assessing MIPD specifically for AAC, including the robotic and laparoscopic approach, are limited. The aim of this study is to compare short- and long-term oncological resection and perioperative outcomes of robotic (RPD), laparoscopic (LPD) and open pancreatoduodenectomy (OPD) performed specifically for AAC.

Dormancy: Metabolite pools prime the cyanobacterial dormancy-resuscitation switch.

Non-N-fixing cyanobacteria enter a state of dormancy when fixed nitrogen becomes limiting. Resuscitation from this state involves a complex program of events. A new study reveals how the dormancy-resuscitation switch is governed by metabolite-level control of glucose-6-phosphate dehydrogenase activity.

Utilization and quality of primary and specialized palliative homecare in nursing home residents vs. community dwellers: a claims data analysis.

Background: There are hardly any data on the extent to which nursing home residents are provided with palliative homecare. We want to add evidence by comparing nursing home residents (who had been living in a nursing home for at least one year) and nursing-care-dependent community dwellers in terms of utilization and quality of palliative homecare.

Methods: We conducted a population-based study with nationwide claims data from deceased beneficiaries of a large German health insurance provider.

University students' health-related quality of life and its determinants. Results from a cross-sectional survey during the COVID-19 pandemic.

Being a university student is a vulnerable period marked by transitions and uncertainties which can impair their physical and mental well-being as well as overall quality of life. The existing literature suggests that certain groups of students might be particularly affected by that. In addition, quality of life might have been further affected by the COVID-19 pandemic.

Cost-effectiveness of a multicomponent intervention against cognitive decline.

Introduction: The societal costs of dementia and cognitive decline are substantial and likely to increase during the next decades due to the increasing number of people in older age groups. The aim of this multicenter cluster-randomized controlled trial was to assess the cost-effectiveness of a multi-domain intervention to prevent cognitive decline in older people who are at risk for dementia.

Methods: We used data from a multi-centric, two-armed, cluster-randomized controlled trial ( trial, ID: DRKS00013555).

Land Use Change Consistently Reduces α- But Not β- and γ-Diversity of Bees.

Land use change threatens global biodiversity and compromises ecosystem functions, including pollination and food production. Reduced taxonomic α-diversity is often reported under land use change, yet the impacts could be different at larger spatial scales (i.e.