Brolucizumab and Platelet Activation and Reactivity.

Purpose: This study explores the potential interaction of brolucizumab with platelets and its effects on platelet activation and reactivity, crucial in retinal vasculitis and retinal vascular occlusion. Safety concerns remain of interest, although brolucizumab showed superior retinal efficacy and reduced injection frequency compared to other licensed anti-VEGF agents.

Methods: Resting and activated platelets of healthy volunteers were pretreated with brolucizumab at the following concentrations 0.

Genome-wide CRISPR-Cas 9 screens identify BCL family members as modulators of response to regorafenib in experimental glioma.

Background: Registered systemic treatment options for glioblastoma patients are limited. The phase II REGOMA trial suggested an improvement of median overall survival in progressive glioblastoma by the multi-tyrosine kinase inhibitor regorafenib. This has not been confirmed by GBM AGILE.

Electrical impedance-based tissue classification for bladder tumor differentiation.

Including sensor information in medical interventions aims to support surgeons to decide on subsequent action steps by characterizing tissue intraoperatively. With bladder cancer, an important issue is tumor recurrence because of failure to remove the entire tumor. Impedance measurements can help to classify bladder tissue and give the surgeons an indication on how much tissue to remove.

Do perilunate dislocations and fracture-dislocations result in different radiological outcomes following wrist alignment reconstruction? A single-center retrospective study including 51 patients with perilunate injuries.

Introduction: Perilunate dislocations (PLD) and perilunate fracture-dislocations (PLFD) are high-energy wrist injuries often linked to significant post-traumatic osteoarthritis. This study aims to determine whether PLD and PLFD yield different radiological outcomes following surgical treatment while identifying prognostic factors for worse outcomes.

Materials And Methods: We retrospectively analyzed 51 patients treated for perilunate injuries between 2000 and 2022.

RAGE is a key regulator of ductular reaction-mediated fibrosis during cholestasis.

Ductular reaction (DR) is the hallmark of cholestatic diseases manifested in the proliferation of bile ductules lined by biliary epithelial cells (BECs). It is commonly associated with an increased risk of fibrosis and liver failure. The receptor for advanced glycation end products (RAGE) was identified as a critical mediator of DR during chronic injury.

Proteomic and Metabolomic Signatures in Prediabetes Progressing to Diabetes or Reversing to Normoglycemia Within 1 Year.

Objective: Progression of prediabetes to type 2 diabetes has been associated with β-cell dysfunction, whereas its remission to normoglycemia has been related to improvement of insulin sensitivity. To understand the mechanisms and identify potential biomarkers related to prediabetes trajectories, we compared the proteomics and metabolomics profile of people with prediabetes progressing to diabetes or reversing to normoglycemia within 1 year.

Research Design And Methods: The fasting plasma concentrations of 1,389 proteins and the fasting, 30-min, and 120-min post-oral glucose tolerance test (OGTT) plasma concentrations of 152 metabolites were measured in up to 134 individuals with new-onset diabetes, prediabetes, or normal glucose tolerance.

Subphenotypes of body composition and their association with cardiometabolic risk - Magnetic resonance imaging in a population-based sample.

Background: For characterizing health states, fat distribution is more informative than overall body size. We used population-based whole-body magnetic resonance imaging (MRI) to identify distinct body composition subphenotypes and characterize associations with cardiovascular disease (CVD) risk.

Methods: Bone marrow, visceral, subcutaneous, cardiac, renal, hepatic, skeletal muscle and pancreatic adipose tissue were measured by MRI in n = 299 individuals from the population-based KORA cohort.

In-depth analysis of serum antibodies against Epstein-Barr virus lifecycle proteins, and EBNA1, ANO2, GlialCAM and CRYAB peptides in patients with multiple sclerosis.

Background: A strong association between multiple sclerosis (MS) and Epstein-Barr virus (EBV) has been established but the exact role of EBV in MS remains controversial. Recently, molecular mimicry between EBNA1 and specific GlialCAM, CRYAB and ANO2 peptides has been suggested as a possible pathophysiological mechanism. The aim of this study was to analyse anti-EBV antibodies in MS patients against (I) EBV lifecycle proteins, (II) putative cross-reactive peptides, and (III) during treatment.

Parasitic infections during pregnancy in Gabon affect glycosylation patterns of maternal and child antibodies.

Antibody glycosylation patterns can affect antibody functionality and thereby contribute to protection against invading pathogens. During pregnancy, maternal antibodies can be transferred through the placenta and contribute to modulating both the mother's and her child's immune responses. Although several studies of IgG glycosylation during pregnancy have been carried out, very few cohorts studied were from sub-Saharan Africa, where exposure to microorganisms and parasites is high.

Genome sequencing of Plasmodium malariae identifies continental segregation and mutations associated with reduced pyrimethamine susceptibility.

Plasmodium malariae parasites are widely observed across the tropics and sub-tropics. This slow-growing species, known to maintain chronic asymptomatic infections, has been associated with reduced antimalarial susceptibility. We analyse 251 P.

COVID-19 and social distancing: pandemic has altered social relationships and contacts in older adults over 4 years.

Introduction: Social isolation is a main risk factor for loneliness, health issues and psychological diseases. With its restriction measures, the coronavirus pandemic has led to an objective reduction in meaningful interactions, communication, and social contacts in general (social isolation). However, it has been shown that older adults cope differently with social isolation.

Spongy-looking microfabrics in the earliest named stromatolite represent deep burial alteration and incipient metamorphism.

The earliest named stromatolite Cryptozoon Hall, 1884 (Late Cambrian, ca. 490 Ma, eastern New York State), was recently re-interpreted as an interlayered microbial mat and non-spiculate (keratosan) sponge deposit. This "classic stromatolite" is prominent in a fundamental debate concerning the significance or even existence of non-spiculate sponges in carbonate rocks from the Neoproterozoic (Tonian) onwards.

UV Hyperspectral Imaging with Xenon and Deuterium Light Sources: Integrating PCA and Neural Networks for Analysis of Different Raw Cotton Types.

Ultraviolet (UV) hyperspectral imaging shows significant promise for the classification and quality assessment of raw cotton, a key material in the textile industry. This study evaluates the efficacy of UV hyperspectral imaging (225-408 nm) using two different light sources: xenon arc (XBO) and deuterium lamps, in comparison to NIR hyperspectral imaging. The aim is to determine which light source provides better differentiation between cotton types in UV hyperspectral imaging, as each interacts differently with the materials, potentially affecting imaging quality and classification accuracy.

Impact of Particle Size and Sintering Temperature on Calcium Phosphate Gyroid Structure Scaffolds for Bone Tissue Engineering.

Due to the chemical composition and structure of the target tissue, autologous bone grafting remains the gold standard for orthopedic applications worldwide. However, ongoing advancements in alternative grafting materials show that 3D-printed synthetic biomaterials offer many advantages. For instance, they provide high availability, have low clinical limitations, and can be designed with a chemical composition and structure comparable to the target tissue.

Standardized Response Assessment in Patients with Advanced Cholangiocarcinoma Treated with Personalized Therapy.

: Current guidelines recommend Cisplatin/Gemcitabine/Durvalumab as first-line treatment for inoperable or recurrent cholangiocarcinoma (CCA). Molecular tumor boards (MTB) have the expertise to support organ-specific tumor boards with evidence-based treatment recommendations for subsequent lines of treatment, based on genomic tumor data and scientific evidence. This study evaluates the adoption of an MTB at a comprehensive cancer center in Germany and whether actionable genetic alterations are associated with specific imaging phenotypes.

PSA testing in primary care: is it time to change our practice?

Background: Historical prostate-specific antigen (PSA)-based screening studies reduced prostate cancer-related deaths but also led to overdiagnosis/overtreatment. Since then, opportunistic PSA testing has increased, and late-stage diagnoses and prostate-cancer related deaths are rising.

Objectives: To review current trends regarding PSA testing in primary care and propose a collaborative approach to improve early prostate cancer detection.

TKK130 is a 3-Hydroxy-Propanamidine (HPA) with Potent Antimalarial Activity and a High Barrier to Resistance.

Malaria continues to pose a significant burden on populations in endemic areas and requires innovative treatment options. Here, we report the synthesis and preclinical evaluation of the novel 3-hydroxypropanamidine (HPA) , which shows excellent antiplasmodial activity against drug-sensitive and -resistant strains. Moreover, in various human cell lines, the compound shows no cytotoxicity and excellent parasite selectivity.

RNA modifications in plant biotic interactions.

The chemical modification of DNA and proteins is an efficient way of regulating molecular and biological function and affects a plethora of signalling pathways in eukaryotes. Similarly, recent progress in epitranscriptomics shows that RNA modifications also play crucial roles in diverse biological processes. Since their discovery in the 1970s, scientists have attempted to decipher the identity and functions of these modifications in different biological systems.

Heterotopic ossification following severe radial head fractures: Clinical outcome and associated factors.

Objectives: This study aimed to evaluate clinical outcome, prevalence, severity, location, range of motion, and possible risk factors of heterotopic ossification (HO) following severe radial head fractures.

Patients And Methods: In this retrospective study, 73 patients (40 males, 33 females; mean age: 51.4±15 years; range, 20 to 82 years) with Mason-Johnston type 3 and 4 radial head fractures were surgically treated with osteosynthesis or radial head arthroplasty (RHA) between September 2014 and February 2021.

Surprise Baby: Abdominoplasty Performed During Unknown Pregnancy.

Abdominoplasty is a commonly performed procedure for patients after significant weight loss and in postpregnancy women. Stable weight and completed family planning are critical for optimal outcomes, as pregnancy postabdominoplasty can increase risks for both mother and fetus and potentially compromise aesthetic results. We present the first reported case of a patient undergoing abdominoplasty while unknowingly pregnant.

Multidisciplinary quantitative and qualitative assessment of IDH-mutant gliomas with full diagnostic deep learning image reconstruction.

Unlabelled: Diagnostic accuracy and therapeutic decision-making for IDH-mutant gliomas in tumor board reviews are based on MRI and multidisciplinary interactions.

Materials And Methods: This study explores the feasibility of deep learning-based reconstruction (DLR) in MRI for IDH-mutant gliomas. The research utilizes a multidisciplinary approach, engaging neuroradiologists, neurosurgeons, neuro-oncologists, and radiotherapists to evaluate qualitative aspects of DLR and conventional reconstructed (CR) sequences.

Probing the Protein Kinases' Cysteinome by Covalent Fragments.

Protein kinases are important drug targets, yet specific inhibitors have been developed for only a fraction of the more than 500 human kinases. A major challenge in designing inhibitors for highly related kinases is selectivity. Unlike their non-covalent counterparts, covalent inhibitors offer the advantage of selectively targeting structurally similar kinases by modifying specific protein side chains, particularly non-conserved cysteines.

How crosstalk between mitochondria, lysosomes, and other organelles can prevent or promote dry age-related macular degeneration.

Organelles such as mitochondria, lysosomes, peroxisomes, and the endoplasmic reticulum form highly dynamic cellular networks and exchange information through sites of physical contact. While each organelle performs unique functions, this inter-organelle crosstalk helps maintain cell homeostasis. Age-related macular degeneration (AMD) is a devastating blinding disease strongly associated with mitochondrial dysfunction, oxidative stress, and decreased clearance of cellular debris in the retinal pigment epithelium (RPE).

Automated total nucleic acid extraction with magnetic beads for the detection of Plasmodium falciparum in large study cohorts.

Background: Molecular methods play an important role in clinical trials assessing anti-malarial drugs and vaccines, as well as in epidemiological studies aimed at detecting Plasmodium species, especially when dealing with large sample sizes. Molecular techniques are more sensitive and generally have a higher throughput compared to the gold standard microscopy. Further optimization can be achieved with automation of nucleic acid isolation, allowing for rapid and precise extraction.