Molecular Insights into α-Synuclein Fibrillation: A Raman Spectroscopy and Machine Learning Approach.

The aggregation of α-synuclein is crucial to the development of Lewy body diseases, including Parkinson's disease and dementia with Lewy bodies. The aggregation pathway of α-synuclein typically involves a defined sequence of nucleation, elongation, and secondary nucleation, exhibiting prion-like spreading. This study employed Raman spectroscopy and machine learning analysis, alongside complementary techniques, to characterize the biomolecular changes during the fibrillation of purified recombinant wild-type α-synuclein protein.

Low Temperature Atomic Layer Deposition of (00l)-Oriented Elemental Bismuth.

This study presents the first successful demonstration of growing elemental bismuth (Bi) thin films via thermal atomic layer deposition (ALD) using Bi(NMe2)3 as the precursor and Sb(SiMe3)3 as the co-reactant. The films were deposited at a relatively low temperature of 100 °C, with a growth per cycle (GPC) of 0.31-0.

Dysregulation of deubiquitinylases: a linchpin of gastrointestinal diseases.

Ubiquitinylation of proteins regulates manifold processes and is reversed by deubiquitinylating enzymes (DUBs), which are therefore implicated in a plethora of cellular processes. DUBs are frequently upregulated in many diseases, while in a few cases downregulation of DUBs is associated with disease progression. This review focuses on the involvement of DUBs in the development and progression of gastrointestinal diseases with a particular emphasis on hepatic steatosis and hepatocellular, cholangio-, esophageal, gastric, colorectal, and pancreatic ductal carcinomas.

Overcoming the technical challenge of venous resection with pancreatectomy: Which factors determine survival?

Background: Pancreatectomy with venous resection (PVR) is nowadays considered standard. However, there is still concern about increased postoperative morbidity and impaired long-term outcome depending on the type of venous resection and reconstruction. The aim was to investigate the predictors of morbidity and long-term survival in patients undergoing PVR in a high-volume center.

Impact of segment length on bony changes following microvascular jaw reconstruction using virtually planned fibula flaps - A retrospective study.

Postoperative bone resorption within the first year after a free fibular flap is a common problem and poses major challenges for subsequent therapies. Due to the concerns of increased bone resorption, short segments in particular, i.e.

Skeletal Editing through Cycloaddition and Subsequent Cycloreversion Reactions.

ConspectusSkeletal editing, which involves adding, deleting, or substituting single or multiple atoms within ring systems, has emerged as a transformative approach in modern synthetic chemistry. This innovative strategy addresses the ever-present demand for developing new drugs and advanced materials by enabling precise modifications of molecular frameworks without disrupting essential functional complexities. Ideally performed at late stages of synthesis, skeletal editing minimizes the need for the cost- and labor-intensive processes often associated with synthesis, thus accelerating the discovery and optimization of complex molecular architectures.

[Legal requirements for information and their influence on patient satisfaction].

The German Patientenrechtegesetz defines, among other things, medical obligations in connection with the provision of information. To date, the extent to which these legal requirements also influence patient satisfaction with information has not been investigated in Germany.The study employed an anonymized patient survey on satisfaction with information, which was recorded using a validated 10-item questionnaire.

[Gender-/Sex-Specific Differences in Clinical Trials in Uro-Oncology].

Subgroup analyses in clinical trials sometimes reveal gender-/sex-dependent differences in cancer outcomes. However, drug approvals are rarely restricted to a specific sex or gender, and recommendations regarding dosage are rarely tailored accordingly. Furthermore, discrepancies exist between the gender-/sex-dependent enrollment rates in clinical trials and real-world incidence or mortality rates.

[Bimodal and multimodal endoscopy of the urinary bladder in diagnosis and treatment].

White light cystoscopy is a precise instrument for the detection and treatment of papillary bladder tumors. Various additional macroscopic detection methods have been established. Some of them, especially PDD or NBI, have been shown to have an additional benefit on the recurrence rate of bladder tumors, so they should be used as part of the diagnosis and treatment when available.

Docking Structures Induced by Substitution Motifs of Softwood Xylan at Various Cellulose Surfaces.

To understand xylan-cellulose interactions in softwood, the adsorption behavior of hexameric softwood xylan proxies with various substitutions was analyzed on the three surfaces of a hexagonal cellulose microfibril. The study found that all surfaces could bind xylan motifs, showing equally high affinity for the hydrophilic (110) and hydrophobic (100) surfaces and significantly lower affinity for the hydrophilic (11̅0) surface. Unsubstituted xylose hexamers had the highest affinity and most ordered adsorption structures, while substitutions generally reduced the affinity and regularity.

Visual and Orthoptic Development After DSAEK for CHED in Children Younger than 8 years: Case Series and Literature Review.

Purpose: Congenital hereditary endothelial dystrophy (CHED) impairs the sensitive phase of visual development. We examined results of Descemet stripping automated endothelial keratoplasty (DSAEK) for CHED regarding the critical period for amblyogenic factors.

Methods: Retrospective analysis of 11 eyes of 6 consecutive patients with CHED younger than 8 years treated with DSAEK and a PubMed-based literature search on management and optimal timing of the intervention.

Trace elements increase replicability of microbial growth.

Trace elements are often omitted from chemically defined growth media. From established properties of trace elements, we deduce that this omission makes experiments unnecessarily sensitive to unavoidable contamination with trace elements. We confirm this experimentally by growing 11 bacterial strains in high replicate with and without supplementing trace elements, keeping all other conditions as fixed as possible to isolate the effect of trace elements.

Formulation screening of lyophilized mRNA-lipid nanoparticles.

Lipid nanoparticles (LNPs) have demonstrated their therapeutic potential as safe and effective drug delivery systems for nucleic acids during the COVID-19 pandemic. However, one of the main challenges during technical CMC (Chemistry, Manufacturing, and Controls) development is their long-term stability at temperatures of 2-8 °C or higher, which may be improved by the removal of water by lyophilization. In this study, we identified lyo-/cryo-protectants for freeze-dried mRNA-LNP formulations beyond conventional excipients such as sucrose and trehalose as T-modifiers using polyA as a surrogate.

A comprehensive report of the clinical and mutational profiles of 30 Iranian malignant infantile osteopetrosis patients.

Osteopetrosis is a group of genetically and clinically diverse inherited disorders characterized by an increase in bone density. The main known cause is an abnormality in the development or function of osteoclasts. Hence, the process of bone resorption is impaired, resulting in: 1- a reduction in bone marrow volume and, subsequently, a decrement in the hematopoietic capacity of bone marrow, which leads to anemia and compromised immunological function; 2- improper bone development, which leads to pressure on peripheral nerves, causing auditory, visual, and movement impairments; and 3- disturbance in the formation of bone microstructure that leads to susceptibility to bone fracture.

Evaluation of stabilizing additives to protect activities of cytochrome P450 enzymes for in vitro drug testing and pharmacogenetic studies: Focus on CYP2D6.

In vitro and ex vivo studies on drug metabolism and stability are vital for drug development and pre-clinical safety assessment. Traditional in vitro models, such as liver enzyme (S9) fractions and microsomes, often fail to account for individual variability. Personalized models, including 3D cell models and organoids, offer promising alternatives but may not fully replicate physiological processes, especially for Cytochrome P450 (CYP) families involved in extrahepatic metabolism.

Investigating the Multigenerational Effects of DDT Residues Exposure on Dental Development in Wistar Rats.

The pesticide Dichlorodiphenyltrichloroethane (DDT) and its degradation by-products (Dichlorodiphenyldichloroethane-DDD and dichlorodiphenyldichloroethylene-DDE) are health concerns. This study aimed to investigate the impact of multigenerational exposure to traces of DDD and DDE on odontogenesis Wistar rats were allocated in 4 groups over 2 generations (F1 and F2). Water was provided ad libitum throughout the animal's life groups: control - natural water; DDD - 0.

Nivolumab plus ipilimumab versus nivolumab in microsatellite instability-high metastatic colorectal cancer (CheckMate 8HW): a randomised, open-label, phase 3 trial.

Background: CheckMate 8HW prespecified dual primary endpoints, assessed in patients with centrally confirmed microsatellite instability-high or mismatch repair-deficient status: progression-free survival with nivolumab plus ipilimumab compared with chemotherapy as first-line therapy and progression-free survival with nivolumab plus ipilimumab compared with nivolumab alone, regardless of previous systemic treatment for metastatic disease. In our previous report, nivolumab plus ipilimumab showed superior progression-free survival versus chemotherapy in first-line microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer in the CheckMate 8HW trial. Here, we report results from the prespecified interim analysis for the other primary endpoint of progression-free survival for nivolumab plus ipilimumab versus nivolumab across all treatment lines.

Chromosome-scale genome assembly reveals how repeat elements shape non-coding RNA landscapes active during newt limb regeneration.

Newts have large genomes harboring many repeat elements. How these elements shape the genome and relate to newts' unique regeneration ability remains unknown. We present here the chromosome-scale assembly of the 20.

VAE-Surv: A novel approach for genetic-based clustering and prognosis prediction in myelodysplastic syndromes.

Background And Objectives: Several computational pipelines for biomedical data have been proposed to stratify patients and to predict their prognosis through survival analysis. However, these analyses are usually performed independently, without integrating the information derived from each of them. Clustering of survival data is an underexplored problem, and current approaches are limited for biomedical applications, whose data are usually heterogeneous and multimodal, with poor scalability for high-dimensionality.

Clinical outcomes and management following progressive disease with anti-PD-(L)1 therapy in patients with advanced Merkel Cell Carcinoma.

Aim: Merkel Cell Carcinoma (MCC) is a rare skin cancer with a rising incidence worldwide. Anti-programmed death-1/ligand-1 (anti-PD-(L)1) therapies are effective for the treatment of advanced MCC. This study examines patterns of response / progression of advanced MCC to anti-PD-(L)1 therapies and describes subsequent management.

Cancer-specific utility instrument for health economic evaluations: A synopsis of the EORTC QLU-C10D user manual and current validity evidence.

The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Utility - Core 10 Dimensions (QLU-C10D) adds a preference-based scoring algorithm to the EORTC measurement portfolio. It is built on the most widely used health-related quality of life (HRQoL) measure in oncology, the EORTC Quality of Life Questionnaire - Core 30 (QLQ-C30), allowing for the calculation of both HRQoL profiles and health utilities. This is an important advancement for integrating cancer-specific values into health economic evaluations and decision making, offering greater content validity and statistical power than some generic measures.

Non-comparability and unplannability as material topoi in antenatal care conversations.

Objective: This paper studies argumentation and its function to establish common ground in pregnancy counseling conversations during the third trimester of the pregnancy, focusing on two material topoi: Non-comparability and Unplannability.

Methods: We take a conversation-analytical and interactional approach and draw on 37 natural occurring counseling conversations, videorecorded during two periods at a university hospital. The conversations are typically between the midwife and the pregnant woman.

Freshwater browning as a hidden threat - Transcriptomic responses in fish gills exposed to fulvic acid.

Human activities and climate change have significantly increased humic substances in freshwater ecosystems over the last few decades. This increase is particularly concerning during seasonal changes or after heavy rainfall, when concentrations can easily increase up to tenfold. This phenomenon, known as "browning," has unknown consequences for aquatic organisms.