Fecal microbiota transplantation to prevent acute graft-versus-host disease: pre-planned interim analysis of donor effect.

Gut microbiota disruptions after allogeneic hematopoietic cell transplantation (alloHCT) are associated with increased risk of acute graft-versus-host disease (aGVHD). We designed a randomized, double-blind placebo-controlled trial to test whether healthy-donor fecal microbiota transplantation (FMT) early after alloHCT reduces the incidence of severe aGVHD. Here, we report the results from the single-arm run-in phase which identified the best of 3 stool donors for the randomized phase.

Topographic corneal changes in children with moderate to severe blepharokeratoconjunctivitis.

Purpose To determine the corneal topographic characteristics of children with blepharokeratoconjunctivitis (BKC), a chronic inflammatory ocular surface disease involving the lid margin, conjunctiva, and cornea. Methods The corneal topography of 21 children diagnosed with BKC between March 2008 and June 2019 at a single institution were reviewed retrospectively. Pachymetry and asymmetry indices were also analyzed.

High-affinity VNARs targeting human hemoglobin: Screening, stability and binding analysis.

Hemoglobin, composed of α- and β-chains, is essential for oxygen transport and is key in diagnosing and treating gastrointestinal and blood disorders. It also aids in detecting blood contamination and estimating transfusion volumes. Immunological methods, based on antigen-antibody interactions, are distinguished by their high sensitivity and accuracy.

Specific Rosetta-based protein-peptide prediction protocol allows the design of novel cholinesterase inhibitor peptides.

The search for novel cholinesterase inhibitors is essential for advancing treatments for neurodegenerative disorders such as Alzheimer's disease (AD). In this study, we employed the Rosetta pepspec module, originally developed for designing peptides targeting protein-protein interactions, to design de novo peptides targeting the peripheral aromatic site (PAS) of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). A total of nine peptides were designed for human AChE (hAChE), T.

Phage M198 and Its Therapeutic Potential.

The rapid worldwide spread of antibiotic resistance is quickly becoming an increasingly concerning problem for human healthcare. Non-antibiotic antibacterial agents are in high demand for many Gram-negative bacterial pathogens, including . -targeting phages are among the most promising alternative therapy options.

Monitoring M-Protein, Therapeutic Antibodies, and Polyclonal Antibodies in a Multiparametric Mass Spectrometry Assay Provides Insight into Therapy Response Kinetics in Patients with Multiple Myeloma.

Multiple Myeloma (MM) is a hematologic malignancy caused by clonally expanded plasma cells that produce a monoclonal immunoglobulin (M-protein), a personalized biomarker. Recently, we developed an ultra-sensitive mass spectrometry method to quantify minimal residual disease (MS-MRD) by targeting unique M-protein peptides. Therapeutic antibodies (t-Abs), key in MM treatment, often lead to deep and long-lasting responses.

Genetic Background of Macular Telangiectasia Type 2.

Macular telangiectasia type 2 (MacTel) is a slowly progressive macular disorder that is often diagnosed late due to the gradual onset of vision loss. Recent advances in diagnostic techniques have facilitated earlier detection and have shown that MacTel is more common than initially thought. The disease is genetically complex, and multiple variants contribute incrementally to the overall risk.

Cell Type Specific Suppression of Hyper-Recombination by Human RAD18 Is Linked to Proliferating Cell Nuclear Antigen K164 Ubiquitination.

RAD18 is a conserved eukaryotic E3 ubiquitin ligase that promotes genome stability through multiple pathways. One of these is gap-filling DNA synthesis at active replication forks and in post-replicative DNA. RAD18 also regulates homologous recombination (HR) repair of DNA breaks; however, the current literature describing the contribution of RAD18 to HR in mammalian systems has not reached a consensus.

Detection and Characterization of Circulating Tumor Cells in Colorectal Cancer Patients via Epithelial-Mesenchymal Transition Markers.

Liquid biopsy methods have gained prominence as minimally invasive tools to improve cancer treatment outcomes. Circulating tumor cells (CTCs) offer valuable insights into both primary and metastatic lesions. However, validating the CTC test results requires confirmation that the detected cells originate from cancer tissue.

Evolving Trends and Patterns of Utilization of Magnetic Resonance-Guided Radiotherapy at a Single Institution, 2018-2024.

: Over the past decade, significant advances have been made in image-guided radiotherapy (RT) particularly with the introduction of magnetic resonance (MR)-guided radiotherapy (MRgRT). However, the optimal clinical applications of MRgRT are still evolving. The intent of this analysis was to describe our institutional MRgRT utilization patterns and evolution therein, specifically as an early adopter within a center endowed with multiple other technology platforms.

Relationship Between Myocardial Strain and Extracellular Volume: Exploratory Study in Patients with Severe Aortic Stenosis Undergoing Photon-Counting Detector CT.

: Diffuse myocardial fibrosis and altered deformation are relevant prognostic factors in aortic stenosis (AS) patients. The aim of this exploratory study was to investigate the relationship between myocardial strain, and myocardial extracellular volume (ECV) in patients with severe AS with a photon-counting detector (PCD)-CT. : We retrospectively included 77 patients with severe AS undergoing PCD-CT imaging for transcatheter aortic valve replacement (TAVR) planning between January 2022 and May 2024 with a protocol including a non-contrast cardiac scan, an ECG-gated helical coronary CT angiography (CCTA), and a cardiac late enhancement scan.

Synthetic transcription factors establish the function of nine amino acid transactivation domains of Komagataella phaffii Mxr1.

The zinc finger transcription factor Mxr1 (methanol expression regulator 1) of the methylotrophic yeast Komagataella phaffii (formerly Pichia pastoris) harbors a DNA-binding domain (DBD) consisting of two CH zinc fingers (Mxr1ZF) between amino acids 36-101 and a previously identified nine amino acid transactivation domain (9aaTAD) between residues 365-373 (TAD A, QELESSLNA). Beyond this, 21 putative 9aaTADs (designated TAD B-V) located between amino acids 401-1155 remain to be characterized. Here, we demonstrate that a compact synthetic transcription factor composed of Mxr1ZF and three tandem copies of TAD A can activate the transcription of Mxr1 target genes for ethanol and methanol metabolism with specificity and efficiency comparable to the full-length protein.

Designed mosaic nanoparticles enhance cross-reactive immune responses in mice.

Nanoparticle vaccines displaying combinations of SARS-like betacoronavirus (sarbecovirus) receptor-binding domains (RBDs) could protect against SARS-CoV-2 variants and spillover of zoonotic sarbecoviruses into humans. Using a computational approach, we designed variants of SARS-CoV-2 RBDs and selected 7 natural sarbecovirus RBDs, each predicted to fold properly and abrogate antibody responses to variable epitopes. RBDs were attached to 60-mer nanoparticles to make immunogens displaying two (mosaic-2s), five (mosaic-5), or seven (mosaic-7) different RBDs for comparisons with mosaic-8b, which elicited cross-reactive antibodies and protected animals from sarbecovirus challenges.

The role of non-respiratory arousals in residual daytime sleepiness in patients with obstructive sleep apnea treated with positive airway pressure: An analysis of the European Sleep Apnea Database registry.

Study Objectives: To assess the impact of the non-respiratory arousal burden at baseline polysomnography (PSG) on residual daytime sleepiness in positive airway pressure (PAP)-treated obstructive sleep apnea (OSA).

Methods: We included OSA patients from the European Sleep Apnea Database registry with available arousal data who had at least 2 treatment follow-up visits. The primary outcome was the Epworth Sleepiness Scale (ESS) score under PAP.

A C4 plant K+ channel accelerates stomata to enhance C3 photosynthesis and water use efficiency.

Accelerating stomatal kinetics through synthetic optogenetics and mutations that enhance guard cell K+ flux has proven a viable strategy to improve water use efficiency and biomass production. Stomata of the model C4 species Gynandropsis gynandra, a relative of the C3 plant Arabidopsis thaliana, are similarly fast to open and close. We identified and cloned the guard cell rectifying outward K+ channel (GROK) of Gynandropsis and showed that GROK is preferentially expressed in stomatal guard cells.

Diverse and highly differentiated lava suite in Jezero crater, Mars: Constraints on intracrustal magmatism revealed by Mars 2020 PIXL.

The Jezero crater floor features a suite of related, iron-rich lavas that were examined and sampled by the Mars 2020 rover Perseverance, and whose textures, minerals, and compositions were characterized by the Planetary Instrument for X-ray Lithochemistry (PIXL). This suite, known as the Máaz formation (fm), includes dark-toned basaltic/trachy-basaltic rocks with intergrown pyroxene, plagioclase feldspar, and altered olivine and overlying trachy-andesitic lava with reversely zoned plagioclase phenocrysts in a K-rich groundmass. Feldspar thermal disequilibrium textures indicate that they were carried from their crustal staging area.

Structure-guided engineering of a mutation-tolerant inhibitor peptide against variable SARS-CoV-2 spikes.

Pathogen mutations present an inevitable and challenging problem for therapeutics and the development of mutation-tolerant anti-infective drugs to strengthen global health and combat evolving pathogens is urgently needed. While spike proteins on viral surfaces are attractive targets for preventing viral entry, they mutate frequently, making it difficult to develop effective therapeutics. Here, we used a structure-guided strategy to engineer an inhibitor peptide against the SARS-CoV-2 spike, called CeSPIACE, with mutation-tolerant and potent binding ability against all variants to enhance affinity for the invariant architecture of the receptor-binding domain (RBD).

Double bowtie design for high sensitivity pediatric spectral CT.

Despite the evident benefits of spectral computed tomography (CT) in delivering qualitative imaging superior to that of conventional CT in adults, its application in pediatric diagnostic imaging is still relatively limited due to various reasons, including design limitations and radiation dose considerations. The use of specialized K-edge filters, in conjunction with other spectral technologies, has been demonstrated to improve spectral quantification accuracy. X-ray flux limitations generally pose challenges in these concepts when applied to adults.

Enhancing diagnostic accuracy in breast cancer: integrating novel machine learning approaches with enhanced image preprocessing for improved mammography analysis.

Purpose: This study explored the use of computer-aided diagnosis (CAD) systems to enhance mammography image quality and identify potentially suspicious areas, because mammography is the primary method for breast cancer screening. The primary aim was to find the best combination of preprocessing algorithms to enable more precise classification and interpretation of mammography images because the selected preprocessing algorithms significantly impact the effectiveness of later classification and segmentation processes.

Material And Methods: The study utilised the mini-MIAS database of mammography images and examined the impact of applying various preprocessing method combinations to differentiate between malignant and benign breast lesions.

Long-term Clinical Outcomes After Syndesmosis Fixation With K-wires in Ankle Fractures With Syndesmotic Instability.

Background: Syndesmotic instability is a significant concern in the management of unstable ankle fractures, occurring in approximately 10% to 13% of these cases. Early recognition and stabilization of syndesmotic injuries are essential to ensure optimal long-term outcomes. Several techniques are currently in use, often involving complex procedure and/or costly devices.

Assessing tick attachments to humans with citizen science data: spatio-temporal mapping in Switzerland from 2015 to 2021 using spatialMaxent.

Background: Ticks are the primary vectors of numerous zoonotic pathogens, transmitting more pathogens than any other blood-feeding arthropod. In the northern hemisphere, tick-borne disease cases in humans, such as Lyme borreliosis and tick-borne encephalitis, have risen in recent years, and are a significant burden on public healthcare systems. The spread of these diseases is further reinforced by climate change, which leads to expanding tick habitats.

An interactive course program on nutrition for medical students: interdisciplinary development and mixed-methods evaluation.

Nutrition plays a crucial role in human and planetary health, as prevailing nutritional patterns significantly contribute to the global non-communicable disease pandemic. Moreover, the global food system is inextricably linked to planetary health deterioration. The relevance of nutrition for individual and planetary health is insufficiently addressed in German medical schools.

High throughput cell stiffness measurement via multiplexed impedance sensors.

Since physiological and pathological events change the mechanical properties of cells, tools that rapidly quantify such changes at the single-cell level can advance the utility of cell mechanics as a label-free biomarker. We demonstrate the capability to probe the population-level elastic modulus and fluidity of MDA-MB-231 cells at a throughput of up to 50 cell/second within a portable microchip. Our sensing scheme adapts a code multiplexing scheme to implement a distributed network of sensors throughout the microchip, thereby compressing all sensing events into a single electrical output.

Mn-Mn Dimers Induced Multimode Emitters in Mn-Activated AZn(PO) (A = K, Rb, and Cs) with Unique [ZnPO] Chains and [ZnO] Groups.

Mn-doped luminescent materials play a significant role in a variety of fields, including modern lighting, displays, and imaging. Mn exhibits a broad and adjustable emission, hinging on the local environment of the crystal field and the interaction of the 3d electrons. However, it is still a challenge to realize the precise control of the emission of Mn ions due to site-prior occupation in a specific lattice.