Small molecule inhibition of ubiquitin C-terminal hydrolase L1 alters cell metabolism proteins and exerts anti- or pro-tumorigenic effects contingent upon chemosensitivity status in high grade serous ovarian cancer.

High grade serous ovarian cancer (HGSOC) is the most lethal of all gynecologic malignancies in which the majority of patients eventually develop chemoresistant recurrent disease. Ubiquitin C-terminal hydrolase L1 (UCHL1) is a deubiquitinating enzyme canonically known for its involvement in neurodegeneration, but recently has been shown to play a key role in tumorigenesis. Furthermore, UCHL1 has garnered attention across a multitude of cancer subtypes as it has the ability to be targeted through small molecule inhibition.

Low-level neurostimulation of the renal nerves as a potential therapeutic strategy for hypertension treatment.

Background: Neurostimulation is an emerging treatment for conditions like hypertension. The renal nerves, comprising sensory afferent and sympathetic efferent fibers, are crucial for blood pressure (BP) regulation. The inhibitory reno-renal reflex, where central integration of renal sensory input reduces sympathetic outflow and systemic BP, presents a promising target for neurostimulation interventions.

Clinical Outcomes of Intramedullary Kirschner Wire Fixation for Unstable Radius and Ulna Fractures in Children: A Prospective Study in Yemen.

Background: Forearm fractures are among the most common pediatric injuries, and unstable fractures often require surgical intervention. Intramedullary Kirchner wire (K-wire) fixation has emerged as a minimally invasive treatment option, offering advantages such as reduced soft tissue damage and shorter hospital stays. This study evaluated the clinical outcomes of K-wire fixation for unstable radius and ulna fractures in children.

Incidence of hypernatremia in dogs treated with single dose activated charcoal for acute toxicant ingestion: multi-center retrospective study (2018-2023).

Objective: To retrospectively evaluate the incidence and clinical significance of hypernatremia in dogs administered a single dose of activated charcoal (AC) or activated charcoal with sorbitol (ACS) for acute toxicant ingestion.

Methods: Retrospective study between the years 2018-2023. Ninety-six dogs evaluated by a university teaching hospital and private practice emergency hospital treated for acute toxicant ingestion with a single dose of activated charcoal, with or without sorbitol.

Spatial encoding and growth-related change of sheep lung radiomic features.

Introduction: Different regions of the small ruminant lung exhibit variable susceptibility to specific lung pathologies. Such susceptibility may be reflected in regional lung radiomic features extracted from computed tomography (CT) images. In this study, we investigated whether region-specific variation in radiomic features exists in ovine lungs and whether these features remain stable over time.

Dietary microalgae enriches eggs with carotenoids and long-chain omega-3 fatty acids, enhancing the antioxidant and immune responses in heat-stressed laying hens.

Introduction: (DS) is a prospective source of bioactive carotenoids, including beta-carotene, zeaxanthin, and omega-3 fatty acids. The effect of dietary supplementation of DS on the productive performance, immune response, and egg quality of heat-stressed laying hens has not been comprehensively studied. We investigated how dietary supplementation affects the deposition of bioactive carotenoids and omega-3 fatty acids in egg yolks of laying hens experiencing summer heat stress, as determined by the Temperature-Humidity Index (THI).

A non-randomized pilot study to test the feasibility of developing a frailty scale for pet cats.

Introduction: Human frailty has long been studied and dozens of "frailty scales" have been developed, but equivalent research is more limited in cats. This pilot study aimed to determine the feasibility of recruiting and retaining veterinary practices and owners, collecting study data, and analyzing results about frailty in older cats.

Methods: Participating feline-exclusive practice veterinarians recruited cats aged 11-20 years, of either sex and of any breed.

Sacroplasty with or without screw fixation for sacral metastatic tumors.

Introduction: Cementation (sacroplasty) with or without ablation has been shown to improve pain and function for patients with sacral metastatic disease. Percutaneous screw fixation with sacroplasty (PSFS) may provide superior outcomes in select patients.

Methods: Thirty patients with sacral metastases who underwent sacroplasty with or without ablation and screw fixation at a single institution were retrospectively reviewed.

Feasibility study of 4D-online monitoring of density gradients induced by lung cancer treatment using carbon ions.

Tumor motion is a major challenge for scanned ion-beam therapy. In the case of lung tumors, strong under- and overdosage can be induced due to the high density gradients between the tumor- and bone tissues compared to lung tissues. This work proposes a non-invasive concept for 4D monitoring of high density gradients in carbon ion beam therapy, by detecting charged fragments.

LLM-IE: a python package for biomedical generative information extraction with large language models.

Objectives: Despite the recent adoption of large language models (LLMs) for biomedical information extraction (IE), challenges in prompt engineering and algorithms persist, with no dedicated software available. To address this, we developed : a Python package for building complete IE pipelines.

Materials And Methods: The supports named entity recognition, entity attribute extraction, and relation extraction tasks.

Standards and infrastructure for multisite deployment of the research participant perception survey.

Objectives: To develop and disseminate a technical framework for administering the Research Participant Perception Survey (RPPS) and aggregating data across institutions using REDCap.

Materials And Methods: Six RPPS Steering Committee (RSC) member institutions met bi-weekly to achieve consensus on survey sampling techniques, data standards, participant and study descriptor variables, and dashboard design.

Results: RSC members implemented the infrastructure to send the RPPS to participants and shared data to the Empowering the Participant Voice Consortium Database.

Control of medical digital twins with artificial neural networks.

The objective of precision medicine is to tailor interventions to an individual patient's unique characteristics. A key technology for this purpose involves medical digital twins, computational models of human biology that can be personalized and dynamically updated to incorporate patient-specific data. Certain aspects of human biology, such as the immune system, are not easily captured with physics-based models, such as differential equations.

Quantification of total uncertainty in the physics-informed reconstruction of CVSim-6 physiology.

When predicting physical phenomena through simulation, quantification of the total uncertainty due to multiple sources is as crucial as making sure the underlying numerical model is accurate. Possible sources include irreducible uncertainty due to noise in the data, uncertainty induced by insufficient data or inadequate parameterization and uncertainty related to the use of misspecified model equations. In addition, recently proposed approaches provide flexible ways to combine information from data with full or partial satisfaction of equations that typically encode physical principles.

A comparison of Gaussian processes and polynomial chaos emulators in the context of haemodynamic pulse-wave propagation modelling.

Computational modelling of the cardiovascular system is a promising future direction for patient-specific healthcare. However, the computational cost of these simulators is a bottleneck for their practical use in clinic for real-time . Emulation can overcome this, yet an extensive investigation into cardiovascular emulators is warranted.

Bayesian Windkessel calibration using optimized zero-dimensional surrogate models.

Bayesian boundary condition (BC) calibration approaches from clinical measurements have successfully quantified inherent uncertainties in cardiovascular fluid dynamics simulations. However, estimating the posterior distribution for all BC parameters in three-dimensional (3D) simulations has been unattainable due to infeasible computational demand. We propose an efficient method to identify Windkessel parameter posteriors: We only evaluate the 3D model once for an initial choice of BCs and use the result to create a highly accurate zero-dimensional (0D) surrogate.

Parameter inference for stochastic reaction models of ion channel gating from whole-cell voltage-clamp data.

Mathematical models of ion channel gating describe the changes in ion channel configurations due to the electrical activity of the cell membrane. Experimental findings suggest that ion channels behave randomly, and therefore stochastic models of ion channel gating should be more realistic than deterministic counterparts. Whole-cell voltage-clamp data allow us to calibrate the parameters of ion channel models.

The Sole Essential Low Molecular Weight Tropomyosin Isoform of Caenorhabditis elegans Is Essential for Pharyngeal Muscle Function.

Tropomyosin is an actin-binding protein that plays roles ranging from regulating muscle contraction to controlling cytokinesis and cell migration. The simple nematode Caenorhabditis elegans provides a useful model for studying the core functions of tropomyosin in an animal, having a relatively simple anatomy and a single tropomyosin gene, lev-11, that produces seven isoforms. Three higher molecular weight isoforms regulate the contraction of body wall and other muscles, but comparatively less is known of the functions of four lower molecular weight isoforms (LEV-11C, E, T, U).

Major Human Leukocyte Antigen Expression in Respiratory Papillomatosis Clinical Specimens.

Objectives: Prior studies have reported low or absent major HLA class I expression on respiratory papilloma cells, conflicting with the recent clinical success of immunotherapy designed to activate HPV-specific T cells in patients with recurrent respiratory papillomatosis (RRP). We aimed to determine major human leukocyte antigen (HLA) class I expression on respiratory papilloma cells in untreated RRP clinical specimens using contemporary techniques.

Methods: Formalin-fixed, paraffin-embedded RRP sections were subjected to signal-amplified multispectral immunofluorescence using the OPAL system to determine major and minor HLA class I expression, and digitally scanned slides were analyzed using digital pathology software.

Structural stigma in healthcare: A novel eLearning course.

Discrimination against individuals with Mental Health and Substance Use (MHSU) challenges adversely influences healthcare. To address shortcomings of existing anti-stigma interventions, a novel eLearning course on dismantling structural stigma was co-designed, piloted, implemented, and evaluated with diverse partners. The course aimed to foster reflection and evidence-informed approaches to recognize and address structural forms of stigma in healthcare contexts.

Alkane Dehydrogenation and H/D Exchange by a Cationic Pincer-Ir(III) Hydride: Cooperative C-H Addition and β-H Elimination Modes Induce Anomalous Selectivity.

We report that the cationic iridium complex (PCP)IrH catalyzes the transfer-dehydrogenation of alkanes to give alkenes and hydrogen isotope exchange (HIE) of alkanes and arenes. Contrary to established selectivity trends found for C-H activation by transition metal complexes, strained cycloalkanes, including cyclopentane, cycloheptane, and cyclooctane, undergo C-H addition much more readily than -alkanes, which in turn are much more reactive than cyclohexane. Aromatic C-H bonds also undergo H/D exchange much less rapidly than those of the strained cycloalkanes, but much more favorably than cyclohexane.

Temporal and spatial equivalence in demographic responses of emperor penguins (Aptenodytes forsteri) to environmental change.

Population ecology and biogeography applications often necessitate the transfer of models across spatial and/or temporal dimensions to make predictions outside the bounds of the data used for model fitting. However, ecological data are often spatiotemporally unbalanced such that the spatial or the temporal dimension tends to contain more data than the other. This unbalance frequently leads model transfers to become substitutions, which are predictions to a different dimension than the predictive model was built on.

Exploring Plant-Based Nutrition for Patients with Substance Use Disorders: A Scoping Review of Dietary Intake and Potential Applications.

Background: Substance use disorders (SUDs) represent a significant global public health challenge, with affected individuals often exhibiting poor dietary habits, nutritional deficiencies, and compromised mental and physical health. This scoping review evaluates existing literature on dietary intake in individuals with SUDs, focusing on the potential benefits of plant-based dietary interventions for improving nutritional status and supporting recovery.

Methods: A scoping review was conducted following PRISMA guidelines.

Evaluating the Effect of Epigallocatechin Gallate (EGCG) in Reducing Folate Levels in Reproductive Aged Women by MTHFR and DHFR Genotype in Combination With Letrozole or Clomiphene.

Previous epidemiological studies have suggested that green tea catechins, including Epigallocatechin-3-gallate (EGCG), the most abundant polyphenol in green tea, may be associated with reduced serum folate levels. This is of particular interest as women of childbearing age may be consuming EGCG from tea, dietary supplements, or involved in active clinical trials studying EGCG or green tea extract. EGCG was reported to shrink uterine fibroids in preclinical and clinical studies.