Targeted animal models for preclinical assessment of cellular and gene therapies in pancreatic and liver diseases: regulatory and practical insights.

Cellular and gene therapy (CGT) products have emerged as a popular approach in regenerative medicine, showing promise in treating various pancreatic and liver diseases in numerous clinical trials. Before these therapies can be tested in human clinical trials, it is essential to evaluate their safety and efficacy in relevant animal models. Such preclinical testing is often required to obtain regulatory approval for investigational new drugs.

AAHPM Assessment Workgroup: Hospice and Palliative Medicine Fellowship Assessment Needs and Directions.

Context: Medical education is moving towards competency based medical education (CBME). This provides opportunities and challenges for the field of Hospice and Palliative Medicine (HPM). The American Academy of Hospice and Palliative Medicine (AAHPM) created the Assessment Workgroup to spearhead a shared vision and process to implement high-quality assessment of fellow performance.

Preclinical and Clinical-Scale Magnetic Particle Imaging of Natural Killer Cells: in vitro and ex vivo Demonstration of Cellular Sensitivity, Resolution, and Quantification.

Purpose: Clinical adoption of NK cell immunotherapy is underway for medulloblastoma and osteosarcoma, however there is currently little feedback on cell fate after administration. We propose magnetic particle imaging (MPI) may have applications for the quantitative detection of NK cells.

Procedures: Human-derived NK-92 cells were labeled by co-incubation with iron oxide nanoparticles (VivoTrax™) for 24 h then excess nanoparticles were washed with centrifugation.

Construction of Zinc-based metal-organic frameworks for visual ratiometric fluorescence detection of tetracycline.

Background: Tetracycline (TC) is frequently utilized as additives in animal feed. The misuse can lead to the residue in food and threaten human health.

Results: A ratiometric fluorescence method for tetracycline detection is developed based on Zinc-based metal-organic framework (Zn-MOF) materials.

A Review of The Opportunities and Challenges with Large Language Models in Radiology: The Road Ahead.

In recent years, generative artificial intelligence (AI), particularly large language models (LLMs) and their multimodal counterparts, Multi-Modal Large Language Models (MM-LLMs), including Vision Language Models (VLMs), have generated considerable interest in the global AI discourse. LLMs, or pre-trained language models (such as ChatGPT, Med-PaLM, LLaMA, etc.), are neural network architectures trained on extensive text data, excelling in language comprehension and generation.

Paper-based triple-readout nanosensor for point-of-care detection of glucose in urine.

Glucose detection is critical for diabetes diagnosis and management. This study aimed to develop an enzyme-free, cascade-based, triple-readout paper sensor utilizing bismuth (Bi)-based metal-organic frameworks/gold nanoparticles (Bi-BDC-NH@Au) for detecting urine glucose. Herein, Bi-BDC-NH@Au exhibited glucose oxidase-like activity and oxidized glucose to generate HO, which then quenched the blue fluorescence of FP@Bi-BDC-NH@Au through an inner filter effect.

Mutant-selective AKT inhibition through lysine targeting and neo-zinc chelation.

Somatic alterations in the oncogenic kinase AKT1 have been identified in a broad spectrum of solid tumours. The most common AKT1 alteration replaces Glu17 with Lys (E17K) in the regulatory pleckstrin homology domain, resulting in constitutive membrane localization and activation of oncogenic signalling. In clinical studies, pan-AKT inhibitors have been found to cause dose-limiting hyperglycaemia, which has motivated the search for mutant-selective inhibitors.

Construction and validation of a pancreatic cancer prognostic model based on genes related to the hypoxic tumor microenvironment.

Background: Pancreatic cancer is one of the most lethal malignancies, characterized by poor prognosis and low survival rates. Traditional prognostic factors for pancreatic cancer offer inadequate predictive accuracy, often failing to capture the complexity of the disease. The hypoxic tumor microenvironment has been recognized as a significant factor influencing cancer progression and resistance to treatment.

Colocalization of Cancer-Associated Biomarkers on Single Extracellular Vesicles for Early Detection of Cancer.

Detection of cancer early, when it is most treatable, remains a significant challenge because of the lack of diagnostic methods sufficiently sensitive to detect nascent tumors. Early-stage tumors are small relative to their tissue of origin, heterogeneous, and infrequently manifest in clinical symptoms. The detection of early-stage tumors is challenging given the lack of tumor-specific indicators (ie, protein biomarkers, circulating tumor DNA) to enable detection using a noninvasive diagnostic assay.

Case report: Longitudinal evaluation and treatment of a melanoma-associated retinopathy patient.

Melanoma-associated retinopathy (MAR) is a paraneoplastic syndrome associated with cutaneous metastatic melanoma in which patients develop vision deficits that include reduced night vision, poor contrast sensitivity, and photopsia. MAR is caused by autoantibodies targeting TRPM1, an ion channel found in melanocytes and retinal ON-bipolar cells (ON-BCs). The visual symptoms arise when TRPM1 autoantibodies enter ON-BCs and block the function of TRPM1, thus detection of TRPM1 autoantibodies in patient serum is a key criterion in diagnosing MAR.

Risk of Stroke or Systemic Embolism According to Baseline Frequency and Duration of Subclinical Atrial Fibrillation: Insights From the ARTESiA Trial.

Background: In the ARTESiA trial (Apixaban for the Reduction of Thromboembolism in Patients With Device-Detected Subclinical Atrial Fibrillation), apixaban, compared with aspirin, reduced stroke or systemic embolism in patients with device-detected subclinical atrial fibrillation (SCAF). Clinical guidelines recommend considering SCAF episode duration when deciding whether to prescribe oral anticoagulation for this population.

Methods: We performed a retrospective cohort study in ARTESiA.

Case Report: Longitudinal Evaluation and Treatment of a Melanoma-Associated Retinopathy Patient.

Melanoma-associated retinopathy (MAR) is a paraneoplastic syndrome associated with cutaneous metastatic melanoma in which patients develop vision deficits that include reduced night vision, poor contrast sensitivity, and photopsia. MAR is caused by autoantibodies targeting TRPM1, an ion channel found in melanocytes and retinal ON-bipolar cells (ON-BCs). The visual symptoms arise when TRPM1 autoantibodies enter ON-BCs and block the function of TRPM1, thus detection of TRPM1 autoantibodies in patient serum is a key criterion in diagnosing MAR.

Phase 1/2 AAV5-hRKp.RPGR (Botaretigene Sparoparvovec) Gene Therapy: Safety and Efficacy in RPGR-Associated X-Linked Retinitis Pigmentosa.

Purpose: To assess the safety and efficacy of AAV5-hRKp.RPGR in participants with retinitis pigmentosa GTPase regulator (RPGR)-associated X-linked retinitis pigmentosa (XLRP).

Design: Open-label, phase 1/2 dose escalation/expansion study (ClinicalTrials.

Traditional Korean diet high in one-carbon nutrients increases global DNA methylation: implication for epigenetic diet.

Purpose: DNA methylation is a major epigenetic phenomenon through which diet affects health and disease. This study aimed to determine the epigenetic influence of the traditional Korean diet (K-diet) on global DNA methylation via one-carbon metabolism.

Methods: A crossover study was conducted on 52 women.

Modulation of FGF pathway signaling and vascular differentiation using designed oligomeric assemblies.

Many growth factors and cytokines signal by binding to the extracellular domains of their receptors and driving association and transphosphorylation of the receptor intracellular tyrosine kinase domains, initiating downstream signaling cascades. To enable systematic exploration of how receptor valency and geometry affect signaling outcomes, we designed cyclic homo-oligomers with up to 8 subunits using repeat protein building blocks that can be modularly extended. By incorporating a de novo-designed fibroblast growth factor receptor (FGFR)-binding module into these scaffolds, we generated a series of synthetic signaling ligands that exhibit potent valency- and geometry-dependent Ca release and mitogen-activated protein kinase (MAPK) pathway activation.

Development and characterization of edible and active coating based on xanthan gum nanoemulsion incorporating betel leaf extract for fresh produce preservation.

Developing an edible and active coating, incorporating environmentally-friendly antimicrobial agents into edible polymers, provides an eco-friendly alternative to conventional packaging and exhibits significant potential in preserving the quality of postharvest food. Herein, we aim to develop a novel edible and active coating based on xanthan gum (XG) nanoemulsion (NE) incorporating betel leaf extract (BLE) for the preservation of fresh produce. The total phenolic content, total flavonoid content, and antioxidant capacity of the methanol extract of BLE at various concentrations were characterized.

Pediococcus pentosaceus ZZ61 enhances growth performance and pathogenic resistance of silkworm Bombyx mori by regulating gut microbiota and metabolites.

Probiotics have attracted considerable attention in animal husbandry due to their positive effect on animal growth and health. This study aimed to screen candidate probiotic strain promoting the growth and health of silkworm and reveal the potential mechanisms. A novel probiotic Pediococcus pentosaceus strain (ZZ61) substantially promoted body weight gain, feed efficiency, and silk yield.

Gut Microbiota Affects Mouse Pregnane X Receptor Agonist Pregnenolone 16α-Carbonitrile-Induced Hepatomegaly by Regulating Pregnane X Receptor and Yes-Associated Protein Activation.

Pregnane X receptor (PXR) is essential in the regulation of liver homeostasis, and the gut microbiota is closely linked to liver physiologic and pathologic status. We previously found that activation of PXR significantly promotes liver enlargement through interaction with yes-associated protein (YAP). However, whether gut microbiota contributes to PXR-induced hepatomegaly and the involved mechanisms remain unclear.

A comprehensive synthetic library of poly-N-acetyl glucosamines enabled vaccine against lethal challenges of Staphylococcus aureus.

Poly-β-(1-6)-N-acetylglucosamine (PNAG) is an important vaccine target, expressed on many pathogens. A critical hurdle in developing PNAG based vaccine is that the impacts of the number and the position of free amine vs N-acetylation on its antigenicity are not well understood. In this work, a divergent strategy is developed to synthesize a comprehensive library of 32 PNAG pentasaccharides.

International consensus guidelines on robotic pancreatic surgery in 2023.

Background: With the rapid development of robotic surgery, especially for the abdominal surgery, robotic pancreatic surgery (RPS) has been applied increasingly around the world. However, evidence-based guidelines regarding its application, safety, and efficacy are still lacking. To harvest robust evidence and comprehensive clinical practice, this study aims to develop international guidelines on the use of RPS.

Dose-dependent reduction of somatic expansions but not Htt aggregates by di-valent siRNA-mediated silencing of MSH3 in HdhQ111 mice.

Huntington's disease (HD) is a progressive neurodegenerative disorder caused by CAG trinucleotide repeat expansions in exon 1 of the HTT gene. In addition to germline CAG expansions, somatic repeat expansions in neurons also contribute to HD pathogenesis. The DNA mismatch repair gene, MSH3, identified as a genetic modifier of HD onset and progression, promotes somatic CAG expansions, and thus presents a potential therapeutic target.

[Promoting fucoxanthin accumulation in by multiple nitrogen supplementation and blue light enhancement].

The aim of this study was to promote fucoxanthin accumulation in by photo-fermentation through optimizing the mode of multiple nitrogen supplementation and blue light enhancement. The results showed that the mixed nitrogen source (tryptone: urea=1:1, N mol/N mol; total nitrogen concentration at 0.02 mol/L) added to the culture system by six times was the best mode in shake flasks.