Development of Betalain-immobilized polylactic acid nanofibers as a green and sustainable sensor for toxic ammonia.

Ammonia has been an important industrial colorless agent. Exposure to gaseous ammonia results in organ damage or even death. Herein, an environmentally friendly colorimetric detector for aqueous and gaseous ammonia was prepared utilizing vapochromic polylactic acid nanofibers.

Effect of Tiered Implementation of Clinical Decision Support System for Acute Kidney Injury and Nephrotoxin Exposure in Cardiac Surgery Patients.

Background:  Nephrotoxin exposure may worsen kidney injury and impair kidney recovery if continued in patients with acute kidney injury (AKI).

Objectives:  This study aimed to determine if tiered implementation of a clinical decision support system (CDSS) would reduce nephrotoxin use in cardiac surgery patients with AKI.

Methods:  We assessed patients admitted to the cardiac surgery intensive care unit at a tertiary care center from January 2020 to December 2021, and August 2022 to September 2023.

TPC2 controls MITF expression and metastasis in melanoma.

Recent findings by Abrahamian et al. (2024) provides new insights into the relationship between Two Pore Channel 2 (TPC2) activity and the development and progression of melanoma. Melanocyte inducing transcription factor (MITF) is a critical regulator of both melanocyte and melanoma behavior.

Esophageal epithelial Ikkβ deletion promotes eosinophilic esophagitis in experimental allergy mouse model.

Background: Eosinophilic esophagitis (EoE) is a chronic T helper type 2 (Th2)-associated inflammatory disorder triggered by food allergens, resulting in esophageal dysfunction through edema, fibrosis, and tissue remodeling. The role of epithelial remodeling in EoE pathogenesis is critical but not fully understood.

Objective: To investigate the role of epithelial IKKβ/NFκB signaling in EoE pathogenesis using a mouse model with conditional Ikkβ knockout in esophageal epithelial cells (Ikkβ).

Dominant negative mutations cause ADA2 deficiency in heterozygous carriers.

Human ADA2 deficiency (DADA2) is an inborn error of immunity with a broad clinical phenotype which encompasses vasculopathy including livedo racemosa and lacunar strokes, as well as hemato-immunological features. Diagnosis is based on the combination of decreased serum ADA2 activity and the identification of biallelic deleterious alleles in the gene. DADA2 carriers harbor a single pathogenic variant in and are mostly considered healthy and asymptomatic.

Deriving Mendelian Randomization-based Causal Networks of Brain Imaging Phenotypes and Bipolar Disorder.

Neuroanatomical variation in individuals with bipolar disorder (BD) has been previously described in observational studies. However, the causal dynamics of these relationships remain unexplored. We performed Mendelian Randomization of 297 structural and functional neuroimaging phenotypes from the UK BioBank and BD using genome-wide association study summary statistics.

Targeted long-read sequencing to quantify methylation of the C9orf72 repeat expansion.

Background: The gene C9orf72 harbors a non-coding hexanucleotide repeat expansion known to cause amyotrophic lateral sclerosis and frontotemporal dementia. While previous studies have estimated the length of this repeat expansion in multiple tissues, technological limitations have impeded researchers from exploring additional features, such as methylation levels.

Methods: We aimed to characterize C9orf72 repeat expansions using a targeted, amplification-free long-read sequencing method.

Aberrant Chitinase 3-Like 1 Expression in Basal Cells Contributes to Systemic Sclerosis Fibrosis.

Systemic sclerosis (SSc) is an autoimmune disease characterized by extensive skin and internal organ fibrosis. However, the mechanism underlying fibrosis remains unclear, and effective treatments for halting or reversing fibrosis are lacking. In this study, single-cell RNA sequencing is used to obtain a comprehensive overview of skin cells from patients with SSc and healthy controls.

Derivative Technologies of Expansion Microscopy and Applications in Biomedicine.

Expansion microscopy (ExM) is an innovative super-resolution imaging technique that utilizes physical expansion to magnify biological samples, facilitating the visualization of cellular structures that are challenging to observe using traditional optical microscopes. The fundamental principle of ExM revolves around employing a specialized hydrogel to uniformly expand biological samples, thereby achieving super-resolution imaging under conventional optical imaging conditions. This technology finds application not only in various biological samples such as cells and tissue sections, but also enables super-resolution imaging of large biological molecules including proteins, nucleic acids, and metabolite molecules.

Exploring Metabolic Approaches for Epithelial Ovarian Cancer Therapy.

Epithelial ovarian cancer (EOC) has the highest mortality rate among malignant tumors of the female reproductive system and the lowest survival rate. This poor prognosis is due to the aggressive nature of EOC, its late-stage diagnosis, and the tumor's ability to adapt to stressors through metabolic reprogramming. EOC cells sustain their rapid proliferation by altering the uptake, utilization, and regulation of carbohydrates, lipids, and amino acids.

A rich component of Fructus Aurantii, meranzin hydrate, exerts antidepressant effects via suppressing caspase4 to regulate glial cell and neuronal functions in the hippocampus.

Fructus Aurantii, a Chinese herbal medicine, has been indicated to have antidepressant effects in our previous study. However, the main component and specific mechanisms of the antidepressant effects of Fructus Aurantii still need to be further revealed. This study aimed to explore the main antidepressant component of Fructus Aurantii and the underlying mechanisms of its antidepressant effects in the hippocampus.

Ensemble and consensus approaches to prediction of recessive inheritance for missense variants in human disease.

Mode of inheritance (MOI) is necessary for clinical interpretation of pathogenic variants; however, the majority of variants lack this information. Furthermore, variant effect predictors are fundamentally insensitive to recessive-acting diseases. Here, we present MOI-Pred, a variant pathogenicity prediction tool that accounts for MOI, and ConMOI, a consensus method that integrates variant MOI predictions from three independent tools.

MAFcounter: An efficient tool for counting the occurrences of k-mers in MAF files.

Motivation: With the rapid expansion of large-scale biological datasets, DNA and protein sequence alignments have become essential for comparative genomics and proteomics. These alignments facilitate the exploration of sequence similarity patterns, providing valuable insights into sequence conservation, evolutionary relationships and for functional analyses. Typically, sequence alignments are stored in formats such as the Multiple Alignment Format (MAF).

Clinical and Genomic Prediction of Coronary Artery Disease Subtypes.

Background: Coronary artery disease (CAD) is a complex, heterogeneous disease with distinct etiological mechanisms. These different etiologies may give rise to multiple subtypes of CAD that could benefit from alternative preventions and treatments. However, so far, there have been no systematic efforts to predict CAD subtypes using clinical and genetic factors.

Molecular and Clinical Characterization of a Founder Mutation Causing G6PC3 Deficiency.

G6PC3 deficiency is a monogenic immunometabolic disorder that causes severe congenital neutropenia type 4. Patients display heterogeneous extra-hematological manifestations, contributing to delayed diagnosis. Here, we investigated the origin and functional consequence of the G6PC3 c.

invertiaDB: A Database of Inverted Repeats Across Organismal Genomes.

Inverted repeats are repetitive elements that can form hairpin and cruciform structures. They are linked to genomic instability, however they also have various biological functions. Their distribution differs markedly across taxonomic groups in the tree of life, and they exhibit high polymorphism due to their inherent genomic instability.

A Primer on Reinforcement Learning in Medicine for Clinicians.

Reinforcement Learning (RL) is a machine learning paradigm that enhances clinical decision-making for healthcare professionals by addressing uncertainties and optimizing sequential treatment strategies. RL leverages patient-data to create personalized treatment plans, improving outcomes and resource efficiency. This review introduces RL to a clinical audience, exploring core concepts, potential applications, and challenges in integrating RL into clinical practice, offering insights into efficient, personalized, and effective patient care.

Intravenous administration of blood-brain barrier-crossing conjugates facilitate biomacromolecule transport into central nervous system.

Delivery of biomacromolecules to the central nervous system (CNS) remains challenging because of the restrictive nature of the blood-brain barrier (BBB). We developed a BBB-crossing conjugate (BCC) system that facilitates delivery into the CNS through γ-secretase-mediated transcytosis. Intravenous administration of a BCC10-oligonucleotide conjugate demonstrated effective transportation of the oligonucleotide across the BBB and gene silencing in wild-type mice, human brain tissues and an amyotrophic lateral sclerosis mouse model.

Time-Lapse Acquisition of Both Freely Secreted Proteome and Exosome Encapsulated Proteome in Live Organoids' Microenvironment.

Proteomic communications in neighboring microenvironments during early organ development is a dynamic process that continuously reshapes human embryonic stem cells (hESCs) developmental fate. Such dynamic proteomic alteration in the microenvironment consists of both freely secreted proteome and exosome-encapsulated proteome. Simultaneous monitoring of the time-lapse shift of both proteomes with live organoids remains technically challenging.

Clinical progression of Parkinson's disease in the early 21st century: Insights from the accelerating medicine partnership (AMP-PD) data.

Background: Parkinson's disease (PD) therapeutic strategies have evolved since levodopa introduction in mid 1900s. To understand their impact and research gaps, this study delineated the clinical progression of PD in recent years.

Methods: Using Accelerating Medicine Partnership-PD (AMP-PD) data harmonized from seven biomarker discovery studies (2010-2020), we extracted: overall [Schwab and England (S&E), PD Questionnaire (PDQ-39)]; motor [Movement Disorders Society Unified PD Rating Scale (MDS-UPDRS)-II and -III and Hoehn & Yahr (HY)]; and non-motor [MDS-UPDRS-I, University of Pennsylvania Smell Identification Test (UPSIT), Montreal Cognitive Assessment (MoCA), and Epworth Sleepiness Scale (ESS)] scores.

Microsatellites explorer: A database of short tandem repeats across genomes.

Short tandem repeats (STRs) are widespread, repetitive elements, with a number of biological functions and are among the most rapidly mutating regions in the genome. Their distribution varies significantly between taxonomic groups in the tree of life and are highly polymorphic within the human population. Advances in sequencing technologies coupled with decreasing costs have enabled the generation of an ever-growing number of complete genomes.

Zr-NMOF tagged with heterobifunctionalized aptamers for highly sensitive, multiplexed and rapid imaging mass cytometry.

Imaging mass cytometry (IMC) permits high-dimensional single-cell spatial proteomics by harnessing mass tags to replace conventional fluorescence tags. However, the current IMC technique commonly adopts metal-chelated polymer (MCP) tags, which are limited in sensitivity, multiplicity and data acquisition speed. Here, we demonstrate nanometal-organic framework (NMOF) tags, which could concurrently augment IMC's sensitivity, multiplicity, and acquisition speed.