Future Directions for Quantitative Systems Pharmacology.

In this chapter, we envision the future of Quantitative Systems Pharmacology (QSP) which integrates closely with emerging data and technologies including advanced analytics, novel experimental technologies, and diverse and larger datasets. Machine learning (ML) and Artificial Intelligence (AI) will increasingly help QSP modelers to find, prepare, integrate, and exploit larger and diverse datasets, as well as build, parameterize, and simulate models. We picture QSP models being applied during all stages of drug discovery and development: During the discovery stages, QSP models predict the early human experience of in silico compounds created by generative AI.

Comparing the Introduction and Implementation of Noninvasive Prenatal Testing (NIPT) in Japan, the Netherlands, and the United States: An Integrative Review.

Previous studies suggest that NIPT's implementation differed widely across countries but offer limited insight into what shaped these differences. To address this gap, we conducted an in-depth analysis of how NIPT was incorporated into prenatal care in the US, the Netherlands, and Japan-countries with similar economic status-to identify actionable lessons. We conducted an integrative literature review on the process of introducing and implementing NIPT, stakeholders' roles, documented considerations in the decision to introduce NIPT, implementation choices, and NIPT uptake.

Complete chloroplast genome of the marine eelgrass (Zosteraceae, Plantae) from Monterey, California.

We present the complete chloroplast genome of the eelgrass from Monterey, California. The genome is circular and 144,675  bp in length. It consists of 82 protein-coding, 31 transfer RNA, and 8 ribosomal RNA genes and is 99.

Current Concepts and Clinical Applications in Cartilage Tissue Engineering.

Cartilage injuries are extremely common in the general population, and conventional interventions have failed to produce optimal results. Tissue engineering (TE) technology has been developed to produce neocartilage for use in a variety of cartilage-related conditions. However, progress in the field of cartilage TE has historically been difficult due to the high functional demand and avascular nature of the tissue.

sp. nov., a bacterium isolated from the roots of the aquatic plant .

A polyphasic taxonomic study was carried out on strain T9W2-O, isolated from the roots of the aquatic plant . This isolate is rod-shaped, forms yellow/orange pigmented colonies and produces the pigment flexirubin. Nearly complete 16S rRNA gene sequence homology related the strain to , with 98.

Cenobamate as add-on treatment for SCN8A developmental and epileptic encephalopathy.

Objectives: Developmental and epileptic encephalopathies (DEEs) caused by pathogenic variants in SCN8A are associated with difficult-to-treat and early-onset seizures, developmental delay/intellectual disability, impaired quality of life, and increased risk of early mortality. High doses of sodium channel blockers are typically used to treat SCN8A-DEE caused by gain-of-function (GoF) variants. However, seizures are often drug resistant, and only a few patients achieve seizure freedom.

mpactR: an R adaptation of the metabolomics peak analysis computational tool (MPACT) for use in reproducible data analysis pipelines.

mpactR automates pre-processing of liquid chromatography-tandem mass spectrometry (LC-MS/MS) data from microbiological samples to correct mispicked peaks, resolve inter-sample variation in abundance across technical replicates, account for in-source ion fragmentation, and remove background noise to yield high-quality mass spectrometry features. The package is available through CRAN and GitHub.

Ablation of satellite cell-specific clock gene, Bmal1, alters force production, muscle damage, and repair following contractile-induced injury.

Following injury, skeletal muscle undergoes repair via satellite cell (SC)-mediated myogenic progression. In SCs, the circadian molecular clock gene, Bmal1, is necessary for appropriate myogenic progression and repair with evidence that muscle molecular clocks can also affect force production. Utilizing a mouse model allowing for inducible depletion of Bmal1 within SCs, we determined contractile function, SC myogenic progression and muscle damage and repair following eccentric contractile-induced injury.

Comparative Performance of the Leading Large Language Models in Answering Complex Rhinoplasty Consultation Questions.

Various large language models (LLMs) can provide human-level medical discussions, but they have not been compared regarding rhinoplasty knowledge. To compare the leading LLMs in answering complex rhinoplasty consultation questions as evaluated by plastic surgeons. Ten open-ended rhinoplasty consultation questions were presented to ChatGPT-4o, Google Gemini, Claude, and Meta-AI LLMs.

Efficient and accurate commissioning and quality assurance of radiosurgery beam via prior-embedded implicit neural representation learning.

Background: Dosimetric commissioning and quality assurance (QA) for linear accelerators (LINACs) present a significant challenge for clinical physicists due to the high measurement workload and stringent precision standards. This challenge is exacerbated for radiosurgery LINACs because of increased measurement uncertainty and more demanding setup accuracy for small-field beams. Optimizing physicists' effort during beam measurements while ensuring the quality of the measured data is crucial for clinical efficiency and patient safety.

Baseline Drug Clearance Predicts Outcomes in Children With Inflammatory Bowel Disease Treated With Vedolizumab: Results From the VedoKids Prospective Multicentre Study.

Background: The pharmacokinetics of biologic agents can differ between children and adults with inflammatory bowel disease (IBD), often necessitating modified paediatric dosing strategies.

Aims: To define the exposure-response relationship of vedolizumab in the paediatric IBD VedoKids cohort including the effect of baseline clearance on deep biochemical remission (normal C-reactive protein [CRP]/erythrocyte sedimentation rate [ESR] and steroid-free remission) at 30 weeks, and to use population pharmacokinetic models to find the best matches between adult and paediatric pharmacokinetic profiles.

Methods: We sought a pharmacokinetic model on 312 serum vedolizumab concentrations from 129 children, assisted by a published adult model as a Bayesian prior.

Pros and Cons of Human Brain Organoids to Study Alzheimer's Disease.

There is increasing pressure for researchers to reduce their reliance on animals, particularly in early-stage research. The main reason for that change arises from the different biological behavior of humans that leads to frequent failure of translating data from bench to bed. The advent of organoid technology ten years ago, along with the feasibility of obtaining brain organoids in most laboratories, has created considerable expectations not exempting frustration.

Circulating Endocannabinoids and Cognitive Function in Older Adults.

The role of endogenous cannabinoids (endocannabinoids; eCBs) in cognitive-related processes has been demonstrated in preclinical studies. However, observational studies are lacking. We examined the associations of multiple circulating eCBs and eCB-like molecules with cognitive function in a sample of dementia-free older adults.

TBC1D15 Inhibits Autophagy of Microglia through Maintaining the Damaged Swelling Lysosome in Alzheimer's Disease.

Autophagy in microglia is essential for the clearance of amyloid-beta (Aβ) and amyloid plaques in Alzheimer's disease. However, reports regarding the levels of autophagy in microglia have been inconsistent; some studies indicate an early enhancement followed by a subsequent reduction, while others describe a persistently weakened state. Notably, there is a lack of systematic studies documenting the temporal changes in microglial autophagy.

The integration of meditation into higher education: a systematic literature review.

Reviewed empirical studies involving meditation-related interventions for college and university students during the past decade. Based on inclusion criteria, 44 studies were selected for the review and categorized into three major areas: attention, academic performance, and mental health (stress/anxiety). Areas were systemically reviewed and synthesized.

Innovative applications of bio-inspired technology in bio-based food packaging.

Traditionally, food packaging was used to extend the shelf life of food or to monitor its condition. Inspired by many biological structures found in nature, bio-inspired functional materials for bio-based food packaging have been shown to have significantly improved capabilities over traditional bio-based food packaging materials in various aspects and to attract consumers through novel freshness preservation features. This review synthesizes recent advances in bio-inspired bio-based food packaging materials that mimic the structure of natural organisms with specific functionalities, with examples of specific biomimetics in different enhancement areas.

Sexual minority stressors and disordered eating behaviors in daily life: a daily diary study of sexual minority cisgender female couples.

Young cisgender sexual minority women (e.g. lesbian, queer) in the U.

Genetically Predicted Gene Expression Effects on Changes in Red Blood Cell and Plasma Polyunsaturated Fatty Acids.

Polyunsaturated fatty acids (PUFAs) including omega-3 and omega-6 are obtained from diet and can be measured objectively in plasma or red blood cells (RBCs) membrane biomarkers, representing different dietary exposure windows. In vivo conversion of omega-3 and omega-6 PUFAs from short- to long-chain counterparts occurs via a shared metabolic pathway involving fatty acid desaturases and elongase. This analysis leveraged genome-wide association study (GWAS) summary statistics for RBC and plasma PUFAs, along with expression quantitative trait loci (eQTL) to estimate tissue-specific genetically predicted gene expression effects for delta-5 desaturase (FADS1), delta-6 desaturase (FADS2), and elongase (ELOVL2) on changes in RBC and plasma biomarkers.

Characterization and molecular targeting of CFIm25 (NUDT21/CPSF5) mRNA using miRNAs.

Changes in protein levels of the mammalian cleavage factor, CFIm25, play a role in regulating pathological processes including neural dysfunction, fibrosis, and tumorigenesis. However, despite these effects, little is known about how CFIm25 (NUDT21) expression is regulated at the RNA level. A potential regulator of NUDT21 mRNA are small non-coding microRNAs (miRNAs).

General Kernel Machine Methods for Multi-Omics Integration and Genome-Wide Association Testing With Related Individuals.

Integrating multi-omics data may help researchers understand the genetic underpinnings of complex traits and diseases. However, the best ways to integrate multi-omics data and use them to address pressing scientific questions remain a challenge. One important and topical problem is how to assess the aggregate effect of multiple genomic data types (e.

Management of two dogs with post-operative new-onset persistent atrial fibrillation following mitral valve repair.

Post-operative new-onset atrial fibrillation (POAF) is a possible complication following cardiac surgery. Digoxin is a drug with positive inotropic and negative chronotropic effects and is listed among antiarrhythmic drugs that can be prescribed in dogs with atrial fibrillation. This report aims at describing the use of digoxin in two dogs with persistent POAF after mitral valve repair.

New Multiomic Studies Shed Light on Cellular Diversity and Neuronal Susceptibility in Parkinson's Disease.

Parkinson's disease is a complex neurodegenerative disorder characterized by degeneration of dopaminergic neurons, with patients manifesting varying motor and nonmotor symptoms. Previous studies using single-cell RNA sequencing in rodent models and humans have identified distinct heterogeneity of neurons and glial cells with differential vulnerability. Recent studies have increasingly leveraged multiomics approaches, including spatial transcriptomics, epigenomics, and proteomics, in the study of Parkinson's disease, providing new insights into pathogenic mechanisms.

Lower Risk of New-Onset Atrial Fibrillation in Conduction System Pacing Compared With Right Ventricular Pacing.

Background: Conduction system pacing (CSP) has been reported to improve clinical outcomes in comparison of right ventricular pacing (RVP). However, the performance between CSP and RVP on the risk of new-onset atrial fibrillation (AF) remains elusive.

Methods: Four online databases were systematically searched up to July 1, 2024.

Clinical Trial: Study to Investigate the Efficacy and Safety of the Alpha-2-Delta Ligand PD-217,014 in Patients With Irritable Bowel Syndrome.

Introduction: Despite the emergence of drugs to treat irritable bowel syndrome (IBS), improving abdominal pain can still be challenging. αδ ligands, such as gabapentin and pregabalin, are sometimes used off-label to tackle this problem. However, evidence for efficacy is limited, and no large-scale studies have been published.