Survey and perspective on verification, validation, and uncertainty quantification of digital twins for precision medicine.

Digital twins in precision medicine provide tailored health recommendations by simulating patient-specific trajectories and interventions. We examine the critical role of Verification, Validation, and Uncertainty Quantification (VVUQ) for digital twins in ensuring safety and efficacy, with examples in cardiology and oncology. We highlight challenges and opportunities for developing personalized trial methodologies, validation metrics, and standardizing VVUQ processes.

Modular organization of enhancer network provides transcriptional robustness in mammalian development.

Enhancer clusters, pivotal in mammalian development and diseases, can organize as enhancer networks to control cell identity and disease genes; however, the underlying mechanism remains largely unexplored. Here, we introduce eNet 2.0, a comprehensive tool for enhancer networks analysis during development and diseases based on single-cell chromatin accessibility data.

Association Between Short-Term Exposure to Ambient PM and Its Components with Hospital Admissions for Patients with Coronary Heart Disease and Comorbid Diabetes Mellitus in Beijing, China.

Existing researches had primarily investigated the associations between various air pollutants and the risk of coronary heart disease (CHD) or diabetes mellitus (DM) separately. However, the significance and effects of PM and its components in patients with CHD and comorbid DM (CHD-DM) remain unclear. Patient data was sourced from the Beijing Municipal Health Commission Information Centre between January 1, 2014, and December 31, 2018.

Data reuse in agricultural genomics research: challenges and recommendations.

The scientific community has long benefited from the opportunities provided by data reuse. Recognizing the need to identify the challenges and bottlenecks to reuse in the agricultural research community and propose solutions for them, the data reuse working group was started within the AgBioData consortium framework. Here, we identify the limitations of data standards, metadata deficiencies, data interoperability, data ownership, data availability, user skill level, resource availability, and equity issues, with a specific focus on agricultural genomics research.

Automated Lesion and Feature Extraction Pipeline for Brain MRIs with Interpretability.

This paper introduces the Automated Lesion and Feature Extraction (ALFE) pipeline, an open-source, Python-based pipeline that consumes MR images of the brain and produces anatomical segmentations, lesion segmentations, and human-interpretable imaging features describing the lesions in the brain. ALFE pipeline is modeled after the neuroradiology workflow and generates features that can be used by physicians for quantitative analysis of clinical brain MRIs and for machine learning applications. The pipeline uses a decoupled design which allows the user to customize the image processing, image registrations, and AI segmentation tools without the need to change the business logic of the pipeline.

Current status of FAP-directed cancer theranostics: a bibliometric analysis.

Fibroblast activation protein (FAP) is a key molecule in the field of oncology, with significant impacts on tumor diagnosis and treatment. Importantly, it has paved the way for the development of radiotracers for quinoline-based FAP inhibitors (FAPIs), which are currently among the most promising radiotracers for PET imaging in cancer. We performed a bibliometric analysis of scientific publications related to FAP and FAPI-based radiotracers, which included the quantification and visualization of current research trends and prospects based on various bibliometric indicators.

A sample size analysis of a mathematical model of longitudinal tumor volume and progression-free survival for Bayesian individual dynamic predictions in recurrent high-grade glioma.

Patients with recurrent high-grade glioma (rHGG) have a poor prognosis with median progression-free survival (PFS) of <7 months. Responses to treatment are heterogenous, suggesting a clinical need for prognostic models. Bayesian data analysis can exploit individual patient follow-up imaging studies to adaptively predict the risk of progression.

Beyond genomic weaving: molecular roles for CTCF outside cohesin loop extrusion.

CCCTC-binding factor (CTCF) is a key regulator of 3D genome organization and transcriptional activity. Beyond its well-characterized role in facilitating cohesin-mediated loop extrusion, CTCF exhibits several cohesin-independent activities relevant to chromatin structure and various nuclear processes. These functions include patterning of nucleosome arrangement and chromatin accessibility through interactions with ATP-dependent chromatin remodelers.

Effects of orally administered clioquinol on the fecal microbiome of horses.

Background: Whereas restoration of fecal consistency after treatment with clioquinol for chronic diarrhea and free fecal water syndrome has been attributed to its antiprotozoal properties, actions of clioquinol on the colonic bacterial microbiota have not been investigated.

Objectives: Characterize the dynamics of fecal microbial diversity before, during, and after PO administration of clioquinol to healthy horses.

Study Design: Experimental prospective cohort study using a single horse group.

Leveraging artificial intelligence and machine learning to accelerate discovery of disease-modifying therapies in type 1 diabetes.

Progress in developing therapies for the maintenance of endogenous insulin secretion in, or the prevention of, type 1 diabetes has been hindered by limited animal models, the length and cost of clinical trials, difficulties in identifying individuals who will progress faster to a clinical diagnosis of type 1 diabetes, and heterogeneous clinical responses in intervention trials. Classic placebo-controlled intervention trials often include monotherapies, broad participant populations and extended follow-up periods focused on clinical endpoints. While this approach remains the 'gold standard' of clinical research, efforts are underway to implement new approaches harnessing the power of artificial intelligence and machine learning to accelerate drug discovery and efficacy testing.

APOE genotype and brain amyloid are associated with changes in the plasma proteome in elderly subjects without dementia.

Objective: Recent work has bolstered the possibility that peripheral changes may be relevant to Alzheimer's disease pathogenesis in the brain. While age-associated blood-borne proteins have been targeted to restore function to the aged brain, it remains unclear whether other dysfunctional systemic states can be exploited for similar benefits. Here, we investigate whether APOE allelic variation or presence of brain amyloid are associated with plasma proteomic changes and the molecular processes associated with these changes.

Geospatial Modeling of Deep Neural Visual Features for Predicting Obesity Prevalence in Missouri: Quantitative Study.

Background: The global obesity epidemic demands innovative approaches to understand its complex environmental and social determinants. Spatial technologies, such as geographic information systems, remote sensing, and spatial machine learning, offer new insights into this health issue. This study uses deep learning and spatial modeling to predict obesity rates for census tracts in Missouri.

High-Throughput Drug Screening in Chondrosarcoma Cells Identifies Effective Antineoplastic Agents Independent of IDH Mutation.

The term chondrosarcoma refers to a rare and heterogeneous group of malignant cartilaginous tumors that are typically resistant to chemotherapy and radiotherapy. Metastatic chondrosarcoma has a poor prognosis, and effective systemic therapies are lacking. Isocitrate dehydrogenase (IDH) mutations represent a potential therapeutic target, but IDH inhibitors alone have shown limited clinical efficacy to date.

Correction: An Artificial Therapist (Manage Your Life Online) to Support the Mental Health of Youth: Co-Design and Case Series.

[This corrects the article DOI: 10.2196/46849.].

RH2Fusion: A universal tool for precise DNA fragment assembly.

Despite its limitations, restriction enzyme (RE)-mediated cleavage remains the prevalent method for generating sticky ends in DNA assembly. Here, we present RNase HII Fusion (RH2Fusion), a robust system for user-defined sticky ends, enabling scarless assembly of multiple DNA fragments alongside simultaneous site-directed mutagenesis (SDM) at multiple sites. In bacterial cells, DNA fragments with ribonucleotide modifications are expected to form complementary 3' overhangs after RNase HII treatment, followed by annealing and recombination via the bacterial self-repair system.

Baseline colitogenicity and acute perturbations of gut microbiota in immunotherapy-related colitis.

Immunotherapy-related colitis (irC) frequently emerges as an immune-related adverse event during immune checkpoint inhibitor therapy and is presumably influenced by the gut microbiota. We longitudinally studied microbiomes from 38 ICI-treated cancer patients. We compared 13 ICI-treated subjects who developed irC against 25 ICI-treated subjects who remained irC-free, along with a validation cohort.

Marine Protected Areas That Preserve Trophic Cascades Promote Resilience of Kelp Forests to Marine Heatwaves.

Under accelerating threats from climate-change impacts, marine protected areas (MPAs) have been proposed as climate-adaptation tools to enhance the resilience of marine ecosystems. Yet, debate persists as to whether and how MPAs may promote resilience to climate shocks. Here, we use 38 years of satellite-derived kelp cover to empirically test whether a network of 58 temperate coastal MPAs in Central and Southern California enhances the resistance of kelp forest ecosystems to, and their recovery from, the unprecedented 2014-2016 marine heatwave regime that occurred in the region.

Dyslipidemia progression and increased lung cancer risk: a prospective cohort study.

Objectives: To investigate the associations of changes in lipidemic profile with the risk of lung cancer incidence, and to elucidate how modifiable risk factors contribute to the associations.

Design And Participants: The prospective study enrolled a cohort of 137,075 individuals with lipidemic profiles spanning from January 1, 1996 to December 31, 2006 in the Taiwan MJ Cohort. Follow-up was extended from the second clinical visit until December 31, 2007, with an average duration of 6.

Neuropsychiatric polygenic scores are weak predictors of professional categories.

Polygenic scores (PGS) enable the exploration of pleiotropic effects and genomic dissection of complex traits. Here, in 421,889 individuals with European ancestry from the Million Veteran Program and UK Biobank, we examine how PGS of 17 neuropsychiatric traits are related to membership in 22 broad professional categories. Overall, we find statistically significant but weak (the highest odds ratio is 1.

Single-cell transcriptomic and neuropathologic analysis reveals dysregulation of the integrated stress response in progressive supranuclear palsy.

Progressive supranuclear palsy (PSP) is a sporadic neurodegenerative tauopathy variably affecting brainstem and cortical structures, and characterized by tau inclusions in neurons and glia. The precise mechanism whereby these protein aggregates lead to cell death remains unclear. To investigate the contribution of these different cellular abnormalities to PSP pathogenesis, we performed single-nucleus RNA sequencing (snRNA-seq) and analyzed 50,708 high quality nuclei targeting the diencephalon, including the subthalamic nucleus and adjacent structures, from human post-mortem PSP brains with varying degrees of pathology compared to controls.

Timing of standard chow exposure determines the variability of mouse phenotypic outcomes and gut microbiota profile.

Standard chow diets influence reproducibility in animal model experiments because chows have different nutrient compositions, which can independently influence phenotypes. However, there is little evidence of the role of timing in the extent of variability caused by chow exposure. Here we measured the impact of different diets (5V5M, 5V0G, 2920X and 5058) and timing of exposure (adult exposure (AE), lifetime exposure (LE) and developmental exposure (DE)) on growth and development, metabolic health indicators and gut bacterial microbiota profiles across genetically identical C57BL/6J mice.