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At least 55 records · Page 3Linked to original sources
PubMed2026

Machine Learning-Driven Prediction of Coronary Artery Disease Risk Based on UK Biobank Plasma Proteomics.

BACKGROUND: Coronary artery disease (CAD) is a leading global cause of mortality, yet the predictive accuracy of conventional risk models is limited. Here, we integrate conventional risk factors, polygenic risk scores, and large-scale proteomics to develop a unified model for enhanced CAD risk prediction. METHODS: Using data from UK Biobank, participants with plasma proteomics and genetic risk data were included after excluding prevalent CAD. Participants from England were split into training (n=32 330) and internal validation (n=13 857) sets, and Scotland/Wales participants formed an external validation set (n=5775). Incident CAD was ascertained from linked health records. A 202-protein proteomic risk score was derived by least absolute shrinkage and selection operator Cox regression, and CatBoost models were trained using conventional risk factors alone and with incremental addition of polygenic risk scores and protein proteomic risk scores; Shapley Additive Explanations-guided forward selection identified a compact protein panel. RESULTS: Across cohorts, the median age was 58 years and ∼45% were men. Protein proteomic risk score was dose-dependently associated with CAD risk. Compared with conventional risk factors alone, integrating polygenic risk scores and protein proteomic risk scores improved discrimination, with the area under the curve increasing from 0.750 (95% CI, 0.732-0.767) to 0.789 (95% CI, 0.772-0.805) in internal validation and from 0.717 (95% CI, 0.683-0.750) to 0.762 (95% CI, 0.732-0.791) in external validation. A 9-protein panel (GDF15 [growth differentiation factor 15], MMP12 [matrix metalloproteinase 12], NPPB [natriuretic peptide B], PGF [placental growth factor], REN [renin], ADGRG2 [adhesion G-protein coupled receptor], ACE2 [angiotensin-converting enzyme 2], CDCP1 [CUB domain-containing protein 1], CXCL17 [C-X-C motif chemokine ligand 17)]) captured most proteomic predictive information. CONCLUSIONS: Our findings demonstrate that integrating conventional risk factors, polygenic risk scores, and proteomic data improves CAD risk prediction. This study highlights the utility of proteomics in precision cardiovascular medicine and simplified risk stratification tools.

Humans↗
PubMed1977

Mental, motor, and social behavior of infants with cleft lip and/or cleft palate.

This is a report of analyses of cross-sectional and longitudinal samples of the mental, motor, and social behavior of children with cleft lip and/or palate as measured by the Bayley Scales for Infant Development. Seventy-five patients of the Lancaster Cleft Palate Clinic were the subjects for the sample. The longitudinal sample consisted of 28 of these Ss for whom there were complete data at 6, 12, 18, and 24 months. The results indicated that there were no significant differences in mental and motor functioning. In both analyses, the social behavior of patients with oral-facial clefts was more passive than the Bayley normative sample. The implications of these findings for future research are discussed.

Child Behavior↗
PubMed2025

Targeted, Genome-scale Overexpression in Proteobacteria.

Targeted, genome-scale gene perturbation screens using Clustered Regularly Interspaced Short Palindromic Repeats interference (CRISPRi) and activation (CRISPRa) have revolutionized eukaryotic genetics, advancing medical, industrial, and basic research. Although CRISPRi knockdowns have been broadly applied in bacteria, options for genome-scale gene overexpression face key limitations. Here, we develop a facile approach for genome-scale overexpression in bacteria we call, "CRISPRtOE" (CRISPR transposition and OverExpression). We first create a platform for comprehensive gene targeting using CRISPR-associated transposons (CAST) and show that transposition occurs at a higher frequency in non-transcribed DNA. We then demonstrate that CRISPRtOE can upregulate gene expression in Proteobacteria with medical and industrial relevance by integrating synthetic promoters of varying strength upstream of target genes. Finally, we employ CRISPRtOE screening at the genome-scale in the model bacterium Escherichia coli and the non-model biofuel producer Zymomonas mobilis, recovering known and novel antibiotic and engineering targets. We envision that CRISPRtOE will be a valuable overexpression tool for antibiotic mode of action, industrial strain optimization, and gene function discovery in bacteria.

Journal Article↗
PubMed2025

Novel Predictive Spatial Biomarker in Non-Small Cell Lung Carcinoma: The Diversity of Niches Unlocking Treatment Sensitivity (DONUTS).

Probabilistic spatial modelling techniques developed on large-scale tumor-immune Atlases (~35M individually mapped cells; 50,000 high power fields) were used to characterize predictive features of treatment-responsive lung cancer. We identified CD8+FoxP3+ cell density as a robust pre-treatment biomarker for outcomes across disease stages and therapy types. In parallel, single-cell RNAseq studies of CD8+FoxP3+ T-cells revealed an activated, early effector phenotype, substantiating an anti-tumor role, and contrasting with CD4+FoxP3+ T-regulatory cells. A spatial biomarker was developed using an empirical probabilistic model to define the immediate cell neighbors or niche surrounding CD8+FoxP3+ cells and proximity to the tumor-stromal boundary. The resultant 'Diversity of Niches Unlocking Treatment Sensitivity (DONUTS)' are more prevalent than the CD8+FoxP3+ cells themselves, mitigating sampling error in small biopsies. Further, the DONUTS only require four markers, are additive to PD-L1, and associate with tertiary lymphoid structure counts. Taken together, the DONUTS represent a next-generation predictive biomarker poised for clinical implementation.

AstroPath↗
PubMed1978

Construct validation of the health belief model.

A multitrait-multimethod design was employed to assess the construct validity of the Health Belief Model. The data were obtained from a nonrepresentative sample of 85 graduate students at The University of Michigan's School of Public Health. The traits consisted of the respondents' perceptions of: health interest, locus of control, susceptibility to influenza, severity of influenza, benefits provided by a flu shot, and the barriers or costs associated with getting a flu shot. Each trait was measured by three methods: a seven-point Likert scale, a fixed-alternative multiple choice scale, and a vignette. The results indicate that the Health Belief Model variables can be measured with a substantial amount of convergent validity using Likert or multiple choice questionnaire items. With regard to discriminant validity, evidence suggests that subjects' perceptions of barriers and benefits are quite different from their perceptions of susceptibility and severity. Perceptions of susceptibility and severity are substantially but not entirely independent. Perceived benefits and barriers demonstrate a strong negative relationship which suggests the possibility that these two variables represent opposite ends of a single continuum and not separate health beliefs. These preliminary results provide the basis for developing brief health belief scales that may be administered to samples of consumers and providers to assess educational needs. Such needs assessment, in turn, could then be used to tailor messages and programs to meet the particular needs of a client group.

Attitude to Health↗
PubMed2025

Multicolor Cell Lineage Tracing Using MAGIC Markers Strategies.

Multicolor MAGIC Markers strategies are useful lineage tracing tools to study brain development at a multicellular scale. In this chapter, we describe an in utero electroporation method to simultaneously label multiple neighboring progenitors and their respective progeny using these multicolor reporters. In utero electroporation enables the introduction of any gene of interest into embryonic neural progenitors lining the brain ventricles through a simple pipeline consisting of a micro-injection followed by the application of electrical pulses. Successful in utero electroporation requires a concise yet complete understanding of each step of the surgical protocol, spanning from the preoperative preparation to the postoperative care, as well as the MAGIC Markers tool outlined in this study. Besides a detailed protocol, we present non-integrative and integrative approaches to demonstrate the range of cell and lineage tracking possibilities of multicolored progenitors and their descent over time.

Cell Lineage↗
PubMed2026

Dynamic Disentanglement Enables Highly Crystalline Fluorinated Polyimide Films Featuring Superior Dielectric Property and Intrinsic Thermal Conductivity.

The advancement of high-frequency communication and miniaturized electronics necessitates dielectric materials that combine high intrinsic thermal conductivity (λ) with low dielectric loss (Df) to mitigate signal delay and thermal accumulation. Conventional strategies, particularly nanocomposite approaches, often struggle to simultaneously achieve high λ and low Df without compromising processability or mechanical integrity. Herein, a semicrystalline polyimide (TAHQ/TFMB) architecture is initially established by circumventing the amorphous nature of fluorinated systems via rigid-rod backbone design and programmed thermal processing. Subsequently, minor dynamically exchangeable siloxane segments (≤ 1 mol%) act as molecular disentanglement switches, triggering topological rearrangement that promotes the formation of widely distributed crystal nuclei and enables the subsequent development of large-scale crystalline domains, ultimately yielding an enhanced crystallinity exceeding 50%. The optimally designed film with merely 0.25 mol% siloxane exhibits an enhanced in-plane λ of 2.33 W·m-1·K-1 and an ultralow Df of 0.00142 at 10 GHz. This synergy facilitates the first realization of a broadband thermoacoustic generator featuring an all-organic substrate and a flexible hairpin bandpass filter with excellent signal transmission performance. Furthermore, the DBPI-0.25 film exhibits excellent thermal stability (Td5% = 478.3°C), superior moisture resistance (water uptake of 0.41%), and good mechanical flexibility, rendering it highly suitable for advanced microelectronics.

crystalline polyimide↗
PubMed2026

Neurocorrelates of nocturnal enuresis in pre-adolescent children.

INTRODUCTION: Nocturnal enuresis (NE) is a common neurodevelopmental condition, yet its underlying neural mechanisms remain unclear. This study leverages the large-scale Adolescent Brain Cognitive Development (ABCD) dataset to identify structural and functional brain correlates associated with active symptoms and the resolution of bedwetting. METHODS: Using cross-sectional data from 3472 participants aged 9-10 years, children were categorized into three groups: active nocturnal enuresis (ANE, n = 225), history of nocturnal enuresis (HNE, n = 1171), and healthy control groups (CG, n = 2076). Multimodal neuroimaging protocol evaluated macrostructural properties via structural MRI (sMRI), microstructural white matter integrity via diffusion MRI (dMRI), and functional connectivity via resting-state fMRI (fMRI). Group differences were evaluated using linear models within an ANCOVA framework, adjusting for intracranial volume and handedness with False Discovery Rate (FDR) correction. RESULTS: Compared to controls, the ANE group exhibited a significant volume deficit in the right caudate, decreased sulcal depth in the left insula, and lower internal correlation within the Cingulo-Opercular Network (CON). Conversely, the dry HNE group demonstrated significant structural adaptations, including bilaterally larger putamen volumes and increased right caudate volume compared to the ANE group. The HNE group also showed increased microstructural density (decreased mean diffusivity) in the bilateral hippocampus and an increased cortical surface area in the left insula. Both NE groups demonstrated persistently reduced functional coupling within the CON. CONCLUSIONS: Nocturnal enuresis appears to be associated with a potential complex central signaling deficits. Reduced internal correlation within the CON across both active and former bedwetters indicates a potential for impairment in processing internal homeostatic bladder signals during sleep.

Humans↗
PubMed2005

Construction of a 2-Mb resolution BAC microarray for CGH analysis of canine tumors.

Recognition of the domestic dog as a model for the comparative study of human genetic traits has led to major advances in canine genomics. The pathophysiological similarities shared between many human and dog diseases extend to a range of cancers. Human tumors frequently display recurrent chromosome aberrations, many of which are hallmarks of particular tumor subtypes. Using a range of molecular cytogenetic techniques we have generated evidence indicating that this is also true of canine tumors. Detailed knowledge of these genomic abnormalities has the potential to aid diagnosis, prognosis, and the selection of appropriate therapy in both species. We recently improved the efficiency and resolution of canine cancer cytogenetics studies by developing a small-scale genomic microarray comprising a panel of canine BAC clones representing subgenomic regions of particular interest. We have now extended these studies to generate a comprehensive canine comparative genomic hybridization (CGH) array that comprises 1158 canine BAC clones ordered throughout the genome with an average interval of 2 Mb. Most of the clones (84.3%) have been assigned to a precise cytogenetic location by fluorescence in situ hybridization (FISH), and 98.5% are also directly anchored within the current canine genome assembly, permitting direct translation from cytogenetic aberration to DNA sequence. We are now using this resource routinely for high-throughput array CGH and single-locus probe analysis of a range of canine cancers. Here we provide examples of the varied applications of this resource to tumor cytogenetics, in combination with other molecular cytogenetic techniques.

Animals↗
PubMed1977

Protein components of very low density lipoproteins from hen's egg yolk.

Egg yolk lipoproteins of very low density were found to contain proteins with cofactor activity for lipoprotein lipase. When delipidated very low density lipoproteins were dissolved in 10 mM HCl and fractionated by gel filtration about two thirds of the protein were in several components with estimated molecular weights of 60000 to more than 170000. The major low-molecular-weight proteins were the dimeric and monomeric forms of a previously characterized 9000-dalton peptide. The cofactor activity was not associated with any of these major proteins. A large-scale fractionation method was developed by which two proteins fractions with cofactor activity for lipoprotein lipase were purified more than thousand-fold. One fraction had a molecular size of about 9000 daltons and the other had a size of about 5000 daltons. Both these fractions could be further separated on the basis of charge into several fractions with cofactor activity. The cofactor proteins were relatively soluble both at high and at low pH. The retained their cofactor activity after denaturation in guanidinium hydrochloride and after reduction. During the initial steps in the purification of the cofactor proteins another low-molecular-weight protein followed the cofactors. It had a single 17500-dalton peptide chain and was present in four variants, three of which contained carbohydrate.

Amino Acids↗
PubMed1979

Formulating therapeutic objectives as a prelude to program evaluation.

The author emphasizes the need for more precise formulation of goals for mental health treatment programs. He describes the Veterans Administration's five-year effort at goal formulation using ideas borrowed from operations research and education. With goals from various VA programs as examples, he illustrates how goal statements can be written with more specificity. He also describes how matching rating-scale items can be developed to measure the degree to which each goal is being met.

Evaluation Studies as Topic↗
PubMed1979

Predictability of treatment outcome in patients with myofascial pain-dysfunction (MPD) syndrome.

Responses to the Minnesota Multiphasic Personality Inventory (MMPI) were used to develop a 29-item scale designed to predict the treatment outcome of 135 patients with Myofascial Pain-Dysfunction (MPD) Syndrome. The results suggested that a single scale to predict treatment outcome would be ineffective due to the absence of consistent personality differences in MPD patients.

Adolescent↗
PubMedDate not supplied

[A micromethod for determination of the adenylate cyclase activity by chromatography on silufol UV-254 plates].

A method is developed for micro-scale separation of the products of enzymatic degradation of ATP (ADP, 5'-AMP, adenosine 3',5'-cytophosphate, adenosine and adenine) by one-dimentional thin-layer chromatography on Silufol UV-254 plates. The method is applicable for determination of activity of adenylate cyclase and of other enzymes involved in metabolism of adenylic derivatives, including the diesterase of 3',5'-cyclic AMP.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1979

A fluorescent derivative of ribosomal protein S18 which permits direct observation of messenger RNA binding.

70 S Escherichia coli ribosomes were reacted with the fluorescent dye N-(iodoacetylaminoethyl)-5-naphthylamine-1-sulfonic acid for 10 min under mild conditions. The resulting ribosomes were fully active. 30 S subunits isolated from these particles were also fully active. They contain approximately 0.7 eq of fluorescent dye. Nearly all of it is attached to protein S18. Competitive reaction with N-ethylmaleimide implies that the fluorescent dye is located at cysteine 10 of the protein. The labeled 30 S particles will recombine with 50 S subunits to form stable 70 S particles. Thus the procedures we have developed allow the large scale preparation of an active fluorescent conjugate of the 70 S ribosome. The fluorescence of the 70 S particles is sensitive to the binding of mRNA, showing both quenching and a shift in emission spectra. Thus it affords a simple way to quantitate mRNA binding directly. In pilot studies without tRNA, the binding constant of the initiation triplet codon adenylyl-(3' leads to 5')-uridylyl-(3' leads to 5')-guanosine to 70 S ribosome was found to be an order of magnitude larger than that of polyuridylic acid.

Escherichia coli↗
PubMed2025

OLS4: a new Ontology Lookup Service for a growing interdisciplinary knowledge ecosystem.

SUMMARY: The Ontology Lookup Service (OLS) is an open source search engine for ontologies which is used extensively in the bioinformatics and chemistry communities to annotate biological and biomedical data with ontology terms. Recently, there has been a significant increase in the size and complexity of ontologies due to new scales of biological knowledge, such as spatial transcriptomics, new ontology development methodologies, and curation on an increased scale. Existing Web-based tools for ontology browsing such as BioPortal and OntoBee do not support the full range of definitions used by today's ontologies. In order to support the community going forward, we have developed OLS4, implementing the complete OWL2 specification, internationalization support for multiple languages, and a new user interface with UX enhancements such as links out to external databases. OLS4 has replaced OLS3 in production at EMBL-EBI and has a backward compatible API supporting users of OLS3 to transition. AVAILABILITY AND IMPLEMENTATION: The source code of OLS is available at https://github.com/EBISPOT/ols4 and DOI 10.5281/zenodo.14960290 with Apache 2.0 License. A freely available implementation is accessible at https://www.ebi.ac.uk/ols4.

Biological Ontologies↗
PubMed1979

A rating scale for tardive dyskinesia.

A rating scale for tardive dyskinesia was developed, consisting of nearly all signs seen by two groups of investigators over a 5-year period. Thirty-four items were included in the scale with a possibility of writing in idiosyncratic signs. The scale was shown to have good reliability and validity in studies carried out by both the New York and Boston groups. It is recommended as a suitable instrument for describing the breadth of tardive dyskinesia syndrome and also for quantifying the disorder. A second scale, "the abbreviated dyskinesia scale", contains 13 items which are more global than the items in the original scale. It also has been shown to be both reliable and valid. Its use is suited to situations requiring less extensively detailed assessments.

Dyskinesia, Drug-Induced↗
PubMed2026

Characterization of a draft chromosome-scale genome assembly for the mutton snapper, Lutjanus analis.

BACKGROUND: The mutton snapper (Lutjanus analis) is a reef fish commonly found in tropical waters of the Western Atlantic Ocean. Genomic studies of this species are needed to support conservation efforts and breeding programs. OBJECTIVE: Here, we report the development of a chromosome-scale reference assembly for the mutton snapper and conduct an initial comparative genomic analysis with other lutjanids. METHODS: The genome of one mutton snapper specimen was sequenced using PAC-Bio HiFi long reads and Illumina short reads. Contigs and scaffolds were assembled in the Flye pipeline and anchored using Hi-C proximity guided assembly. Gene prediction and functional annotations were obtained in AUGUSTUS and eggNOG-mapper, respectively. The mutton snapper genome was compared to those of other lutjanids to infer gene family evolution and chromosome synteny conservation. RESULTS: Assembly and polishing yielded 946 contigs and 926 scaffolds (N50 of 3.16 Mb, complete BUSCO score 98.1%) that were anchored using Hi-C scaffolding in 24 draft chromosomes. The anchored assembly featured a N50 of 42.47 Mb and contained 97.6% of the unanchored assembly length. The 24 mutton snapper chromosomes showed a one-to-one syntenic relationship with their counterparts in medaka, and other Lutjanids. AUGUSTUS predicted 29,023 genes, 24,335 of which (83.85%) could be functionally annotated. Gene family evolution analysis revealed 1,014 significantly expanded or contracted hierarchical ortholog groups in mutton snapper. Expansions and contractions were linked to several biological functions including growth, oocyte maturation, and response to exogenous stressors. CONCLUSION: The draft genome will be a valuable tool for forthcoming applied genomic studies of mutton snapper.

Animals↗