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PubMed2026

A One Health approach to Antimicrobial Resistance: Concepts, challenges, and advances in omics.

Antimicrobial resistance (AMR) is a global threat driven by the interplay between microbial evolution and human activity. Antimicrobial use in human and veterinary medicine, as well as in agriculture, accelerates the selection and dissemination of resistant bacteria and genes across interconnected human, animal, and environmental reservoirs. These dynamic exchanges render single-sector interventions ineffective. A One Health approach integrating human, animal, and environmental health is therefore essential to understand and mitigate the emergence and spread of AMR. This chapter focuses on bacterial antimicrobial resistance, addressing key concepts, major challenges, and emerging technologies within a One Health framework. Advances in next-generation sequencing and omics technologies have transformed our capacity to resolve AMR at unprecedented scale and resolution. These tools enable the tracking of resistance genes and high-risk clones across ecosystems, uncover transmission pathways, and identify key drivers of dissemination. Such insights support real-time epidemiological surveillance, outbreak detection, and targeted interventions. However, translating these advances into routine practice remains a major challenge, requiring harmonized methodologies, data integration, and cross-sector coordination. Addressing AMR demands sustained collaboration across disciplines and stakeholders, including clinicians, veterinarians, farmers, researchers, policymakers, industry, and the public. And framing AMR as a shared ecological and societal responsibility underscores the urgency of coordinated global action. We call for the urgent integration of One Health principles into surveillance, policy, and innovation to preserve antimicrobial effectiveness and safeguard future health.

Humans↗

PubMed1992

Mixed microprocessor-random logic approach for innovative pacing systems.

Modern pacing systems are becoming more and more sophisticated. Conversion of the information supplied by a sensor into suitable parameters for a rate controlling algorithm and the management of complex timing are common tasks for an integrated circuit (IC) in cardiac pacing. An effective solution consists of using a microprocessor to implement algorithms and pacing modes in a flexible way. The key point of using the same hardware resources for different tasks on a time sharing basis allows the design of a less complex IC when compared to a random logic structure with the same performances. The major design problems in a full microprocessor solution are its relatively low operating speed due to the low frequency clock necessary for low current drain, and the sequential structure of the machine itself. This can lead to unacceptable timing inaccuracy in all situations requiring the management of complex decision trees. In order to take full benefit from the advantages of a microprocessor structure without these drawbacks, a mixed microprocessor-random logic approach has been investigated. This architecture uses a microprocessor core to perform all high level nonreal-time operations (setup of the pacing cycle, data reduction and processing, data integrity checks) while a set of random logic peripherals is used for all critical timing aspects.

Algorithms↗

PubMed2024

ONCOLINER: A new solution for monitoring, improving, and harmonizing somatic variant calling across genomic oncology centers.

The characterization of somatic genomic variation associated with the biology of tumors is fundamental for cancer research and personalized medicine, as it guides the reliability and impact of cancer studies and genomic-based decisions in clinical oncology. However, the quality and scope of tumor genome analysis across cancer research centers and hospitals are currently highly heterogeneous, limiting the consistency of tumor diagnoses across hospitals and the possibilities of data sharing and data integration across studies. With the aim of providing users with actionable and personalized recommendations for the overall enhancement and harmonization of somatic variant identification across research and clinical environments, we have developed ONCOLINER. Using specifically designed mosaic and tumorized genomes for the analysis of recall and precision across somatic SNVs, insertions or deletions (indels), and structural variants (SVs), we demonstrate that ONCOLINER is capable of improving and harmonizing genome analysis across three state-of-the-art variant discovery pipelines in genomic oncology.

Humans↗

PubMed1989

A relational database of protein structures designed for flexible enquiries about conformation.

A relational database of protein structure has been developed to enable rapid and flexible enquiries about the occurrence of many aspects of protein architecture. The coordinates of 294 proteins from the Brookhaven Data Bank have been processed by standard computer programs to generate many additional terms that quantify aspects of protein structure. These terms include solvent accessibility, main-chain and side-chain dihedral angles, and secondary structure. In a relational database, the information is stored in tables with columns holding the different terms and rows holding the different entries for the terms. The different relational base tables store the information about the protein coordinate set, the different chains in the protein, the amino acid residues and ligands, the atomic coordinates, the salt bridges, the hydrogen bonds, the disulphide bridges and the close tertiary contacts. The database was established under ORACLE management system. Enquiries are constructed in ORACLE using SQL (structured query language) which is simple to use and alleviates the need for extensive computer programs. A single table can be searched for entries that meet various criteria, e.g. all protein solved to better than a given resolution. The power of the database occurs when several tables, or the entries in a single table, are cross-correlated. For example the dihedral angles of proline in the fourth position in an alpha-helix in high resolution structures can be rapidly obtained. The structural database provides a powerful tool to obtain empirical rules about protein conformation. This database of protein structures is part of a joint project between Birkbeck College and Leeds University to establish an integrated data resource of protein sequences and structures (ISIS) that encodes the complex patterns of residues and coordinates that define protein conformation. The entire data resource (ISIS) will provide a system to guide all areas of protein modelling including structure prediction, site-directed mutagenesis and de novo protein design. The availability of ISIS is described in the paper.

Computer Simulation↗

PubMed2026

Comparative genomics reveals genotype-phenotype concordance and cryptic resistomes in clinical Pseudomonas aeruginosa.

BACKGROUND: Pseudomonas aeruginosa (P. aeruginosa) is a major pathogen because of its adaptability. It shows rapid evolution of multidrug resistance (MDR). Phenotype-based diagnostics often fail to detect silent resistance determinants and early adaptive changes. This study integrates phenotypic profiling with whole-genome sequencing (WGS) to examine resistance architecture in clinical isolates from eastern India. METHODS: From 1295 culture-positive P. aeruginosa specimens collected at a tertiary care hospital in eastern India. Using predefined criteria, representative MDR and non-MDR isolates were selected, including distinct resistance phenotypes, specimen-source diversity, and hospital and community-acquired settings; multivariate analysis of resistance profiles illustrated phenotypic diversity. Antimicrobial susceptibility assessed using VITEK-2 and Kirby-Bauer disk diffusion, species identity confirmed by 16 S rRNA sequencing, and genomic analysis processed through a reference-guided workflow. Antimicrobial Resistance (AMR) determinants were identified through CARD, and phylogenetic tree constructed from 454 publicly available P. aeruginosa genomes. RESULTS: MDR exhibited greater sequence divergence relative to PA14 (~ 69,000 variants) than the non-MDR isolate (~ 58,700 variants), with > 92% coverage at ≥ 30X depth. Strong genotype-phenotype concordance observed in MDR isolates across five antibiotic classes, associated with β-lactamase variants (PDC-67, OXA-396) and regulatory adaptations (ArmR, cprS). The non-MDR isolate harboured gyrA (T83I) resistance-associated mutations, PDC-1, and OXA-847 without phenotypic expression, indicating silent resistome. Phylogenetically, MDR isolates clustered tightly within the phylogeny, while the non-MDR isolate formed a distinct lineage. CONCLUSION: Observed genomic differences align with adaptation under antimicrobial selection, though confirmation requires larger collections. The non-MDR isolate retained a silent resistome. Findings highlight limitations of phenotype-only diagnostics, support genomic data integration, and emphasize transcriptomics for hidden resistance expression and regulatory dynamics.

Pseudomonas aeruginosa↗

PubMed1985

Costs of mandates for outpatient mental health care in private health insurance.

Various methods for estimating the cost of mandated mental health benefits have been devised, each resulting in substantially different estimates. These methods neglect to distinguish between the two components of cost to the insurer: social cost (due to increased utilization) and shifted cost (from other sources of payment). We apply a method we developed for estimating the two types of costs of mandates for outpatient mental health services that integrates data from insurers with information from the literature on financing of mental health services. We applied our method to legislation recently proposed in Massachusetts that would double the mandated minimum benefit level from +500 to +1,000. We expect payments by the largest carrier in the state to increase by a factor of 1.65. More than half of this increase represents shifted costs rather than new costs to society.

Ambulatory Care↗

PubMed1989

Comprehensive quality assessment approach for flow cytometric immunophenotyping of human lymphocytes.

Flow cytometric immunophenotypic (IPT) evaluation has become an important adjunct to clinical patient management and epidemiological studies. This has precipitated a need for stringent quality assessment (QA) procedures to ascertain data integrity. We evaluated a QA approach to monitor all elements of the immunophenotyping process, inclusive of blood collection and processing procedures as well as of staining reagent and instrument performance. Central to our approach was preparation each day, in parallel with clinical analytes, of lymphocytes from healthy donors, selected from a 15 donor panel. IPT parameters evaluated over a 19 month period included frequencies of CD3+, CD4+, CD8+, and CD20+ lymphocytes and the ratio of CD4+ to CD8+ lymphocytes. The sensitivity for analytical error detection was reflected by median coefficients of variation of these parameters within individual panel donors, which were 4.1%, 4.5%, 3.9%, 8.2%, and 10.1%, respectively. IPT parameter values were determined each day for two of the panel donors, then averaged and standardized to obtain a quality or Q variate, which was the basis of QA. Error detection sensitivity decreased 0.6-1.7% and the number of false rejections increased 1.2-3.3% when one panel donor rather than two was used daily for QA. This study also illuminated important aspects of what constitutes the norm for longitudinal IPT parameter variation in healthy individuals including: 1) a generally low degree of temporal parameter variation within individual donors, but 2) significant differences between donors with respect to variance estimates for CD3+ and CD8+ lymphocyte frequencies and CD4+/CD8+ lymphocyte ratios, and 3) an apparent seasonal pattern of variation in CD4+ T-cell frequencies.

Antibodies, Monoclonal↗

PubMed2026

Bioinformatics Analysis and Experimental Validation of Key Genes Associated With Hypoxia and Ischemia in Myocardial Infarction.

BACKGROUND: This study aimed to screen and identify core hypoxia-ischemia-related genes associated with myocardial infarction (MI). METHOD: Two transcriptomic datasets, GSE97320 and GSE48060, were retrieved from the Gene Expression Omnibus (GEO) database. After data integration and batch effect elimination, differential expression analysis was performed to screen differentially expressed genes (DEGs), and the corresponding visualization analysis was conducted. Hypoxia-ischemia-related genes were acquired from the GeneCards database; hypoxia-ischemia related genes (HIRGs) were subsequently identified by intersecting the retrieved genes with screened DEGs. Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were implemented to explore the biological functions and underlying signaling pathways of HIRGs. A combination of protein-protein interaction (PPI) network analysis and random forest (RF) algorithm was applied to screen hub genes from HIRGs. The external GEO dataset GSE66360 was utilized to validate the expression patterns of candidate hub genes. Furthermore, an acute myocardial infarction (AMI) mouse model was established, and quantitative real-time polymerase chain reaction (qPCR) was performed to detect the mRNA expression levels of hub genes in myocardial tissues for in vivo validation. RESULTS: A total of 633 DEGs and 308 hypoxia-ischemia-related genes were screened in the present study, among which 21 overlapping HIRGs were obtained. PLAUR and IL1B were finally identified as two hub genes from HIRGs based on PPI network and random forest algorithm. The qPCR results revealed that the expression levels of PLAUR and IL1B were significantly upregulated in the AMI group compared with the sham operation group (p < 0.05). CONCLUSION: The present findings demonstrated that PLAUR and IL1B serve as pivotal genes involved in the pathological hypoxia-ischemia process of AMI. These two genes may act as novel biomarkers and promising therapeutic targets for the recognition and clinical intervention of hypoxia-ischemia injury following AMI.

Myocardial Infarction↗

PubMed2026

Application of Omics Technologies for Cowpea Improvement.

Cowpea (Vigna unguiculata) is a vital crop for food security, nutrition, and climate resilience in sub-Saharan African and other semi-arid regions. However, its improvement is constrained by the complexity of polygenic traits such as drought tolerance, pest resistance, and seed quality. Conventional breeding, while foundational, remains insufficient to address these challenges at the required pace. Recent advances in multi-omics technologies, including genomics, transcriptomics, proteomics, and metabolomics, provide new opportunities to dissect complex traits, identify candidate genes, and accelerate the development of resilient, high-yielding cultivars. This review presents a critical synthesis of current applications of omics technologies in cowpea improvement, highlighting their contributions to stress adaptation, nutritional enhancement, and precision breeding. The review also examines key technical and institutional constraints limiting the adoption of omics-assisted breeding in cowpea, including inadequate research infrastructure, challenges in multi-omics data integration, and limited technical capacity across breeding programs in sub-Saharan Africa. It discusses strategies to address these barriers through regional collaboration, investment in bioinformatics capacity, and the integration of computational approaches into breeding pipelines. Overall, the review concludes that combining multi-omics technologies with artificial intelligence and machine learning has strong potential to improve genotype-phenotype prediction, accelerate breeding decisions, and support the development of climate-resilient and nutritionally enhanced cowpea cultivars.

cowpea↗

PubMed1976

A critical evaluation of the relationship between the presynaptic network, synaptic vesicles and dense projections in central synapses.

Synapses of the oculomotor nucleus of Echidna have been examined ultrastructurally with the aim of integrating data obtained from osmicated and nonosmicated PTA stained material. Particular emphasis has been laid on the relationship between the synaptic vesicles of the osmicated material and the presynaptic network and vesicular grid of the PTA material. This relationship has been explored qualitatively by examining osmicated material of varying qualities of fixation. Such material contains dense projections in addition to synaptic vesicles, and various vesicular network appearances. A variety of measurement techniques have shown that the PTA network is characterised by reticular strands, spaces, and regular hexagonal units smaller than vesicles, these observations prompting the formulation of a "vesicle-network coincidence" model of the presynaptic terminal. This model has been tested by tracing the profiles of vesicles within the PTA network and comparing their size and shape frequency distributions with those of osmicated synaptic vesicles. The distributions have been found to be essentially similar, suggesting that vesicles can be located within the network, and that the hexagonal network units are formed only in the presence of an underlying vesicular matrix. Additionally, the following points have emerged: 1) the dense projections in the two types of material appear to be quivalent; 2) a loose correlation exists between dense projections and vesicles in osmicated terminals, increase in the area of the dense projections being associated with a decrease in the area of the vesicles; 3) network and dense projection units are similar. In view of the similarity between network and dense projection units, the demonstrated vesicular basis of the network raises the question of whether dense projections are entirely independent structures, or whether they depend in part for their existence on the nearby presence of synaptic vesicles.

Animals↗

PubMed1987

Visualization on full spine radiographs of the anatomical connections of the centres of the segmental body mass supported by each vertebra and measured in vivo.

A gamma-ray scanner has been used to develop in vivo a rapid, noninvasive technique for the estimation of the mass of successive body scans, and the positions of the centres of those masses. The integrated data are computed to calculate the mass supported by each vertebra and the coordinates of the centre of these masses. These coordinates are transferred from the coordinate system of the gamma ray table to the coordinate system of the X-ray radiographs. In this way, the anatomical relations of the centres of these masses are visualized on the frontal and sagittal full spine radiographs. The method allowed the estimation of various biomechanical parameters such as the height of half the body mass or the compressive load on a specific vertebra. These new parameters were found to be similar to equivalent parameters in the literature. Therefore, these comparisons validate the method. Fourteen normal subjects were tested, and their mean data are proposed as reference.

Adult↗

PubMed1982

Stimulant drug effects in developmental disorders and hyperactivity--toward a resolution of disparate findings.

An attempt is made to integrate data from a variety of clinical populations and from the animal literature. Evidence is presented suggesting that mentally retarded and autistic children generally show a poor response to stimulant medication, whereas hyperactive and normal children respond beneficially. Cognitive research in mentally retarded and autistic children is reviewed, and it is suggested that both diagnostic groups suffer from attentional difficulties, the mechanisms of which may be very similar. The literature on stimulant-induced stereotypy in animals is discussed, with emphasis on the clinical implications for autism and mental retardation. An attentional model is proposed to account for type of therapeutic response to stimulant medication. This is followed by a possible method for testing the model and by specific predictions relating to subject characteristics and response.

Amphetamines↗

PubMed2025

Exploring potential targets and molecular mechanisms of traumatic brain injury exacerbated by Benzo(a)pyrene via network toxicology and molecular dynamics simulation.

Benzo(a)pyrene (BaP) is a common environmental pollutant from combustion sources that promotes oxidative stress, neuroinflammation and disruption of blood-brain barrier (BBB). However, its contribution to worsening traumatic brain injury (TBI) remains unclear. In this study, we aimed to assess the contribution of BaP to secondary injury in TBI. By integrating data from e.g., the Comparative Toxicogenomics Database, GeneCards, and Online Mendelian Inheritance in Man, 121 overlapping core targets were identified between BaP and TBI. Enrichment analyses via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, combined with protein-protein interaction networks and topological algorithms (degree, closeness centrality, betweenness centrality, average shortest path length, topological coefficient and partner of multi-edged node pairs), highlighted five hub genes (TP53, EGFR, AKT1, ACTB, and TNF) implicated in mitogen-activated protein kinase signaling, oxidative stress, and neuroinflammation. Molecular docking showed strong binding affinities of BaP to these hub proteins, with energies from -9.3 to -12.1 kcal/mol, tighter than co-crystal ligands and existing protein-binding drugs. Molecular dynamics simulations confirmed interaction stability through low root-mean-square deviation (< 0.5 nm), fluctuation, and radius of gyration values. Calculation of binding free energies using MM-PBSA validated the strong binding affinity between BaP and binding pockets of each hub genes. Toxicity prediction analysis revealed an oral LD50 of 316 mg/kg for BaP, with high probabilities for neurotoxicity, BBB permeability, carcinogenicity, and mutagenicity, associated with aryl hydrocarbon receptor activation. These findings reveal a "neurovascular homeostasis disruption" network underlying BaP-exacerbated TBI pathology and highlight potential targets to reduce pollution-related risks in TBI management.

Benzo(a)pyrene↗

PubMed1980

Dimensional changes in the dental arches of orthodontically treated cases.

Integrated data from lateral cephalometric radiographs and study models of fifty-three patients were studied to assess the interactions between dimensional changes occurring during orthodontic treatment and the postretention stability of these changes. A new technique was developed to study distal movement of canines. Distal movement of canines did not ensure a stable increase in intercanine width. There was no significant relationship between mesiodistal position of the first molars and changes in intermolar width. Eruption of the first molar in the postretention period was associated with greater stability in overbite. There was no great degree of correlation between depth of the curve of Spee and inclination of the occlusal plane or between changes in arch length and changes in inclinations of the incisors.

Cephalometry↗

PubMed1989

Examination of automated polypeptide sequencing using standard phenyl isothiocyanate reagent and subpicomole high-performance liquid chromatographic analysis.

The feasibility of accurate protein sequencing at the subpicomole level, using automated Edman chemistry and "on-line" HPLC analysis, was studied. Several modifications of the standard system were first introduced. A larger portion of the phenylthiohydantoin amino acids (70%) is analyzed. Dissolution in 10% acetonitrile is improved by short periodic bursts of argon. Losses on the column of subpicomole amounts of analytes, in the presence and absence of scavengers, were quantitated; they are related to destruction rather than to unspecific sticking to the stationary phase. Baseline drift, for a large part caused by the presence of ultraviolet absorbing N,N-dimethylphenylthiourea in solvent B, is completely eliminated by the addition of a twofold molar excess of tryptophan to solvent A. This allows real time recording of the 269-nm absorption detector signal at 0.0005 absorption unit full scale. The combined modifications result in an eightfold increase in sensitivity over standard methods. Sequence calling at the 2 to 10 pmol level, through visual inspection of chromatograms, becomes increasingly simple this way. Once the sequenceable signal drops below the 1 pmol level in the course of a run, meticulous comparison and matching of the preliminary calls with a spreadsheet of peak integration data are necessary for accurate assignments. Reliable sequencing, with signals at the subpicomole level, is now feasible for stretches of over 10 residues. Contaminating amino acids and polypeptides and incompletely removed reaction by-products constitute a major problem for analysis at this level. Future limits to sensitivity of Edman sequencing will primarily depend on improved micropreparations of proteins in cleaner environments, higher purity reagents and solvents, instrument miniaturization, and solid-phase techniques.

Amino Acid Sequence↗

PubMed1978

Clinical data evaluation and the PL health control information system.

In a health control service environment, that is, a periodic, membership AMHTS type of comprehensive health check-up system, where clinical data evaluation especially an evaluation in terms of subject-specific normal ranges, is most important, the medical information system is required to handle: (1) Various network types files; (2) real-time immediacy; (3) an asserted reliability to meet personal health control purposes. As in other computer applications already successfully used, an indexed direct assess method (IDAM) developed is our solution. It allows us to provide multiple indices for the file network, instead of inverted files, a unique index-to-record relationship, preventing any unrecoverable chaining destruction and, thereby, provides any network type access a stable access time. Furthermore, for research purposes, a data integrity for on-line access and batch access was attained as well as a retrieval language system with a multiple key retrieval function.

Diagnosis, Computer-Assisted↗

PubMed1984

Oxygen consumption in collagenase-liberated rat adipocytes in relation to cell size and age.

Oxygen consumption of collagenase-liberated rat adipocytes was measured by two different techniques: a microspectrophotometric method using hemoglobin as indicator of respiration and a technique using the oxygen electrode. These two completely different techniques gave similar values for oxygen consumption. With the spectrophotometric method, the oxygen consumption of single fat cells was determined. A close positive correlation (r = greater than 0.90) between oxygen consumption and fat cell size was observed in each tissue examined. With the oxygen electrode technique, oxygen consumption of adipocyte suspensions from young (40 days, 180 g) and old (90 days, 480 g) rats was examined. Fat cells of the suspensions were separated into classes of different size by a flotation technique. A significant positive correlation between fat cell size and oxygen consumption was observed in both young (r = 0.88) and old (r = 0.95) rats. However, the slope was much steeper in young rats. At a cell weight of 0.1 microgram the oxygen consumption was 0.364 and 0.086 microL O2/10(6) cells/min-1 in young and old rats, respectively. In the literature, a number of separate metabolic pathways have been found to be related positively to fat cell size and negatively to age. We conclude that these scattered metabolic observations are in agreement with integrated data on energy expenditure as evaluated from oxygen consumption. Estimations of the energy expenditure of adipose tissue indicates that this tissue is responsible for about 1% and 0.5% of the total energy expenditure in young and old rats, respectively.

Adipose Tissue↗

PubMed1995

Ins and outs of LFA-1.

Leukocyte function-associated molecule 1 (LFA-1) is an integrin that plays a major role in the immune system. Recent findings demonstrate that LFA-1 has a two-way signaling function, mediating cell adhesion and stimulating intracellular processes at the same time. Here, Marijke Lub, Yvette van Kooyk and Carl Figdor discuss the 'inside-out' and 'outside-in' signaling properties of LFA-1, as a prototype leukocyte integrin, in normal and malignant T cells. They integrate data into a model that highlights the role of the cytoskeleton in the regulation of LFA-1.

Animals↗