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At least 829 records · Page 46Linked to original sources
PubMed2026

Genome-wide characterization of NOD-like receptor genes links NLR repertoire evolution to spleen immune responses after Aeromonas hydrophila challenge in the Chinese spiny frog (Quasipaa spinosa).

NOD-like receptors (NLRs) are cytosolic pattern-recognition receptors that detect pathogen-associated and damage-associated molecular patterns and mediate innate immune signaling in vertebrates. However, the genomic repertoire, evolutionary diversification, and infection-associated expression of NLR genes remain poorly defined in non-model amphibians. In this study, 66 NLR genes were identified from the Chinese spiny frog (Quasipaa spinosa) genome and designated as QsNLR1-QsNLR66. These genes were unevenly distributed across chromosomes and were classified into three phylogenetic groups, with most members exhibiting conserved motif architectures. Gene duplication analysis indicated that dispersed duplication was the main contributor to QsNLR expansion. Synteny analysis detected five conserved orthologous gene pairs between Q. spinosa and Pelophylax nigromaculatus, suggesting partial conservation of NLR genomic organization between the two amphibians. Ka/Ks analysis showed that several duplicated gene pairs, including NLRC3-like/QsNLR36 and NLRC3-like/QsNLR50, exhibited Ka/Ks ratios greater than one, suggesting potential sequence divergence after duplication. Spleen RNA sequencing (RNA-seq) after Aeromonas hydrophila challenge revealed enrichment of immune-related Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Weighted gene co-expression network analysis linked several QsNLRs to infection-associated modules, among which QsNLR57 was co-expressed with CYBB, ADAM17, SPI1, and HK2. RT-qPCR using time-matched phosphate-buffered saline (PBS) controls showed distinct temporal patterns, with stronger induction of QsNLR29, QsNLR57, and QsNLR66 and weaker or delayed responses of QsNLR50 and QsNLR56. These results characterize the NLR repertoire of Q. spinosa and identify infection-associated QsNLR candidates for future studies of antibacterial immunity in amphibians.

Animals↗
PubMed1997

Long-term identification of streptomycetes using pyrolysis mass spectrometry and artificial neural networks.

Sixteen reference strains and thirteen fresh isolates of three putatively novel Streptomyces species were examined six times over twenty months using pyrolysis mass spectrometry to examine the long-term reproducibility of the procedure. The reference strains and new isolates were correctly identified using information in each of the datasets and operational fingerprinting, but direct statistical comparison of the datasets for strain identification was unsuccessful between datasets. Artificial neural networks were also used to identify the strains held in the datasets. Neural networks trained with pyrolysis mass spectra from a single dataset were found to successfully identify the reference strains and fresh isolates in that dataset but were unable to identify many of the strains in the other datasets. However, a neural network trained on representative pyrolysis mass spectra from each of the first three datasets were found to identify the reference strains and fresh isolates in those three datasets and in the three subsequent datasets. Therefore, artificial neural network analysis of pyrolysis mass spectrometric data can provide a rapid, cost-effective, accurate and long-term reproducible way of identifying and typing microorganisms.

Humans↗
PubMed2025

Single-cell analysis of dup15q syndrome reveals developmental and postnatal molecular changes in autism.

Duplication 15q (dup15q) syndrome is a leading genetic cause of autism spectrum disorder, offering a key model for studying autism-related mechanisms. Using single-cell and single-nucleus RNA sequencing of cortical organoids from dup15q patient-derived iPSCs and post-mortem brain samples, we identify increased glycolysis, disrupted layer-specific marker expression, and aberrant morphology in deep-layer neurons during fetal-stage organoid development. In adolescent-adult postmortem brains, upper-layer neurons exhibit heightened transcriptional burden related to synaptic signaling, a pattern shared with idiopathic autism. Using spatial transcriptomics, we confirm these cell-type-specific disruptions in brain tissue. By gene co-expression network analysis, we reveal disease-associated modules that are well preserved between postmortem and organoid samples, suggesting metabolic dysregulation that may lead to altered neuron projection, synaptic dysfunction, and neuron hyperexcitability in dup15q syndrome.

Humans↗
PubMed2024

Transcriptome analysis under pecan scab infection reveals the molecular mechanisms of the defense response in pecans.

Pecan scab, caused by the fungal pathogen Venturia effusa, is the most devastating disease of pecan (Carya illinoinensis) in the southeastern United States. Resistance to this pathogen is determined by a complex interaction between host genetics and disease pathotype with even field-susceptible cultivars being resistant to most scab isolates. To understand the underlying molecular mechanisms of scab resistance in pecan, we performed a transcriptome analysis of the pecan cultivar, 'Desirable', in response to inoculation with a pathogenic and a non-pathogenic scab isolate at three different time points (24, 48, and 96 hrs. post-inoculation). Differential gene expression and gene ontology enrichment analyses showed contrasting gene expression patterns and pathway enrichment in response to the contrasting isolates with varying pathogenicity. The weighted gene co-expression network analysis of differentially expressed genes detected 11 gene modules. Among them, two modules had significant enrichment of genes involved with defense responses. These genes were particularly upregulated in the resistant reaction at the early stage of fungal infection (24 h) compared to the susceptible reaction. Hub genes in these modules were predominantly related to receptor-like protein kinase activity, signal reception, signal transduction, biosynthesis and transport of plant secondary metabolites, and oxidoreductase activity. Results of this study suggest that the early response of pathogen-related signal transduction and development of cellular barriers against the invading fungus are likely defense mechanisms employed by pecan cultivars against non-virulent scab isolates. The transcriptomic data generated here provide the foundation for identifying candidate resistance genes in pecan against V. effusa and for exploring the molecular mechanisms of disease resistance.

Carya↗
PubMed2026

ACE2 and Parkinsonism‑related bone metabolic alterations: signaling pathways and hub gene analysis.

Clinical co-occurrence of Parkinson's disease (PD) and age-related bone loss in elderly patients has garnered increasing attention, yet its molecular mechanisms remain incompletely elucidated. This study used an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model in Ace2-/y mice to investigate the regulatory mechanisms of bone-brain axis-related genes and signaling pathways. Behavioral tests assessed motor and non-motor symptoms. Immunohistochemistry, Western blot, and histopathological staining analyzed dopaminergic neuron activity, microglial activation, and bone metabolic abnormalities. GEO dataset transcriptomics and weighted gene co-expression network analysis (WGCNA) identified key hub genes, with receiver operating characteristic (ROC) curves evaluating their diagnostic value in public single-disease transcriptome data. MPTP significantly exacerbated motor dysfunction and depression-like behaviors; Ace2 deletion lowered total Wnt, β-catenin, BMP and IGF-1 protein abundance alongside reduced phosphorylation ratios of their downstream kinases in brain and bone, while upregulating RANKL/RANK/OPG-associated inflammatory mediators, accompanied by elevated total α-synuclein, Casp3 and Bax protein levels. The parallel reduction of these signaling proteins only suggests potential perturbation of related cascades; WGCNA identified 10 hub genes (e.g., DNM1, OCRL, OPA1), whose dysregulation was linked to synaptic dysfunction and inflammation. ROC analysis based on single-disease datasets showed high diagnostic accuracy for PD and `osteoporosis (OP) (AUC: 0.683-0.981), with core genes influencing synaptic, MAPK, Rap1, and Ras pathways. These preclinical findings indicate that Ace2 deficiency is associated with concurrent pathological abnormalities in the brain and transient bone metabolic disturbance under short-term MPTP treatment in growing young male mice; coordinated dysregulation of shared signaling pathways was observed in the two tissues, consistent with a potential bone-brain axis pathological phenotype, though causal bidirectional tissue cross-talk cannot be confirmed in the current experimental design, providing candidate targets that warrant further validation.

Animals↗
PubMed1999

An electronic network for the surveillance of antimicrobial resistance in bacterial nosocomial isolates in Greece. The Greek Network for the Surveillance of Antimicrobial Resistance.

The present article reports an evaluation of the national electronic network for the continuous monitoring of antimicrobial resistance in Greece. The network employs a common electronic code and data format and uses WHONET software. Our four years' experience with the network confirms its practicality. A total of 22 hospitals in Greece are currently using the software, of which 19 participate in the network. Analysis of the information obtained has greatly helped in identifying the main factors responsible for the emergence of antimicrobial resistance in the participating hospitals. The data collected have also helped to identify priorities for further investigation of the genetic and molecular mechanisms responsible for the emergence of resistance and facilitated development of hospital-based empirical therapy of infections. In conclusion, the implementation of national networks for the surveillance of antimicrobial resistance should be regarded as a priority.

Computer Communication Networks↗
PubMed2025

Transcriptome-wide analysis reveals potential roles of CFD and ANGPTL4 in fibroblasts regulating B cell lineage for extracellular matrix-driven clustering and novel avenues for immunotherapy in breast cancer.

BACKGROUND: The remodeling of the extracellular matrix (ECM) plays a pivotal role in tumor progression and drug resistance. However, the compositional patterns of ECM in breast cancer and their underlying biological functions remain elusive. METHODS: Transcriptome and genome data of breast cancer patients from TCGA database was downloaded. Patients were classified into different clusters by using non-negative matrix factorization (NMF) based on signatures of ECM components and regulators. Weighted Gene Co-expression Network Analysis (WGCNA) was used to identify core genes related to ECM clusters. Additional 10 independent public cohorts including Metabric, SCAN_B, GSE12276, GSE16446, GSE19615, GSE20685, GSE21653, GSE58644, GSE58812, and GSE88770 were collected to construct Training or Testing cohort, following machine learning calculating ECM correlated index (ECI) for survival analysis. Pathway enrichment and correlation analysis were used to explore the relationship among ECM clusters, ECI and TME. Single-cell transcriptome data from GSE161529 was processed for uncovering the differences among ECM clusters. RESULTS: Using NMF, we identified three ECM clusters in the TCGA database: C1 (Neuron), C2 (ECM), and C3 (Immune). Subsequently, WGCNA was employed to pinpoint cluster-specific genes and develop a prognostic model. This model demonstrated robust predictive power for breast cancer patient survival in both the Training cohort (n = 5,392, AUC = 0.861) and the Testing cohort (n = 1,344, AUC = 0.711). Upon analyzing the tumor microenvironment (TME), we discovered that fibroblasts and B cell lineage were the core cell types associated with the ECM cluster phenotypes. Single-cell RNA sequencing data further revealed that angiopoietin like 4 (ANGPTL4)+ fibroblasts were specifically linked to the C2 phenotype, while complement factor D (CFD)+ fibroblasts characterized the other ECM clusters. CellChat analysis indicated that ANGPTL4+ and CFD+ fibroblasts regulate B cell lineage via distinct signaling pathways. Additionally, analysis using the Kaplan-Meier Plotter website showed that CFD was favorable for immunotherapy response, whereas ANGPTL4 negatively impacted the outcomes of cancer patients receiving immunotherapy. CONCLUSION: We identified distinct ECM clusters in breast cancer patients, irrespective of molecular subtypes. Additionally, we constructed an effective prognostic model based on these ECM clusters and recognized ANGPTL4+ and CFD+ fibroblasts as potential biomarkers for immunotherapy in breast cancer.

Humans↗
PubMed2001

Automated mode-of-action detection by metabolic profiling.

Rapid classification and identification of the mode-of-action of bioactive compounds applied to plants can be achieved by a robust and easy-to-use metabolic-profiling method. This method uses artificial neural network analysis of one-dimensional proton NMR spectra of aqueous plant extracts to rapidly classify changes in the total metabolic profile caused by application of crop protection chemicals.

Automation↗
PubMed2026

Multiomics Integration Identifies a Molecular Subtype of Intrahepatic Cholangiocarcinoma With Enhanced Benefit From Adjuvant Therapy.

Intrahepatic cholangiocarcinoma (iCCA) is a molecularly heterogeneous liver cancer with a poor prognosis. Improved stratification is needed to guide postoperative therapy. In this study, we applied integrative multiomics analysis to classify iCCA and identify biomarkers predictive of adjuvant treatment benefit. Using publicly available datasets (including whole exome sequencing, RNA sequencing, proteomics, and phosphoproteomics from FU-iCCA cohort and a transcriptomic cohort GSE244807), we defined 3 robust molecular subtypes of iCCA. These subtypes exhibited distinct genomic alterations, pathway activation, and immune microenvironments, with significant differences in overall survival (OS). Through protein-protein interaction network analysis and consensus feature selection using 10 clustering algorithms, we prioritized 8 marker genes distinguishing the subtypes. A Cox proportional-hazards model constructed from these markers stratified patients into high- and low-risk groups. High-risk iCCA, characterized by elevated expression of markers such as CLDN18, MUC1, and MUC5AC, had significantly worse OS in the absence of adjuvant therapy. Notably, in an independent validation of 174 patients with iCCA who underwent resection (single-center cohort), high expression of any of these 3 markers were associated with markedly prolonged OS in patients who received adjuvant chemotherapy or chemoembolization, compared with those who did not. In contrast, marker-negative patients showed no clear benefit from adjuvant therapy. In conclusion, our multiomics approach identified a high-risk, mucin-enriched subtype of iCCA. CLDN18, MUC1, and MUC5AC emerge as candidate predictive biomarkers for adjuvant chemotherapy benefit in iCCA, warranting prospective validation to improve personalized postoperative management.

Humans↗
PubMed1998

Dbp6p is an essential putative ATP-dependent RNA helicase required for 60S-ribosomal-subunit assembly in Saccharomyces cerevisiae.

A previously uncharacterized Saccharomyces cerevisiae open reading frame, YNR038W, was analyzed in the context of the European Functional Analysis Network. YNR038W encodes a putative ATP-dependent RNA helicase of the DEAD-box protein family and was therefore named DBP6 (DEAD-box protein 6). Dbp6p is essential for cell viability. In vivo depletion of Dbp6p results in a deficit in 60S ribosomal subunits and the appearance of half-mer polysomes. Pulse-chase labeling of pre-rRNA and steady-state analysis of pre-rRNA and mature rRNA by Northern hybridization and primer extension show that Dbp6p depletion leads to decreased production of the 27S and 7S precursors, resulting in a depletion of the mature 25S and 5.8S rRNAs. Furthermore, hemagglutinin epitope-tagged Dbp6p is detected exclusively within the nucleolus. We propose that Dbp6p is required for the proper assembly of preribosomal particles during the biogenesis of 60S ribosomal subunits, probably by acting as an rRNA helicase.

Amino Acid Sequence↗
PubMed1998

HIV seroprevalence, risk behaviors, and cognitive factors among Asian and Pacific Islander American men who have sex with men: a summary and critique of empirical studies and methodological issues.

The goals of this article are to (a) summarize and discuss published empirical studies addressing HIV seroprevalence rates and HIV-related behaviors and cognitive factors among Asian and Pacific Islander American (API) men who have sex with men (MSM) in the United States, (b) examine existing population-based research methodologies for studying HIV and AIDS prevention, (c) describe a conceptual framework to facilitate the identification of ecologically sound or culturally appropriate and competent methodologies for studying HIV prevention among API MSM, and (d) discuss methodological issues and recommend alternative methodologies to better understand this population in HIV prevention. A total of eight published empirical studies reported the HIV seroprevalence rates, HIV-risk behaviors, and attitudes toward HIV and AIDS among API MSM. Specifically, seven studies reported HIV seroprevalence rates that were based on either self-disclosure of HIV status or HIV test results among the study participants. Four studies also reported findings about the relationships between HIV-related behaviors and cognitive factors. There are five population-based databases on HIV and AIDS epidemiology and surveillance which have been managed by the Centers for Disease Control and Prevention. Findings from the seven studies indicate that API MSM are as likely to engage in HIV-risk behaviors as other groups. The present analysis reveals that conventional surveillance or epidemiological techniques (e.g., random digit telephone dialing), based on a singular model of populations, are not appropriate to address culturally, linguistically and racially/ethnically diverse groups of API MSM. To address the diversity of this group, ecologically sound or culturally appropriate and competent research methodologies are needed. Thus, a conceptual framework for such methodologies with examples was reviewed. Two alternative methodologies, network analysis and venue-based sampling, were briefly discussed.

Asian↗
PubMed2026

Integrative multi-omics analyses suggest a candidate microbial metabolite-associated host gene network in ulcerative colitis.

Ulcerative colitis (UC) is associated with gut microbial dysbiosis, but the host molecular alterations potentially linked to microbially derived metabolites remain incompletely understood. We integrated Mendelian randomization (MR), microbial metabolite annotation, computational target prediction, colonic transcriptomics, network analysis, and machine learning. MiBioGen microbiome GWAS data were used as exposures and FinnGen Release 12 ULCERENTER as the outcome. Metabolites linked to MR-prioritized taxa were retrieved from GutMGene, and human targets were predicted using SwissTargetPrediction and SEA. UC-related genes were defined by integrating differential expression analysis and WGCNA and then intersected with predicted metabolite targets. MR prioritized one family and eight genera showing nominal genetically supported associations with UC, but none remained significant after Benjamini-Hochberg FDR correction. Three prioritized genera were linked to 15 microbe-metabolite records, corresponding to 13 unique metabolites; nine were retained for target prediction, yielding 277 unique predicted human targets. Transcriptomic analysis identified 1,530 DEGs and a 312-gene MEgrey60 module, with 273 overlapping genes, producing 1,569 unique UC-related genes. Their intersection with the 277 predicted targets yielded 47 candidate genes. Enrichment analyses highlighted mainly metabolic and lipid-related processes. Random Forest showed the highest mean AUC across the two independent external benchmarking cohorts, and SHAP prioritized EPHX1, HSD17B2, IGFBP5, and MMP10. IBDome analysis showed inflammation-associated expression differences in these genes. This study provides a genomics-informed, hypothesis-generating framework that prioritizes candidate microbe-metabolite-host relationships in UC for future experimental validation.

Humans↗
PubMed2005

Delayed disease progression after allogeneic cell vaccination in hormone-resistant prostate cancer and correlation with immunologic variables.

PURPOSE: There are a significant number of patients with asymptomatic hormone-resistant prostate cancer who have increasing prostate-specific antigen (PSA) levels but little or no evaluable disease. The immunogenicity and minimal toxicity associated with cell-based vaccine therapy makes this approach attractive for these patients. EXPERIMENTAL DESIGN: We have evaluated a vaccine comprising monthly intradermal injection of three irradiated allogeneic prostate cell lines (8 x 10(6) cells each) over 1 year. The first two doses were supplemented with bacille Calmette-Guérin as vaccine adjuvant. Twenty-eight hormone-resistant prostate cancer patients were enrolled. Patients were assessed clinically and PSA levels were measured monthly. Radiologic scans (X-ray, computed tomography, and bone scan) were taken at baseline and at intervals throughout the treatment period. Comprehensive monthly immunologic monitoring was undertaken including proliferation studies, activation markers, cytokine protein expression, and gene copy number. This longitudinal data was analyzed through predictive modeling using artificial neural network feed-forward/back-propagation algorithms with multilayer perceptron architecture. RESULTS: Eleven of the 26 patients showed statistically significant, prolonged decreases in their PSA velocity (PSAV). None experienced any significant toxicity. Median time to disease progression was 58 weeks, compared with recent studies of other agents and historical control values of around 28 weeks. PSAV-responding patients showed a titratable T(H)1 cytokine release profile in response to restimulation with a vaccine lysate, while nonresponders showed a mixed T(H)1 and T(H)2 response. Furthermore, immunologic profile correlated with PSAV response by artificial neural network analysis. We found predictive power not only in expression of cytokines after maximal stimulation with phorbol 12-myristate 13-acetate, but also the method of analysis (qPCR measurement of IFN-gamma > qPCR measurement tumor necrosis factor-alpha > protein expression of IFN-gamma > protein expression of interleukin 2). CONCLUSIONS: Whole cell allogeneic vaccination in hormone-resistant prostate cancer is nontoxic and improves the natural history of the disease. Longitudinal changes in immunologic function in vaccinated patients may be better interpreted through predictive modeling using tools such as the artificial neural network rather than periodic "snapshot" readouts.

Aged↗
PubMed1998

Computational modelling of optic flow selectivity in MSTd neurons.

In neurophysiological experiments examining the selectivity of MSTd neurons to visual motion components of optic flow stimuli in monkeys, Duffy and Wurtz (1991) reported cells with double-component (plano-radial and plano-circular) and triple-component (plano-radial-circular) selectivities, while Graziano et al (1994) reported neurons selective to a continuum of optic flow stimuli including spiral motion. Here, we address these reported findings under simulated experimental conditions by examining the development of optic flow selectivity in the hidden units of a two-layer back-propagation network. We also examine network motion sensitivity during simulated psychophysical tests via the addition of a competitive decision layer. Network analysis with neurophysiological stimuli identified a majority of hidden units whose position invariance and motion selectivity were consistent with MSTd responses to the visual motion components of optic flow stimuli reported by Duffy and Wurtz and Graziano et al. Furthermore, the hidden units developed a continuum of optic flow selectivities independent of the biases associated with the specification of the motion selectivity in the output layer. During psychophysical testing, network responses showed motion sensitivities which met or exceeded human performance. Within the limitations imposed by the learning algorithm, the psychophysical results were consistent with a model of global motion perception via local integration along complex motion trajectories.

Animals↗
PubMed1998

mtDNA haplogroup X: An ancient link between Europe/Western Asia and North America?

On the basis of comprehensive RFLP analysis, it has been inferred that approximately 97% of Native American mtDNAs belong to one of four major founding mtDNA lineages, designated haplogroups "A"-"D." It has been proposed that a fifth mtDNA haplogroup (haplogroup X) represents a minor founding lineage in Native Americans. Unlike haplogroups A-D, haplogroup X is also found at low frequencies in modern European populations. To investigate the origins, diversity, and continental relationships of this haplogroup, we performed mtDNA high-resolution RFLP and complete control region (CR) sequence analysis on 22 putative Native American haplogroup X and 14 putative European haplogroup X mtDNAs. The results identified a consensus haplogroup X motif that characterizes our European and Native American samples. Among Native Americans, haplogroup X appears to be essentially restricted to northern Amerindian groups, including the Ojibwa, the Nuu-Chah-Nulth, the Sioux, and the Yakima, although we also observed this haplogroup in the Na-Dene-speaking Navajo. Median network analysis indicated that European and Native American haplogroup X mtDNAs, although distinct, nevertheless are distantly related to each other. Time estimates for the arrival of X in North America are 12,000-36,000 years ago, depending on the number of assumed founders, thus supporting the conclusion that the peoples harboring haplogroup X were among the original founders of Native American populations. To date, haplogroup X has not been unambiguously identified in Asia, raising the possibility that some Native American founders were of Caucasian ancestry.

Asia, Western↗
PubMed2025

Transmission of extended spectrum β-lactamase-producing Escherichia coli and antimicrobial resistance gene flow across One Health compartments in eastern Africa: a whole-genome sequence analysis from a prospective cohort study.

BACKGROUND: The One Health paradigm considers interdependence of human, animal, and environmental health. However, there is little evidence from high-income countries to support the importance of a One Health approach to addressing spread of antimicrobial resistance (AMR). Given AMR is a global threat, understanding how the close interactions of humans with animals and the environment in low-income settings affect the spread of AMR is important. We aimed to investigate diversity and transmission of extended spectrum β-lactamase (ESBL)-producing Escherichia coli across household-linked One Health compartments using genomic data. METHODS: We sequenced whole genomes of ESBL-producing E coli isolates from humans, animals, and the environment from a prospective, longitudinal cohort study conducted in Malawi (April 29, 2019, to Dec 3, 2020) and Uganda (July 16, 2020, to Aug 6, 2021). In the cohort study, 259 households were enrolled at baseline in Malawi and 92 in Uganda from a mix of urban, peri-urban, and rural areas. Households were followed up at months 1, 3, and 6 in Malawi and at months 1, 2, and 4 in Uganda. Samples collected at each visit included human and animal stool, environmental samples from hand-contact areas, food, and water, and broader environmental samples such as river water. Samples were cultured in buffered peptone water and then ESBL chromogenic agar to isolate ESBL-producing E coli. ESBL-producing E coli isolates underwent whole-genome sequencing. We performed phylogenetic analyses, and in-silico multi-locus sequence typing, characterised AMR determinants and linked genotypes with sample location, ecological source, and other covariates. We performed fine-scale single nucleotide polymorphism (SNP) and network analysis to infer strain and plasmid transmission across ecological compartments. The primary outcome was colonisation with ESBL-producing E coli. Secondary outcomes were genomic clusters and ESBL genomic determinants within and between One Health compartments. FINDINGS: We found high diversity of ESBL-producing E coli, with 170 sequence types and 166 genomic clusters identified from 2344 genomes, including 1814 genomes from Malawi (907 human, 221 animal, and 686 environmental) and 530 genomes from Uganda (380 human, 147 animal, and three environmental). Sequence type (ST)131 dominated in Malawi (209 [11·5%] of 1814 genomes), and ST10 dominated in Uganda (45 [8·5%] of 530 genomes). Common ESBL genes blaCTX-M-15 (1604 [68·4%] of 2344 genomes) and blaCTX-M-27 (336 [14·3%] of 2344 genomes) were carried on a complex network of 55 and 30 different plasmids. This diversity of plasmids presented multiple pathways for dissemination and revealed high force of selection. Phylogenetic analyses revealed common intermixing of isolates between humans, animals, and the environment. SNP transmission analysis revealed ecologically overlapping clusters, suggesting ESBL-producing E coli co-circulation both within and between compartments with frequent spillover events. Applying a five-SNP threshold, we inferred 463 human-environment transmission events, 146 human-animal events, and 142 animal-environment events. INTERPRETATION: Our work suggests that a One Health approach is crucial to addressing AMR in eastern Africa. Improving water, sanitation, and hygiene systems will create a safer environment, reduce spillovers of AMR bacteria between compartments, and eventually reduce AMR reservoirs in the environment and in animals. FUNDING: Medical Research Council, National Institute for Health and Care Research, and Wellcome Trust.

Humans↗
PubMed2006

Men who have sex with men and women: a unique risk group for HIV transmission on North Carolina College campuses.

OBJECTIVE: To better understand the role that men who have sex with men and women (MSM/W) play in the spread of HIV in young adults in North Carolina, we determined the prevalence of MSM/W among newly diagnosed HIV-infected men, compared social and behavioral characteristics of this group with MSM and MSW, and examined the sexual networks associated with HIV-infected college students among these groups. METHODS: We reviewed state HIV surveillance records for all new diagnoses of HIV in males 18 to 30 years living in North Carolina between January 1, 2000, and December 31, 2004. RESULTS: Of 1,105 records available for review, 15% were MSM/W and 13% were college students. Compared with MSM, MSM/W were more likely to be enrolled in college, to report >10 sex partners in the year before diagnosis, or have sex partners who were also MSM/W. Sexual network analysis of the HIV-infected college students revealed that MSM/W occupied a central position. Of 20 individuals who described themselves as either MSW or abstinent at the time of their initial voluntary counseling and testing visit, 80% reported that they were either MSM or MSM/W during follow up. DISCUSSION: MSM/W represent a unique risk group within the population of MSM that deserve further investigation. College MSM/W appear to occupy a unique, central place in the network of HIV-infected students.

Adolescent↗
PubMed1998

The prediction of common bile duct stones using a neural network.

BACKGROUND: The role of preoperative ERCP and endoscopic sphincterotomy (ES) in the diagnosis and treatment of suspected common bile duct stones (CBDS) in the laparoscopic age is controversial. The preoperative diagnosis of CBDS by ERCP and the removal of CBDS by ES are advantageous because of technical difficulties in performing laparoscopic exploration of the common bile duct. Approximately 50% of preoperative ERCP examinations are normal, however. The noninvasive diagnosis of CBDS has assumed new importance, but it has proved to be an elusive goal. Neural networks are a form of artificial computer intelligence that have been used successfully to interpret ECGs and to diagnose myocardial infarcts. The purpose of this study was to determine whether a neural network could be trained to predict CBDS accurately in patients at high risk of having duct stones. STUDY DESIGN: We trained a back-propagation neural network to predict the presence of CBDS. Retrospective data from patients who had a cholecystectomy and either a preoperative ERCP or intraoperative cholangiogram were used to build the network, and it was tested using unseen data. RESULTS: One hundred forty patients were used to train the network, and 16 patients were used to test it. The trained network was able to predict CBDS in 100% of the patients in both the training and test sets. CONCLUSIONS: Screening of high-risk patients for CBDS by neural network analysis is highly accurate. This promising new, noninvasive, and inexpensive technique can potentially decrease the need for preoperative ERCP by 50%, but additional prospective evaluation is indicated.

Adult↗