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At least 757 records · Page 42Linked to original sources
PubMed2003

Community membership and social networks in mental health self-help agencies.

This article explores community membership among self-help agency (SHA) participants. It is suggested that SHAs foster the enhancement of peer-oriented social networks, leading to the experience of shared community. Social network analysis was used to examine the structure of support mechanisms, and to assess levels of community membership through peer inclusion. Results indicate that both individual and organizational characteristics play roles in predicting peer presence in social networks. Organizational empowerment is a key factor, with the SHA emerging as a promising locus for peer support development through enhanced social networks. Implications for the organization of consumer-based services are discussed.

Adult↗
PubMed2026

Early oligodendrocyte dysfunction signature in Alzheimer's disease: Insights from DNA methylomics and transcriptomics.

Much research into the aetiology of Alzheimer's disease (AD) has focused on neuronal cell types, while studies on the contribution of glial cells, particularly oligodendrocytes (OLGs), are only starting to emerge. Altered brain DNA methylation, an epigenetic modification that provides the interplay between genetics and environmental cues to tightly regulate gene expression, is well documented in AD. Yet, cell-type-specific investigations remain limited. Here, we examine the role of DNA methylation and OLGs in AD, and how such changes may impact gene expression. We performed weighted-gene correlation network analysis (WGCNA) on multiple brain omics AD datasets across species: human DNA methylation data from 4 brain regions, human brain single-nuclei RNA sequencing data and mouse brain RNA sequencing data. We compared AD-associated network modules enriched for OLG genes across AD brain regions, as well as with other neurodegenerative disease DNA methylation datasets. We identified a DNA methylation signature associated with AD, enriched for OLGs, and preserved across brain regions representing early and late AD pathology stages. Genes within this signature showed altered expression in AD OLGs, confirming cell-type specificity and relevance to AD. This OLG signature was also preserved in transgenic mice with early Aβ pathology and in other neurodegenerative diseases without Aβ pathology. We reveal a consistent pattern of OLG dysfunction spanning early to late stages of AD, across DNA methylation and gene expression. Our findings highlight OLG-associated DNA methylation changes as important in AD pathogenesis, and possibly in other neurodegenerative diseases, opening new avenues for therapeutic development.

Alzheimer Disease↗
PubMed2000

Visual confrontation naming and hippocampal function: A neural network study using quantitative (1)H magnetic resonance spectroscopy.

Prior research on the relationship between visual confrontation naming and hippocampal function has been inconclusive. The present study examined this relationship using quantitative (1)H magnetic resonance spectroscopy ((1)H-MRS) to operationalize the function of the left and right hippocampi. The 60-item Boston Naming Test (BNT) was used to measure naming. Our sample included 46 patients with medically intractable, focal mesial temporal lobe epilepsy who had been screened for all pathology other than mesial temporal sclerosis. Statistics included Pearson correlations and neural network analysis (multilayer perceptron and radial basis function). Baseline BNT performance correlated significantly with left (1)H-MRS hippocampal ratios. Thirty-six per cent of the variance in baseline BNT performance was explained by a neural network model using left and right (1)H-MRS ratios(creatine/N-acetylaspartate) as input. This was elevated to 49% when input from the right hippocampus was lesioned mathematically. In a second model, left (1)H-MRS hippocampal ratios were modelled using measures of semantic and episodic memory as input (including the BNT). Explained variance in left (1)H-MRS hippocampal ratios fell from 60.8 to 3.6% when input from BNT and another semantic memory measure was degraded mathematically. These results provide evidence that the speech-dominant hippocampus is a significant component of the overall neuroanatomical network of visual confrontation naming. Clinical and theoretical implications are explored.

Adult↗
PubMed2004

Identification of the CRP regulon using in vitro and in vivo transcriptional profiling.

The Escherichia coli cyclic AMP receptor protein (CRP) is a global regulator that controls transcription initiation from more than 100 promoters by binding to a specific DNA sequence within cognate promoters. Many genes in the CRP regulon have been predicted simply based on the presence of DNA-binding sites within gene promoters. In this study, we have exploited a newly developed technique, run-off transcription/microarray analysis (ROMA) to define CRP-regulated promoters. Using ROMA, we identified 176 operons that were activated by CRP in vitro and 16 operons that were repressed. Using positive control mutants in different regions of CRP, we were able to classify the different promoters into class I or class II/III. A total of 104 operons were predicted to contain Class II CRP-binding sites. Sequence analysis of the operons that were repressed by CRP revealed different mechanisms for CRP inhibition. In contrast, the in vivo transcriptional profiles failed to identify most CRP-dependent regulation because of the complexity of the regulatory network. Analysis of these operons supports the hypothesis that CRP is not only a regulator of genes required for catabolism of sugars other than glucose, but also regulates the expression of a large number of other genes in E.coli. ROMA has revealed 152 hitherto unknown CRP regulons.

Base Sequence↗
PubMed2006

Cognitive dysfunction in NF1 knock-out mice may result from altered vesicular trafficking of APP/DRD3 complex.

BACKGROUND: It has been estimated that more than 50% of patients with Neurofibromatosis type 1 (NF1) have neurobehavioral impairments which include attention deficit/hyperactivity disorder, visual/spatial learning disabilities, and a myriad of other cognitive developmental problems. The biological mechanisms by which NF1 gene mutations lead to such cognitive deficits are not well understood, although excessive Ras signaling and increased GABA mediated inhibition have been implicated. It is proposed that the cognitive deficits in NF1 are the result of dysfunctional cellular trafficking and localization of molecules downstream of the primary gene defect. RESULTS: To elucidate genes involved in the pathogenic process, gene expression analysis was performed comparing the expression profiles in various brain regions for control and Nf1+/- heterozygous mice. Gene expression analysis was performed for hippocampal samples dissected from postnatal day 10, 15, and 20 mice utilizing the Affymetrix Mouse Genome chip (Murine 430 2.0). Analysis of expression profiles between Nf1+/- and wild-type animals was focused on the hippocampus because of previous studies demonstrating alterations in hippocampal LTP in the Nf1+/- mice, and the region's importance in visual/spatial learning. Network analysis identified links between neurofibromin and kinesin genes, which were down regulated in the Nf1+/- mice at postnatal days 15 and 20. CONCLUSION: Through this analysis, it is proposed that neurofibromin forms a binding complex with amyloid precursor protein (APP) and through filamin proteins interacts with a dopamine receptor (Drd3). Though the effects of these interactions are not yet known, this information may provide novel ideas about the pathogenesis of cognitive defects in NF1 and may facilitate the development of novel targeted therapeutic interventions.

Amyloid beta-Protein Precursor↗
PubMedDate not supplied

The relevance of social network concepts to sexually transmitted disease control.

Many of the concepts of social network analysis have been tacit assumptions of sexually transmitted disease control efforts for decades. With the advent of AIDS in the 1980s, an overt rapprochement between these two fields--previously separated by culture, context, and language--was made. Social network constructs have immediate appeal to disease control workers, who view many diseases as following the conduits of social interactions. STDs and HIV, in turn, provide network analysts and those who model disease transmission with substantial sets of empirical data that test and illuminate theory. Disease control efforts can be enhanced by incorporating network concepts overtly into current practices. Such concepts offer a path to better delineation of groups at risk, to a better understanding of the interaction of personal risk taking and the social context, and to evaluation of control mechanisms.

Female↗
PubMedDate not supplied

Classification of ultrasonic image texture by statistical discriminant analysis of neutral networks.

In this paper the ability of two common statistical discriminant analysis procedures are compared with two commercial neural network software packages. The major objective of this study was to determine which of the procedures could best discriminate between normal and abnormal ultrasonic liver textures. The same set of features were input into both statistical discriminant analysis procedures and both neural network models. Preliminary results have found the restricted Coulomb Energy (RCE) neural network model to have a testing accuracy of 90.6% which is approximately 10% better than any of the other techniques investigated.

Algorithms↗
PubMed2026

Proteomics-Based Identification of the Pyroptosis-Related Biomarker PCSK9 and Its Association With the Pathogenesis of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a common autoimmune disease, and early diagnosis is critical for effective treatment. This study aims to identify potential biomarkers related to pyroptosis through serum proteomics analysis, offering new insights for the early diagnosis of RA. We enrolled 100 participants, including 50 patients with RA and 50 healthy controls. Serum samples were collected and analyzed using high-resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS) for proteomics profiling. Differential protein expression analysis and functional annotation revealed significant upregulation of pyroptosis-related proteins in the serum of patients with RA. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, along with protein-protein interaction (PPI) network analysis, showed that these proteins are involved in inflammation and immune pathways, particularly the activation of the NOD-like receptor protein 3 (NLRP3) inflammasome. Enzyme-linked immunosorbent assay (ELISA) validation confirmed a significant increase in PCSK9 levels in patients with RA, suggesting that PCSK9 may play a key role in the pathogenesis of RA. This study provides new directions for biomarker research in RA, particularly regarding the potential involvement of the pyroptosis pathway, with significant clinical application prospects.

Humans↗
PubMed2003

Adolescent mothers and breastfeeding: experiences and support needs--an exploratory study.

The experiences and support needs of adolescent mothers who commenced breastfeeding were elicited using focus groups and in-depth semistructured interviews. The study took place in the North West of England, UK. The qualitative data were analyzed using thematic networks analysis. Five themes related to experiences emerged: feeling watched and judged, lacking confidence, tiredness, discomfort, and sharing accountability. A further 5 themes were developed to describe the adolescents' support needs: emotional support, esteem support, instrumental support, informational support, and network support. These forms of support were most effective when provided together in a synergistic way and within a trusting relationship. Key supporters identified were the mother's mother, the partner, and the midwife employed in a teenage pregnancy coordinator role. Health professionals need to further explore the ways in which relationships may be developed and sustained that provide the range of support required by adolescent mothers to enable them to continue breastfeeding.

Adolescent↗
PubMed1998

XOR has no local minima: A case study in neural network error surface analysis.

This paper presents a case study of the analysis of local minima in feedforward neural networks. Firstly, a new methodology for analysis is presented, based upon consideration of trajectories through weight space by which a training algorithm might escape a hypothesized local minimum. This analysis method is then applied to the well known XOR (exclusive-or) problem, which has previously been considered to exhibit local minima. The analysis proves the absence of local minima, eliciting significant aspects of the structure of the error surface. The present work is important for the study of the existence of local minima in feedforward neural networks, and also for the development of training algorithms which avoid or escape entrapment in local minima.

Journal Article↗
PubMed2005

Non-mechanistic modelling of complex biofilm reactors and the role of process operation history.

Using the example of a membrane-supported biofilm reactor for industrial effluent treatment, different non-mechanistic approaches for the modelling of complex bioprocesses are presented and evaluated. The models were obtained employing feedforward artificial neural network analysis for the association of process operation with process performance. Three modelling approaches are discussed, i.e. autonomous static (AS) modelling, non-autonomous static (NAS) modelling, as well as a novel approach termed dynamic modelling with embedding of artificial neural network inputs. They are compared with regard to their ability to infer process performance for two different pollutant case studies, employing 1,2-dichloroethane and 3-chloro-4-methylaniline, respectively. The suitability of the different approaches was found to be strongly dependent on process configuration. Especially in configurations where lag times are apparent, the dynamic modelling approach was found to be superior, and process performance prediction was found to be strongly dependent on the history of process operation.

Algorithms↗
PubMed2025

Tumor Signatures of Physical Fitness: Insights from a Preclinical Model.

PURPOSE: Cardiorespiratory fitness (CRF) and muscle strength are associated with cancer risk/mortality in adults. However, there is yet no evidence for pediatric tumors. This study investigated the association of CRF and muscle strength with several tumor-related phenotypes in an aggressive childhood malignancy, high-risk neuroblastoma. METHODS: Twelve mice-bearing orthotopic high-risk neuroblastomas were studied. CRF and muscle strength were assessed using treadmill and grip strength testing, respectively. The following tumor-related outcomes were studied: survival, clinical severity, tumor weight/volume, metastasis, and intratumor immune infiltrates. In addition, tumor samples underwent quantitative proteomic analysis via liquid chromatography-tandem mass spectrometry. Spearman correlations (or logistic regression) were performed between CRF/muscle strength and the abovementioned variables. Proteins that were significantly correlated with CRF or muscle strength were mapped into protein-protein interaction (PPI) networks using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. RESULTS: CRF was inversely correlated with clinical severity score ( r = -0.657, P = 0.020). Of 6840 identified tumor proteins, 76 correlated significantly with CRF (19 positively, 57 negatively), whereas 194 correlated with muscle strength (97 positively, 97 negatively). Proteins correlated with CRF were primarily involved in metabolic and structural pathways, including angiotensinogen and elastin. In turn, muscle strength-associated proteins were more abundant and included keratin family proteins (e.g., keratin, type I cytoskeletal 14, and type II cytoskeletal 5), proteins involved in cell adhesion (e.g., desmoglein-1-alpha), and translational regulators (e.g., eukaryotic initiation factor 4A). Network analysis revealed significant enrichment in structural organization and cellular adhesion pathways. CONCLUSIONS: Besides the association of CRF with clinical severity of the tumor, distinct novel tumor proteomic signatures associated with CRF and muscle strength were identified, highlighting potential mechanisms linking physical fitness with childhood cancer biology.

Muscle Strength↗
PubMed2026

Functional mapping of the Trypanosoma cruzi serinome by fluorophosphonate activity-based protein profiling.

Serine hydrolases (SHs) constitute one of the largest enzyme superfamilies in eukaryotes, yet their roles in Trypanosoma cruzi, the causative agent of Chagas disease, remain largely uncharacterized. Here, we report an activity-based chemoproteomic map of the T. cruzi epimastigote serinome by combining genome-informed in silico curation with whole-cell activity-based protein profiling (ABPP) using a panel of cell-permeable fluorophosphonate (FP)-alkyne probes. Whole-cell labelling followed by label-free quantitative proteomics (LFQ-MS) identified 37 enriched SH-like proteins, including 35 with conserved or partially conserved catalytic triad/dyad features, spanning lipases, peptidases, esterases, and previously uncharacterized hydrolases. The 35 SHs represent approximately 63% of the 56 predicted SHs retained after catalytic-site curation. Domain architecture analysis revealed broad structural diversity, while orthologue-based localization data suggested association with multiple subcellular compartments, including glycosomal, mitochondrial, and endosomal localizations. Gene Ontology enrichment highlighted lipid metabolic and catabolic processes as dominant functional themes, and protein-protein interaction network analysis supported functional connectivity among the captured enzymes. Several identified SHs, including oligopeptidase B, prolyl oligopeptidase Tc80, serine carboxypeptidase CPB1, and phospholipase A1 (PLA1) have previously been characterized in trypanosomatids, with roles linked to parasite virulence or host-pathogen interactions. Together, these findings establish a fluorophosphonate-based chemoproteomic resource for the kinetoplastid community and prioritize probe-accessible active T. cruzi SHs for future functional validation and antiparasitic inhibitor discovery.

Activity-based protein profiling↗
PubMed2025

Integrated network pharmacology, molecular docking and experimental validation to investigate the mechanism of tannic acid in nasopharyngeal cancer.

Tannic acid (TA) is the primary bioactive component in the gallnut (Galla chinensis) and has exhibited the anticancer effects. However, the mechanism of its anti-cancer activity in nasopharyngeal carcinoma (NPC) remains unclear. This research aims to explore the underlying mechanism of TA in the treatment of nasopharyngeal cancer using network pharmacology, molecular docking and experimental validation. Firstly, the targets of TA and NPC were predicted and collected through databases, and the intersection targets were identified. Subsequently, protein-protein interaction (PPI) network analysis, Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes Genomes (KEGG) pathway enrichment analysis, molecular docking and molecular dynamics (MD) simulation were conducted to uncover the potential mechanisms of TA in treatment of NPC. Finally, in vitro experiments were utilized to verify the mechanism of TA with anticancer activity in NPC. The results of network pharmacology revealed 42 intersection targets between NPC-related targets and TA-related targets. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling was identified as the main target pathway of TA against NPC. Additionally, molecular docking and MD simulation confirmed the closely binding affinities of TA with AKT1. Furthermore, the results of in vitro experiments demonstrated that TA exerts anticancer activity against NPC by targeting the PI3K/AKT signaling pathway, leading to the suppression of cell proliferation. TA is a promising therapeutic candidate for NPC through PI3K/AKT signaling pathway. These results provide insights into the clinical application of TA, particularly when considered in combination with other therapeutic modalities.

Molecular Docking Simulation↗
PubMed1997

[Extended Kalman filtering trained neural networks and multicomponent analysis of amino acids].

The principle of neural networks was briefly described. Backpropagation (BP) is a widely used algorithm to train NN with slow convergence and local optima. In order to overcome the above weakness of BP, a novel learning algorithm, extanded Kalman filtering (EKF, EF), was proposed with high performance. EFNN was used for simultaneous multi-component analysis with good results and no separation.

Algorithms↗
PubMed2002

Modeling DNA sequence-based cis-regulatory gene networks.

Gene network analysis requires computationally based models which represent the functional architecture of regulatory interactions, and which provide directly testable predictions. The type of model that is useful is constrained by the particular features of developmentally active cis-regulatory systems. These systems function by processing diverse regulatory inputs, generating novel regulatory outputs. A computational model which explicitly accommodates this basic concept was developed earlier for the cis-regulatory system of the endo16 gene of the sea urchin. This model represents the genetically mandated logic functions that the system executes, but also shows how time-varying kinetic inputs are processed in different circumstances into particular kinetic outputs. The same basic design features can be utilized to construct models that connect the large number of cis-regulatory elements constituting developmental gene networks. The ultimate aim of the network models discussed here is to represent the regulatory relationships among the genomic control systems of the genes in the network, and to state their functional meaning. The target site sequences of the cis-regulatory elements of these genes constitute the physical basis of the network architecture. Useful models for developmental regulatory networks must represent the genetic logic by which the system operates, but must also be capable of explaining the real time dynamics of cis-regulatory response as kinetic input and output data become available. Most importantly, however, such models must display in a direct and transparent manner fundamental network design features such as intra- and intercellular feedback circuitry; the sources of parallel inputs into each cis-regulatory element; gene battery organization; and use of repressive spatial inputs in specification and boundary formation. Successful network models lead to direct tests of key architectural features by targeted cis-regulatory analysis.

DNA↗
PubMed2026

Pharmacological Interventions for Weight Reduction in Patients With Schizophrenia Treated With Antipsychotics: A Systematic Review and Network Meta-Analysis.

IMPORTANCE: Significant weight gain is a concerning adverse effect of antipsychotic medications experienced by patients with schizophrenia spectrum disorders (SSDs). Its high prevalence and significant contribution to cardiometabolic morbidity in this population warrant better consensus on the management of antipsychotic-induced weight gain and related comorbidity. OBJECTIVES: To evaluate the association between pharmacological interventions and changes in body weight among antipsychotic-treated patients with SSDs. DATA SOURCES: Ovid MEDLINE, Embase, PsycINFO, the Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL, ClinicalTrials.gov, and the International Clinical Trials Registry Platform (ICTRP) Search Portal were searched up to December 5, 2025. STUDY SELECTION: Randomized clinical trials examining any pharmacological intervention for weight reduction in antipsychotic-treated patients with SSDs were included. No restrictions to study duration were applied. DATA EXTRACTION AND SYNTHESIS: A systematic review and frequentist random-effects network meta-analysis was conducted. Certainty in the evidence was assessed using the Confidence in Network Meta-Analysis (CINeMA) tool. The first round of data analysis took place between May 2025 to November 2025 and was updated in December 2025. MAIN OUTCOMES AND MEASURES: The primary outcome was change in body weight following treatment with pharmacological agent vs placebo or standard care. Secondary outcomes included other anthropometric and metabolic parameters. RESULTS: A total of 95 studies examining 39 individual pharmacological interventions were included in this review (pooled N = 5898). The network meta-analysis found that semaglutide (mean difference [MD], -10.98 kg; 95% CI, -13.33 to -8.62; k = 3; moderate certainty), liraglutide (MD, -5.43 kg; 95% CI, -8.54 to -2.33; k = 2; moderate certainty), topiramate (MD, -3.95 kg; 95% CI, -5.89 to -2.02; k = 5; moderate certainty), metformin (MD, -3.86 kg; 95% CI, -5.02 to -2.70; k = 16; moderate certainty), and exenatide (MD, -2.97 kg; 95% CI, -5.83 to -0.11; k = 3; moderate certainty) were associated with the most significant reductions in body weight compared to placebo. Other interventions including ramelteon, nizatidine, and aripiprazole were also found to be associated with weight-reducing effects but with very low certainty of evidence. Clinically meaningful weight change of 5% or greater was observed with semaglutide and metformin. Beneficial effects on other metabolic outcomes were also noted with several of the medications, and there were no major concerns with gastrointestinal adverse effects or leaving the study early (ie, dropouts) between interventions. CONCLUSIONS AND RELEVANCE: This systematic review and network meta-analysis found substantial variability in weight-related outcomes across pharmacological interventions for antipsychotic-treated individuals with SSDs. Semaglutide, liraglutide, topiramate, metformin, and exenatide were associated with the greatest reductions in body weight and were supported by the highest-certainty evidence, providing guidance for clinicians managing antipsychotic-associated weight gain.

Humans↗
PubMedDate not supplied

The pressure and flow distribution within a filtering capillary network.

A model is developed to estimate the parameters controlling glomerular function by network analysis. The topological and dimensional parameters are obtained by reconstructing a Wistar rat glomerulus. The model allows the calculation of blood and plasma flow distribution between the glomerular branches, their contribution to filtration and the drop of intracapillary hydrostatic pressure along the network. The program adjusts the blood flow distribution and the red cells partition at divergent nodes, the afferent intracapillary hydrostatic pressure and the hydrodynamic conductance of the glomerular wall in order to satisfy the following conditions. The intracapillary pressures at a convergent node must be the same whatever pathway is followed to reach that node; the mean integrated intracapillary hydrostatic pressure and the single nephron glomerular filtration rate must equal their experimental value. Convergence is obtained applying the Newton-Raphson method.

Animals↗