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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&#xa0;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&#x2009;<&#x2009;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↗

Assessment of young children using the Achenbach System of Empirically Based Assessment (ASEBA).

After providing a brief review of three other approaches to assessment of preschool children (DSM-IV diagnoses, "Zero to Three" diagnoses, and temperament scales), this paper focuses on the Achenbach System of Empirically Based Assessment (ASEBA). The empirically based assessment paradigm provides user-friendly, cost-effective, reliable, and valid procedures for assessing children's behavioral/emotional problems from the perspectives of multiple informants. The ASEBA preschool forms, the Child Behavior Checklist for ages 1.5-5 (CBCL/1.5-5) and the Caregiver-Teacher Report Form (C-TRF), are usable by many different kinds of professionals in diverse settings. The CBCL/1.5-5 also includes the Language Development Survey (LDS), which provides a quick screen for delays in vocabulary and word combinations. The problem items of the CBCL/1.5-5 and the C-TRF are scored on both empirically based syndromes and DSM-oriented scales, which are normed on the same general population sample. Variations in children's functioning across contexts and interaction partners make it essential to obtain and integrate data from multiple sources. Therefore, ASEBA software provides side-by-side comparisons of item and scale scores from up to eight assessment forms per child. Clinical and research applications of ASEBA preschool forms are summarized in the paper, and strengths and limitations are discussed.

Child, Preschool↗

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↗

Common interchange standards for proteomics data: Public availability of tools and schema.

The Proteomics Standards Initiative (PSI) aims to define community standards for data representation in proteomics and to facilitate data comparision, exchange and verification. To this end, a Level 1 Molecular Interaction XML data exchange format has been developed which has been accepted for publication and is freely available at the PSI website (http.//psidev.sf.net/). Several major protein interaction databases are already making data available in this format. A draft XML interchange format for mass spectrometry data has been written and is currently undergoing evaluation whilst work is ongoing to develop a proteomics data integration model, MIAPE.

Computational Biology↗

Modeling transcriptional control in gene networks--methods, recent results, and future directions.

Mathematical models are useful for providing a framework for integrating data and gaining insights into the static and dynamic behavior of complex biological systems such as networks of interacting genes. We review the dynamic behaviors expected from model gene networks incorporating common biochemical motifs, and we compare current methods for modeling genetic networks. A common modeling technique, based on simply modeling genes as ON-OFF switches, is readily implemented and allows rapid numerical simulations. However, this method may predict dynamic solutions that do not correspond to those seen when systems are modeled with a more detailed method using ordinary differential equations. Until now, the majority of gene network modeling studies have focused on determining the types of dynamics that can be generated by common biochemical motifs such as feedback loops or protein oligomerization. For example, these elements can generate multiple stable states for gene product concentrations, state-dependent responses to stimuli, circadian rhythms and other oscillations, and optimal stimulus frequencies for maximal transcription. In the future, as new experimental techniques increase the ease of characterization of genetic networks, qualitative modeling will need to be supplanted by quantitative models for specific systems.

Animals↗

Automated integration of external databases: a knowledge-based approach to enhancing rule-based expert systems.

Expert system applications in the biomedical domain have long been hampered by the difficulty inherent in maintaining and extending large knowledge bases. We have developed a knowledge-based method for automatically augmenting such knowledge bases. The method consists of automatically integrating data contained in commercially available, external, online databases with data contained in an expert system's knowledge base. We have built a prototype system, named DBX, using this technique to augment an expert system's knowledge base as a decision support aid and as a bibliographic retrieval tool. In this paper, we describe this prototype system in detail, illustrate its use, and discuss the lessons we have learned in its implementation.

Artificial Intelligence↗

The effect of raloxifene on the incidence of ovarian cancer in postmenopausal women.

OBJECTIVE: The aim of this study was to determine the incidence of ovarian cancer in postmenopausal women treated with raloxifene compared with placebo. METHODS: This analysis comprises integrated data from seven randomized, placebo-controlled trials of raloxifene (N = 9837). Ovarian cancer cases were identified from the safety database and reviewed by a gynecologic adjudication review board. RESULTS: Sixteen cases of ovarian cancer were reported: 8 women (79.4/100,000 patient-years) on placebo and 8 (37.4/100,000 patient-years) on pooled raloxifene doses. The relative risk of ovarian cancer associated with raloxifene therapy was 0.50 (95% confidence interval, 0.19-1.35). CONCLUSION: Raloxifene use was not associated with an increased risk for ovarian cancer.

Aged↗

Database challenges and solutions in neuroscientific applications.

In the scientific community, the quality and progress of various endeavors depend in part on the ability of researchers to share and exchange large quantities of heterogeneous data with one another efficiently. This requires controlled sharing and exchange of information among autonomous, distributed, and heterogeneous databases. In this paper, we focus on a neuroscience application, Neuroanatomical Rat Brain Viewer (NeuART Viewer) to demonstrate alternative database concepts that allow neuroscientists to manage and exchange data. Requirements for the NeuART application, in combination with an underlying network-aware database, are described at a conceptual level. Emphasis is placed on functionality from the user's perspective and on requirements that the database must fulfill. The most important functionality required by neuroscientists is the ability to construct brain models using information from different repositories. To accomplish such a task, users need to browse remote and local sources and summaries of data and capture relevant information to be used in building and extending the brain models. Other functionalities are also required, including posing queries related to brain models, augmenting and customizing brain models, and sharing brain models in a collaborative environment. An extensible object-oriented data model is presented to capture the many data types expected in this application. After presenting conceptual level design issues, we describe several known database solutions that support these requirements and discuss requirements that demand further research. Data integration for heterogeneous databases is discussed in terms of reducing or eliminating semantic heterogeneity when translations are made from one system to another. Performance enhancement mechanisms such as materialized views and spatial indexing for three-dimensional objects are explained and evaluated in the context of browsing, incorporating, and sharing. Policies for providing the system with fault tolerance and avoiding possible intellectual property abuses are presented. Finally, two existing systems are evaluated and compared using the identified requirements.

Animals↗

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↗

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↗

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↗

Effectiveness of yohimbine in the treatment of erectile disorder: four meta-analytic integrations.

The results of four independent yet convergent meta-analyses to examine the efficacy of yohimbine in the treatment of erectile disorder are reported. These meta-analyses integrated data from (i) controlled clinical trials of yohimbine (when used alone), (ii) uncontrolled trials examining yohimbine (alone), (iii) controlled trials of yohimbine when used in combination with other drugs, and (iv) uncontrolled trials of yohimbine plus other drugs. Results document a consistent tendency for yohimbine, and for other medications containing yohimbine, to enhance erectile functioning relative to placebo. We also identify methodological and reporting difficulties that characterize much of the literature.

Alkaloids↗

Extension and use of a physical map of the Thinopyrum-derived Lr19 translocation.

Twenty-nine deletion mutant lines were used to extend a physical map of the Lr19 translocated chromosome segment. One hundred and forty-four Sse8387I/MseI and 32 EcoRI/MseI primer combinations were used to obtain 95 Thinopyrum-specific AFLP markers. The physical map confirmed that terminal deletions had mostly occurred, however, it appears that intercalary deletions and primer or restriction site mutations were also induced. The markers allowed for grouping of the deletion mutant lines into 19 clusters, with 7 AFLP markers mapping in the same marker bin as Lr19. Primary and secondary Lr19 allosyndetic recombinants were subsequently physically mapped employing AFLP, RFLP, SCAR and microsatellite markers and the data integrated with the deletion map. A further shortened, tertiary Lr19 recombinant was derived following homologous recombination between the proximally shortest secondary recombinant, Lr19-149-299, and distally shortest recombinant, Lr19-149-478. The tertiary recombinant could be confirmed employing the mapped markers and it was possible to identify new markers on this recombinant that can be used to reduce the translocation still further.

Chromosome Mapping↗

Laser-based detection of PAHs and BTXE-aromatics in oil polluted soil samples.

Time-resolved laser-induced fluorescence spectroscopy and fiber optics are applied for the detection of aromatic hydrocarbons in oil contaminated water and soil samples. Time-integrated data accumulation of fluorescence intensities in an "early" and in a "late" time window with respect to the exciting laser pulse simplifies the method in such a way that it becomes very attractive for practical applications. For ultraviolet laser excitation at 337 nm and recording fluorescence signals at 400 nm, typical detection limits of the present set-up are 0.5 mg engine oil/L in water and 5 mg engine oil/kg in soil. A discrimination between BTXE-aromatics and PAHs in oil polluted soil or water samples is possible, when more than one laser wavelength in the ultraviolet is used for the excitation. The possibilities for a thermal discrimination between different aromatics are also discussed.

Journal Article↗

A conceptual model for defining and assessing land management units using a fuzzy modeling approach in GIS environment.

Appropriate land management decisions are important for current and future use of the land to ensure its sustainability. This requires that land management units (LMUs) be specified to enable the identification of specific parameters employed in decision making processes. This paper presents the development of a conceptual model, within geographic information systems (GIS), for defining and assessing LMUs from available biophysical information. The model consists of two main components (sub-models): land quality-based suitability analysis and soil erosion estimation. Using a fuzzy set methodology, the first sub-model was constructed to derive a land suitability index (LSI) for a cropping land utilization type. The LSI thus highlights the suitability grades of every pixel in the study area on a continuous basis. A submodel of soil erosion was established based on the Revised Universal Soil Loss Equation (RUSLE) utilising the same spatial data bases employed for structuring the LSI. Using a soil loss tolerance principle, a fuzzy membership function of average annual soil loss (called soil loss index, SLI) was established, leading to compatibility between LSI and SLI for data integration. LMUs were then derived from various combinations of LSI and SLI. The methodology developed shows the significance of the model for refining available land suitability evaluation systems, which take no account of expected land degradation (from erosion) due to a nominated land use. It also provides a valuable guideline for cost-effective GIS applications in the identification and assessment of homogeneous land units, using available spatial information sets, at a finer scale.

Conservation of Natural Resources↗

What evidence do we have to replace in-hospital implantable cardioverter defibrillator follow-up?

INTRODUCTION: Due to the increasing number of patients with an implantable cardioverter defibrillator (ICD), new options for ICD patient follow-up management are required. METHODS: Patients with ICD indication according to the guidelines received an ICD with Home Monitoring technology. The devices enabled the transmission of the relevant episode, therapy, and system integrity data. Patients were followed for 12 months with routine controls every 3 months. The physician analyzed the Home Monitoring data before the routine follow-up visit (FU) and gave a forecast on the necessity of the pending FU, which was compared with the evaluation after the FU. Based on the derived forecast reliability, a patient management scheme was developed and its impact on patient safety was assessed retrospectively. RESULTS: A total of 271 patients were enrolled (40 f, mean age 62+/-12 years, mean LVEF 39+/-15%, 65% ischemic heart disease, 20% cardiomyopathy) and followed for 339+/-109 days. Of 908 pairs of Home Monitoring data and FU data evaluation, 129 there were false negative results for 92 patients. Safety concerns from false negative forecasts can be minimized with a patient management scheme containing the following elements: 1) never skip the first routine FU; 2) never skip a routine FU for a patient having already shown pacing threshold problems; 3) perform FU following hospitalizations; 4) perform FU following episode detection by the ICD; and 5) perform a routine FU if the patient reports symptoms. The retrospective analysis showed, that if the patients had been managed using this scheme, 503 of 1079 routine FU could have been skipped with only one safety concern, a three month delay in the detection of silent paroxysmal atrial fibrillation in one patient. CONCLUSIONS: Home Monitoring in ICD therapy over 12 months is feasible. The data transmitted relevantly contribute to a remarkable reduction of follow-up burden and enable the individualization of routine follow-up.

Adult↗

Genome-wide meta-analysis for rheumatoid arthritis.

Meta-analysis is being increasingly used as a tool for integrating data from different studies of complex phenotypes, because the power of any one study to identify causal loci is limited. We applied a novel meta-analytical approach (Loesgen et al. in Genet Epidemiol 21(Suppl 1):S142-S147, 2001) in compiling results from four studies of rheumatoid arthritis in Caucasians including two studies from NARAC (Jawaheer et al. in Am J Hum Genet 68:927-936, 2001; Jawaheer et al. in Arthritis Rheum 48:906-916, 2003), one study from the UK (MacKay et al. in Arthritis Rheum 46:632-639, 2001) and one from France (Cornelis et al. in Proc Natl Acad Sci USA 95:10746-10750, 1998). For each study, we obtained NPL scores by performing interval mapping (2 cM intervals) using GeneHunter2 (Kruglyak et al. in Am J Hum Genet 58:1347-1363, 1996; Markianos et al. in Am J Hum Genet 68:963-977, 2001). The marker maps differed among the three consortium groups, therefore, the marker maps were aligned after the interval mapping was completed and the NPL scores that were within 1 cM of each other were combined using the method of Loesgen et al. (Genet Epidemiol 21(Suppl 1):S142-S147, 2001) by calculating the weighted average of the NPL score. This approach avoids some problems in analysis encountered by using GeneHunter2 when some markers in the sample are not genotyped. This procedure provided marginal evidence (P<0.05) of linkage on chromosome 1, 2, 5 and 18, strong evidence (P<0.01) on chromosomes 8 and 16, and overwhelming evidence in the HLA region of chromosome 6.

Arthritis, Rheumatoid↗

Fine mapping of the MLK-3 gene within 11q13 and its exclusion as the MEN1 susceptibility gene.

MLK-3 kinase is a widely expressed serine/ threonine kinase that bears multiple protein interaction domains and regulates signals mediated by the stress-responsive pathway. Thus, MLK-3 signaling affects numerous cellular processes, raising the possibility that MLK-3 might play a role in oncogenesis. In this report, we describe the fine mapping of the MLK-3 gene within the 11q13.1 chromosomal region. By integrating data from somatic cell hybrids and double color fluorescence in situ hybridization on metaphase chromosomes and DNA fibers. MLK-3 has been assigned approximately 1 Mb telomeric of PYGM, close to the D11S546 locus. Since the MEN1 susceptibility locus is also located within the 11q13.1 region, we have carried out Southern and Northern blot analyses, as well as protein truncation assays to establish whether abnormalities in MLK-3 lead to the development of this familial cancer syndrome. Our observations exclude MLK-3 as the MEN1 gene.

Animals↗