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Results for “Structural validation”

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At least 109 records · Page 6Linked to original sources
PubMed1988

An examination of the factor structure and convergent and discriminant validity of the SCL-90R in an outpatient clinic population.

This study investigated the factor structure of the SCL-90R using an outpatient psychology clinic population. Six relatively homogeneous and stable factors were identified: Depression, Somatization, Anger-Hostility, Paranoid-Psychoticism, Phobic Anxiety, and Obsessive-Compulsive. However, a principal component analysis revealed that the first factor accounted for a large percentage of the variance, suggesting that this instrument measures a general dimension of psychopathology. In addition, significant correlations between the SCL-90R symptom dimensions and both the BDI and several MMPI scales were found. The results of the study lead to questions regarding the utility of the SCL-90R.

Adolescent↗
PubMed2026

Multitargeted comparative evaluation suggests 2-Aoeobenoxmide shows favourable in silico binding compared to Tucatinib against ERα, HER2, AKT1, EGFR, and PIK3CA in breast cancer.

Breast cancer is a leading cause of cancer-related morbidity and mortality globally, with the WHO reporting approximately 2.3 million new cases and 685,000 deaths annually. Drug resistance in breast cancer complicates treatment, with mutations in critical proteins contributing to therapy failure. Key oncogenic proteins involved in breast cancer progression-namely ERα (a ligand-activated nuclear receptor; PDB: 1A52) and the kinase domains of HER2 (PDB ID: 3PP0), AKT1 (PDB ID: 4EJN), EGFR (PDB ID: 4I23) and PIK3CA (PDB ID: 7R9V)-are pivotal in tumour progression and resistance mechanisms. Targeting these proteins using multitargeted therapeutic strategies may overcome resistance by disrupting key signalling pathways involved in cell proliferation, survival, and metastasis. Such combinatorial approaches promise to improve treatment efficacy and patient outcomes in cases of resistant breast cancer. In this study, we performed multitarget docking on prepared and validated protein structures against the ZINC natural compound library using HTVS, SP, and XP, with pose validation using MM-GBSA. We identified 2-Aoeobenoxmide (2-[1-(2-amino-2-oxo-ethoxy)-6-oxo-benzo[c]chromen-3-yl]oxyacetamide, ZINC134008) with docking and MM-GBSA scores ranging from -8.162 to -10.327 kcal/mol and from -47.18 to -57.62 kcal/mol, respectively, and compared the results with the FDA-approved drug Tucatinib, which exhibited lower binding affinity scores. We further evaluated pharmacokinetic properties using QikProp and electronic properties using DFT (Jaguar) and compared the descriptors of 2-Aoeobenoxmide with those of Tucatinib and with accepted reference ranges. We also performed the WaterMap for 5 nanoseconds (ns), computed various energies, interactions and hydration sites, and the comparison suggests that 2-Aoeobenoxmide shows more favourable hydration-site displacement and binding interactions than Tucatinib. Additionally, a 100 ns MD Simulation has resulted in far less deviation, fluctuations, and intermolecular interactions than Tucatinib, suggesting stable protein-ligand interactions, while the binding free energy and total complex energy computed across 0-1000 frames of the MD trajectories indicate that 2-Aoeobenoxmide is a promising in silico candidate. Importantly, because the entire study is computational, the findings should be interpreted as in silico hypotheses, and experimental validation through in vitro and in vivo assays is warranted before any clinical translation is considered.

Humans↗
PubMed1990

Regional cerebral blood flow in pigs estimated by microspheres.

Regional cerebral blood flow in anaesthetized pigs is determined with the microsphere method. Five regions of cortical grey matter and three white subcortical areas in each hemisphere are examined together with anatomically classic structures. The validity of the biopsies was confirmed by freeze drying of the tissue. Three flow measurements in a group of six animals showed large interindividual variations whereas regions with the same structure in the particular animal showed a high degree of uniformity. Symmetrical regions in the two hemispheres were similar with a coefficient of variation between sides of less than 5%. The coefficient of variation of the particular flow measurements were 15%. The different brain structures have four discernible flow levels. White subcortical matter has three different flow values and forms together with medulla oblongata and hippocampus the low flow area. Flow in grey cortical matter is of the same magnitude as in unanaesthetized animals and constitutes together with thalamus, mesencephalon, pons and cerebellar hemispheres the intermediate flow level. The high flow areas are nucleus caudatus and lentiformis together with the cerebellar vermis. The choroid plexus, pituitary gland and pineal gland all have very high flow values and seem, in contrast to the rest of the brain, insensitive to the CO2-tension in arterial blood and global cerebral metabolism. Microsphere estimation of regional blood flow seems to be an appropriate technique for evaluating regional cerebral blood with a high degree of spatial resolution in repeated flow measurements.

Animals↗
PubMed1979

A factor-analytic examination of the unitary OR concept.

Recent studies have generated a four-system structure proposed as a replacement for Sokolov's unitary OR concept. This conceptualisation developed from a logical consideration of stimulus--response relationships based upon mean response magnitudes over subjects, and paid no attention to individual response types. It is conceivable that no individual subject exhibited responses compatible with such a formulation. This paper addressed that problem by using factor analysis as a means of descriptively summarising the data of each subject, and examining its compatibility with both unitary and four-system structures. Of 72 subjects, none exhibited a factor structure compatible with Sokolov's unitary concept, while 70 exhibited structures compatible with the four-system structure. These results support the validity of the structure proposed to replace the unitary OR.

Arousal↗
PubMed2026

Phenotyping strategies for chronic overlapping pain conditions and internalizing disorders in Veterans: Prevalence, comorbidity, and latent structure as evidence for construct validity.

Chronic overlapping pain conditions (COPCs), internalizing (INT) disorders, and opioid use disorder (OUD) are common, comorbid, and difficult to phenotype at scale. Electronic health record (EHR) studies commonly define cases using Any Code (AC; ≥1 ICD-9/10 code) and Multiple Code (MC; ≥1 inpatient or ≥2 outpatient codes) phenotyping strategies, but it is unclear whether these thresholds change only case numbers or also the clinical relationships among conditions. This cross-sectional study included approximately 950,000 Million Veteran Program participants with ≥2 visits. AC and MC phenotypes for 17 conditions spanning COPCs, INT, and OUD were compared in prevalence, case characteristics, comorbidity, and latent structure. Random-thinning analysis compared AC-MC differences to case reduction alone. Construct validity was evaluated through correspondence with expected patterns of association and latent organization. Back pain (AC=58.1%; MC=48.1%), major depressive disorder (41.5%; 36.2%), and post-traumatic stress disorder (32.6%; 29.1%) were most prevalent. MC excluded 33.5% of AC cases on average, and MC cases had greater healthcare utilization, diagnostic burden, opioid exposure, and psychiatric medication use than AC-only cases. The observed mean absolute correlation change (mean |Δr|=0.014) was smaller than in all 1000 random-thinning replicates. Both strategies supported a correlated, four-factor model consistent with "Anxious Misery," "Fear," "Diffuse Pain," and "Head Pain" (AC: CFI=0.987, RMSEA=0.015; MC: CFI=0.987, RMSEA=0.014). The MC strategy reduced prevalence and altered case composition but maintained the expected comorbidity and latent organization patterns among conditions. Findings provide evidence of phenotype construct validity and inform selection of EHR phenotyping strategies for epidemiological and genomic research. PERSPECTIVE: Commonly used EHR phenotyping strategies tested in nearly one million Veterans produce broadly similar latent organization across comorbid and prevalent chronic overlapping pain conditions, internalizing disorders, and opioid use disorder. Findings support construct validity and clarify trade-offs involving case inclusion, recorded burden, and healthcare observation in large-scale research.

Chronic overlapping pain conditions↗
PubMed1985

Primary and secondary structure of 26S ribosomal RNA of Oenothera mitochondria.

The primary structure of 26S ribosomal RNA from mitochondria of the dicotyledoneous plant Oenothera berteriana is inferred from the sequence of a cloned rDNA restriction fragment. A tentative secondary structure model valid for Oenothera and for the major part of maize mitochondrial 26S rRNA has been constructed in analogy to the refined german model for E. coli L-rRNA (Maly and Brimacombe 1983). The derived structure generally matches the eubacterial model providing further support to the E. coli consensus structure. Some structural features however show eukaryotic characteristics. Possible interactions between L-rRNA, 5S rRNA and initiator-tRNA are discussed.

Base Sequence↗
PubMed2026

Genomic and epigenetic regulatory mechanisms in exercise-based rehabilitation processes: Cellular and tissue remodeling, microvascular adaptation, and circulating biomarkers.

While exercise-based rehabilitation is known to positively impact functionally related parameters, the role of genomic and epigenomic responses coordinated with cellular, extracellular matrix (ECM), mitochondrial, and microvascular adaptations remains insufficiently investigated. This narrative review summarizes mechanistic evidence linking exercise-associated mechanical, metabolic, hypoxia-redox, inflammatory, and hemodynamic stimuli with tissue remodeling and clinically relevant biomarkers. Current findings indicate that integrin-focal adhesion kinase (FAK) signaling and Hippo YAP/TAZ pathways contribute to mechanical signal transduction, cytoskeletal regulation, and gene expression, whereas metabolic adaptation, ATP homeostasis, and protein synthesis are regulated through AMPK-PGC-1α, SIRT1, and mTOR-dependent pathways. Epigenetic mechanisms, including DNA methylation, histone modifications, chromatin remodeling, and noncoding RNA regulation, further influence cell-specific responses in myofibers, satellite cells, fibro-adipogenic progenitors, endothelial cells, pericytes, and immune cells. In addition, VEGF-VEGFR2, eNOS-NO, and KLF2/KLF4 signaling, together with extracellular matrix turnover and inflammation resolution, contribute to tissue repair and microvascular adaptation during rehabilitation. Importantly, acute exercise-induced molecular responses should not be interpreted as direct evidence of sustained tissue adaptation. Circulating microRNAs, extracellular vesicles, cell-free DNA, collagen-related markers, and vascular proteins represent promising approaches for monitoring rehabilitation-related changes; however, their clinical translation remains limited by challenges related to tissue specificity, biomarker kinetics, analytical variability, and the need for standardized validation alongside structural and functional outcomes.

AMPK–PGC-1α signaling↗
PubMed1991

Reassessing the validity and reliability of the MMPI Alexithymia Scale.

In the past decade, alexithymia has emerged as a heuristically useful personality construct used to explain the pathogenesis of a variety of physical illnesses, including classical psychosomatic diseases, somatization disorders, hypochondriasis, and somatoform pain disorders. Unfortunately, research evaluating the alexithymia construct has been conducted with little attention to assessing the psychometric properties of various scales used to measure it. In two separate studies, we examined various scale and item properties as well as the factor structure and validity of the Minnesota Multiphasic Personality Inventory Alexithymia Scale (MMPI-A), one of the most commonly used scales to assess alexithymia. In Study 1, the 22 items that comprise the MMPI-A were extracted from a computerized MMPI data bank which included separate samples of psychiatric inpatients and outpatients. Poor item-to-scale characteristics and only moderate levels of internal reliability were found for both samples. Factor analysis produced factors that were poorly related to the theoretical domains of the alexithymia construct. In Study 2, we found little support for validity of the scale as those patients identified as alexithymic and nonalexithymic by the MMPI-A did not differ on several theoretically relevant scales. These results question seriously the value of the MMPI-A in investigating the alexithymia construct.

Adult↗
PubMed2024

Molecular basis for antibody recognition of multiple drug-peptide/MHC complexes.

The HapImmuneTM platform exploits covalent inhibitors as haptens for creating major histocompatibility complex (MHC)-presented tumor-specific neoantigens by design, combining targeted therapies with immunotherapy for the treatment of drug-resistant cancers. A HapImmune antibody, R023, recognizes multiple sotorasib-conjugated KRAS(G12C) peptides presented by different human leukocyte antigens (HLAs). This high specificity to sotorasib, coupled with broad HLA-binding capability, enables such antibodies, when reformatted as T cell engagers, to potently and selectively kill sotorasib-resistant KRAS(G12C) cancer cells expressing different HLAs upon sotorasib treatment. The loosening of HLA restriction could increase the patient population that can benefit from this therapeutic approach. To understand the molecular basis for its unconventional binding capability, we used single-particle cryogenic electron microscopy to determine the structures of R023 bound to multiple sotorasib-peptide conjugates presented by different HLAs. R023 forms a pocket for sotorasib between the VH and VL domains, binds HLAs in an unconventional, angled way, with VL making most contacts with them, and makes few contacts with the peptide moieties. This binding mode enables the antibody to accommodate different hapten-peptide conjugates and to adjust its conformation to different HLAs presenting hapten-peptides. Deep mutational scanning validated the structures and revealed distinct levels of mutation tolerance by sotorasib- and HLA-binding residues. Together, our structural information and sequence landscape analysis reveal key features for achieving MHC-restricted recognition of multiple hapten-peptide antigens, which will inform the development of next-generation therapeutic antibodies.

Humans↗
PubMed1991

Structure-activity relationships of chemical mutagens and carcinogens.

In recent years, octanol-water partition coefficients (P) have been used in toxicology studies to correlate chemical structure and biological activity. Generally, only limited attempts are made to show how a new correlation equation relates to those previously published, especially when different activities are involved. Evidence is presented to show that there is often a high degree of self-consistency between the dependence of activity on hydrophobicity (defined by log P) from different systems. Examples are drawn from nonspecific toxicity, mutagenicity and carcinogenicity. It is suggested that this kind of lateral correlation is an important means for validating structure-activity relationships.

Alcohols↗
PubMed2026

Sperm subpopulations differing in mitochondrial abundance show divergent nuclear allele frequencies.

Mammalian ejaculates contain heterogeneous sperm subpopulations that differ in subcellular architecture and developmental history, despite appearing morphologically uniform. The extent to which this cellular heterogeneity reflects underlying nuclear genomic structure within a sire remains largely unexplored. Mitochondrial architecture in sperm is established during spermatogenesis, with final assembly and organization occurring during spermiogenesis under nuclear genomic control, positioning variation in mitochondrial abundance and organization as a potential phenomic indicator of within-sire allelic segregation. Here, we tested whether sperm subpopulations defined by differing mitochondrial abundance exhibit systematic differences in nuclear allele representation. Boar sperm were resolved into low and high mitochondrial subpopulations using fluorescence-activated cell sorting based on MitoTracker™ Green fluorescence while excluding debris, doublets, and non-viable cells. Epifluorescence microscopy confirmed that high MitoTracker™ Green fluorescence sperm possessed longer mitochondrial sheaths, validating a structural distinction between subpopulations. Whole-genome sequencing of paired mitochondrial subpopulations from three boars was performed, and allelic ratio distortion was evaluated relative to heterozygous baseline populations. Analyses across heterozygous loci genome-wide identified candidate allele frequency shifts between mitochondrial-defined subpopulations, suggesting non-random segregation of alleles within ejaculates. Using a minimum sequencing depth of 30 reads in both sorted fractions, 182 candidate SNPs were identified with evidence of allele-frequency differences between mitochondrial fluorescence-defined subpopulations. These findings suggest that sperm mitochondrial abundance can potentially serve as an indirect, high-throughput marker of nuclear genomic heterogeneity within sires. This proof-of-concept framework establishes a foundation for future studies integrating sperm phenotyping, genome-wide allele-frequency analysis and functional validation to better characterize gamete-level heterogeneity.

Male↗
PubMed1985

Epidemiology: reflections on testing the validity of psychiatric interviews.

Laboratory tests that validate psychiatric disorder are unavailable. Accordingly, the validity of structured diagnostic interviews such as the Diagnostic Interview Schedule have been assessed through a double-blind test-retest design. This approach compares the Diagnostic Interview Schedule to a clinician's assessment and evaluates its results by three statistics: sensitivity and specificity, for which the clinician's interview serves as the standard, and K, which measures concordance between the two interviews. This design is found wanting on several counts: the reinterview may be answered differently because of clinical change or because of its meaning to the respondent; the clinician's interview may be an erratic standard; and the statistics are affected by both prevalence and severity of disorder. Furthermore, the statistics may not predict the accuracy of prevalence estimates made by the interview or its ability to detect correlates of disorder. Some alternative approaches are suggested.

Clinical Trials as Topic↗
PubMed1978

Wechsler Memory Scale: a selective review of the literature.

Research on the Wechsler Memory Scale (WMS) is reviewed with respect to questions of its reliability, factor structure, construct validity, and utility. The relationship of Memory Quotient to Full Scale IQ is explored and the conditions under which disparity between the two scores may be clinically useful indicated. Despite its numerous limitations, the WMS has been a sensitive test of short-term verbal memory. As such, it may be helpful in identifying impairment of the dominant (left) temporal lobe and its medial hippocampal connections. The test is badly in need of re-standardization, however, and suggestions for improving the instrument are made.

Adult↗
PubMed1989

Effect of neuroleptics on positive and negative symptoms and the deficit state.

The concept of negative symptoms tries to operationalize a deficit syndrome observed in schizophrenia, but also in other disorders. The instruments for the measurement developed so far are unclear in their dimensional structure and validity. Further methodological development is needed. A new scale for measuring negative symptoms was derived from the AMDP-system and applied to results of drug trials with clozapine, fluperlapine, and haloperidol. The three drugs were equally effective on negative symptoms of acute and chronic schizophrenics.

Antipsychotic Agents↗
PubMed1992

Development of a computer application for headache diagnosis: the Headache Diagnostic System.

A computer-assisted decision support system for headache classification and diagnosis is presented. The system provides: structured headache data collection, automated data quality control and management, and automated headache classification. The system is based upon headache classification and diagnostic criteria recently developed by the International Headache Society. Development, logical structure and validation of the system are discussed. The system is shown to provide a general improvement in headache classification reliability and has utility for validation and improvement of present headache classification criteria.

Adult↗
PubMed1987

Reconstruction of NOESY maps. A requirement for a reliable conformational analysis of biomolecules using 2D NMR.

The modelling of the conformation of a biomolecule in solution is based mainly on the internuclear distances deduced from measurements of nuclear Overhauser effects (nOe) in NOESY correlation maps. The distances are then used as restraints in the energy minimization procedure, which leads to one or several optimized conformations. A general and safe technique for validating these structures with respect to the experimental data is here proposed: from the internuclear distances, the relaxation matrix can be computed under the assumption of a unique rotational correlation time. By stepwise integration of these relaxation equations, the NOESY maps can be accurately reconstructed for any mixing time. Because multi-spin effects are correctly taken into account, any difference between the experimental and theoretical maps can be easily interpreted in terms of conformation, and possible inconsistencies due to conformational averaging can be pointed out. The technique is illustrated for a bacterial lipopeptide, mycosubtilin, the spectrum of which is completely assigned.

Biopolymers↗
PubMed1983

An assessment of the evidence for the role of ribonucleoprotein particles in the maturation of eukaryote mRNA.

This article has sought to draw together, on the one hand, what is known of mRNA processing and its control and, on the other hand, what is known of the structure and validity of hnRNP and snRNP particles. At the same time, it has attempted to synthesize these two themes into a critical assessment of the evidence which suggests that the particles are intimately involved in processing. It cannot be said that the case is proven. The evidence is compelling but circumstantial. The last few years have seen the development of the first in vitro splicing systems (Weingartner and Keller, 1981; Goldenberg and Raskus, 1981; Kole and Weissman, 1982), the isolation of monoclonal antibodies to defined snRNP (Lerner et al., 1981a; Billings et al., 1982) and hnRNP proteins (Hugle et al., 1982), and the ability to use artificial lipid vesicles to transfer antisera (Lenk et al., 1982) and radioactive snRNA (Gross and Cetron, 1982) into cells. It is to be hoped that further refinements of these and other techniques will allow us to solve this, one of the major outstanding problems of molecular biology.

Animals↗