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Validation and coding of the NIC taxonomy structure. Iowa Intervention Project. Nursing Interventions Classification.

Processes for validation and coding of the taxonomy for the Nursing Interventions Classification (NIC) are described. A sample of nurses expert in theory development rated the NIC taxonomy using five criteria. Following identification of a stable structure, the taxonomy was coded with each intervention receiving a unique number. A coded and valid taxonomic structure facilitates use of the classification in computerization and makes possible the collection of comparable data. A coded classification can also be used in reimbursement systems.

Cluster Analysis

Cross validation of the Hypnotic Induction Profile factor structure: simultaneous confirmatory factor analysis of two published samples.

This study cross-validated factor structure and psychometric characteristics of the Hypnotic Induction Profile (HIP). Earlier studies identified two constructs of the HIP, but their methodology did not allow empirical confirmation of the number of factors. I have used a new methodology, confirmatory factor analysis, and submitted the data from the previous studies to a simultaneous, multisample, factor analysis. The results showed that the HIP indeed consists of two factors. Although the HIP two-factor model is statistically adequate, 7 of the 10 scales have very low item reliability. Issues of measurement error and clinical implications of the study are also discussed in relation to the current findings.

Factor Analysis, Statistical

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

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

Valid and invalid implementations of GOR secondary structure predictions.

GOR algorithms have long been a standard methodology for predicting protein secondary structure from primary sequence. We have developed two short validation sequences for the GOR I and GOR II algorithms. Use of these sequences with seven commercial and non-commercial implementations of these algorithms demonstrated that several were incorrect implementations, including two of the three commercial modules implementing the GOR I algorithm. This may be due to an easy misinterpretation of the GOR I algorithm and related data tables. We present the validation sequences and discuss implications of this widely propagated error on secondary and tertiary structure prediction, using several proteins of known structure in three different structural classes as examples. A valid GOR I implementation predicts secondary structure increases the accuracy of predictions by from 1-13 percentage points over an invalid implementation based on the easy misinterpretation. A valid implementation of the GOR I and GOR II algorithms is available from the authors.

Algorithms

Quality of life after intensive care with the sickness impact profile.

OBJECTIVES: a) to validate the structure of the Sickness Impact Profile scale (SIP) when applied to intensive care patients after discharge from the hospital; b) to explore the influence of age upon the various components of quality of life. DESIGN: Prospective study. SETTING: Patients admitted to 36 Dutch ICUs. METHODS: 6,247 patients out of 13,000 consecutive admissions to the ICUs answered a SIP questionnaire 6 months after discharge from the hospital. The 3,655 returned questionnaire were analyzed after aggregating the respondents into 6 age groups: from group 1: 17-29 up to group 4: > 70 years of age. INTERVENTION: Self-administration of SIP one year after discharge, measuring 5 independent categories (IC) and two dimensions: physical (PD) and psychosocial (PSD). RESULTS: The total SIP-score oscillated between 5.8 +/- 8.2 (group I) and 10.5 +/- 9.5 (group 4). Group 3 had also a high score (9.4 +/- 11.2). Overall, the quality of life of patients was dominated by dysfunction on the categories composing the physical dimension, with exception of patients with ages between 30 and 50 years, in which dysfunction on the categories composing the psychosocial dimension was dominant. The structure of the SIP in the study was similar to that described to the original instrument. CONCLUSIONS: The study validated the use of the SIP QOL-instrument on patients after intensive care. Age influenced consistently the various components of quality of life.

Activities of Daily Living

The Beck Depression Inventory: testing and cross-validating a second-order factorial structure for Swedish nonclinical adolescents.

The intent of the present study was to test for the validity and equivalency of a second-order factorial structure of the Beck Depression Inventory for and across three independent samples (n1 = 661; n2 = 239; n3 = 196) of nonclinical Swedish adolescents. The model under study derived from a cross-validated study of Canadian high school adolescents. Model fitting, testing and equating were based on the analysis of covariance structures within the framework of a confirmatory factor analytic model. Of major importance was the tenability of the hypothesized model for Swedish adolescents. Only minor differences where found among samples, which involved correlated errors and one cross-loading (Sample 2). Results are expected to be of substantial interest to both researchers and clinicians whose concerns focus on depression as it bears on this population.

Adolescent

The development of a measure of enculturation for Native American youth.

Enculturation is the process by which individuals learn about and identify with their ethnic minority culture. It is distinguished from acculturation which refers to the process by which an ethnic minority individual is assimilated into the majority culture. Three studies with Native American youths are reported that describe the development of a measure of enculturation for Native American youths. Development of a measure of enculturation provides a foundation upon which to build a body of literature that focuses on strengths in a youth's life rather than on deficits. Results of the first study (n = 120), a confirmatory factor analysis, indicated that cultural affinity, native American identity, and family involvement in traditional activities adequately represent the construct of ecnulturation. The study also provides some convergent validity for this interpretation. The second study examines factor invariance for enculturation among youths with data from over 2 years (n = 69). The factor structure was similar across time. The third study replicates the factor structure and validity analyses with a new sample (n = 42). Usefulness of the measure for assessing protective factors and stressing ethnicity over simple assessment of race categories is discussed.

Adolescent

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

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

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

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

A brief method for assessing social development: structure, reliability, stability, and developmental validity of the Interpersonal Competence Scale.

The Interpersonal Competence Scale (ICS-T) is a set of brief rating scales for teachers and parents. It consists of 18 items that assess social and behavioural characteristics of children and youths. The ICS-T yields three primary factors: AGG (argues, trouble at school, fights), POP (popular with boys, popular with girls, lots of friends), and ACA (spelling, math). Subsidiary factors include AFF (smile, friendly), OLY (appearance, sports, wins), and INT (shyness, sad, worry). The psychometric properties of the scale (internal structure, reliability, long-term stability) are presented and evaluated over successive ages. The scale factors have been linked to contemporaneous observations of behavior and social network membership. Developmental validity of the ICS-T includes the significant prediction of later school dropout and teenage parenthood. The ICS-T scale is described, along with instructions for use and scoring.

Adolescent

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

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

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

Stabilization of beta-ribbon structures in peptides using disulfide bonds.

The effect of a disulfide crosslink between two peptide chains on the stability of beta-ribbon secondary structures formed by these peptides has been investigated. Based on structural principles, we hypothesized that introduction of an unstrained disulfide crosslink at appropriate locations on two peptide chains should have a stabilizing effect on the beta-ribbon structure formed by these two peptide chains. To test this hypothesis, we designed and synthesized two sets of 9-residue peptides incorporating cysteine in one and (S)-alpha-amino-epsilon-mercaptohexanoic acid in the other. Comparison of the CD data clearly show that the dimer containing a disulfide bond between the longer sidechains of (S)-alpha-amino-epsilon-mercaptohexanoic acid shows dramatically higher beta-ribbon character as compared to the dimer with cystine disulfide bond, thus validating our structural hypothesis.

Amino Acid Sequence