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PubMed2026

A machine learning-derived intratumoral heterogeneity-related signature predicts the prognosis for and therapeutic response in patients with skin cutaneous melanoma.

BACKGROUND: Reliable biomarkers for predicting prognosis and therapeutic response in skin cutaneous melanoma (SKCM) remain limited. This study aimed to develop an intratumoral heterogeneity (ITH)-related prognostic signature for SKCM using integrative machine learning. METHODS: RNA sequencing (RNA-seq) data from 472 SKCM patients in The Cancer Genome Atlas (TCGA) and 214 patients in the GSE65904 cohort were analyzed. ITH scores were calculated using the DEPTH2 algorithm. Differentially expressed genes (DEGs) were identified between high- and low-ITH groups [|log2fold change (FC)| &#x2265;1, false discovery rate (FDR) <0.05]. Based on 38 prognostic DEGs identified by univariate Cox regression, we employed an integrative framework of 101 machine learning algorithm combinations to construct prognostic models in the TCGA training cohort. The model with the highest average concordance index (C-index) was validated in the GSE65904 cohort and selected as the prognostic ITH-related signature (PIRS). Associations of the PIRS risk score with tumor mutational burden (TMB), immune cell infiltration, immune checkpoint gene expression, and drug sensitivity were systematically evaluated. Model performance was assessed using receiver operating characteristic (ROC) curves and Cox regression analyses. RESULTS: A 38-gene PIRS was constructed using the plsRcox algorithm. Patients with high PIRS risk scores exhibited significantly poorer overall survival (OS) in both the TCGA and Gene Expression Omnibus (GEO) cohorts. The PIRS was identified as an independent prognostic factor, with area under the curve (AUC) values of 0.779, 0.734, and 0.756 for 1-, 3-, and 5-year survival, respectively. High-risk samples displayed significantly lower TMB (P<0.05), reduced immune and stromal cell infiltration (P<0.001), downregulated immune function, and decreased expression of immune checkpoint genes. Additionally, high- and low-PIRS risk score groups exhibited distinct sensitivity patterns to different classes of targeted agents. CONCLUSIONS: The machine learning-derived PIRS robustly predicts prognosis in SKCM patients. Its clinical application is promising for optimizing patient risk stratification and treatment decisions, though further prospective validation is warranted.

Skin cutaneous melanoma (SKCM)↗
PubMed2001

Assessment of health economics in Alzheimer's disease (AHEAD) based on need for full-time care.

OBJECTIVE: To develop a framework for estimating the long-term health and economic consequences of AD based on patient characteristics at a given point in time. METHODS: A pharmacoeconomic model (Assessment of Health Economics in Alzheimer's Disease, AHEAD) was developed based on equations that relate the probability of needing full-time care (FTC) over time to patient characteristics summarized in index scores. These equations were developed from published data on interquartile times until FTC is needed and until death, using nonlinear regressions of the resulting index-specific hazards. These equations were then incorporated into a hidden Markov framework that allows for calculation of expected time to FTC and to death, as well as of the economic consequences of disease progression. There are three major states in the model: not requiring FTC ("pre-FTC"), requiring FTC, and death. RESULTS: Outcomes for five sample patients are derived to illustrate application of the AHEAD model. The impact of altering disease markers in these patients is also considered. CONCLUSION: The need for a generally applicable tool to forecast long-term outcomes based on relatively short-term data is becoming increasingly acute with the advent of new therapies for AD. The AHEAD model provides a relatively simple framework for the prediction of time to FTC requirement based on short-term observed data such as those from clinical trials. Although subject to the uncertainties inherent in modeling, the model nevertheless provides a standard estimation technique that may facilitate comparisons between existing and emerging therapies.

Aged↗
PubMed2000

Assessment of neuropsychologic impairments after head injury: interrater reliability and factorial and criterion validity of the Neurobehavioral Rating Scale-Revised.

OBJECTIVE: To study interrater reliability and factorial and criterion validity of the Neurobehavioral Rating Scale-Revised (NRS-R). DESIGN: Validity study on persons with traumatic brain injury (TBI) and test-retest reliability study on a randomly selected subset of patients. Factor analyses, kappa statistics, intraclass correlation coefficients, and Cronbach's alphas were used. SETTING: Inpatients from 15 French hospitals, mainly rehabilitation units. Other recruitment sites included a neurology hospital unit and a psychiatry hospital specifically devoted to TBI rehabilitation. PATIENTS: Two hundred eighty-six TBI patients ages 16 to 70 years (convenience sample). RESULTS: For the reliability study, the average of percentages of agreement among the items was 74.3% and the average of kappa statistics was .40. Factor analyses disclosed a maximum likelihood extraction of 5 correlated factors (F), explaining 42.2% of total variance: (F1) deficits in intentional behavior and in memory, (F2) lowering of emotional state, (F3) emotional and behavioral hyperactivation, (F4) lowering of arousal state and of attention, and (F5) language and speech problems. Results support the criterion validity of the factors. Reliability of the factor scores and internal consistencies of factors were very good. CONCLUSIONS: Results describe some important properties of the NRS-R and, through an understanding of its underlying structure and relationships with the patients' clinical characteristics, contribute to the conceptual framework of neuropsychologic impairments after TBI.

Adolescent↗
PubMed1984

A scale to measure physician beliefs about psychosocial aspects of patient care.

This report describes the development and initial validation of a self-report instrument designed to measure beliefs about psychosocial aspects of patient care held by primary care physicians. The strategy used was borrowed from psychological measurement: a rational scale was constructed based on an existing theoretical framework concerning the physician's role, what the patient wants and physicians' reactions to their patients as people. The validation step compared scale scores obtained by diverse groups of providers. Psychometric characteristics of the Physician Belief Scale are adequate: scores follow an approximately normal distribution with the mean near the midpoint of possible scores. Lower scores on the Scale represent a more psychosocial approach to patient care. Initial construct validation was successful: physicians from four disciplines obtained scores congruent with expectations about the psychosocial orientations of the disciplines. A reliable and valid measure has been developed to assess physicians' psychosocial beliefs. The instrument may be used to evaluate effectiveness of behavioral science teaching, describing regional or other differences in physician beliefs within and between specialties and estimating changes in provider beliefs.

Attitude of Health Personnel↗
PubMed2003

A radiation hybrid map of bovine chromosome 24 and comparative mapping with human chromosome 18.

We present herein a bovine chromosome 24 (BTA24) radiation hybrid (RH) map using 40 markers scored on a panel of 90 RHs. Of these markers, 29 loci were ordered with odds of at least 1000:1 in a framework map. An average retention frequency of 17.4% was observed, with relatively higher frequencies near the centromere. The length of the comprehensive map was 640 centiray5000 (cR5000) with an average marker interval of approximately 17.3 cR5000. The observed locus order is generally consistent with currently published bovine linkage and physical maps. Nineteen markers were either Type I loci or closely associated with expressed sequences and thus could be used to compare the BTA24 RH map with human mapping information. All genes located on BTA24 were located on human chromosome 18, and previously reported regions of conserved synteny were extended. The comparative data revealed the presence of at least six conserved regions between these chromosomes.

Animals↗
PubMed2026

Comprehensive evaluation of AlphaFold/OpenFold prediction of experimentally unresolved proteins through novel metrics.

Predicting accurate protein structures is essential for understanding molecular mechanisms, interpreting the impact of sequence variation, and supporting translational applications ranging from drug discovery to clinical genomics. Recent advances in deep-learning-based predictors such as AlphaFold2, OpenFold, and AlphaFold3 have transformed structural biology, enabling routine in silico modeling even for challenging or previously uncharacterized proteins. However, systematic benchmarking of these tools-especially for novel targets and single amino acid variants-remains limited. Conventional global metrics often fail to capture biologically meaningful discrepancies. By evaluating multiple implementations of AlphaFold2 and OpenFold, together with ColabFold and the AlphaFold3 server, across 10 different proteins and 222 single amino acid protein variants encompassing a wide range of sizes, structures, and functions, we show that although widely used global indicators-like mean pLDDT, pTM-score, and RMSD-frequently suggest comparable performance, substantial local-level differences remain elusive. To address this gap, we introduce a comparative framework leveraging Bland-Altman agreement analysis, to evaluate per-residue C&#x3b1;-confidence differences and Per-Residue profiles (PRPs), complemented by Uniform Manifold Approximation and Projection (UMAP). This approach reveals marked localized divergences, particularly within flexible or intrinsically disordered regions, where both predictor choice and single-residue substitutions trigger the largest conformational shifts. We further demonstrate that using reduced homology databases has minimal impact on predicted structural quality, offering computationally efficient alternatives. Collectively, our findings underscore the importance of integrating global and residue-specific evaluations to more accurately assess robustness, agreement, and practical usability across contemporary protein structure prediction methods.

Proteins↗
PubMed2005

A likelihood approach for quantitative-trait-locus mapping with selected pedigrees.

Selective sampling is a cost-effective design for mapping quantitative trait loci (QTLs). A unified framework, which naturally combines two complementary sources of linkage information in the data, is proposed for the mapping of QTLs using selected pedigrees. Score statistics for detecting linkage are introduced for single-locus models (univariate or bivariate phenotypes) and two-locus epistasis models. A computer implementation of the methods for single-locus univariate-phenotype models is provided for nuclear families with arbitrary number of sibs and is freely available.

Algorithms↗
PubMed1998

Drug policies and harms: a conceptual framework.

Existing indicators of drug-related policies and harms - official statistics, treatment data, and so on - are difficult to interpret and to compare across jurisdictions. We propose a conceptual framework including key dimensions of policy and harm. The framework is designed to guide creation of a new dataset in which existing empirical data can be used to assign city-specific scores on policy and harm dimensions. By an interpretive process involving local experts and a coordinating body, we believe that existing data can be evaluated and synthesized to derive these scores. We also propose a cumulative case-study method of querying the dataset to test hypotheses regarding relationships between policies and harms.

Crime↗
PubMed2025

A large-scale study across the avian clade identifies ecological drivers of neophobia.

Neophobia, or aversion to novelty, is important for adaptability and survival as it influences the ways in which animals navigate risk and interact with their environments. Across individuals, species and other taxonomic levels, neophobia is known to vary considerably, but our understanding of the wider ecological drivers of neophobia is hampered by a lack of comparative multispecies studies using standardized methods. Here, we utilized the ManyBirds Project, a Big Team Science large-scale collaborative open science framework, to pool efforts and resources of 129 collaborators at 77 institutions from 24 countries worldwide across six continents. We examined both difference scores (between novel object test and control conditions) and raw data of latency to touch familiar food in the presence (test) and absence (control) of a novel object among 1,439 subjects from 136 bird species across 25 taxonomic orders incorporating lab, field, and zoo sites. We first demonstrated that consistent differences in neophobia existed among individuals, among species, and among other taxonomic levels in our dataset, rejecting the null hypothesis that neophobia is highly plastic at all taxonomic levels with no evidence for evolutionary divergence. We then tested for effects of ecological factors on neophobia, including diet, sociality, habitat, and range, while accounting for phylogeny. We found that (i) species with more specialist diets were more neophobic than those with more generalist diets, providing support for the Neophobia Threshold Hypothesis; (ii) migratory species were also more neophobic than nonmigratory species, which supports the Dangerous Niche Hypothesis. Our study shows that the evolution of avian neophobia has been shaped by ecological drivers and demonstrates the potential of Big Team Science to advance our understanding of animal behavior.

Animals↗
PubMed2004

Predicting molecular interactions in silico: II. Protein-protein and protein-drug docking.

This article reviews the docking field starting from basic docking algorithms and describing the latest advances. We present the algorithmic framework and classify the state of-the-art methods. We point out the bottlenecks of the methods, like flexibility, absence of absolute scoring functions and explain what types of information can potentially be added to improve the results.

Algorithms↗
PubMed2004

Psychometric analysis of the Minnesota Test of Critical Thinking.

With the increase over the past two decades in interest in critical thinking instruction, reliable and valid means for measuring critical thinking are necessary. The Minnesota Test of Critical Thinking was developed to measure critical thinking as defined by the American Philosophical Association in 1990. The present purpose was to explore the structure and reliability of the intervention and its instantiation of the critical thinking framework. Analyses of responses from 151 adult participants gave estimates of reliability varying from .29 to .78. A factor analysis of the test scores supported critical thinking conceptualized as a single, latent trait. With further refinement, the invention should become a valuable measure of general critical thinking skills of upper-division secondary and postsecondary students.

Adult↗
PubMed1993

A comparison of ICD-10 and DSM-III-R criteria for substance abuse and dependence.

As part of DSM-IV field trials for substance use disorders, 100 inpatients from two psychiatric substance abuse units were interviewed using a modified version of the Substance Abuse Module (SAM) to ascertain substance use diagnoses according to ICD-10 and DSM-III-R criteria. Both criteria sets developed from the theoretical framework presented by Gross and Edwards (1976) and thus, they should demonstrate close concurrence in diagnoses of dependence and abuse/harmful use. The kappa scores obtained in these analyses demonstrate good to excellent agreement on the diagnoses of dependence across substances. There was poor agreement between DSM-III-R and ICD-10 for abuse/harmful use diagnoses. Although there is generally good agreement between DSM-III-R and ICD-10 for substance dependence diagnoses, important differences exist between the two criteria sets both for the diagnoses of abuse and harmful use, and for the diagnosis of marijuana dependence. These differences are primarily due to the inclusion of social problems and repeated use of substances in hazardous situations as DSM-III-R criteria.

Alcoholism↗
PubMedDate not supplied

Modeling the effects of health status and the educational infrastructure on the cognitive development of Tanzanian schoolchildren.

This paper models the proximate determinants of school attendance and scores on cognitive and educational achievement tests and on school examinations of over 600 schoolchildren from the Control group of a randomized trial in Tanzania, where children in the Intervention group heavily infected with hookworm and schistosomiasis received treatment. The modeling approach used a random effects framework and incorporated the inter-relationships between school attendance and performance on various tests, controlling for children's health status, socioeconomic variables, grade level, and the educational infrastructure. The empirical results showed the importance of variables such as children's height and hemoglobin concentration for the scores, especially on educational achievement tests that are easy to implement in developing countries. Also, teacher experience and work assignments were significant predictors of the scores on educational achievement tests, and there was some evidence of multiplicative effects of children's heights and work assignments on the test scores. Lastly, some comparisons were made for changes in test scores of treated children in the Intervention group with the untreated children in the Control group.

Absenteeism↗
PubMed2000

Using the Baldrige management system framework in health care: the Veterans Health Administration experience.

BACKGROUND: In 1998 the Veterans Health Administration (VHA) developed the Quality Achievement Recognition Grant, a competitive grant application open to all Veterans Integrated Service Networks (VISNs) within the VHA system and based on the Baldrige management framework. Eight of the 22 VISNs attended the educational programs and initiated the grant application process; 7 completed applications. Team award experts from VHA and external sources reviewed, scored, and wrote feedback reports to all applicants and conducted four site visits. IDENTIFICATION OF BEST PRACTICES AND RECOMMENDATIONS FOR FUTURE APPLICANTS: Each application was compared to examples of ideal applications to identify areas of excellence and areas for improvement. In general, the best applicants identified and described key processes and articulated the methods used to evaluate and improve processes. For example, they were able to identify the process used to incorporate key constituents into the strategy development process. One applicant developed a series of management advisory committees, the membership of which includes veterans' service organizations, academic affiliates, community members, and congressional delegates, which were tapped to develop a strategic plan. Leading applicants in the future are likely to be able to demonstrate evidence of deployment and constant review of the strategy and to emphasize the human resources plan into the strategic planning and deployment. CONCLUSIONS: The Baldrige management framework is a useful tool for identification of areas of achievement and areas for improvement within the VHA. Potential applicants for the award could benefit from ensuring coherence across the application, placing a greater emphasis on work systems, and incorporating more extensive analysis of market conditions.

Awards and Prizes↗
PubMed2006

Proteomics, part II: the emerging role of proteomics over genomics in spontaneous preterm labor/birth.

UNLABELLED: Conventional wisdom holds that complications of immature organ systems such as respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, and bronchopulmonary dysplasia are the primary causes of the high neonatal morbidity and mortality attendant preterm delivery. However, recent evidence suggests that a major cause of prematurity-associated neonatal pathology is the fetal and neonatal response to inflammation/infection. Although functional genomics offered the promise of providing answers to many of these questions, the identification of the genes intrinsic to human parturition proved to be a difficult task. Proteomic profiling of the amniotic fluid (AF) provides a precise means for detection of inflammation by revealing the presence of 4 biomarkers (defensins-2 and -1, calgranulin-C, and calgranulin-A) that are highly predictive of intrauterine inflammation (MR score). The MR score is especially useful as it presents a gradient of disease activity progressing from "absent" to "mild" to "severe" inflammation. Thus, it provides the ability to identify patients who may benefit from interventions in utero in a modern diagnostic-therapeutic framework. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to explain that the cause or causes of preterm delivery are still unknown, recall that functional genomics has not given the answer to these causes, and state that proteomic profiling of amniotic fluid, through mass-restricted (MR) scoring, may be predictive of intrauterine inflammation and allow for potential diagnosis and potential therapy.

Animals↗
PubMed2026

Development and Validation of a Clinical Polygenic Risk Report in U.S.-Based Health Systems for 8 Cardiovascular Conditions.

BACKGROUND: Polygenic risk scores (PRS) stratify inherited cardiovascular risk, but their path to clinical implementation remains unclear. OBJECTIVES: We aimed to develop and validate integrated PRS for 8 cardiovascular conditions and outline a framework for their clinical reporting. METHODS: We analyzed genotype and clinical data from 245,394 All of Us Research Program participants. Publicly available PRS for 8 traits-coronary artery disease, atrial fibrillation, type 2 diabetes, venous thromboembolism (VTE), thoracic aortic aneurysm (TAA), extreme hypertension, severe hypercholesterolemia, and elevated lipoprotein(a)-were combined using PRSmix, an elastic-net approach. Integrated PRS were externally validated in 53,306 Mass General Brigham Biobank participants using logistic regression, adjusting for age, sex, and ancestry. RESULTS: Of 53,306 genotyped Mass General Brigham Biobank participants (55.6% women, mean age 53 &#xb1; 17 years), integrated PRS demonstrated robust discrimination and appropriate calibration across 8 cardiovascular traits. Comparing high genetic risk (top 10% of PRS distribution, or top 20% for rarer TAA and VTE) vs average risk (26th-75th percentiles, or 21st-80th percentiles for TAA and VTE) yielded ORs: coronary artery disease (3.7 [95% CI: 3.4-4.1]), type 2 diabetes (3.1 [95% CI: 2.8-3.3]), atrial fibrillation (3.0 [95% CI: 2.7-3.3]), VTE (1.9 [95% CI: 1.6-2.0]), TAA (1.7 [95% CI: 1.5-1.9]), hypertension (2.1 [95% CI: 1.8-2.3]), hypercholesterolemia (4.1 [95% CI: 3.7-4.5]), and lipoprotein(a) (41.0 [95% CI: 27.0-62.2]). Incorporating integrated PRS into clinical models improved risk classification, while prospective analyses confirmed significant associations with incident cardiovascular outcomes. CONCLUSIONS: Integrated PRS offer an implementable framework for genetic risk reporting, and are now available as a clinically orderable test. Broader prospective validation studies are needed to further establish clinical utility.

Humans↗
PubMed2000

A cognitive task analysis for dental hygiene.

To be an effective assessment tool, a simulation-based examination must be able to evoke and interpret observable evidence about targeted knowledge, strategies, and skills in a manner that is logical and defensible. Dental Interactive Simulations Corporation's first assessment effort is the development of a scoring algorithm for a simulation-based dental hygiene initial licensure examination. The first phase in developing a scoring system is the completion of a cognitive task analysis (CTA) of the dental hygiene domain. In the first step of the CTA, a specifications map was generated to provide a framework of the tasks and knowledge that are important to the practice of dental hygiene. Using this framework, broad classes of behaviors that would tend to distinguish along the dental hygiene expert-novice continuum were identified. Nine paper-based cases were then designed with the expectation that the solutions of expert, competent, and novice dental hygienists would differ. Interviews were conducted with thirty-one dental hygiene students/practitioners to capture solutions to the paper-based cases. Transcripts of the interviews were analyzed to identify performance features that distinguish among the interviewees on the basis of their expertise. These features were more detailed and empirically grounded than the originating broad classes and better serve to ground the design of a scoring system. The resulting performance features were collapsed into nine major categories: 1) gathering and using information, 2) formulating problems and investigating hypotheses, 3) communication and language, 4) scripting behavior, 5) ethics, 6) patient assessment, 7) treatment planning, 8) treatment, and 9) evaluation. The results of the CTA provide critical information for defining the necessary elements of a simulation-based dental hygiene examination.

Algorithms↗