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Trunk strength testing with iso-machines. Part 2: Experimental evaluation of the Cybex II Back Testing System in normal subjects and patients with chronic low back pain.

This experimental evaluation of Cybex II isokinetic measurement was based on 70 normal subjects and 120 patients with chronic low back pain. It considered: reliability and learning effect; discrimination of individual patients versus normal subjects; relationship to clinical measures; assessment of effort; and a prospective 2-year follow-up of normal subjects to predict future low back pain.

Adult↗

Proteomic signatures and predictive modeling of cadmium-associated anxiety in middle-aged and elderly populations: an environmental exposure association study.

BACKGROUND: Emerging evidence implicates environmental contaminants such as cadmium (Cd) as modifiable risk factors for anxiety. Despite growing recognition of heavy metal toxicity in neuropsychiatric disorders, the molecular mechanisms linking environmental exposure to anxiety pathogenesis remain poorly understood. METHODS: Based on the established cohort of individuals with cognitive impairment in cadmium-contaminated areas, this cross-sectional association study enrolled 50 middle-aged and elderly hospitalized patients from these regions, adhering to the STROBE guidelines. Blood concentrations of cadmium (Cd), lead (Pb), and mercury (Hg) were analyzed in relation to anxiety severity assessed via the Hamilton Anxiety Rating Scale (HAMA). Plasma proteomic profiling was performed using data-independent acquisition (DIA) quantitative technology with an LC-MS/MS platform (timsTOF Pro, Bruker Daltonics), systematically characterizing 2,531 proteins across all samples. Machine learning techniques, specifically XGBoost and LASSO, were employed to identify biomarkers that were subsequently validated through mediation analysis and animal experiments, allowing for the screening of key protein signatures. Finally, clinical variables were integrated to construct a comprehensive model, which was then thoroughly evaluated. RESULTS: Anxious individuals exhibited significantly higher blood Cd levels than controls (&#x3b2;&#x2009;=&#x2009;0.50, 95% CI: 0.07-0.93, p&#x2009;<&#x2009;0.01), with anxiety positively correlating with depression (r&#x2009;=&#x2009;0.62, p&#x2009;=&#x2009;0.003) and inversely with ApoE3 genotype prevalence. Proteomics identified 120 differentially expressed proteins in anxious patients, enriched in oxidative phosphorylation and neurodegenerative pathways. CCDC126 emerged as a cadmium-associated biomarker, validated in rat models exposed to Cd. Combining CCDC126, blood Cd, Pb, and hypertension, a clinical prediction model achieved robust discrimination (AUC&#x2009;=&#x2009;0.80, validation cohort). CONCLUSIONS: This first integrative environmental-proteomic study highlights cadmium's synergistic role in anxiety pathophysiology and psychiatric comorbidity. The predictive model offers translatable potential for early risk stratification, while CCDC126 provides mechanistic insights for targeted interventions in populations exposed to environmental pollutants.

Cadmium↗

Natural language processing-based model to predict radiation pneumonitis in patients with locally advanced non-small cell lung cancer undergoing chemoradiotherapy: a retrospective cohort study.

BACKGROUND: Radiation pneumonitis (RP) remains a significant treatment-related toxicity in patients with unresectable, locally advanced non-small cell lung cancer (NSCLC) undergoing chemoradiotherapy (CRT). Most existing predictive models rely on static baseline demographic or dosimetry variables and lack real-time clinical applicability. We developed a novel predictive framework that integrates longitudinal symptom data extracted from clinical notes using natural language processing (NLP) with clinical and dosimetry features to improve early RP prediction. METHODS: We retrospectively identified 227 patients with locally advanced NSCLC treated with definitive CRT at a high-volume cancer center in the United States. We included all patients older than 18 years who were diagnosed between Jan 1, 2006, and Dec 31, 2022 with histologically or cytologically confirmed unresectable Stage 2 or 3 NSCLC and treated with conformal radiotherapy to a minimum dose of &#x2265;45 Gy with or without chemotherapy. Of these, 31 RP events were identified through manual adjudication using radiologic criteria and chart review. NLP was used to extract the temporal relationship of 16 pre-specified symptoms with treatment from over 100,000 clinical notes spanning pre- and during-treatment intervals. We trained and validated machine learning models on combinations of baseline clinical data, radiation dosimetry, and NLP-derived symptom features. Model performance was evaluated using a nested cross-validation framework, with an outer cross-validation loop reserved for performance assessment and an inner cross-validation loop used for model training and integration, and summarized using area under the receiver operating characteristic curve (AUC) and partial AUC (pAUC) at high specificity thresholds. Clinical utility was evaluated using decision curve analysis (DCA). FINDINGS: The best-performing model incorporated longitudinal NLP features and achieved a median AUC of 0.759 (90% confidence interval 0.753-0.766), significantly outperforming baseline models using only dosimetry (AUC 0.613) or clinical variables (AUC 0.635). NLP-based features such as cough trajectory, shortness of breath, and wheezing were among the most important predictors. Inclusion of NLP-derived symptom data improved early identification of high-risk patients, particularly in the clinically relevant high-specificity range (pAUC 0.021 vs. 0.010 for dosimetry alone). DCA showed that the calibrated MLP model provided greater net benefit than default strategies of treating all or no patients across clinically relevant threshold possibilities. INTERPRETATION: In this early work, NLP-based extraction of longitudinal symptoms from routine clinical documentation meaningfully enhances RP prediction in patients undergoing CRT for NSCLC. This approach leverages existing electronic health record infrastructure to deliver real-time, scalable, and interpretable risk estimates, offering a pathway toward potential early intervention and personalized toxicity management. The model and DCA requires external and prospective validation before clinical deployment; as such, future work should focus on this validation and integration into clinical decision support systems. FUNDING: AstraZeneca.

Chemoradiotherapy↗

Relating clinical and neurophysiological assessment of spasticity by machine learning.

Spasticity following spinal cord injury (SCI) is most often assessed clinically using a five-point Ashworth score (AS). A more objective assessment of altered motor control may be achieved by using a comprehensive protocol based on a surface electromyographic (sEMG) activity recorded from thigh and leg muscles. However, the relationship between the clinical and neurophysiological assessments is still unknown. In this paper we employ three different classification methods to investigate this relationship. The experimental results indicate that, if the appropriate set of sEMG features is used, the neurophysiological assessment is related to clinical findings and can be used to predict the AS. A comprehensive sEMG assessment may be proven useful as an objective method of evaluating the effectiveness of various interventions and for follow-up of SCI patients.

Artificial Intelligence↗

Ecological models of human performance based on affordance, emotion and intuition.

This paper proposes a complementary approach to Rasmussen's taxonomy of the human skill-, rule-, and knowledge-based performance models by combining the ecological concept of affordances with the neural concepts of human emotion and intuition. The classical cognitive engineering framework is extended through the neuro-ecological approach, including personal human attributes important in exercising control over the work environment. The proposed affordance-, emotion-, and intuition-based models correspond to the three types of human performance, namely: learning, adaptive and tuning control, respectively. The new framework is not a predictive model of the operator behaviour, but rather it describes the processes of neuro-ecological control of the human environment.

Cognition↗

Controlling false-negative errors in microarray differential expression analysis: a PRIM approach.

MOTIVATION: Theoretical considerations suggest that current microarray screening algorithms may fail to detect many true differences in gene expression (Type II analytic errors). We assessed 'false negative' error rates in differential expression analyses by conventional linear statistical models (e.g. t-test), microarray-adapted variants (e.g. SAM, Cyber-T), and a novel strategy based on hold-out cross-validation. The latter approach employs the machine-learning algorithm Patient Rule Induction Method (PRIM) to infer minimum thresholds for reliable change in gene expression from Boolean conjunctions of fold-induction and raw fluorescence measurements. RESULTS: Monte Carlo analyses based on four empirical data sets show that conventional statistical models and their microarray-adapted variants overlook more than 50% of genes showing significant up-regulation. Conjoint PRIM prediction rules recover approximately twice as many differentially expressed transcripts while maintaining strong control over false-positive (Type I) errors. As a result, experimental replication rates increase and total analytic error rates decline. RT-PCR studies confirm that gene inductions detected by PRIM but overlooked by other methods represent true changes in mRNA levels. PRIM-based conjoint inference rules thus represent an improved strategy for high-sensitivity screening of DNA microarrays. AVAILABILITY: Freestanding JAVA application at http://microarray.crump.ucla.edu/focus

Algorithms↗

A robust meta-classification strategy for cancer diagnosis from gene expression data.

One of the major challenges in cancer diagnosis from microarray data is to develop robust classification models which are independent of the analysis techniques used and can combine data from different laboratories. We propose a meta-classification scheme which uses a robust multivariate gene selection procedure and integrates the results of several machine learning tools trained on raw and pattern data. We validate our method by applying it to distinguish diffuse large B-cell lymphoma (DLBCL) from follicular lymphoma (FL) on two independent datasets: the HuGeneFL Affmetrixy dataset of Shipp et al. (www. genome.wi.mit.du/MPR /lymphoma) and the Hu95Av2 Affymetrix dataset (DallaFavera's laboratory, Columbia University). Our meta-classification technique achieves higher predictive accuracies than each of the individual classifiers trained on the same dataset and is robust against various data perturbations. We also find that combinations of p53 responsive genes (e.g., p53, PLK1 and CDK2) are highly predictive of the phenotype.

Algorithms↗

On selecting features from splice junctions: an analysis using information theoretic and machine learning approaches.

The computational recognition of precise splice junctions is a challenge faced in the analysis of newly sequenced genomes. This is challenging due to the fact that the distribution of sequence patterns in these regions is not always distinct. Our objective is to understand the sequence signatures at the splice junctions, not simply to create an artificial recognition system. We use a combination of a neural network based calliper randomization approach and an information theoretic based feature selection approach for this purpose. This has been done in an effort to understand regions that harbor information content and to extract features relevant for the prediction of splice junctions. The analysis using the neural network based calliper randomization approach revealed regions important in the internal representation of the network model. The calliper approach captured both correlated as well as independently important features. The feature selection approach captures features that are independently informative. The two different methods can capture features with different properties. Comparative analysis of the results using both the methods help to infer about the kind of information present in the region.

Alternative Splicing↗

Protein therapeutics: promises and challenges for the 21st century.

Recent advances in massively parallel experimental and computational technologies are leading to radically new approaches to the early phases of the drug production pipeline. The revolution in DNA microarray technologies and the imminent emergence of its analogue for proteins, along with machine learning algorithms, promise rapid acceleration in the identification of potential drug targets, and in high-throughput screens for subpopulation-specific toxicity. Similarly, advances in structural genomics in conjunction with in vitro and in silico evolutionary methods will rapidly accelerate the number of lead drug candidates and substantially augment their target specificity. Taken collectively, these advances will usher in an era of predictive medicine, which will move medical practice from reactive therapy after disease onset, to proactive prevention.

Animals↗

Automated protein classification using consensus decision.

We propose a novel technique for automatically generating the SCOP classification of a protein structure with high accuracy. High accuracy is achieved by combining the decisions of multiple methods using the consensus of a committee (or an ensemble) classifier. Our technique is rooted in machine learning which shows that by judicially employing component classifiers, an ensemble classifier can be constructed to outperform its components. We use two sequence- and three structure-comparison tools as component classifiers. Given a protein structure, using the joint hypothesis, we first determine if the protein belongs to an existing category (family, superfamily, fold) in the SCOP hierarchy. For the proteins that are predicted as members of the existing categories, we compute their family-, superfamily-, and fold-level classifications using the consensus classifier. We show that we can significantly improve the classification accuracy compared to the individual component classifiers. In particular, we achieve error rates that are 3-12 times less than the individual classifiers' error rates at the family level, 1.5-4.5 times less at the superfamily level, and 1.1-2.4 times less at the fold level.

Algorithms↗

Proteome-wide structural and interaction analysis using cross-linking mass spectrometry and its applications.

Deciphering the mechanisms of protein-protein interactions (PPIs) and protein structural changes within the native cellular environment is crucial for advancing drug discovery. In vivo chemical cross-linking coupled with mass spectrometry (XL-MS) captures weak, transient, and higher-order interactions that are often dysregulated under altered physiological conditions and remain challenging to detect using conventional methods. Applications of in vivo XL-MS range from targeted mapping of PPIs to large-scale identification of interactome networks within the cells. The integration of quantitative approaches further facilitates comparison across different physiological conditions. The recent incorporation of machine learning (ML) tools into XL-MS workflows is transforming the depth and efficiency of this technology. AI-driven algorithms now enable more accurate identification of cross-linked peptides and the mapping of interaction topologies. Furthermore, the synergistic coupling of in vivo XL-MS data with AI-assisted structural modeling platforms such as AlphaFold allows dynamic and high-throughput prediction of protein networks. This review discusses the broader applications of in vivo XL-MS in complex biological samples, ranging from organelles and cells to whole tissues, and highlights how AI integration is expanding structural biology toward a systems-level understanding of proteome architecture.

Mass Spectrometry↗

Decision tree based information integration for automated protein classification.

We propose a novel technique for automatically generating the SCOP classification of a protein structure with high accuracy. We achieve accurate classification by combining the decisions of multiple methods using the consensus of a committee (or an ensemble) classifier. Our technique, based on decision trees, is rooted in machine learning which shows that by judicially employing component classifiers, an ensemble classifier can be constructed to outperform its components. We use two sequence- and three structure-comparison tools as component classifiers. Given a protein structure and using the joint hypothesis, we first determine if the protein belongs to an existing category (family, superfamily, fold) in the SCOP hierarchy. For the proteins that are predicted as members of the existing categories, we compute their family-, superfamily-, and fold-level classifications using the consensus classifier. We show that we can significantly improve the classification accuracy compared to the individual component classifiers. In particular, we achieve error rates that are 3-12 times less than the individual classifiers' error rates at the family level, 1.5-4.5 times less at the superfamily level, and 1.1-2.4 times less at the fold level.

Algorithms↗

A model of force and impedance in human arm movements.

This paper describes a simple computational model of joint torque and impedance in human arm movements that can be used to simulate three-dimensional movements of the (redundant) arm or leg and to design the control of robots and human-machine interfaces. This model, based on recent physiological findings, assumes that (1) the central nervous system learns the force and impedance to perform a task successfully in a given stable or unstable dynamic environment and (2) stiffness is linearly related to the magnitude of the joint torque and increased to compensate for environment instability. Comparison with existing data shows that this simple model is able to predict impedance geometry well.

Arm↗

Efforts towards a precision medicine approach in juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is the commonest group of childhood arthritides. Despite the availability of advanced therapeutics, many children and young people (CYP) with JIA experience disease flares, and in some, chronic joint damage. Tailoring treatment based on unique biological profiles would benefit CYP with JIA given their variable clinical presentation and disease course. To date, biomarkers to predict treatment response are lacking. With advances in single cell technologies, we are now able to profile the genes and proteins of target tissues at unprecedented resolution to define the biological basis of disease and guide novel treatment approaches. The complex analyses and combination of biological and clinical outcome data from large datasets across disease phenotypes have become possible with the development of computational and machine learning methods. Here, we summarize the strategies to integrate data through multimodal based approaches to maximize precision medicine and research priorities for CYP with JIA.

Humans↗

Toward multistrategy parallel and distributed learning in sequence analysis.

Machine learning techniques have been shown to be effective in sequence analysis tasks. However, current learning algorithms, which are typically serial main-memory-based, are not capable of handling the vast amounts of information being generated by the Human Genome Project. The multistrategy parallel learning approach presented in this paper is an attempt to scale existing learning algorithms. Learning speed is improved through running multiple learning processes in parallel and prediction accuracy is improved through multiple learners. Our approaches are independent of the learning algorithms used. This paper focuses on one of the MSPL approaches and preliminary empirical results that we present are encouraging.

Algorithms↗

QSAR study of 1,4-dihydropyridine calcium channel antagonists based on gene expression programming.

The gene expression programming, a novel machine learning algorithm, is used to develop quantitative model as a potential screening mechanism for a series of 1,4-dihydropyridine calcium channel antagonists for the first time. The heuristic method was used to search the descriptor space and select the descriptors responsible for activity. A nonlinear, six-descriptor model based on gene expression programming with mean-square errors 0.19 was set up with a predicted correlation coefficient (R2) 0.92. This paper provides a new and effective method for drug design and screening.

Algorithms↗

Causal protein-signaling networks derived from multiparameter single-cell data.

Machine learning was applied for the automated derivation of causal influences in cellular signaling networks. This derivation relied on the simultaneous measurement of multiple phosphorylated protein and phospholipid components in thousands of individual primary human immune system cells. Perturbing these cells with molecular interventions drove the ordering of connections between pathway components, wherein Bayesian network computational methods automatically elucidated most of the traditionally reported signaling relationships and predicted novel interpathway network causalities, which we verified experimentally. Reconstruction of network models from physiologically relevant primary single cells might be applied to understanding native-state tissue signaling biology, complex drug actions, and dysfunctional signaling in diseased cells.

Algorithms↗

The use of misclassification costs to learn rule-based decision support models for cost-effective hospital admission strategies.

Cost-effective health care is at the forefront of today's important health-related issues. A research team at the University of Pittsburgh has been interested in lowering the cost of medical care by attempting to define a subset of patients with community-acquire pneumonia for whom outpatient therapy is appropriate and safe. Sensitivity and specificity requirements for this domain make it difficult to use rule-based learning algorithms with standard measures of performance based on accuracy. This paper describes the use of misclassification costs to assist a rule-based machine-learning program in deriving a decision-support aid for choosing outpatient therapy for patients with community-acquired pneumonia.

Algorithms↗