OBJECTIVE: The cerebellum is involved in higher-order mental processing as well as sensorimotor functions. Although structural abnormalities in the cerebellum have been demonstrated in schizophrenia, neuroimaging techniques are not yet applicable to identify them given the lack of biomarkers. We aimed to develop a robust diagnostic model for schizophrenia using radiomic features from T1-weighted magnetic resonance imaging (T1-MRI) of the cerebellum.
METHODS: A total of 336 participants (174 schizophrenia; 162 healthy controls [HCs]) were allocated to training (122 schizophrenia; 115 HCs) and test (52 schizophrenia; 47 HCs) cohorts. We obtained 2568 radiomic features from T1-MRI of the cerebellar subregions. After feature selection, a light gradient boosting machine classifier was trained. The discrimination and calibration of the model were evaluated. SHapley Additive exPlanations (SHAP) was applied to determine model interpretability.
RESULTS: We identified 17 radiomic features to differentiate participants with schizophrenia from HCs. In the test cohort, the radiomics model had an area under the curve, accuracy, sensitivity, and specificity of 0.89 (95% confidence interval: 0.82-0.95), 78.8%, 88.5%, and 75.4%, respectively. The model explanation by SHAP suggested that the second-order size zone non-uniformity feature from the right lobule IX and first-order energy feature from the right lobules V and VI were highly associated with the risk of schizophrenia.
CONCLUSIONS: The radiomics model focused on the cerebellum demonstrates robustness in diagnosing schizophrenia. Our results suggest that microcircuit disruption in the posterior cerebellum is a disease-defining feature of schizophrenia, and radiomics modeling has potential for supporting biomarker-based decision-making in clinical practice.

Delayed diagnosis of patients with sepsis or septic shock is associated with increased mortality and morbidity. UPLC-MS and NMR spectroscopy were used to measure panels of lipoproteins, lipids, biogenic amines, amino acids, and tryptophan pathway metabolites in blood plasma samples collected from 152 patients within 48 h of admission into the Intensive Care Unit (ICU) where 62 patients had no sepsis, 71 patients had sepsis, and 19 patients had septic shock. Patients with sepsis or septic shock had higher concentrations of neopterin and lower levels of HDL cholesterol and phospholipid particles in comparison to nonsepsis patients. Septic shock could be differentiated from sepsis patients based on different concentrations of 10 lipids, including significantly lower concentrations of five phosphatidylcholine species, three cholesterol esters, one dihydroceramide, and one phosphatidylethanolamine. The Supramolecular Phospholipid Composite (SPC) was reduced in all ICU patients, while the composite markers of acute phase glycoproteins were increased in the sepsis and septic shock patients within 48 h admission into ICU. We show that the plasma metabolic phenotype obtained within 48 h of ICU admission is diagnostic for the presence of sepsis and that septic shock can be differentiated from sepsis based on the lipid profile.

In the field of audiology, achieving accurate discrimination of auditory impairments remains a formidable challenge. Conditions such as deafness and tinnitus exert a substantial impact on patients\' overall quality of life, emphasizing the urgent need for precise and efficient classification methods. This study introduces an innovative approach, utilizing Multi-View Brain Network data acquired from three distinct cohorts: 51 deaf patients, 54 with tinnitus, and 42 normal controls. Electroencephalogram (EEG) recording data were meticulously collected, focusing on 70 electrodes attached to an end-to-end key with 10 regions of interest (ROI). This data is synergistically integrated with machine learning algorithms. To tackle the inherently high-dimensional nature of brain connectivity data, principal component analysis (PCA) is employed for feature reduction, enhancing interpretability. The proposed approach undergoes evaluation using ensemble learning techniques, including Random Forest, Extra Trees, Gradient Boosting, and CatBoost. The performance of the proposed models is scrutinized across a comprehensive set of metrics, encompassing cross-validation accuracy (CVA), precision, recall, F1-score, Kappa, and Matthews correlation coefficient (MCC). The proposed models demonstrate statistical significance and effectively diagnose auditory disorders, contributing to early detection and personalized treatment, thereby enhancing patient outcomes and quality of life. Notably, they exhibit reliability and robustness, characterized by high Kappa and MCC values. This research represents a significant advancement in the intersection of audiology, neuroimaging, and machine learning, with transformative implications for clinical practice and care.

Quantitative plasma lipoprotein and metabolite profiles were measured on an autonomous community of the Basque Country (Spain) cohort consisting of hospitalized COVID-19 patients (n = 72) and a matched control group (n = 75) and a Western Australian (WA) cohort consisting of (n = 17) SARS-CoV-2 positives and (n = 20) healthy controls using 600 MHz 1H nuclear magnetic resonance (NMR) spectroscopy. Spanish samples were measured in two laboratories using one-dimensional (1D) solvent-suppressed and T2-filtered methods with in vitro diagnostic quantification of lipoproteins and metabolites. SARS-CoV-2 positive patients and healthy controls from both populations were modeled and cross-projected to estimate the biological similarities and validate biomarkers. Using the top 15 most discriminatory variables enabled construction of a cross-predictive model with 100% sensitivity and specificity (within populations) and 100% sensitivity and 82% specificity (between populations). Minor differences were observed between the control metabolic variables in the two cohorts, but the lipoproteins were virtually indistinguishable. We observed highly significant infection-related reductions in high-density lipoprotein (HDL) subfraction 4 phospholipids, apolipoproteins A1 and A2,that have previously been associated with negative regulation of blood coagulation and fibrinolysis. The Spanish and Australian diagnostic SARS-CoV-2 biomarkers were mathematically and biologically equivalent, demonstrating that NMR-based technologies are suitable for the study of the comparative pathology of COVID-19 via plasma phenotyping.

To investigate the systemic metabolic effects of SARS-CoV-2 infection, we analyzed 1H NMR spectroscopic data on human blood plasma and co-modeled with multiple plasma cytokines and chemokines (measured in parallel). Thus, 600 MHz 1H solvent-suppressed single-pulse, spin-echo, and 2D J-resolved spectra were collected on plasma recorded from SARS-CoV-2 rRT-PCR-positive patients (n = 15, with multiple sampling timepoints) and age-matched healthy controls (n = 34, confirmed rRT-PCR negative), together with patients with COVID-19/influenza-like clinical symptoms who tested SARS-CoV-2 negative (n = 35). We compared the single-pulse NMR spectral data with in vitro diagnostic research (IVDr) information on quantitative lipoprotein profiles (112 parameters) extracted from the raw 1D NMR data. All NMR methods gave highly significant discrimination of SARS-CoV-2 positive patients from controls and SARS-CoV-2 negative patients with individual NMR methods, giving different diagnostic information windows on disease-induced phenoconversion. Longitudinal trajectory analysis in selected patients indicated that metabolic recovery was incomplete in individuals without detectable virus in the recovery phase. We observed four plasma cytokine clusters that expressed complex differential statistical relationships with multiple lipoproteins and metabolites. These included the following: cluster 1, comprising MIP-1β, SDF-1α, IL-22, and IL-1α, which correlated with multiple increased LDL and VLDL subfractions; cluster 2, including IL-10 and IL-17A, which was only weakly linked to the lipoprotein profile; cluster 3, which included IL-8 and MCP-1 and were inversely correlated with multiple lipoproteins. IL-18, IL-6, and IFN-γ together with IP-10 and RANTES exhibited strong positive correlations with LDL1-4 subfractions and negative correlations with multiple HDL subfractions. Collectively, these data show a distinct pattern indicative of a multilevel cellular immune response to SARS CoV-2 infection interacting with the plasma lipoproteome giving a strong and characteristic immunometabolic phenotype of the disease. We observed that some patients in the respiratory recovery phase and testing virus-free were still metabolically highly abnormal, which indicates a new role for these technologies in assessing full systemic recovery.

Insomnia has not been explored as it relates to recovery after mild traumatic brain injury (mTBI). We aimed to evaluate the prevalence of insomnia among Ontario workers with delayed recovery from mTBI, and its relationship with sociodemographic, TBI- and claim-related, behavioral, and clinical factors.
This was a cross-sectional study carried out over a period of 24 months in a large rehabilitation hospital in Ontario. To assess the prevalence of insomnia, we used the Insomnia Severity Index (ISI). Data were collected from standardized questionnaires, insurer records, and clinical assessment at the time of recruitment. Bivariate associations were calculated using the Spearman\'s correlation coefficient or analysis of variance. We established stepwise multivariate linear regression models of factors associated with insomnia. Additional analyses, including the assessment of the internal consistency of the ISI, were performed.
Of the 94 participants diagnosed with mTBI, clinical insomnia was reported by 69.2%. The mean age was 45.20 ± 9.94 years; 61.2% were men. No sex-related differences were observed in insomnia prevalence or severity. Insomnia was significantly associated with certain sociodemographic, claim-related, behavioral, and clinical variables. In the multivariable regression analysis, several determinants explained 53% of the insomnia variance. The internal consistency of the ISI, as measured by Cronbach\'s α, was 0.86.
Insomnia is common in persons with delayed recovery from mTBI, and is significantly associated with potentially modifiable clinical and nonclinical variables. Care of persons with brain injury requires greater attention with regard to the diagnosis and management of insomnia and associated disorders.