Brain simulation augments machine-learning-based classification of dementia.

Introduction: Computational brain network modeling using The Virtual Brain (TVB) simulation platform acts synergistically with machine learning (ML) and multi-modal neuroimaging to reveal mechanisms and improve diagnostics in Alzheimer's disease (AD). Methods: We enhance large-scale whole-brain simulation in TVB with a cause-and-effect model linking local amyloid beta (Aß) positron emission tomography (PET) with altered excitability. We use PET and magnetic resonance imaging (MRI) data from 33 participants of the Alzheimer's Disease Neuroimaging Initiative (ADNI3) combined with frequency compositions of TVB-simulated local field potentials (LFP) for ML classification. Results: The combination of empirical neuroimaging features and simulated LFPs significantly outperformed the classification accuracy of empirical data alone by about 10% (weighted F1-score empirical 64.34% vs. combined 74.28%). Informative features showed high biological plausibility regarding the AD-typical spatial distribution. Discussion: The cause-and-effect implementation of local hyperexcitation caused by Aß can improve the ML-driven classification of AD and demonstrates TVB's ability to decode information in empirical data using connectivity-based brain simulation.

[Quality of life in Mexican women with breast cancer at different stages and its association with sociodemographic characteristics, comorbidities and procedural factors at the Mexican Institute of Social Security]. / Calidad de vida en mujeres Mexicanas con cáncer de mama en diferentes etapas clínicas y su asociación con características socio-demográficas, estados co-mórbidos y características del proceso de atención en el Instituto Mexicano del Seguro Social.

INTRODUCTION: Quality of life is the most studied PRO (patient reported outcome) in cancer patients. With early diagnosis and better treatments in breast cancer, this entity has been transformed in a chronic disease with longer survival. The joint effects of diseases and treatment on quality of life are each day more important to consider in survival patients. OBJECTIVE: To evaluate quality of life, socioeconomic factors, co-morbidities, and the attendance process impact on quality of life in breast cancer women with different clinical stages attending at the Instituto Mexicano del Seguro Social using the EORCT QLQ-C30 RESULTS: The scores of EORTC QLQ-C30 (v3) were: Global health status / QoL: 73.47 (± 20.81), physical functioning 76.98 (± 20.85), role functioning 76.60 (± 27.57), emotional functioning 64.53 (± 26.81), cognitive functioning 74.47 (± 26.02), social functioning 84.96 (± 23.20), fatigue 31.94 (± 25.45), nausea and vomiting 19.49 (± 26.93), pain 28.95 (± 27.27), dyspnea 15.29 (± 24.62), insomnia 35.13 (± 32.10), appetite lost 18.04 (± 28.75), 18.04 (± 28.75), constipation 19.20 (± 32.11), diarrhea 12.9 (± 24.25), financial difficulties 40.57 (± 37.26). The scores with EORTC QLQ-BR23 were: body image 74.84 (± 31.69), sexual functioning 13.73 (± 22.55), sexual enjoyment 32.86 (± 36.17), future perspectives 51.69 (± 38.00), systemic therapy side effects 30.82 (± 20.71), breast symptoms 22.85 (± 23.49), arm symptoms 27.53 (± 24.75), upset by hair loss 43.80 (± 44.01). CONCLUSIONS: Clinical stage in breast cancer is associated with differences in the scores from fatigue, nausea and vomiting and financial difficulties according to the evolution of the disease and the physical detriment associated. Socio-demographic features were related role functioning, fatigue and pain in single women with higher scores.

[Evaluation of patient satisfaction with the quality of health care received within the EORTC IN-PATSAT32 trial by patients with breast and colorectal cancer, and non-Hodgkin lymphoma at different stages. Correlation with sociodemographic characteristics, comorbidities and other procedural variables at the Mexican Institute of Social Security]. / Análisis de la satisfacción con los cuidados en salud a través del cuestionario EORTC IN-PATSAT32 en pacientes con cáncer de mama, linfoma no Hodgkin y cáncer colo-rectal en diferentes etapas clínicas. Relación con las características socio-demográficas, estados co-mórbidos y variables del proceso de atención en el Instituto Mexicano del Seguro Social.

INTRODUCTION: In Mexico cancer is a public health burden. Nowadays the health care systems pay special attention to patient's perception and satisfaction of the health care received. Satisfaction with quality of health care has an impact in the adherence to the treatment. OBJECTIVE: To evaluate the satisfaction with the quality of health care received at the IMSS in a group of cancer patients [non Hodgkin lymphoma (NHL), breast and colorectal cancer]. Socio-demographic features, co-morbid diseases, and attendance processes impact on satisfaction are also evaluated. RESULTS: 476 cancer patients were studied: 314 with breast cancer, 92 with NHL and 70 with colorectal cancer. In women with breast cancer the mean score to nurses' interpersonal skills in non-classified disease group and clinical stage III group were: 73.64 ± 32.53, 90.00 ± 18.25 respectively (p=0.005), nurses' availability in non-classified and clinical stage III group were: 69.71 ± 30.25, 89.21 ± 19.00 respectively (p=0.003). In subjects with NHL the mean scores for doctors' technical skills in clinical stage I and III groups, were: 63.69 ± 37.78, 80.30 ± 18.46 respectively (p=0.017), doctors' information provision scores in subject in clinical stage I and IV were: 49.40 ± 40.75, 79.49 ± 24.63 respectively (p=0.043). In the group of colorectal cancer patients the mean of the score to exchange of information between clinical stage II and clinical stage III group were 50.00 ± 41.83, 84.21 ± 22.37 respectively (p=0.036). Were not observed association between attendance processes features and general satisfaction. CONCLUSIONS: In Mexico 50% of cancer patients are attended at the IMSS. The continued evaluation of the satisfaction with health care received by the health care service users is important to enhance attention's quality.

[Evaluation of health-related quality of life in patients with non-Hodgkin lymphoma and colorectal cancer at different stages, attending the Mexican Institute of Social Security]. / Evaluación de la calidad de vida en pacientes con linfoma no Hodgkin y cáncer colo-rectal en diferentes etapas clínicas atendidos en el Instituto Mexicano del Seguro Social.

INTRODUCTION: In Mexico during 2008, were reported 127,604 new cancer cases, 6,347 of them were colorectal cancer cases and 4,276 non-Hodgkin lymphoma (NHL) cases. OBJECTIVE: To evaluate health related quality of life in non-Hodgkin lymphoma and colorectal cancer cases in different clinical stages, attended in a High Specialty Medical facility at the Instituto Mexicano del Seguro Social, during a 13 month period. RESULTS: 162 patients were included, 56.8% (n=92) with NHL and 43.2% (n=70) with colorectal cancer. The scores obtained in the NHL group were: Global health status/QoL: 67.75 (± 27.55), physical functioning 69.64 (± 29.98), role functioning 71.38 (± 33.73), emotional functioning 69.7 (± 26.57), cognitive functioning 75.36 (± 28.01), social functioning 79.35 (± 29.38), fatigue 35.27 (± 28.27), nausea and vomiting 13.41 (± 21.85), pain 28.08 (± 30.25), dyspnea 19.20 (± 32.11), insomnia 30.80 (± 38.03), appetite lost 26.45 (± 36.16), constipation 19.20 (± 32.11), diarrhea 12.32 (± 26.48), financial difficulties 26.09 (± 35.57). In colorectal cancer patients the scores were: Global health status/QoL: 68.21 (± 24.46), physical functioning 67.38 (± 30.45), role functioning 65.48 (± 35.70), emotional functioning 66.43 (± 26.84), cognitive functioning 78.57 (± 26.49), social functioning 75.24 (± 31.05), fatigue 37.78 (± 31.62), nausea and vomiting 20.00 (± 28.32), pain 37.38 (± 34.45), dyspnea 11.90 (± 26.64), insomnia 28.09 (± 35.73), appetite lost 23.81 (± 36.40), constipation 19.05 (± 32.88), diarrhea 20.95 (± 31.17), financial difficulties 34.76 (± 38.67). CONCLUSIONS: With these basal results is important a follow-up with special attention to the treatment and attendance processes, in patients with this neoplasms and their impact on the quality of life.

Linking Molecular Pathways and Large-Scale Computational Modeling to Assess Candidate Disease Mechanisms and Pharmacodynamics in Alzheimer's Disease.

Introduction: While the prevalence of neurodegenerative diseases associated with dementia such as Alzheimer's disease (AD) increases, our knowledge on the underlying mechanisms, outcome predictors, or therapeutic targets is limited. In this work, we demonstrate how computational multi-scale brain modeling links phenomena of different scales and therefore identifies potential disease mechanisms leading the way to improved diagnostics and treatment. Methods: The Virtual Brain (TVB; thevirtualbrain.org) neuroinformatics platform allows standardized large-scale structural connectivity-based simulations of whole brain dynamics. We provide proof of concept for a novel approach that quantitatively links the effects of altered molecular pathways onto neuronal population dynamics. As a novelty, we connect chemical compounds measured with positron emission tomography (PET) with neural function in TVB addressing the phenomenon of hyperexcitability in AD related to the protein amyloid beta (Abeta). We construct personalized virtual brains based on an averaged healthy connectome and individual PET derived distributions of Abeta in patients with mild cognitive impairment (MCI, N = 8) and Alzheimer's Disease (AD, N = 10) and in age-matched healthy controls (HC, N = 15) using data from ADNI-3 data base (http://adni.loni.usc.edu). In the personalized virtual brains, individual Abeta burden modulates regional Excitation-Inhibition balance, leading to local hyperexcitation with high Abeta loads. We analyze simulated regional neural activity and electroencephalograms (EEG). Results: Known empirical alterations of EEG in patients with AD compared to HCs were reproduced by simulations. The virtual AD group showed slower frequencies in simulated local field potentials and EEG compared to MCI and HC groups. The heterogeneity of the Abeta load is crucial for the virtual EEG slowing which is absent for control models with homogeneous Abeta distributions. Slowing phenomena primarily affect the network hubs, independent of the spatial distribution of Abeta. Modeling the N-methyl-D-aspartate (NMDA) receptor antagonism of memantine in local population models, reveals potential functional reversibility of the observed large-scale alterations (reflected by EEG slowing) in virtual AD brains. Discussion: We demonstrate how TVB enables the simulation of systems effects caused by pathogenetic molecular candidate mechanisms in human virtual brains.