Diagnosis and Prognosis Using Machine Learning Trained on Brain Morphometry and White Matter Connectomes

Accurate, reliable prediction of risk for Alzheimer’s disease (AD) is essential for early, diseasemodifying therapeutics. Multimodal MRI, such as structural and diffusion MRI, is likely to contain complementary information of neurodegenerative processes in AD. Here we tested the utility of commonly available multimodal MRI (T1-weighted structure and diffusion MRI), combined with high-throughput brain phenotyping—morphometry and connectomics—and machine learning, as a diagnostic tool for AD. We used, firstly, a clinical cohort at a dementia clinic (study 1: Ilsan Dementia Cohort; N=211; 110 AD, 64 mild cognitive impairment [MCI], and 37 subjective memory complaints [SMC]) to test and validate the diagnostic models; and, secondly, Alzheimer’s Disease Neuroimaging Initiative (ADNI)-2 (study 2) to test the generalizability of the approach and the prognostic models with longitudinal follow up data. Our machine learning models trained on the morphometric and connectome estimates (number of features=34,646) showed optimal classification accuracy (AD/SMC: 97% accuracy, MCI/SMC: 83% accuracy; AD/MCI: 97% accuracy) with iterative nested cross-validation in a single-site study, outperforming the benchmark model (FLAIR-based white matter hyperintensity volumes). In a generalizability study using ADNI-2, the combined connectome and morphometry model showed similar or superior accuracies (AD/HC: 96%; MCI/HC: 70%; AD/MCI: 75% accuracy) as CSF biomarker model (t-tau, p-tau, and Amyloid β, and ratios). We also predicted MCI to AD progression with 69% accuracy, compared with the 70% accuracy using CSF biomarker model. The optimal classification accuracy in a single-site dataset and the reproduced results in multisite dataset show the feasibility of the high-throughput imaging analysis of multimodal MRI and data-driven machine learning for predictive modeling in AD

Genetic evaluation of domestic walnut cultivars trading on Korean tree markets using microsatellite markers

Walnut (Juglans regia L.) is regarded as a healthy food because of its high nutritional composition and various health benefits. Although several walnut cultivars are being actively traded for domestic plantation or ornament in Korea, no particular effort has been made to evaluate genetic quality management of walnut cultivars in domestic tree markets. In this study, as an effort to evaluate the status of walnut seedling trade, we collected walnut seedlings of diverse cultivars from domestic tree markets and several locations in Korea and performed genotype analysis for the collections using microsatellite markers (76 individuals belonging to eight domestic cultivars). We used 12 markers that were previously reported to be informative and polymorphic in walnuts. The number of alleles that was detected from the collections using these markers ranged from 6 to 16, with heterozygosity values ranging from 0.03 to 0.75. Dendrogram revealed that the domestic walnut cultivars trading on tree markets could be genotypically distinguished from various foreign cultivars. However, genotyping data also showed that individual plants belonging to identical cultivars were sporadically distributed on the dendrogram, indicating that walnut cultivars trading on domestic tree markets seem to be poorly managed.Keywords: Walnut (Juglans regia L.), microsatellite markers, tree market, seedling trade, domestic cultivars, foreign cultivars, cultivar managementAfrican Journal of Biotechnology Vol. 11(29), pp. 7366-7374, 10 April, 201

Proteomic analysis of synaptic protein turnover in the anterior cingulate cortex after nerve injury

Synaptic proteins play an important role for the regulation of synaptic plasticity. Numerous studies have identified and revealed individual synaptic protein functions using protein overexpression or deletion. In neuropathic pain nociceptive stimuli conveyed from the periphery repetitively stimulate neurons in the central nerve system, brain and spinal cord. Neuronal activities change the turnover (synthesis and degradation) rate of synaptic proteins. Thus, the analysis of synaptic protein turnover rather than just expression level change is critical for studying the role of synaptic proteins in synaptic plasticity. Here, we analyzed synaptosomal proteome in the anterior cingulate cortex (ACC) to identify protein turnover rate changes caused by peripheral nerve injury. Whereas PKCγ levels were not altered, we found that the proteins turnover rate decreased after peripheral nerve injury. Our results suggest that postsynaptic PKCγ synthesized by neuronal activities in the ACC is translocated to the postsynaptic membrane with an extended half-life.This work was supported by two National Research Foundation (NRF) of Korea grants funded by the Korean government (MSIP) [NRF2012R1A3A1050385 to BKK and 2018R1C1B6008530 to HGK] and the Max Planck Society to CWT and DIP

Favorable response to doxorubicin combination chemotherapy does not yield good clinical outcome in patients with metastatic breast cancer with triple-negative phenotype

<p>Abstract</p> <p>Background</p> <p>We analyzed the responses to first line treatment and clinical outcomes of metastatic breast cancer patients treated with palliative doxorubicin/cyclophosphamide (AC) according to molecular cancer subtype.</p> <p>Methods</p> <p>A retrospective analysis was performed for 110 metastatic breast cancer patients selected on the basis of palliative AC treatment and the availability of immunohistochemical data for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2/neu) status.</p> <p>Results</p> <p>Of the 110 patients analyzed, 71 (64.5%) were hormone receptor positive (HR+), 14 (12.7%) were HER2+, and 25 (22.7%) were triple negative (TN). There were no differences in age, stage at diagnosis, total number of cycles of palliative chemotherapy, incidence of visceral metastasis, and metastatic sites with the exception of liver among breast cancer subtypes. The overall response rates to AC were 55.9% for the HR+ subgroup, 42.9% for the HER2+ subgroup, and 56.5% for the TN subgroup. The progression-free survival (PFS) in patients with HER2+ and TN were significantly shorter than in the HR+ (median PFS, 9.1 <it>vs </it>8.1 <it>vs </it>11.5 months, respectively; p = 0.0002). The overall survival (OS) was 25.4 months in the TN subgroup and 27.3 months in HER2+ subgroup. The median OS for these two groups was significantly shorter than for patients in the HR+ subgroup (median, 38.5 months; 95% CI, 30.1-46.9 months; p < 0.0001).</p> <p>Conclusions</p> <p>The response to palliative AC chemotherapy did not differ among breast cancer subtypes. Despite chemosensitivity for palliative AC, the TN subtype has a shorter overall survival than non-TN subtypes. Innovative treatment strategies should be developed to slow the course of disease.</p

Successful mobilization using a combination of plerixafor and G-CSF in pediatric patients who failed previous chemomobilization with G-CSF alone and possible complications of the treatment

Peripheral blood stem cell (PBSC) mobilization, which uses plerixafor (AMD 3100), a newly developed specific inhibitor of the CXCR4 receptor, in combination with granulocyte-colony stimulating factor(G-CSF), has been shown to enhance the stem cell mobilization in adult patients, but pediatric data are scarce. We documented our experience with this drug in 6 Korean pediatric patients who had failed in chemomobilization, using G-CSF, alone. All patients were mobilized CD34+ cells (median, 11.08 × 106/kg: range, 6.34-28.97 × 106/kg) successfully within 2 to 3 cycles of apheresis, without complications. A total of 7 autologous transplantations were performed, including 1 tandem transplantation. However, 2 patients with brain tumors showed severe pulmonary complications, including spontaneous pneumomediastinum. This is the first study of PBSC mobilization with plerixafor in Asian pediatric patients. Furthermore our study suggests that mobilization with plerixafor may be effective in Korean pediatric patients, who have previously been heavily treated and have failed PBSC mobilization with classical chemomobilization, using G-CSF. However, further studies are needed to examine the possible complications of autologous transplantation, using a mobilized plerixafor product in children