An Application of Deep Belief Networks in Early Warning for Cerebrovascular Disease Risk

To reduce the incidence of cerebrovascular disease and mortality, identifying the risks of cerebrovascular disease in advance and taking certain preventive measures are significant. This article was aimed to investigate the risk factors of cerebrovascular disease (CVD) in the primary prevention, and to build an early warning model based on the existing technology. The authors use the information entropy algorithm of rough set theory to establish the index system suitable for early warning model. Then, using the limited Boltzmann machine and direction propagation algorithm, the depth trust network is established by building and stacking RBM, and the back propagation is used to fine-tune the parameters of the network at the top layer. Compared with the LM-BP early-warning model, the deep confidence network model is more effective than traditional artificial neural network, which can help to identify the risk of cerebrovascular disease in advance and promote the primary prevention.

Short structural variants as informative genetic markers for ALS disease risk and progression

There is considerable variability in disease progression for patients with amyotrophic lateral sclerosis (ALS) including the age of disease onset, site of disease onset, and survival time. There is growing evidence that short structural variations (SSVs) residing in frequently overlooked genomic regions can contribute to complex disease mechanisms and can explain, in part, the phenotypic variability in ALS patients. Here, we discuss SSVs recently characterized by our laboratory and how these discoveries integrate into the current literature on ALS, particularly in the context of application to future clinical trials. These markers may help to identify and differentiate patients for clinical trials that have a similar ALS disease mechanism(s), thereby reducing the impact of participant heterogeneity. As evidence accumulates for the genetic markers discovered in SQSTM1, SCAF4, and STMN2, we hope to improve the outcomes of future ALS clinical trials.

Whole Grain Consumption and Inflammatory Markers: A Systematic Literature Review of Randomized Control Trials

Whole grain foods are rich in nutrients, dietary fibre, a range of antioxidants, and phytochemicals, and may have potential to act in an anti-inflammatory manner, which could help impact chronic disease risk. This systematic literature review aimed to examine the specific effects of whole grains on selected inflammatory markers from human clinical trials in adults. As per the Preferred Reporting Items for Systematic Reviews (PRISMA) protocol, the online databases MEDLINE, Embase, Cochrane, CINAHL, and Scopus were searched from inception through to 31 August 2021. Randomized control trials (RCTs) ≥ 4 weeks in duration, reporting ≥1 of the following: C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor (TNF), were included. A total of 31 RCTs were included, of which 16 studies recruited overweight/obese individuals, 12 had pre-existing conditions, two were in a healthy population, and one study included participants with prostate cancer. Of these 31 RCTs, three included studies with two intervention arms. A total of 32 individual studies measured CRP (10/32 were significant), 18 individual studies measured IL-6 (2/18 were significant), and 13 individual studies measured TNF (5/13 were significant). Most often, the overweight/obese population and those with pre-existing conditions showed significant reductions in inflammatory markers, mainly CRP (34% of studies). Overall, consumption of whole grain foods had a significant effect in reducing at least one inflammatory marker as demonstrated in 12/31 RCTs.

The Association between Exposure to Residential Indoor Volatile Organic Compounds and Measures of Central Arterial Stiffness in Healthy Middle-Aged Men and Women

It is well reported that individuals spend up to 90% of their daily time indoors, with between 60% to 90% of this time being spent in the home. Using a cross-sectional study design in a population of 111 healthy adults (mean age: 52.3 ± 9.9 years; 65% women), we investigated the association between exposure to total volatile organic compounds (VOCs) in indoor residential environments and measures of central arterial stiffness, known to be related to cardiovascular risk. Indoor VOC concentrations were measured along with ambulatory measures of pulse pressure (cPP), augmentation index (cAIx) and cAIx normalized for heart rate (cAIx75), over a continuous 24-h period. Pulse wave velocity (cfPWV) was determined during clinical assessment. Multiple regression analysis was performed to examine the relationship between measures of arterial stiffness and VOCs after adjusting for covariates. Higher 24-h, daytime and night-time cAIx was associated with an interquartile range increase in VOCs. Similar effects were shown with cAIx75. No significant effects were observed between exposure to VOCs and cPP or cfPWV. After stratifying for sex and age (≤50 years; >50 years), effect estimates were observed to be greater and significant for 24-h and daytime cAIx in men, when compared to women. No significant effect differences were seen between age groups with any measure of arterial stiffness. In this study, we demonstrated that residential indoor VOCs exposure was adversely associated with some measures of central arterial stiffness, and effects were different between men and women. Although mechanistic pathways remain unclear, these findings provide a possible link between domestic VOCs exposure and unfavourable impacts on individual-level cardiovascular disease risk.

Vitamin D receptor gene polymorphism predicts left ventricular hypertrophy in maintenance hemodialysis

Background To verify that the single nucleotide polymorphisms (SNP) of vitamin D receptor (VDR) may lead to genetic susceptibility to left ventricular hypertrophy (LVH), the present study was designed to study four SNPs of VDR associated with LVH in maintenance hemodialysis (MHD) patients of Han nationality. Methods 120 MHD patients were recruited at Department of Nephrology, Zhongnan Hospital of Wuhan University to analyze the expression of genotype, allele and haplotype of Fok I, Bsm I, Apa I and Taq I in blood samples, and to explore their correlation with blood biochemical indexes and ventricular remodeling. Results The results showed that the risks of CVD included gender, dialysis time, heart rate, SBP, glycated hemoglobin, calcium, iPTH and CRP concentration. Moreover, LAD, LVDd, LVDs, IVST and LVMI in B allele of Bsm I increased significantly. Fok I, Apa I and Taq I polymorphisms have no significant difference between MHD with LVH and without LVH. Further study showed that VDR expression level decreased significantly in MHD patients with LVH, and the B allele was positively correlated with VDR Expression. Conclusion VDR Bsm I gene polymorphism may predict cardiovascular disease risk of MDH patients, and provided theoretical basis for early detection and prevention of cardiovascular complications.

Endothelial Dysfunction: An Intermediate Clinical Feature between Urolithiasis and Cardiovascular Diseases

An epidemiological relationship between urolithiasis and cardiovascular diseases has extensively been reported. Endothelial dysfunction is an early pathogenic event in cardiovascular diseases and has been associated with oxidative stress and low chronic inflammation in hypertension, coronary heart disease, stroke or the vascular complications of diabetes and obesity. The aim of this study is to summarize the current knowledge about the pathogenic mechanisms of urolithiasis in relation to the development of endothelial dysfunction and cardiovascular morbidities. Methods: A non-systematic review has been performed mixing the terms “urolithiasis”, “kidney stone” or “nephrolithiasis” with “cardiovascular disease”, “myocardial infarction”, “stroke”, or “endothelial dysfunction”. Results: Patients with nephrolithiasis develop a higher incidence of cardiovascular disease with a relative risk estimated between 1.20 and 1.24 and also develop a higher vascular disease risk scores. Analyses of subgroups have rendered inconclusive results regarding gender or age. Endothelial dysfunction has also been strongly associated with urolithiasis in clinical studies, although no systemic serum markers of endothelial dysfunction, inflammation or oxidative stress could be clearly related. Analysis of urine composition of lithiasic patients also detected a higher expression of proteins related to cardiovascular disease. Experimental models of hyperoxaluria have also found elevation of serum endothelial dysfunction markers. Conclusions: Endothelial dysfunction has been strongly associated with urolithiasis and based on the experimental evidence, should be considered as an intermediate and changeable feature between urolithiasis and cardiovascular diseases. Oxidative stress, a key pathogenic factor in the development of endothelial dysfunction has been also pointed out as an important factor of lithogenesis. Special attention must be paid to cardiovascular morbidities associated with urolithiasis in order to take advantage of pleiotropic effects of statins, angiotensin receptor blockers and allopurinol.

Epidemic networks and potential sources of bacterial wilt infection in a potato seed network in Kenya.

Potato seed systems in Kenya are largely informal, characterized by high seed degeneration due to the buildup of seed- and soil-borne diseases, including bacterial wilt caused by Ralstonia solanacearum. Informal sources of seed include neighbors, local markets and farmer-saved seed, and present a risk for spread and establishment of disease. To understand the larger context of potato disease risk in Kenya, we used network analysis to evaluate (1) epidemic risk through potato trade networks centered around East Africa, and (2) locations in East Africa likely to be particularly important for epidemic management because of their high potato cropland connectivity. We evaluated the interactions of the key stakeholders in a potato seed system and used network analysis to identify locations that are likely to be important for the spread of infection of R. solanacearum in a potato seed distribution network in Meru, Kenya. Household details, seed sources, quantities sold, pest incidence and management practices, knowledge about seed degeneration and farmers' sources of information on potato production were obtained and analyzed. The survey revealed that self-saved, neighbors, seed companies, friends, exchange, and markets are the main seed sources. Only 43% of total seed transacted was certified. Users of uncertified seeds have high disease risk, and this is an especially important risk if their roles in the network give them the potential to be 'superspreaders' of disease.

Clinical Trials in High-Risk Medulloblastoma: Evolution of the SIOP-Europe HR-MB Trial

Medulloblastoma patients receive adapted therapies stratified according to their risk-profile. Favourable, standard, and high disease-risk groups are each defined by the status of clinical and pathological risk factors, alongside an evolving repertoire of diagnostic and prognostic biomarkers. Medulloblastoma clinical trials in Europe are coordinated by the International Society for Paediatric Oncology (SIOP-Europe) brain tumour group. Favourable and standard-risk patients are eligible for the SIOP-PNET5-MB clinical trial protocol. In contrast, therapies for high-risk disease worldwide have, to date, encompassed a range of different treatment philosophies, with no clear consensus on approach. Higher radiotherapy doses are typically deployed, delivered either conventionally or in hyper-fractionated/accelerated regimens. Similarly, both standard and high-dose chemotherapies were assessed. However, trials to date in high-risk medulloblastoma have commonly been institutional or national, based on modest cohort sizes, and have not evaluated the relative performance of different strategies in a randomised fashion. We describe the concepts and design of the SIOP-E high-risk medulloblastoma clinical trial (SIOP-HR-MB), the first international biomarker-driven, randomised, clinical trial for high-risk medulloblastoma. SIOP-HR-MB is programmed to recruit >800 patients in 16 countries across Europe; its primary objectives are to assess the relative efficacies of the alternative established regimens. The HR-MB patient population is molecularly and clinically defined, and upfront assessments incorporate a standardised central review of molecular pathology, radiology, and radiotherapy quality assurance. Secondary objectives include the assessment of (i) novel therapies within an upfront ‘window’ and (ii) therapy-associated neuropsychology, toxicity, and late effects, alongside (iii) the collection of materials for comprehensive integrated studies of biological determinants within the SIOP-HR-MB cohort.

ABCA7, a Genetic Risk Factor Associated with Alzheimer’s Disease Risk in African Americans

African American/Black adults are twice as likely to have Alzheimer’s disease (AD) compared to non-Hispanic White adults. Genetics partially contributes to this disparity in AD risk, among other factors, as there are several genetic variants associated with AD that are more prevalent in individuals of African or European ancestry. The phospholipid-transporting ATPase ABCA7 (ABCA7) gene has stronger associations with AD risk in individuals with African ancestry than in individuals with European ancestry. In fact, ABCA7 has been shown to have a stronger effect size than the apolipoprotein E (APOE) ɛ4 allele in African American/Black adults. ABCA7 is a transmembrane protein involved in lipid homeostasis and phagocytosis. ABCA7 dysfunction is associated with increased amyloid-beta production, reduced amyloid-beta clearance, impaired microglial response to inflammation, and endoplasmic reticulum stress. This review explores the impact of ABCA7 mutations that increase AD risk in African American/Black adults on ABCA7 structure and function and their contributions to AD pathogenesis. The combination of biochemical/biophysical and ‘omics-based studies of these variants needed to elucidate their downstream impact and molecular contributions to AD pathogenesis is highlighted.