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Abstract Background Dealing with the high dimension of both neuroimaging data and genetic data is a difficult problem in the association of genetic data to neuroimaging. In this article, we tackle the latter problem with an eye toward developing solutions that are relevant for disease prediction. Supported by a vast literature on the predictive power of neural networks, our proposed solution uses neural networks to extract from neuroimaging data features that are relevant for predicting Alzheimer’s Disease (AD) for subsequent relation to genetics. The neuroimaging-genetic pipeline we propose is comprised of image processing, neuroimaging feature extraction and genetic association steps. We present a neural network classifier for extracting neuroimaging features that are related with the disease. The proposed method is data-driven and requires no expert advice or a priori selection of regions of interest. We further propose a multivariate regression with priors specified in the Bayesian framework that allows for group sparsity at multiple levels including SNPs and genes. Results We find the features extracted with our proposed method are better predictors of AD than features used previously in the literature suggesting that single nucleotide polymorphisms (SNPs) related to the features extracted by our proposed method are also more relevant for AD. Our neuroimaging-genetic pipeline lead to the identification of some overlapping and more importantly some different SNPs when compared to those identified with previously used features. Conclusions The pipeline we propose combines machine learning and statistical methods to benefit from the strong predictive performance of blackbox models to extract relevant features while preserving the interpretation provided by Bayesian models for genetic association. Finally, we argue in favour of using automatic feature extraction, such as the method we propose, in addition to ROI or voxelwise analysis to find potentially novel disease-relevant SNPs that may not be detected when using ROIs or voxels alone.

Abstract Unlike other histological types of epithelial ovarian carcinoma, clear cell ovarian carcinoma (CCOC) has poor response to therapy. In many other carcinomas, expression of the hypoxia-related enzyme Carbonic anhydrase IX (CAIX) by cancer cells is associated with poor prognosis, while the presence of CD8 + tumor-infiltrating lymphocytes (TIL) is positively prognostic. We employed [18F]EF5-PET/CT imaging, transcriptome profiling, and spatially-resolved histological analysis to evaluate relationships between CAIX, CD8, and survival in CCOC. Tissue microarrays (TMAs) were evaluated for 218 cases in the Canadian COEUR study. Non-spatial relationships between CAIX and CD8 were investigated using Spearman rank correlation, negative binomial regression and gene set enrichment analysis. Spatial relationships at the cell level were investigated using the cross K-function. Survival analysis was used to assess the relationship of CAIX and CD8 with patient survival for 154 cases. CD8 + T cell infiltration positively predicted survival with estimated hazard ratio 0.974 (95% CI 0.950, 1000). The negative binomial regression analysis found a strong TMA effect (p-value

Introduction: Ionizing radiation (IR) is effectively used in the treatment of oral malignancies; however, it might also significantly harm the surrounding tissues. Whey protein isolate (WP) is a protein derived from milk that exhibits a wide range of bioactivities. Therefore, the present research aimed to delineate the mitigating impact of WP against gamma irradiation-induced lingual damage.Methods: Rats were randomized into 5 groups: Control (saline, orally, 14 days), WP (WP; 0.5 g/kg b. w., orally, 14 days), IR (saline, orally, 14 days, exposed to 6 and 3 Gy on days 4 and 6, respectively), WP+IR (WP was given orally for 14 days before and after IR exposure; exposed to 6 and 3 Gy on days 4 and 6, respectively), and IR+WP (WP, orally, started 24 h after 1st IR exposure till the end of the experiment) groups. Samples were collected at two-time intervals (on the 7th and 14th days).Results and Discussion: Oxidative stress was stimulated upon IR exposure in tongue, indicated by boosted malondialdehyde (MDA) level, along with a decrease in the total antioxidant capacity (TAC) level, superoxide dismutase (SOD), and catalase (CAT) activities. Additionally, IR exposure depicted an increase of serum IgE, inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin (IL)-6, along with overexpression mRNA levels of nuclear factor kappa-B transcription factor/p65 (NF-κB/p65), and down-regulation of nuclear factor erythroid 2–related factor 2 (NRF2) and heme oxygenase (HO-1) mRNA levels in tongue tissue. Moreover, IR triggered alterations in lingual histological architecture. The antioxidant and anti-inflammatory properties of WP mitigated oxidative damage, inflammation, and desquamation that were brought on following IR exposure. The protective administration of WP markedly decreases IR-induced lingual harm compared to the mitigation protocol. Our findings recommend WP supplements to the diets of cancer patients undergoing IR that might aid radioprotective effects.

We discuss hypothesis testing and compare different theories in light of observed or experimental data as fundamental endeavors in the sciences. Issues associated with the p-value approach and null hypothesis significance testing are reviewed, and the Bayesian alternative based on the Bayes factor is introduced, along with a review of computational methods and sensitivity related to prior distributions. We demonstrate how Bayesian testing can be practically implemented in several examples, such as the t-test, two-sample comparisons, linear mixed models, and Poisson mixed models by using existing software. Caveats and potential problems associated with Bayesian testing are also discussed. We aim to inform researchers in the many fields where Bayesian testing is not in common use of a well-developed alternative to null hypothesis significance testing and to demonstrate its standard implementation.

In a host of business applications, biomedical and epidemiological studies, the problem of multicollinearity among predictor variables is a frequent issue in longitudinal data analysis for linear mixed models (LMM). We consider an efficient estimation strategy for high-dimensional data application, where the dimensions of the parameters are larger than the number of observations. In this paper, we are interested in estimating the fixed effects parameters of the LMM when it is assumed that some prior information is available in the form of linear restrictions on the parameters. We propose the pretest and shrinkage estimation strategies using the ridge full model as the base estimator. We establish the asymptotic distributional bias and risks of the suggested estimators and investigate their relative performance with respect to the ridge full model estimator. Furthermore, we compare the numerical performance of the LASSO-type estimators with the pretest and shrinkage ridge estimators. The methodology is investigated using simulation studies and then demonstrated on an application exploring how effective brain connectivity in the default mode network (DMN) may be related to genetics within the context of Alzheimer’s disease.

Electroencephalography/Magnetoencephalography (EEG/MEG) source localization involves the estimation of neural activity inside the brain volume that underlies the EEG/MEG measures observed at the sensor array. In this paper, we consider a Bayesian finite spatial mixture model for source reconstruction and implement Ant Colony System (ACS) optimization coupled with Iterated Conditional Modes (ICM) for computing estimates of the neural source activity. Our approach is evaluated using simulation studies and a real data application in which we implement a nonparametric bootstrap for interval estimation. We demonstrate improved performance of the ACS-ICM algorithm as compared to existing methodology for the same spatiotemporal model.

BackgroundLeaf senescence is an oxidative process, and most of the catabolic events involved in senescence are propagated irreversibly once initiated. ResultsSalinity hastened the senescence of wheat flag leaves, decreased the concentrations of chlorophyll, total carotenoids, ascorbic acid, total phenol, calcium, potassium, magnesium, K+/Na+ ratio and soluble proteins, as well as the activities of catalase and peroxidase. Conversely, salinity increased sodium, chloride, and the chlorophylla:b ratio, as well as membrane permeability, hydrogen peroxide, and malondialdehyde synthesis. Both antioxidants application reduced the hydrogen peroxide accumulation, lipid peroxidation, membrane permeability, sodium and chloride content over control plants. The antioxidants enzyme activities were significantly increased by antioxidant spray. Enhanced accumulation of ascorbate, phenol, carotenoids, calcium, potassium and magnesium was seen in antioxidants-sprayed plants compared with control plants at 65 days after sowing. Under moderate and sever salinity levels application of both antioxidants alleviated the harmful effects of salinity on leaf senescence related parameter. The higher levels of antioxidants and low level of H2O2 in flag leaf may be the prerequisite for delayed leaf senescence in antioxidants-sprayed plants. ConclusionsIt can be concluded that ascorbic acid-sprayed plants can postpone the leaf senescence by peroxide/phenolic/ascorbate system which is involved in scavenging the ROS produced during leaf senescence.

BackgroundThe common bean plants "Phaseolus vulgaris L." is frequently attacked by the two spotted spider mite (TSSM) Tetranychus urticae, causing a substantial decrease in bean plant growth and yield as well as leaflet structure. Therefore, for commercial bean cultivation in the field controlling TSSM infection is necessary. ResultsFoliar application of salicylic acid (SA) or methyl jasmonate (MeJA) on common bean plants before or after two spotted spider mite infestation proved to be effective in reducing infestations. In most concentrations these elicitors significantly improved common bean plant growth i.e. had a positive effect on plant height, number of branches, shoot dry weight and leaf area per plant and bean yield. SA at 100 mg/l had the strongest positive effect. Moreover, application of elicitors significantly altered leaflet anatomical characters i.e. increased thickness of leaflet blade, thickness of palisade and spongy parenchyma as well as thickness of midrib region of the leaflet and changed the dimension of vascular bundles. Alternatively, TSSM infestation had the opposite effect on these leaflet anatomical characters.ConclusionWe conclude that SA or MeJA could be used for controlling TSSM infestation, to improve plant growth and to improve bean yield in the field.

BackgroundHumic acid or chitosan has been shown to increase plant growth, yield and improving physiological processes in plant, but its roles on alleviating the harmful effect of cadmium on plant growth and some physiological processes in plants is very rare. Pot experiments were conducted to study the role of 100 and 200 mg/kg dry soil from either humic acid or chitosan on counteracted the harmful effects of cadmium levels (100 and 150 mg/kg dry soil) on radish plant growth and some physiological charactersResultsCadmium at 100 and 150 mg kg-1 soil decreased significantly length, fresh and dry weights of shoot and root systems as well as leaf number per plant in both seasons. Chlorophyll, total sugars, nitrogen, phosphorus, potassium, relative water content, water deficit percentage and soluble proteins as well as total amino acids contents were also decreased. Meanwhile, cadmium concentration in plants was increased. On the other hand, application of chitosan or humic acid as soil addition at the concentration of 100 or 200 mg kg-1 increased all the above mentioned parameters and decreased cadmium concentrations in plant tissues. Chitosan at 200 mg kg-1 was the most effective than humic acid at both concentrations in counteracting the harmful effect of cadmium stress on radish plant growth.ConclusionIn conclusion, both natural chelators, in particular, chitosan at 200 mg/kg dry soil can increase the capacity of radish plant to survive under cadmium stress due to chelating the Cd in the soil, and then reduced Cd bio-availability.

BackgroundSalinity stress causes ion toxicity and osmotic imbalances, leading to oxidative stress in plants. Antioxidants are considered ameliorators of saline stress and could develop salinity tolerance in crop plants. To ascertain the role of antioxidants in inducing osmotic adjustment in salt stressed wheat flag leaf in terms of compatible solutes accumulation, water relations parameters and osmotic adjustment as well as flag leaf area and grain yield per plant, in addition, flag leaf anatomy were examined.ResultsSalt stress up to 11.5 dSm-1 causes a significant reduction in water potential, osmotic potential, as well as relative water content, and water content. On the other hand, turgor potential and osmotic adjustment were significantly increased due to inducing increasing the higher accumulation of compatible osmolytes which leads to decreasing flag leaf area and grain yield per plant.Application of both antioxidants, in particular, ascorbic acid increased significantly flag leaf area, and grain yield per plant due to osmotic adjustment and maintaining leaf turgor potential as a consequence of increasing leaf water potential, water content and relative water content as compared to control plants. On the other hand, application of both antioxidants under all salinity levels, nullify the harmful effects of salinity on flag leaf area and grain yield per plant due to increasing osmolyte accumulation, maintaining turgor potential and osmotic adjustment.Anatomically, increasing salinity levels decreased thickness of leaf blade at midrib region, thickness of mesophyll tissue, tangential dimension of midrib vascular bundle, thickness of upper and lowerepidermis, thickness of big motor cell, and tangential dimension of big xylem vessel. Treatment with either ascorbic acid or tocopherol at 100 mg/L and their interactions with salinity increased all the above mentioned parameters in both nonsalinized and salinized plants. Ascorbic acid is the most effective in this concern.ConclusionIn conclusion, wheat plants responded to an increased ion influx in their cells by increasing the osmolytes synthesis and accumulation under salt stress, which further increased with antioxidants treatment and helped in maintaining the osmotic balance.

Reaction of artemisinin (1) with ethanolamine, followed by acid treatment produced the lactam (4S,8S,9S,13S,1R,5R,12R)-11-aza-11-(2-hydroxyethyl)-1,5,9-trimethyl-14,15-dioxatetracyclo [10.2.1.0.0]pentadecan-10-one (4) and the diol (1S,2S,6S,7S,5R,8R)-4-aza-5,6-dihydroxy-4-(2-hydroxyethyl)-2,8-dimethyl-7-(3-oxobutyl) bicyclo[4.4.0]decan-3-one (7). When ethylenediamine was used instead of the ethanolamine, the dimeric lactam (1S,4S,8S,9S,13S,5R,12R)-11-[2-((1S,4S,8S,9S,13S,5R,12R)-11-aza-1,5,9-trimethyl-14,15-dioxa-10-oxotetracyclo[10.2.1.0.0] pentadec-11-yl)ethyl]-11-aza-1,5,9-tri-methyl-14,15-dioxatetracyclo-[10.2.1.0.0]-pentadecan-10-one (8) was obtained. All compounds are new azaartemisinin derivatives lacking the peroxide functionality. These compounds were evaluated for antimalarial and cytotoxic activities. Only the dimer 8 was found to possess antimalarial activity, while only the diol 7 exhibited cytotoxic activity against human breast ductal carcinoma.

With the rapid growth of modern technology, many biomedical studies are being conducted to collect massive datasets with volumes of multi-modality imaging, genetic, neurocognitive, and clinical information from increasingly large cohorts. Simultaneously extracting and integrating rich and diverse heterogeneous information in neuroimaging and/or genomics from these big datasets could transform our understanding of how genetic variants impact brain structure and function, cognitive function, and brain-related disease risk across the lifespan. Such understanding is critical for diagnosis, prevention, and treatment of numerous complex brain-related disorders (e.g., schizophrenia and Alzheimer's disease). However, the development of analytical methods for the joint analysis of both high-dimensional imaging phenotypes and high-dimensional genetic data, a big data squared (BD2) problem, presents major computational and theoretical challenges for existing analytical methods. Besides the high-dimensional nature of BD2, various neuroimaging measures often exhibit strong spatial smoothness and dependence and genetic markers may have a natural dependence structure arising from linkage disequilibrium. We review some recent developments of various statistical techniques for imaging genetics, including massive univariate and voxel-wise approaches, reduced rank regression, mixture models, and group sparse multi-task regression. By doing so, we hope that this review may encourage others in the statistical community to enter into this new and exciting field of research.

Introduction Birth trauma rates in term of neonates is a quality measure used by the Joint Commission. In the United States birth trauma rates occurs at a rate of 37 per 1000 live births and are on the decline. However, this decline has been significantly lower among term neonates born in rural facilities. There is a critical lack of evidence toward the influence geographical risk factors has on birth trauma rates for neonatal patients. We sought to measure rural community and hospital characteristics associated with birth trauma. Methods A retrospective longitudinal study design was used to examine inpatient medical discharge data across 103 hospitals of neonates at birth from 2013 to 2018. Discharge data was linked to the American Hospital Association annual survey. We used a multi-level mixed effect model to investigate the relationship between individual and hospital-level attributes associated with increased risk of birth trauma among neonatal patients. Results We found that rural hospitals were 3.99 times (p < 0.001) more likely to experience higher birth trauma than urban hospitals. Medium sized hospitals were 2.11 times (p < 0.001) more likely to experience higher birth trauma. Hospitals who indicate having a safety culture were more likely (p < 0.05) to have high rates of birth trauma. Discussion Neonates born at rural hospitals, were more likely to experience a birth-related injury. Policy strategies focusing on improving health care quality in rural areas are critical to mitigating this increased risk of birth trauma. Further research is required to assess how physician characteristics may impact birth trauma rates., Author(s): Hanadi Y. Hamadi [sup.1] , Jing Xu [sup.1] , Aurora A. Tafili [sup.2] , Farouk S. Smith [sup.1] , Aaron C. Spaulding [sup.3] Author Affiliations: (1) grid.266865.9, 0000 0001 [...]