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We present a machine learning and computer vision approach for a localized, automated, and standardized scoring of Crohn's disease (CD) severity in the small bowel, overcoming the current limitations of manual measurements CT enterography (CTE) imaging and qualitative assessments, while also considering the complex anatomy and distribution of the disease. Two radiologists introduced a severity score and evaluated disease severity at 7.5 mm intervals along the curved planar reconstruction of the distal and terminal ileum using 236 CTE scans. A hybrid model, combining deep-learning, 3-D CNN, and Random Forest model, was developed to classify disease severity at each mini-segment. Precision, sensitivity, weighted Cohen's score, and accuracy were evaluated on a 20% hold-out test set. The hybrid model achieved precision and sensitivity ranging from 42.4% to 84.1% for various severity categories (normal, mild, moderate, and severe) on the test set. The model's Cohen's score (κ = 0.83) and accuracy (70.7%) were comparable to the inter-observer agreement between experienced radiologists (κ = 0.87, accuracy = 76.3%). The model accurately predicted disease length, correlated with radiologist-reported disease length (r = 0.83), and accurately identified the portion of total ileum containing moderate-to-severe disease with an accuracy of 91.51%. The proposed automated hybrid model offers a standardized, reproducible, and quantitative local assessment of small bowel CD severity and demonstrates its value in CD severity assessment. • Crohn's disease (CD) severity scores were assessed by two radiologists at 7.5 mm intervals (mini-segments) along the curved planar reconstruction (CPR) of the ileum, originating from the ileocecal valve, using 236 CTE unique scans of patients diagnosed with CD. • An AI model, combining clinically inspired and non-traditional features through a designed 3-D CNN and Random Forest model, achieved desirable disease severity classification at each mini-segment. It demonstrated an accuracy of 91.51% for moderate-to-severe disease. • The model's performance, as measured by weighted Cohen's score (κ = 0.83, accuracy 70.7%), was comparable to inter-observer agreement between experienced radiologists (κ = 0.87, accuracy = 76.3%) on the test set. [ABSTRACT FROM AUTHOR]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jml.2009.12.002 Byline: Gregory L. Murphy (a), Brian H. Ross (b) Keywords: Concepts; Induction; Category-based induction Abstract: In one form of category-based induction, people make predictions about unknown properties of objects. There is a tension between predictions made based on the object's specific features (e.g., objects above a certain size tend not to fly) and those made by reference to category-level knowledge (e.g., birds fly). Seven experiments with artificial categories investigated these two sources of induction by looking at whether people used information about correlated features within categories, suggesting that they focused on feature-feature relations rather than summary categorical information. The results showed that people relied heavily on such correlations, even when there was no reason to think that the correlations exist in the population. The results suggested that people's use of this strategy is largely unreflective, rather than strategically chosen. These findings have important implications for models of category-based induction, which generally ignore feature-feature relations. Author Affiliation: (a) Department of Psychology, New York University, United States (b) Beckman Institute and Department of Psychology, University of Illinois at Urbana-Champaign, United States Article History: Received 4 September 2009; Revised 9 December 2009

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jml.2005.10.005 Byline: Andrea L. Patalano (a), Seth Chin-Parker (b), Brian H. Ross (c) Keywords: Categories; Reasoning; Inference; Coherence Abstract: Category-based inference is crucial for using past experiences to make sense of new ones. One challenge to inference of this kind is that most entities in the world belong to multiple categories (e.g., a jogger, a professor, and a vegetarian). We tested the hypothesis that the degree of coherence of a category -- the degree to which category features go together in light of prior knowledge -- influences the extent to which one category will be used over another in property inference. The first two experiments demonstrate that when multiple social categories are available, high coherence categories are selected and used as the basis of inference more often than less coherent ones. The second two experiments provide evidence that ease of category-based explanation of properties is a viable account for coherence differences. We conclude that degree of coherence meaningfully applies to natural social categories, and is an important influence on category use in reasoning. Author Affiliation: (a) Department of Psychology, Wesleyan University, 207 High St., Middletown, CT 06459-0408, USA (b) Denison University, USA (c) University of Illinois at Urbana-Champaign, USA Article History: Received 25 July 2005; Revised 20 October 2005 Article Note: (footnote) [star] This work was supported by National Science Foundation Grant SBR 97-20304. We thank Nick Haslam and Gregory Murphy for comments on an earlier draft of this paper. Thanks also to Melissa Paulson and Jane Erickson for their assistance in data collection.

Seven studies were conducted to analyze how people represent, access and make inferences about foods. The representation of the category was evaluated by category generation, item sortings and category ratings. Results showed that the high-level category of foods was organized simultaneously by taxonomic categories for the kind of food. Findings also indicated that multiple categories and methods of categorizing can be utilized in a single domain at one time.

Rationale and Objectives: Glioblastoma image evaluation utilizes Magnetic Resonance Imaging contrast-enhanced, T1-weighted, and noncontrast T2-weighted fluid-attenuated inversion recovery (FLAIR) acquisitions. Disease progression assessment relies on changes in tumor diameter, which correlate poorly with survival. To improve treatment monitoring in glioblastoma, we investigated serial voxel-wise comparison of anatomically-aligned FLAIR signal as an early predictor of GBM progression.Materials and Methods: We analyzed longitudinal normalized FLAIR images (rFLAIR) from 52 subjects using voxel-wise Parametric Response Mapping (PRM) to monitor volume fractions of increased (PRMrFLAIR+), decreased (PRMrFLAIR-), or unchanged (PRMrFLAIR0) rFLAIR intensity. We determined response by rFLAIR between pretreatment and 10 weeks posttreatment. Risk of disease progression in a subset of subjects (N = 26) with stable disease or partial response as defined by Response Assessment in Neuro-Oncology (RANO) criteria was assessed by PRMrFLAIR between weeks 10 and 20 and continuously until the PRMrFLAIR+ exceeded a defined threshold. RANO defined criteria were compared with PRM-derived outcomes for tumor progression detection.Results: Patient stratification for progression-free survival (PFS) and overall survival (OS) was achieved at week 10 using RANO criteria (PFS: p <0.0001; OS: p <0.0001), relative change in FLAIR-hyperintense volume (PFS: p = 0.0011; OS: p <0.0001), and PRMrFLAIR+ (PFS: p <0.01; OS: p <0.001). PRMrFLAIR+ also stratified responding patients' progression between weeks 10 and 20 (PFS: p <0.05; OS: p = 0.01) while changes in FLAIR-volume measurements were not predictive. As a continuous evaluation, PRMrFLAIR+ exceeding 10% stratified patients for PFA after 5.6 months (p<0.0001), while RANO criteria did not stratify patients until 15.4 months (p <0.0001).Conclusion: PRMrFLAIR may provide an early biomarker of disease progression in glioblastoma. [ABSTRACT FROM AUTHOR]

Eleven different experiments conducted to analyze feature prediction of object dependency on categorization reveal that multiple categories have no influence on category-based prediction and that a single category exerts more influence on predictions. Correlations between predicted features and input features control category-based predictions. The results of the experiment cannot be explained by any particular theory.

Four experiments examine a reminding-based generalization view of category learning. According to this proposal, when subjects categorize a new instance by the use of an earlier instance, they learn about the aspects common to the two instances and this knowledge may be used in later categorization. Experiment 1 demonstrates that which earlier instance is used to categorize a new instance affects performance on a later category test. Two assumptions of this view are then tested. Experiment 2 provides evidence for the necessity of distinct instance representations to obtain this effect. Experiment 3 shows that the reminding effect is due to the presence of the common aspects and not simply to the increased availability of the instance of which one is reminded. The final experiment extends the reminding-based learning idea to a situation in which feature relevance is provided. This study shows that the reminding determines whether this relevance has an effect later on categorization time for individual features. Discussion focuses on the implications of these results for theories of category learning.

In patients undergoing neoadjuvant chemoradiotherapy (nCRT) followed by surgery for locally advanced esophageal squamous cell carcinoma (ESCC), patients with a pathologic complete response (pCR) have the greatest benefit. The purpose of this study was to identify morphomic factors obtained from pretreatment computed tomography scans associated with a pCR in ESCC. We retrospectively analyzed patients with ESCC treated with nCRT who underwent esophagectomy between 2006 and 2016. Clinical and morphomic characteristics pre-nCRT were analyzed to identify factors associated with pCR using univariate and multivariable analyses. There were 183 patients with ESCC included in this study, and 45 (24.6%) patients achieved pCR. The overall survival in patients with pCR was better than that in patients without pCR (5.8 years vs 1.2 years; P <.001). On univariate analysis, increased age, radiation dose greater than or equal to 4000 cGy, and larger subcutaneous adipose tissue area were correlated with pCR. On multivariable logistic regression, increased age (odds ratio, 1.53; P =.03), radiation dose greater than or equal to 4000 cGy (odds ratio, 2.19; P =.04), and larger dorsal muscle group normal-density area (odds ratio, 1.59; P =.03) were independently associated with pCR. Increased age, radiation dose greater than or equal to 4000 cGy, and larger dorsal muscle group normal-density area were significantly associated with pCR. These factors may be useful in determining which patients are most likely to benefit from nCRT followed by esophagectomy. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: Chronic obstructive pulmonary disease is a heterogeneous disease characterized by small airway abnormality and emphysema. We hypothesized that a voxel-wise computed tomography analytic approach would identify patterns of disease progression in smokers.Materials and Methods: We analyzed 725 smokers in spirometric GOLD stages 0-4 with two chest CTs 5 years apart. Baseline inspiration, follow-up inspiration and follow-up expiration images were spatially registered to baseline expiration so that each voxel had correspondences across all time points and respiratory phases. Voxel-wise Parametric Response Mapping (PRM) was then generated for the baseline and follow-up scans. PRM classifies lung as normal, functional small airway disease (PRMfSAD), and emphysema (PRMEMPH).Results: Subjects with low baseline PRMfSAD and PRMEMPH predominantly had an increase in PRMfSAD on follow-up; those with higher baseline PRMfSAD and PRMEMPH mostly had increases in PRMEMPH. For GOLD 0 participants (n = 419), mean 5-year increases in PRMfSAD and PRMEMPH were 0.3% for both; for GOLD 1-4 participants (n = 306), they were 0.6% and 1.6%, respectively. Eighty GOLD 0 subjects (19.1%) had overall radiologic progression (30.0% to PRMfSAD, 52.5% to PRMEMPH, and 17.5% to both); 153 GOLD 1-4 subjects (50.0%) experienced progression (17.6% to PRMfSAD, 48.4% to PRMEMPH, and 34.0% to both). In a multivariable model, both baseline PRMfSAD and PRMEMPH were associated with development of PRMEMPH on follow-up, although this relationship was diminished at higher levels of baseline PRMEMPH.Conclusion: A voxel-wise longitudinal PRM analytic approach can identify patterns of disease progression in smokers with and without chronic obstructive pulmonary disease. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: Chronic obstructive pulmonary disease is a heterogeneous disease characterized by small airway abnormality and emphysema. We hypothesized that a voxel-wise computed tomography analytic approach would identify patterns of disease progression in smokers.Materials and Methods: We analyzed 725 smokers in spirometric GOLD stages 0-4 with two chest CTs 5 years apart. Baseline inspiration, follow-up inspiration and follow-up expiration images were spatially registered to baseline expiration so that each voxel had correspondences across all time points and respiratory phases. Voxel-wise Parametric Response Mapping (PRM) was then generated for the baseline and follow-up scans. PRM classifies lung as normal, functional small airway disease (PRMfSAD), and emphysema (PRMEMPH).Results: Subjects with low baseline PRMfSAD and PRMEMPH predominantly had an increase in PRMfSAD on follow-up; those with higher baseline PRMfSAD and PRMEMPH mostly had increases in PRMEMPH. For GOLD 0 participants (n = 419), mean 5-year increases in PRMfSAD and PRMEMPH were 0.3% for both; for GOLD 1-4 participants (n = 306), they were 0.6% and 1.6%, respectively. Eighty GOLD 0 subjects (19.1%) had overall radiologic progression (30.0% to PRMfSAD, 52.5% to PRMEMPH, and 17.5% to both); 153 GOLD 1-4 subjects (50.0%) experienced progression (17.6% to PRMfSAD, 48.4% to PRMEMPH, and 34.0% to both). In a multivariable model, both baseline PRMfSAD and PRMEMPH were associated with development of PRMEMPH on follow-up, although this relationship was diminished at higher levels of baseline PRMEMPH.Conclusion: A voxel-wise longitudinal PRM analytic approach can identify patterns of disease progression in smokers with and without chronic obstructive pulmonary disease. [ABSTRACT FROM AUTHOR]

A large body of evidence suggests that dietary supplementation with omega-3 fatty acids may ameliorate depressed mood. The magnitude of the effect varies between studies, however, ranging from none at all to being of clinical significance. Given that substantial comorbidity occurs between mood and anxiety disorders, suggesting that they have one or more pathophysiological mechanisms in common, we hypothesized that omega-3 fatty acids may be acting primarily to reduce anxiety rather than depression per se , a possibility which could underlie their variable effects on mood. To test this hypothesis rats were fed for 8 weeks with diets containing one of three types of omega-3 fatty acids, alpha-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid, as well as a low omega-3 fatty acid control diet. Although brain omega-3 fatty acid concentrations were altered by dietary supplementation with eicospentaenoic acid and docosahexaenoic acid, no significant change in anxiety related behaviors were observed compared to the control group as assessed by the elevated-plus maze test. Our data therefore do not support an anxiolytic effect of omega-3 fatty acids and suggest that any effect of these lipids on mood likely occurs by a mechanism unrelated to reducing anxiety. [ABSTRACT FROM AUTHOR]

The biochemical activities involved in signal transduction in cells are under tight spatiotemporal regulation. To study the effects of the spatial patterning and temporal dynamics of biochemical activities on downstream signaling, researchers require methods to manipulate signaling pathways acutely and rapidly. In this review, we summarize recent developments in the design of three broad classes of molecular tools for perturbing signal transduction, classified by their type of input signal: chemically induced, optically induced, and magnetically induced. [ABSTRACT FROM AUTHOR]

Demethylation of industrial lignin has been for long coveted as a pathway to the production of an abundant natural substitute for fossil-oil derived phenol. In an attempt to possibly identify a novel Kraft lignin-demethylating enzyme, we surveyed a collection of fungi by using selected ion flow tube-mass spectrometry (SIFT-MS). This method readily identifies methanol resulting from lignin demethylation activity. Absidia cylindrospora , and unidentified Cylindrocladium sp. and Aspergillus sp. were shown to metabolize lignin via different pathways, based on the HPLC analysis of lignin fragments. Of these three, Cylindrocladium and Aspergillus were shown to retain most of the lignin intact after 3 weeks in culture, while removing about 40% of the available methoxy groups. Our results demonstrate that after optimization of culture and lignin recovery methods, biological modification of Kraft lignin may be a feasible pathway to obtaining demethylated lignin for further industrial use. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: The longitudinal relationship between regional air trapping and emphysema remains unexplored. We have sought to demonstrate the utility of parametric response mapping (PRM), a computed tomography (CT)-based biomarker, for monitoring regional disease progression in chronic obstructive pulmonary disease (COPD) patients, linking expiratory- and inspiratory-based CT metrics over time.Materials and Methods: Inspiratory and expiratory lung CT scans were acquired from 89 COPD subjects with varying Global Initiative for Chronic Obstructive Lung Disease (GOLD) status at 30 days (n = 13) or 1 year (n = 76) from baseline as part of the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) clinical trial. PRMs of CT data were used to quantify the relative volumes of normal parenchyma (PRM(Normal)), emphysema (PRM(Emph)), and functional small airways disease (PRM(fSAD)). PRM measurement variability was assessed using the 30-day interval data. Changes in PRM metrics over a 1-year period were correlated to pulmonary function (forced expiratory volume at 1 second [FEV1]). A theoretical model that simulates PRM changes from COPD was compared to experimental findings.Results: PRM metrics varied by ∼6.5% of total lung volume for PRM(Normal) and PRM(fSAD) and 1% for PRM(Emph) when testing 30-day repeatability. Over a 1-year interval, only PRM(Emph) in severe COPD subjects produced significant change (19%-21%). However, 11 of 76 subjects showed changes in PRM(fSAD) greater than variations observed from analysis of 30-day data. Mathematical model simulations agreed with experimental PRM results, suggesting fSAD is a transitional phase from normal parenchyma to emphysema.Conclusions: PRM of lung CT scans in COPD patients provides an opportunity to more precisely characterize underlying disease phenotypes, with the potential to monitor disease status and therapy response. [ABSTRACT FROM AUTHOR]

Background: Interprofessional education (IPE) in health care describes a process for training that places health care learners from different professional disciplines into an environment or situation in which shared or linked educational goals are pursued. IPE represents a new way of thinking about education as a value proposition directed at high-quality interprofessional patient care and as such is an innovative strategy endorsed in statements by the Institute of Medicine and the World Health Organization. The requirements of the American College of Surgeons−accredited Education Institutes (ACS-AEIs) for Comprehensive (Level I) accreditation state that education and training activities at the accredited institutes (simulation centers) must be multidisciplinary in nature. Until recently, concepts of shared interprofessional educational goals and facilitation of interdisciplinary colearning have not been addressed explicitly by the Consortium of ACS-AEIs. Methods: In March 2012, the ACS Education Division convened a forum on IPE at the Annual Meeting of the Consortium of ACS-accredited Education Institutes in Chicago, IL. Five different ACS-AEI perspectives on IPE and training were presented, covering (1) simulation-based crisis resource management training for operating room teams, (2) the use of multidisciplinary simulation at an academic medical center-based simulation facility, (3) the development of a collaborative IPE curriculum between nursing and medical schools at a major university, (4) the development of a simulation-based interprofessional obstetrics educational program at a university medical center, and (5) the development of an interprofessional macrosystem simulation program in conjunction with opening a new hospital facility. We describe these experiences and present them as best practices in simulation-based IPE in surgery. Conclusion: These IPE experiences in the ACS-AEIs reflect varied and robust approaches to integrated interdisciplinary teaching and learning. Demands and directives to increase these types of educational activities in the near future will have to be met with a wider range of offerings and greater specific knowledge and expertise within the ACS-AEI Consortium. [Copyright &y& Elsevier]

Abstract: Oxidative stress has been reported to be elevated in mental illness. Preliminary evidence suggests this phenomenon can be assessed non-invasively by determining breath levels of the omega-3 polyunsaturated fatty acid (PUFA) oxidation product ethane. This study compares alkane levels in chronic, medicated, patients with schizophrenia or bipolar disorder with those in healthy controls. Both ethane and butane levels were significantly increased in patients with schizophrenia or bipolar disorder, although elevated butane levels were likely due to increased ambient gas concentrations. Ethane levels were not correlated with symptom severity or with erythrocyte omega-3 PUFA levels. Our results support the hypothesis that oxidative stress is elevated in patients with schizophrenia and bipolar disorder leading to increased breath ethane abundance. This does not appear to be caused by increased abundance of omega-3 PUFA, but rather is likely due to enhanced oxidative damage of these lipids. As such, breath hydrocarbon analysis may represent a simple, non-invasive means to monitor the metabolic processes occurring in these disorders. [Copyright &y& Elsevier]

Abstract: Effects of spontaneous seizures on extracellular glutamate and glutamine were studied in the kainate-induced rat model of epilepsy in the chronic phase. Extracellular fluid from the CA1–CA3 regions of the hippocampus was collected with a 2-mm microdialysis probe every 2min for 5h. EEG seizures with no or mild behavioral components caused 2- to 6-fold elevation of extracellular glutamate. Concomitantly, extracellular glutamine decreased at t =5h to 48% of the initial value (n =6). The changes in extracellular glutamate and glutamine correlated with the frequency and magnitude of seizure activity. In contrast, no change in either metabolite was observed in kainate-injected rats that did not undergo seizure during microdialysis (n =6). In hippocampal tissue (9.4±1.1mg) that contained the region sampled by microdialysis and the site of kainate injection, intracellular glutamine concentration was significantly reduced in the seizure group, compared to that in no-seizure group. The observed elevation of extracellular glutamate strongly suggests that neurotransmitter glutamate was released at a rate faster than the rate of its uptake into glia, possibly due to down-regulation of the transporter. This reduces the availability of substrate glutamate for glutamine synthesis, as corroborated by the observed reduction of intracellular glutamine. This is likely to reduce the rate of glutamine efflux from glia and result in the observed decrease of extracellular glutamine. There remains an intriguing possibility that seizure-induced decrease of extracellular glutamine also reflects its increased uptake into neurons to replenish neurotransmitter glutamate during enhanced epileptiform activity. [ABSTRACT FROM AUTHOR]

Abstract: Anxiety disorders are a common group of psychiatric illnesses which have significant personal, family and societal costs. Current treatments have limited efficacy in many patients highlighting a need for new therapeutic approaches to be explored. Anxiety disorders exhibit marked comorbity with mood disorders suggesting the existence of mechanistic similarities. Such a notion is supported by observations that some conventional pharmacotherapies are both effective antidepressants and anxiolytics. As such, given that omega-3 PUFA supplementation may be effective in the treatment of major depressive disorder it is reasonable to propose that they may also possess anxiolytic properties. Experimental data in support of such a hypothesis is currently lacking although reduced abundance of omega-3 PUFA have been reported in patients with anxiety, while supplementation with omega-3 PUFA appears to inhibit activation of the HPA axis and can ameliorate some of the symptoms of anxiety. Clinical investigations carried out to date have, however, involved small numbers of participants. Larger trials using a variety of omega-3 PUFA species in clinically well-defined patients with anxiety will be required to demonstrate a therapeutic role for omega-3 PUFA in these disorders. Given the excellent side effect profile of omega-3 PUFA as well as their strong theoretical rationale, such future trials appear justified. [Copyright &y& Elsevier]

Late gadolinium enhanced (LGE) cardiovascular magnetic resonance (CMR) has proven to be the gold standard for viability assessment. LGE CMR is also useful for identifying the nature of cardiac masses or lesions. We report a case of a rare primary cystic tumor of the atrioventricular node, in which CMR proved to be valuable. [ABSTRACT FROM AUTHOR]

Abstract: This study directly assessed whether there was a change in the level of exhaled ethane, which provides a non-invasive, quantitative, direct measure of n-3 lipid peroxidation, in the breath of patients with schizophrenia. Samples of alveolar air were obtained from 20 subjects with schizophrenia and 23 age- and sex-matched healthy control subjects. The air samples were analyzed for ethane using mass spectrometry. The mean level of ethane in the schizophrenia sample [5.15 (S.E. 0.56) ppb] was significantly higher than that of the healthy controls [2.63 (S.E. 0.31) ppb; p <0.0005]. A further sub-analysis showed that nicotine dependence was unlikely to be the cause of this difference. These results suggest that the measurement of exhaled ethane levels may offer a non-invasive direct biomarker of increased n-3 lipid peroxidation in schizophrenia. [Copyright &y& Elsevier]

Summary: ω −3 Fatty acids are a type of polyunsaturated fatty acid (PUFA). A growing body of evidence suggests that this form PUFA is a useful and well tolerated treatment for major depressive disorder, a common and serious mental illness. The efficacy of ω −3 PUFA is routinely explained as being due to a deficiency caused by inadequate dietary intake of this class of fatty acid. The hypothesis considered states that low ω −3 PUFA abundance in patients with major depressive and related disorders is due to an underlying genetically determined abnormality. The hypothesis can explain why although a specific and consistent deficit in ω −3, but not ω −6, PUFA occurs in major depressive and related disorders, the literature does not consistently support the notion that this is due to deficient dietary intake. Specifically it is hypothesized that having genetically determined low activity of fatty acid CoA ligase 4 and/or Type IV phospholipase A2 combined with the low dietary availability of ω −3 PUFA results in reduced cellular uptake of ω −3 PUFA and constitutes a risk factor for depression. The hypothesis also has important consequences for the pharmacological treatment of depression in that it predicts that administering agents which enhance phospholipid synthesis, particularly those containing ethanolamine such as CDP-ethanolamine, should be effective antidepressants especially when co-administered with ω −3 PUFA. [Copyright &y& Elsevier]

Abstract: The brain is unique among organs in many respects, including its mechanisms of lipid synthesis and energy production. The nervous system-specific metabolite N-acetylaspartate (NAA), which is synthesized from aspartate and acetyl-coenzyme A in neurons, appears to be a key link in these distinct biochemical features of CNS metabolism. During early postnatal central nervous system (CNS) development, the expression of lipogenic enzymes in oligodendrocytes, including the NAA-degrading enzyme aspartoacylase (ASPA), is increased along with increased NAA production in neurons. NAA is transported from neurons to the cytoplasm of oligodendrocytes, where ASPA cleaves the acetate moiety for use in fatty acid and steroid synthesis. The fatty acids and steroids produced then go on to be used as building blocks for myelin lipid synthesis. Mutations in the gene for ASPA result in the fatal leukodystrophy Canavan disease, for which there is currently no effective treatment. Once postnatal myelination is completed, NAA may continue to be involved in myelin lipid turnover in adults, but it also appears to adopt other roles, including a bioenergetic role in neuronal mitochondria. NAA and ATP metabolism appear to be linked indirectly, whereby acetylation of aspartate may facilitate its removal from neuronal mitochondria, thus favoring conversion of glutamate to alpha ketoglutarate which can enter the tricarboxylic acid cycle for energy production. In its role as a mechanism for enhancing mitochondrial energy production from glutamate, NAA is in a key position to act as a magnetic resonance spectroscopy marker for neuronal health, viability and number. Evidence suggests that NAA is a direct precursor for the enzymatic synthesis of the neuron specific dipeptide N-acetylaspartylglutamate, the most concentrated neuropeptide in the human brain. Other proposed roles for NAA include neuronal osmoregulation and axon-glial signaling. We propose that NAA may also be involved in brain nitrogen balance. Further research will be required to more fully understand the biochemical functions served by NAA in CNS development and activity, and additional functions are likely to be discovered. [Copyright &y& Elsevier]

Abstract: Omega-3 polyunsaturated fatty acids (PUFA) are increasingly finding use as treatments for a variety of medical conditions. PUFA supplementation can, however, result in increased oxidative stress causing elevated turnover rate of membrane phospholipids, impairment of membrane integrity and increased formation of inflammatory mediators. The aim of this study was to determine which antioxidant compounds were most effective in ameliorating the stimulation of phospholipid turnover by oxidative stress. U937 cells were supplemented with eicosapentaenoic acid and either ascorbic acid, α-tocopherol, β-carotene or astaxanthin prior to being challenged with oxidant. Although all antioxidants were found to be effective in decreasing oxidant-stimulated peroxide formation, only α-tocopherol significantly decreased oxidant-stimulated release of 3H-labeled arachidonic acid (AA), while ascorbic acid markedly increased release. All antioxidants except α-tocopherol decreased oxidant-stimulated 3H-AA uptake. Our data suggest that antioxidants are not equally effective in combating the effects of oxidative stress upon membrane phospholipid turnover, and that optimal protection will require mixtures of antioxidants. [Copyright &y& Elsevier]

The article presents an overview of the past, presents and future directions of the periodical "Neoplasia." There has been an increase in the number of articles submitted to the periodical as of 2005. It editorial office has managed to maintain high standard of scientific quality. Since its inception in 1999, it has been a significant cancer journal. The periodical is planning to initiate new open access policy.

Provides information on the "Neoplasia" journal. Vision of the journal; Overall impact and acceptance of "Neoplasia"; Significant changes for "Neoplasia" in 2005.

Background: Recent evidence has suggested an important role for lipids in the etiology and treatment of depression. Methylnicotinate-induced vasodilation can be used to investigate lipid-dependent signalling mechanisms involving the phospholipase A2 (PLA2)/cyclooxygenase pathway, an important signalling system involved in the action of several neurotransmitters including serotonin. To investigate whether abnormalities in this signalling system may occur in depressive illness, we undertook a study of methylnicotinate response in unipolar depression (UD).Methods: Methylnicotinate was applied to the forearm of 20 patients with depression and 38 age and sex-matched healthy volunteers (HV). The resulting erythema was assessed over a 15-min period.Results: Methylnicotinate-induced erythema was reduced in subjects with depression compared to HV at 5 min after application, it returned to normal after 15 min. Thus, although the maximal response to methylnicotinate appears normal, patients with UD exhibit an apparently delayed response.Limitations: The major limitation is that all unipolar patients were medicated at the time of testing.Conclusions: Our results support the hypothesis that UD may be associated with abnormalities in lipid-associated signalling systems, and may provide insight into how lipid intake may modulate depressive symptoms. [ABSTRACT FROM AUTHOR]

The automatic synthesis of procedural textures for 3D surfaces using genetic programming is investigated. Genetic algorithms employ a search strategy inspired by Darwinian natural evolution. Genetic programming uses genetic algorithms on tree structures, which are interpretable as computer programs or mathematical formulae. We define a texture generation language in the genetic programming system, which is then used to evolve textures having particular characteristics of interest. The texture generation language used here includes operators useful for texture creation, for example, mathematical operators, colour functions and noise functions. In order to be practical for 3D model rendering, the language includes primitives that access surface information for the point being rendered, such as coordinates values, normal vectors, and surface gradients. A variety of experiments successfully generated procedural textures that displayed visual characteristics similar to the target textures used during training. [Copyright &y& Elsevier]

Phospholipids are essential components of cell membranes which may also function to mediate some of the behavioural effects of dopamine receptor stimulation caused by psychostimulant drugs. Neuroimaging and pharmacological data suggest that abnormal brain metabolism of phospholipids might explain some of the consequences of chronic exposure to drugs of abuse including drug craving. We previously reported decreased activity of calcium-stimulated phospholipase A2 (Ca-PLA2) in autopsied putamen of human cocaine users. To establish the specificity of this change in phospholipid metabolism and whether decreased Ca-PLA2 might be a general feature of all abused drugs which enhance dopaminergic neurotransmission, we measured activity of 11 major phospholipid metabolic enzymes in dopamine-rich (putamen) and poor brain areas of chronic users of cocaine and of methamphetamine. Enzyme changes were restricted to the putamen which showed decreased (−21%, as compared with the control subjects) Ca-PLA2 activity in users of methamphetamine and reduced (−31%) activity of phosphocholine cytidylyltransferase (PCCT), the rate-limiting enzyme of phosphatidylcholine synthesis, in the cocaine users. We suggest that chronic exposure to psychostimulant drugs might cause a compensatory downregulation of Ca-PLA2 in dopamine-rich brain areas due to excessive dopamine-related stimulation of the enzyme. Decreased striatal Ca-PLA2 and/or PCCT activity in cocaine users might also help to explain why CDP choline, which enhances phospholipid synthesis, reduces craving in some users of the drug cocaine. [Copyright &y& Elsevier]

Gentropy is a genetic programming system that evolves two-dimensional procedural textures. It synthesizes textures by combining mathematical and image manipulation functions into formulas. A formula can be reevaluated with arbitrary texture-space coordinates, to generate a new portion of the texture in texture space. Most evolutionary art programs are interactive, and require the user to repeatedly choose the best images from a displayed generation. Gentropy uses an unsupervised approach, where one or more target texture image is supplied to the system, and represent the desired texture features, such as colour, shape and smoothness (contrast). Then, Gentropy evolves textures independent of any further user involvement. The evolved texture will not be identical to the target texture, but rather, will exhibit characteristics similar to it. When more than one texture is supplied as a target, multi-objective feature analysis is performed. These feature tests may be combined and given different priorities during evaluation. It is therefore possible to use several target images, each with its own fitness function measuring particular visual characteristics. Gentropy also permits the use of multiple subpopulations, each of which may use its own texture evaluation criteria and target texture. [Copyright &y& Elsevier]

The article describes the publishing success of the journal "Neoplasia" in 2012.

An introduction to this issue of "Neoplasia," in which the author discusses the rules pertaining to manuscript submission and publication, is presented.

The author reflects on the tremendous success of the journal during the past year and the principle that motivated the board members to commit to the endeavor and provide a platform for the rapid dissemination of information to advance the fields of basic and clinical cancer research. The dislikes about the peer review systems and the approach to significantly improve it were also tackled. Also, the author thanks the participants of the experiment to initiate changes to the peer-review process.

The author discusses the success of the magazine "Neoplasia." He says that the magazine provides a platform for fair minded, constructive criticism of manusripts for the rapid distribution of information in clinical cancer research. He also discusses different approach for peer review system. He also thanks the readers for using the magazine to spread the reseach and for being willing to be a participant in a experiment to initiate change to the peer-review process.