bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential Effects of Simulated Cortical Network Lesions on Synchrony and EEG Complexity
Authors: Ibáñez-Molina Antonio José , Iglesias-Parro Sergio , Escudero Javier
Published: May 2018

Brain function has been proposed to arise as a result of the coordinated activity between distributed brain areas. An important issue in the study of brain activity is the characterization of the synchrony among these areas and the resulting complexity of the system. However, the variety of ways to define and, hence, measure brain synchrony and complexity has sometimes led to inconsistent results. Here, we study the relationship between synchrony and commonly used complexity estimators of electroencephalogram (EEG) activity and we explore how simulated lesions in anatomically based cortical networks would affect key functional measures of activity. We explored this question using different types of neural network lesions while the brain dynamics was modeled with a time-delayed set of 66 Kuramoto oscillators. Each oscillator modeled a region of the cortex (node), and the connectivity and spatial location between different areas informed the creation of a network structure (edges). Each type of lesion consisted on successive lesions of nodes or edges during the simulation of the neural dynamics. For each type of lesion, we measured the synchrony among oscillators and three complexity estimators (Higuchi’s Fractal Dimension, Sample Entropy and Lempel-Ziv Complexity) of the simulated EEGs. We found a general negative correlation between EEG complexity metrics and synchrony but Sample Entropy and Lempel-Ziv showed a positive correlation with synchrony when the edges of the network were deleted. This suggests an intricate relationship between synchrony of the system and its estimated complexity. Hence, complexity seems to depend on the multiple states of interaction between the oscillators of the system. Our results can contribute to the interpretation of the functional meaning of EEG complexity.
The Genome Biology of Effector Gene Evolution in Filamentous Plant Pathogens
Authors: Sánchez-Vallet Andrea , Fouché Simone , Fudal Isabelle , Hartmann Fanny E. , Soyer Jessica L. , Tellier Aurélien , Croll Daniel
Published: May 2018

Filamentous pathogens, including fungi and oomycetes, pose major threats to global food security. Crop pathogens cause damage by secreting effectors that manipulate the host to the pathogen's advantage. Genes encoding such effectors are among the most rapidly evolving genes in pathogen genomes. Here, we review how the major characteristics of the emergence, function, and regulation of effector genes are tightly linked to the genomic compartments where these genes are located in pathogen genomes. The presence of repetitive elements in these compartments is associated with elevated rates of point mutations and sequence rearrangements with a major impact on effector diversification. The expression of many effectors converges on an epigenetic control mediated by the presence of repetitive elements. Population genomics analyses showed that rapidly evolving pathogens show high rates of turnover at effector loci and display a mosaic in effector presence-absence polymorphism among strains. We conclude that effective pathogen containment strategies require a thorough understanding of the effector genome biology and the pathogen's potential for rapid adaptation.
Does partial titin degradation affect sarcomere length nonuniformities and force in active and passive myofibrils?
Authors: Joumaa V. , Bertrand F. , Liu S. , Poscente S. , Herzog W.
Published: May 2018

The aim of this study was to determine the role of titin in preventing the development of sarcomere length nonuniformities following activation and after active and passive stretch by determining the effect of partial titin degradation on sarcomere length nonuniformities and force in passive and active myofibrils. Selective partial titin degradation was performed using a low dose of trypsin. Myofibrils were set at a sarcomere length of 2.4 µm and then passively stretched to sarcomere lengths of 3.4 and 4.4 µm. In the active condition, myofibrils were set at a sarcomere length of 2.8 µm, activated, and actively stretched by 1 µm/sarcomere. The extent of sarcomere length nonuniformities was calculated for each sarcomere as the absolute difference between sarcomere length and the mean sarcomere length of the myofibril. Our main finding is that partial titin degradation does not increase sarcomere length nonuniformities after passive stretch and activation compared with when titin is intact but increases the extent of sarcomere length nonuniformities after active stretch. Furthermore, when titin was partially degraded, active and passive stresses were substantially reduced. These results suggest that titin plays a crucial role in actively stretched myofibrils and is likely involved in active and passive force production.
Molecular basis of the counteraction by calcium channel blockers of cyclosporine nephrotoxicity
Authors: Hammoud Safaa H. , Alkhansa Sahar , Mahjoub Neamah , Omar Amal G. , El-Mas Mahmoud M. , Eid Assaad A.
Published: May 2018

Nephrotoxicity is a serious side effect for the immunosuppressant drug cyclosporine A(CSA). In this study, we tested the hypothesis that administration of calcium channel blockers such as verapamil or nifedipine ameliorates renal CSA-induced renal dysfunction. Furthermore, our study investigates the roles of inflammatory, oxidative, and fibrotic pathways in CSA-induced renal dysfunction. Six groups of male rats ( n = 6/group) were used and received one of the following treatments for seven consecutive days: vehicle (Cremophor EL ip), CSA (25 mg·kg−1·day−1ip), verapamil (2 mg·kg−1·day−1ip), nifedipine (3 mg·kg−1·day−1ip), CSA in the presence or absence of either verapamil, or nifedipine. Biochemical and histomorphometric analyses showed that rats treated with CSA exhibited clear signs of nephrotoxicity that included 1) proteinuria and elevations in serum creatinine and blood urea nitrogen, 2) mesangial expansion, 3) increases in glomerular and tubular type IV collagen expression, and 4) increases in the glomerulosclerosis and tubulointerstitial fibrosis indices. Although the single administration of nifedipine or verapamil had no significant effect on renal pathology, or its biochemical and physiological function, the concurrent use of either calcium channel blockers significantly and equipotently ameliorated the biochemical, morphological, and functional derangements caused by CSA. More importantly, we report that the oxidative (reactive oxygen species production, NADPH-oxidase activity, and dual oxidase 1/2 levels), fibrotic (transforming growth factor-β1 expression), and inflammatory (NF-κB expression) manifestations of renal toxicity induced by CSA were significantly reversed upon administration of nifedipine or verapamil. Together, these results highlight the efficacy of calcium channel-blocking agents in attenuating CSA-induced nephrotoxicity and predisposing biochemical and molecular machineries.
Multifactorial Analysis of Mortality in Screening Detected Lung Cancer
Authors: Digumarthy Subba R. , De Man Ruben , Canellas Rodrigo , Otrakji Alexi , Wang Ge , Kalra Mannudeep K.
Published: May 2018

We hypothesized that severity of coronary artery calcification (CAC), emphysema, muscle mass, and fat attenuation can help predict mortality in patients with lung cancer participating in the National Lung Screening Trial (NLST). Following regulatory approval from the Cancer Data Access System (CDAS), all patients diagnosed with lung cancer at the time of the screening study were identified. These subjects were classified into two groups: survivors and nonsurvivors at the conclusion of the NLST trial. These groups were matched based on their age, gender, body mass index (BMI), smoking history, lung cancer stage, and survival time. CAC, emphysema, muscle mass, and subcutaneous fat attenuation were quantified on baseline low-dose chest CT (LDCT) for all patients in both groups. Nonsurvivor group had significantly greater CAC, decreased muscle mass, and higher fat attenuation compared to the survivor group (p<0.01). No significant difference in severity of emphysema was noted between the two groups (p>0.1). We thus conclude that it is possible to create a quantitative prediction model for lung cancer mortality for subjects with lung cancer detected on screening low-dose CT (LDCT).
The Tribological and Sealing Properties of PFA Composites
Authors: Sujuan Ye , Quan Yu , Kunquan Li , Feng Tan , Qing Fan , Guibin Tan , Xing Huang
Published: May 2018

The polytetrafluoroethylene (PTFE) and perfluoroalkoxyperfluoropropyl vinyl ether (PFA) composites were prepared using carbon fiber (CF) and glass fiber (GF) as fillers. The effects of these fillers on the tribological and sealing properties were investigated. The tribological and sealing properties of the composites were evaluated by a wear tester and a seal test rig. Results showed that the incorporation of CF and GF both improved the wear resistance with composites, approaching wear rates as low as 10−6 mm3/N·m and lowered the seal’s leakage of the PTFE/PFA composites. As described here, CF was more effective than GF in improving the wear rate. Notably, the wear rate of the PFA/CF composite is much less than that of the PTFE composites as the transfer film on the couple ring is much more unique, thick, smooth, and compact. The leakage of carbon fiber-filled PFA composite seal was lowered to 66% less than the traditional PTFE composite seals, which indicates better sealing properties.
Lymphatic Endothelial Cell in Endemic Bancroftian Filariasis: A Focus on the Lymphatics of the Tunica Vaginalis Testis
Authors: Figueredo-Silva Jose , Norões Joaquim , Dreyer Gerusa
Published: May 2018

Background. In endemic areas, lymphangiectasia is the fundamental alteration to liveWuchereria bancroftiadult worms which, in adult males, are usually found in the lymphatic vessels of the spermatic cord; accordingly, hydrocele/filaricele is the most common clinical manifestation of bancroftian filariasis. The pathogenic role of the lymphatic endothelial cells (LECs) and the status of mesothelial cells (MCs) samples of the parietal layer (PL) of the tunica vaginalis testis were examined.Methods. The PL of thirty-two patients, excised for different reasons, was examined by histology and immunohistochemistry using the D2-40 monoclonal antibody for identification of LECs and CK-7 antibody for recognition of mesothelial cells (MCs).Results. The most important findings were (a) marked lymphangiectasia, especially in hydroceles with minor evolution time; (b) the first report of lymphatic stomata and submesothelial lacunae in filarial acute hydrocele; (c) the likely participation of LECs in filarial granuloma; (d) the potential phenotypic transition of LECs into myofibroblasts in severe chylocele; and (e) mesothelial reactive hyperplasia, a hallmark of filaricele, varying in intensity from mild to severe, sometimes mimicking a mesothelial neoplasia.Conclusion. The data suggest that LECs have an active role in the pathogenesis of bancroftian hydrocele and, possibly, in other clinical forms of lymphatic filariasis.
Weighted Proportional Fair Scheduling for Downlink Nonorthogonal Multiple Access
Authors: Hojeij Marie-Rita , Abdel Nour Charbel , Farah Joumana , Douillard Catherine
Published: May 2018

A weighted proportional fair (PF) scheduling method is proposed in the context of nonorthogonal multiple access (NOMA) with successive interference cancellation (SIC) at the receiver side. The new scheme introduces weights that adapt the classical PF metric to the NOMA scenario, improving performance indicators and enabling new services. The distinguishing value of the proposal resides in its ability to improve long‐term fairness and total system throughput while achieving a high level of fairness in every scheduling slot. Finally, it is shown that the additional complexity caused by the weight calculation has only a limited impact on the overall scheduler complexity, while simulation results confirm the claimed improvements, making the proposal an appealing alternative for resource allocation in a cellular downlink system.
Prevalence, Awareness, Treatment, and Control of Hypertension and Its Risk Factors in (Central) Vietnam
Authors: Hien Ho Anh , Tam Nguyen Minh , Tam Vo , Derese Anselme , Devroey Dirk
Published: May 2018

Introduction. The objective of this study is to describe the prevalence, awareness, treatment, and control of hypertension and its associated risk factors in (Central) Vietnam. Methods. In this cross-sectional study, a multistage sampling was used to select 969 participants from the general population aged from 40 to 69 years. The cardiovascular risk factors were collected throughout the interviews with a standardized questionnaire. Multivariate logistic regression analysis was conducted to test the relationship between the prevalence, awareness, treatment, and control of hypertension and the prevalence of risk factors. Results. The prevalence of hypertension was 44.8%. It was higher in men than in women (51.3% versus 39.7%, p < 0.001). In total 67.3% (74.5% in women, 60.1% in men; p = 0.001) of the participants were aware of their hypertension, 33.2% (37.5% in women, 28.9% in men; p = 0.01) of the participants were treated, and 12.2% (16.7% in women, 7.8% in men; p < 0.001) of the hypertensive participants’ hypertension was controlled. Age, gender, place of residence, body mass index, and diabetes were found to be independent risk factors for hypertension. Conclusion. The prevalence of hypertension in Vietnam is high, and the proportion of treated and controlled patients is rather low.
Modeling and Predicting Stochastic Merging Behaviors at Freeway On-Ramp Bottlenecks
Authors: Sun Jian , Zuo Kang , Jiang Shun , Zheng Zuduo
Published: May 2018

Merging behavior is inevitable at on-ramp bottlenecks and is a significant factor in triggering traffic breakdown. In modeling merging behaviors, the gap acceptance theory is generally used. Gap acceptance theory holds that when a gap is larger than the critical gap, the vehicle will merge into the mainline. In this study, however, analyses not only focus on the accepted gaps, but also take the rejected gaps into account, and the impact on merging behavior with multi-rejected (more than once rejecting behavior) gaps was investigated; it shows that the multi-rejected gaps have a great influence on the estimation of critical gap and merging prediction. Two empirical trajectory data sets were collected and analyzed: one at Yan’an Expressway in Shanghai, China, and the other at Highway 101 in Los Angeles, USA. The study made three main contributions. First, it gives the quantitative measurement of the rejected gap which is also a detailed description of non-merging event and investigated the characteristics of the multi-rejected gaps; second, taking the multi-rejected gaps into consideration, it further expanded the concept of the “critical gap” which can be a statistic one and the distribution function of merging probability with respect to such gaps was analyzed by means of survival analysis. This way could make the full use of multi-rejected gaps and accepted gaps and reduce the sample bias, thus estimating the critical gap accurately; finally, considering multi-rejected gaps, it created logistic regression models to predict merging behavior. These models were tested using field data, and satisfactory performances were obtained.
The Utility of Next-Generation Sequencing for Primary Immunodeficiency Disorders: Experience from a Clinical Diagnostic Laboratory
Authors: Bisgin Atil , Boga Ibrahim , Yilmaz Mustafa , Bingol Gulbin , Altintas Derya
Published: May 2018

Introduction. Primary immune deficiency disorders (PIDs) are a group of diseases with profound defects in immune cells. The traditional diagnostics have evolved from clinical evaluation, flow cytometry, western blotting, and Sanger sequencing to focusing on small groups of genes. However, this is not sufficient to confirm the suspicion of certain PIDs. Our innovative approach to diagnostics outlines the algorithm for PIDs and the clinical utility of immunophenotyping with a custom-designed multigene panel. Materials and Methods. We have designed a diagnostic algorithm based on flow cytometry studies to classify the patients; then the selected multigene panel was sequenced. In silico analysis for mutations was carried out using SIFT, Polyphen-2, and MutationTaster. Results and Discussion. The causative mutation was identified in 46% of PIDs. Based on these results, this new algorithm including immune phenotyping and NGS for PIDs was suggested for the clinical use. Conclusions. This study provides a thorough validation of diagnostic algorithm and indicates that still the traditional methods can be used to collect significant information related to design of most current diagnostics. The benefits of such testing are for diagnosis and prevention including the prenatal and preimplantation diagnosis, prognosis, treatment, and research.
Playing the Melanoma Endgame
Authors: Teh Jessica L.F. , Aplin Andrew E.
Published: May 2018

Treatments for melanoma are of two main types: targeted therapies and immune checkpoint inhibitors. However, both are effective in only a subset of patients and are limited by acquired resistance. Here, the authors present the preclinical basis to broadly target different forms of therapy-resistant melanoma. Clin Cancer Res; 24(19); 4629–30. ©2018 AACR.

See related article by Zhang et al., p. 4771
Orally Bioavailable and Blood–Brain Barrier-Penetrating ATM Inhibitor (AZ32) Radiosensitizes Intracranial Gliomas in Mice
Authors: Karlin Jeremy , Allen Jasmine , Ahmad Syed F. , Hughes Gareth , Sheridan Victoria , Odedra Rajesh , Farrington Paul , Cadogan Elaine B. , Riches Lucy C. , Garcia-Trinidad Antonio , Thomason Andrew G. , Patel Bhavika , Vincent Jennifer , Lau Alan , Pike Kurt G. , Hunt Thomas A. , Sule Amrita , Valerie Nicholas C.K. , Biddlestone-Thorpe Laura , Kahn Jenna , Beckta Jason M. , Mukhopadhyay Nitai , Barlaam Bernard , Degorce Sebastien L. , Kettle Jason , Colclough Nicola , Wilson Joanne , Smith Aaron , Barrett Ian P. , Zheng Li , Zhang Tianwei , Wang Yingchun , Chen Kan , Pass Martin , Durant Stephen T. , Valerie Kristoffer
Published: May 2018

Inhibition of ataxia-telangiectasia mutated (ATM) during radiotherapy of glioblastoma multiforme (GBM) may improve tumor control by short-circuiting the response to radiation-induced DNA damage. A major impediment for clinical implementation is that current inhibitors have limited central nervous system (CNS) bioavailability; thus, the goal was to identify ATM inhibitors (ATMi) with improved CNS penetration. Drug screens and refinement of lead compounds identified AZ31 and AZ32. The compounds were then tested in vivo for efficacy and impact on tumor and healthy brain. Both AZ31 and AZ32 blocked the DNA damage response and radiosensitized GBM cells in vitro. AZ32, with enhanced blood–brain barrier (BBB) penetration, was highly efficient in vivo as radiosensitizer in syngeneic and human, orthotopic mouse glioma model compared with AZ31. Furthermore, human glioma cell lines expressing mutant p53 or having checkpoint-defective mutations were particularly sensitive to ATMi radiosensitization. The mechanism for this p53 effect involves a propensity to undergo mitotic catastrophe relative to cells with wild-type p53. In vivo, apoptosis was >6-fold higher in tumor relative to healthy brain after exposure to AZ32 and low-dose radiation. AZ32 is the first ATMi with oral bioavailability shown to radiosensitize glioma and improve survival in orthotopic mouse models. These findings support the development of a clinical-grade, BBB-penetrating ATMi for the treatment of GBM. Importantly, because many GBMs have defective p53 signaling, the use of an ATMi concurrent with standard radiotherapy is expected to be cancer-specific, increase the therapeutic ratio, and maintain full therapeutic effect at lower radiation doses. Mol Cancer Ther; 17(8); 1637–47. ©2018 AACR.
Subfoveal Choroidal Thickness in Eyes with Neovascular Age-Related Macular Degeneration Treated with Anti-Vascular Endothelial Growth Factor Agents
Authors: Kanadani Tereza Cristina Moreira , Veloso Carlos Eduardo , Nehemy Márcio B.
Published: May 2018

Purpose: We aimed to assess the subfoveal choroidal thickness (SFChT) and the effect of treatment with anti-vascular endothelial growth factor (anti-VEGF) agents on the SFChT in age-related macular degeneration (AMD) subtypes. Methods: We enrolled 128 eyes of 107 patients with neovascular AMD (60 women; 47 men; mean age, 73.6 ± 8.9 years), and prospectively evaluated the best-corrected visual acuity (BCVA) and SFChT at baseline and at 3, 6, and 12 months after treatment with anti-VEGF agents. Patients were assigned to the typical AMD, polypoidal choroidal vasculopathy (PCV), and retinal angiomatous proliferation (RAP) subgroups. Results: In total, 85 (66.4%), 31 (24.2%), and 12 (9.4%) eyes were assigned to the typical AMD, PCV, and RAP subgroups, respectively. The baseline mean BCVA was 0.75 ± 0.26, 0.72 ± 0.21, and 0.77 ± 0.24 logMAR in the typical AMD, PCV, and RAP subgroups, respectively (p = 0.774). The mean baseline SFChT was 203.20 ± 35.80, 271.80 ± 24.50, and 182.93 ± 31.31 µm, respectively (p < 0.001). Mean SFChT significantly decreased from baseline to 3, 6, and 12 months after treatment. The RAP subtype presented a significantly higher decrease in SFChT compared to the other subtypes (p = 0.01). The percentage reduction in SFChT was not significantly correlated with the number of injections (r = –0.02; p = 0.823). No association was observed between baseline SFChT and final visual acuity at 12 months (r = 0.0; p = 0.586). Conclusions: SFChT was greatest in eyes with PCV and least in eyes with RAP. The reduction in SFChT after treatment was greater in the RAP cases. The decrease in SFChT after 12 months of anti-VEGF treatment was not associated with the number of injections and there was no correlation between the baseline SFChT and visual acuity in all AMD subtypes.
Lower Plasma Klotho Concentrations Are Associated with Vascular Dementia but Not Late-Onset Alzheimer’s Disease
Authors: Brombo Gloria , Bonetti Francesco , Ortolani Beatrice , Morieri Mario Luca , Bosi Cristina , Passaro Angelina , Vigna Giovanni B. , Borgna Caterina , Arcidicono Maria Vittoria , Tisato Veronica , Zuliani Giovanni
Published: May 2018

Background: The protein Klotho is involved in biological processes related to longevity, cardiovascular health, and cognition. Serum Klotho levels have been associated with better cognition in animal models; moreover, lower Klotho concentrations in cerebrospinal fluid from subjects with late-onset Alzheimer’s disease (LOAD) have been reported. Objective: Our study aimed to examine the possible relationship between Klotho plasma concentrations and cognitive status in the elderly. Methods: We evaluated plasma Klotho levels in a sample of 320 elderly patients admitted to a Memory Clinic. Four groups of subjects were enrolled, including cognitively intact individuals complaining about memory loss (controls) and patients affected by LOAD, mild cognitive impairment, or vascular dementia (VD). The sample was stratified by plasma Klotho tertiles. Results: Lower levels of plasma Klotho (1st tertile) were associated with older age, higher prevalence of VD, single/multiple lacunar infarcts and leukoaraiosis, coronary heart disease and stroke, and higher levels of creatinine, homocysteine, and high-sensitivity C-reactive protein. On multivariate logistic regression analysis, the risk of VD was 3- and 4-fold in subjects belonging to the 1st tertile (≤514.8 pg/mL, OR 3.54, 95% CI 1.05–11.93) and 2nd tertile (> 514.8, < 659.1 pg/mL, OR 4.28, 95% CI 1.30–14.06) compared to the 3rd tertile (≥659.1 pg/mL). A significantly increased VD risk was found for Klotho values < 680 pg/mL. Conclusion: In a sample of elderly individuals, we found a significant association between low plasma Klotho levels and VD, but not LOAD. This finding suggests that, although these 2 forms of dementia might overlap, some physiopathological mechanisms related to VD and LOAD remain distinct.
Predictive Factors for the Long-Term Deterioration of Pulmonary Function in Interstitial Lung Disease Associated with Anti-Aminoacyl-tRNA Synthetase Antibodies
Authors: Yamakawa Hideaki , Hagiwara Eri , Kitamura Hideya , Iwasawa Tae , Otoshi Ryota , Aiko Naoto , Katano Takuma , Shintani Ryota , Ikeda Satoshi , Okuda Ryo , Sekine Akimasa , Baba Tomohisa , Iso Shinichiro , Kuwano Kazuyoshi , Sato Shinji , Ogura Takashi
Published: May 2018

Background: Little has been reported on long-term pulmonary function trends among patients with interstitial lung disease associated with anti-aminoacyl-tRNA synthetase antibodies (ARS-ILD). Objectives: To clarify the factors predictive of progression in ARS-ILD based on patients’ initial clinical and radiological features. Methods: The clinical courses of 88 patients with > 1 year of follow-up data on pulmonary function tests (PFTs) were retrospectively analyzed. Disease behavior was categorized into three groups: (1) improved or (2) worsened (defined as increases or decreases, respectively, of > 10% in forced vital capacity and > 15% in %diffusing capacity of lung carbon monoxide) or (3) stable based on PFT changes compared between 1-year results as the initial data and results at 3 years to assess the long-term course. Results: In the initial course of 75 patients with ARS-ILD who received anti-inflammatory therapy within 6 months after diagnosis, 48 patients (64.0%) improved and 6 patients (8.0%) worsened. The radiological patterns in the patients with ARS-ILD included nonspecific interstitial pneumonia (NSIP) in 46.7% and NSIP with organizing pneumonia overlap in 52.0% of the cases. One-third of the initially improved patients who worsened over the long-term course were assigned to the unstable group. By multivariate logistic analysis, middle lobe traction bronchiectasis was a significant predictive factor for the patients in the unstable group. Conclusions: Most patients with ARS-ILD receiving anti-inflammatory therapy had improved or remained stable in the first year. However, over the long-term course, some patients worsened despite their initial improvement. Even though the extent of the disease is limited, middle lobe traction bronchiectasis in ARS-ILD may be a useful predictor of poor long-term disease behavior.
Subcaudate Tractotomy White Matter Anatomy and Variability: A Diffusion Tensor Imaging Study
Authors: Bhatia Kartik D. , Henderson Luke A. , Hsu Eugene , Yim Mark
Published: May 2018

Background: Subcaudate tractotomy is a functional ablative procedure performed for treatment-resistant psychiatric disease, targeting the white matter tracts ventral to the head of the caudate nucleus. The white matter anatomy of this region has extensive interindividual variability, and this is thought to impact upon the treatment response to ablative and deep brain stimulation procedures. Objective: We aim to assess in detail the white matter tract anatomy and topographic variability underlying subcaudate tractotomy. Methods: 74 non-depressed adult volunteers underwent MRI including diffusion tensor imaging. Individualized regions of interest were formed in both hemispheres using native non-normalized data to simulate a subcaudate tractotomy. Tractography and analysis were performed and the exact tract locations measured including mean distances and standard deviations to assess variability. Results: The cingulum bundle, uncinate fasciculus, corticostriatal fibres, and corticothalamic fibres were consistently demonstrated. The location of the cingulum bundle was consistent across subjects, but there was extensive interindividual variability in the topographic location of the other tracts. Conclusion: We have demonstrated a detailed analysis of the white matter tracts and their anatomical variability underlying subcaudate tractotomy. This has significant implications for neurosurgical targeting.
Disease Burden, Psychological Well-Being and Attitudes regarding the Set of Emergency Medication in Adults with Insect Venom Allergy
Authors: Schaarschmidt Marthe-Lisa , Gutknecht Mandy , Schoeben Lisa , Schmieder Astrid
Published: May 2018

Background: Insect venom allergy is common and greatly impairs patients’ quality of life. Additionally, low compliance with carrying emergency medication is reported. The aim of our study was to analyze the disease burden, levels of anxiety and depression, and to evaluate attitudes towards the set of emergency medication in affected patients. Methods: Between April 2016 and January 2017, patients ≥18 years visiting our department because of an insect venom allergy were asked to complete a paper-based questionnaire. The questionnaire assessed willingness to pay (WTP), the Hospital Anxiety and Depression Scale (HADS), subjective anxiety levels, willingness to carry the set of emergency medication, self-assurance in using it, compliance with carrying it, and reasons for not always carrying it. Results: 55 patients (81.8% wasp allergy) were included. On average, WTP for a complete cure was EUR 1,727 (median: 500). Using the HADS, 14.5% showed definite anxiety disorders while 5.5% had significant depression disorders. Most patients stated to carry the emergency medication “always” (25.5%) or “almost always” (47.3%). “Forgetfulness” (36.4%) was reported as the main reason for not always carrying the medication, followed by “too big” (18.2%). Conclusions: In our patient cohort, insect venom allergy was associated with a moderate disease burden and a good compliance with carrying the emergency medication. However, several of our participants demonstrated borderline or significant anxiety and/or depression disorders. In this regard, this study highlights the necessity to regularly ask the patient about the psychological well-being to identify patients needing psychological support.
Direct Potentiation of Capsaicin Current by Histamine and Its Effect by Suplatast on Rat Trigeminal Ganglia Neurons
Authors: Zhou Jian-Rong , Shirasaki Tetsuya , Soeda Fumio , Yokomizo Kazumi , Takahama Kazuo
Published: May 2018

In this study, we investigated the effect of histamine on capsaicin-induced current and its influence by suplatast in rat trigeminal ganglia neurons using a patch-clamp technique. We found that histamine directly potentiated capsaicin-induced currents in rat sensory neurons, and suplatast had little effect on this potentiation. Since it has been known that suplatast suppresses histamine release from mast cells, it is possible that suplatast inhibits the activation of nociceptive fibers in the pathological condition via prevention of histamine-induced potentiation of the transient receptor potential vanilloid 1 receptor-mediated currents.
MiR-598 Suppresses Invasion and Migration by Negative Regulation of Derlin-1 and Epithelial-Mesenchymal Transition in Non-Small Cell Lung Cancer
Authors: Yang Fengming , Wei Ke , Qin Zhiqiang , Liu Weitao , Shao Chuchu , Wang Chaoshan , Ma Ling , Xie Mengyan , Shu Yongqian , Shen Hua
Published: May 2018

Background/Aims: MicroRNAs regulate a wide range of biological processes of non-small cell lung cancer (NSCLC). Although miR-598 has been reported to act as a suppressor in osteosarcoma and colorectal cancer, the physiological function of miR-598 in NSCLC remains unknown. In this study, the role of miR-598 in NSCLC was investigated. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to estimate the expression of miR-598 and Derlin-1 (DERL1) in both NSCLC tissues and cell lines. Immunohistochemistry (IHC) analyzed the association between the miR-598 expression and epithelial-mesenchymal transition (EMT) hallmark genes (E-cadherin, Vimentin) by staining the tumors representative of the high- and low-expression groups. The effect of miR-598 and DERL1 on invasion and migration was determined in vitro using transwell and wound-healing assays. The molecular mechanism underlying the relevance between miR-598 and DERL1 was elucidated by luciferase assay and Western blot. Western blot assessed the expression levels of EMT hallmark genes in cell lines. Xenograft tumor formation assay was conducted as an in vivo experiment. Results: In this study, a relatively low level of miR-598 and high DERL1 expressions were found in NSCLC specimens and cell lines. IHC results established a positive correlation between the miR-598 expression and E-cadherin and a negative with Vimentin. DERL1 was verified as a direct target of miR-598 by luciferase assay. In vitro, the over-expression of miR-598 negatively regulated DERL1 and EMT for the suppression of invasion and migration. In vivo, the over-expression of miR-598 could inhibit tumor cell metastasis in NSCLC. Conclusions: These findings for the first time revealed that miR-598, as a tumor suppressor, negatively regulate DERL1 and EMT to suppress the invasion and migration in NSCLC, thereby putatively serving as a novel therapeutic target for NSCLC clinical treatment.
N-Cadherin Attenuates High Glucose-Induced Nucleus Pulposus Cell Senescence Through Regulation of the ROS/NF-κB Pathway
Authors: Hou Gang , Zhao Huiqing , Teng Haijun , Li Pei , Xu Wenbin , Zhang Junbin , Lv Lulu , Guo Zhiliang , Wei Li , Yao Hui , Xu Yichun
Published: May 2018

Background/Aims: Diabetes mellitus (DM) is a potential etiology of disc degeneration. N-cadherin (N-CDH) helps maintain the cell viability, cell phenotype and matrix biosynthesis of nucleus pulposus (NP) cells. Here, we mainly aimed to investigate whether N-CDH can attenuate high glucose-induced NP cell senescence and its potential mechanism. Methods: Rat NP cells were cultured in a base culture medium and base culture medium with a 0.2 M glucose concentration. Recombinant lentiviral vectors were used to enhance N-CDH expression in NP cells. Senescence-associated β-galactosidase (SA-β-Gal) activity was measured by SA-β-Gal staining. NP cell proliferation was evaluated by CCK-8 assay. Telomerase activity and intracellular reactive oxygen species (ROS) content were tested by specific chemical kits according to the manufacturer’s instructions. G0/G1 cell cycle arrest was evaluated by flow cytometry. Real-time PCR and Western blotting were used to analyze mRNA and protein expressions of senescence markers (p16 and p53) and matrix macromolecules (aggrecan and collagen II). Additionally, p-NF-κB expression was also analyzed by Western blotting to evaluate NF-κB pathway activity. Results: High glucose significantly decreased N-CDH expression, increased ROS generation and NF-κB pathway activity, and promoted NP cell senescence, which was reflected in the increase in SA-β-Gal activity and senescence marker (p16 and p53) expression, compared to the control group. High glucose decreased telomerase activity and cell proliferation potency. However, N-CDH overexpression partially attenuated NP cell senescence, decreased ROS content and inhibited the activation of the NF-κB pathway under the high glucose condition. Conclusion: High glucose decreases N-CDH expression and promotes NP cell senescence. N-CDH overexpression can attenuate high glucose-induced NP cell senescence through the regulation of the ROS/ NF-κB pathway. This study suggests that N-CDH is a potential therapeutic target to slow DM-mediated disc NP degeneration.
Systemic Immune-Inflammation Index (SII) is Useful to Predict Survival Outcomes in Patients After Liver Transplantation for Hepatocellular Carcinoma within Hangzhou Criteria
Authors: Fu Hongyuan , Zheng Jun , Cai Jianye , Zeng Kaining , Yao Jia , Chen Liang , Li Hui , Zhang Jiebin , Zhang Yingcai , Zhao Hui , Yang Yang
Published: May 2018

Background: There is growing evidence that the systemic immune-inflammation index (SII), a novel prognostic biomarker based on peripheral lymphocyte, neutrophil, and platelet counts, is associated with poor prognosis for several tumors. However, the prognostic value of SII in patients with hepatocellular carcinoma (HCC) who undergo liver transplantation (LT) remains unclear. The aim of this study was to determine the correlation between SII and prognosis in these patients. Methods: This retrospective study involved 150 patients with HCC who underwent LT within the Hangzhou criteria. The optimal cut-off value was determined by receiver-operating characteristic (ROC) curve analysis to stratify the patients into those with a high SII and those with low SII. The Kaplan-Meier method and the Cox proportional hazards model were used to evaluate the prognostic value of SII. Finally, we calculated the area under the ROC curve to compare the prognostic power of SII, platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and monocyte-to-lymphocyte ratio (MLR). Results: Patients were divided into high SII (≥ 226) and low SII (< 226) groups. Five-year overall survival (OS) was lower in the high SII group than in the low SII group (56.1% vs. 82.4%, p = 0.002). SII ≥ 226 × 109/L, maximum tumor size> 5 cm, microvascular invasion, and poor differentiation were independent prognostic factors for OS. However, SII did not predict 5-year recurrence-free survival (high vs. low SII: 64.1% vs. 78.4%, p = 0.073). The area under the ROC curve was greater for SII than for PLR, NLR, and MLR. Conclusions: Preoperative SII may be a powerful prognostic biomarker in patients with HCC who undergo LT within the Hangzhou criteria. SII is superior to PLR, NLR, and MLR for prediction of OS in these patients.
Type 2 Diabetes Promotes Cell Centrosome Amplification via AKT-ROS-Dependent Signalling of ROCK1 and 14-3-3σ
Authors: Wang Pu , Lu Yu Cheng , Wang Jie , Wang Lan , Yu Hanry , Li Yuan Fei , Kong Alice , Chan Juliana , Lee Shaochin
Published: May 2018

Background/Aims: Type 2 diabetes is associated with oxidative stress and DNA damage which can cause centrosome amplification. Thus, the study investigated centrosome amplification in type 2 diabetes and the underlying mechanisms. Methods: Centrosome numbers in human peripheral blood mononuclear blood cells (PBMC) from healthy subjects and patients with type 2 diabetes were compared to access the association between type 2 diabetes and centrosome amplification. Colon cancer cells were used to investigate the molecular mechanisms underlying the centrosome amplification triggered by high glucose, insulin and palmitic acid. Western blot analysis was used to quantify the level of protein and protein phosphorylation. Immunofluorescent staining was performed to detect centrosomes. ROS was quantified using flow cytometry technique. Transcriptpmic profiling was performed using Illumina HiSeqTM500 platform. Results: We found that centrosome amplification was increased PBMC from the type 2 diabetic patients, which correlated with the levels of fasting blood glucose and HbA1c. High glucose, insulin and palmitic acid, alone or in combinations, induced ROS production and centrosome amplification. Together, they increased AKT activation as well as the expression, binding and centrosome translation of ROCK1 and 14-3-3σ. Results from further analyses showed that AKT-ROS-dependent upregulations of expression, binding and centrosome translocation of ROCK1 and 14-3-3σ was the molecular pathway underlying the centrosome amplification in vitro triggered by high glucose, insulin and palmitic acid. Moreover, the key in vitro molecular signalling events activated by high glucose, insulin and palmitic acid were verified in PBMC from the patients with type 2 diabetes. Conclusion: Our results show that type 2 diabetes promotes cell centrosome amplification, and suggest that the diabetic pathophysiological factors-activated AKT-ROS-dependent signalling of ROCK1 and 14-3-3σ is the underlying molecular mechanism.
Pliny The Elder and the Description of Rome as Capital of the World (The Mediterranean?)
Authors: Teixeira Ivana Lopes
Published: May 2018

O objetivo deste artigo, “Plínio, o Antigo, e a Descrição de Roma como Capital do Mundo (Mediterrâneo?)” é apresentar algumas considerações de Plínio, o Antigo, sobre a cidade de Roma como capital do mundo e da Itália como centro do Império Romano, a partir da leitura da História Natural, relacionando estas considerações a alguns paradigmas historiográficos sobre o mundo clássico e mediterrânico. Parte destas considerações dizem respeito à pesquisa de doutorado em desenvolvimento na FFLCH/USP , sob orientação do Prof. Dr. Norberto L. Guarinello, denominada “A Noção de Identidade Romana em Plínio, o Antigo, e a História Natural como um ‘Projeto’ Político - Pedagógico”, e parte é fruto dos encontros do Laboratório de Estudos do Império Romano e Mediterrâneo Antigo, LEIR - MA/USP, em torno da problemática das fronteiras e da integração dos povos antigos no/do Mediterrâneo, como paradigma historiográfico.
Por uma didática da História Antiga no Ensino Superior
Authors: Morales Fábio Augusto
Published: May 2018

Este artigo visa discutir as implicações ético-políticas e teórico-práticas do ensino de História Antiga em universidades brasileiras atualmente. A discussão está dividida de acordo com cinco variáveis que afetam a elaboração da disciplina: seu lugar nas estruturas de cursos de graduação, seus objetivos, seus objetos, seus métodos e os repertórios de professores e alunos. Argumenta-se que a História Antiga é um lugar estratégico para a reflexão sobre os fundamentos científicos da História, bem como para a crítica de velhas e a proposição de novas narrativas históricas.
Right Ventricular Dysfunction and Long-Term Risk of Sudden Cardiac Death in Patients With and Without Severe Left Ventricular Dysfunction
Authors: Naksuk Niyada , Tan Nicholas , Padmanabhan Deepak , Kancharla Krishna , Makkar Nayani , Yogeswaran Vidhushei , Gaba Prakriti , Kaginele Pranita , Riley David C. , Sugrue Alan M. , Rosenbaum Andrew N. , El-Harasis Majd A. , Asirvatham Samuel J. , Kapa Suraj , McLeod Christopher J.
Published: May 2018

Background:

Right ventricular systolic dysfunction (RVD) often coexists with various cardiopulmonary diseases. However, the association between RVD and risk of sudden cardiac death (SCD) has not been well studied. This study examined the risk of SCD associated with RVD in patients with heterogeneous underlying cardiac diseases.

Methods:

The Mayo Clinic cardiac care unit database included 5463 consecutive patients with complete echocardiographic evaluation to assess right ventricular systolic function and RVD severity. Prospective surveillance follow-up was obtained for all patients. SCD was adjudicated when a malignant ventricular arrhythmia was documented as the primary rhythm leading to death.

RESULTS:

The prevalence of mild RVD and moderate-severe RVD was 14.9% and 17.1%, respectively. Patients with RVD were more likely to have a history of congestive heart failure, cardiac arrest, pulmonary disease, and lower baseline left ventricular ejection fraction compared with those with normal right ventricular systolic function. During a median follow-up of 14 months, the incidence of SCD was highest in patients with moderate-severe RVD (7.4% versus 4.4% in mild RVD versus 1.6% in normal right ventricular function;
P
<0.001). After adjustment for baseline characteristics, mild RVD (adjusted hazard ratio, 1.57;
P
=0.046) and moderate-severe RVD (adjusted hazard ratio, 1.91;
P
=0.006) were independently associated with an increased risk of SCD. Moderate-severe RVD remained an independent predictor of SCD for patients with left ventricular ejection fraction >35% without or with preexisting implantable cardioverter-defibrillator (adjusted hazard ratio, 4.12;
P
=0.003 and adjusted hazard ratio, 5.04;
P
<0.001, respectively).

Conclusions:

Presence of RVD in patients with a history of preexisting cardiac disease is an independent predictor of SCD irrespective of left ventricular ejection fraction.
Systematics of the plant bug tribe Hyaliodini (Hemiptera, Heteroptera, Miridae, Deraeocorinae) from Australia and New Caledonia: phylogenetic analysis and discussion of deraeocorine relationships, and four new genera and thirteen new species
Authors: Hosseini Reza , Cassis Gerasimos
Published: May 2018

A systematic review of the tribe Hyaliodini from Australia and New Caledonia is given. Four new genera and 13 new species of Hyaliodini described: Bolbomiris gen. n. (B. cola sp. n., B. samuelsoni sp. n.), Epelisentis gen. n. (E. celiae sp. n., E. gressitti sp. n.), Plikomiris gen. n. (P. freycinetiaphilus sp. n., P. monteithi sp. n.) and Torunotum gen. n. (T. badius sp. n., T. hystrix sp. n., T. oviformis sp. n., T. pindaii sp. n. and T. psydrax sp. n.), as well as Femurocoris madeleinensis sp. n., Montagneria yahouensis sp. n. Femurocoris Carvalho and Montagneria Akingbohungbe and their type species are redescribed, as is M. cuneatus (Distant). Stethoconus praefectus (Distant) is reported from Australia for the first time. A dichotomous key, illustrations of male genitalia, scanning electron micrographs and habitus photographs are provided. A phylogenetic analysis of a morphological dataset was undertaken resulting in a monophyletic Hyaliodini, and the New Caledonian hyaliodines form a subclade. A discussion of the infra-subfamilial classification of the Deraeocorinae is given.
Sensitive Hg2+ Ion Detection Using Metal Enhanced Fluorescence of Novel Polyvinyl Pyrrolidone (PVP)-Templated Gold Nanoparticles
Authors: Dong Kailong , Zhou Jiasheng , Yang Taiqun , Dai Shan , Tan Hao , Chen Yuting , Pan Haifeng , Chen Jinquan , Audit Benjamin , Zhang Sanjun , Xu Jianhua
Published: May 2018

In this study, we report a straightforward strategy for Hg2+ ion detection. Fluorescent Au nanoparticles (NPs) were one-pot synthesized using a polymer (polyvinyl pyrrolidone [PVP]) as both capping and fluorescence agent. The as-synthesized PVP-Au NPs showed a remarkably rapid response selectively for Hg2+ ions compared to 14 other metal ions. The detection limit of Hg2+ was estimated at 100 nM. We discuss the emission and quenching mechanism of the PVP-Au NPs, the former being attributed to metal enhanced fluorescence and the latter being related to static quenching by Hg2+. The fluorescence of PVP-Au NPs offers an efficient and reliable strategy for Hg2+ ions detection. They therefore have a great potential for applications in health and environmental monitoring.
Elected MPs, Traditional Chiefs, and Local Public Goods: Evidence on the Role of Leaders in Co-Production From Rural Zambia
Authors: Baldwin Kate
Published: May 2018

What types of leaders are effective in organizing public goods that require community contributions? In many settings, both citizens and state agencies provide financing, labor, and oversight of local projects. This article analyzes the effects of elected Members of Parliament (MPs) and hereditary chiefs in facilitating co-produced public goods in Zambia. MPs have electoral motivations to provide public goods but may not be well-positioned to organize community contributions. Chiefs lack electoral incentives but typically have long time horizons and local social connections. I analyze the effects of both types of leaders on the provision of co-produced public goods through a natural experiment. I take advantage of lapses in leadership following the deaths of leaders in office to show that chiefs have a significant effect on co-produced public goods but MPs do not. Auxiliary analysis suggests that chiefs’ effect on community contributions depends on the length of their time horizons.