bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved Thermally Activated Building System Design Method Considering Integration of Air Systems
Authors: Chung Woong June , Lim Jae-Han
Published: June 2018

The purpose of the thermally activated building system design is to maintain the thermal comfort of the building indoor environment by securing enough thermal output of the system. For preventing the condensation on the thermally activated building system, the air system is mostly integrated with the thermally activated building system. However, the common design method in the standards only considers the thermal performance of the system itself and cannot reflect the effects of the air system. Thus, the design process of the thermally activated building system should include the consideration about the latent load and ventilation. In order to reflect the effect of the air system, the amount of sensible load removed by the thermally activated building system and air system should be included in the design process. The sensible load handled by the air system highly depends on the type of the air system and design consideration to prevent the condensation and maintain the indoor air quality. In this study, the air system choosing process was included by simulating and observing the sensible load removed by different types of the air system, and thermal performance adjustment in the design process was proposed.
Protective Effects of a Polyphenol‐Rich Extract from Syzygium cumini (L.) Skeels Leaf on Oxidative Stress‐Induced Diabetic Rats
Authors: Chagas Vinicyus Teles , Coelho Rafaella Moraes Rego de Sousa , Gaspar Renato Simões , da Silva Samira Abdalla , Mastrogiovanni Mauricio , Mendonça Cáritas de Jesus , Ribeiro Maria Nilce de Souza , Paes Antonio Marcus de Andrade , Trostchansky Andres
Published: June 2018

Syzygium cumini (L.) Skeels has been reported to exert anti‐inflammatory and cardiometabolic activities due to its high content of polyphenols. We characterized the chemical composition and assessed the antidiabetic effects of a novel polyphenol‐rich extract (PESc) obtained from S. cumini leaf. Rats were injected with alloxan (150 mg/kg, ip, ALX group) and followed up for 7 days. Some were orally treated with PESc (50 mg/kg/day) for 7 days before and after diabetes induction (ALX‐PP) or only for 7 days after alloxan injection (ALX‐P). ALX‐P and ALX‐PP decreased fasting glycemia in 37 and 43%, respectively, as compared to ALX. Triglycerides and total cholesterol serum levels were also significantly reduced in comparison to ALX. PESc presented high polyphenol concentration (71.78 ± 8.57 GAE/100 g), with flavonoid content of 8.21 ± 0.42 QE/100 g. Upon HPLC‐MS/MS and MS/MS studies, five main polyphenols—gallic acid, quercetin, myricetin, and its derivatives—were identified. Myricetin was predominant (192.70 ± 16.50 μg/mg PESc), followed by measurable amounts of gallic acid (11.15 ± 0.90 μg/mg PESc) and quercetin (4.72 ± 0.06 μg/mg PESc). Kinetic assessment of total antioxidant capacity revealed PESc high potency, since maximum response was reached within 5 min reaction time in a concentration‐dependent manner. Specific antioxidant activity of PESc was assessed against both DPPH• and ABTS•+, showing strong activity (IC50: 3.88 ± 1.09 and 5.98 ± 1.19 μg/mL, resp.). PESc also inhibited lipoxygenase activity (IC50: 27.63 ± 8.47), confirming its antioxidant activity also on biologically relevant radicals. Finally, PESc induced insulin secretion by directly stimulating INS‐1E β cells in the absence of any cytotoxic effect. Overall, our results support that PESc is a potent antioxidant phytocomplex with potential pharmacological use as a preventive antidiabetic natural product.
Detecting Anomalies in Meteorological Data Using Support Vector Regression
Authors: Lee Min-Ki , Moon Seung-Hyun , Yoon Yourim , Kim Yong-Hyuk , Moon Byung-Ro
Published: June 2018

Significant errors exist in automated meteorological data, and identifying them is very important. In this paper, we present a novel method for determining abnormal values in meteorological observations based on support vector regression (SVR). SVR is used to predict the observation value from a spatial perspective. The difference between the estimated value and the actual observed value determines if the observed value is abnormal or not. In addition, SVR input variables are deliberately selected to improve SVR performance and shorten computing time. In the selection process, a multiobjective genetic algorithm is used to optimize the two objective functions. In experiments using real-world data sets collected from accredited agencies, the proposed estimation method using SVR reduced the RMSE by an average of 45.44% whilst maintaining competitive computing times compared to baseline estimators.
Spatiotemporal Variability of Arctic Soil Moisture Detected from High-Resolution RADARSAT-2 SAR Data
Authors: Collingwood Adam , Charbonneau François , Shang Chen , Treitz Paul
Published: June 2018

Various methods are used to determine soil moisture information from synthetic aperture radar (SAR) data, but none specific to High Arctic regions and their unique physical characteristics. This research presents a method for determining, at high spatial and temporal resolutions, surface soil moisture and its changes through time in the Canadian High Arctic. An artificial neural network (ANN) is implemented using input variables derived from RADARSAT-2 SAR data and previously modelled surface roughness information. The model is applied to SAR data collected at various incidence angles and acquisition dates across two study sites on Melville Island, Nunavut. The model results in absolute soil moisture errors of approximately 15% (r2 = 0.46) for the primary study sites and 12% (r2 = 0.26) for the verification study area. The ANN model is accurate for modelling (i) the spatial distribution of soil moisture and (ii) the changes in moisture through time across the study areas, two characteristics that are very important for inputs to hydrologic or climate models. In addition, the models appear to be scalable when applied at coarser spatial resolutions, showing potential for large-area mapping or modelling.
Antidepressant-Like Effects of Gyejibokryeong-hwan in a Mouse Model of Reserpine-Induced Depression
Authors: Park Bo-Kyung , Kim Yu Ri , Kim Young Hwa , Yang Changsop , Seo Chang-Seob , Jung In Chul , Jang Ik-Soon , Kim Seung-Hyung , Lee Mi Young
Published: June 2018

Treatment with the antihypertensive agent reserpine depletes monoamine levels, resulting in depression. In the present study, we evaluated the antidepressant effects of Gyejibokryeong-hwan (GBH), a traditional Korean medicine, in a mouse model of reserpine-induced depression. Mice were treated with reserpine (0.5 mg·kg−1, i.p.) or phosphate-buffered saline (PBS, i.p., normal) once daily for 10 days. GBH (50, 100, 300, and 500 mg·kg−1), PBS (normal, control), fluoxetine (FXT, 20 mg·kg−1), or amitriptyline (AMT, 30 mg·kg−1) was administered orally 1 h prior to reserpine treatment. Mouse behavior was examined in the forced swim test (FST), tail suspension test (TST), and open-field test (OFT) following completion of the treatment protocol. Administration of GBH reduced immobility time in the FST and TST and significantly increased the total distance traveled in the OFT. Plasma serotonin levels were significantly lower in control mice than in normal mice, although these decreases were significantly attenuated to a similar extent by treatment with GBH, FXT, or AMT. Reserpine-induced increases in plasma corticosterone were also attenuated by GBH treatment. Moreover, GBH attenuated reserpine-induced increases in interleukin- (IL-) 1β, IL-6, and tumor necrosis factor- (TNF-) α mRNA expression in the hippocampus. In addition, GBH mice exhibited increased levels of brain-derived neurotrophic factor (BDNF) and a higher ratio of phosphorylated cAMP response element-binding protein (p-CREB) to CREB (p-CREB/CREB) in the hippocampus. Our results indicated that GBH can ameliorate depressive-like behaviors, affect the concentration of mood-related hormones, and help to regulate immune/endocrine dysfunction in mice with reserpine-induced depression, likely via activation of the BDNF-CREB pathway. Taken together, these findings indicate that GBH may be effective in treating patients with depression.
Xihuang Pill Induces Apoptosis of Human Glioblastoma U‐87 MG Cells via Targeting ROS‐Mediated Akt/mTOR/FOXO1 Pathway
Authors: Shao Meng , He Zhenqiang , Yin Zhixin , Ma Peihong , Xiao Qian , Song Yafeng , Huang Ziming , Ma Yujie , Qiu Yuqin , Zhao Aizhi , Zhou Taicheng , Wang Qirui
Published: June 2018

Xihuang pill (XHP), a traditional Chinese herbal formula, has long been used as an effective agent against multiple tumors. The aim of this study is to evaluate the effects of XHP on the growth inhibition and apoptosis in glioblastoma U‐87 MG cells. Gas chromatography‐mass spectrometry (GC‐MS) was performed for constituent analysis of XHP. Cell viability, cell cycle arrest, generation of reactive oxygen species (ROS), and apoptosis were measured by CCK‐8 assay, PI/RNase staining, DCFH‐DA assay, TUNEL assay, Annexin V‐FITC/PI double staining, and JC‐1 assay, respectively. The role of XHP in the regulation of Akt/mTOR/FOXO1 interaction was clarified by using Western Blotting (WB), immunofluorescence (IF), pharmacological inhibitor or antioxidant, and siRNA silencing. The results suggested that XHP could inhibit U‐87 MG cells growth and arrest cells in S‐phase cell cycle significantly and that the generation of ROS, collapse of mitochondrial membrane potential, enhancement of Bax/Bcl‐xL ratio, and reduction of the precursor forms of caspase‐9 and caspase‐3 caused by XHP prompted that a ROS‐mediated mitochondria‐dependent apoptosis was possibly involved. Furthermore, XHP affected the Akt/mTOR/FOXO1 pathway via inhibiting the phosphorylation of Akt, mTOR, and FOXO1 and increasing both prototype and nuclear translocation of FOXO1. Inhibition of Akt, mTOR, and FOXO1 by specific inhibitors or siRNA could interpose the apoptotic induction. In conclusion, we demonstrate for the first time that XHP may regulate glioblastoma U‐87 MG cell apoptosis via ROS‐mediated Akt/mTOR/FOXO1 pathway.
Research on Real-Time Local Rainfall Prediction Based on MEMS Sensors
Authors: Chao Zeyi , Pu Fangling , Yin Yuke , Han Bin , Chen Xiaoling
Published: June 2018

A more accurate and timely rainfall prediction is needed for flood disaster reduction and prevention in Wuhan. The in situ microelectromechanical systems’ (MEMS) sensors can provide high time and spatial resolution of weather parameter measurement, but they suffer from stochastic measurement error. In order to apply MEMS sensors in real-time rainfall prediction in Wuhan, firstly, seasonal trend decomposition using Loess (STL) algorithm is utilized to decompose the observed time series into trend, seasonal, and remainder components. The trend of the observed series is compared with the corresponding trend of the data downloaded from the authoritative website with the same weather parameter in terms of Euclidean distance and cosine similarity. The similarity demonstrates that the observation of MEMS sensors is believable. Secondly, the long short-term memory (LSTM) is used to predict the real-time rainfall based on the observed data. Compared with autoregressive and moving average (ARMA), random forest (RF), support vector machine (SVM), and back propagation neural networks (BPNNs), LSTM not only performs as well as ARMA in real-time rainfall prediction but also outperforms the other four models in seasonal rainfall pattern description and seasonal real-time rainfall prediction. Our experiment results show that more detailed, timely, and accurate rainfall prediction can be achieved by using LSTM on the MEMS weather sensors.
Comparisons of Tensile Fracturing Behaviors of Hydraulic Fully Graded and Wet‐Screened Concretes: A Mesoscale Study
Authors: Xu Lei , Jin Yongmiao , Jing Shuaizhao , Liu Jie , Huang Yefei , Zhou Changqiao
Published: June 2018

The widely used wet‐screening method in the experimental testing of hydraulic fully graded concrete inevitably results in a gap between the real mechanical parameters of hydraulic fully graded concrete specimens and those of the corresponding wet‐screened specimens and therefore necessitates the comparative study on their mechanical behaviors. To this end, a two‐dimensional mesoscale modeling methodology is developed for simulating the tensile fracturing behaviors of hydraulic fully graded and wet‐screened concretes, and extensive Monte Carlo simulations are performed. The individual effects of specimen size variation, variation of gradation and volume fraction of coarse aggregates, and the weaker interfacial transition zones surrounding the large coarse aggregates to be removed by wet‐screening are detailed followed by the discussion on the combined effect of these three main factors. All the mean values of the macroscopic mechanical parameters related to tensile fracturing behaviors are found to show significant change in response to wet‐screening, and the underlying differentiation mechanism and governing factor(s) are identified. Furthermore, it is shown that the randomness of the investigated parameters can be roughly described by the Gaussian distribution, and the dispersion of each of the investigated parameters of hydraulic fully graded concrete is higher than that of the corresponding wet‐screened concrete.
Scabies Outbreak Investigation and Risk Factors in East Badewacho District, Southern Ethiopia: Unmatched Case Control Study
Authors: Sara Jarso , Haji Yusuf , Gebretsadik Achamyelesh
Published: June 2018

Introduction. Scabies is one of the common public health problem but neglected parasitic diseases caused bySarcoptes scabieivar.hominis.Global scabies prevalence in both sexes was 204 million. In Ethiopia, scabies is also a common public health issue but there is lack of studies regarding outbreak investigation and risk factors in the study area. This study was aimed to investigate the scabies suspected outbreak and risk factors in East Badewacho District, Southern Ethiopia, 2016.Methods. A community-based unmatched case control (1 : 2 ratios) study was conducted in East Badewacho District, using collected scabies line listed data and face-to-face interview to assess risk factors during October 23–30, 2016. The data were collected using structured questionnaire, and then the data were coded, entered, cleaned, and analyzed using SPSS statistical software, whereas, line listed data was entered into Microsoft excel for descriptive analyses. Odds ratios (OR) and 95% confidence interval (CI) were computed to determine associated factors.Results. A total of 4,532 scabies cases line listed with overall attack rate of 110/1,000 population. The mean age was 12 years, and most affected age group was 5–14 years. Independent risk factors found to be statistically associated with scabies infestation were age less than 15 years (AOR = 2.62, 95% CI: 1.31–5.22), family size greater than 5 members (AOR = 2.63, 95% CI: 1.10–6.27), bed sharing with scabies cases (AOR = 12.47, 95% CI: 3.05–50.94), and home being affected by flooding (AOR = 22.32, 95% CI: 8.46–58.90).Conclusion. Outbreak of scabies occurred in East Badewacho District. Age less than 15 years, family size greater than five members, sleeping with others, and home being affected by flooding are the risk factors. Providing risk factors related health education on prevention and controls especially, at community level and schools, is recommended.
Optimization Method for Transit Signal Priority considering Multirequest under Connected Vehicle Environment
Authors: Xianmin Song , Mili Yuan , Di Liang , Lin Ma
Published: June 2018

Aiming at reducing per person delay, this paper presents an optimization method for Transit Signal Priority (TSP) considering multirequest under connected vehicle environment, which is based on the travel time prediction model. Conventional arrival time of transit depended on the detection information and the front road state, which restricted the effect of priority seriously. According to the bidirectional and real-time information transmission under connected vehicle environment, this paper establishes a more accurate forecasting model of bus travel time. Based on minimizing the total person delay at the intersection, the decision mechanism of multirequest is devised to meet the priority needs of buses with different arrival times. And the green time compensation algorithm is developed after considering the arrival information of the buses in the next cycle of compensational phase. Finally, the paper combines the COM interface of VISSIM and Matlab to achieve the proposed method under connected vehicle environment. Four control methods were tested when the VCR was 0.5, 0.7, and 0.9. The results illustrated that the proposed method reduced per person delay by 18.57%, 11.88%, and 18.96% and decreased the private vehicle delay by 3.73%, 7.62%, and 13.10%, respectively.
The Clinical Significance of Changes in the Expression Levels of MicroRNA-1 and Inflammatory Factors in the Peripheral Blood of Children with Acute-Stage Asthma
Authors: Tian Man , Zhou Ying , Jia Haoyuan , Zhu Xuming , Cui Yubao
Published: June 2018

This study assessed the changes and clinical significance of microRNA-1 (miR-1) and inflammatory factors in the peripheral blood of children with acute-stage asthma. 100 children with acute-stage asthma (study group) and 100 healthy children (control group) were enrolled. For all enrolled children, the peripheral blood levels of miR-1, interleukin-4 (IL-4), IL-5, IL-8, tumor necrosis factor-alpha (TNF-α), and interferon-γ (IFN-γ) were measured. The relative expression levels of miR-1 and IFN-γ in the peripheral blood of children in the study group were significantly lower than those in the control group, whereas expression levels of IL-4, IL-5, IL-8, and TNF-α were significantly higher. Moreover, these levels changed to a greater extent in patients with severe disease (P < 0.05). Further analyses showed that the miR-1 expression level positively correlated with IFN-γ and negatively correlated with IL-4, IL-5, IL-8, and TNF-α expression levels (P < 0.05). ROC curve analysis to identify diagnostic specificity and sensitivity showed that, for diagnosing exacerbation in asthma, the area under the curve (AUC) for miR-1 was the highest (AUC = 0.900, P < 0.05) of all tested markers; this held true for diagnosing severe asthma as well (AUC = 0.977, P < 0.05). Compared to healthy children, children with acute-stage asthma had a low miR-1 expression level and a Th1/Th2 imbalance in their peripheral blood. The changes were closely related, became more exaggerated with an increase in disease severity, and could be used as auxiliary variables for diagnosing asthma exacerbation and evaluating disease severity.
Profiling of Stem/Progenitor Cell Regulatory Genes of the Synovial Joint by Genome-Wide RNA-Seq Analysis
Authors: Zhou Yue , Chen Mo , Ricupero Christopher L. , He Ling , Wu Jiaqian , Chen Kenian , Friedman Richard A. , Guarnieri Paolo , Wang Zuolin , Zhou Xuedong , Mao Jeremy J.
Published: June 2018

Synovial joints suffer from arthritis and trauma that may be severely debilitative. Despite robust investigations in the roles of individual genes in synovial joint development and arthritis, little is known about global profiles of genes that regulate stem/progenitor cells of a synovial joint. The temporomandibular joint is a poorly understood synovial arthrosis with few clinical treatment options. Here, we isolated the articular and mature zones of the mandibular condyle by laser capture microdissection, performed genome-wide profiling, and analyzed molecular signaling pathways relevant to stem/progenitor cell functions. A total of 804 genes were differentially expressed between the articular and mature zones. Pathway analyses revealed 29 enriched signaling pathways, including the PI3K-Akt, Wnt, and Toll-like receptor signaling pathways that may regulate stem/progenitor cell homeostasis and differentiation into the chondrocyte lineage. Upstream regulator analyses further predicted potential upstream key regulators such as Xbp1, Nupr1, and Hif1a, and associated underlying mechanism networks were described. Among the multiple candidates of growth and transcriptional factors that may regulate stem/progenitor cells, we immunolocalized Sox9, Ihh, Frzb, Dkk1, Lgr5, and TGFβ3 in the articular and mature zones. These findings provide a comprehensive genetic mapping of growth and transcriptional genes in the articular and mature zones of a synovial joint condyle. Differentially expressed genes may play crucial roles in the regulation of stem/progenitor cells in development, homeostasis, and tissue regeneration.
Loss of Estrogen-Regulated MIR135A1 at 3p21.1 Promotes Tamoxifen Resistance in Breast Cancer
Authors: Zhang Weijie , Wu Mingming , Chong Qing-Yun , Zhang Min , Zhang Xiao , Hu Lan , Zhong Yanghao , Qian Pengxu , Kong Xiangjun , Tan Sheng , Li Gaopeng , Ding Keshuo , Lobie Peter E. , Zhu Tao
Published: June 2018

The dysregulation of miRNAs has been increasingly recognized as a critical mediator of cancer development and progression. Here, we show that frequent deletion of the MIR135A1 locus is associated with poor prognosis in primary breast cancer. Forced expression of miR-135a decreased breast cancer progression, while inhibition of miR-135a with a specific miRNA sponge elicited opposing effects, suggestive of a tumor suppressive role of miR-135a in breast cancer. Estrogen receptor alpha (ERα) bound the promoter of MIR135A1 for its transcriptional activation, whereas tamoxifen treatment inhibited expression of miR-135a in ERα+ breast cancer cells. miR-135a directly targeted ESR1, ESRRA, and NCOA1, forming a negative feedback loop to inhibit ERα signaling. This regulatory feedback between miR-135a and ERα demonstrated that miR-135a regulated the response to tamoxifen. The tamoxifen-mediated decrease in miR-135a expression increased the expression of miR-135a targets to reduce tamoxifen sensitivity. Consistently, miR-135a expression was downregulated in ERα+ breast cancer cells with acquired tamoxifen resistance, while forced expression of miR-135a partially resensitized these cells to tamoxifen. Tamoxifen resistance mediated by the loss of miR-135a was shown to be partially dependent on the activation of the ERK1/2 and AKT pathways by miR-135a–targeted genes. Taken together, these results indicate that deletion of the MIR135A1 locus and decreased miR-135a expression promote ERα+ breast cancer progression and tamoxifen resistance.

Significance: Loss of miR-135a in breast cancer disrupts an estrogen receptor-induced negative feedback loop, perpetuating disease progression and resistance to therapy.

Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/17/4915/F1.large.jpg. Cancer Res; 78(17); 4915–28. ©2018 AACR.
Enhanced Glycolysis Supports Cell Survival in EGFR-Mutant Lung Adenocarcinoma by Inhibiting Autophagy-Mediated EGFR Degradation
Authors: Kim Ji Hye , Nam Boas , Choi Yun Jung , Kim Seon Ye , Lee Jung-Eun , Sung Ki Jung , Kim Woo Sung , Choi Chang-Min , Chang Eun-Ju , Koh Jae Soo , Song Joon Seon , Yoon Shinkyo , Lee Jae Cheol , Rho Jin Kyung , Son Jaekyoung
Published: June 2018

Oncogenic EGFR is essential for the development and growth of non–small cell lung cancer (NSCLC), but the precise roles of EGFR in lung cancer metabolism remain unclear. Here, we show that EGFR mutation-mediated enhancement of glycolysis is critical for EGFR stability. EGFR knockdown significantly decreased levels of glycolytic pathway intermediates via transcriptional regulation of glycolytic genes. EGFR mutation-enhanced glycolysis was required for fueling the tricarboxylic acid cycle, a critical component of EGFR stability. Nonsustained ATP production enhanced reactive oxygen species accumulation and subsequent JNK-mediated activation of autophagy, which in turn induced EGFR degradation. Our data show that EGFR-mutant NSCLCs require EGFR mutation-enhanced glycolysis to maintain EGFR stability. This pathway may serve as an attractive therapeutic target for EGFR-mutant NSCLCs.

Significance: Enhanced glycolysis by EGFR mutation is required for maintaining EGFR levels via inhibition of JNK-induced autophagy. This provides a promising rationale for use of JNK activators in patients with EGFR-mutated NSCLC. Cancer Res; 78(16); 4482–96. ©2018 AACR.
Cotargeting Ephrin Receptor Tyrosine Kinases A2 and A3 in Cancer Stem Cells Reduces Growth of Recurrent Glioblastoma
Authors: Qazi Maleeha A. , Vora Parvez , Venugopal Chitra , Adams Jarrett , Singh Mohini , Hu Amy , Gorelik Maryna , Subapanditha Minomi K. , Savage Neil , Yang Jiahe , Chokshi Chirayu , London Max , Gont Alexander , Bobrowski David , Grinshtein Natalie , Brown Kevin R. , Murty Naresh K. , Nilvebrant Johan , Kaplan David , Moffat Jason , Sidhu Sachdev , Singh Sheila K.
Published: June 2018

Glioblastoma (GBM) carries a dismal prognosis and inevitably relapses despite aggressive therapy. Many members of the Eph receptor tyrosine kinase (EphR) family are expressed by GBM stem cells (GSC), which have been implicated in resistance to GBM therapy. In this study, we identify several EphRs that mark a therapeutically targetable GSC population in treatment-refractory, recurrent GBM (rGBM). Using a highly specific EphR antibody panel and CyTOF (cytometry by time-of-flight), we characterized the expression of all 14 EphR in primary and recurrent patient-derived GSCs to identify putative rGBM-specific EphR. EPHA2 and EPHA3 coexpression marked a highly tumorigenic cell population in rGBM that was enriched in GSC marker expression. Knockdown of EPHA2 and EPHA3 together led to increased expression of differentiation marker GFAP and blocked clonogenic and tumorigenic potential, promoting significantly higher survival in vivo. Treatment of rGBM with a bispecific antibody against EPHA2/A3 reduced clonogenicity in vitro and tumorigenic potential of xenografted recurrent GBM in vivo via downregulation of AKT and ERK and increased cellular differentiation. In conclusion, we show that EPHA2 and EPHA3 together mark a GSC population in rGBM and that strategic cotargeting of EPHA2 and EPHA3 presents a novel and rational therapeutic approach for rGBM.

Significance: Treatment of rGBM with a novel bispecific antibody against EPHA2 and EPHA3 reduces tumor burden, paving the way for the development of therapeutic approaches against biologically relevant targets in rGBM. Cancer Res; 78(17); 5023–37. ©2018 AACR.
The Light Chain IgLV3-21 Defines a New Poor Prognostic Subgroup in Chronic Lymphocytic Leukemia: Results of a Multicenter Study
Authors: Stamatopoulos Basile , Smith Thomas , Crompot Emerence , Pieters Karlien , Clifford Ruth , Mraz Marek , Robbe Pauline , Burns Adam , Timbs Adele , Bruce David , Hillmen Peter , Meuleman Nathalie , Mineur Philippe , Firescu Radu , Maerevoet Marie , De Wilde Virginie , Efira André , Philippé Jan , Verhasselt Bruno , Offner Fritz , Sims David , Heger Andreas , Dreau Hélène , Schuh Anna
Published: June 2018

Purpose: Unmutated (UM) immunoglobulin heavy chain variable region (IgHV) status or IgHV3-21 gene usage is associated with poor prognosis in chronic lymphocytic leukemia (CLL) patients. Interestingly, IgHV3-21 is often co-expressed with light chain IgLV3-21, which is potentially able to trigger cell-autonomous BCR-mediated signaling. However, this light chain has never been characterized independently of the heavy chain IgHV3-21.

Experimental Design: We performed total RNA sequencing in 32 patients and investigated IgLV3-21 prognostic impact in terms of treatment-free survival (TFS) and overall survival (OS) in 3 other independent cohorts for a total of 813 patients. IgLV3-21 presence was tested by real-time PCR and confirmed by Sanger sequencing.

Results: Using total RNA sequencing to characterize 32 patients with high-risk CLL, we found a high frequency (28%) of IgLV3-21 rearrangements. Gene set enrichment analysis revealed that these patients express higher levels of genes responsible for ribosome biogenesis and translation initiation (P < 0.0001) as well as MYC target genes (P = 0.0003). Patients with IgLV3-21 rearrangements displayed a significantly shorter TFS and OS (P < 0.05), particularly those with IgHV mutation. In each of the three independent validation cohorts, we showed that IgLV3-21 rearrangements—similar to UM IgHV status—conferred poor prognosis compared with mutated IgHV (P < 0.0001). Importantly, we confirmed by multivariate analysis that this was independent of IgHV mutational status or subset #2 stereotyped receptor (P < 0.0001).

Conclusions: We have demonstrated for the first time that a light chain can affect CLL prognosis and that IgLV3-21 light chain usage defines a new subgroup of CLL patients with poor prognosis. Clin Cancer Res; 24(20); 5048–57. ©2018 AACR.
Real-Life Clinical Effectiveness of Razumab® (the World’s First Biosimilar of Ranibizumab) in Retinal Vein Occlusion: A Subgroup Analysis of the Pooled Retrospective RE-ENACT Study
Authors: Sharma Shashikant , Khan Mujtaba A. , Chaturvedi Alok ,   RE-ENACT Study Investigators Group
Published: June 2018

Background: This subgroup analysis of the RE-ENACT study evaluates the effectiveness of Razumab® (the world’s first biosimilar of ranibizumab by Intas Pharmaceuticals Ltd.) in Indian patients with retinal vein occlusion (RVO). Methods: The data on patients with RVO who had received ≥3 injections of Razumab® between January and August 2016 were analyzed. Endpoints were: improvement in best corrected visual acuity (BCVA), and a decrease in central macular thickness (CMT), intraretinal fluid (IRF), and subretinal fluid (SRF) from baseline at weeks 4, 8, and 12. Results: Of 160 patients, the majority (61.87%) were men. The mean (±SE) BCVA improved from baseline (0.76 ± 0.04) to week 4 (0.73 ± 0.03; p = 0.0656), which attained significance at week 8 (0.55 ± 0.02; p < 0.0001) and week 12 (0.47 ± 0.02; p < 0.0001). The mean (±SE) CMT significantly decreased from baseline (447.60 ± 10.91 μm) to week 4 (431.84 ± 10.92 μm; p = 0.0028), week 8 (339.28 ± 8.12 μm; p < 0.0001), and week 12 (298.23 ± 6.68 μm; p < 0.0001). The proportion of patients with IRF and SRF significantly (p < 0.0001) decreased from baseline to weeks 4, 8, and 12 (IRF: from 70.63 to 45.63, 39.38, and 30.00%, respectively; SRF: from 65.63 to 37.50, 28.13, and 24.38%, respectively). A subgroup analysis of branch RVO and central RVO showed similar results. No new safety concerns were observed. Conclusion: Razumab® (biosimilar of ranibizumab) effectively improved visual acuity and disease outcomes in patients with RVO in a real-world setting with no new safety concerns.
Heboidophrenia and Pseudo-Psychopathic Schizophrenia: Current Knowledge and Critical Perspective
Authors: De Page Louis , Englebert Jérôme
Published: June 2018

In this article, based on literature review, we present an integrated description of heboidophrenia and pseudo-psychopathic schizophrenia. Both diagnostic constructs describe latent psychotic processes inextricably bound with psychopathic features. Although both have been described in different eras and research threads, they are that similar that we could not find divergences. We formulated operational criteria for clinical and research purpose. The recognition of this syndrome improves risk management, treatment, and legal decisions.
Prognostic Indicators in Stage IV Surgically Treated Gastric Cancer Patients: A Retrospective Multi-Institutional Study
Authors: Biondi Alberto , D’Ugo Domenico , Cananzi Ferdinando , Rausei Stefano , Sicoli Federico , Santullo Francesco , Laurino Antonio , Ruspi Laura , Belia Francesco , Quagliuolo Vittorio , Persiani Roberto
Published: June 2018

Introduction: The role of gastric resection in treating metastatic gastric adenocarcinoma is controversial. In the present study, we reviewed the short- and long-term outcomes of stage IV patients undergoing surgery. Methods: A retrospective review was conducted that assessed patients undergoing elective surgery for incurable gastric carcinoma. Short- and long-term results were evaluated. Results: A total of 122 stage IV gastric cancer patients were assessed. Postoperative mortality was 5.7%, and the overall rate of complications was 35.2%. The overall survival rate at 1 and 3 years was 58 and 19% respectively; the median survival was 14 months. Improved survival was observed for the factors age less than 60 years (p = 0.015), site of metastases (p = 0.022), extended lymph node dissection (p = 0.044), absence of residual disease after surgery (p = 0.001), and administration of adjuvant chemotherapy (p = 0.016). Multivariate analysis showed that residual disease and adjuvant chemotherapy were independent prognostic factors. Conclusions: The results of this study suggest that surgery combined with systemic chemotherapy in selected patients with stage IV gastric cancer can improve survival.
Cost-Effectiveness of a Multifaceted Podiatry Intervention for the Prevention of Falls in Older People: The REducing Falls with Orthoses and a Multifaceted Podiatry Intervention Trial Findings
Authors: Corbacho Belen , Cockayne Sarah , Fairhurst Caroline , Hewitt Catherine E. , Hicks Kate , Kenan Anne-Maree , Lamb Sarah E. , MacIntosh Caroline , Menz Hylton B. , Redmond Anthony C. , Rodgers Sara , Scantlebury Arabella , Watson Judith , Torgerson David J. ,   on behalf of the REFORM study
Published: June 2018

Background: Falls are a major cause of morbidity among older people. Multifaceted interventions may be effective in preventing falls and related fractures. Objective: To evaluate the cost-effectiveness alongside the REducing Falls with Orthoses and a Multifaceted podiatry intervention (REFORM) trial. Methods: REFORM was a pragmatic multicentre cohort randomised controlled trial in England and Ireland; 1,010 participants (> 65 years) were randomised to receive either a podiatry intervention (n = 493), including foot and ankle strengthening exercises, foot orthoses, new footwear if required, and a falls prevention leaflet, or usual podiatry treatment plus a falls prevention leaflet (n = 517). Primary outcome: incidence of falls per participant in the 12 months following randomisation. Secondary outcomes: proportion of fallers and quality of life (EQ-5D-3L) which was converted into quality-adjusted life years (QALYs) for each participant. Differences in mean costs and QALYs at 12 months were used to assess the cost-effectiveness of the intervention relative to usual care. Cost-effectiveness analyses were conducted in accordance with National Institute for Health and Clinical Excellence reference case standards, using a regression-based approach with costs expressed in GBP (2015 price). The base case analysis used an intention-to-treat approach on the imputed data set using multiple imputation. Results: There was a small, non-statistically significant reduction in the incidence rate of falls in the intervention group (adjusted incidence rate ratio 0.88, 95% CI 0.73–1.05, p = 0.16). Participants allocated to the intervention group accumulated on average marginally higher QALYs than the usual care participants (mean difference 0.0129, 95% CI –0.0050 to 0.0314). The intervention costs were on average GBP 252 more per participant compared to the usual care participants (95% CI GBP –69 to GBP 589). Incremental cost-effectiveness ratios ranged between GBP 19,494 and GBP 20,593 per QALY gained, below the conventional National Health Service cost-effectiveness thresholds of GBP 20,000 to GBP 30,000 per additional QALY. The probability that the podiatry intervention is cost-effective at a threshold of GBP 30,000 per QALY gained was 0.65. The results were robust to sensitivity analyses. Conclusion: The benefits of the intervention justified the moderate cost. The intervention could be a cost-effective option for falls prevention when compared with usual care in the UK.
Reduction of Peripapillary Vessel Density by Optical Coherence Tomography Angiography from the Acute to the Atrophic Stage in Non-Arteritic Anterior Ischaemic Optic Neuropathy
Authors: Rebolleda Gema , Díez-Álvarez Laura , García Marín Yoel , de Juan Victoria , Muñoz-Negrete Francisco J.
Published: June 2018

Purpose: To analyse superficial peripapillary vascularization in non-arteritic anterior ischaemic optic neuropathy (NAION) at acute and atrophic (3 months) stage. Procedures: Prospective case-control study including 6 patients with NAION and 10 age-matched healthy controls evaluated with optical coherence tomography angiography (OCT-A; Angioplex-Cirrus) at acute and atrophic stage. Apart from the ­commercially provided measurements for vessel density (VD) and perfusion density (PD), a custom image analysis was used to quantify the peripapillary capillary density (PCD). Results: NAION-group demonstrated a significant decrease in the PCD, VD and PD compared with fellow unaffected and control groups at acute and atrophic stage. At 3 months, the average and the temporal sector in PCD correlated with logMAR VA (–0.943, p = 0.005 and –0.829, p = 0.042 for average and temporal sectors respectively) and with MD (0.943, p = 0.005; and 0.899; p = 0.015, respectively). Over 3 months, there was a significant PCD reduction at the temporal sector and at the inner circle in VD and PD, which correlated with ganglion cell–inner plexiform layer (GCIPL) thinning over the 3 months period after the acute NAION (0.749, p = 0.020; 0.885, p = 0.002; 0.767, p = 0.016 respectively). Conclusion: Both strategies demonstrated a significant peripapillary microvascular dropout in NAION, but the customized analysis detected them ­earlier. A progressive vessel reduction occurs within the first 3 months, which correlates with GCIPL thinning.
Changes in Hemagglutinin and Neuraminidase Genes of pH1N1 Influenza Virus Strains Collected from a North Indian Tertiary Care Hospital during 2015
Authors: Jain Amita , Prakash Shantanu , Jain Bhawana
Published: June 2018

Objective: The study was conducted to analyze changes in HA and NA genes of pandemic pH1N1 strains, collected from North Indian tertiary care hospital during 2015 and studied the nucleotide change since 2009. Differences in clinical features of cases positive and negative for influenza viruses were also studied. Methods: All samples referred for H1N1 testing, were tested for influenza viruses. Randomly selected 25 strains of pH1N1 were studied for nucleotide sequences of HA & NA gene. The nucleotide changes occurring since 2009 were studied by mutational and phylogenetic analysis. Clinical details of cases were recorded and analysed. Results: A total of 3319 cases of acute respiratory infections (ILI/SARI) were tested for influenza viruses during Jan to April 2015, of which 815 cases tested positive for pH1N1. Nucleotide variation of 2015 strains, from influenza A/California/07/2009 strain at HA1 and NA1 gene was 1.9% and 3.8% respectively. Both HA1 and NA1 coding sequence showed eight mutations. Four of HA1(K180Q, S202T, S220T, and A273T) and NA1 (N200S, V241I, N248D, and N270K) mutations were observed in all pH1N1 study strains. Conclusions: Strains of pH1N1 isolated during year 2015 diverged from previously circulating strains. Their association with severity of illness needs to be further studied.
Influence of Chemotherapy on Allergen-Specific IgE
Authors: Whiteside Sarah , Markova Marketa , Chin Alex , Lam Cynthia , Dharmani-Khan Poonam , Modi Monica , Khan Faisal , Storek Jan
Published: June 2018

Background: Atopy is defined as excess allergen-specific IgE (A-IgE). IgE is produced by plasma cells that differentiate from allergen-specific B cells. B cells are known to be killed by chemotherapy; however, it is not known whether A-IgE-secreting plasma cells are killed or inhibited by chemotherapy. If yes, serum A-IgE levels would be expected to decrease after chemotherapy. Objectives: We aimed to determine whether A-IgE levels in atopic individuals (serum A-IgE ≥0.35 kUA/L) decrease into the nonatopic range (< 0.35 kUA/L) after chemotherapy. Methods: In 105 patients undergoing chemotherapy for acute leukemia, we measured serum A-IgE before and after chemotherapy. In a subset of these patients, we also measured B cell counts before and after chemotherapy. Results: Of the 105 patients, 36 were atopic. In these patients, median A-IgE level before chemotherapy was 1.6 kUA/L whereas the median level after chemotherapy was 0.6 kUA/L (p < 0.001). In 12/36 (33%) patients, A-IgE levels decreased into the nonatopic range. In nonatopic patients (n = 69), the median A-IgE level also dropped: from 0.04 kUA/L before to 0.03 kUA/L after chemotherapy (p = 0.001). Among the total patients (n = 105), the median pre:post-chemotherapy A-IgE ratio was 1.8 (2.6 in atopic and 1.5 in nonatopic patients). In contrast, the median ratio of pre:post-chemotherapy B cell counts was 87.6. Conclusions: A-IgE levels decrease after chemotherapy but markedly less than B cell counts. Thus, at least some A-IgE plasma cells appear to survive chemotherapy.
The Dopamine Receptor D2 C957T Polymorphism Modulates Early Components of Event-Related Potentials in Visual Word Recognition Task
Authors: Golimbet Vera E. , Garakh Zhanna V. , Zaytseva Yuliya , Alfimova Margarita V. , Lezheiko Tatyana V. , Kondratiev Nikolay V. , Shmukler Alexander B. , Gurovich Isaac Ya. , Strelets Valeria B.
Published: June 2018

Background: Visual word recognition is one of the central topics in cognitive psychology and cognitive neuroscience. Genetic factors are known to contribute to the visual word recognition, but no genes associated with this process have been identified so far. We studied the impact of the DRD2 C957T polymorphism on the efficiency of visual word recognition by measuring its neuronal correlates and behavioral parameters. Early (~200 ms) components of event-related potentials (ERP) were recorded during a lexical decision task. The DRD2 C957T polymorphism is thought to be associated with D2 receptor’s availability and binding potential. Earlier studies have demonstrated the influence of this variation on perception and processing of verbal stimuli. The DRD2 C957T is also associated with schizophrenia, with the C allele being the risk allele. Methods: Electroencephalogram, genetic, and behavioral data were collected from 96 healthy individuals (53.1% men). ERPs were recorded for words and pseudowords in implicit and explicit tasks. Two regions of interests in the left ventral temporal cortex, whose role in early visual word processing is well established, were selected for analysis. Results: The results showed the main effect of the DRD2 C957T polymorphism on P200 amplitude. Carriers of the TT genotype had higher P200 amplitudes compared to subjects with schizophrenia risk C allele. Within-group comparisons demonstrated a better ability to adjust attention to orthographic stimuli depending on task demands and lexicality in the TT group. Conclusion: The results of the study suggest that the DRD2 C957T polymorphism modulates early stages of visual word recognition.
The Outcome of Complex Hepato-Pancreato-Biliary Surgery for Elderly Patients: A Propensity Score Matching Analysis
Authors: Takagi Kosei , Umeda Yuzo , Yoshida Ryuichi , Nobuoka Daisuke , Kuise Takashi , Fushimi Takuro , Fujiwara Toshiyoshi , Yagi Takahito
Published: June 2018

Background/Aims: Postoperative mortality and morbidity rates after hepato-pancreato-biliary (HPB) surgery remain high, and the number of elderly patients requiring such surgery has been increasing. This study aimed to investigate postoperative outcomes of complex HPB surgery for elderly patients. Methods: We retrospectively reviewed perioperative data of 721 patients who underwent complex HPB surgery between 2010 and 2015. The patients were divided into 2 groups: elderly (≥75 years) and non-elderly (< 75 years). Surgical outcomes of both groups were compared after propensity score-matching analysis. Subsequently, risk factors for serious postoperative morbidity were identified by multivariate analysis. Results: Before matching, the elderly group (n = 170) had more comorbidities, such as cardiovascular and renal disease, than the non-elderly group (n = 551). Matching yielded elderly (n = 170) and non-elderly groups (n = 170) with similar preoperative backgrounds. The mortality and morbidity rates did not differ significantly between the groups. In multivariate analyses, operative time (OR 1.79; p = 0.005) and blood loss (OR 1.66; p = 0.03) were identified as independent risk factors for serious postoperative morbidity, whereas older age did not have a predictive impact (OR 1.16; p = 0.52). Conclusions: Although elderly ­patients had more comorbidities and higher incidences of postoperative mortality and several complications before matching, their postoperative outcomes were equivalent to those of non-elderly patients after matching.
Case Series: Pediatric Shunt Tunnel Catheter Infection
Authors: Pease Matthew , Dewan Sheri , Greene Stephanie
Published: June 2018

Shunt infections are common pediatric neurosurgical cases with high morbidity that almost always requires surgical removal of the shunt, external ventricular drain placement, and delayed shunt replacement. Tunnel infections are well-described clinical entities occurring with indwelling catheters, whereby the indwelling tunnel portion of a line becomes externally infected with a sterile central lumen. These infections are typically treated with line replacement or antibiotics depending on clinical circumstances. We describe 2 cases of shunt tunnel infection. Both cases presented as erythema over the thoracic portion of the shunt without signs of CNS infection, with only a remote history of shunt surgery and no recent systemic illness. One case was treated with a course of antibiotics, and the other with surgical removal and eventual replacement. Both children made full recoveries. Our case series juxtaposes 2 alternative successful strategies for treating the rare entity of shunt tunnel infection.
Effect of Vitamin D Supplementation on Some Inflammatory Biomarkers in Type 2 Diabetes Mellitus Subjects: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Yu Yanting , Tian Liqiang , Xiao Yanyu , Huang Guowei , Zhang Meilin
Published: June 2018

Background/Aims: The mechanism, by which vitamin D influences inflammatory biomarkers in type 2 diabetes mellitus (T2DM), is not very well known. Thus, a meta-analysis of randomized controlled trials was conducted to assess the effect of vitamin D supplementation on some inflammatory biomarkers in T2DM subjects. Methods: We searched randomized controlled trials from PubMed and the Cochrane Library in October 2017 and conducted a meta-analysis to evaluate the effectiveness of vitamin D supplementation on high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Either a fixed-effects or a random-effects model was used to calculate pooled effects. Results: We identified 13 studies that met our inclusion criteria. The results indicated that the vitamin D supplementation significant decreased the hs-CRP level by 0.45 μg/mL, whereas the vitamin D supplementation did not  influence the TNF-α and IL-6. Subgroup analysis showed that vitamin D significantly lowered hs-CRP by 0.34 μg/mL among trials with a daily vitamin D dose ≤4,000 IU and by 0.31 μg/mL among trials with time of vitamin D supplementation > 12 weeks. Conclusions: Vitamin D supplementation is beneficial for the reduction of hs-CRP inT2DM subjects but does not have a significant influence on TNF-α and IL-6 in T2DM subjects.