bluuebunny/crossref_metadata_2025 huggingface dataset:
Water-Handling Patterns and Associated Microbial Profiles in relation to Hygiene in Babati Town, Tanzania
Authors: Tesha Irene , Machunda Revocatus , Njau Karoli , Mpolya Emmanuel
Published: May 2019

Introduction. In rapidly urbanizing centres in Tanzania, water supply infrastructure lags behind the speed of urbanization, affecting water availability and accessibility. We believe that inhabitants’ access water using various ways which are characterizable and understanding them could inform about the risks to hygiene-related diseases. This study aimed at characterizing water-handling chains and their microbial profiles in Babati town to inform hygiene education policy and water supply planning. Methodology. A cross-sectional study design employing a proportional sampling for each of the 8 wards was conducted between November 2016 and March 2017. A total of 564 samples of water were collected using the USA EPA procedures from 37 randomly selected households. Water samples were collected from the common sources of water as well as from the downstream points to multiple storage containers. Using EPA membrane filtration techniques, two microorganisms were tested: fecal coliforms and Salmonella typhi. Results. Three water-handling chains/patterns in Babati town were determined, and they were as follows: (i) untreated-source-to-treated-reservoir-to-households (untrS2trR2HH) chain, (ii) untreated-source-to-untreated-reservoir-to-households (untrS2untrR2HH) chain; (iii) untreated-source-straight-to-households (untrS2HH) chain. In terms of the microbial profile, the most contaminated water-handling chain was the untreated-source-straight-to-households (untrS2HH). The number of users in these three chains was not statistically significantly different (p=0.5226), meaning that all people utilized the various chains almost equally, depending on the water situation. Most households (83%) did not treat their drinking water making those using the untreated-source-to-household chain (untrS2HH) most vulnerable to waterborne diseases. Conclusion. Determination of water-handling chains among the household is a novel approach which allows an understanding of the points at which highest fecal loading occurs. This approach therefore may inform the development of policies in the areas of household hygiene education, drinking water treatment, and water supply planning in urbanized towns in Tanzania and other developing countries.
Temperature Changes over the CORDEX-MENA Domain in the 21st Century Using CMIP5 Data Downscaled with RegCM4: A Focus on the Arabian Peninsula
Authors: Almazroui Mansour
Published: May 2019

This paper examined the temperature changes from the COordinated Regional climate Downscaling Experiment (CORDEX) over the Middle East and North Africa (MENA) domain called CORDEX-MENA. The focus is on the Arabian Peninsula in the 21st century, using data from three Coupled Model Intercomparison Project Phase 5 (CMIP5) models downscaled by RegCM4, a regional climate model. The analysis includes surface observations along with RegCM4 simulations and changes in threshold based on extreme temperature at the end of the 21st century relative to the base period (1971–2000). Irrespective of the driving CMIP5 models, the RegCM4 simulations show enhanced future temperature changes for RCP8.5 as compared to RCP4.5. The Arabian Peninsula will warm at a faster rate (0.83°C per decade) as compared to the entire domain (0.79°C per decade) for RCP8.5 during the period 2071–2100. Moreover, the number of hot days (Tmax ≥ 50°C) (cold nights: Tmin ≤ 5°C) will increase (decrease) faster in the Arabian Peninsula as compared to the entire domain. This increase (decrease) of hot days (cold nights) will be more prominent in the far future (2071–2100) as compared to the near future (2021–2050) period. Moreover, the future changes in temperature over the main cities in Saudi Arabia are also projected. The RegCM4-based temperature simulation data from two suitable CMIP5 models are recommended as a useful database for further climate-change-related studies.
Genetic Clearness Novel Strategy of Group IBacillusSpecies Isolated from Fermented Food and Beverages by Using Fibrinolytic Enzyme Gene Encoding a Serine-Like Enzyme
Authors: Kaya-Ongoto Moïse Doria , Kayath Christian Aimé , Nguimbi Etienne , Lebonguy Aimé Augustin , Nzaou Stech Anomène Eckzechel , Elenga Wilson Paola Sandra , Ahombo Gabriel
Published: May 2019

Fibrinolytic enzyme gene (fibE) is widely conserved amongBacillusspp. belonging to group I species. This is encoding a serine-like enzyme (FibE) secreted in extracellular medium. This present work aims to assess the molecular usefulness of this novel conserved housekeeping gene among group IBacillusspp. to identify and discriminate some related strains in traditional fermented food and beverages in Republic of Congo. First of all 155 isolates have been screened for enzymatic activities using caseinolytic assays. PCR techniques and nested PCR method using specific primers and correlated with 16S RNA sequencing were used. Blotting techniques have been performed for deep comparison with molecular methods. As a resultB. amyloliquefaciens (1),B. licheniformis (1),B. subtilis (1),B. pumilus (3),B. altitudinis(2),B. atrophaeus (1), andB. safensis (3)have been specifically identified among 155 isolates found in fermented food and beverages. Genetic analysis and overexpression of glutathione S-transferases (GSTs) fused to mature protein of FibE inEscherichia coliBL21 and TOP10 showed 2-fold higher enzymatic activities by comparison with FibE wild type one. Immunodetection should be associated but this does not clearly discriminateBacillusbelonging to group I.
Optimization Method for Irregular Piled Raft Foundation on Layered Soil Media
Authors: Xie Yunfei , Chi Shichun
Published: May 2019

Important buildings such as nuclear power plants always require stricter control of differential settlement than ordinary buildings. Therefore, it is necessary to provide an optimized design for the piled raft foundations of important buildings. In this paper, a new optimization method (using different pile diameters and different pile spacing) was proposed for the design of piled raft foundations. This method adjusts the pile diameters and pile spacing according to the stress distribution at the pile top of the initial design to achieve a more uniform settlement of the raft and stress distribution on top of piles, which can solve the differential settlement problems caused by uneven loads of the superstructure. After optimized design, the differential settlement and integral bending moment of the raft decreased more than 64% and 52%, respectively, and the differential stress on top of piles decreased by at least 63%. The new method proposed in this paper could be applied to large‐scale piled raft foundations with complex superstructure loads.
Prevalence and Predictors of Dysmenorrhea, Its Effect, and Coping Mechanisms among Adolescents in Shai Osudoku District, Ghana
Authors: Acheampong Kwabena , Baffour-Awuah Dorothy , Ganu Daniel , Appiah Stalla , Pan Xionfeng , Kaminga Atipatsa , Liu Aizhong
Published: May 2019

Background. Dysmenorrhea has been the most common gynecological problem worldwide. Reports of dysmenorrhea are greatest among individuals in their late teens and 20s and usually declining with age. It has also been reported that dysmenorrhea affects more than 80% of women in the reproductive age. The study objective was to examine the predictors of dysmenorrhea, its effect, and coping mechanisms among adolescents in Shai Osudoku District, Ghana. Methods. We conducted a cross-sectional study in September and November 2017 in selected schools in Shai Osudoku District, Ghana. We employed self-administered questionnaire to obtain data from adolescents volunteered to participate in the study. We analyzed the data using the SPSS programme IBM version 20. We used the Pearson chi-square test and multiple logistic regression analysis to assess the association between exposure variables and the outcome variable. The odds ratio was reported to establish the risk of dysmenorrhea at a confidence interval of 95%, and statistical significance was assumed at p<0.05. Results. The prevalence of dysmenorrhea was 68.1% (95% CI, 65.0–72.0) with one-third recounting their pain as severe. The pain during menstruation negatively influences the daily physical activities (22.5%), school attendance (6.9%), concentration during classes’ hours (27.9%), and academic performance (31.1%) of the respondents. Besides, adolescents who do not live with their parent experienced a 53.1% increase in odds of self-reporting dysmenorrhea (AOR, 1.53 (95% CI, 1.02–2.23)). Similarly, respondents who had irregular menstrual cycle experienced a 72.5% increase in odds of self-reporting dysmenorrhea (AOR, 1.73 (95% CI, 1.16–2.57)). Finally, a significant association between irregular menstrual cycle (p<0.01), not lived with their parent (p<0.04), and self-reported dysmenorrhea was found. Conclusion. This study establishes that dysmenorrhea is high among adolescents in Shai Osudoku District which negatively affects the daily activity of majority of them.
Dynamic Early Warning Method for Major Hazard Installation Systems in Chemical Industrial Park
Authors: Kong Yaguang , Xie Chenfeng , Zheng Song , Jiang Peng , Guan Meng , Wang Fang
Published: May 2019

The production and storage of major hazard installations (MHIs) bring potential risks to chemical industrial park (CIP). In the production system of MHIs, its dangerous degree is mainly determined by key parameters, and abnormal key parameters often lead to accidents. To predict the real‐time risk values of MHIs and improve accident prevention ability of CIP, we need a method that can combine dynamic prediction and assessment. Quantitative risk assessment (QRA) is not capable of modelling risk variations during the operation of a process. Therefore, this paper adopts the data‐driven approach. Inspired by visual qualitative analysis and quantitative analysis, a dynamic early warning method is proposed for MHIs. We can get the future trend of these key parameters by using strongly correlation variables to predict key parameters. Fuzzy evaluation analysis is performed on the risk levels of key parameters, and the dynamic evaluation index of these MHIs is obtained. This method can be applied to the dynamic evaluation of MHIs system in CIP. It can contribute to the safety of CIP in some aspects.
Coupling Ratio‐Based Design and Seismic Performance of Modular Prefabricated Hybrid Coupled Walls
Authors: Shi Yun , Zhang Yumin , Dai Jianbo , Weng Guangyuan
Published: May 2019

Based on the advantages of modular prefabricated multistory steel structure, a full‐bolt‐connected modular steel coupling beam‐hybrid coupled wall system is presented. Further, a method of estimating the coupling ratio (CR) is proposed according to the continuous link method. A CR‐based seismic design procedure is determined such that the structure utilizes the lateral stiffness of the shear wall, which is necessary to avoid structural damage under frequently occurring earthquakes. However, it also exhibits excellent ductility of the coupling beams, which is necessary for dissipating energy under infrequent earthquakes. Subsequently, nonlinear hysteretic analyses are conducted from finite element analysis software ABAQUS, and a parametric study based on the finite element technique is performed to identify the optimal value of the coupling ratio. Results indicate that the seismic performance of modular prefabricated HCWs was excellent, and the basic requirements for ductile behavior and lateral stiffness were satisfied for CR values from 50% to 60%. The obtained results confirm the accuracy of the CR‐based seismic design method proposed in this study and are supported by the selection of the design parameter at the initial design stage.
Low-Rank Deep Convolutional Neural Network for Multitask Learning
Authors: Su Fang , Shang Hai-Yang , Wang Jing-Yan
Published: May 2019

In this paper, we propose a novel multitask learning method based on the deep convolutional network. The proposed deep network has four convolutional layers, three max-pooling layers, and two parallel fully connected layers. To adjust the deep network to multitask learning problem, we propose to learn a low-rank deep network so that the relation among different tasks can be explored. We proposed to minimize the number of independent parameter rows of one fully connected layer to explore the relations among different tasks, which is measured by the nuclear norm of the parameter of one fully connected layer, and seek a low-rank parameter matrix. Meanwhile, we also propose to regularize another fully connected layer by sparsity penalty so that the useful features learned by the lower layers can be selected. The learning problem is solved by an iterative algorithm based on gradient descent and back-propagation algorithms. The proposed algorithm is evaluated over benchmark datasets of multiple face attribute prediction, multitask natural language processing, and joint economics index predictions. The evaluation results show the advantage of the low-rank deep CNN model over multitask problems.
Challenges and Prospects of Digital Core-Reconstruction Research
Authors: Zhu Linqi , Zhang Chong , Zhang Chaomo , Zhou Xueqing , Zhang Zhansong , Nie Xin , Liu Weinan , Zhu Boyuan
Published: May 2019

The simulation of various rock properties based on three-dimensional digital cores plays an increasingly important role in oil and gas exploration and development. The accuracy of 3D digital core reconstruction is important for determining rock properties. In this paper, existing 3D digital core-reconstruction methods are divided into two categories: 3D digital cores based on physical experiments and 3D digital core stochastic reconstructions based on two-dimensional (2D) slices. Additionally, 2D slice-based digital core stochastic reconstruction techniques are classified into four types: a stochastic reconstruction method based on 2D slice mathematical-feature statistical constraints, a stochastic reconstruction method based on statistical constraints that are related to 2D slice morphological characteristics, a physics process-based stochastic reconstruction method, and a hybrid stochastic reconstruction method. The progress related to these various stochastic reconstruction methods, the characteristics of constructed 3D digital cores, and the potential of these methods are analysed and discussed in detail. Finally, reasonable prospects are presented based on the current state of this research area. Currently, studies on digital core reconstruction, especially for the 3D digital core stochastic reconstruction method based on 2D slices, are still very rough, and much room for improvement remains. In particular, we emphasize the importance of evaluating functions, multiscale 3D digital cores, multicomponent 3D digital cores, and disciplinary intersection methods in the 3D construction of digital cores. These four directions should provide focus, alongside challenges, for this research area in the future. This review provides important insights into 3D digital core reconstruction.
Lipoprotein-Associated Phospholipase A2 Activity and Mass as Independent Risk Factor of Stroke: A Meta-Analysis
Authors: Hu Gaifeng , Liu Deping , Tong Huiyu , Huang Weijun , Hu Yunzhao , Huang Yuli
Published: May 2019

Background. The association between lipoprotein-associated phospholipase A2 (Lp-PLA2) and stroke risk is inconsistent. We conducted a meta-analysis to determine whether elevated Lp-PLA2 is a risk factor for stroke. Methods. Studies were included if they reported Lp-PLA2 mass and/or activity levels and adjusted risk estimates of stroke. The primary outcome was overall stroke incidence. The combined results were shown as relative risks (RRs) with 95% confidence intervals (CI) for per 1 standard deviation (SD) higher value of Lp-PLA2 and the highest versus lowest Lp-PLA2 category. Results. Twenty-two studies involving 157,693 participants were included for analysis. After adjusting for conventional risk factors, the RRs for overall stroke with 1 SD higher Lp-PLA2 activity and mass were 1.07 (95% CI 1.02–1.13) and 1.11 (95% CI 1.04–1.19), respectively. The RRs of ischemic stroke with 1 SD higher Lp-PLA2 activity and mass were 1.08 (95% CI 1.01–1.15) and 1.11 (95% CI 1.02–1.22), respectively. When comparing the highest and lowest levels of Lp-PLA2, the RRs of stroke for Lp-PLA2 activity and mass were 1.26 (95% CI 1.03–1.54) and 1.56 (95% CI 1.21–2.00), respectively. Finally, when comparing the highest and lowest levels of Lp-PLA2, the pooled RRs of ischemic stroke for Lp-PLA2 activity and mass were 1.29 (95% CI 1.07–1.56) and 1.68 (95% CI 1.12–2.53), respectively. Conclusions. Elevated baseline Lp-PLA2 levels, detected either by activity or mass, are associated with increased stroke risk.
Does Colonic Diverticulosis Raise the Risk of Colorectal Adenoma in Patients with Colorectal Cancer?
Authors: Kim Yeon-Ji , Kim Dae Bum , Chung Woo Chul , Lee Ji Min
Published: May 2019

Background. The aim of this study was to evaluate the risk of development of colorectal adenomas in patients with colorectal cancer (CRC) with and without colonic diverticulosis.Methods. We performed a retrospective cohort study that included patients with CRC between 2008 and 2011. All patients underwent preoperative colonoscopic and barium enema examinations. Follow-up colonoscopic examinations were performed within 1 year and between 3 and 5 years postoperatively. The incidence of colorectal adenomas was compared based on the presence or absence of diverticulosis. Additionally, multivariate logistic regression analysis was performed to identify the factors independently associated with the development of synchronous and metachronous colorectal adenomas.Results. Of the 168 patients with CRC included in the study, 55 showed colonic diverticulosis. Synchronous colorectal adenomas were more common in CRC patients with diverticulosis than in those without diverticulosis (P>0.001). Multivariate regression analysis showed that colonic diverticulosis (odds ratio (OR) 3.874, 95% confidence interval (CI) 1.843–8.144,P>0.001) and obesity (body mass index>25.0 kg/m2, OR 2.395, 95% CI 1.089–5.270,P=0.030) were associated with an increased risk of synchronous colorectal adenomas. The presence of synchronous colorectal adenomas increased the risk of metachronous colorectal adenomas (OR 4.407, 95% CI 1.855–10.473,P>0.001).Conclusions. Colonic diverticulosis was associated with synchronous colorectal adenomas in patients with CRC, which is eventually increasing the risk of metachronous adenomas.
Facing High EEG Signals Variability during Classification Using Fractal Dimension and Different Cutoff Frequencies
Authors: Salazar-Varas R. , Vazquez Roberto A.
Published: May 2019

In the development of a brain-computer interface (BCI), some issues should be regarded in order to improve its reliability and performance. Perhaps, one of the most challenging issues is related to the high variability of the brain signals, which directly impacts the accuracy of the classification. In this sense, novel feature extraction techniques should be explored in order to select those able to face this variability. Furthermore, to improve the performance of the selected feature extraction technique, the parameters of the filter applied in the preprocessing stage need to be properly selected. Then, this work presents an analysis of the robustness of the fractal dimension as feature extraction technique under high variability of the EEG signals, particularly when the training data are recorded one day and the testing data are obtained on a different day. The results are compared with those obtained by an autoregressive model, which is a technique commonly used in BCI applications. Also, the effect of properly selecting the cutoff frequencies of the filter in the preprocessing stage is evaluated. This research is supported by several experiments carried out using a public data set from the BCI international competition, specifically data set 2a from BCIIC IV, related to motor tasks. By a statistical test, it is demonstrated that the performance achieved using the fractal dimension is significantly better than that reached by the AR model. Also, it is demonstrated that the selection of the appropriate cutoff frequencies improves significantly the performance in the classification. The increase rate is approximately of 17%.
Evaluation of Gait Variable Change over Time as Transtibial Amputees Adapt to a New Prosthesis Foot
Authors: Zhang Xueyi , Fiedler Goeran , Liu Zhicheng
Published: May 2019

A variety of prescribed accommodation periods have been used in published prosthesis intervention studies that have examined biomechanical outcomes. Few investigators included repeated measurements in their study design, leaving questions as to how measured outcomes change as amputees acclimate to a new prosthesis. This paper is the product of our investigation as to whether measured gait variables were affected by the duration of accommodation period, and to assess the relationship between measured outcomes and the subjective perception of the participants. A sample of transtibial amputees were recruited for this study. Gait data was collected by wearable sensor repeatedly, starting immediately after fitting the interventional foot and extending over a subsequent four days. Participants indicated their perceived accommodation quality on a visual analog scale (VAS). A total of twelve commonly used spatiotemporal gait parameters were analyzed. Friedman tests were used to determine overall differences across time points in both early (one hour) and late (day two through five) accommodation phases, for each gait variable. Statistically significant changes across the early phase were found for variables gait speed χ2(2)=8.000, p=0.018, cadence χ2(2)=7.185, p=0.028, and double support time on the sound side χ2(2)=8.615, p=0.013. Across days two through five, no gait variable significantly changed. VAS scores correlated strongly with step count (r=1.000, p<0.001) and cadence (r=0.857, p=0.014). Longer accommodation periods resulted in less deviations of gait variables for the clinical assessment in the process of prosthetic rehabilitation. Trying out prosthetic interventions for less than one hour has yielded unreliable outcomes.
Vehicle Trajectory Reconstruction for Signalized Intersections with Low-Frequency Floating Car Data
Authors: Wang Hua , Gu Changlong , Ochieng Washington Yotto
Published: May 2019

Floating car data are beneficial in estimating traffic conditions in wide areas and are playing an increasing role in traffic surveillance. However, widespread application is limited by low-sample frequency which makes it hard to get a complete picture of a vehicle’s motion. An accurate and reliable reconstruction of a vehicle’s trajectory could effectively result in a higher sampling frequency enabling a more accurate estimation of road traffic parameters. Existing methods require additional information such as nearby vehicles, signal timing strategies, and queue patterns which are not always available. To address this problem, this paper presents a method used with low-sample frequency data to reconstruct vehicle trajectories through intersections, without the need for extra information. Furthermore, the additional parameters for the speed-time curve distributions for deceleration rate and acceleration rate are generated. A piecewise deceleration and acceleration model is developed to calculate the acceleration rate for different travel modes in the trajectory. The distribution parameters of the acceleration data for each travel mode are then estimated using a new Expectation Maximization (EM) algorithm. The acceleration statistics are then used to reconstruct the corresponding parts of the trajectory. Compared to the reference trajectories (truth), the test results show that the method developed in this paper achieves improvement in accuracy ranging from 16 to 67% over the commonly used linear interpolation method. In addition, the proposed method is not very sensitive to the sampling interval of the floating car data, unlike the linear interpolation method where the error grows rapidly with increasing sampling interval.
A Novel Comprehensive Model of Suitability Analysis for Matching Area in Underwater Geomagnetic Aided Inertial Navigation
Authors: Zhang Hongmei , Yang Le , Li Minglong
Published: May 2019

Geomagnetic aided inertial navigation is a way to use the geophysical field for navigation. It can locate the carrier position by the correlation between geomagnetic data and running track. It is an effective mean to realize autonomous navigation. Matching area suitability is one of the important factors affecting geomagnetic aided inertial navigation. Through the suitability analysis of matching areas, the areas with obvious geomagnetic features and rich information are selected as matching areas, which can effectively improve the real‐time and accuracy of geomagnetic aided navigation. However, matching area suitability analysis for geomagnetic aided navigation is a complex process and needs to consider diverse factors, based on which a decision may be made. The area suitability analysis inherently can be considered as a multicriterion decision analysis (MCDA) problem. This paper presented a novel comprehensive model combining principal component analysis (PCA) and analytical hierarchy process (AHP) to evaluate the suitability of the navigation matching area. Firstly, according to the features of the areas, key feature parameters and the corresponding weights are determined by PCA and AHP, respectively. Then comprehensive evaluation values of the navigation matching areas are calculated through the comprehensive model. Finally, experiments were implemented in Bohai Bay; the correlation‐matching algorithm is applied to verify the validity of the model in the areas. The experiment results well indicate the consistency between the comprehensive evaluation value and the matching area suitability. It is reasonable to regard the comprehensive evaluation value as a basis for area suitability analysis.
Protective Effects of Angong Niuhuang Pill on Early Atherosclerosis in ApoE-/- Mice by Reducing the Inflammatory Response
Authors: Chai Yushuang , Yin Zhen , Fan Qinghong , Zhang Zhe , Ye Kaihe , Xu Yimin , Xiao Wei , Chai Xiaomeng , Zhu Tao , Nie Hong
Published: May 2019

Atherosclerosis (AS) is the primary cause of cardiocerebrovascular disease, and inflammation is responsible for the initiation of its pathogenesis. Therefore, targeting inflammatory pathways to prevent AS progression is an ideal strategy. Angong Niuhuang pill (ANP) is a well-known traditional Chinese medicine and has been widely used for thousands of years to treat central nervous system and cardiovascular diseases. In this study, we investigated the role of ANP in reducing inflammation during early AS, using a high-fat diet-induced ApoE−/− mouse model of AS. Compared to those with simvastatin, ANP had no significant effect on serum triglyceride, low-density lipoprotein, and high-density lipoprotein levels. However, it effectively inhibited splenic and vascular inflammation. This agent also reduced the Th17/CD4+T ratio and mRNA expression of IL-6 and increased the Treg/CD4+T ratio and mRNA expression of TGF-β1. Thus, ANP restored Th17/Treg homeostasis in the spleen. It also regulated pro- and anti-inflammatory cytokine expression in the aorta in a similar manner. Further, it downregulated the expression of chemokine receptors (CCR2, CXCR3), their ligands (MCP-1, MCP-2, and MCP-3), and cell adhesion molecules (VCAM-1, ICAM-1) in arterial vessels. These results indicate that ANP can ameliorate the development of early AS, mainly by reducing inflammation instead of acting as an antihyperlipidemic drug.
Modulation of Target Antigen Density Improves CAR T-cell Functionality and Persistence
Authors: Ramakrishna Sneha , Highfill Steven L. , Walsh Zachary , Nguyen Sang M. , Lei Haiyan , Shern Jack F. , Qin Haiying , Kraft Ira L. , Stetler-Stevenson Maryalice , Yuan Constance M. , Hwang Jennifer D. , Feng Yang , Zhu Zhongyu , Dimitrov Dimiter , Shah Nirali N. , Fry Terry J.
Published: May 2019

Purpose:

Chimeric antigen receptor T-cell (CART) therapy targeting CD22 induces remission in 70% of patients with relapsed/refractory acute lymphoblastic leukemia (ALL). However, the majority of post-CD22 CART remissions are short and associated with reduction in CD22 expression. We evaluate the implications of low antigen density on the activity of CD22 CART and propose mechanisms to overcome antigen escape.

Experimental Design:

Using ALL cell lines with variable CD22 expression, we evaluate the cytokine profile, cytotoxicity, and in vivo CART functionality in the setting of low CD22 expression. We develop a high-affinity CD22 chimeric antigen receptor (CAR) as an approach to improve CAR sensitivity. We also assess Bryostatin1, a therapeutically relevant agent, to upregulate CD22 and improve CAR functionality.

Results:

We demonstrate that low CD22 expression negatively impacts in vitro and in vivo CD22 CART functionality and impairs in vivo CART persistence. Moreover, low antigen expression on leukemic cells increases naïve phenotype of persisting CART. Increasing CAR affinity does not improve response to low-antigen leukemia. Bryostatin1 upregulates CD22 on leukemia and lymphoma cell lines for 1 week following single-dose exposure, and improves CART functionality and in vivo persistence. While Bryostatin1 attenuates IFNγ production by CART, overall in vitro and in vivo CART cytotoxicity is not adversely affected. Finally, administration of Bryostain1 with CD22 CAR results in longer duration of in vivo response.

Conclusions:

We demonstrate that target antigen modulation is a promising strategy to improve CD22 CAR efficacy and remission durability in patients with leukemia and lymphoma.

See related commentary by Guedan and Delgado, p. 5188
Targeting IDH1 as a Prosenescent Therapy in High-grade Serous Ovarian Cancer
Authors: Dahl Erika S. , Buj Raquel , Leon Kelly E. , Newell Jordan M. , Imamura Yuka , Bitler Benjamin G. , Snyder Nathaniel W. , Aird Katherine M.
Published: May 2019

Epithelial ovarian cancer (EOC) is the deadliest gynecologic cancer. High-grade serous carcinoma (HGSC) is the most frequently diagnosed and lethal histosubtype of EOC. A significant proportion of patients with HGSC relapse with chemoresistant disease. Therefore, there is an urgent need for novel therapeutic strategies for HGSC. Metabolic reprogramming is a hallmark of cancer cells, and targeting metabolism for cancer therapy may be beneficial. Here, we found that in comparison with normal fallopian tube epithelial cells, HGSC cells preferentially utilize glucose in the TCA cycle and not for aerobic glycolysis. This correlated with universally increased TCA cycle enzyme expression in HGSC cells under adherent conditions. HGSC disseminates as tumor cell spheroids within the peritoneal cavity. We found that wild-type isocitrate dehydrogenase I (IDH1) is the only TCA cycle enzyme upregulated in both adherent and spheroid conditions and is associated with reduced progression-free survival. IDH1 protein expression is also increased in patients with primary HGSC tumors. Pharmacologic inhibition or knockdown of IDH1 decreased proliferation of multiple HGSC cell lines by inducing senescence. Mechanistically, suppression of IDH1 increased the repressive histone mark H3K9me2 at multiple E2F target gene loci, which led to decreased expression of these genes. Altogether, these data suggest that increased IDH1 activity is an important metabolic adaptation in HGSC and that targeting wild-type IDH1 in HGSC alters the repressive histone epigenetic landscape to induce senescence.

Implications:

Inhibition of IDH1 may act as a novel therapeutic approach to alter both the metabolism and epigenetics of HGSC as a prosenescent therapy.
IMPULS: Impulsivity-Focused Group Intervention to Reduce Binge Eating Episodes in Patients with Binge Eating Disorder – A Randomised Controlled Trial
Authors: Schag Kathrin , Rennhak Sina K. , Leehr Elisabeth J. , Skoda Eva-Maria , Becker Sandra , Bethge Wolfgang , Martus Peter , Zipfel Stephan , Giel Katrin Elisabeth
Published: May 2019

Background: Impulsivity is a risk factor for binge eating disorder, and binge eating (BE) equates to impulsive eating behaviour. Hence, we developed IMPULS, a cognitive behavioural group intervention focusing on impulsive eating. Methods: We randomised 41 patients to the IMPULS group and 39 to the control group. The IMPULS group participated in the IMPULS treatment, while both groups completed weekly self-observations. We compared both groups concerning BE episodes in the past 4 weeks at the end of treatment (primary outcome). As secondary outcomes, we investigated eating pathology, depression, general impulsivity and body mass index (BMI) at the end of treatment and in a 3-month follow-up. Results: The primary outcome failed, because BE episodes in the past 4 weeks were reduced in both groups at the end of treatment. At follow-up, the IMPULS group showed further improvement, contrary to the control group. The BE days/episodes in the 2 months before were overall reduced in both groups. Eating pathology was reduced in the IMPULS group at the end of treatment and partly in both groups at the follow-up. Depression was only reduced in the IMPULS group. General impulsivity and BMI did not change. Conclusions: The IMPULS study has a negative primary outcome. However, secondary outcomes indicate that the IMPULS treatment might be promising, as BE, eating pathology and depression were reduced in the IMPULS group. The initially reduced BE in the control group might represent a short-term effect from the self-observations. General impulsivity and BMI might need a longer time or more intensive treatment to change.
Racial Disparities, Outcomes, and Surgical Utilization among Hispanics with Esophageal Cancer: A Surveillance, Epidemiology, and End Results Program Database Analysis
Authors: Gupta Dave R. , Liu Yuan , Jiang Renjian , Walid Shaib , Higgins Kristin , Landry Jerome , McDonald Mark , Willingham Field F. , El-Rayes Bassel F. , Saba Nabil F.
Published: May 2019

Background: Hispanic patients with esophageal cancer (EC) have racially disparate survival outcomes compared with white patients. Objectives:We explored the impact on survival of racial differences in socioeconomic factors, tumor characteristics, and rates of surgical utilization in patients with EC. Method:Using the SEER (Surveillance, Epidemiology, and End Results) registry, we identified 22,531 cases of EC in Hispanic and white patients between the ages of 18 and 65 years in 2003–2014. Of these, 6,250 cases had locoregional EC. Patients were categorized according to age, gender, education, tumor grade, histology, primary tumor site, and surgical status. Postdiagnosis survival was examined over time and compared by race and stratified by surgical status. Results: Compared with whites, Hispanics with EC had significantly higher unadjusted mortality (hazard ratio [HR] 1.11; 95% confidence interval [CI] 1.06–1.17; p < 0.001) as did Hispanics with locoregional EC (HR 1.15; 95% CI 1.03–1.29; p = 0.01). In the multivariate analysis, several socioeconomic and tumor factors were found to be independently associated with survival by race, including county of residence income and prevalence of smoking, tumor grade, stage, and primary site, and surgical utilization. After adjusting for demographic and tumor characteristics, surgical utilization in patients with locoregional EC had a significant interaction with race on overall mortality (p = 0.01). Hispanics with locoregional EC were significantly less likely to receive surgery than whites (46 vs. 60%; p < 0.001) and not receiving surgery was associated with a significantly lower overall survival (HR 2.84; 95% CI 2.65–3.04; p < 0.001). Conclusions: A lower rate of surgery among Hispanics with potentially resectable esophageal cancer was associated with a decreased survival rate when compared to whites, even when adjusting for relevant socioeconomic and tumor factors. These data support the need to better address patient barriers to surgical treatment and the systemic biases present in medical care.
The International Academy of Cytology Yokohama System for Reporting Breast Fine Needle Aspiration Biopsy Cytopathology: A Single Institutional Retrospective Study of the Application of the System Categories and the Impact of Rapid Onsite Evaluation
Authors: Wong Stephen , Rickard Mary , Earls Peter , Arnold Lauren , Bako Barnabas , Field Andrew S.
Published: May 2019

Objectives: To review the performance and utility of the International Academy of Cytology (IAC) Yokohama System for Reporting Breast Fine Needle Aspiration Biopsy (FNAB) Cytology five category stratification and evaluate the impact of rapid onsite evaluation (ROSE). Method: A retrospective analysis of breast FNAB cytology cases with matched histopathological results at a single institution over a 32 months period using a structured reporting system with 5 diagnostic categories (“inadequate/insufficient,” “benign,” “atypical,” “suspicious of malignancy” and “malignant”) closely paralleling the proposed IAC System. Results: Of 2,696 breast FNAB cases, there were 579 with matched histopathology and 456 of these had ROSE. ROSE decreased the number in the “insufficient” category (17.1% without ROSE to 4.0% with ROSE) and increased the number in the “malignant” (17.9 to 39.0%) with a lesser impact on the “atypical,” “benign” and “suspicious of malignancy” categories. The performance data showed a positive predictive value of 96.4%, negative predictive value of 97.6%, and a risk of malignancy of a FNAB categorized as “insufficient” to be 2.6%, “benign” 1.7%, “atypical” 15.7%, “suspicious of malignancy” 84.6%, and “malignant” 99.5%. Conclusion: Breast FNAB is an accurate test enabling effective diagnosis of breast lesions. ROSE improved the performance by decreasing the proportion of “insufficient” and “atypical” and increasing the “suspicious of malignancy” and “malignant” diagnoses and enabling immediate triage for further biopsy where necessary.
Decreased Bleeding Incidence with Direct Oral Anticoagulants Compared to Vitamin K Antagonist and Low-Molecular-Weight Heparin in Patients with Sickle Cell Disease and Venous Thromboembolism
Authors: Patel Ameet , Williams Hants , Baer Maria R.  , Zimrin Ann B. , Law Jennie Y.
Published: May 2019

Background: Venous thromboembolism (VTE) is a recognized complication of sickle cell disease (SCD), yet the optimal pharmacologic anticoagulant is unknown. Methods: A retrospective single-institution cohort study of patients with SCD complicated by first VTE from January 2009 through July 2017 was performed using ICD 9/10 codes. Data collected included the anticoagulant used, VTE recurrence, and incidence of bleeding. Results: 109 patients with VTE were identified. SCD genotypes included HbSS in 92 (84%), HbSC in 13 (12%), and HbS-β+ thalassemia in 4 (4%). After the initial VTE event, 32 patients received a vitamin K antagonist (VKA), 34 for low-molecular-weight heparin (LMWH), and 43 for direct oral anticoagulants (DOACs). 16 patients (15%) experienced a clinically significant bleeding event, including 9 on VKA, 5 on LMWH, and 2 on DOACs. At a median follow-up of 11.8 (range, 3.4–60) months, 33 patients had a recurrent VTE, including 10 on VKA, 10 on LMWH, and 13 on DOACs (p = 0.833). Bleeding incidence was least with the DOACs, which were associated with fewer bleeding events (OR 0.22), and greatest with VKA (OR 1.55) (p < 0.05). Conclusion: There was no difference between VTE recurrence and choice of anticoagulation in SCD patients with VTE. Bleeding events were lower for DOACs compared to VKA or LMWH.
Eating with the enemy? Mimic complex between a stingless bee and assassin bugs
Authors: Alvarez Leopoldo Jesús , Zamudio Fernando , Melo Maria Cecilia
Published: May 2019

In this study, we record for the first time the genus Notocyrtus (Heteroptera, Reduviidae) from Argentina based on three species: Notocyrtus dorsalis (Gray), Notocyrtus dispersus Carvalho & Costa, and Notocyrtus foveatus Stål. We also describe and illustrate a mimetic complex comprising the three Notocyrtus species and Tetragona clavipes (Fabricius) (Apidae, Meliponini), that were collected on Bahuinia forficata Link (Leguminosae: Caesalpinioideae). We include biological comments on the plant-reduvid-bee interaction and hypothesize about the functionality of the mimetic complex described.
Distribution, threats and conservation of the White-collared Kite (Leptodon forbesi, Accipitridae), the most threatened raptor in the Neotropics
Authors: Pereira Glauco Alves , Araújo Helder Farias Pereira de , Azevedo Júnior Severino Mendes de , Angelieri Cíntia Camila Silva , Silveira Luís Fábio
Published: May 2019

The White-collared Kite (Leptodon forbesi) is an endemic and threatened raptor of the Brazilian Atlantic Forest. Here we present the known records of the species, describe the vegetation types where it was found and show Ecological Niche Models generated using Maxent algorithm. Most of the presence data were recorded in open ombrophilous forest and seasonal semideciduous forest in the states of Alagoas and Pernambuco. Maxent model had a good performance (AUC = 0.982 ± 0.004 SD), showing higher suitability for the species from Paraíba to Alagoas states. Maxent average model revealed a distribution range of 20,344 km² and an area of occupancy of 1,636.89 km². The most suitable areas for the species are those near watercourses and streams. We suggest the creation of protected areas, including private ones, and possible restoration actions to connect the most suitable forest fragments, along with the captive breeding, as the most appropriate strategies for the conservation of the White-collared Kite.
Proteomic Bioprofiles and Mechanistic Pathways of Progression to Heart Failure
Authors: Ferreira João Pedro , Verdonschot Job , Collier Timothy , Wang Ping , Pizard Anne , Bär Christian , Björkman Jens , Boccanelli Alessandro , Butler Javed , Clark Andrew , Cleland John G. , Delles Christian , Diez Javier , Girerd Nicolas , González Arantxa , Hazebroek Mark , Huby Anne-Cécile , Jukema Wouter , Latini Roberto , Leenders Joost , Levy Daniel , Mebazaa Alexandre , Mischak Harald , Pinet Florence , Rossignol Patrick , Sattar Naveed , Sever Peter , Staessen Jan A. , Thum Thomas , Vodovar Nicolas , Zhang Zhen-Yu , Heymans Stephane , Zannad Faiez
Published: May 2019

Background

Identifying the mechanistic pathways potentially associated with incident heart failure (HF) may provide a basis for novel preventive strategies.

Methods and Results

To identify proteomic biomarkers and the potential underlying mechanistic pathways that may be associated with incident HF defined as the first hospitalization for HF, a nested-matched case-control design was used with cases (incident HF) and controls (without HF) selected from 3 cohorts (>20 000 individuals). Controls were matched on cohort, follow-up time, age, and sex. Two independent sample sets (a discovery set with 286 cases and 591 controls and a replication set with 276 cases and 280 controls) were used to discover and replicate the findings. Two hundred fifty-two circulating proteins in the plasma were studied. Adjusting for the matching variables age, sex, and follow-up time (and correcting for multiplicity of tests), 89 proteins were found to be associated with incident HF in the discovery phase, of which 38 were also associated with incident HF in the replication phase. These 38 proteins pointed to 4 main network clusters underlying incident HF: (1) inflammation and apoptosis, indicated by the expression of the TNF (tumor necrosis factor)-family members; (2) extracellular matrix remodeling, angiogenesis and growth, indicated by the expression of proteins associated with collagen metabolism, endothelial function, and vascular homeostasis; (3) blood pressure regulation, indicated by the expression of natriuretic peptides and proteins related to the renin-angiotensin-aldosterone system; and (4) metabolism, associated with cholesterol and atherosclerosis.

Conclusions

Clusters of biomarkers associated with mechanistic pathways leading to HF were identified linking inflammation, apoptosis, vascular function, matrix remodeling, blood pressure control, and metabolism. These findings provide important insight on the pathophysiological mechanisms leading to HF.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT02556450.
Proteasome-Dependent Regulation of Distinct Metabolic States During Long-Term Culture of Human iPSC-Derived Cardiomyocytes
Authors: Ebert Antje , Joshi Amit U. , Andorf Sandra , Dai Yuanyuan , Sampathkumar Shrivatsan , Chen Haodong , Li Yingxin , Garg Priyanka , Toischer Karl , Hasenfuss Gerd , Mochly-Rosen Daria , Wu Joseph C.
Published: May 2019

Rationale:

The immature presentation of human induced pluripotent stem cell–derived cardiomyocytes (iPSC-CMs) is currently a challenge for their application in disease modeling, drug screening, and regenerative medicine. Long-term culture is known to achieve partial maturation of iPSC-CMs. However, little is known about the molecular signaling circuitries that govern functional changes, metabolic output, and cellular homeostasis during long-term culture of iPSC-CMs.

Objective:

We aimed to identify and characterize critical signaling events that control functional and metabolic transitions of cardiac cells during developmental progression, as recapitulated by long-term culture of iPSC-CMs.

Methods and Results:

We combined transcriptomic sequencing with pathway network mapping in iPSC-CMs that were cultured until a late time point, day 200, in comparison to a medium time point, day 90, and an early time point, day 30. Transcriptomic landscapes of long-term cultured iPSC-CMs allowed mapping of distinct metabolic stages during development of maturing iPSC-CMs. Temporally divergent control of mitochondrial metabolism was found to be regulated by cAMP/PKA (protein kinase A)- and proteasome-dependent signaling events. The PKA/proteasome-dependent signaling cascade was mediated downstream by Hsp90 (heat shock protein 90), which in turn modulated mitochondrial respiratory chain proteins and their metabolic output. During long-term culture, this circuitry was found to initiate upregulation of iPSC-CM metabolism, resulting in increased cell contractility that reached a maximum at the day 200 time point.

Conclusions:

Our results reveal a PKA/proteasome- and Hsp90-dependent signaling pathway that regulates mitochondrial respiratory chain proteins and determines cardiomyocyte energy production and functional output. These findings provide deeper insight into signaling circuitries governing metabolic homeostasis in iPSC-CMs during developmental progression.