bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Tetramethylpyrazine on Atherosclerosis and SCAP/SREBP‐1c Signaling Pathway in ApoE−/− Mice Fed with a High‐Fat Diet
Authors: Zhang Ying , Ren Pan , Kang Qunfu , Liu Weihong , Li Sinai , Li Ping , Liu Hongxu , Shang Juju , Zhang Lei , Gong Yanbing , Zhou Mingxue
Published: April 2017

Lipid metabolism dysregulation plays a crucial role in the occurrence of atherosclerosis (As). SCAP/SREBP signaling is the main pathway for regulating lipid metabolism. Tetramethylpyrazine (TMP), a Traditional Chinese Medicine (TCM) for treating angina pectoris, has antiatherosclerotic effects and ameliorates blood lipids disturbance. However, its precise mechanism remains unclear. This study investigated the mechanism of TMP in ameliorating As in mice model. After six weeks of high‐fat diet, 30 ApoE−/− mice were randomized (n = 10) and treated with Lipitor, TMP, or distilled water for six weeks. The serum blood lipids and insulin levels were measured. The expressions of PAQR3, Insig‐1, SCAP, SREBP‐1c, IRS‐1, PI3K, Akt, and mTORC‐1 in the adipose tissues were determined. The results showed that TMP could significantly decrease blood lipids levels, insulin, and corrected plaque area of the ApoE−/− mice as compared to the untreated mice (P < 0.05, P < 0.01). Moreover, TMP could significantly downregulate the expressions of SCAP, SREBP‐1c, PAQR3, IRS‐1, PI3K, Akt, and mTORC1 (P < 0.01). Thus, TMP may ameliorate lipid metabolism disorder and As by downregulating PAQR3 and inhibiting SCAP/SREBP‐1c signaling pathway. In addition, PI3K/Akt/mTORC1 signaling pathway may be involved in this process.
Adsorption of Cr(VI) onto Hybrid Membrane of Carboxymethyl Chitosan and Silicon Dioxide
Authors: Deng Yanling , Kano Naoki , Imaizumi Hiroshi
Published: April 2017

In this study, a new adsorbent material was synthesized by using carboxymethyl chitosan and silicon dioxide. The hybrid membrane was used as an adsorbent for the removal of Cr(VI) from aqueous solutions. The adsorption potential of Cr(VI) by the hybrid materials was investigated by varying experimental conditions such as pH, contact time, and the dosage of the hybrid membrane. Adsorption isotherms of Cr(VI) onto the hybrid membrane were studied with varying initial concentrations under optimum experiment conditions. The surface property of the hybrid membrane was characterized by SEM (scanning electron microscope) and Fourier transform infrared spectrometer (FTIR). The concentrations of Cr(VI) in solution are determined by ICP-AES (inductively coupled plasma atomic emission spectrometry). The present study investigates the adsorption mechanisms of Cr(VI) onto the hybrid membrane. The results provide new insight, demonstrating that the modified hybrid membrane can be an efficient adsorbent for Cr(VI) from the aqueous solution.
Depression Disorder Classification of fMRI Data Using Sparse Low-Rank Functional Brain Network and Graph-Based Features
Authors: Wang Xin , Ren Yanshuang , Zhang Wensheng
Published: April 2017

Study of functional brain network (FBN) based on functional magnetic resonance imaging (fMRI) has proved successful in depression disorder classification. One popular approach to construct FBN is Pearson correlation. However, it only captures pairwise relationship between brain regions, while it ignores the influence of other brain regions. Another common issue existing in many depression disorder classification methods is applying only single local feature extracted from constructed FBN. To address these issues, we develop a new method to classify fMRI data of patients with depression and healthy controls. First, we construct the FBN using a sparse low-rank model, which considers the relationship between two brain regions given all the other brain regions. Moreover, it can automatically remove weak relationship and retain the modular structure of FBN. Secondly, FBN are effectively measured by eight graph-based features from different aspects. Tested on fMRI data of 31 patients with depression and 29 healthy controls, our method achieves 95% accuracy, 96.77% sensitivity, and 93.10% specificity, which outperforms the Pearson correlation FBN and sparse FBN. In addition, the combination of graph-based features in our method further improves classification performance. Moreover, we explore the discriminative brain regions that contribute to depression disorder classification, which can help understand the pathogenesis of depression disorder.
Association between Asymptomatic Unilateral Internal Carotid Artery Stenosis and Electrophysiological Function of the Retina and Optic Nerve
Authors: Machalińska Anna , Kowalska-Budek Aleksandra , Kawa Miłosz Piotr , Kazimierczak Arkadiusz , Safranow Krzysztof , Kirkiewicz Marta , Wilk Grażyna , Lubiński Wojciech , Gutowski Piotr , Machaliński Bogusław
Published: April 2017

Purpose. This study was designed to assess retinal and optic nerve bioelectrical function in patients with unilateral asymptomatic but hemodynamically significant internal carotid artery stenosis (ICAS).Methods. Forty-two subjects with a diagnosis of unilateral ICAS and 34 controls were analyzed. Full-field electroretinogram (ERG), pattern electroretinogram (PERG), and pattern visual-evoked potentials, as well as optical coherence tomography and ophthalmological examination, were performed. Data analysis included eyes ipsilateral to ICAS (EIS) and eyes contralateral to ICAS (ECS).Results. Intraocular pressure was significantly decreased in EIS and ECS compared to that in the controls. In the macula, both the cube average thickness and cube volume values were significantly reduced both in EIS and ECS compared to those in the controls. Similarly, PERG P50 and N95 wave amplitudes were significantly smaller in EIS and ECS compared to those in the controls. The ERG rod b-wave and rod-cone a-wave amplitudes were decreased, and implicit times were significantly prolonged, whereas the OP wave index was reduced in EIS compared to that in the controls. No differences in IOP, OCT, or ERG and PERG parameters were identified between EIS and ECS.Conclusions.Our study demonstrated that retinal bioelectrical function is negatively affected by ICAS despite the absence of objective clinical signs and symptoms of ocular ischemia.
Therapeutic Potentials of Synapses after Traumatic Brain Injury: A Comprehensive Review
Authors: Wen Zunjia , Li Dong , Shen Meifen , Chen Gang
Published: April 2017

Massive studies have focused on the understanding of the pathobiology of cellular and molecular changes and injury mechanisms after traumatic brain injury (TBI), but very few studies have specially discussed the role of synapses in the context of TBI. This paper specifically highlights the role and therapeutic potentials of synapses after TBI. First, we review and conclude how synapses interact with constant structural, metabolic, neuroendocrine, and inflammatory mechanisms after TBI. Second, we briefly describe several key synaptic proteins involved in neuroplasticity, which may be novel neuronal targets for specific intervention. Third, we address therapeutic interventions in association with synapses after TBI. Finally, we concisely discuss the study gaps in the synapses after TBI, in hopes that this would provide more insights for future studies. Synapses play an important role in TBI; while the understandings on the synaptic participation in the treatments and prognosis of TBI are lacking, more studies in this area are warranted.
Variable Speed Limit Signs: Control and Setting Locations in Freeway Work Zones
Authors: Wang Wei , Cheng Zeyang
Published: April 2017

Variable Speed Limit Sign (VSLS) Systems enable speed limits to be changed dynamically in response to traffic conditions so that traffic incidents can be reduced significantly on freeway work zones. In this paper, we examined how many and where VSLS are to be placed and the speed limits to be set and proposed a bilevel programming model to perform this decision making operation. The appropriate speed limits and deployments of VSLS were got by case study, and they were analyzed by a simulation to prove the empirical features of traffic breakdown at freeway work zones. Then the results of model comparison and simulation evaluation illustrate that the proposed method outperforms existing models in terms of maximizing information benefit and minimizing average queue length, total delay, and total stop frequency on the freeway work zone.
Clinical Assessment of the Congenital Absence of Palmaris Longus and Flexor Digitorum Superficialis Muscles in Young Saudi Population
Authors: Alzahrani Mohammed Talal , Almalki Mohammad Abdullah , Al-Thunayan Turki Abdullah , Almohawis Amjaad Hamad , Al Turki Ahmed Turki , Umedani Loung
Published: April 2017

Introduction.Congenital Palmaris Longus (PL) absence was found in 15%–20.25% of population globally. This condition and Flexor Digitorum Superficialis (FDS) tendon absence in little finger are not known in Saudi Arabia. We studied prevalence of PL and FDS agenesis in Saudi Arabian population.Methods.A random cross-sectional study was carried out after an ethical approval in the Riyadh universities. Schaeffer’s test was used to examine PL absence. The Modified test was used to examine FDS absence. Data was analyzed using Microsoft Excel and the SPSS Software version 22.Results.The volunteers, 331, males 164 (49.5%) and females 167 (50.5%), mean age of 23 (SD ± 5.3), showed right hand dominance in 294 (88.8%) and bilateral absence of PL and FDS in 15.1% and 14.8%, respectively. The hand dominance showed no significant relation between PL and FDS absence,pvalue = 0.788, 0.835, respectively. Generally, we found a weak correlation between absence of the PL and FDS,pvalue ≥ 0.595.Conclusion.The bilateral absence of PL and FDS was found as 15.1% and 14.8%, respectively. Variation of the FDS tendon absence was an independent entity for the PL absence. The dominance of hands was not related to the tested variables found in PL and FDS agenesis.
Mining of Microbial Genomes for the Novel Sources of Nitrilases
Authors: Sharma Nikhil , Thakur Neerja , Raj Tilak , Savitri  , Bhalla Tek Chand
Published: April 2017

Next-generation DNA sequencing (NGS) has made it feasible to sequence large number of microbial genomes and advancements in computational biology have opened enormous opportunities to mine genome sequence data for novel genes and enzymes or their sources. In the present communication in silico mining of microbial genomes has been carried out to find novel sources of nitrilases. The sequences selected were analyzed for homology and considered for designing motifs. The manually designed motifs based on amino acid sequences of nitrilases were used to screen 2000 microbial genomes (translated to proteomes). This resulted in identification of one hundred thirty-eight putative/hypothetical sequences which could potentially code for nitrilase activity. In vitro validation of nine predicted sources of nitrilases was done for nitrile/cyanide hydrolyzing activity. Out of nine predicted nitrilases, Gluconacetobacter diazotrophicus, Sphingopyxis alaskensis, Saccharomonospora viridis, and Shimwellia blattae were specific for aliphatic nitriles, whereas nitrilases from Geodermatophilus obscurus, Nocardiopsis dassonvillei, Runella slithyformis, and Streptomyces albus possessed activity for aromatic nitriles. Flavobacterium indicum was specific towards potassium cyanide (KCN) which revealed the presence of nitrilase homolog, that is, cyanide dihydratase with no activity for either aliphatic, aromatic, or aryl nitriles. The present study reports the novel sources of nitrilases and cyanide dihydratase which were not reported hitherto by in silico or in vitro studies.
Fix‐and‐Optimize and Variable Neighborhood Search Approaches for Stochastic Multi‐Item Capacitated Lot‐Sizing Problems
Authors: Li Liuxi , Song Shiji , Wu Cheng , Wang Rui
Published: April 2017

We discuss stochastic multi‐item capacitated lot‐sizing problems with and without setup carryovers (also known as link lot size), S‐MICLSP and S‐MICLSP‐L. The two models are motivated from a real‐world steel enterprise. To overcome the nonlinearity of the models, a piecewise linear approximation method is proposed. We develop a new fix‐and‐optimize (FO) approach to solve the approximated models. Compared with the existing FO approach(es), our FO is based on the concept of “k‐degree‐connection” for decomposing the problems. Furthermore, we also propose an integrative approach combining our FO and variable neighborhood search (FO‐VNS), which can improve the solution quality of our FO approach by diversifying the search space. Numerical experiments are performed on the instances following the nature of realistic steel products. Our approximation method is shown to be efficient. The results also show that the proposed FO and FO‐VNS approaches significantly outperform the recent FO approaches, and the FO‐VNS approaches can be more outstanding on the solution quality with moderate computational effort.
Node-Structured Integrative Gaussian Graphical Model Guided by Pathway Information
Authors: Kim SungHwan , Jhong Jae-Hwan , Lee JungJun , Koo Ja-Yong , Lee ByungYong , Han SungWon
Published: April 2017

Up to date, many biological pathways related to cancer have been extensively applied thanks to outputs of burgeoning biomedical research. This leads to a new technical challenge of exploring and validating biological pathways that can characterize transcriptomic mechanisms across different disease subtypes. In pursuit of accommodating multiple studies, the joint Gaussian graphical model was previously proposed to incorporate nonzero edge effects. However, this model is inevitably dependent on post hoc analysis in order to confirm biological significance. To circumvent this drawback, we attempt not only to combine transcriptomic data but also to embed pathway information, well-ascertained biological evidence as such, into the model. To this end, we propose a novel statistical framework for fitting joint Gaussian graphical model simultaneously with informative pathways consistently expressed across multiple studies. In theory, structured nodes can be prespecified with multiple genes. The optimization rule employs the structured input-output lasso model, in order to estimate a sparse precision matrix constructed by simultaneous effects of multiple studies and structured nodes. With an application to breast cancer data sets, we found that the proposed model is superior in efficiently capturing structures of biological evidence (e.g., pathways). An R software package nsiGGM is publicly available at author’s webpage.
Volatile Composition and Enantioselective Analysis of Chiral Terpenoids of Nine Fruit and Vegetable Fibres Resulting from Juice Industry By-Products
Authors: Marsol-Vall Alexis , Sgorbini Barbara , Cagliero Cecilia , Bicchi Carlo , Eras Jordi , Balcells Mercè
Published: April 2017

Fruit and vegetable fibres resulting as by-products of the fruit juice industry have won popularity because they can be valorised as food ingredients. In this regard, bioactive compounds have already been studied but little attention has been paid to their remaining volatiles. Considering all the samples, 57 volatiles were identified. Composition greatly differed between citrus and noncitrus fibres. The former presented over 90% of terpenoids, with limonene being the most abundant and ranging from 52.7% in lemon to 94.0% in tangerine flesh. Noncitrus fibres showed more variable compositions, with the predominant classes being aldehydes in apple (57.5%) and peach (69.7%), esters (54.0%) in pear, and terpenoids (35.3%) in carrot fibres. In addition, enantioselective analysis of some of the chiral terpenoids present in the fibre revealed that the enantiomeric ratio for selected compounds was similar to the corresponding volatile composition of raw fruits and vegetables and some derivatives, with the exception of terpinen-4-ol andα-terpineol, which showed variation, probably due to the drying process. The processing to which fruit residues were submitted produced fibres with low volatile content for noncitrus products. Otherwise, citrus fibres analysed still presented a high volatile composition when compared with noncitrus ones.
Estimating Snow Depth and Snow Water Equivalence Using Repeat-Pass Interferometric SAR in the Northern Piedmont Region of the Tianshan Mountains
Authors: Li Hui , Wang Zuo , He Guangjun , Man Wang
Published: April 2017

Snow depth and Snow Water Equivalence (SWE) are important parameters for hydrological applications. In this application, a theoretical method of snow depth estimation with repeat-pass InSAR measurements was proposed, and a preliminary sensitivity analysis of snow phase changes versus the incident angle and snow density was developed. Moreover, the snow density and incident angle parameters were analyzed and calibrated, and the local incident angle was used as a substitute for the satellite incident angle to improve the snow depth estimation. From the results, the coherence images showed that a high degree of coherence can be found for dry snow, and, apart from the effect of snow, land use/cover change due to a long temporal baseline and geometric distortion due to the rugged terrain were the main constraints for InSAR technique to measure snow depth and SWE in this area. The result of snow depth estimation between July 2008 and February 2009 demonstrated that the average snow depth was about 20 cm, which was consistent with the field survey results. The areal coverage of snow distribution estimated from the snow depth and SWE results was consistent with snow cover obtained from HJ-1A CCD optical data at the same time.
Pathogenic Variant in ACTB, p.Arg183Trp, Causes Juvenile-Onset Dystonia, Hearing Loss, and Developmental Delay without Midline Malformation
Authors: Conboy Erin , Vairo Filippo , Waggoner Darrel , Ober Carole , Das Soma , Dhamija Radhika , Klee Eric W. , Pichurin Pavel
Published: April 2017

ACTB encodes the β-actin, and pathogenic variations in this gene have typically been associated with Baraitser-Winter cerebrofrontofacial syndrome, a congenital malformation syndrome characterized by short stature, craniofacial anomalies, and cerebral anomalies. Here, we describe the third case with the p.Arg183Trp variant in ACTB causing juvenile-onset dystonia. Our patient has severe, intractable dystonia, developmental delay, and sensorineural hearing loss, besides hyperintensities in the caudate nuclei and putamen on the brain MRI, which is a distinct but overlapping phenotype with the previously reported case of identical twins with the same alteration in ACTB.
Clinical Analysis of Ocular Parameters Contributing to Intraoperative Pain during Standard Phacoemulsification
Authors: Kang Yong Koo , Kim Myung Jun , Kim Hong Kyun , Chun Bo Young
Published: April 2017

Purpose. To study the correlation between ocular parameters and subjective pain that patients perceived during phacoemulsification.Methods. Medical records of 142 patients who underwent standard phacoemulsification under topical anesthesia between March and August 2016 were retrospectively reviewed. The pain during phacoemulsification and 1 h after surgery was assessed and compared using a visual analog scale. In addition, demographic data, preoperative biometric parameters, and intraoperative surgical parameters were recorded.Results. Mean age of patients was 67.49 ± 12.50 years. The mean pain score was 2.26 ± 0.85 during phacoemulsification and 0.40 ± 0.69 postoperatively. Intraoperative pain was significantly associated with higher preoperative intraocular pressure (β = 0.220,P=0.016), greater anterior chamber depth (β = 0.210,P=0.028), and greater axial length (β = 0.181,P=0.043).Conclusions. To reduce the subjective pain when patients have high preoperative intraocular pressure, large anterior chamber depth, or great axial length, supplementary procedures may be required.
A Randomized Clinical Trial Comparing the Effectiveness of Electroacupuncture versus Medium‐Frequency Electrotherapy for Discogenic Sciatica
Authors: Zhang Xue , Wang Yang , Wang Zhao , Wang Chao , Ding Wentao , Liu Zhishun
Published: April 2017

Objective. To investigate the short‐ and long‐term effects of electroacupuncture (EA) compared with medium‐frequency electrotherapy (MFE) on chronic discogenic sciatica. Methods. One hundred participants were randomized into two groups to receive EA (n = 50) or MFE (n = 50) for 4 weeks. A 28‐week follow‐up of the two groups was performed. The primary outcome measure was the average leg pain intensity. The secondary outcome measures were the low back pain intensity, Oswestry Disability Index (ODI), patient global impression (PGI), drug use frequency, and EA acceptance. Results. The mean changes in the average leg pain numerical rating scale (NRS) scores were 2.30 (1.86–2.57) and 1.06 (0.62–1.51) in the EA and MFE groups at week 4, respectively. The difference was significant (P < 0.001). The long‐term follow‐up resulted in significant differences. The average leg pain NRS scores decreased by 2.12 (1.70–2.53) and 0.36 (−0.05–0.78) from baseline in the EA and MFE groups, respectively, at week 28. However, low back pain intensity and PGI did not differ significantly at week 4. No serious adverse events occurred. Conclusions. EA showed greater short‐term and long‐term benefits for chronic discogenic sciatica than MFE, and the effect of EA was superior to that of MFE. The study findings warrant verification. This trial was registered under identifier ChiCTR-IPR-15006370.
Incidence and Contributing Factors of Persistent Hyperglycemia at 6–12 Weeks Postpartum in Iranian Women with Gestational Diabetes: Results from LAGA Cohort Study
Authors: Nouhjah Sedigheh , Shahbazian Hajieh , Shahbazian Nahid , Jahanshahi Alireza , Jahanfar Shayesteh , Cheraghian Bahman
Published: April 2017

Background. A history of gestational diabetes is an important predictor of many metabolic disturbances later in life.Method. Life after gestational diabetes Ahvaz Study (LAGAs) is an ongoing population-based cohort study. Up to February 2016, 176 women with gestational diabetes underwent a 75 g oral glucose tolerance test (OGTT) at 6–12 weeks postpartum in Ahvaz (southwestern of Iran). Gestational diabetes was diagnosed according to the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria and the American Diabetes Association (ADA) criteria applied for diagnosis of postpartum prediabetes and diabetes. Univariate and multivariate regression analysis were done.Results. Overall incidence of early postpartum glucose intolerance was 22.2% (95% CI, 16.3–29.0), 17.6% prediabetes (95% CI, 12.3–24.1) and 4.5% diabetes (95% CI, 2.0–8.8%). Independent risk factors for glucose intolerance were FPG ≥ 100 at the time of OGTT (OR 3.86; 95% CI; 1.60–9.32), earlier diagnosis of GDM (OR 0.92; 95% CI; 0.88–0.97), systolic blood pressure (OR 1.02; 95% CI; 1.002–1.04), and insulin or metformin therapy (OR 3.14; 95% CI; 1.20–8.21).Conclusion. Results determined a relatively high rate of glucose intolerance at 6–12 weeks after GDM pregnancy. Early postpartum screening of type 2 diabetes is needed particularly in women at high risk of type 2 diabetes.
Electromagnetic Shielding Characteristics of Eco-Friendly Foamed Concrete Wall
Authors: Cho Sung-Sil , Kim Jin-Man , Hong Ic-Pyo
Published: April 2017

The electromagnetic shielding characteristics according to the material composition of foamed concrete, which was manufactured to reduce environmental pollution and to economically apply it in actual building walls, were researched herein. Industrial by-products such as ladle furnace slag (LFS), gypsum, and blast furnace slag (BFS) were added to manufacture foamed concrete with enhanced functionalities such as lightweight, heat insulation, and sound insulation. The electrical characteristics such as permittivity and loss tangent according to the foam and BFS content were calculated and measured. Free space measurement was used to measure the electromagnetic shielding characteristics of the actually manufactured foamed concrete. It was confirmed that electromagnetic signals were better blocked when the foam content was low and the BFS content was high in the measured frequency bands (1–8 GHz) and that approximately 90% of the electromagnetic signals were blocked over 4 GHz.
Color Confinement and Spatial Dimensions in the Complex-Sedenion Space
Authors: Weng Zi-Hua
Published: April 2017

The paper aims to apply the complex-sedenions to explore the wave functions and field equations of non-Abelian gauge fields, considering the spatial dimensions of a unit vector as the color degrees of freedom in the complex-quaternion wave functions, exploring the physical properties of the color confinement essentially. J. C. Maxwell was the first to employ the quaternions to study the electromagnetic fields. His method inspires subsequent scholars to introduce the quaternions, octonions, and sedenions to research the electromagnetic field, gravitational field, and nuclear field. The application of complex-sedenions is capable of depicting not only the field equations of classical mechanics, but also the field equations of quantum mechanics. The latter can be degenerated into the Dirac equation and Yang-Mills equation. In contrast to the complex-number wave function, the complex-quaternion wave function possesses three new degrees of freedom, that is, three color degrees of freedom. One complex-quaternion wave function is equivalent to three complex-number wave functions. It means that the three spatial dimensions of unit vector in the complex-quaternion wave function can be considered as the “three colors”; naturally the color confinement will be effective. In other words, in the complex-quaternion space, the “three colors” are only the spatial dimensions, rather than any property of physical substance.
An Ex Vivo Platform for the Prediction of Clinical Response in Multiple Myeloma
Authors: Silva Ariosto , Silva Maria C. , Sudalagunta Praneeth , Distler Allison , Jacobson Timothy , Collins Aunshka , Nguyen Tuan , Song Jinming , Chen Dung-Tsa , Chen Lu , Cubitt Christopher , Baz Rachid , Perez Lia , Rebatchouk Dmitri , Dalton William , Greene James , Gatenby Robert , Gillies Robert , Sontag Eduardo , Meads Mark B. , Shain Kenneth H.
Published: April 2017

Multiple myeloma remains treatable but incurable. Despite a growing armamentarium of effective agents, choice of therapy, especially in relapse, still relies almost exclusively on clinical acumen. We have developed a system, Ex vivo Mathematical Myeloma Advisor (EMMA), consisting of patient-specific mathematical models parameterized by an ex vivo assay that reverse engineers the intensity and heterogeneity of chemosensitivity of primary cells from multiple myeloma patients, allowing us to predict clinical response to up to 31 drugs within 5 days after bone marrow biopsy. From a cohort of 52 multiple myeloma patients, EMMA correctly classified 96% as responders/nonresponders and correctly classified 79% according to International Myeloma Working Group stratification of level of response. We also observed a significant correlation between predicted and actual tumor burden measurements (Pearson r = 0.5658, P < 0.0001). Preliminary estimates indicate that, among the patients enrolled in this study, 60% were treated with at least one ineffective agent from their therapy combination regimen, whereas 30% would have responded better if treated with another available drug or combination. Two in silico clinical trials with experimental agents ricolinostat and venetoclax, in a cohort of 19 multiple myeloma patient samples, yielded consistent results with recent phase I/II trials, suggesting that EMMA is a feasible platform for estimating clinical efficacy of drugs and inclusion criteria screening. This unique platform, specifically designed to predict therapeutic response in multiple myeloma patients within a clinically actionable time frame, has shown high predictive accuracy in patients treated with combinations of different classes of drugs. The accuracy, reproducibility, short turnaround time, and high-throughput potential of this platform demonstrate EMMA's promise as a decision support system for therapeutic management of multiple myeloma. Cancer Res; 77(12); 3336–51. ©2017 AACR.
Circulating DNA Demonstrates Convergent Evolution and Common Resistance Mechanisms during Treatment of Colorectal Cancer
Authors: Thierry Alain R. , Pastor Brice , Jiang Zhi-Qin , Katsiampoura Anastasia D. , Parseghian Christine , Loree Jonathan M. , Overman Michael J. , Sanchez Cynthia , Messaoudi Safia El , Ychou Marc , Kopetz Scott
Published: April 2017

Purpose: Liquid biopsies allow the tracking of clonal dynamics and detection of mutations during treatment.

Experimental Design: We evaluated under blinded conditions the ability of cell-free DNA (cfDNA) to detect RAS/BRAF mutations in the plasma of 42 metastatic colorectal cancer patients treated on a phase Ib/II trial of FOLFOX and dasatinib, with or without cetuximab.

Results: Prior to treatment, sequencing of archival tissue detected mutations in 25 of 42 patients (60%), while the cfDNA assay detected mutations in 37 of 42 patients (88%). Our cfDNA assay detected mutations with allele frequencies as low as 0.01%. After exposure to treatment, 41 of 42 patients (98%) had a cfDNA-detected RAS/BRAF mutation. Of 21 patients followed with serial measurements who were RAS/BRAF mutant at baseline, 11 (52%) showed additional point mutation following treatment and 3 (14%) no longer had detectable levels of another mutant allele. Of RAS/BRAF wild-type tumors at baseline, 4 of 5 (80%) showed additional point mutations. cfDNA quantitative measurements from this study closely mirrored changes in CEA and CT scan results, highlighting the importance of obtaining quantitative data beyond the mere presence of a mutation.

Conclusions: Our findings demonstrate the development of new RAS/BRAF mutations in patients regardless of whether they had preexisting mutations in the pathway, demonstrating a convergent evolutionary pattern. Clin Cancer Res; 23(16); 4578–91. ©2017 AACR.
Prenatal Nonvisualization of the Gallbladder: A Diagnostic and Prognostic Dilemma
Authors: Ruiz Aina , Robles Ana , Salva Francisca , Filgueira Ana , Díaz Cristina , Juan Miquel , Tubau Albert
Published: April 2017

Introduction: Nonvisualization of the fetal gallbladder has been associated with benign conditions such as isolated gallbladder agenesis or severe diseases such as biliary atresia (BA). Recently, gamma-glutamyl transpeptidase (GGTP) fetal blood levels were reported as useful after 22 weeks. Objective: To determine the contribution of fetal blood GGTP levels after 22 weeks, based on 2 cases. Case 1: 20+4-week secundipara, with subcutaneous edema and pleural effusion. At 24+4 weeks, the gallbladder could not be visualized. Progressive hydrops deterioration was observed. 32+2-week magnetic resonance imaging (MRI) confirmed nonvisualization of the gallbladder. BA was suspected. The patient decided to terminate the pregnancy and fetal blood sample was obtained at feticide. GGTP was 573 IU/L. Fetal necropsy confirmed BA. Case 2: At the 22+6- and 24+0-week ultrasound scan, the gallbladder could not be visualized. Amniocentesis was offered, but declined by the patient. MRI at 35+0 weeks failed also to visualize it. Fetal cord blood sample at delivery was obtained, and GGTP was 129 IU/L. Ultrasound confirmed gallbladder agenesis with normal extra- and intrahepatic bile ducts. Conclusion: Cases of nonvisualized gallbladder after 22 weeks have rarely been reported in the literature. Until now, no standard management has been proposed. Our cases support the potential usefulness of fetal blood digestive enzymes.
EEG - A Valuable Biomarker of Brain Injury in Preterm Infants
Authors: Pavlidis Elena , Lloyd Rhodri O. , Boylan Geraldine B.
Published: April 2017

This review focuses on the role of electroencephalography (EEG) in monitoring abnormalities of preterm brain function. EEG features of the most common developmental brain injuries in preterm infants, including intraventricular haemorrhage, periventricular leukomalacia, and perinatal asphyxia, are described. We outline the most common EEG biomarkers associated with these injuries, namely seizures, positive rolandic sharp waves, EEG suppression/increased interburst intervals, mechanical delta brush activity, and other deformed EEG waveforms, asymmetries, and asynchronies. The increasing survival rate of preterm infants, in particular those that are very and extremely preterm, has led to a growing demand for a specific and shared characterization of the patterns related to adverse outcome in this unique population. This review includes abundant high-quality images of the EEG patterns seen in premature infants and will provide a valuable resource for everyone working in developmental neuroscience.
Molecular Mechanisms Leading to Splanchnic Vasodilation in Liver Cirrhosis
Authors: Di Pascoli Marco , Sacerdoti David , Pontisso Patrizia , Angeli Paolo , Bolognesi Massimo
Published: April 2017

In liver cirrhosis, portal hypertension is a consequence of enhanced intrahepatic vascular resistance and portal blood flow. Significant vasodilation in the arterial splanchnic district is crucial for an increase in portal flow. In this pathological condition, increased levels of circulating endogenous vasodilators, including nitric oxide, prostacyclin, carbon monoxide, epoxyeicosatrienoic acids, glucagon, endogenous cannabinoids, and adrenomedullin, and a decreased vascular response to vasoconstrictors are the main mechanisms underlying splanchnic vasodilation. In this review, the molecular pathways leading to splanchnic vasodilation will be discussed in detail.
Comparison of pro re nata versus Bimonthly Injection of Intravitreal Aflibercept for Typical Neovascular Age-Related Macular Degeneration
Authors: Mori Ryusaburo , Tanaka Koji , Haruyama Miho , Kawamura Akiyuki , Furuya Koichi , Yuzawa Mitsuko
Published: April 2017

Purpose: The aim of this study was to clarify the 1-year outcomes of pro re nata (PRN) and bimonthly intravitreal injections of aflibercept (IVA) for typical neovascular age-related macular degeneration (tAMD) after the initial 3 monthly IVA. Methods: We conducted a prospective, interventional study. Fifty-eight treatment-naïve patients with tAMD were randomly assigned to the PRN (30 patients) or the bimonthly (28 patients) treatment group. Both groups initially received 3 monthly IVA. Visual acuity, central macular retinal thickness (CRT), and central choroidal thickness (CCT) were evaluated at 12 months. Subanalysis was performed to identify factors associated with the best-corrected visual acuity (BCVA). Results: BCVA was significantly improved only in the bimonthly group at 12 months. CRT and CCT were significantly decreased in both groups. Subanalysis showed that the only factor associated with BCVA improvement at 12 months was the existence of pigment epithelial detachment at baseline. Conclusions: BCVA showed significant improvement only in the bimonthly group but not in the PRN group at 12 months.
Multi-Imaging Method to Assay the Contractile Mechanical Output of Micropatterned Human iPSC-Derived Cardiac Myocytes
Authors: Ribeiro Alexandre J.S. , Schwab Olivier , Mandegar Mohammad A. , Ang Yen-Sin , Conklin Bruce R. , Srivastava Deepak , Pruitt Beth L.
Published: April 2017

Rationale:

During each beat, cardiac myocytes (CMs) generate the mechanical output necessary for heart function through contractile mechanisms that involve shortening of sarcomeres along myofibrils. Human-induced pluripotent stem cells (hiPSCs) can be differentiated into CMs (hiPSC-CMs) that model cardiac contractile mechanical output more robustly when micropatterned into physiological shapes. Quantifying the mechanical output of these cells enables us to assay cardiac activity in a dish.

Objective:

We sought to develop a computational platform that integrates analytic approaches to quantify the mechanical output of single micropatterned hiPSC-CMs from microscopy videos.

Methods and Results:

We micropatterned single hiPSC-CMs on deformable polyacrylamide substrates containing fluorescent microbeads. We acquired videos of single beating cells, of microbead displacement during contractions, and of fluorescently labeled myofibrils. These videos were independently analyzed to obtain parameters that capture the mechanical output of the imaged single cells. We also developed novel methods to quantify sarcomere length from videos of moving myofibrils and to analyze loss of synchronicity of beating in cells with contractile defects. We tested this computational platform by detecting variations in mechanical output induced by drugs and in cells expressing low levels of myosin-binding protein C.

Conclusions:

Our method can measure the cardiac function of single micropatterned hiPSC-CMs and determine contractile parameters that can be used to elucidate mechanisms that underlie variations in CM function. This platform will be amenable to future studies of the effects of mutations and drugs on cardiac function.
More Than a Tacit Alliance
Authors: Lin Mao
Published: April 2017

It is well known that President Richard M. Nixon’s 1972 visit to the People’s Republic of China (prc) established an anti-Soviet alliance between Beijing and Washington that reshaped the global Cold War power balance. Naturally, scholars have focused on strategic issues such as the Sino-Soviet split, the Vietnam War, Taiwan, and other factors of “high politics” to understand the u.s.-China rapprochement. However, one can no longer dismiss u.s.-prc trade in the 1970s, albeit small in total volume, as insignificant and thus unimportant to the reconciliation. This article first examines how the Johnson and Nixon administrations conceived trade as a useful tool to improve relations with Communist China. It then explores how the Americans and Chinese carried out trade between themselves in the 1970s. It argues that many Americans were enthusiastic about u.s.-prc trade because they believed that reopened economic relations with the United States would persuade the prc to abandon its Communist model of modernization and move closer to following the capitalist example. If the United States could promote China’s attraction to its capitalist model for future development, then their shared economic interests and developmental visions would consolidate further the u.s.-China strategic alliance. In this sense, promoting trade was a way for the United States to apply soft power to change the prc.
Prehistoric Bantu-Khoisan language contact
Authors: Pakendorf Brigitte , Gunnink Hilde , Sands Bonny , Bostoen Koen
Published: April 2017

Click consonants are one of the hallmarks of “Khoisan” languages of southern Africa. They are also found in some Bantu languages, where they are usually assumed to have been copied from Khoisan languages. We review the southern African Bantu languages with clicks and discuss in what way they may have obtained these unusual consonants. We draw on both linguistic data and genetic results to gain insights into the sociocultural processes that may have played a role in the prehistoric contact. Our results show that the copying of clicks accompanied large-scale inmarriage of Khoisan women into Bantu-speaking communities and took place in situations where the Khoisan communities may have had relatively high prestige. In the Kavango-Zambezi transfrontier region, these events must have occurred at an early stage of the Bantu immigration, possibly because small groups of food producers entering a new territory were dependent on the autochthonous communities for local knowledge.
A new species of habitat–forming Suberites (Porifera, Demospongiae, Suberitida) in the Benguela upwelling region (South Africa)
Authors: SAMAAI TOUFIEK , MADURAY SESHNEE , JANSON LIESL , GIBBONS MARK J , NGWAKUM BENEDICTA , TESKE PETER R
Published: April 2017

S. dandelenae sp. nov. is described from the west coast of South Africa and occurs at depths of 80–500 m among unconsolidated sediments. Specimens can reach 40 cm in length and in some areas off South Africa, up to 18 tons/km2 can be collected in a single demersal trawl. Morphologically, the sponge is straw yellow, massive with rounded lobes and has a velvety surface: it is characterized by subradiate, irregular reticulation of bundles of tylostyles and tylostrongyles. Specimens of S. dandelenae sp. nov. have three size classes of tylostyles with the largest tylostyle lengths being 516 μm (441–614 μm), medium tylostyle lengths being 352 μm (307–422 μm) and the shortest tylostyle lengths being 215 μm (153–288 μm). Apart from the presence of tylostyles, some specimens of S. dandelenae sp. nov. also possess centrotylostongyles/oxeas, tylostrongyles and microacanthostrongyles spicules. We have used morphological characters to distinguish this species and a molecular marker (cox1) to conform that all specimens are the same species. At the spicular level, S. dandelenae sp. nov. is characterized by a complex of spicule types that vary with specimen size. Following a histological investigation and re–description of the holotypes of S. ficus (Johnston, 1842) and S. tylobtusus Lévi, 1958, and comparisons with S. carnosus (Johnston, 1842), S. stilensis Burton, 1933, and other Suberites species described from the African region, it is clear that the new species is different in spicule morphology, spicule size and external morphology. For example, microacanthostrongyles are not present in S. tylobtusus and S. carnosus, whilst S. ficus possesses a second, non–spinose category of microstrongyles. Suberites tylobtusus has tylostyles that are sometimes polytylote, with heads either well formed, pear shaped or reduced, in only one size catogory. The 'tylobtuse' condition of the tylostyles is also different to the kidney–shaped and centrotylostrongyles found in S. dandelenae sp. nov. Suberites stilensis Burton, 1933 has larger and thicker tylostyles (800 μm length x 10 μm thick) than those of S. dandelenae sp. nov. A comparative analysis of partial cox1 sequences from morphologically diverse specimens of S. dandelenae sp. nov. with published material indicates that all specimens comprise a monophyletic clade. The combined morphological and genetic data support the designation of Suberites dandelenae sp. nov.
A revision of the South African riffle beetle genus Leielmis Delève, 1964 (Coleoptera: Elmidae)
Authors: BILTON DAVID T.
Published: April 2017

The riffle beetle genus Leielmis Delève, 1964 is redescribed and shown to contain three species, all of which are apparently endemic to the South African Cape, where they live in permanent mountain streams with cold running water. A lectotype is designated for Helmis georyssoides Grouvelle, 1890, and two additional species (L. gibbosus sp. nov. and L. hirsutus sp. nov.) are described for the first time. Following study of the type series, L. georyssoides is shown to be endemic to Table Mountain; most specimens previously assigned to this taxon representing an additional species (L. gibbosus sp. nov.), widespread in the interior Cape Fold Mountains. The record of Leielmis from Angola is considered highly doubtful. Comparative notes and a key are provided to allow the identification of known species of the genus.
Additional three new species of Anarsia Meyrick (Lepidoptera, Gelechiidae) from Cambodia and Vietnam
Authors: PARK KYU-TEK , BAE YANG-SEOP
Published: April 2017

Three new species of the genus Anarsia Zeller (Lepidoptera, Gelechiidae) are described: A. huensis Park, sp. nov. from Vietnam, and A. pursatica Park, sp. nov. and A. degeneralis Park, sp. nov. from Cambodia. Images of adults and genitalia for the new species are illustrated. A check list of the known species from both countries is provided.
Using High-Resolution Reanalysis Data to Explore Localized Western North America Hydroclimate Relationships with ENSO
Authors: Heyer Joshua P. , Brewer Simon C. , Shinker Jacqueline J.
Published: April 2017

Many studies have used observational data to explore associations between El Niño–Southern Oscillation (ENSO) and western North America (NA) hydroclimate at regional spatial scales. However, relationships between tropical Pacific sea surface temperature (SST) variability and western NA hydroclimate at local scales using reanalysis data are less understood. Here, the current understanding of relationships between large-scale tropical Pacific SST variability and western NA hydroclimate is extended to localized headwaters. To accomplish this, high-resolution reanalysis data (i.e., monthly mean surface precipitation rate, 2-m temperature, 850-mb specific humidity, and 500-mb omega) were used for gridpoint correlation analyses with Niño-3.4 SST and El Niño Modoki indices. Reanalysis time series data were provided by the National Centers for Environmental Prediction North American Regional Reanalysis (NARR) product. To validate the accuracy of NARR surface data, observational Livneh precipitation and temperature data were used. Resulting correlations between tropical Pacific indices and NARR surface precipitation and 2-m temperature are consistent with previous research both spatially and temporally, indicating that the strongest correlations occur primarily over southwestern NA during the winter (DJF). The results herein demonstrate the potential of high-resolution reanalysis data to reveal distinct correlations over topographically complex watersheds in the U.S. Intermountain West (IMW) over the recent record, 1979–2015. The use of the high-resolution NARR product as a viable option to explore western NA hydroclimate is demonstrated here.
Dynamics of the Disrupted 2015/16 Quasi-Biennial Oscillation
Authors: Coy Lawrence , Newman Paul A. , Pawson Steven , Lait Leslie R.
Published: April 2017

A significant disruption of the quasi-biennial oscillation (QBO) occurred during the Northern Hemisphere (NH) winter of 2015/16. Since the QBO is the major wind variability source in the tropical lower stratosphere and influences the rate of ascent of air entering the stratosphere, understanding the cause of this singular disruption may provide new insights into the variability and sensitivity of the global climate system. Here this disruptive event is examined using global reanalysis winds and temperatures from 1980 to 2016. Results reveal record maxima in tropical horizontal momentum fluxes and wave forcing of the tropical zonal mean zonal wind over the NH 2015/16 winter. The Rossby waves responsible for these record tropical values appear to originate in the NH and were focused strongly into the tropics at the 40-hPa level. Two additional NH winters, 1987/88 and 2010/11, were also found to have large tropical lower-stratospheric momentum flux divergences; however, the QBO westerlies did not change to easterlies in those cases.
Wave Events: Climatology, Trends, and Relationship to Northern Hemisphere Winter Blocking and Weather Extremes
Authors: Martineau Patrick , Chen Gang , Burrows D. Alex
Published: April 2017

Diagnostics of finite-amplitude local wave activity (LWA) are applied to the 500-hPa geopotential height field to diagnose persistent synoptic weather events of anomalously large wave activity in the Northern Hemisphere. By considering the cyclonic and anticyclonic components of LWA separately, persistent weather systems associated with large-amplitude troughs and ridges are detected. While anticyclonic wave events are predominantly found over Europe and Alaska, cyclonic wave events usually occur over East Asia and northeastern Canada. Those preferred regions correspond to the location of planetary-scale ridges and troughs, which contribute, together with transient anomalies, to the formation of wave events. Although wave events are not blocking events per definition, they are typically associated with increased blocking in their vicinity. Their spatial relationship to blocking, however, varies depending on their cyclonic or anticyclonic nature and the type of wave-breaking signatures. Wave events are also shown to be accompanied by warm or cold temperature extremes, whose spatial pattern depends on the type of events, cyclonic or anticyclonic, and the sector affected. Trends in the frequency of wave events indicate that cyclonic wave events and the associated cold extremes affecting East Asia have become more frequent in recent decades and could be linked to recent trends toward La Niña–like conditions in the Pacific and trends toward the negative phase of Arctic Oscillation.