bluuebunny/crossref_metadata_2025 huggingface dataset:
Electroencephalographic connectivity measures predict learning of a motor sequencing task
Authors: Wu Jennifer , Knapp Franziska , Cramer Steven C. , Srinivasan Ramesh
Published: November 2017

Individuals vary significantly with respect to rate and degree of improvement with motor practice. While the regions that underlie motor learning have been well described, neurophysiological factors underlying differences in response to motor practice are less well understood. The present study examined both resting-state and event-related EEG coherence measures of connectivity as predictors of response to motor practice on a motor sequencing task using the dominant hand. Thirty-two healthy young right-handed participants underwent resting EEG before motor practice. Response to practice was evaluated both across the single session of motor practice and 24 h later at a retention test of short-term motor learning. Behaviorally, the group demonstrated statistically significant gains both in single-session “motor improvement” and across-session “motor learning.” A resting-state measure of whole brain coherence with primary motor cortex (M1) at baseline robustly predicted subsequent motor improvement (validated R2 = 0.55) and motor learning (validated R2 = 0.68) in separate partial least-squares regression models. Specifically, greater M1 coherence with left frontal-premotor cortex (PMC) at baseline was characteristic of individuals likely to demonstrate greater gains in both motor improvement and motor learning. Analysis of event-related coherence with respect to movement found the largest changes occurring in areas implicated in planning and preparation of movement, including PMC and frontal cortices. While event-related coherence provided a stronger prediction of practice-induced motor improvement (validated R2 = 0.73), it did not predict the degree of motor learning (validated R2 = 0.16). These results indicate that connectivity in the resting state is a better predictor of consolidated learning of motor skills.

NEW & NOTEWORTHY Differences in response to motor training have significant societal implications across a lifetime of motor skill practice. By evaluating both resting-state and event-related measures of brain function, our findings highlight interindividual differences in brain connectivity providing unique insights into differences in response to motor training. These findings have wide-ranging implications in settings ranging from advanced professional motor training to rehabilitation after brain injury.
A computational analysis of signal fidelity in the rostral nucleus of the solitary tract
Authors: Boxwell Alison , Terman David , Frank Marion , Yanagawa Yuchio , Travers Joseph B.
Published: November 2017

Neurons in the rostral nucleus of the solitary tract (rNST) convey taste information to both local circuits and pathways destined for forebrain structures. This nucleus is more than a simple relay, however, because rNST neurons differ in response rates and tuning curves relative to primary afferent fibers. To systematically study the impact of convergence and inhibition on firing frequency and breadth of tuning (BOT) in rNST, we constructed a mathematical model of its two major cell types: projection neurons and inhibitory neurons. First, we fit a conductance-based neuronal model to data derived from whole cell patch-clamp recordings of inhibitory and noninhibitory neurons in a mouse expressing Venus under the control of the VGAT promoter. We then used in vivo chorda tympani (CT) taste responses as afferent input to modeled neurons and assessed how the degree and type of convergence influenced model cell output frequency and BOT for comparison with in vivo gustatory responses from the rNST. Finally, we assessed how presynaptic and postsynaptic inhibition impacted model cell output. The results of our simulations demonstrated 1) increasing numbers of convergent afferents (2–10) result in a proportional increase in best-stimulus firing frequency but only a modest increase in BOT, 2) convergence of afferent input selected from the same best-stimulus class of CT afferents produced a better fit to real data from the rNST compared with convergence of randomly selected afferent input, and 3) inhibition narrowed the BOT to more realistically model the in vivo rNST data.

NEW & NOTEWORTHY Using a combination of in vivo and in vitro neurophysiology together with conductance-based modeling, we show how patterns of convergence and inhibition interact in the rostral (gustatory) solitary nucleus to maintain signal fidelity. Although increasing convergence led to a systematic increase in firing frequency, tuning specificity was maintained with a pattern of afferent inputs sharing the best-stimulus compared with random inputs. Tonic inhibition further enhanced response fidelity.
Distribution and function of the muscarinic receptor subtypes in the cardiovascular system
Authors: Saternos Hannah C. , Almarghalani Daniyah A. , Gibson Hayley M. , Meqdad Mahmood A. , Antypas Raymond B. , Lingireddy Ajay , AbouAlaiwi Wissam A.
Published: November 2017

Muscarinic acetylcholine receptors belong to the G protein-coupled receptor superfamily and are widely known to mediate numerous functions within the central and peripheral nervous system. Thus, they have become attractive therapeutic targets for various disorders. It has long been known that the parasympathetic system, governed by acetylcholine, plays an essential role in regulating cardiovascular function. Unfortunately, due to the lack of pharmacologic selectivity for any one muscarinic receptor, there was a minimal understanding of their distribution and function within this region. However, in recent years, advancements in research have led to the generation of knockout animal models, better antibodies, and more selective ligands enabling a more thorough understanding of the unique role muscarinic receptors play in the cardiovascular system. These advances have shown muscarinic receptor 2 is no longer the only functional subtype found within the heart and muscarinic receptors 1 and 3 mediate both dilation and constriction in the vasculature. Although muscarinic receptors 4 and 5 are still not well characterized in the cardiovascular system, the recent generation of knockout animal models will hopefully generate a better understanding of their function. This mini review aims to summarize recent findings and advances of muscarinic involvement in the cardiovascular system.
Physical Simulation of Colayer Water Flooding in Low Permeability Carbonate Reservoir in Middle East
Authors: Shi Xingwang , Yang Zhengming , Zhang Yapu , Zhu Guangya , Xiao Qianhua
Published: November 2017

To study the flow mechanism under different displacement modes of low permeability carbonate reservoir in the Middle East and to improve the utilization of various types of reservoirs, the physical simulation experiments of water flooding by different displacement methods were carried out. Selecting two types of rock samples with different permeability levels, two-layer coinjection and separated production experiments by samples I and III and conventional water flooding experiments by samples II and IV were carried out. In addition, by using low magnetic field nuclear magnetic resonance, the development effect of microscopic pore structure under the different injection-production models was analyzed. Results show that, compared with the coinjection, the recovery rate of sample I was higher than II, 19.30%; sample III was lower than IV, 23.22%; and the comprehensive recovery degree reduced by 3.92%. NMR data also show that the crude oil is mainly distributed in the large pore throat; after water flooding, the displacement is also within the large pore throat, whereas the small pore throat is mainly obtained by the effect of infiltration absorption. The above studies provide a laboratory basis and foundation for the further development of low permeability carbonate reservoir in different Middle East strata.
Intensive Care in a Patient with Toxic Epidermal Necrolysis
Authors: Wallenborn J. , Fischer M.
Published: November 2017

Toxic epidermal necrolysis (TEN) is a serious adverse drug reaction with high lethality, which usually requires intensive-medical care. A 44-year-old man developed generalized exanthema with increasing exfoliation and mucosal involvement after taking allopurinol, ibuprofen, and etoricoxib. The clinical diagnosis of TEN was histologically confirmed. Prednisolone therapy with 3 mg/kg body weight (BW) was not able to prevent further progress to finally 80% of the body surface, and infliximab 5 mg/kg BW was given as a single dose. This prevented further progression of the TEN. Despite marked improvement in skin findings, the ICU stay was prolonged by a complex analgosedation, transient kidney failure, volume management, positioning therapy, and vegetatively impeded weaning. Moreover, there was colonization with multiresistant bacteria (MRSA and VRE). Nonetheless, the patient could be restored to health and was released after four weeks. Infliximab seems to be effective in the treatment of TEN, especially in cases of rapid progression. Moreover, patients with TEN are difficult to handle in intensive-medical care, whereby attention should especially be paid to sufficient pain therapy, and the positioning of the patient is a particular challenge.
Rolling Bearing Fault Signal Extraction Based on Stochastic Resonance-Based Denoising and VMD
Authors: Gu Xiaojiao , Chen Changzheng
Published: November 2017

Aiming at the difficulty of early fault vibration signal extraction of rolling bearing, a method of fault weak signal extraction based on variational mode decomposition (VMD) and quantum particle swarm optimization adaptive stochastic resonance (QPSO-SR) for denoising is proposed. Firstly, stochastic resonance parameters are optimized adaptively by using quantum particle swarm optimization algorithm according to the characteristics of the original fault vibration signal. The best stochastic resonance system parameters are output when the signal to noise ratio reaches the maximum value. Secondly, the original signal is processed by optimal stochastic resonance system for denoising. The influence of the noise interference and the impact component on the results is weakened. The amplitude of the fault signal is enhanced. Then the VMD method is used to decompose the denoised signal to realize the extraction of fault weak signals. The proposed method was applied in simulated fault signals and actual fault signals. The results show that the proposed method can reduce the effect of noise and improve the computational accuracy of VMD in noise background. It makes VMD more effective in the field of fault diagnosis. The proposed method is helpful to realize the accurate diagnosis of rolling bearing early fault.
Factors Affecting Health Related Quality of Life in Hospitalized Patients with Heart Failure
Authors: Audi Georgia , Korologou Aggeliki , Koutelekos Ioannis , Vasilopoulos Georgios , Karakostas Kostas , Makrygianaki Kleanthi , Polikandrioti Maria
Published: November 2017

This study identified factors affecting health related quality of life (HRQOL) in 300 hospitalized patients with heart failure (HF). Data were collected by the completion of a questionnaire which included patients’ characteristics and the Minnesota Living with Heart Failure Questionnaire (MLHFQ). Analysis of data showed that the median of the total score of MLHFQ was 46 and the median of the physical and mental state was 22 and 6, respectively. Also, participants who were householders or had “other” professions had lower score of 17 points and therefore better quality of life compared to patients who were civil/private employees (p<0.001 and p<0.001, resp.). Patients not receiving anxiolytics and antidepressants had lower quality of life scores of 6 and 15.5 points, respectively, compared to patients who received (p=0.003 and p<0.001, resp.). Patients with no prior hospitalization had lower score of 7 points compared to those with prior hospitalization (p=0.002), whereas patients not retired due to the disease had higher score of 7 points (p=0.034). Similar results were observed for the physical and mental state. Improvement of HF patients’ quality of life should come to the forefront of clinical practice.
Distributed Sequential Consensus in Networks: Analysis of Partially Connected Blockchains with Uncertainty
Authors: Prieto-Castrillo Francisco , Kushch Sergii , Corchado Juan Manuel
Published: November 2017

This work presents a theoretical and numerical analysis of the conditions under which distributed sequential consensus is possible when the state of a portion of nodes in a network is perturbed. Specifically, it examines the consensus level of partially connected blockchains under failure/attack events. To this end, we developed stochastic models for both verification probability once an error is detected and network breakdown when consensus is not possible. Through a mean field approximation for network degree we derive analytical solutions for the average network consensus in the large graph size thermodynamic limit. The resulting expressions allow us to derive connectivity thresholds above which networks can tolerate an attack.
Prevalence ofHelicobacter pylori vacAGenotypes andcagAGene in Dental Plaque of Asymptomatic Mexican Children
Authors: Mendoza-Cantú Alejandra , Urrutia-Baca Víctor Hugo , Urbina-Ríos Cynthia Sofía , De la Garza-Ramos Myriam Angélica , García-Martínez Martha Elena , Torre-Martínez Hilda H. H.
Published: November 2017

The variability inHelicobacter pylori vacAandcagAgenes has been related to the progression of the gastrointestinal disease; also the presence ofH. pyloriin the oral cavity has been associated with periodontal disease in adults, but, in children without dyspeptic symptoms, little is known about this. We evaluated the prevalence ofH. pyloriand the presence ofvacA/cagAgenotypes in the oral cavity of Mexican children without dyspeptic symptoms. The gingival status was measured, and dental plaque samples (n=100) were taken. 38% of children were positive forH. pylori16S rRNA gene by qPCR. A significant association betweenH. pylorioral infection and gingival status was observed (P<0.001). In 34.6% (9/26) of mild gingivitis cases,s1m2genotype was found, whiles1m1was typed in 50% (3/6) of moderate gingivitis. ThecagAprevalence amongH. pylori-positive children was 80.8% (21/26), 83.3% (5/6), and 16.7% (1/6) of cases of mild gingivitis, moderate gingivitis, and nongingivitis, respectively (P<0.001). Thes1m1/cagA+ combinational genotype was the most detected in children with gingivitis. Our results suggest that the prevalence ofH. pyloriand detection ofvacA/cagAgenotypes-associated gastrointestinal disease in the oral cavity could be related to the progression of gingivitis in asymptomatic children.
Convergence Properties for Uncertain Sequence
Authors: You Cuilian , Yan Lijuan
Published: November 2017

Uncertainty theory is a branch of axiomatic mathematics for modeling belief degrees. Since convergence for uncertain sequences plays a very important role in uncertainty theory and applications, we investigated some properties of convergence in measure in this paper. In addition, some theorems and properties of convergence in p‐distance were studied.
Spectroscopic Characterization of Omeprazole and Its Salts
Authors: Vrbanec Tomislav , Šket Primož , Merzel Franci , Smrkolj Matej , Grdadolnik Jože
Published: November 2017

During drug development, it is important to have a suitable crystalline form of the active pharmaceutical ingredient (API). Mostly, the basic options originate in the form of free base, acid, or salt. Substances that are stable only within a certain pH range are a challenge for the formulation. For the prazoles, which are known to be sensitive to degradation in an acid environment, the formulation is stabilized with alkaline additives or with the application of API formulated as basic salts. Therefore, preparation and characterization of basic salts are needed to monitor any possible salinization of free molecules. We synthesized salts of omeprazole from the group of alkali metals (Li, Na, and K) and alkaline earth metals (Mg, Ca). The purpose of the presented work is to demonstrate the applicability of vibrational spectroscopy to discriminate between the OMP and OMP-salt molecules. For this reason, the physicochemical properties of 5 salts were probed using infrared and Raman spectroscopy, NMR, TG, DSC, and theoretical calculation of vibrational frequencies. We found out that vibrational spectroscopy serves as an applicable spectroscopic tool which enables an accurate, quick, and nondestructive way to determine the characteristic of OMP and its salts.
Output Feedback Control for Asymptotic Stabilization of Spacecraft with Input Saturation
Authors: Pukdeboon Chutiphon
Published: November 2017

This paper investigates the attitude stabilization problem of rigid spacecraft subject to actuator constraints, external disturbances, and attitude measurements only. An output feedback control framework with input saturation is proposed to solve this problem. The general saturation function is utilized in the proposed controller design and a unified control method is developed for the asymptotic stabilization of rigid spacecraft without velocity measurements. Asymptotic stability is proven by Lyapunov stability theory. Moreover, a new nonlinear disturbance observer is designed to compensate for external disturbances. Then, a composite controller is presented by combining a unified saturated output feedback control with a nonlinear disturbance observer. Desirable features of the proposed control scheme include the intuitive structure, robustness against external disturbances, avoidance of model information and velocity measurements, and ability to ensure that the actuator constraints are not violated. Finally, numerical simulations have been carried out to verify the effectiveness of the proposed control method.
Tricuspid Valve Endocarditis due to Streptococcus bovis in a Patient with Ventricular Septal Defect: A Rare Manifestation—Case Report and Review of the Literature
Authors: Pushpakumara J. , Mudiyanse G. , Jayawardana A. , Siriwardana J. , Shyamali N. L. A. , Indrakumar J.
Published: November 2017

Streptococcus bovis endocarditis has 18%–62% association with colonic neoplasms with multivalvular involvement and affects mainly elderly males leading to severe cardiac dysfunction, septic embolization, and neurological complications. The aortic valve is the commonest valve to be affected followed by aortic and mitral valves together. However, involvement of tricuspid valve is extremely rare. There are no reported cases of Streptococcus bovis endocarditis affecting the tricuspid valve in the presence of ventricular septal defect with left to right shunt. We report the case of a 25-year-old female with ventricular septal defect who was diagnosed to have tricuspid valve endocarditis caused by Streptococcus bovis. Her detailed colonoscopy, upper gastrointestinal endoscopy, liver biochemistry, and ultrasound scan of the abdomen were normal. She made a very good recovery with six weeks of intravenous antibiotics. This is the first case of tricuspid valve endocarditis caused by Streptococcus bovis in association with ventricular septal defect without any colonic lesions.
Comparison of Attenuated Total Reflectance Mid-Infrared, Near Infrared, and 1H-Nuclear Magnetic Resonance Spectroscopies for the Determination of Coffee’s Geographical Origin
Authors: Medina Jessica , Caro Rodríguez Diana , Arana Victoria A. , Bernal Andrés , Esseiva Pierre , Wist Julien
Published: November 2017

The sensorial properties of Colombian coffee are renowned worldwide, which is reflected in its market value. This raises the threat of fraud by adulteration using coffee grains from other countries, thus creating a demand for robust and cost-effective methods for the determination of geographical origin of coffee samples. Spectroscopic techniques such as Nuclear Magnetic Resonance (NMR), near infrared (NIR), and mid-infrared (mIR) have arisen as strong candidates for the task. Although a body of work exists that reports on their individual performances, a faithful comparison has not been established yet. We evaluated the performance of 1H-NMR, Attenuated Total Reflectance mIR (ATR-mIR), and NIR applied to fraud detection in Colombian coffee. For each technique, we built classification models for discrimination by species (C. arabica versus C. canephora (or robusta)) and by origin (Colombia versus other C. arabica) using a common set of coffee samples. All techniques successfully discriminated samples by species, as expected. Regarding origin determination, ATR-mIR and 1H-NMR showed comparable capacity to discriminate Colombian coffee samples, while NIR fell short by comparison. In conclusion, ATR-mIR, a less common technique in the field of coffee adulteration and fraud detection, emerges as a strong candidate, faster and with lower cost compared to 1H-NMR and more discriminating compared to NIR.
DAFIESKU: A System for Acquiring Mobile Physiological Data
Authors: Simón Maider , Sarasua Ezekiel , Gamecho Borja , Larraza-Mendiluze Edurne , Garay-Vitoria Nestor
Published: November 2017

Gathering physiological data when they are performing experiments requires a great effort from researchers. Very often, a considerable time is required to prepare the signal acquisition equipment, conduct the experiments, and properly label the data of each participant. Nevertheless this data is valuable for the analysis of personal characteristics, such as behavior, health conditions, and preferences. With the aim of assisting researchers with such tedious tasks, we have developed the DAFIESKU system. This system serves to acquire several types of physiological data. DAFIESKU facilitates the creation of new datasets with physiological data by means of mobile and wearable devices. The usability of the system was evaluated in two case studies in a two-step iterative process. Before conducting the second case study, the whole system was improved using the feedback obtained from the first case study. The results achieved show that usability was enhanced in the second version of DAFIESKU.
Alcohol Consumption in Diabetic Patients with Nonalcoholic Fatty Liver Disease
Authors: Patel Preya J. , Smith David , Connor Jason P. , Horsfall Leigh U. , Hayward Kelly L. , Hossain Fabrina , Williams Suzanne , Johnson Tracey , Stuart Katherine A. , Brown Nigel N. , Saad Nivene , Clouston Andrew D. , Irvine Katharine M. , Russell Anthony W. , Valery Patricia C. , Powell Elizabeth E.
Published: November 2017

Aim. To examine the association between lifetime alcohol consumption and significant liver disease in type 2 diabetic patients with NAFLD. Methods. A cross-sectional study assessing 151 patients with NAFLD at risk of clinically significant liver disease. NAFLD fibrosis severity was classified by transient elastography; liver stiffness measurements ≥8.2 kPa defined significant fibrosis. Lifetime drinking history classified patients into nondrinkers, light drinkers (always ≤20 g/day), and moderate drinkers (any period with intake >20 g/day). Result. Compared with lifetime nondrinkers, light and moderate drinkers were more likely to be male (p=0.008) and to be Caucasian (p=0.007) and to have a history of cigarette smoking (p=0.000), obstructive sleep apnea (p=0.003), and self-reported depression (p=0.003). Moderate drinkers required ≥3 hypoglycemic agents to maintain diabetic control (p=0.041) and fibrate medication to lower blood triglyceride levels (p=0.044). Compared to lifetime nondrinkers, light drinkers had 1.79 (95% CI: 0.67–4.82; p=0.247) and moderate drinkers had 0.91 (95% CI: 0.27–3.10; p=0.881) times the odds of having liver stiffness measurements ≥8.2 kPa (adjusted for age, gender, and body mass index). Conclusions. In diabetic patients with NAFLD, light or moderate lifetime alcohol consumption was not significantly associated with liver fibrosis. The impact of lifetime alcohol intake on fibrosis progression and diabetic comorbidities, in particular obstructive sleep apnea and hypertriglyceridemia, requires further investigation.
Daptomycin-Induced Acute Eosinophilic Pneumonia: Late Onset and Quick Recovery
Authors: Rachid Mohamad , Ahmad Khansa , Saunders-Kurban Meghan , Fatima Aelia , Shah Aditya , Nahhas Anas
Published: November 2017

Background. Daptomycin is a cyclic lipopeptide antibiotic that provides great coverage for gram positive cocci. From the early years of daptomycin use, concerns were raised regarding the pulmonary side effects of daptomycin and potential development of acute eosinophilic pneumonia (AEP) secondary to daptomycin therapy. Discussion. AEP could be idiopathic or induced by drugs or toxins. It is a distinct entity from atopic diseases and autoimmune, parasitic, or fungal infections that can also cause pulmonary eosinophilia. Multiple medications are associated with acute eosinophilic pneumonia. Multiple cases of daptomycin-induced AEP have been reported in the literature. Diagnosis of AEP is based on clinical history, laboratory tests, and radiographic studies. Obtaining bronchoalveolar lavage or lung biopsy is needed to confirm the diagnosis. Timing of the drug use and clinical presentation is crucial in the diagnosis of drug-induced AEP. Discontinuation of the offending drug and systemic corticosteroids are the mainstay treatment with great outcomes and recovery. Conclusion. We present a case of AEP caused by daptomycin, with complete recovery after discontinuation of daptomycin and administration of steroids. The patient had AEP after almost 6 weeks of daptomycin therapy which has never been reported in literature and our patient achieved complete recovery with appropriate management.
Psychometric Evaluation of the Persian Version of Barkley Adult Attention Deficit/Hyperactivity Disorder Screening Tool among the Elderly
Authors: Sadeghi Mostafa , Sadeghi-Bazargani Homayoun , Amiri Shahrokh
Published: November 2017

Background. The Barkley Adult Attention Deficit/Hyperactivity Disorder (ADHD) Rating Scale-IV (BAARS-IV) was developed, and it demonstrated good psychometric properties. The BAARS-IV includes 27 questions on the symptoms of adult ADHD. The purpose of the present study is to investigate the psychometric testing of the Persian version of BAARS-IV among the elderlies in Tabriz City. Method. This cross-sectional study was conducted in Tabriz City—in the west of Iran—in 2015 via enrolling of 121 old-aged people. We did the process of translation and adaptation of BAARS-IV and examined its concurrent validity, internal consistency, and test-retest reliability. Result. The BAARS-IV demonstrated good internal consistency and test-retest reliability. Correlations between the BAARS-IV and the CAARS-S: SV were high and evidence supporting concurrent validity was revealed. Cronbach’s alpha for the overall scale and subscales stood at 0.89, 0.81, 0.66, 0.56, and 0.82, respectively. Conclusion. The Persian BAARS-IV showed acceptable reliability and validity. BAARS-IV was determined to be composed of internally consistent and psychometrically sound items.
Integrative Analysis of Histopathological Images and Genomic Data Predicts Clear Cell Renal Cell Carcinoma Prognosis
Authors: Cheng Jun , Zhang Jie , Han Yatong , Wang Xusheng , Ye Xiufen , Meng Yuebo , Parwani Anil , Han Zhi , Feng Qianjin , Huang Kun
Published: November 2017

In cancer, both histopathologic images and genomic signatures are used for diagnosis, prognosis, and subtyping. However, combining histopathologic images with genomic data for predicting prognosis, as well as the relationships between them, has rarely been explored. In this study, we present an integrative genomics framework for constructing a prognostic model for clear cell renal cell carcinoma. We used patient data from The Cancer Genome Atlas (n = 410), extracting hundreds of cellular morphologic features from digitized whole-slide images and eigengenes from functional genomics data to predict patient outcome. The risk index generated by our model correlated strongly with survival, outperforming predictions based on considering morphologic features or eigengenes separately. The predicted risk index also effectively stratified patients in early-stage (stage I and stage II) tumors, whereas no significant survival difference was observed using staging alone. The prognostic value of our model was independent of other known clinical and molecular prognostic factors for patients with clear cell renal cell carcinoma. Overall, this workflow and the shared software code provide building blocks for applying similar approaches in other cancers. Cancer Res; 77(21); e91–100. ©2017 AACR.
A Galaxy Implementation of Next-Generation Clustered Heatmaps for Interactive Exploration of Molecular Profiling Data
Authors: Broom Bradley M. , Ryan Michael C. , Brown Robert E. , Ikeda Futa , Stucky Mark , Kane David W. , Melott James , Wakefield Chris , Casasent Tod D. , Akbani Rehan , Weinstein John N.
Published: November 2017

Clustered heatmaps are the most frequently used graphics for visualization of molecular profiling data in biology. However, they are generally rendered as static, or only modestly interactive, images. We have now used recent advances in web technologies to produce interactive “next-generation” clustered heatmaps (NG-CHM) that enable extreme zooming and navigation without loss of resolution. NG-CHMs also provide link-outs to additional information sources and include other features that facilitate deep exploration of the biology behind the image. Here, we describe an implementation of the NG-CHM system in the Galaxy bioinformatics platform. We illustrate the algorithm and available computational tool using RNA-seq data from The Cancer Genome Atlas program's Kidney Clear Cell Carcinoma project. Cancer Res; 77(21); e23–26. ©2017 AACR.
An Image Analysis Resource for Cancer Research: PIIP—Pathology Image Informatics Platform for Visualization, Analysis, and Management
Authors: Martel Anne L. , Hosseinzadeh Dan , Senaras Caglar , Zhou Yu , Yazdanpanah Azadeh , Shojaii Rushin , Patterson Emily S. , Madabhushi Anant , Gurcan Metin N.
Published: November 2017

Pathology Image Informatics Platform (PIIP) is an NCI/NIH sponsored project intended for managing, annotating, sharing, and quantitatively analyzing digital pathology imaging data. It expands on an existing, freely available pathology image viewer, Sedeen. The goal of this project is to develop and embed some commonly used image analysis applications into the Sedeen viewer to create a freely available resource for the digital pathology and cancer research communities. Thus far, new plugins have been developed and incorporated into the platform for out of focus detection, region of interest transformation, and IHC slide analysis. Our biomarker quantification and nuclear segmentation algorithms, written in MATLAB, have also been integrated into the viewer. This article describes the viewing software and the mechanism to extend functionality by plugins, brief descriptions of which are provided as examples, to guide users who want to use this platform. PIIP project materials, including a video describing its usage and applications, and links for the Sedeen Viewer, plug-ins, and user manuals are freely available through the project web page: http://pathiip.org. Cancer Res; 77(21); e83–86. ©2017 AACR.
Cistrome Cancer: A Web Resource for Integrative Gene Regulation Modeling in Cancer
Authors: Mei Shenglin , Meyer Clifford A. , Zheng Rongbin , Qin Qian , Wu Qiu , Jiang Peng , Li Bo , Shi Xiaohui , Wang Binbin , Fan Jingyu , Shih Celina , Brown Myles , Zang Chongzhi , Liu X. Shirley
Published: November 2017

Cancer results from a breakdown of normal gene expression control, so the study of gene regulation is critical to cancer research. To gain insight into the transcriptional and epigenetic factors regulating abnormal gene expression patterns in cancers, we developed the Cistrome Cancer web resource (http://cistrome.org/CistromeCancer/). We conducted the systematic integration and modeling of over 10,000 tumor molecular profiles from The Cancer Genome Atlas (TCGA) with over 23,000 ChIP-seq and chromatin accessibility profiles from our Cistrome collection. The results include reconstruction of functional enhancer profiles, “super-enhancer” target genes, as well as predictions of active transcription factors and their target genes for each TCGA cancer type. Cistrome Cancer reveals novel insights from integrative analyses combining chromatin profiles with tumor molecular profiles and will be a useful resource to the cancer gene regulation community. Cancer Res; 77(21); e19–22. ©2017 AACR.
dcmqi: An Open Source Library for Standardized Communication of Quantitative Image Analysis Results Using DICOM
Authors: Herz Christian , Fillion-Robin Jean-Christophe , Onken Michael , Riesmeier Jörg , Lasso Andras , Pinter Csaba , Fichtinger Gabor , Pieper Steve , Clunie David , Kikinis Ron , Fedorov Andriy
Published: November 2017

Quantitative analysis of clinical image data is an active area of research that holds promise for precision medicine, early assessment of treatment response, and objective characterization of the disease. Interoperability, data sharing, and the ability to mine the resulting data are of increasing importance, given the explosive growth in the number of quantitative analysis methods being proposed. The Digital Imaging and Communications in Medicine (DICOM) standard is widely adopted for image and metadata in radiology. dcmqi (DICOM for Quantitative Imaging) is a free, open source library that implements conversion of the data stored in commonly used research formats into the standard DICOM representation. dcmqi source code is distributed under BSD-style license. It is freely available as a precompiled binary package for every major operating system, as a Docker image, and as an extension to 3D Slicer. Installation and usage instructions are provided in the GitHub repository at https://github.com/qiicr/dcmqi. Cancer Res; 77(21); e87–90. ©2017 AACR.
“Personalized Cancer Therapy”: A Publicly Available Precision Oncology Resource
Authors: Kurnit Katherine C. , Bailey Ann M. , Zeng Jia , Johnson Amber M. , Shufean Md. Abu , Brusco Lauren , Litzenburger Beate C. , Sánchez Nora S. , Khotskaya Yekaterina B. , Holla Vijaykumar , Simpson Amy , Mills Gordon B. , Mendelsohn John , Bernstam Elmer , Shaw Kenna , Meric-Bernstam Funda
Published: November 2017

High-throughput genomic and molecular profiling of tumors is emerging as an important clinical approach. Molecular profiling is increasingly being used to guide cancer patient care, especially in advanced and incurable cancers. However, navigating the scientific literature to make evidence-based clinical decisions based on molecular profiling results is overwhelming for many oncology clinicians and researchers. The Personalized Cancer Therapy website (www.personalizedcancertherapy.org) was created to provide an online resource for clinicians and researchers to facilitate navigation of available data. Specifically, this resource can be used to help identify potential therapy options for patients harboring oncogenic genomic alterations. Herein, we describe how content on www.personalizedcancertherapy.org is generated and maintained. We end with case scenarios to illustrate the clinical utility of the website. The goal of this publicly available resource is to provide easily accessible information to a broad oncology audience, as this may help ease the information retrieval burden facing participants in the precision oncology field. Cancer Res; 77(21); e123–6. ©2017 AACR.
TumorMap: Exploring the Molecular Similarities of Cancer Samples in an Interactive Portal
Authors: Newton Yulia , Novak Adam M. , Swatloski Teresa , McColl Duncan C. , Chopra Sahil , Graim Kiley , Weinstein Alana S. , Baertsch Robert , Salama Sofie R. , Ellrott Kyle , Chopra Manu , Goldstein Theodore C. , Haussler David , Morozova Olena , Stuart Joshua M.
Published: November 2017

Vast amounts of molecular data are being collected on tumor samples, which provide unique opportunities for discovering trends within and between cancer subtypes. Such cross-cancer analyses require computational methods that enable intuitive and interactive browsing of thousands of samples based on their molecular similarity. We created a portal called TumorMap to assist in exploration and statistical interrogation of high-dimensional complex “omics” data in an interactive and easily interpretable way. In the TumorMap, samples are arranged on a hexagonal grid based on their similarity to one another in the original genomic space and are rendered with Google's Map technology. While the important feature of this public portal is the ability for the users to build maps from their own data, we pre-built genomic maps from several previously published projects. We demonstrate the utility of this portal by presenting results obtained from The Cancer Genome Atlas project data. Cancer Res; 77(21); e111–4. ©2017 AACR.
The Digital Slide Archive: A Software Platform for Management, Integration, and Analysis of Histology for Cancer Research
Authors: Gutman David A. , Khalilia Mohammed , Lee Sanghoon , Nalisnik Michael , Mullen Zach , Beezley Jonathan , Chittajallu Deepak R. , Manthey David , Cooper Lee A.D.
Published: November 2017

Tissue-based cancer studies can generate large amounts of histology data in the form of glass slides. These slides contain important diagnostic, prognostic, and biological information and can be digitized into expansive and high-resolution whole-slide images using slide-scanning devices. Effectively utilizing digital pathology data in cancer research requires the ability to manage, visualize, share, and perform quantitative analysis on these large amounts of image data, tasks that are often complex and difficult for investigators with the current state of commercial digital pathology software. In this article, we describe the Digital Slide Archive (DSA), an open-source web-based platform for digital pathology. DSA allows investigators to manage large collections of histologic images and integrate them with clinical and genomic metadata. The open-source model enables DSA to be extended to provide additional capabilities. Cancer Res; 77(21); e75–78. ©2017 AACR.
Cannabis Use and Incidence of Testicular Cancer: A 42-Year Follow-up of Swedish Men between 1970 and 2011
Authors: Callaghan Russell C. , Allebeck Peter , Akre Olof , McGlynn Katherine A. , Sidorchuk Anna
Published: November 2017

Background: Given current drug policy reforms to decriminalize or legalize cannabis in numerous countries worldwide, the current study assesses the relation between cannabis use and the development of testicular cancer.

Methods: The study included a population-based sample (n = 49,343) of young men ages 18–21 years who underwent conscription assessment for Swedish military service in 1969–1970. The conscription process included a nonanonymous questionnaire eliciting information about drug use. Conscription information was linked to Swedish health and administrative registry data. Testicular cancers diagnosed between 1970 and 2011 were identified by International Classification of Diseases-7/8/9/10 testicular cancer codes in the Swedish National Patient Register, the Cancer Register, or the Cause of Death Register. Cox regression modeling was used to estimate the hazards associated with cannabis use and time to diagnosis of testicular cancer.

Results: No evidence was found of a significant relation between lifetime “ever” cannabis use and the subsequent development of testicular cancer [n = 45,250; 119 testicular cancer cases; adjusted HR (aHR), 1.42; 95% confidence interval (CI), 0.83–2.45]. “Heavy” cannabis use (defined as usage of more than 50 times in lifetime, as measured at conscription) was associated with the incidence of testicular cancer (n = 45,250; 119 testicular cancer cases; aHR 2.57; 95% CI, 1.02–6.50).

Conclusions: The current study provides additional evidence to the limited prior literature suggesting cannabis use may contribute to the development of testicular cancer.

Impact: Emerging changes to cannabis drug policy should consider the potential role of cannabis use in the development of testicular cancer. Cancer Epidemiol Biomarkers Prev; 26(11); 1644–52. ©2017 AACR.
The Future of Surveillance in the Context of Cancer Predisposition: Through the Murky Looking Glass
Authors: Malkin David , Nichols Kim E. , Schiffman Joshua D. , Plon Sharon E. , Brodeur Garrett M.
Published: November 2017

At least 10% of children with cancer harbor a disease-associated pathogenic variant in a known cancer predisposition gene. It is widely accepted that pathogenic variants affecting other genes, epigenetic factors, or abnormalities in additional gene products may contribute to the etiology of many more childhood cancers. Effective preventive measures exist for only a few cancer types associated with predisposing conditions, but the development and implementation of surveillance protocols aimed at reducing morbidity and mortality in at-risk children through the early detection of cancer has emerged as an important clinical tool. The articles in this Clinical Cancer Research series present international consensus generated recommendations for surveillance for a wide spectrum of cancer predisposition syndromes affecting children. In this article, we explore the challenges and opportunities for researchers and practitioners in the many fields affiliated with pediatric cancer, and we offer insights into what the future might hold as we continue our efforts to mitigate the impact of cancer susceptibility on children, their families and society. Clin Cancer Res; 23(21); e133–e7. ©2017 AACR.

See all articles in the online-only CCR Pediatric Oncology Series.
Prevalence of Aflatoxin-Associated TP53R249S Mutation in Hepatocellular Carcinoma in Hispanics in South Texas
Authors: Jiao Jingjing , Niu Weibo , Wang Ying , Baggerly Keith , Ye Yuanqing , Wu Xifeng , Davenport Dewitt , Almeda Jose Luis , Betancourt-Garcia Monica M. , Forse R. Armour , Stevenson Heather L. , Watt Gordon P. , McCormick Joseph B. , Fisher-Hoch Susan P. , Beretta Laura
Published: November 2017

We aimed to determine whether aflatoxin dietary exposure plays a role in the high incidence of hepatocellular carcinoma (HCC) observed among Hispanics in South Texas. We measured TP53R249S somatic mutation, hallmark of aflatoxin etiology in HCC, using droplet digital PCR and RFLP. TP53R249S mutation was detected in 3 of 41 HCC tumors from Hispanics in South Texas (7.3%). We also measured TP53R249S mutation in plasma cell-free DNA (cfDNA) from 218 HCC patients and 96 Hispanic subjects with advanced fibrosis or cirrhosis, from South Texas. The mutation was detected only in Hispanic and Asian HCC patients, and patients harboring TP53R249S mutation were significantly younger and had a shorter overall survival. The mutation was not detected in any Hispanic subject with advanced fibrosis or cirrhosis. Genes involved in cell-cycle control of chromosomal replication and in BRCA1-dependent DNA damage response were enriched in HCCs with TP53R249S mutation. The E2F1 family members, E2F1 and E2F4, were identified as upstream regulators. TP53R249S mutation was detected in 5.7% to 7.3% of Hispanics with HCC in South Texas. This mutation was associated with a younger age and worse prognosis. TP53R249S was however not detected in Hispanics in South Texas with cirrhosis or advanced fibrosis. Aflatoxin exposure may contribute to a small number of HCCs in Hispanics in South Texas, but the detection of TP53R249S mutation in plasma cfDNA is not a promising biomarker of risk assessment for HCC in subjects with cirrhosis or advanced fibrosis in this population. Cancer Prev Res; 11(2); 103–12. ©2017 AACR.
Next-Generation Sequencing in Diagnostic Pathology
Authors: Ilyas Mohammad
Published: November 2017

Interrogation of tissue informs on patient management through delivery of a diagnosis together with associated clinically relevant data. The diagnostic pathologist will usually evaluate the morphological appearances of a tissue sample and, occasionally, the pattern of expression of a limited number of biomarkers. Recent developments in sequencing technology mean that DNA and RNA from tissue samples can now be interrogated in great detail. These new technologies, collectively known as next-generation sequencing (NGS), generate huge amounts of data which can be used to support patient management. In order to maximize the utility of tissue interrogation, the molecular data need to be interpreted and integrated with the morphological data. However, in order to interpret the molecular data, the pathologist must understand the utility and the limitations of NGS data. In this review, the principles behind NGS technologies are described. In addition, the caveats in the interpretation of the data are discussed, and a scheme is presented to “classify” the types of data which are generated. Finally, a glossary of new terminology is included to help pathologists become familiar with the lexicon of NGS-derived molecular data.
Effects of Wearable Sensor-Based Balance and Gait Training on Balance, Gait, and Functional Performance in Healthy and Patient Populations: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Gordt Katharina , Gerhardy Thomas , Najafi Bijan , Schwenk Michael
Published: November 2017

Background: Wearable sensors (WS) can accurately measure body motion and provide interactive feedback for supporting motor learning. Objective: This review aims to summarize current evidence for the effectiveness of WS training for improving balance, gait and functional performance. Methods: A systematic literature search was performed in PubMed, Cochrane, Web of Science, and CINAHL. Randomized controlled trials (RCTs) using a WS exercise program were included. Study quality was examined by the PEDro scale. Meta-analyses were conducted to estimate the effects of WS balance training on the most frequently reported outcome parameters. Results: Eight RCTs were included (Parkinson n = 2, stroke n = 1, Parkinson/stroke n = 1, peripheral neuropathy n = 2, frail older adults n = 1, healthy older adults n = 1). The sample size ranged from n = 20 to 40. Three types of training paradigms were used: (1) static steady-state balance training, (2) dynamic steady-state balance training, which includes gait training, and (3) proactive balance training. RCTs either used one type of training paradigm (type 2: n = 1, type 3: n = 3) or combined different types of training paradigms within their intervention (type 1 and 2: n = 2; all types: n = 2). The meta-analyses revealed significant overall effects of WS training on static steady-state balance outcomes including mediolateral (eyes open: Hedges' g = 0.82, CI: 0.43-1.21; eyes closed: g = 0.57, CI: 0.14-0.99) and anterior-posterior sway (eyes open: g = 0.55, CI: 0.01-1.10; eyes closed: g = 0.44, CI: 0.02-0.86). No effects on habitual gait speed were found in the meta-analysis (g = -0.19, CI: -0.68 to 0.29). Two RCTs reported significant improvements for selected gait variables including single support time, and fast gait speed. One study identified effects on proactive balance (Alternate Step Test), but no effects were found for the Timed Up and Go test and the Berg Balance Scale. Two studies reported positive results on feasibility and usability. Only one study was performed in an unsupervised setting. Conclusion: This review provides evidence for a positive effect of WS training on static steady-state balance in studies with usual care controls and studies with conventional balance training controls. Specific gait parameters and proactive balance measures may also be improved by WS training, yet limited evidence is available. Heterogeneous training paradigms, small sample sizes, and short intervention durations limit the validity of our findings. Larger studies are required for estimating the true potential of WS technology.