bluuebunny/crossref_metadata_2025 huggingface dataset:
Automated identification of molecular effects of drugs (AIMED)
Authors: Fathiamini Safa , Johnson Amber M , Zeng Jia , Araya Alejandro , Holla Vijaykumar , Bailey Ann M , Litzenburger Beate C , Sanchez Nora S , Khotskaya Yekaterina , Xu Hua , Meric-Bernstam Funda , Bernstam Elmer V , Cohen Trevor
Published: April 2016

Introduction Genomic profiling information is frequently available to oncologists, enabling targeted cancer therapy. Because clinically relevant information is rapidly emerging in the literature and elsewhere, there is a need for informatics technologies to support targeted therapies. To this end, we have developed a system for Automated Identification of Molecular Effects of Drugs, to help biomedical scientists curate this literature to facilitate decision support.

Objectives To create an automated system to identify assertions in the literature concerning drugs targeting genes with therapeutic implications and characterize the challenges inherent in automating this process in rapidly evolving domains.

Methods We used subject-predicate-object triples (semantic predications) and co-occurrence relations generated by applying the SemRep Natural Language Processing system to MEDLINE abstracts and ClinicalTrials.gov descriptions. We applied customized semantic queries to find drugs targeting genes of interest. The results were manually reviewed by a team of experts.

Results Compared to a manually curated set of relationships, recall, precision, and F2 were 0.39, 0.21, and 0.33, respectively, which represents a 3- to 4-fold improvement over a publically available set of predications (SemMedDB) alone. Upon review of ostensibly false positive results, 26% were considered relevant additions to the reference set, and an additional 61% were considered to be relevant for review. Adding co-occurrence data improved results for drugs in early development, but not their better-established counterparts.

Conclusions Precision medicine poses unique challenges for biomedical informatics systems that help domain experts find answers to their research questions. Further research is required to improve the performance of such systems, particularly for drugs in development.
An in silico framework for integrating epidemiologic and genetic evidence with health care applications: ventilation-related pneumothorax as a case illustration
Authors: Torosyan Yelizaveta , Hu Yuzhi , Hoffman Sarah , Luo Qianlai , Carleton Bruce , Marinac-Dabic Danica
Published: April 2016

Objective To illustrate an in silico integration of epidemiologic and genetic evidence that is being developed at the Center for Devices and Radiological Health/US Food and Drug Administration as part of regulatory research on postmarket device performance. In addition to using conventional epidemiologic evidence from registries, this innovative approach explores the vast potential of open-access omics databases for identifying genetic evidence pertaining to devices.

Material and methods A retrospective analysis of Agency for Healthcare Research and Quality (AHRQ)/Healthcare Cost and Utilization Project (HCUPNet) data (2002–2011) was focused on the ventilation-related iatrogenic pneumothorax (Vent-IP) outcome in discharges with mechanical ventilation (MV) and continuous positive airway pressure (CPAP). The derived epidemiologic evidence was analyzed in conjunction with pre-existing genomic data from Gene Expression Omnibus/National Center for Biotechnology Information and other databases.

Results AHRQ/HCUPNet epidemiologic evidence showed that annual occurrence of Vent-IP did not decrease over a decade. While the Vent-IP risk associated with noninvasive CPAP comprised about 0.5%, the Vent-IP risk due to longer-term MV reached 2%. Along with MV posing an independent risk for Vent-IP, female sex and white race were found to be effect modifiers, resulting in the highest Vent-IP risk among mechanically ventilated white females. The Vent-IP risk was also potentiated by comorbidities associated with spontaneous pneumothorax (SP) and fibrosis. Consistent with the epidemiologic evidence, expression profiling in a number of animal models showed that the expression of several collagens and other SP/fibrosis-related genes was modified by ventilation settings.

Conclusion Integration of complementary genetic evidence into epidemiologic analysis can lead to a cost- and time-efficient discovery of the risk predictors and markers and thus can facilitate more efficient marker-based evaluation of medical product performance.
Optimizing vitamin D naming conventions in computerized order entry to support high-value care
Authors: White Andrew A , McKinney Christy M , Hoffman Noah G , Sutton Paul R
Published: April 2016

Objective: To reduce wasteful ordering of rare 1,25-OH vitamin D lab tests through use of a noninterruptive decision support tool.

Materials and Methods: We conducted a time series quality improvement study at 2 academic hospitals. The titles of vitamin D tests and the order in which they appeared in search results were changed to reflect the purpose and rarity of the tests. We used interruptive time series analyses to evaluate the changes we made.

Results: The estimated number of monthly tests ordered at the 2 hospitals increased, by 24.8 and 14.2, following the introduction of computerized provider order entry (CPOE) (both P < .001). When we changed the titles of the tests, the estimated number of monthly tests decreased at the 2 hospitals, by 22.1 and 11.3 (both P < .001). The search order did not affect test utilization.

Discussion: Changing catalog names in CPOE systems for infrequently used tests can reduce unintentional overuse. Users may prefer this to interruptive or restrictive interventions.

Conclusion: CPOE vendors and users should refine interfaces by incorporating human factors engineering. Health care institutions should monitor test utilization for unintended changes after CPOE implementation.
Testing electronic health records in the “production” environment: an essential step in the journey to a safe and effective health care system
Authors: Wright Adam , Aaron Skye , Sittig Dean F
Published: April 2016

Thorough and ongoing testing of electronic health records (EHRs) is key to ensuring their safety and effectiveness. Many health care organizations limit testing to test environments separate from, and often different than, the production environment used by clinicians. Because EHRs are complex hardware and software systems that often interact with other hardware and software systems, no test environment can exactly mimic how the production environment will behave. An effective testing process must integrate safely conducted testing in the production environment itself, using test patients. We propose recommendations for how to safely incorporate testing in production into current EHR testing practices, with suggestions regarding the incremental release of upgrades, test patients, tester accounts, downstream personnel, and reporting.
The pharmacist and the EHR
Authors: Nelson Scott D , Poikonen John , Reese Thomas , El Halta David , Weir Charlene
Published: April 2016

The adoption of electronic health records (EHRs) across the United States has impacted the methods by which health care professionals care for their patients. It is not always recognized, however, that pharmacists also actively use advanced functionality within the EHR. As critical members of the health care team, pharmacists utilize many different features of the EHR. The literature focuses on 3 main roles: documentation, medication reconciliation, and patient evaluation and monitoring. As health information technology proliferates, it is imperative that pharmacists’ workflow and information needs are met within the EHR to optimize medication therapy quality, team communication, and patient outcomes.
An appraisal of published usability evaluations of electronic health records via systematic review
Authors: Ellsworth Marc A , Dziadzko Mikhail , O'Horo John C , Farrell Ann M , Zhang Jiajie , Herasevich Vitaly
Published: April 2016

Objective: In this systematic review, we aimed to evaluate methodological and reporting trends present in the current literature by investigating published usability studies of electronic health records (EHRs).

Methods: A literature search was conducted for articles published through January 2015 using MEDLINE (Ovid), EMBASE, Scopus, and Web of Science, supplemented by citation and reference list reviews. Studies were included if they tested the usability of hospital and clinic EHR systems in the inpatient, outpatient, emergency department, or operating room setting.

Results: A total of 4848 references were identified for title and abstract screening. Full text screening was performed for 197 articles, with 120 meeting the criteria for study inclusion.

Conclusion: A review of the literature demonstrates a paucity of quality published studies describing scientifically valid and reproducible usability evaluations at various stages of EHR system development. A lack of formal and standardized reporting of EHR usability evaluation results is a major contributor to this knowledge gap, and efforts to improve this deficiency will be one step of moving the field of usability engineering forward.
Lower alert rates by clustering of related drug interaction alerts
Authors: Heringa Mette , Siderius Hidde , Floor-Schreudering Annemieke , de Smet Peter A G M , Bouvy Marcel L
Published: April 2016

Objective: We aimed to investigate to what extent clustering of related drug interaction alerts (drug-drug and drug-disease interaction alerts) would decrease the alert rate in clinical decision support systems (CDSSs).

Methods: We conducted a retrospective analysis of drug interaction alerts generated by CDSSs in community pharmacies. Frequently generated combinations of alerts were analyzed for associations in a 5% random data sample (dataset 1). Alert combinations with similar management recommendations were defined as clusters. The alert rate was assessed by simulating a CDSS generating 1 alert per cluster per patient instead of separate alerts. The simulation was performed in dataset 1 and replicated in another 5% data sample (dataset 2).

Results: Data were extracted from the CDSSs of 123 community pharmacies. Dataset 1 consisted of 841 572 dispensed prescriptions and 298 261 drug interaction alerts. Dataset 2 was comparable. Twenty-two frequently occurring alert combinations were identified. Analysis of these associated alert combinations for similar management recommendations resulted in 3 clusters (related to renal function, electrolytes, diabetes, and cardiovascular diseases). Using the clusters in alert generation reduced the alert rate within these clusters by 53–70%. The overall number of drug interaction alerts was reduced by 11% in dataset 1 and by 12% in dataset 2. This corresponds to a decrease of 21 alerts per pharmacy per day.

Discussion and conclusion: Using clusters of drug interaction alerts with similar management recommendations in CDSSs can substantially decrease the overall alert rate. Further research is needed to establish the applicability of this concept in daily practice.
Performance test of RM CLEAN and its evaluation with chi-square value
Authors: Miyashita Yoshimitsu , Ideguchi Shinsuke , Takahashi Keitaro
Published: April 2016

RM CLEAN is a standard method to reconstruct the distribution of cosmic magnetic fields and polarized sources along the line of sight (LOS) from the observed polarization spectrum. This method is similar to the CLEAN algorithm for aperture synthesis of radio telescope images but it is rather unclear in what cases RM CLEAN works well. In this paper, we evaluate the performance of RM CLEAN by simulating spectro-polarimetric observations of two compact sources located in the same LOS, varying the relative initial polarization angle and Faraday depth systematically. In particular, we focus on whether the two polarized sources can be resolved in the Faraday depth space and how well the source parameters can be estimated. We confirm the previous studies that two sources cannot be resolved when they are closely located in the Faraday depth space for specific values of the relative initial polarization angle. Further, we calculate the chi-square value for the fit between the mock polarization spectrum data and the one from RM CLEAN. We find that the chi-square value is not always significantly large even when RM CLEAN gives wrong results.
Breast MRI in the Diagnostic and Preoperative Workup Among Medicare Beneficiaries With Breast Cancer
Authors: Onega Tracy , Weiss Julia E. , Buist Diana S.M. , Tosteson Anna N.A. , Henderson Louise M. , Kerlikowske Karla , Goodrich Martha E. , O’Donoghue Cristina , Wernli Karen J. , DeMartini Wendy B. , Virnig Beth A. , Bennette Caroline S. , Hubbard Rebecca A.
Published: April 2016

Purpose:

We compared the frequency and sequence of breast imaging and biopsy use for the diagnostic and preoperative workup of breast cancer according to breast magnetic resonance imaging (MRI) use among older women.

Materials and Methods:

Using SEER-Medicare data from 2004 to 2010, we identified women with and without breast MRI as part of their diagnostic and preoperative breast cancer workup and measured the number and sequence of breast imaging and biopsy events per woman.

Results:

A total of 10,766 (20%) women had an MRI in the diagnostic/preoperative period, 32,178 (60%) had mammogram and ultrasound, and 10,669 (20%) had mammography alone. MRI use increased across study years, tripling from 2005 to 2009 (9%–29%). Women with MRI had higher rates of breast imaging and biopsy compared with those with mammogram and ultrasound or those with mammography alone (5.8 vs. 4.1 vs. 2.8, respectively). There were 4254 unique sequences of breast events; the dominant patterns for women with MRI were an MRI occurring at the end of the care pathway. Among women receiving an MRI postdiagnosis, 26% had a subsequent biopsy compared with 51% receiving a subsequent biopsy in the subgroup without MRI.

Conclusions:

Older women who receive breast MRI undergo additional breast imaging and biopsy events. There is much variability in the diagnostic/preoperative work-up in older women, demonstrating the opportunity to increase standardization to optimize care for all women.
Mental Health Utilization Patterns During a Stepped, Collaborative Care Effectiveness Trial for PTSD and Depression in the Military Health System
Authors: Belsher Bradley E. , Jaycox Lisa H. , Freed Michael C. , Evatt Daniel P. , Liu Xian , Novak Laura A. , Zatzick Douglas , Bray Robert M. , Engel Charles C.
Published: April 2016

Background:

Integrated health care models aim to improve access and continuity of mental health services in general medical settings. STEPS-UP is a stepped, centrally assisted collaborative care model designed to improve posttraumatic stress disorder (PTSD) and depression care by providing the appropriate intensity and type of care based on patient characteristics and clinical complexity. STEPS-UP demonstrated improved PTSD and depression outcomes in a large effectiveness trial conducted in the Military Health System. The objective of this study was to examine differences in mental health utilization patterns between patients in the stepped, centrally assisted collaborative care model relative to patients in the collaborative care as usual-treatment arm.

Methods:

Patients with probable PTSD and/or depression were recruited at 6 large military treatment facilities, and 666 patients were enrolled and randomized to STEPS-UP or usual collaborative care. Utilization data acquired from Military Health System administrative datasets were analyzed to determine mental health service use and patterns. Clinical complexity and patient characteristics were based on self-report questionnaires collected at baseline.

Results:

Compared with the treatment as usual arm, STEPS-UP participants received significantly more mental health services and psychiatric medications across primary and specialty care settings during the year of their participation. Patterns of service use indicated that greater clinical complexity was associated with increased service use in the STEPS-UP group, but not in the usual-care group.

Conclusions:

Results suggest that stepped, centrally assisted collaborative care models may increase the quantity of mental health services patients receive, while efficiently matching care on the basis of the clinical complexity of patients.
End-of-Life Care Intensity and Hospice Use
Authors: Wang Shi-Yi , Aldridge Melissa D. , Gross Cary P. , Canavan Maureen , Cherlin Emily , Johnson-Hurzeler Rosemary , Bradley Elizabeth
Published: April 2016

Objectives:

Despite increased hospice use over the last decade, end-of-life care intensity continues to increase. To understand this puzzle, we sought to examine regional variation in intensive end-of-life care and determine its associations with hospice use patterns.

Methods:

Using Medicare claims for decedents aged 66 years and above in 2011, we assessed end-of-life care intensity in the last 6 months of life across hospital referral regions (HRRs) as measured by proportion of decedents per HRR experiencing hospitalization, emergency department use, intensive care unit (ICU) admission, and number of days spent in hospital (hospital-days) and ICU (ICU-days). Using hierarchical generalized linear models and adjusting for patient characteristics, we examined whether these measures were associated with overall hospice use, very short (≤7 d), medium (8–179 d), or very long (≥180 d) hospice enrollment, focusing on very short stay.

Results:

End-of-life care intensity and hospice use patterns varied substantially across HRRs. Regional-level end-of-life care intensity was positively correlated with very short hospice enrollment. Comparing HRRs in the highest versus the lowest quintiles of intensity in end-of-life care, regions with more intensive care had higher rates of very short hospice enrollment, with adjusted odds ratios (AOR) 1.14 [99% confidence interval (CI), 1.04–1.25] for hospitalization; AOR, 1.23 (CI, 1.12–1.36) for emergency department use; AOR, 1.25 (CI, 1.14–1.38) for ICU admission; AOR, 1.10 (CI, 1.00–1.21) for hospital-days; and AOR, 1.20 (CI, 1.08–1.32) for ICU-days.

Conclusions:

At the regional level, increased end-of-life care intensity was consistently associated with very short hospice use.
In Situ Visualization of the Dynamics in Xylem Embolism Formation and Removal in the Absence of Root Pressure: A Study on Excised Grapevine Stems
Authors: Knipfer Thorsten , Cuneo Italo F. , Brodersen Craig R. , McElrone Andrew J.
Published: April 2016

Gas embolisms formed during drought can disrupt long-distance water transport through plant xylem vessels, but some species have the ability to remove these blockages. Despite evidence suggesting that embolism removal is linked to the presence of vessel-associated parenchyma, the underlying mechanism remains controversial and is thought to involve positive pressure generated by roots. Here, we used in situ x-ray microtomography on excised grapevine stems to determine if embolism removal is possible without root pressure, and if the embolism formation/removal affects vessel functional status after sample excision. Our data show that embolism removal in excised stems was driven by water droplet growth and was qualitatively identical to refilling in intact plants. When stem segments were rehydrated with H2O after excision, vessel refilling occurred rapidly (<1 h). The refilling process was substantially slower when polyethylene glycol was added to the H2O source, thereby providing new support for an osmotically driven refilling mechanism. In contrast, segments not supplied with H2O showed no refilling and increased embolism formation. Dynamic changes in liquid/wall contact angles indicated that the processes of embolism removal (i.e. vessel refilling) by water influx and embolism formation by water efflux were directly linked to the activity of vessel-associated living tissue. Overall, our results emphasize that root pressure is not required as a driving force for vessel refilling, and care should be taken when performing hydraulics measurements on excised plant organs containing living vessel-associated tissue, because the vessel behavior may not be static.
Anthropometric discriminators of type 2 diabetes among White and Black American adults
Authors: Hardy Dale S. , Stallings Devita T. , Garvin Jane T. , Gachupin Francine C. , Xu Hongyan , Racette Susan B.
Published: April 2016

Background

The aim of the present study was to determine the best anthropometric discriminators of type 2 diabetes mellitus (T2DM) among White and Black males and females in a large US sample.

Methods

We used Atherosclerosis Risk in Communities study baseline data (1987–89) from 15 242 participants (1827 with T2DM) aged 45–65 years. Anthropometric measures included a body shape index (ABSI), body adiposity index (BAI), body mass index, waist circumference (WC), waist:  height ratio (WHtR), and waist:  hip ratio (WHR). All anthropometric measures were standardized to Z‐scores. Using logistic regression, odds ratios for T2DM were adjusted for age, physical activity, and family history of T2DM. The Akaike information criterion and receiver operating characteristic C‐statistic were used to select the best‐fit models.

Results

Body mass index, WC, WHtR, and WHR were comparable discriminators of T2DM among White and Black males, and were superior to ABSI and BAI in predicting T2DM (P < 0.0001). Waist circumference, WHtR, and WHR were the best discriminators among White females, whereas WHR was the best discriminator among Black females. The ABSI was the poorest discriminator of T2DM for all race–gender groups except Black females. Anthropometric values distinguishing T2DM cases from non‐cases were lower for Black than White adults.

Conclusions

Anthropometric measures that included WC, either alone or relative to height (WHtR) or hip circumference (WHR), were the strongest discriminators of T2DM across race–gender groups. Body mass index was a comparable discriminator to WC, WHtR, and WHR among males, but not females.
Palaeovalleys in foreland ramp settings: what happens as accommodation decreases down dip?
Authors: Jerrett Rhodri M. , Flint Stephen S. , Brunt Rufus L.
Published: April 2016

Recent advances in our understanding of palaeovalleys are largely guided by examples from passive margins, in which accommodation increases down depositional dip. This study tests these models against a dataset from the Pennsylvanian Breathitt Group of the central Appalachian foreland basin, USA. This fluvio‐deltaic succession contains extensive erosionally based fluvio‐estuarine sand bodies that can be tracked over 80 km down depositional dip from a proximal zone of high accommodation close to the orogenic margin to a distal, lower accommodation zone close to the cratonic margin of the basin. The sand bodies are up to 25 m thick, multi‐storey and characterized in their lower parts by strongly amalgamated storeys containing sandy fluvial to estuarine bar accretion elements, and in their middle to upper parts by more fully preserved storeys up to 10 m thick and laterally extensive over 100s of metres. The upper storeys include abandonment channel‐fills of heterolithic marine or marginal marine deposits or muddy to sandy point‐bar elements. Three major regional‐scale architectures include: (i) Tabular sand bodies that everywhere incise open marine prodelta and mouth bar facies and are interpreted as palaeovalleys formed during falling stage and lowstand systems tracts, when eustatic sea‐level fall outpaced tectonic subsidence across the entire study area. (ii) Sand bodies that incise genetically related floodplain lake and/or bay‐fill minor mouth bar deposits up depositional dip and open marine prodelta and mouth bar facies down dip. These stacked distributary channel deposits map down dip into palaeovalleys and formed when up dip subsidence rate resulted in positive, but reduced rate of accommodation creation, while lower tectonic subsidence rate down‐dip resulted in incision. (iii) Sand bodies that incise genetically related floodplain, lake and/or bay‐fill minor mouth bars up dip and pass down‐dip into genetically related unconfined floodplain, prodelta and mouth bar deposits. These sand bodies represent stacked distributary channel fills and channel amalgamation was the product of high rates of lateral migration, typical of the behaviour of channels above their backwater reach. Case (2) sand bodies demonstrate that in rapidly subsiding foreland basins, cross‐shelf palaeovalleys may form down depositional dip from aggradational, distributive fluival strata. Additionally, the genetic relationship between stacked distributary channels and palaeovalleys supports recent models for palaeovalley formation that emphasize diachronous, cut‐and‐fill during falling stage and lowstands of relative sea level.
Casticin Induced Apoptosis in A375.S2 Human Melanoma Cells through the Inhibition of NF-κB and Mitochondria-Dependent Pathways In Vitro and Inhibited Human Melanoma Xenografts in a Mouse Model In Vivo
Authors: Shiue Yin-Wen , Lu Chi-Cheng , Hsiao Yu-Ping , Liao Ching-Lung , Lin Jing-Pin , Lai Kuang-Chi , Yu Chien-Chih , Huang Yi-Ping , Ho Heng-Chien , Chung Jing-Gung
Published: April 2016

Casticin, a polymethoxyflavone occurring in natural plants, has been shown to have anticancer activities. In the present study, we aims to investigate the anti-skin cancer activity of casticin on melanoma cells in vitro and the antitumor effect of casticin on human melanoma xenografts in nu/nu mice in vivo. A flow cytometric assay was performed to detect expression of viable cells, cell cycles, reactive oxygen species production, levels of [Formula: see text] and caspase activity. A Western blotting assay and confocal laser microscope examination were performed to detect expression of protein levels. In the in vitro studies, we found that casticin induced morphological cell changes and DNA condensation and damage, decreased the total viable cells, and induced G2/M phase arrest. Casticin promoted reactive oxygen species (ROS) production, decreased the level of [Formula: see text], and promoted caspase-3 activities in A375.S2 cells. The induced G2/M phase arrest indicated by the Western blotting assay showed that casticin promoted the expression of p53, p21 and CHK-1 proteins and inhibited the protein levels of Cdc25c, CDK-1, Cyclin A and B. The casticin-induced apoptosis indicated that casticin promoted pro-apoptotic proteins but inhibited anti-apoptotic proteins. These findings also were confirmed by the fact that casticin promoted the release of AIF and Endo G from mitochondria to cytosol. An electrophoretic mobility shift assay (EMSA) assay showed that casticin inhibited the NF-[Formula: see text]B binding DNA and that these effects were time-dependent. In the in vivo studies, results from immuno-deficient nu/nu mice bearing the A375.S2 tumor xenograft indicated that casticin significantly suppressed tumor growth based on tumor size and weight decreases. Early G2/M arrest and mitochondria-dependent signaling contributed to the apoptotic A375.S2 cell demise induced by casticin. In in vivo experiments, A375.S2 also efficaciously suppressed tumor volume in a xenotransplantation model. Therefore, casticin might be a potential therapeutic agent for the treatment of skin cancer in the future.
Investigation of Pionic Contribution in the Lepton and Antilepton Production Cross Section in p-Cu and p-Pt Collision
Authors: Rostami R. , Zolfagharpour F.
Published: April 2016

For detailed explanation of the experimental results of lepton production cross section in hadronic collisions such as nucleon-nucleon or nucleon-nuclei, it is of great importance to use quarks and sea quarks distribution function inside free and bound nucleons. In this paper, the role of pion cloud inside the nucleus in the structure function of Cu and Pt nuclei and the EMC ratio of these nuclei were investigated by using harmonic oscillator model. Then, in the framework of the Drell-Yan process and conventional nuclear theory, GRV’s quarks distribution functions and pionic quarks distribution functions were used to calculate lepton and antilepton production cross section in p-Cu and p-Pt scattering. From the results and based on the mentioned model, by considering pionic contribution, the theoretical results are improved.
Predicted 3D Model of the Rabies Virus Glycoprotein Trimer
Authors: Fernando Bastida-González , Yersin Celaya-Trejo , José Correa-Basurto , Paola Zárate-Segura
Published: April 2016

The RABVG ectodomain is a homotrimer, and trimers are often called spikes. They are responsible for the attachment of the virus through the interaction with nicotinic acetylcholine receptors, neural cell adhesion molecule (NCAM), and the p75 neurotrophin receptor (p75NTR). This makes them relevant in viral pathogenesis. The antigenic structure differs significantly between the trimers and monomers. Surfaces rich in hydrophobic amino acids are important for trimer stabilization in which the C-terminal of the ectodomain plays an important role; to understand these interactions between the G proteins, a mechanistic study of their functions was performed with a molecular model of G protein in its trimeric form. This verified its 3D conformation. The molecular modeling of G protein was performed by a I-TASSER server and was evaluated via a Rachamandran plot and ERRAT program obtained 84.64% and 89.9% of the residues in the favorable regions and overall quality factor, respectively. The molecular dynamics simulations were carried out on RABVG trimer at 310 K. From these theoretical studies, we retrieved the RMSD values from Cαatoms to assess stability. Preliminary model of G protein of rabies virus stable at 12 ns with molecular dynamics was obtained.
Fault Localization Analysis Based on Deep Neural Network
Authors: Zheng Wei , Hu Desheng , Wang Jing
Published: April 2016

With software’s increasing scale and complexity, software failure is inevitable. To date, although many kinds of software fault localization methods have been proposed and have had respective achievements, they also have limitations. In particular, for fault localization techniques based on machine learning, the models available in literatures are all shallow architecture algorithms. Having shortcomings like the restricted ability to express complex functions under limited amount of sample data and restricted generalization ability for intricate problems, the faults cannot be analyzed accurately via those methods. To that end, we propose a fault localization method based on deep neural network (DNN). This approach is capable of achieving the complex function approximation and attaining distributed representation for input data by learning a deep nonlinear network structure. It also shows a strong capability of learning representation from a small sized training dataset. Our DNN-based model is trained utilizing the coverage data and the results of test cases as input and we further locate the faults by testing the trained model using the virtual test suite. This paper conducts experiments on the Siemens suite and Space program. The results demonstrate that our DNN-based fault localization technique outperforms other fault localization methods like BPNN, Tarantula, and so forth.
Detection of Periodic Leg Movements by Machine Learning Methods Using Polysomnographic Parameters Other Than Leg Electromyography
Authors: Umut İlhan , Çentik Güven
Published: April 2016

The number of channels used for polysomnographic recording frequently causes difficulties for patients because of the many cables connected. Also, it increases the risk of having troubles during recording process and increases the storage volume. In this study, it is intended to detect periodic leg movement (PLM) in sleep with the use of the channels except leg electromyography (EMG) by analysing polysomnography (PSG) data with digital signal processing (DSP) and machine learning methods. PSG records of 153 patients of different ages and genders with PLM disorder diagnosis were examined retrospectively. A novel software was developed for the analysis of PSG records. The software utilizes the machine learning algorithms, statistical methods, and DSP methods. In order to classify PLM, popular machine learning methods (multilayer perceptron,K-nearest neighbour, and random forests) and logistic regression were used. Comparison of classified results showed that whileK-nearest neighbour classification algorithm had higher average classification rate (91.87%) and lower average classification error value (RMSE = 0.2850), multilayer perceptron algorithm had the lowest average classification rate (83.29%) and the highest average classification error value (RMSE = 0.3705). Results showed that PLM can be classified with high accuracy (91.87%) without leg EMG record being present.
Bacillus pumilusSeptic Arthritis in a Healthy Child
Authors: Shivamurthy V. M. , Gantt Soren , Reilly Christopher , Tilley Peter , Guzman Jaime , Tucker Lori
Published: April 2016

We report a case of septic arthritis caused by aBacillusspecies,B. pumilus, occurring in a healthy child. This organism rarely causes serious infections and has only been described in newborns and immunocompromised individuals or as a skin infection. This child developed an indolent joint swelling after a minor skin injury, and symptoms were initially thought most consistent with chronic arthritis. The case demonstrates that clinicians should consider joint infection in children presenting with acute monoarticular swelling, even without prominent systemic features.
Control-Scheduling Codesign Exploiting Trade-Off between Task Periods and Deadlines
Authors: Cha Hyun-Jun , Jeong Woo-Hyuk , Kim Jong-Chan
Published: April 2016

A control task’s performance heavily depends on its sampling frequency and sensing-to-actuation delay. More frequent sampling, that is, shorter period, improves the control performance. Similarly, shorter delay also has a positive effect. Moreover, schedulability is also a function of periods and deadlines. By taking into account the control performance and schedulability at the same time, this paper defines a period and deadline selection problem for fixed-priority systems. Our problem is to find the optimal periods and deadlines for given tasks that maximize the overall system performance. As our solution, this paper presents a novel heuristic algorithm that finds a high-quality suboptimal solution with very low complexity, which makes the algorithm practically applicable to large size task sets.
Needle Tip Position and Bevel Direction Have No Effect in the Fluoroscopic Epidural Spreading Pattern in Caudal Epidural Injections: A Randomized Trial
Authors: Kwon Won Kyoung , Kim Ah Na , Lee Pil Moo , Park Cheol Hwan , Kim Jae Hun
Published: April 2016

Background.Caudal epidural steroid injections (CESIs) are an effective treatment for pain. If the injection spreads in a specific pattern depending on the needle position or bevel direction, it would be possible to inject the agent into a specific and desired area.Objectives.We conducted a prospective randomized trial to determine if the needle position and bevel direction have any effect on the epidural spreading pattern in CESI.Methods.Demographic data of the patient were collected. During CESI, the needle position (middle or lateral) and direction (ventral or dorsal) were randomly allocated. Following fluoroscope-guided injection of 4 mL contrast media and 10 mL of injectates, the epidural spreading patterns (ventral or dorsal, bilateral or lateral) were imaged.Results.In the 210 CESIs performed, the needle tip position and bevel direction did not influence the epidural spreading patterns at L4-5 and L5-S1 disc levels. A history of Lumbar spine surgery was associated with a significantly limited spread to each disc level. A midline needle tip position was more effective than the lateral position in spreading to the distant disc levels.Conclusions.Neither the needle tip position nor the bevel direction affected the epidural drug spreading pattern during CESI.
Fixation Improvement through Biofeedback Rehabilitation in Stargardt Disease
Authors: Scuderi G. , Verboschi F. , Domanico D. , Spadea L.
Published: April 2016

Stargardt disease is the most common hereditary macular degeneration in juveniles. It is characterized by macular dystrophy associated with loss of central vision in the first or second decade of life, a “beaten-metal” appearance in the fovea or parafoveal region, yellowish flecks around the macula or in posterior area of the retina, progressive atrophy of the bilateral foveal retinal pigment epithelium, and the “dark choroid” sign on fundus fluorescein angiography in most cases. We report a case of Stargardt disease in a 26-year-old Caucasian female submitted to rehabilitative training with microperimetry MP-1 to find a new preferred retinal locus (PRL) and to train her to better her quality of life. Best corrected visual acuity, mean retinal sensitivity, fixation, bivariate contour ellipse area, and speed reading were evaluated before and after the training and results were discussed.
Lung Transplant Recipient with Pulmonary Alveolar Proteinosis
Authors: Tokman Sofya , Hahn M. Frances , Abdelrazek Hesham , Panchabhai Tanmay S. , Patel Vipul J. , Walia Rajat , Omar Ashraf
Published: April 2016

Pulmonary alveolar proteinosis (PAP) is a progressive lung disease characterized by accumulated surfactant-like lipoproteinaceous material in the alveoli and distal bronchioles. This accumulation is the result of impaired clearance by alveolar macrophages. PAP has been described in 11 solid organ transplant recipients, 9 of whom were treated with mammalian target of rapamycin inhibitors. We report a case of a lung transplant recipient treated with prednisone, mycophenolate mofetil (MMF), and tacrolimus who ultimately developed PAP, which worsened when MMF was replaced with everolimus.
Prediction Study on PCI Failure of Reactor Fuel Based on a Radial Basis Function Neural Network
Authors: Wei Xinyu , Wan Jiashuang , Zhao Fuyu
Published: April 2016

Pellet-clad interaction (PCI) is one of the major issues in fuel rod design and reactor core operation in water cooled reactors. The prediction of fuel rod failure by PCI is studied in this paper by the method of radial basis function neural network (RBFNN). The neural network is built through the analysis of the existing experimental data. It is concluded that it is a suitable way to reduce the calculation complexity. A self-organized RBFNN is used in our study, which can vary its structure dynamically in order to maintain the prediction accuracy. For the purpose of the appropriate network complexity and overall computational efficiency, the hidden neurons in the RBFNN can be changed online based on the neuron activity and mutual information. The presented method is tested by the experimental data from the reference, and the results demonstrate its effectiveness.
Immune Cells in Cancer Therapy and Drug Delivery
Authors: Eyileten Ceren , Majchrzak Kinga , Pilch Zofia , Tonecka Katarzyna , Mucha Joanna , Taciak Bartlomiej , Ulewicz Katarzyna , Witt Katarzyna , Boffi Alberto , Krol Magdalena , Rygiel Tomasz P.
Published: April 2016

Recent studies indicate the critical role of tumour associated macrophages, tumour associated neutrophils, dendritic cells, T lymphocytes, and natural killer cells in tumourigenesis. These cells can have a significant impact on the tumour microenvironment via their production of cytokines and chemokines. Additionally, products secreted from all these cells have defined specific roles in regulating tumour cell proliferation, angiogenesis, and metastasis. They act in a protumour capacityin vivoas evidenced by the recent studies indicating that macrophages, T cells, and neutrophils may be manipulated to exhibit cytotoxic activity against tumours. Therefore therapy targeting these cells may be promising, or they may constitute drug or anticancer particles delivery systems to the tumours. Herein, we discussed all these possibilities that may be used in cancer treatment.
Maximum Temperature and Relaxation Time in Wet Surface Grinding for a General Heat Flux Profile
Authors: González-Santander J. L.
Published: April 2016

We solve the boundary-value problem of the heat transfer modeling in wet surface grinding, considering a constant heat transfer coefficient over the workpiece surface and a general heat flux profile within the friction zone between wheel and workpiece. We particularize this general solution to the most common heat flux profiles reported in the literature, that is, constant, linear, parabolic, and triangular. For these cases, we propose a fast method for the numerical computation of maximum temperature, in order to avoid the thermal damage of the workpiece. Also, we provide a very efficient method for the numerical evaluation of the transient regime duration (relaxation time).
Minimally Invasive Spinal Surgery with Intraoperative Image-Guided Navigation
Authors: Kim Terrence T. , Johnson J. Patrick , Pashman Robert , Drazin Doniel
Published: April 2016

We present our perioperative minimally invasive spine surgery technique using intraoperative computed tomography image-guided navigation for the treatment of various lumbar spine pathologies. We present an illustrative case of a patient undergoing minimally invasive percutaneous posterior spinal fusion assisted by the O-arm system with navigation. We discuss the literature and the advantages of the technique over fluoroscopic imaging methods: lower occupational radiation exposure for operative room personnel, reduced need for postoperative imaging, and decreased revision rates. Most importantly, we demonstrate that use of intraoperative cone beam CT image-guided navigation has been reported to increase accuracy.
Biosimilars in Developed and Developing East and Southeast Asian Countries: Japan, South Korea, and Malaysia—Overview, Evolution, and Regulations Assessment
Authors: Bas Tomas Gabriel , Oliu Castillo Carolina
Published: April 2016

The development of biological products has experienced continuous growth over the past three decades. The expiration of patent protection for many biological medicines has led to the development of biosimilars in many countries around the world. This paper reviews the literature on biosimilar drugs and covers their therapeutic status, clinical trials, approved biosimilars, and regulatory guidelines in Japan, South Korea, and Malaysia. The literature suggests that biosimilars are comparable but not identical to the reference product. They are not a generic version of an innovative product and do not ensure therapeutic equivalence. Biosimilars present more challenges than conventional generics and their marketing approval is also much more complicated. Guidelines for biosimilars were published in Japan in July 2009 by the Ministry of Health, Labour and Welfare (MHLW), in South Korea in March 2009 by the Ministry of Food and Drug Safety (MFDS), and in Malaysia in July 2008 by the National Pharmaceutical Control Bureau (NPCB).
Trends of Prevalence of Uncontrolled Risk Factors for Cerebrocardiovascular Disease: Southern Italy from 1988/9 to 2008/9
Authors: Capuano Vincenzo , Lamaida Norman , Capuano Ernesto , Capuano Rocco , Capuano Eduardo , Mazzotta Gianfranco
Published: April 2016

The aim of this study was to determine the trends of cardiovascular risk factor prevalence between 1988/9 and 2008/9 in the 25–74-year-old population in an area of Southern Italy. We compared three cross-sectional studies conducted in random population samples, in 1988/9, 1998/9, and 2008/9 in Salerno, Italy. The methodology of data collection (lipid profile, systolic and diastolic blood pressure, glycaemia, and smoking) and conducting tests which the population underwent during the three phases was standardized and comparable. Prevalence of diabetes, hypertension, hypercholesterolemia, and smoking was calculated and standardized for age. A total of 3491 subjects were included. From 1988/9 to 2008/9, in males, the prevalence of all four risk factors was reduced. In women, there was a clear reduction of hypertension, a similar prevalence of hypercholesterolemia, and an increase of smoking and diabetes. In the area of Salerno, our data confirm that the global prevalence of the major risk factors is decreasing in men, but their absolute values are still far from optimization. In women, diabetes and smoking showed a negative trend, therefore requiring targeted interventions. These data are now used as a base for executive targeted programs to improve prevention of cardiovascular disease in our community.
Cat Swarm Optimization Based Functional Link Artificial Neural Network Filter for Gaussian Noise Removal from Computed Tomography Images
Authors: Kumar M. , Mishra S. K. , Sahu S. S.
Published: April 2016

Gaussian noise is one of the dominant noises, which degrades the quality of acquired Computed Tomography (CT) image data. It creates difficulties in pathological identification or diagnosis of any disease. Gaussian noise elimination is desirable to improve the clarity of a CT image for clinical, diagnostic, and postprocessing applications. This paper proposes an evolutionary nonlinear adaptive filter approach, using Cat Swarm Functional Link Artificial Neural Network (CS-FLANN) to remove the unwanted noise. The structure of the proposed filter is based on the Functional Link Artificial Neural Network (FLANN) and the Cat Swarm Optimization (CSO) is utilized for the selection of optimum weight of the neural network filter. The applied filter has been compared with the existing linear filters, like the mean filter and the adaptive Wiener filter. The performance indices, such as peak signal to noise ratio (PSNR), have been computed for the quantitative analysis of the proposed filter. The experimental evaluation established the superiority of the proposed filtering technique over existing methods.
Clinical Profile of Dengue Fever in Children: A Study from Southern Odisha, India
Authors: Mishra Shubhankar , Ramanathan Ramya , Agarwalla Sunil Kumar
Published: April 2016

Background. In India, dengue epidemics are becoming more frequent (WHO, 2008). The majority of dengue viral infections are self-limiting, but complications may cause high morbidity and mortality.Objectives. To assess the clinical profile of the dengue infection in children less than 14 years of age and to evaluate the outcomes of dengue fever from September 2013 to August 2015 at the Pediatric Department of Maharaja Krishna Chandra Gajapati Medical College, the largest tertiary care hospital of southern Odisha.Results. A total of 97 cases were classified into 84 (86.59%) nonsevere and 13 (13.40%) severe dengue cases. The most common age of presentation was above 11 yrs. The mean age of admission was 8.7 yrs. The most common presenting symptom was fever seen in 100% and hepatomegaly (43.8%), the most common physical finding. Gastrointestinal bleeding was markedly seen in severe dengue (76.9%). Elevation in aspartate transaminase (SGOT) was found in 47.42% and thrombocytopenia in 27.5%. The correlation between hepatomegaly and elevated SGOT was significant (Pvalue 0.0346). Case fatality rate (CFR) was 1.03%. The mean duration of hospitalisation was 3.8 days.Conclusion. In children, if symptoms like fever, pain, rashes, and vomiting are associated with hepatomegaly and elevated SGOT in context of low TPC, a strong possibility of dengue fever is present, especially in an epidemic setting. Early suspicion and effective management can reduce the severity.