bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatiotemporal Evolution of Atmospheric Ammonia Columns over the Indo-Gangetic Plain by Exploiting Satellite Observations
Authors: Tanvir Aimon , Khokhar Muhammad Fahim , Javed Zeeshan , Sandhu Osama , Mustansar Tehreem , Shoaib Asadullah
Published: July 2019

This study was aimed at presenting a continuous and spatially coherent picture of ammonia (NH3) distribution over the Indo-Gangetic Plain (IGP) by exploiting satellite observations. Atmospheric columns of ammonia were mapped over South Asia by using TES observations on board NASA’s Aura satellite. Monthly mean data were used to identify emission sources of atmospheric ammonia across the South Asian region. Data were analysed to explore temporal trends, seasonal cycles, and hot spots of atmospheric ammonia within the study area. The results show that the IGP region has the most ammonia concentrations in terms of column densities, and hence this region has been identified as an ammonia hot spot. This is attributed majorly to extensive agricultural activity. Time series showed a slight increase in ammonia column densities over the study area from 2004 to 2011. Different seasonal cycles were identified across the IGP region with maximum NH3 columns observed during the month of July in most of the subregions. Seasonality in an ammonia column is driven by different cropping patterns and meteorological conditions in the IGP subregions. Global emission inventories of atmospheric ammonia were largely overestimating as compared to satellite observations.
Evaluation of Photocatalytic and Protein Adsorption Properties of Anodized Titanium Plate Immersed in Simulated Body Fluid
Authors: Sawada Ryoji , Katou Yuya , Shibata Hirofumi , Katayama Max , Nonami Toru
Published: July 2019

Titanium-based materials are widely used for implant treatments such as artificial dental roots. Surface treatment has the potential to improve not only the biocompatibility but also the chemical and mechanical durability of the surface without changing the mechanical properties of the metal. A relatively thick titanium oxide film can be formed by the anodic oxidation method. Phosphoric acid or sulfuric acid electrolytic solution has previously been used for anodic oxidation. Such anodized films have excellent film hardness, abrasion resistance, and adhesion. In this study, titanium plate was anodized using an aqueous solution of sulfuric acid in which titanium oxide powder was suspended. A 2800-nm-thick titanium oxide film was formed, which was thicker than that obtained using phosphoric acid electrolyte. The titanium plate was immersed in simulated body fluid for 1 day to evaluate the photocatalytic activity and protein adsorption ability, and a homogeneous crack-free hydroxyapatite layer was formed. This titanium plate showed high methylene blue bleaching capacity. The adsorption ability of the acidic protein of the anodized titanium plate subjected to the above treatment was high. This suggests that this titanium plate has antimicrobial properties and protein adsorption ability. Thus, we report that a titanium plate, anodized with a sulfuric acid aqueous electrolyte solution containing suspended TiO2 powder and immersed in simulated body fluid, might behave as an antibacterial and highly biocompatible implant material.
Investigation on Seismic Damage Model Test of a High Concrete Gravity Dam Based on Application of FBG Strain Sensor
Authors: Wang Mingming , Chen Jianyun , Wei Hai , Song Bingyue , Xiao Weirong
Published: July 2019

A 203‐m‐high gravity dam being built in earthquake‐prone areas needs to be investigated very carefully to determine its dynamic responses, damage mechanism, and safety evaluation. The dynamic characteristics, seismic responses, failure mode, and safety evaluation of the above structure are presented through dynamic fracture test for small‐scale model on shaking table. Because the strength of the model material is very low, the traditional strain gauge is also not easy to be glued to the surface of model. It is difficult to measure the accurate strain data of small‐scale model during testing. Therefore, Fiber Bragg Grating (FBG) strain sensor is presented to obtain the strain of small‐scale model during testing, due to its high sensitivity. The dynamic strain and residual strain are obtained with the FBG sensors embedded in model. The FBG sensor is adhered to model material completely and shows advantages of ease for installation, high sensitivity, and reliability compared with traditional resistance strain gauge. The model during testing is submitted with earthquake wave from the Chinese Code. In the experiment, the peak ground acceleration (PGA) of the first crack in the model indicates the safety level of the gravity dam. The crack locations and forms determine the damageable part of gravity dam under intense earthquake. After the final analysis, the safety evaluation result of the gravity dam under strong earthquake is given in order to guide the implementation of the project.
Impact of Speller Size on a Visual P300 Brain-Computer Interface (BCI) System under Two Conditions of Constraint for Eye Movement
Authors: Ron-Angevin R. , Garcia L. , Fernández-Rodríguez Á. , Saracco J. , André J. M. , Lespinet-Najib V.
Published: July 2019

The vast majority of P300-based brain-computer interface (BCI) systems are based on the well-known P300 speller presented by Farwell and Donchin for communication purposes and an alternative to people with neuromuscular disabilities, such as impaired eye movement. The purpose of the present work is to study the effect of speller size on P300-based BCI usability, measured in terms of effectiveness, efficiency, and satisfaction under overt and covert attention conditions. To this end, twelve participants used three speller sizes under both attentional conditions to spell 12 symbols. The results indicated that the speller size had, in both attentional conditions, a significant influence on performance. In both conditions (covert and overt), the best performances were obtained with the small and medium speller sizes, both being the most effective. The speller size did not significantly affect workload on the three speller sizes. In contrast, covert attention condition produced very high workload due to the increased resources expended to complete the task. Regarding users’ preferences, significant differences were obtained between speller sizes. The small speller size was considered as the most complex, the most stressful, the less comfortable, and the most tiring. The medium speller size was always considered in the medium rank, which is the speller size that was evaluated less frequently and, for each dimension, the worst one. In this sense, the medium and the large speller sizes were considered as the most satisfactory. Finally, the medium speller size was the one to which the three standard dimensions were collected: high effectiveness, high efficiency, and high satisfaction. This work demonstrates that the speller size is an important parameter to consider in improving the usability of P300 BCI for communication purposes. The obtained results showed that using the proposed medium speller size, performance and satisfaction could be improved.
Determination of the Surface Roughness Parameter and Wind Shear Exponent of Kisii Region from the On-Site Measurement of Wind Profiles
Authors: Laban Ongaki N. , Maghanga Christopher M. , Joash Kerongo
Published: July 2019

The research sought to investigate the surface roughness parameter (Zo) and wind shear exponent (α) of Kisii region (elevation 1710m above sea level, 0.68°S, 34.79°E). A six-month experiment was set at three sites of Kisii region. Two PRO AcuRite 01036 Wireless Weather Stations with pro+ 5-in-1 Sensors were placed at different hub heights above the ground and data were sent and received by a display board set at a room through remote sensing at an interval of 12 minutes. Data was collected from the display board through the pc connect software, grouped into discrete data and then calculated to represent mean wind speed, diurnal variation, daily variation, and monthly variations. The calculated averages of wind speeds at hub heights of 10m and 13m were then used to determine the wind shear exponent and surface roughness parameter of the sites. The wind shear exponents were found to be 0.92, 0.41, and 0.54 for Nyamecheo, Kisii University, and Ikobe stations, respectively, with an average of 0.64. The roughness parameter was also calculated and found to be 3.75, 1.32, and 1.96 for Nyamecheo, Kisii University (KSU), and Ikobe, respectively, with an average of 2.35.
Dynamic Multiobjective Software Project Scheduling Optimization Method Based on Firework Algorithm
Authors: Cheng Jian , Ji Jianjiao , Guo Yi-nan , Ji Junhua
Published: July 2019

Software project scheduling is essentially a kind of project scheduling problem with limited human resources. During the development process of a software product, reworking the completed projects, reassessing the workload, and changing the number of employees or their skills are the frequently occurring dynamic issues having direct influences on designing a scheduling scheme. Taking the development cost and duration, the robustness, and the stability of the scheduling schemes as the objective functions, software project scheduling is modeled as a dynamic four‐objective optimization problem. The various programming habits among the employees form the specific constraints for the reworking tasks, and the skills of the employees vary due to the effects of learning and forgetting. To solve this problem, an improved multiobjective firework algorithm with a novel explosion operator and reservation strategy is incorporated with rescheduling methods to fully guide the evolution by using the historical evolutionary knowledge. The experimental results indicate that the proposed method has better scheduling performance, and the optimal scheduling schemes have better robustness and stability.
Knee–Hip–Spine Syndrome: Improvement in Preoperative Abnormal Posture following Total Knee Arthroplasty
Authors: Oshima Yasushi , Watanabe Nobuyoshi , Iizawa Norishige , Majima Tokifumi , Kawata Mitsuhiro , Takai Shinro
Published: July 2019

An ergonomic upright body posture is maintained by the alignment of the spine, pelvis, and lower extremities, and the muscle strength of body trunk and lower extremities. The posture varies with age because of the degenerative changes in the involved structures and the weakening of the muscles. The compensatory mechanisms underlying these changes have recently been evaluated, and the loss of lumbar lordosis results in spinal kyphosis, pelvic retroversion, hip extension, knee flexion, and ankle dorsiflexion. These mechanisms are referred to as the hip–spine and knee–spine syndromes. The spine, hip, and knee are anatomically connected, and the pain and discomfort of the lower back, hip, and knee frequently arise due to degenerative changes of these structures. Thus, these mechanisms are considered as the knee–hip–spine syndrome. Spinal fusion, total hip arthroplasty, and total knee arthroplasty are the surgical procedures for severe degeneration, and their clinical outcomes for the affected sites are promising. However, despite surgeries, other structures may degenerate and result in complications, such as proximal junctional kyphosis and hip dislocation, following spinal fusion. Therefore, it is necessary to evaluate each patient under specific conditions and to treat each section while considering associations between the target structure and entire body. The purpose of this article is to introduce postural maintenance, variations with age, and improvements with surgical interventions of spine, hip, and knee as the knee–hip–spine syndrome.
Combining Diagnostic Imaging and Pathology for Improving Diagnosis and Prognosis of Cancer
Authors: Schillaci Orazio , Scimeca Manuel , Toschi Nicola , Bonfiglio Rita , Urbano Nicoletta , Bonanno Elena
Published: July 2019

In the era of personalized medicine, the management of oncological patients requires a translational and multidisciplinary approach. During early phases of cancer development, biochemical alterations of cell metabolism occur much before the formation of detectable tumour masses. Current molecular imaging techniques, targeted to the study of molecular kinetics, employ molecular tracers capable of detecting cancer lesions with both high sensitivity and specificity while also providing essential information for both prognosis and therapy. On the contrary, complementary and crucial information is provided by histopathological examination and ancillary techniques such as immunohistochemistry. Thus, the successful collaboration between diagnostic imaging and anatomic pathology can represent a fundamental step in the “tortuous” but decisive path towards personalized medicine.
Do Patients with Implants Experience Strong Sensations That Lead to Early Termination of MRI Examinations?
Authors: Steinbacher J. , McCoy M. R. , Klausner F. , Wallner W. , Oellerer A. , Machegger L.
Published: July 2019

Purpose. Many patients with metallic implants are aware of the potential dangers in an MRI environment. Some implants cause sensations perceptible by the patient during an MRI scan. We wanted to find out if patients having an implant abort MRI scans more often than patients without implants. Furthermore, we wanted to know if the number of implants of a patient has an influence on the number of aborted MRI scans. As we use 3T MRI scanners from different manufacturers we wanted to see the influence of the “ScanWise” software option where scan parameters are adapted automatically to the maximal allowed limits of implant values. This publication should help to reduce possible anxiety in patients with implants. Materials and Methods. From May 15th 2017 until July 17th 2018 the implant type of patients was recorded. We looked how often aborted MRI scans coincided with the occurrence of implants and the MRI scanner type used. Results. 4088 examinations were collected for the analysis. No influence of implants on aborted MRI scans was registered. No influence of the number of implants on aborted MRI scans was registered. No influence of the use of “ScanWise” software on aborted MRI scans was registered when different scanners were compared. Conclusion. “MR Safe” or “MR Conditional” labelled implants did not have an impact on the MRI examinations. “ScanWise” software does not affect how MRI examinations are tolerated.
Feature Selection Method Based on Partial Least Squares and Analysis of Traditional Chinese Medicine Data
Authors: Huang Canyi , Du Jianqiang , Nie Bin , Yu Riyue , Xiong Wangping , Zeng Qingxia
Published: July 2019

The partial least squares method has many advantages in multivariable linear regression, but it does not include the function of feature selection. This method cannot screen for the best feature subset (referred to in this study as the “Gold Standard”) or optimize the model, although contrarily using the L1 norm can achieve the sparse representation of parameters, leading to feature selection. In this study, a feature selection method based on partial least squares is proposed. In the new method, exploiting partial least squares allows extraction of the latent variables required for performing multivariable linear regression, and this method applies the L1 regular term constraint to the sum of the absolute values of the regression coefficients. This technique is then combined with the coordinate descent method to perform multiple iterations to select a better feature subset. Analyzing traditional Chinese medicine data and University of California, Irvine (UCI), datasets with the model, the experimental results show that the feature selection method based on partial least squares exhibits preferable adaptability for traditional Chinese medicine data and UCI datasets.
On a 2D Model of Avascular Tumor with Weak Allee Effect
Authors: Feng Peng , Dai Zhewei , Wallace Dorothy
Published: July 2019

Recent studies reveal that Allee effect may play important roles in the growth of tumor. We present one of the first mathematical models of avascular tumor that incorporates the weak Allee effect. The model considers the densities of tumor cells in three stages: proliferating cells, quiescent cells, and necrotic cells. We investigate how Allee effect impacts the growth of the avascular tumor. We also investigate the effect of apoptosis of proliferating cells and necrosis of quiescent cells. The system is numerically solved in 2D using different sets of parameters. We show that Allee effect and apoptosis play important roles in the growth of tumor and the formation of necrotic core.
Effect of Calcium and Vitamin D Supplements as an Adjuvant Therapy to Metformin on Menstrual Cycle Abnormalities, Hormonal Profile, and IGF-1 System in Polycystic Ovary Syndrome Patients: A Randomized, Placebo-Controlled Clinical Trial
Authors: Kadoura Sally , Alhalabi Marwan , Nattouf Abdul Hakim
Published: July 2019

Objective. This study aims to investigate the effect of combining calcium and vitamin D supplements with metformin on menstrual cycle abnormalities, gonadotropins, and IGF-1 system in vitamin D-deficient/insufficient PCOS women. Study Design. This is a randomized, placebo-controlled clinical trial. Setting. This study was performed in Damascus University of Obstetrics and Gynecology Hospital and Orient Hospital, in Damascus, Syria. Materials and Methods. Forty PCOS women with 25-OH-vitamin D < 30 ng/ml were randomly assigned to take either metformin (1500 mg/daily) plus placebo or metformin (1500 mg/daily) plus calcium (1000 mg/daily) and vitamin D3 (6000 IU/daily) orally for 8 weeks. Serum levels of gonadotropins (luteinizing hormone (LH) and follicle-stimulating hormone (FSH)), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding protein-1 (IGFBP-1) were detected at the baseline during the early follicular phase of a spontaneous or induced menstrual cycle and after 8 weeks of intervention (except for the final gonadotropins levels which were assayed from samples obtained during the early follicular phase of a spontaneous menstrual cycle). Results. Thirty-four patients (85%) completed the study. After 8 weeks of intervention, calcium and vitamin D co-supplementation led to a significant increase in 25-OH-vitamin D levels and calcium levels in the supplementation group compared to the other group (change in 25-OH-vitamin D levels: +19.38 ± 7.78 vs +0.11 ± 4.79 ng/ml, respectively; p value=0.0001) (change in calcium levels: +0.83 ± 0.82 vs +0.01 ± 0.86 mg/dl, respectively; p value=0.014). An improvement in menstrual cycle irregularity was detected in 38.5% and 58.8% of patients in metformin-placebo group and metformin-calcium-vitamin D group, respectively; but the change was statistically significant only in the supplementation group (p value=0.002). Nevertheless, the means of changes from baseline in gonadotropins levels (serum levels of LH, FSH, and LH to FSH ratio) and the studied parameters of IGF-1 system (serum levels of IGF-1, IGFBP-1, and IGF-1 to IGFBP-I ratio) did not differ significantly between the two groups. Conclusions. Calcium and vitamin D supplements can support metformin effect on regulation of menstrual cycle irregularity in vitamin D-deficient/insufficient PCOS patients, but this effect is not associated with any significant changes in gonadotropins or IGF-1 system. These results suggest a possible role of calcium and vitamin D supplements in managing PCOS. However, further studies are needed to identify the underlying mechanisms. The Clinical Trial Registration Number is NCT03792984.
Global Dynamics of a 3 × 6 System of Difference Equations
Authors: Qureshi S. M. , Khan A. Q.
Published: July 2019

In the proposed work, global dynamics of a 3×6 system of rational difference equations has been studied in the interior of R+3. It is proved that system has at least one and at most seven boundary equilibria and a unique +ve equilibrium under certain parametric conditions. By utilizing method of Linearization, local dynamical properties about equilibria have been investigated. It is shown that every +ve solution of the system is bounded, and equilibrium P0 becomes a globally asymptotically stable if α1<α2,α4<α5, α7<α8. It is also shown that every +ve solution of the system converges to P0. Finally theoretical results are verified numerically.
Carcinoembryonic Antigen Levels and Survival in Stage III Colon Cancer:Post hocAnalysis of the MOSAIC and PETACC-8 Trials
Authors: Auclin Edouard , Taieb Julien , Lepage Come , Aparicio Thomas , Faroux Roger , Mini Enrico , Folprecht Gunnar , Salazar Ramon , Benetkiewicz Magdalena , Banzi Maria , Louvet Christophe , Van Laethem Jean-Luc , Tabernero Josep , Hickish Tamas , de Gramont Aimery , André Thierry , Vernerey Dewi
Published: July 2019

Background:

We explored and validated the association of postoperative carcinoembryonic antigen (CEA) with disease-free survival (DFS) and overall survival (OS) in stage III colon cancer.

Methods:

Patients with stage III colon cancer from the MOSAIC and PETACC-8 trials were enrolled. The relation between CEA and outcomes was continuously modeled with the restricted cubic splines (RCS) method. Association of CEA with outcomes was assessed by the Kaplan–Meier method, with two risk groups among patients with a CEA level ≤5 ng/mL. Multivariate Cox proportional hazard models were constructed.

Results:

The CEA level was available in 1,292 (96%) and 2,477 (97%) patients in the discovery and validation cohorts. The RCS analysis confirmed that patients with a CEA level >5 ng/mL were at highest risk of recurrence or death and those with a CEA level ≤5 ng/mL presented a heterogeneous risk population. In the discovery cohort, the 3-year DFS rate was 75%, 65%, and 45% in a group of patients with CEA level of 0–1.30 ng/mL (n = 630), 1.30–5 ng/mL (n = 613), and >5 ng/mL (n = 49), respectively (P < 0.001). CEA was independently associated with endpoints. All findings were confirmed in the validation cohort.

Conclusions:

Postoperative CEA level was highly and independently associated with DFS and OS, especially in patients with a CEA level of ≤5 ng/mL, suggesting that this cutoff is not optimal.

Impact:

CEA levels should be applied more accurately in future trials and clinical practice.
Genomic Correlates of Disease Progression and Treatment Response in Prospectively Characterized Gliomas
Authors: Jonsson Philip , Lin Andrew L. , Young Robert J. , DiStefano Natalie M. , Hyman David M. , Li Bob T. , Berger Michael F. , Zehir Ahmet , Ladanyi Marc , Solit David B. , Arnold Angela G. , Stadler Zsofia K. , Mandelker Diana , Goldberg Michael E. , Chmielecki Juliann , Pourmaleki Maryam , Ogilvie Shahiba Q. , Chavan Shweta S. , McKeown Andrew T. , Manne Malbora , Hyde Allison , Beal Kathryn , Yang T. Jonathan , Nolan Craig P. , Pentsova Elena , Omuro Antonio , Gavrilovic Igor T. , Kaley Thomas J. , Diamond Eli L. , Stone Jacqueline B. , Grommes Christian , Boire Adrienne , Daras Mariza , Piotrowski Anna F. , Miller Alexandra M. , Gutin Philip H. , Chan Timothy A. , Tabar Viviane S. , Brennan Cameron W. , Rosenblum Marc , DeAngelis Lisa M. , Mellinghoff Ingo K. , Taylor Barry S.
Published: July 2019

Purpose:

The genomic landscape of gliomas has been characterized and now contributes to disease classification, yet the relationship between molecular profile and disease progression and treatment response remain poorly understood.

Experimental Design: We integrated prospective clinical sequencing of 1,004 primary and recurrent tumors from 923 glioma patients with clinical and treatment phenotypes.

Results:

Thirteen percent of glioma patients harbored a pathogenic germline variant, including a subset associated with heritable genetic syndromes and variants mediating DNA repair dysfunctions (29% of the total) that were associated with somatic biallelic inactivation and mechanism-specific somatic phenotypes. In astrocytomas, genomic alterations in effectors of cell-cycle progression correlated with aggressive disease independent of IDH mutation status, arose preferentially in enhancing tumors (44% vs. 8%, P < 0.001), were associated with rapid disease progression following tumor recurrence (HR = 2.6, P = 0.02), and likely preceded the acquisition of alkylating therapy-associated somatic hypermutation. Thirty-two percent of patients harbored a potentially therapeutically actionable lesion, of whom 11% received targeted therapies. In BRAF-mutant gliomas, response to agents targeting the RAF/MEK/ERK signaling axis was influenced by the type of mutation, its clonality, and its cellular and genomic context.

Conclusions:

These data reveal genomic correlates of disease progression and treatment response in diverse types of glioma and highlight the potential utility of incorporating genomic information into the clinical decision-making for patients with glioma.
Clinical Response of Live-Attenuated, Listeria monocytogenes Expressing Mesothelin (CRS-207) with Chemotherapy in Patients with Malignant Pleural Mesothelioma
Authors: Hassan Raffit , Alley Evan , Kindler Hedy , Antonia Scott , Jahan Thierry , Honarmand Somayeh , Nair Nitya , Whiting Chan C. , Enstrom Amanda , Lemmens Ed , Tsujikawa Takahiro , Kumar Sushil , Choe Gina , Thomas Anish , McDougall Katherine , Murphy Aimee L. , Jaffee Elizabeth , Coussens Lisa M. , Brockstedt Dirk G.
Published: July 2019

Purpose:

Malignant pleural mesothelioma (MPM) is an aggressive cancer associated with poor prognosis. CRS-207 is a live-attenuated Listeria monocytogenes engineered to express mesothelin, a tumor-associated antigen highly expressed in MPM. CRS-207 induces antitumor immune responses and increases susceptibility of neoplastic cells to immune-mediated killing.

Patients and Methods:

Patients with unresectable MPM, ECOG 0 or 1, and adequate organ and pulmonary function were enrolled in this multicenter, open-label phase Ib study. They received two priming infusions of 1 × 109 CFU CRS-207, followed by pemetrexed/cisplatin chemotherapy, and CRS-207 booster infusions. Primary objectives were safety and induction of immune response. Secondary/exploratory objectives included tumor response, progression-free survival (PFS), overall survival (OS), immune subset analysis, and gene-expression profiling of tumor.

Results:

Of 35 evaluable patients, 89% (31/35) had disease control with one complete response (3%), 19 partial responses (54%), and 10 stable disease (29%). The estimated median duration of response was 5.0 months (95% CI, 3.9–11.5). The median PFS and OS were 7.5 (95% CI, 7.0–9.9) and 14.7 (95% CI, 11.2–21.9) months, respectively. Tumor size reduction was observed post–CRS-207 infusion prior to chemotherapy in 11 of 35 (31%) patients. No unexpected treatment-related serious adverse events or deaths were observed. IHC analysis of pre- and post–CRS-207 treatment tumor biopsies revealed possible reinvigoration and proliferation of T cells, increased infiltration of dendritic and natural killer cells, increased CD8:Treg ratio, and a shift from immunosuppressive M2-like to proinflammatory M1-like macrophages following CRS-207 administration.

Conclusions:

Combination of CRS-207 and chemotherapy induced significant changes in the local tumor microenvironment and objective tumor responses in a majority of treated patients.
The Use of Ribavirin as an Anticancer Therapeutic: Will It Go Viral?
Authors: Casaos Joshua , Gorelick Noah L. , Huq Sakibul , Choi John , Xia Yuanxuan , Serra Riccardo , Felder Raphael , Lott Tarik , Kast Richard E. , Suk Ian , Brem Henry , Tyler Betty , Skuli Nicolas
Published: July 2019

The growing cost of medical care worldwide, particularly in oncology, has incentivized researchers and physicians to repurpose clinically used drugs to alleviate the financial burden of drug development and offer potential new therapeutics. Recent works have demonstrated anticancer properties of the FDA-approved drug ribavirin, a synthetic guanosine analogue and antiviral molecule used over the past four decades for the treatment of hepatitis C. The efficacy of ribavirin in cancer has been explored through several preclinical models and ongoing clinical trials in multiple cancers, including acute myeloid leukemia, oropharyngeal squamous cell carcinoma, and metastatic breast cancer. In this review, we summarize the role of ribavirin as an antiviral medication and focus our attention on its recent use as an antitumoral agent. We highlight current knowledge of the potential use and mechanisms of action of ribavirin in cancer. Because current therapeutics for patients with cancer still fail to cure, introducing new forms of treatment is essential. Converging evidence suggests that ribavirin represents a promising addition to a generation of newly repurposed safe and effective anticancer agents.
Focus Marking and Prosodic Boundary Strength in French
Authors: Michelas Amandine , German James S.
Published: July 2019

Background/Aims:In French, the size of a focus constituent is not reliably marked through pitch accent assignment as in many stress accent languages. While it has been argued that the distribution of lower-level prosodic boundaries plays a role, this is at best a weak cue to focus, leaving open the question of whether other marking strategies are available. In this study, we assess whether the right edge of a contrastive focus constituent is marked by differences in prosodic boundary strength.Methods:We elicited utterances with target words in six combinations of focus and syntactic contexts using an interactive production task.Results:The results show that if a given location is realized as an accentual phrase boundary in an all-focus context, then it is realized as an intermediate phrase boundary when it coincides with the right edge of a narrow-focus constituent. A location that is an intermediate phrase boundary in an all-focus context, however, remains unchanged under narrow focus.Conclusion:These findings suggest that focus constituents are constrained to align with a minimum prosodic domain size in French (i.e., the intermediate phrase), and that French does not rely on a general strategy of prosodic enhancement for marking focus.
In vitro Engineering of a Skin Substitute Based on Adipose-Derived Stem Cells
Authors: Paganelli Alessia , Benassi Luisa , Pastar Irena , Pellegrini Massimo , Azzoni Paola , Vaschieri Cristina , Pisciotta Alessandra , Carnevale Gianluca , Pellacani Giovanni , Magnoni Cristina
Published: July 2019

In the field of wound healing, stem cell-based strategies are gaining importance for their regenerative potential. Adipose-derived stem cells (ADSCs) are a particular subset of mesenchymal stem cells present in the stromal-vascular fraction of the adipose tissue, today considered very attractive for their relative abundance and accessibility in the human body. However, ADSCs are still not routinely used in normal clinical practice. Several studies have also reported ADSC transplantation in association with biomaterials in an attempt to enhance the local retention and growth rate of the cells. The aim of our study was to evaluate the ability of ADSCs to build a dermal scaffold to be potentially used as a dermal substitute in the field of wound healing, with optimal biocompatibility and mechanical properties. ADSCs were defined as CD90-, CD73-, and CD105-positive cells. ADSCs turned out to be capable of secreting all the main components of the extracellular matrix (ECM) upon stimulation, thus efficiently producing a collagen and fibronectin-containing dermal matrix. We also checked whether the ADSC-produced dermal scaffold could be seeded with keratinocytes. The scaffolding material directly produced by ADSCs has several advantages when compared to the commercially available ones: it is easily obtained from the patients and it is 100% biocompatible and supports cell-ECM interaction. Moreover, it represents a possible powerful therapeutic tool for patients with chronic ulcers since it appears to be potentially grafted with keratinocytes layers, thus bypassing the classical two-step grafting procedure.
Novel MECP2 Mutation c.1162_1172del; p.Pro388* in Two Patients with Symptoms of Atypical Rett Syndrome
Authors: Bernstein Ulrike , Demuth Stephanie , Puk Oliver , Eichhorn Birgit , Schulz Solveig
Published: July 2019

We report 2 cases of girls with MECP2 gene variants who do not have typical clinical features of Rett syndrome except for intellectual disability and seizures. Both patients present with adipositas, macrocephalia, precocious puberty, and seizures. They have prominent eyebrows and a short neck as well as short and plump fingers. Sequencing by NGS revealed a novel variant c.1162_1172del; p.Pro388* in both patients.
Occurrence of Mycoplasma hyopneumoniae in slaughter pigs from Southern Brazil
Authors: Pacce Violetta Dias , Oliveira Natasha Rodrigues de , Jorge Sérgio , Dellagostin Odir Antônio
Published: July 2019

Mycoplasma hyopneumoniae is the causative agent of enzootic pneumonia (EP), a disease that is highly prevalent and globally distributed, causing significant economic losses to the swine industry. Disease progression is characterized by reduced feed conversion and the development of lung lesions. Considering the limited information about the epidemiology of EP in Southern Brazil, the main objective of this study was to determine the occurrence of M. hyopneumoniae in swine lung samples and to evaluate the scores of lung lesions caused by local strains. A total of 120 samples was randomly collected and processed. DNA was extracted from lung tissue to perform nested-PCR and lungs were inspected to evaluate the presence of the pneumonia-like gross lesions of M. hyopneumoniae. The results showed 95.8% positive samples, while the lung lesion score analysis showed suggestive lesions in 60% of samples. The detection of positive samples in nested-PCR was associated with the presence of pneumonia-like gross lesions (P < 0.01). The results demonstrate a high occurrence of EP in slaughter pigs from southern Brazil.
Sexualidade, um direito (secundário)? Atravessamentos entre sexualidade, socioeducação e punição
Authors: D'Angelo Luisa Bertrami , Hernández Jimena De Garay
Published: July 2019

Este artigo faz parte da pesquisa sobre sexualidade e juventude realizada de março 2015 a outubro de 2016, em três unidades de internação do Departamento Geral de Ações Socioeducativas do Rio de Janeiro, sendo duas unidades masculinas e a única unidade feminina do estado. A partir da perspectiva metodológica da cartografia, acompanhamos durante esses anos diversos processos nas unidades, entrevistando jovens e profissionais de diferentes segmentos. Apresentamos aqui reflexões sobre os debates que suscitamos no campo a respeito da sexualidade na socioeducação, procurando englobar as experiências e percepções dos/as jovens, dos/as agentes socioeducativos/as, do corpo de profissionais técnicos/as, do quadro docente e da direção, articulando os dispositivos de gênero, classe social, geração e raça para pensar nas produções de tecnologias e mecanismos de controle e na lógica punitiva que parece reger o cotidiano institucional. Pensando, assim, nas tensões que movimentam (ou cristalizam) os debates sobre sexualidade nestes contextos, propomos algumas reflexões a respeito de como a sexualidade é, também, alvo destas políticas punitivas e de contenção, uma vez que é classificada, hierarquizada, cerceada, vigiada e limitada nestes espaços.
Reflections on Randomized Trials and Observational Studies
Authors: Collins Sir Rory , Rutherford John D.
Published: July 2019

Rory Collins is the Head, Nuffield Department of Population Health, University of Oxford, Principal Investigator and Chief Executive, UK Biobank, and the British Heart Foundation Professor of Medicine and Epidemiology at the University of Oxford. He was born in Hong Kong and received his medical degree from St Thomas’s Hospital Medical School, University of London. He was Knighted for Services to Science in 2011 and became a Fellow of the Royal Society in 2015. He has delivered the Paul Dudley White International Lecture of the American Heart Association and the Royal Society of Medicine William Harvey Lecture, and he has received both the European Society of Cardiology Gold Medal and the British Cardiovascular Society MacKenzie Medal.
Effect of Intensive Blood Pressure Reduction on Left Ventricular Mass, Structure, Function, and Fibrosis in the SPRINT-HEART
Authors: Upadhya Bharathi , Rocco Michael V. , Pajewski Nicholas M. , Morgan Tim , Blackshear Joseph , Hundley William Greg , Oparil Suzanne , Soliman Elsayed Z. , Cohen Debbie L. , Hamilton Craig A. , Cho Monique E. , Kostis William J , Papademetriou Vasilios , Rodriguez Carlos J. , Raj Dominic S. , Townsend Ray , Vasu Sujethra , Zamanian Sara , Kitzman Dalane W. ,   for the SPRINT Research Group
Published: July 2019

In observational studies, left ventricular mass (LVM) and structure are strong predictors of mortality and cardiovascular events. However, the effect of hypertension treatment on LVM reduction and its relation to subsequent outcomes is unclear, particularly at lower blood pressure (BP) targets. In an ancillary study of SPRINT (Systolic Blood Pressure Intervention Trial), where participants were randomly assigned to intensive BP control (target systolic BP target <120 mm Hg) versus standard BP control (<140 mm Hg), cardiac magnetic resonance imaging was performed at baseline and 18-month follow-up to measure: LVM, volumes, ejection fraction, and native T1 mapping for myocardial fibrosis. At baseline, 337 participants were examined (age: 64±9 years, 45% women); 300 completed the 18-month exam (153 intensive control and 147 standard control). In the intensive versus standard BP control group at 18 months, there was no difference in change in LVM (mean±SE =−2.7±0.5 g versus −2.3±0.7 g;
P
=0.368), ejection fraction, or native T1 (
P
=0.79), but there was a larger decrease in LVM/end-diastolic volume ratio (−0.04±0.01 versus −0.01±0.01;
P
=0.002) a measure of concentric LV remodeling. There were fewer cardiovascular events in the intensive control group, but no significant association between the reduced events and change in LVM or any other cardiac magnetic resonance imaging measure. In SPRINT-HEART, contrary to our hypothesis, there were no significant between-group differences in LVM, function, or myocardial T1 at 18-month follow-up. These results suggests that mediators other than these LV measures contribute to the improved cardiovascular outcomes with intensive BP control.
The Design Theory of Contemporary “Chinese” Fashion
Authors: Tsui Christine
Published: July 2019

This paper examines the basic design theories underpinning contemporary Chinese fashion by exploring a fundamental question: are there any common features that can be summarized about Chinese fashion, and, if yes, what is Chinese fashion? Chinese fashion in this paper means clothing that is in “Chinese” style and designed by People's Republic of China (PRC) designers. To answer the specific question, I undertook in-depth interviews with selected Chinese designers and then supplemented these with a textual analysis of interviews published previously in prominent Chinese fashion journals.

This study shows the Chinese style exhibiting features of “implied beauty” in aesthetic, flat form in shape, and harmony in spirit. I synthesize the three features into one Chinese character, HE. HE literally encompasses rich meanings: harmony, peace, implicit but evoking, reserved, pure, natural, and any synonyms of these words. The character indicates an implied beauty system of China—presenting the beauty in an implicit and subtle form. Implied beauty urges viewers to imagine the beauty that is between visibility and invisibility under the clothing, rather than to sense the beauty by directly seeing the body of the wearer through the eyes. The primary form in Chinese style clothing as a reflection of implied beauty is the flat form, meaning that the clothing is cut without any darts or seam lines to reduce the volume differences between the bust line, the waist line, and the hip line. The cutting hides body rather than reveals body. Finally, in spirit Chinese fashion reflects the core Chinese philosophy of harmony, which means being in tune with both the social and the natural environment.
When Not to Classify: Anomaly Detection of Attacks (ADA) on DNN Classifiers at Test Time
Authors: Miller David , Wang Yujia , Kesidis George
Published: July 2019

A significant threat to the recent, wide deployment of machine learning–based systems, including deep neural networks (DNNs), is adversarial learning attacks. The main focus here is on evasion attacks against DNN-based classifiers at test time. While much work has focused on devising attacks that make small perturbations to a test pattern (e.g., an image) that induce a change in the classifier's decision, until recently there has been a relative paucity of work defending against such attacks. Some works robustify the classifier to make correct decisions on perturbed patterns. This is an important objective for some applications and for natural adversary scenarios. However, we analyze the possible digital evasion attack mechanisms and show that in some important cases, when the pattern (image) has been attacked, correctly classifying it has no utility---when the image to be attacked is (even arbitrarily) selected from the attacker's cache and when the sole recipient of the classifier's decision is the attacker. Moreover, in some application domains and scenarios, it is highly actionable to detect the attack irrespective of correctly classifying in the face of it (with classification still performed if no attack is detected). We hypothesize that adversarial perturbations are machine detectable even if they are small. We propose a purely unsupervised anomaly detector (AD) that, unlike previous works, (1) models the joint density of a deep layer using highly suitable null hypothesis density models (matched in particular to the nonnegative support for rectified linear unit (ReLU) layers); (2) exploits multiple DNN layers; and (3) leverages a source and destination class concept, source class uncertainty, the class confusion matrix, and DNN weight information in constructing a novel decision statistic grounded in the Kullback-Leibler divergence. Tested on MNIST and CIFAR image databases under three prominent attack strategies, our approach outperforms previous detection methods, achieving strong receiver operating characteristic area under the curve detection accuracy on two attacks and better accuracy than recently reported for a variety of methods on the strongest (CW) attack. We also evaluate a fully white box attack on our system and demonstrate that our method can be leveraged to strong effect in detecting reverse engineering attacks. Finally, we evaluate other important performance measures such as classification accuracy versus true detection rate and multiple measures versus attack strength.
Natural, Neutral, and Hedonic States in Plato
Authors: Cheng Wei
Published: July 2019

This paper aims to clarify Plato’s notions of the natural and the neutral state in relation to hedonic properties. Contra two extreme trends among scholars—people either conflate one state with the other, or keep them apart as to establish an unsurmountable gap between both states, I argue that neither view accurately reflects Plato’s position because the natural state is real and can coincide with the neutral state in part, whereas the latter, as an umbrella term, can also be realized in a non-natural condition. The clarification of the relation between the two states will shed light on the degree to which Plato admits and constrains the hedonic value for a good human life; further, this will call attention to some (not well explored) parallel thoughts in the medical tradition to which Plato is indebted.
Hasan Al-Banna and the Modern Muslim Self: Subjectivity Formation and the Search for an Islamic Order in Early 20th-Century Egypt
Authors: Jung Dietrich , Zalaf Ahmed el
Published: July 2019

The Muslim Brotherhood represents an exemplary case for the discussion of Islam and modernity. Founded in 1928 in Egypt by Hasan al-Banna, it developed from a religious movement into a well-organized institution and a cadre party with mass appeal. The Muslim Brotherhood assumed the role of a major social vehicle for the promotion of a specifically Islamic imagination of modernity and related forms of modern Muslim subjectivity. This article explores the ideas of Hasan al-Banna and their historical context from a distinct theoretical perspective. It poses questions with regard to ways in which he constructed an Islamic modern social order and meaningful Muslim selfhoods. Thereby, it understands the Muslim Brotherhood as an inherent part of the emergence of global modernity as “world history.”
Imitating Virtue
Authors: Hampson Margaret
Published: July 2019

Moral virtue is, for Aristotle, famously acquired through the practice of virtuous actions. But how should we understand the activity of Aristotle’s moral learner, and how does her activity result in the acquisition of virtue? I argue that by understanding Aristotle’s learner as engaged in the emulative imitation of a virtuous agent, we can best account for her development. Such activity crucially involves the adoption of the virtuous agent’s perspective, from which I argue the learner is positioned so as to appreciate the value of virtuous action—its fineness—and what it would be to act finely herself.
Beloved Companion or Problem Animal
Authors: Iliopoulou Maria A. , Carleton Carla L. , Reese Laura A.
Published: July 2019

The term Pit bull is widely used. However, is it assigned a specific definition, or is it associated with overly inclusive and contradictory meanings? At the beginning of the 1900s, dogs identified as Pit bulls were known for their love of children. Media sensationalism has contributed to a shift in perceptions of Pit bulls from favorite companion animals to problem nonhuman animals. Thus, the process of constructing “problem animals” is examined. A qualitative study was conducted to explore what the term Pit bull represents for a sample of fifty-six adults. The data collection tool was the Personal Meaning Map. Respondents seemed to have vague and conflicting definitions of Pit bulls. For some, they are gentle companions, but for others they are gang-related status symbols. For some, Pit bulls represent one breed, whereas for others they represent many breeds. Finally, they were perceived to be both victims of cruelty and predators.
“Getting Rid of the Dog”: Adult Recall of a Childhood Experience
Authors: Edwards Mary E. , Gringart Eyal , Drake Deirdre
Published: July 2019

Dog relinquishment is common practice across Australia and in many other countries. The psychological impact of dog relinquishment is an under-researched area. While a few studies have shown that the dog relinquishment experience can be emotionally distressing and cognitively challenging for adults, nothing is known about the impact of the experience on children. This paper reports on the recollections of 10 adults, who in qualitative interviews in Western Australia, described their childhood experience of dog relinquishment. The findings suggest that children experiencing dog relinquishment feel powerless and voiceless, having no influence or say in what happens to their dogs. The experience can be cognitively and emotionally distressing, especially for children who are close to their dogs. Getting rid of a child’s loved dog can damage the parent-child relationship. In addition, the thoughts and feelings associated with losing their dogs in this way can remain long after the event.