bluuebunny/crossref_metadata_2025 huggingface dataset:
TinyDroid: A Lightweight and Efficient Model for Android Malware Detection and Classification
Authors: Chen Tieming , Mao Qingyu , Yang Yimin , Lv Mingqi , Zhu Jianming
Published: October 2018

With the popularity of Android applications, Android malware has an exponential growth trend. In order to detect Android malware effectively, this paper proposes a novel lightweight static detection model, TinyDroid, using instruction simplification and machine learning technique. First, a symbol-based simplification method is proposed to abstract the opcode sequence decompiled from Android Dalvik Executable files. Then, N-gram is employed to extract features from the simplified opcode sequence, and a classifier is trained for the malware detection and classification tasks. To improve the efficiency and scalability of the proposed detection model, a compression procedure is also used to reduce features and select exemplars for the malware sample dataset. TinyDroid is compared against the state-of-the-art antivirus tools in real world using Drebin dataset. The experimental results show that TinyDroid can get a higher accuracy rate and lower false alarm rate with satisfied efficiency.
LQR Based Optimal Topology of Hybrid-Weighted Multiagent Systems
Authors: Liu Shuai , Ji Zhijian , Yu Haisheng , Hou Ting
Published: October 2018

In this paper, the optimal topology structure is studied for hybrid-weighted leader-follower multiagent systems (MASs). The results are developed by taking advantage of linear quadratic regulator (LQR) theory. We show that the multiagent star composite structure is the optimal topology which can enable the MAS to achieve the bipartite consensus. In particular, we prove that the optimal topology corresponding to the multiagent system with the first-order static leader and the second-order dynamic leader is, respectively, a hybrid-weighted star composite structure and an unevenly hybrid-weighted star composite structure. The results of the paper indicate that, in addition to the necessary information communication between leader and followers, the information exchange among followers increases the control cost of the system.
Acupuncture on the Stress‐Related Drug Relapse to Seeking
Authors: Roh Hyo Sun , Park Bo Ra , Jang Eun Young , Kim Jin Sook , Gwak Young S.
Published: October 2018

Drug addiction is a chronic relapsing disease, which causes serious social and economic problems. The most important trial for the successful treatment of drug addiction is to prevent the high rate of relapse to drug‐seeking behaviors. Opponent process as a motivational theory with excessive drug seeking in the negative reinforcement of drug dependence reflects both loss of brain reward system and recruitment of brain stress system. The negative emotional state produced by brain stress system during drug withdrawal might contribute to the intense drug craving and drive drug‐seeking behaviors via negative reinforcement mechanisms. Decrease in dopamine neurotransmission in the nucleus accumbens and recruitment of corticotropin‐releasing factor in the extended amygdala are hypothesized to be implicated in mediating this motivated behavior. Also, a brain stress response system is hypothesized to increase drug craving and contribute to relapse to drug‐seeking behavior during the preoccupation and anticipation stage of dependence caused by the exposure to stress characterized as the nonspecific responses to any demands on the body. Acupuncture has proven to be effective for reducing drug addiction and stress‐related psychiatric disorders, such as anxiety and depression. Furthermore, acupuncture has been shown to correct reversible brain malfunctions by regulating drug addiction and stress‐related neurotransmitters. Accordingly, it seems reasonable to propose that acupuncture attenuates relapse to drug‐seeking behavior through inhibition of stress response. In this review, a brief description of stress in relapse to drug‐seeking behavior and the effects of acupuncture were presented.
Tailoring Aerogel for Thermal Spray Applications in Aero‐Engines: A Screening Study
Authors: Bheekhun Nadiir , Abu Talib Abd Rahim , Hassan Mohd Roshdi
Published: October 2018

Irregular silica aerogel particles had been tailored to a regular spherical shape within the proper granulometric size range for thermal spraying. Silica aerogel is an ultralow dense and highly porous nanomaterial with its thermal conductivity being the lowest than any solids. Although silica aerogels possess fascinating physical properties, their implementation is limited to aerogel‐doped blankets in the aerospace industry. Due to space constraints, these heat insulative and fireproof blankets are not encouraged by aero‐engine manufacturers, and hence, alternatives are being sought. Although it was thought that an aerogel‐based thermally sprayed coating may be applicable, aerogel powders are extremely challenging to be injected and deposited by thermal spray guns because of their inappropriate granulometric and morphological properties. Consequently, this study intends to tailor the aerogel powders accordingly. Aerogel‐based slurries with yttria‐stabilized zirconia as a secondary ceramic were prepared and spray‐dried according to a modified Taguchi experimental design in order to appreciate the effect of both the slurry formulation and drying conditions such as the solid content, the ratio of yttria‐stabilized zirconia : aerogel added, the amount of dispersant and binder, inlet temperature, atomization pressure, and feeding rate on the aforementioned characteristics of the resulting spray‐dried powder. Uniformity was found to be the most influenced one (F‐ratio = 62.40) by the overall spray‐drying process. Solid content had the most significant effect on median particle size (p value = 0.035) and volume fraction (p value = 0.010) but did not affect uniformity significantly (p value = 0.065). Furthermore, a strong positive and significant correlation existed (Pearson’s r = 0.930) between median particle size and volume fraction. Based on the derived relationships, an optimised condition to achieve the maximum median particle size was then predicted and verified experimentally. The optimised aerogel‐based spray‐dried powder had a median particle size, volume fraction, and uniformity of 28.93 ± 0.726 μm, 64.45 ± 0.535, and 0.475 ± 0.002, respectively. Finally, the morphology of the optimised powder was noticed to have been changed from irregular shapes to spherical or donut‐like granules which made them within the frame of thermally sprayable. However, when the optimised spray‐dried powder was weighed, the quantity was found to be 10% only from the total weight of ceramics within the slurry prior to spray‐drying, which makes it uneconomically reasonable for subsequent thermal spraying.
New Solvent for Polyamide 66 and Its Use for Preparing a Single-Polymer Composite-Coated Fabric
Authors: Jabbari Mostafa , Skrifvars Mikael , Åkesson Dan , Taherzadeh Mohammad J.
Published: October 2018

Polyamides (PAs) are one of the most important engineering polymers; however, the difficulty in dissolving them hinders their applications. Formic acid (FA) is the most common solvent for PAs, but it has industrial limitations. In this contribution, we proposed a new solvent system for PAs by replacing a portion of the FA with urea and calcium chloride (FAUCa). Urea imparts the hydrogen bonding and calcium ion from the calcium chloride, as a Lewis acid was added to the system to compensate for the pH decrease due to the addition of urea. The results showed that the proposed solvent (FAUCa) could readily dissolve PAs, resulting in a less decrease in the mechanical properties during the dissolution. The composite prepared using the FAUCa has almost the same properties as the one prepared using the FA solution. The solution was applied on a polyamide 66 fabric to make an all-polyamide composite-coated fabric, which then was characterized. The FAUCa solution had a higher viscosity than the one prepared using the neat FA solvent, which can be an advantage in the applications which need higher viscosity like preparing the all-polyamide composite-coated fabric. A more viscous solution makes a denser coating which will increase the water /gas tightness. In conclusion, using the FAUCa solvent has two merits: (1) replacement of 40% of the FA with less harmful and environmentally friendly chemicals and (2) enabling for the preparation of more viscous solutions, which makes a denser coating.
Approach to the Weight Estimation in the Conceptual Design of Hybrid-Electric-Powered Unconventional Regional Aircraft
Authors: Centracchio Francesco , Rossetti Monica , Iemma Umberto
Published: October 2018

The present work deals with the development of an innovative approach to the weight estimation in the conceptual design of a Hybrid-Electric-Powered (HEP) Blended Wing Body (BWB) commercial aircraft. In the last few decades, the improvement of the environmental impact of civil aviation has been the major concern of the aeronautical engineering community, in order to guarantee the sustainable development of the system in presence of a constantly growing market demand. The sustained effort in the improvement of the overall efficiency of conventional aircraft has produced a new generation of vehicles with an extremely low level of emissions and noise, capable of covering the community requirements in the short term. Unfortunately, the remarkable improvements achieved represent the asymptotic limit reachable through the incremental enhancement of existing concepts. Any further improvement to conform to the strict future environmental target will be possible only through the introduction of breakthrough concepts. The aeronautical engineering community is thus concentrating the research on unconventional airframes, innovative low-noise technologies, and alternative propulsion systems. The BWB is one of the most promising layouts in terms of noise emissions and chemical pollution. The further reduction of fuel consumption that can be achieved with gas/electric hybridisation of the power-plant is herein addressed in the context of multidisciplinary analyses. In particular, the payload and range limits are assessed in relation to the technological development of the electric components of the propulsion system. The present work explores the potentialities of an energy-based approach for the initial sizing of a HEP unconventional aircraft in the early conceptual phase of the design. A detailed parametric analysis has been carried out to emphasise how payload, range, and degree of hybridisation are strictly connected in terms of feasible mission requirements and related to the reasonable expectations of development of electric components suitable for aeronautical applications.
A Source Hiding Identity-Based Proxy Reencryption Scheme for Wireless Sensor Network
Authors: Ge Chunpeng , Xia Jinyue , Wu Aaron , Li Hongwei , Wang Yao
Published: October 2018

Wireless sensor network (WSN), which extends the typical Internet environment to Internet of Things, has been deployed in various environments such as safety monitoring, intelligent transportation, and smart home. In a WSN, encryption is typically used to protect data that are stored in wireless devices. However some features like data sharing can be affected if the traditional encryption is used. A secure mechanism should support a gateway of the network to directly convert a user’s encrypted data (encrypted pollution data) to a new user’s encryption without exposing the underlying plaintext data during the whole sharing phase. In this work, a new source hiding identity-based proxy reencryption scheme (SHIB-PRE) is proposed to deal with the issue. The proposed SHIB-PRE scheme supports a proxy (gateway or cloud server) to transform a user’s encrypted date to a new user’s ciphertext as long as the proxy has the proxy reencryption key. In SHIB-PRE, the encrypted pollution data is kept secure from the proxy and the relationship between a source ciphertext and a reencrypted ciphertext is concealed from the outside eavesdropper. In this paper, we give an introduction to the definition of a source hiding identity-based proxy reencryption and its chosen plaintext security model. Further, a concrete construction will be presented and proven chosen plaintext secure under the q-DDHE assumption in the standard model.
An Improved Computationally Efficient Method for Finding the Drazin Inverse
Authors: Bin Jebreen Haifa , Chalco-Cano Yurilev
Published: October 2018

Drazin inverse is one of the most significant inverses in the matrix theory, where its computation is an intensive and useful task. The objective of this work is to propose a computationally effective iterative scheme for finding the Drazin inverse. The convergence is investigated analytically by applying a suitable initial matrix. The theoretical discussions are upheld by several experiments showing the stability and convergence of the proposed method.
Impact of Capacity Drop on Commuting Systems under Uncertainty
Authors: Zhang Wenwei , Zhao Hui , Jiang Rui
Published: October 2018

This paper analyzes the impact of capacity drop on commuters’ travel choice behaviors under uncertainty. For clarity, we assume that the capacity drop is triggered by the queue forming at the bottleneck under the hypercongestion circumstances, and the stochasticity of the drop could not be neglected. Considering the uncertainty of travel time, we establish a bottleneck model with commuters choosing their departure time according to the mean travel cost. From the proposed model, analytical solutions are achieved and therefore several properties are presented, including monotonicity of travel cost and departure rate, and the relationship between dispersion degree and length of peak period. To alleviate traffic congestion at the bottleneck and avoid capacity drop, we design a time-varying toll scheme and a step toll scheme. Evolution of queue length in equilibrium is discussed based on the Laih model. Numerical examples are also presented to demonstrate the established model and the effectiveness of the proposed toll schemes.
Association between Objectively Measured Physical Activity and Gait Patterns in People with Parkinson’s Disease: Results from a 3-Month Monitoring
Authors: Porta Micaela , Pilloni Giuseppina , Pili Roberta , Casula Carlo , Murgia Mauro , Cossu Giovanni , Pau Massimiliano
Published: October 2018

Background. Although physical activity (PA) is known to be beneficial in improving motor symptoms of people with Parkinson’s disease (pwPD), little is known about the relationship between gait patterns and features of PA performed during daily life. Objective. To verify the existence of possible relationships between spatiotemporal and kinematic parameters of gait and amount/intensity of PA, both instrumentally assessed. Methods. Eighteen individuals affected by PD (10F and 8M, age 68.0 ± 10.8 years, 1.5 ≤ Hoehn and Yahr (H&Y) < 3) were required to wear a triaxial accelerometer 24 h/day for 3 consecutive months. They also underwent a 3D computerized gait analysis at the beginning and end of the PA assessment period. The number of daily steps and PA intensity were calculated on the whole day, and the period from 6:00 to 24:00 was grouped into 3 time slots, using 3 different cut-point sets previously validated in the case of both pwPD and healthy older adults. 3D gait analysis provided spatiotemporal and kinematic parameters of gait, including summary indexes of quality (Gait Profile Score (GPS) and Gait Variable Score (GVS)). Results. The analysis of hourly trends of PA revealed the existence of two peaks located in the morning (approximately at 10) and in the early evening (between 18 and 19). However, during the morning time slot (06:00–12:00), pwPD performed significantly higher amounts of steps (4313 vs. 3437 in the 12:00–18:00 time slot, p<0.001, and vs. 2889 in the 18:00–24:00 time slot, p=0.021) and of moderate-to-vigorous PA (43.2% vs. 36.3% in the 12:00–18:00 time slot, p=0.002, and vs. 31.4% in the 18:00–24:00 time slot, p=0.049). The correlation analysis shows that several PA intensity parameters are significantly associated with swing-phase duration (rho = −0.675 for sedentary intensity, rho = 0.717 for moderate-to-vigorous intensity, p<0.001), cadence (rho = 0.509 for sedentary intensity, rho = −0.575 for moderate-to-vigorous intensity, p<0.05), and overall gait pattern quality as expressed by GPS (rho = −0.498 to −0.606 for moderate intensity, p<0.05) and GVS of knee flexion-extension (rho = −0.536 for moderate intensity, p<0.05). Conclusions. Long-term monitoring of PA integrated by the quantitative assessment of spatiotemporal and kinematic parameters of gait may represent a useful tool in supporting a better-targeted prescription of PA and rehabilitative treatments in pwPD.
Shear Parameters of Rammed Earth Material: Results from Different Approaches
Authors: El-Nabouch R. , Bui Q.-B. , Perrotin P. , Plé O.
Published: October 2018

Rammed earth (RE) is a construction material which is manufactured by compacting the soil in a formwork, in different layers. Several recent studies have investigated this material. The seismic performance of RE buildings is an important topic which needs to be carefully investigated. The complex numerical model seems a performant approach to investigate the seismic performance of a whole building. To correctly establish the model, the shear parameters of the material, which are the cohesion and the friction angle, should be identified. This paper first presents experimental studies on the shear parameters of RE through the direct shear tests, at two different scales. The differences of the results at different scales are analyzed. Then, the obtained experimental values are used in a numerical model to simulate the shear behavior of RE walls which are loaded by a constant vertical stress and pushed horizontally on the top. From the obtained results, the values for numerical models are recommended.
Synthesis of Poly(N-vinylcaprolactam)-Grafted Magnetite Nanocomposites for Magnetic Hyperthermia
Authors: Morfin-Gutiérrez A. , Meléndez-Ortiz H. Iván , Puente-Urbina B. A. , García-Cerda L. A.
Published: October 2018

In this study, the synthesis, characterization, and application of poly(N-vinylcaprolactam)-grafted magnetite nanocomposites for magnetic hyperthermia are reported. Superparamagnetic magnetite nanoparticles (MagNPs) with sizes in the range of 10–16 nm were synthesized by the coprecipitation method and then functionalized with vinyltrimethoxysilane (VTMS). MagNPs-VTMS coated with poly(N-vinylcaprolactam) (PNVCL) were prepared by free radical polymerization. The obtained materials were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), vibration sample magnetometry (VSM), and Fourier transform infrared spectroscopy (FT-IR). The heating ability was evaluated under a magnetic field using a solid state induction heating equipment at 10.2 kA/m and 362 kHz. The MagNPs-PNVCL nanocomposites showed a behavior close to superparamagnetic materials, which is appropriated for magnetic hyperthermia treatment; in concentrations of 8 mg/mL, they were able to heat up, increasing the temperature up to 42°C in a period of time lower than 10 minutes.
Numerical Modeling of Thermal‐Dependent Creep Behavior of Soft Clays under One‐Dimensional Condition
Authors: Zhu Qi-Yin , Qi Ping
Published: October 2018

Creep is a common phenomenon for soft clays. The paper focuses on investigating the influence of temperature on the time‐dependent stress‐strain evolution. For this purpose, the temperature‐dependent creep behavior for the soft clay has been investigated based on experimental observations. A thermally related equation is proposed to bridge the thermal creep coefficient with temperature. By incorporating the equation to a selected one‐dimensional (1D) elastic viscoplastic (EVP) model, a thermal creep‐based EVP model was developed which takes into account the influence of temperature on creep. Simulations of oedometer tests on reconstituted clay are made through coupled consolidation analysis. The bonding effect of the soil structure on compressive behavior for intact clay is studied. By incorporating the influence of the soil structure, the thermal creep EVP model is extended for intact clay. Experimental predictions for thermal creep oedometer tests are simulated at different temperatures and compared to that obtained from reconstituted clay. The results show that the influence of temperature on the creep behavior for intact clay is significant, and the model, this paper proposed, can successfully reproduce the thermal creep behavior of the soft clay under the 1D loading condition.
Development of an Academic Course in Person-Centred Care for Students in Higher Education: Teachers’ Perspectives
Authors: Rosengren Kristina , Danielsson Louise , Jansson Inger , Wallengren Catarina
Published: October 2018

Few studies describe the development of academic courses with interprofessional perspectives. Therefore, the aim of this study was to describe teachers’ experiences with developing an academic course in person-centred care (PCC). Data collection was divided into three parts: (1) written material/documentation describing the process (text and pictures, 16 meetings), (2) SWOT analysis in relation to being a lecturer (n=7), and (3) interviews with the lecturers (n=4). The data were analysed using mixed methods, descriptive statistics (1) and qualitative content analysis (2-3). The results are presented in three categories (Co-creating a pilot course, Challenges of managing unfamiliar knowledge, and Wanting to understand new educational approach). This study highlights three challenges: (1) unfamiliarity with the field of person-centred care and selected educational activities and teaching skills; (2) unfamiliar colleagues, which delayed partnership efforts; and (3) limited experience working with other lecturers in light of the institute’s structure and routines. However, these challenges served as both barriers and facilitators; the lecturers developed knowledge and experiences from collaborations (educational and/or content skills/knowledge) focusing on resources and skills.
The EGFR T790M Mutation Is Acquired through AICDA-Mediated Deamination of 5-Methylcytosine following TKI Treatment in Lung Cancer
Authors: El Kadi Najwa , Wang Luo , Davis April , Korkaya Hasan , Cooke Alexander , Vadnala Varun , Brown Noah A. , Betz Bryan L. , Cascalho Marilia , Kalemkerian Gregory P. , Hassan Khaled A.
Published: October 2018

Almost all patients with EGFR-driven lung cancer who are treated with EGFR tyrosine kinase inhibitors (TKI) develop resistance to treatment. A single base (c.2369C>T) transition mutation, EGFR T790M, is the most frequent resistance event after first-generation exposure to EGFR TKIs. Whether T790M mutation is acquired or is selected from a preexisting clone has been a matter of significant debate. In this study, we show that treatment with EGFR TKIs leads to activation of the NFκB pathway, which in turn induces expression of activation-induced cytidine deaminase (AICDA). In turn, AICDA causes deamination of 5-methylcytosine to thymine at position c.2369 to generate the T790M mutation. Pharmacologic inhibition of the NFκB pathway or knockout of AICDA decreased the frequency or prevented the development of T790M mutation, respectively. In addition, patients treated with first-line EGFR TKI displayed increased expression of AICDA and detection of the T790M mutation upon progression. These results identify the mechanism of T790M acquisition and present an opportunity to target the process to delay or prevent it.

Significance:

These findings identify the mechanism behind acquisition of a common resistance mutation to TKI treatment in lung cancer.
Glioma Cell Secretion: A Driver of Tumor Progression and a Potential Therapeutic Target
Authors: Almiron Bonnin Damian A. , Havrda Matthew C. , Israel Mark A.
Published: October 2018

Cellular secretion is an important mediator of cancer progression. Secreted molecules in glioma are key components of complex autocrine and paracrine pathways that mediate multiple oncogenic pathologies. In this review, we describe tumor cell secretion in high-grade glioma and highlight potential novel therapeutic opportunities. Cancer Res; 78(21); 6031–9. ©2018 AACR.
Decision Support and Navigation to Increase Colorectal Cancer Screening Among Hispanic Patients
Authors: Myers Ronald E. , Stello Brian , Daskalakis Constantine , Sifri Randa , González Evelyn T. , DiCarlo Melissa , Johnson Melanie B. , Hegarty Sarah E. , Shaak Kyle , Rivera Alicia , Gordils-Molina Lucas , Petrich Anett , Careyva Beth , de-Ortiz Rosa , Diaz Liselly
Published: October 2018

Background:

Effective strategies are needed to raise colorectal cancer screening rates among Hispanics.

Methods:

We surveyed and randomized 400 Hispanic primary care patients either to a Decision Support and Navigation Intervention (DSNI) Group (n = 197) or a Standard Intervention (SI) Group (n = 203). Both groups received a colorectal cancer screening kit [bilingual informational booklet, fecal immunochemical stool blood test (SBT), and colonoscopy screening instructions]. The DSNI Group received a telephone contact from a patient navigator. The navigator clarified screening test preference and likelihood of test performance, helped to develop a screening plan, and provided guidance through test performance. An endpoint telephone survey and medical chart review were completed. Multivariable analyses were conducted to assess 12-month screening adherence, change in decision stage, and knowledge and perceptions.

Results:

Screening adherence was significantly higher in the DSNI Group than the SI Group [OR, 4.8; 95% confidence interval (CI), 3.1–7.6]. The DSNI Group, compared with the SI Group, also displayed higher SBT screening [OR, 4.2; 95% CI, 2.6–6.7), higher colonoscopy screening (OR, 8.8; 95% CI, 4.1–18.7), and greater forward change in screening decision stage (OR, 4.9; 95% CI, 2.6–9.5). At endpoint, study groups did not differ in screening knowledge or perceptions.

Conclusions:

The DSNI had a greater positive impact on colorectal cancer screening outcomes than the SI.

Impact:

Health system implementation of DSNI strategies may help to reduce Hispanic colorectal cancer screening disparities in primary care.
Breast Cancer Mortality in Older and Younger Patients in California
Authors: Tao Li , Schwab Richard B. , San Miguel Yazmin , Gomez Scarlett Lin , Canchola Alison J. , Gago-Dominguez Manuela , Komenaka Ian K. , Murphy James D. , Molinolo Alfredo A. , Martinez Maria Elena
Published: October 2018

Background:

Breast cancer in younger patients is reported to be more aggressive and associated with lower survival; however, factors associated with age-specific mortality differences have not been adequately assessed.

Methods:

We used data from the population-based California Cancer Registry for 38,509 younger (18–49 years) and 121,573 older (50 years and older) women diagnosed with stage I to III breast cancer, 2005–2014. Multivariable Cox regression models were used to estimate breast cancer–specific mortality rate ratios (MRR) and 95% confidence intervals (CI), stratified by tumor subtype, guideline treatment, and care at an NCI-designated cancer center (NCICC).

Results:

Older breast cancer patients at diagnosis experienced 17% higher disease-specific mortality than younger patients, after multivariable adjustment (MRR = 1.17; 95% CI, 1.11–1.23). Higher MRRs (95% CI) were observed for older versus younger patients with hormone receptor (HR)+/HER2– (1.24; 1.14–1.35) and HR+/HER2+ (1.38; 1.17–1.62), but not for HR–/HER2+ (HR = 0.94; 0.79–1.12) nor triple-negative breast cancers (1.01; 0.92–1.11). The higher mortality in older versus younger patients was diminished among patients who received guideline-concordant treatment (MRR = 1.06; 95% CI, 0.99–1.14) and reversed among those seen at an NCICC (MRR = 0.86; 95% CI, 0.73–1.01).

Conclusions:

Although younger women tend to be diagnosed with more aggressive breast cancers, adjusting for these aggressive features results in older patients having higher mortality than younger patients, with variations by age, tumor subtype, receipt of guideline treatment, and being cared for at an NCICC.

Impact:

Higher breast cancer mortality in older compared with younger women could partly be addressed by ensuring optimal treatment and comprehensive patient-centered care.
Total Serum Cholesterol and Pancreatic Cancer: A Nested Case–Control Study
Authors: Chen William Chang-Yuen , Boursi Ben , Mamtani Ronac , Yang Yu-Xiao
Published: October 2018

Background:

Pancreatic cancer is the third leading cause of cancer-related death in the United States. Total serum cholesterol (TSC) may predict cancer risk, although its role independent of statins remains elusive. We examined the association between TSC and pancreatic cancer risk independent of statins.

Methods:

A nested case–control analysis was conducted among statin-naïve patients within The Health Improvement Network (THIN), a United Kingdom–based general practice database. Cases were >40 years old and diagnosed with pancreatic cancer after at least 6 months of follow-up. Controls were selected by incidence density sampling and matched by age, sex, practice site, and follow-up. Primary exposure was TSC (mmol/L) prior to index date. Conditional logistic regression estimated ORs for pancreatic cancer risk associated with TSC. Sensitivity analyses were conducted among nondiabetics.

Results:

Among 1,241 cases and 3,307 matched controls, an average 8% reduction was observed in pancreatic cancer risk per mmol/L increase in TSC [OR 0.92, 95% confidence interval (CI): 0.85–1.00; nondiabetics: OR 0.91, 95% CI: 0.83–0.99]. When TSC was measured at 12-month intervals prior to diagnosis, the OR between TSC and pancreatic cancer was 0.88 at 0 to 12 months (95% CI: 0.77–1.00; nondiabetics: OR 0.81, 95% CI: 0.68–0.96). No significant association was seen at subsequent discrete intervals before index date.

Conclusions:

TSC is a significant predictor of short-term risk for pancreatic cancer. This risk increase associated with lower TSC was independent of statins.

Impact:

TSC could serve as a biomarker for risk stratification, screening, and early diagnosis of pancreatic cancer in future clinical prediction models.
Stress Resilience in Late Adolescence and Survival among Cancer Patients: A Swedish Register-Based Cohort Study
Authors: Udumyan Ruzan , Montgomery Scott , Fang Fang , Valdimarsdottir Unnur , Fall Katja
Published: October 2018

Background:

Chronic stress has been suggested to play a role in cancer progression, but few studies have so far examined the potential influence of stress susceptibility. This national register-based cohort study utilizes a unique data source to investigate whether a stress resilience measure is associated with survival in cancer patients.

Methods:

The cohort includes 9,318 Swedish male cancer patients born during 1952 to 1956 who had their stress resilience evaluated at a semistructured interview with a psychologist during mandatory conscription examination in late adolescence.

Results:

Over a median of 3 years of follow-up from cancer diagnosis, a total of 2,541 patients died (2,322 from cancer). Overall, low (23%) compared with high (25%) stress resilience was associated with increased mortality (adjusted hazard ratio estimated by Cox regression 1.45; 95% confidence interval 1.28–1.65), particularly among men with carcinomas of the oropharynx (2.62, 1.24–5.56), upper respiratory tract (4.64, 1.05–20.41), and prostate (2.20, 1.04–4.62), as well as with Hodgkin lymphoma (3.52, 1.40–8.86). An association was evident for both cancer types associated with smoking (1.35, 1.10–1.66) and malignancies without an established smoking etiology (1.32, 1.12–1.56). The association between low stress resilience and mortality could partly be explained by tumor stage, marital status, and psychiatric comorbidity at cancer diagnosis.

Conclusions:

We observed an association between low stress resilience and mortality among men diagnosed with cancer, particularly oropharyngeal cancer, upper respiratory tract cancers, prostate cancer, and Hodgkin lymphoma.

Impact:

These results suggest that individual variation in stress resilience may influence survival among men with some cancer types.
Body Fatness, Adipose Tissue Compartments, and Biomarkers of Inflammation and Angiogenesis in Colorectal Cancer: The ColoCare Study
Authors: Himbert Caroline , Ose Jennifer , Nattenmüller Johanna , Warby Christy A. , Holowatyj Andreana N. , Böhm Jürgen , Lin Tengda , Haffa Mariam , Gigic Biljana , Hardikar Sheetal , Scherer Dominique , Zielske Lin , Schrotz-King Petra , Kölsch Torsten , Siegel Erin M. , Shibata David , Ulrich Alexis , Schneider Martin , Hursting Stephen D. , Kauczor Hans-Ulrich , Ulrich Cornelia M.
Published: October 2018

Background:

Adiposity has been linked to both risk and prognosis of colorectal cancer; however, the impact of different fat areas [visceral (VFA) vs. subcutaneous fat area (SFA)] is unclear. We investigated associations between adiposity and biomarkers of inflammation and angiogenesis among patients with colorectal cancer.

Methods:

Preoperative serum samples and computed tomography scans were obtained from 188 patients diagnosed with primary invasive stage I–IV colorectal cancer enrolled in the ColoCare Study. Adiposity was assessed by area-based quantification of VFA, SFA, and VFA:SFA ratio on spinal levels L3/L4 and L4/L5. Circulating levels of inflammation (CRP, SAA, sICAM-1, and sVCAM-1) and angiogenesis (VEGF-A and VEGF-D) were assessed from patient sera on the Meso Scale Discovery platform. Partial correlations and regression analyses, adjusted for age, sex, and tumor stage, were performed.

Results:

VFA was moderately correlated with CRP and SAA (CRP: L3/L4 and L4/L5:r = 0.21, P = 0.01; SAA: L3/L4:r = 0.17, P = 0.04). The correlation between SFA and the measured biomarkers were weak (r ≤ 0.13, not significant). The ratio of VFA:SFA at L3/L4 was moderately correlated with VEGF-A (r = 0.28, P = 0.0008) and SAA (r = 0.24, P = 0.006), and less so with CRP (r = 0.18, P = 0.04) and sICAM-1 (r = 0.18, P = 0.04). Similar correlations were found for the VFA:SFA ratio at L4/L5.

Conclusions:

We observed an association between visceral adiposity and biomarkers of inflammation and angiogenesis in colorectal cancer. In particular, the VFA:SFA ratio was correlated with circulating levels of the proangiogenic biomarker VEGF-A.

Impact:

Our findings support a direct association of visceral adipose tissue with inflammatory and angiogenic processes, which play fundamental roles in the development and progression of colorectal cancer.
Efficacy and Safety of Pirfenidone in Advanced Idiopathic Pulmonary Fibrosis
Authors: Yoon Hee-Young , Kim Dong Soon , Song Jin Woo
Published: October 2018

Background: Although phase 3 trials showed significant efficacy and acceptable safety profiles for pirfenidone in mild-to-moderate idiopathic pulmonary fibrosis (IPF), data on advanced IPF are limited. Objectives: The study aimed to evaluate the efficacy and safety of pirfenidone in advanced IPF patients. Methods: The clinical data of 138 IPF patients (advanced group: 27%) treated with pirfenidone were retrospectively reviewed and compared between advanced and non-advanced groups. Advanced IPF was defined as (1) forced vital capacity (FVC) < 50% predicted or (2) diffusing capacity for carbon monoxide < 30% predicted. Results: The mean treatment duration was 51.3 weeks, and lung function analysis was performed in 81 patients (17 in the advanced group). Changes in FVC and total lung capacity (TLC) were significantly reduced at 6 months after treatment in both the advanced (ΔFVC [6 months]: –6.3 [before] vs. 0.7% predicted [after]; ΔTLC: –5.3 vs. 0.8) and non-advanced (ΔFVC: –3.4 vs. 0.5; ΔTLC: –3.1 vs. –0.9) groups. The rate of decline in FVC and TLC was significant before treatment, but not after treatment in the advanced (FVC: –1.27 [before] vs. 0.21% predicted/month [after]; TLC: –0.89 vs. –0.15) and non-advanced (FVC: –0.60 vs. –0.20; TLC: –0.54 vs. –0.17) groups. The advanced group showed a similar rate of adverse events (AEs) (78.4 vs. 88.1%, p = 0.270), but more serious AEs (40.5 vs. 10.9%, p < 0.001) including death (24.3 vs. 5.0%, p = 0.002). Conclusions: In advanced IPF, pirfenidone showed similar efficacy and safety to non-advanced IPF except for serious AEs, which may be due to the advanced status itself.
Comparison of 577-nm Multispot and Standard Single-Spot Photocoagulation for Diabetic Retinopathy
Authors: Passos Renato M. , Belucio-Neto José , Xavier Camilla O. , Novais Eduardo A. , Maia Mauricio , Farah Michel Eid
Published: October 2018

Objective: To compare two different laser strategies of panretinal photocoagulation for diabetic retinopathy. Methods: Single-center, randomized study including 41 eyes treated with 577-nm multispot laser with a 20-ms pulse duration (group 1) or a 532-nm single-spot laser with a 100-ms pulse duration (group 2). The outcomes included best-corrected visual acuity (BCVA) and imaging changes at baseline, 6 and 12 months, laser parameters, and results of subjective pain analysis. Results: At 12 months, the treatments did not differ significantly in BCVA, central retinal thicknesses (CRTs), improved macular edema, vitreomacular interface changes, patient-reported pain scores, or angiographic responses. Group 1 had significantly fewer treatment sessions but used more laser spots (p < 0.001). Conclusion: The multispot laser required fewer applications with more spots delivered to compensate for lower fluency, showing similar patient tolerance to single-spot laser. Both groups maintained the initial visual acuities and CRTs; about 50% of cases had vitreomacular interface changes and improved macular edema, with similar angiographic improvements after 12 months.
Predictors of Outcomes in Patients with Prolonged Weaning with Focus on Respiratory Tract Pathogens and Infection
Authors: Hommelsheim Catharina , Sichau Mathias , Heipel Roland , Müller Eckhard , Gatermann Sören , Pfeifer Michael , Ewig Santiago
Published: October 2018

Background: The impact of respiratory tract pathogens and infection on outcomes in patients with prolonged weaning is largely unknown. Objective: We studied predictors of weaning outcomes (death and failure to achieve spontaneous ventilation) in a population treated during a 3.5-year period in a specialized and certified weaning centre. Methods: Patient data were retrieved retrospectively from the clinical charts. Complete datasets were available in 173 patients. The following parameters were investigated as potential predictors of both endpoints: age; comorbidities; tracheobronchial pathogens; bacteraemia, pneumonia and number of pneumonias; and number of inhouse treatment cycles (none vs. ≥1). Results: Tracheobronchial pathogens, pneumonia, bacteraemia and the number of antibiotic cycles all significantly increased weaning duration and hospitalisation times. Independent predictors of death were atrial fibrillation (OR 2.6, 95% CI 1.2–5.8, p = 0.02) and tracheobronchial multiresistant Pseudomonas aeruginosa (OR 3.9, 95% CI 1.4–11.0, p = 0.01). Independent predictors of failure to achieve spontaneous ventilation included chronic obstructive pulmonary disease (OR 2.8, 95% CI 1.0–7.8, p = 0.045); neuromuscular disease (OR 8.3, 95% CI 1.2–27.2, p = 0.02); tracheobronchial P. aeruginosa (OR 3.3, 95% CI 1.3–9.3, p = 0.01); Stenotrophomonas maltophilia (OR 7.9, 95% CI 1.4–51.6, p = 0.02); and pneumonia (OR 4.4, 95% CI 1.5–10.9, p = 0.003). Conclusions: The impact of respiratory tract pathogens and infection on weaning outcomes was remarkable. Predictors of death and failure to achieve spontaneous ventilation differed considerably. A priority may be to investigate preventive strategies against colonisation and infection with respiratory pathogens, particularly P. aeruginosa.
In vitro and in vivo GABAA Receptor Interaction of the Propanidid Metabolite 4-(2-[Diethylamino]-2-Oxoethoxy)-3-Methoxy-Benzeneacetic Acid
Authors: Cenani Alessia , Brosnan Robert J. , Knych Heather K.
Published: October 2018

Background: Propanidid is a γ-aminobutyric acid type A (GABAA) receptor agonist general anesthetic and its primary metabolite is 4-(2-[diethylamino]-2-oxoethoxy)-3-methoxy-benzeneacetic acid (DOMBA). Despite having a high water solubility at physiologic pH that might predict low-affinity GABAA receptor interactions, DOMBA is reported to have no effect on GABAA receptor currents, possibly because the DOMBA concentrations studied were simply insufficient to modulate GABAA receptors. Our objectives were to measure the propanidid and DOMBA concentration responses on ­GABAA receptors and to measure the behavioral responses of DOMBA in mice at concentrations that affect GABAA receptor currents in vitro. Methods: GABAA receptors were expressed in oocytes using clones for the human GABAA α1, β2 and γ2s subunits. The effects of DOMBA (0.2–10 mmol/L) and propanidid (0.001–1 mmol/L) on oocyte GABAA currents were studied using standard 2-electrode voltage clamp techniques. Based on in vitro results, 6 mice received ­DOMBA 32 mg intraperitoneal and were observed for occurrence of neurologic effects and DOMBA plasma concentration was measured by liquid chromatography tandem mass spectrometry. Results: DOMBA both directly activates GABAA receptors and antagonizes its GABA-mediated opening in a concentration-dependent manner at concentrations between 5–10 and 0.5–10 mmol/L respectively. In vivo, DOMBA produced rapid onset sedation at plasma concentrations that correlate with direct GABAA receptor activation. Conclusion: DOMBA modulation of GABAA receptors is associated with sedation in mice. Metabolites of propanidid analogues currently in development may similarly modulate GABAA, and impaired elimination of these metabolites could produce clinically relevant neurophysiologic effects.
Risk Factors of Intra-Amniotic Infection Related to Induction with Single-Balloon Catheter: A Case-Control Study
Authors: Zhang Yongqing , Yu Ying , Chen Luping , Zhao Wei , Chu Ketan , Han Xiujun
Published: October 2018

Aims: To investigate the risk factors of intra-amniotic infection (IAI) related to induction with single-balloon catheter (SBC). Methods: A retrospective, case-control study including 58 cases of IAI patients who underwent induction with SBC was conducted in Women’s Hospital, School of Medicine, Zhejiang University. For each case, 8 women who delivered during the same month and had no infection after SBC induction were selected for control. Results: Compared with the control group, the IAI group had a higher rate of nulliparity (87.93 vs. 70.69%; p = 0.006), BMI > 30 kg/m2 (29.31 vs. 15.95%; p = 0.011), and amniotic fluid index (AFI) < 8 cm (32.8 vs. 15.1%; p = 0.001). The diameter of cervical dilatation when membranes ruptured in IAI group was smaller than that in the control group (2.0 [1.5] vs. 3.0 [8.0] cm; p < 0.001). Time from start of induction to vaginal delivery was longer than that in the control group (47.0 [19.75] vs. 27.0 [16.0] h; p < 0.001). After logistic regression, the 5 factors associated with IAI for those who underwent SBC induction were nulliparity, BMI > 30 kg/m2, AFI < 8 cm, diameter of cervical dilatation < 3 cm when membranes ruptured and time from start of induction to vaginal delivery of more than 48 h. Conclusions: Focus on these risk factors could result in earlier prophylaxis so that the incidence of IAI could be reduced.
Severe de novo Ulcerative Colitis following Ixekizumab Therapy
Authors: Philipose Jobin , Ahmed Moiz  , Idiculla Pretty S. , Mulrooney Stephen M. , Gumaste Vivek V.
Published: October 2018

Ixekizumab is a selective monoclonal antibody targeting interleukin-17A, approved for the treatment of chronic plaque psoriasis. It has rarely been associated with inflammatory bowel disease (IBD) in randomized trials only. We report a unique case of severe new-onset ulcerative colitis in a young male complicated by cytomegalovirus infection who was on ixekizumab therapy for plaque psoriasis. We recommend that clinicians should exercise caution before prescribing ixekizumab as it seems to induce and exacerbate IBD.
Advanced Neuroimaging in Stroke Patient Selection for Mechanical Thrombectomy
Authors: Tsivgoulis Georgios , Katsanos Aristeidis H. , Schellinger Peter D. , Köhrmann Martin , Caso Valeria , Palaiodimou Lina , Magoufis Georgios , Arthur Adam , Fischer Urs , Alexandrov Andrei V.
Published: October 2018

Background and Purpose—

There is clinical equipoise about the use of advanced imaging for selecting acute ischemic stroke patients eligible for mechanical thrombectomy (MT) during the first 6 hours from symptom onset. However, accumulating evidence indicates that advanced neuroimaging represents an invaluable and time-independent prognostic factor.

Methods—

We performed a systematic review and meta-analysis of available randomized clinical trials to evaluate the impact of patient selection with advanced neuroimaging on the 3-month: (1) functional independence (modified Rankin Scale score, 0–2), (2) favorable functional outcome (modified Rankin Scale scores, 0–1), (3) all-cause mortality, and (4) functional improvement (assessed with ordinal analysis of the modified Rankin Scale-scores). We compared patients with perfusion imaging documented penumbra to patients who did not have documented penumbra or perfusion imaging.

Results—

Among the 10 eligible randomized clinical trials (2227 total patients, mean age: 67 years), 5 studies reported the use of advanced imaging. Studies using advanced neuroimaging showed higher treatment effects of MT on 3-month functional independence (odds ratio [OR], 3.79; 95% CI, 2.71–5.28 versus OR, 1.89; 95% CI, 1.52–2.35;
P
for subgroup differences <0.001), favorable functional outcome (OR, 3.16; 95% CI, 1.94–5.14 versus OR, 1.75; 95% CI, 1.30–2.34;
P
for subgroup differences=0.04), and functional improvement (common OR, 2.66; 95% CI, 1.95–3.63 versus common OR, 1.60; 95% CI, 1.32–1.95;
P
for subgroup differences=0.007) compared with studies using conventional neuroimaging. The pooled rate of successful reperfusion after MT was higher in studies with advanced neuroimaging (
P
for subgroup differences=0.003). No difference in the mortality and symptomatic intracranial hemorrhage rates was found between the 2 groups. No evidence of heterogeneity was documented in all reported analyses.

Conclusions—

The present indirect comparisons indicate that acute ischemic stroke patient selection for MT using advanced neuroimaging appears to be associated with improved clinical outcomes. The use of advanced neuroimaging for both the selection and prediction of prognosis for MT candidates should not depend on the elapsed time from symptom onset.
God in the Crucified People
Authors: Adiprasetya Joas
Published: October 2018

This article examines Martin Luther’s theology of the cross (theologia crucis) and its implications for the Asian struggle for humanity. It is argued that, although Luther’s influence on many Asian theologians is significant, his inconsistent position with regard to sociopolitical issues requires Asian theologians to reinterpret their own theologies of the cross beyond Luther’s initial position. Moreover, the article explores Kosuke Koyama’s appropriation of Luther’s theologia crucis in the Asian context by imaginatively constructing his own theology of the cross that critically addresses Asian sociopolitical realities.