bluuebunny/crossref_metadata_2025 huggingface dataset:
The Clinical Cost of Delays in Switching Therapy
Authors: Walmsley Sharon
Published: May 2016

Management of the HIV patient with treatment experience continues to improve and evolve. New guidelines suggest that the goal of therapy should be maximal virological suppression. This is best achieved by using combinations of agents to which the virus is most likely to have some susceptibility and, where possible, by using agents within a new therapeutic class. The cases discussed demonstrate how the use of a potent regimen as salvage therapy can have good clinical, immunological and virological outcomes. However, if the salvage regimen selected is not potent enough to achieve these goals, the durability of the response is limited. The key lesson is that these strategies should be built on potency and agents should not be held back in case the strategy fails.
Treatment Strategy: Role of Enfuvirtide in Managing Treatment-Limiting Side Effects
Authors: Tsoukas Christos
Published: May 2016

Side effects can limit the options available to physicians for the treatment of HIV infection. Management of these side effects is essential, to avoid cessation of treatment. The entry inhibitor enfuvirtide can be useful as one of three active agents in an HIV treatment regimen as a way to both reduce treatment-limiting side effects and provide an efficacious agent for viral control. In the present case, the patient had a problematic and lengthy treatment history, with numerous concomitant conditions. His latest regimen, which includes an agent in a new drug class (enfuvirtide), has maintained HIV suppression while minimizing toxicity.
Patient Care and Support Measures Overcome Reluctance to Initiate New Regimen Containing Enfuvirtide
Authors: Trottier Benoit
Published: May 2016

Patients can be resistant to initiation of enfuvirtide therapy because of concerns about self-injection and related issues. Because the introduction of a new drug class can substantially enhance the efficacy of an antiretroviral regimen, supporting the patient in the introduction of enfuvirtide, a safe and efficacious agent in a new class, offers therapeutic benefits. In the present patient, who showed resistance to all three of the major antiretroviral drug classes, enfuvirtide was successfully introduced with clinic and peer support group assistance. The patient’s acceptance was enhanced by the use of a needle-free injection system (Biojector), with minimal side effects and significantly improved virological and immunological control.
Laparoscopic Treatment of Type III Mirizzi Syndrome by T-Tube Drainage
Authors: Yetışır Fahri , Şarer Akgün Ebru , Acar H. Zafer , Polat Yılmaz , Osmanoglu Gokhan , Aygar Muhittin , Ciftciler A. Erdinc , Parlak Omer
Published: May 2016

Mirizzi syndrome (MS) is an impacted stone in the cystic duct or Hartmann’s pouch that mechanically obstructs the common bile duct. We would like to report laparoscopic treatment of type III MS. A 75-year-old man was admitted with the complaint of abdominal pain and jaundice. The patient was accepted as MS type III according to radiological imaging and intraoperative view. Laparoscopic subtotal cholecystectomy, extraction of impacted stone by opening anterior surface of dilated cystic duct and choledochus, and repair of this opening by using the remaining part of gallbladder over the T-tube drainage were performed in a patient with type III MS. Application of reinforcement suture over stump was done in light of the checking with oliclinomel N4 injection trough the T-tube. At the 18-month follow-up, he was symptom-free with normal liver function tests.
Effects of End-Terminal Capping on Transthyretin (105–115) Amyloid Protofibrils Using Steered Molecular Dynamics
Authors: Lee Myeongsang , Choi Hyunsung , Na Sungsoo
Published: May 2016

Numerous degenerative diseases are associated with amyloidosis, which can be caused by amyloid proteins. These amyloid proteins are generated from misfolded and denatured amyloid monomers under physiological conditions. Changes in protonation state, pH, ionic strength, and temperature, in addition to mutations, are related to the promotion of amyloidosis. Specifically, an understanding of the mechanical characteristics of amyloid protofibrils is important, since amyloid growth proceeds by a mechanism involving cycles of fragmentation and elongation. However, there remains a lack of knowledge of amyloid structural conformations and their mechanical characteristics, particularly considering end-terminal capping effects. In the present study, we investigated the mechanical characteristics of transthyretin amyloid protein (TTR), which have been implicated in cardiovascular disease, and specifically considered the contribution of end-terminal capping effects. Using steered molecular dynamics (SMD) simulations, we report different structural behaviors between uncapped and capped TTR amyloid protofibrils. We show that end-terminal capping strengthens the structural stability and improves the mechanical properties of amyloid protofibrils. This study provides useful information concerning the structural and mechanical characteristics of TTR amyloid protofibrils, with a particular emphasis on end-terminal capping effects.
The Effective Ransomware Prevention Technique Using Process Monitoring on Android Platform
Authors: Song Sanggeun , Kim Bongjoon , Lee Sangjun
Published: May 2016

Due to recent indiscriminate attacks of ransomware, damage cases including encryption of users’ important files are constantly increasing. The existing vaccine systems are vulnerable to attacks of new pattern ransomware because they can only detect the ransomware of existing patterns. More effective technique is required to prevent modified ransomware. In this paper, an effective method is proposed to prevent the attacks of modified ransomware on Android platform. The proposed technique specifies and intensively monitors processes and specific file directories using statistical methods based on Processor usage, Memory usage, and I/O rates so that the process with abnormal behaviors can be detected. If the process running a suspicious ransomware is detected, the proposed system will stop the process and take steps to confirm the deletion of programs associated with the process from users. The information of suspected and exceptional processes confirmed by users is stored in a database. The proposed technique can detect ransomware even if you do not save its patterns. Its speed of detection is very fast because it can be implemented in Android source code instead of mobile application. In addition, it can effectively determine modified patterns of ransomware and provide protection with minimum damage.
Comparison of the Success of Two Techniques for the Endotracheal Intubation with C-MAC Video Laryngoscope Miller Blade in Children: A Prospective Randomized Study
Authors: Sinha Renu , Sharma Ankur , Ray Bikash Ranjan , Kumar Pandey Ravinder , Darlong Vanlalnghka , Punj Jyotsna , Chandralekha Chandralekha , Upadhyay Ashish Datt
Published: May 2016

Background. Ease of endotracheal intubation with C-MAC video laryngoscope (VLS) with Miller blades 0 and 1 has not been evaluated in children.Methods. Sixty children weighing 3–15 kg with normal airway were randomly divided into two groups. Intubation was done with C-MAC VLS Miller blade using either nonstyletted endotracheal tube (ETT) (group WS) or styletted ETT (group S). The time for intubation and total procedure, intubation attempts, failed intubation, blade repositioning or external laryngeal maneuver, and complications were recorded.Results. The median (minimum/maximum) time for intubation in group WS and group S was 19.5 (9/48) seconds and 13.0 (18/55) seconds, respectively (p=0.03). The median (minimum/maximum) time for procedure in group WS was 30.5 (18/72) seconds and in group S was 24.5 (14/67) seconds, respectively (p=0.02). Intubation in first attempt was done in 28 children in group WS and in 30 children in group S. Repositioning was required in 14 children in group WS and in 7 children in group S (p=0.06). There were no failure to intubate, desaturation, and bradycardia in both groups.Conclusion. Styletted ETT significantly reduces time for intubation and time for procedure in comparison to nonstyletted ETT.
Measurement and Prediction Method of Compressibility Factor at High Temperature and High Pressure
Authors: Zhu Xiaoxun , Xu Bochao , Han Zhonghe
Published: May 2016

In order to get the compressibility factorZof working fluid under different conditions, experimental measurement method ofZunder high pressure and high temperature and data mining method were studied in this paper. Experimental measurement method based on real gas state equation and prediction method based on Least Squares Support Vector Machine were proposed. First, an experimental method for measuringZat high temperature and high pressure was designed; in this method the temperature, pressure, and density (mass and volume) of corresponding state were measured and substituted into the actual gas equation of state, and thenZcan be calculated. Meanwhile, in order to obtain continuous value inT-pplane, Squares Support Vector Machines are introduced to establish the prediction model ofZ. Take Hexamethyldisiloxane, for example; the experimental data ofZwas obtained using the experimental method. Meanwhile the prediction model ofZ, which can be used as calculation function ofZ, was established based on those experimental data, and theZ(T: 500 K~800 K,p: 1.3 MPa~2.25 MPa) was calculated by using this calculation function. By comparison with this published data, it was found that the average relative error was 2.14%.
Approximation of the Monte Carlo Sampling Method for Reliability Analysis of Structures
Authors: Shadab Far Mahdi , Wang Yuan
Published: May 2016

Structural load types, on the one hand, and structural capacity to withstand these loads, on the other hand, are of a probabilistic nature as they cannot be calculated and presented in a fully deterministic way. As such, the past few decades have witnessed the development of numerous probabilistic approaches towards the analysis and design of structures. Among the conventional methods used to assess structural reliability, the Monte Carlo sampling method has proved to be very convenient and efficient. However, it does suffer from certain disadvantages, the biggest one being the requirement of a very large number of samples to handle small probabilities, leading to a high computational cost. In this paper, a simple algorithm was proposed to estimate low failure probabilities using a small number of samples in conjunction with the Monte Carlo method. This revised approach was then presented in a step-by-step flowchart, for the purpose of easy programming and implementation.
Risk Factors for Macro- and Microvascular Complications among Older Adults with Diagnosed Type 2 Diabetes: Findings from The Irish Longitudinal Study on Ageing
Authors: Tracey Marsha L. , McHugh Sheena M. , Fitzgerald Anthony P. , Buckley Claire M. , Canavan Ronan J. , Kearney Patricia M.
Published: May 2016

Objective. To explore risk factors for macro- and microvascular complications in a nationally representative sample of adults aged 50 years and over with type 2 diabetes in Ireland.Methods. Data from the first wave of The Irish Longitudinal Study on Ageing (TILDA) (2009–2011) was used in cross-sectional analysis. The presence of doctor diagnosis of diabetes, risk factors, and macro- and microvascular complications were determined by self-report. Gender-specific differences in risk factor prevalence were assessed with the chi-squared test. Binomial regression analysis was conducted to explore independent associations between established risk factors and diabetes-related complications.Results. Among 8175 respondents, 655 were classified as having type 2 diabetes. Older age, being male, a history of smoking, a lower level of physical activity, and a diagnosis of high cholesterol were independent predictors of macrovascular complications. Diabetes diagnosis of 10 or more years, a history of smoking, and a diagnosis of hypertension were associated with an increased risk of microvascular complications. Older age, third-level education, and a high level of physical activity were protective factors (p<0.05).Conclusions. Early intervention to target modifiable risk factors is urgently needed to reduce diabetes-related morbidity in the older population in Ireland.
Antihistamine-Induced Hepatitis: 2 Cases Involving Loratidine
Authors: Arshad Hafiz , Khan Arsalan , Assad Usama , Kittaneh Muaiad , Berkelhammer Charles
Published: May 2016

Antihistamine-induced hepatitis is rare. We present 2 cases of antihistamine-induced hepatitis with autoimmune features, caused by loratidine. One case was confirmed by rechallenge. Identifying and discontinuing the offending agent are essential for treatment.
Sports Motion Recognition Using MCMR Features Based on Interclass Symbolic Distance
Authors: Wei Yu , Jiao Libin , Wang Shenling , Bie Rongfang , Chen Yinfeng , Liu Dalian
Published: May 2016

Human motion and gesture recognition receive much concern in sports field, such as physical education and fitness for all. Although plenty of mature applications appear in sports training using photography, video camera, or professional sensing devices, they are either expensive or inconvenient to carry. MEMS devices would be a wise choice for students and ordinary body builders as they are portable and have many built-in sensors. In fact, recognition of hand gestures is discussed in many studies using inertial sensors based on similarity matching. However, this kind of solution is not accurate enough for human movement recognition and cost much time. In this paper, we discuss motion recognition in sports training using features extracted from distance estimation of different kinds of sensors. To deal with the multivariate motion sequence, we propose a solution that applies Max-Correlation and Min-Redundancy strategy to select features extracted with interclass distance similarity estimation. With this method, we are able to screen out proper features that can distinguish motions in different classes effectively. According to the results of experiment in real world application in dance practice, our solution is quite effective with fair accuracy and low time cost.
Improvement of the Texture of Yogurt by Use of Exopolysaccharide Producing Lactic Acid Bacteria
Authors: Han Xue , Yang Zhe , Jing Xueping , Yu Peng , Zhang Yingchun , Yi Huaxi , Zhang Lanwei
Published: May 2016

19Streptococcus thermophiluswith high exopolysaccharide production were isolated from traditional Chinese fermented dairy products. The exopolysaccharide and viscosity of milk fermented by these 19 isolates were assayed. The strains ofStreptococcus thermophiluszlw TM11 were selected because its fermented milk had the highest exopolysaccharide content (380 mg/L) and viscosity (7716 mpa/s). ThenStreptococcus thermophiluszlw TM11 was combined withLactobacillus delbrueckiisubsp.bulgaricus3 4.5 and the combination was named SH-1. The quality of the yogurt fermented by SH-1 and two commercial starter cultures (YO-MIX 465, YF-L711) were compared. It was shown that the exopolysaccharide content of yogurt fermented by SH-1 was similar to that of yogurt fermented by YF-L711 and significantly higher than YO-MIX 465 (p<0.05). In addition, the yogurt fermented by SH-1 had the lowest syneresis (8.5%) and better texture and sensory than the samples fermented by YO-MIX 465 and YF-L711. It manifested that the selected higher exopolysaccharide production starter SH-1 could be used as yogurt starter and reduce the amount of adding stabilizer, which can compare with the imported commercial starter culture.
Arabic Translation and Psychometric Evaluation of the Depression Literacy Questionnaire among Adolescents
Authors: Darraj Hussain Ahmed , Mahfouz Mohamed Salih , Al Sanosi Rashad Mohamed , Badedi Mohammed , Sabai Abdullah , AL Refaei Abdulrahman , Mutawm Hussain
Published: May 2016

Background. Depression is a serious mental health disease. Globally, it is estimated that almost 350 million people suffer from depression. It is important to assess depression literacy including knowledge and beliefs about mental disorders among adolescents.Objective. This study was conducted to validate the Arabic version of the Depression Literacy Questionnaire (D-Lit) among adolescents.Methods. A cross-sectional study was conducted among a sample size of 120 adolescents. Statistical analysis included face validation, confirmatory factor analysis, and reliability testing. A test-retest was carried out within a two-week interval.Results. The mean score for depression literacy among participants was 8.6 (SD = 4.48), the median was 8, and the interquartile range was 7. Preliminary construct validation analysis confirmed that factor analysis was appropriate for the Arabic version of D-Lit. The total internal consistency was measured by Cronbach’s alpha coefficient and split-half test and the results were 0.78 and 0.71, respectively. The test-retest reliability measured by Pearson’s correlation was 0.92 and spearman rho was equal to 0.91.Conclusions. Face validity, construct validity, and reliability analysis were found satisfactory for the Arabic version of D-Lit. The Arabic D-Lit was found valid and reliable to be used in the future studies.
Association between Accessory Gene Regulator Polymorphism and Mortality among Critically Ill Patients Receiving Vancomycin for Nosocomial MRSA Bacteremia: A Cohort Study
Authors: Cechinel Angélica , Machado Denise P. , Turra Eduardo , Pereira Dariane , dos Santos Rodrigo P. , Rosa Regis G. , Goldani Luciano Z.
Published: May 2016

Background. Polymorphism of the accessory gene regulator group II (agr) in methicillin-resistantStaphylococcus aureus(MRSA) is predictive of vancomycin failure therapy. Nevertheless, the impact of group IIagrexpression on mortality of patients with severe MRSA infections is not well established.Objective. The goal of our study was to evaluate the association betweenagrpolymorphism and all-cause in-hospital mortality among critically ill patients receiving vancomycin for nosocomial MRSA bacteremia.Methods. All patients with documented bacteremia by MRSA requiring treatment in the ICU between May 2009 and November 2011 were included in the study. Cox proportional hazards regression was performed to evaluate whetheragrpolymorphism was associated with all-cause in-hospital mortality. Covariates included age, APACHE II score, initial C-reactive protein plasma levels, initial serum creatinine levels, vancomycin minimum inhibitory concentration, vancomycin serum levels, and time to effective antibiotic administration.Results. The prevalence of group I and group IIagrexpression was 52.4% and 47.6%, respectively. Bacteremia by MRSA group III or group IVagrwas not documented in our patients. The mean APACHE II of the study population was 24.3 (standard deviation 8.5). The overall cohort mortality was 66.6% (14 patients). After multivariate analysis, initial plasma C-reactive protein levels (P=0.01), initial serum creatinine levels (P=0.008), and expression of group IIagr(P=0.006) were positively associated with all-cause in-hospital mortality. Patients with bacteremia by MRSA with group IIagrexpression had their risk of death increased by 12.6 times when compared with those with bacteremia by MRSA with group Iagrexpression.Conclusion. Group IIagrpolymorphism is associated with an increase in mortality in critically ill patients with bacteremia by MRSA treated with vancomycin.
Stem Cell Therapy for Treatment of Ocular Disorders
Authors: Sivan Padma Priya , Syed Sakinah , Mok Pooi-Ling , Higuchi Akon , Murugan Kadarkarai , Alarfaj Abdullah A. , Munusamy Murugan A. , Awang Hamat Rukman , Umezawa Akihiro , Kumar Suresh
Published: May 2016

Sustenance of visual function is the ultimate focus of ophthalmologists. Failure of complete recovery of visual function and complications that follow conventional treatments have shifted search to a new form of therapy using stem cells. Stem cell progenitors play a major role in replenishing degenerated cells despite being present in low quantity and quiescence in our body. Unlike other tissues and cells, regeneration of new optic cells responsible for visual function is rarely observed. Understanding the transcription factors and genes responsible for optic cells development will assist scientists in formulating a strategy to activate and direct stem cells renewal and differentiation. We review the processes of human eye development and address the strategies that have been exploited in an effort to regain visual function in the preclinical and clinical state. The update of clinical findings of patients receiving stem cell treatment is also presented.
Renal Cancer Stem Cells: Characterization and Targeted Therapies
Authors: Peired Anna Julie , Sisti Alessandro , Romagnani Paola
Published: May 2016

Renal cell carcinoma (RCC) is a major neoplasm with high incidence in western countries. Tumors are heterogeneous and are composed of differentiated cancer cells, stromal cells, and cancer stem cells (CSCs). CSCs possess two main properties: self‐renewal and proliferation. Additionally, they can generate new tumors once transplanted into immunodeficient mice. Several approaches have been described to identify them, through the expression of cell markers, functional assays, or a combination of both. As CSCs are involved in the resistance mechanisms to radio‐ and chemotherapies, several new strategies have been proposed to directly target CSCs in RCC. One approach drives CSCs to differentiate into cancer cells sensitive to conventional treatments, while the other proposes to eradicate them selectively. A series of innovative therapies aiming at eliminating CSCs have been designed to treat other types of cancer and have not been experimented with on RCC yet, but they reveal themselves to be promising. In conclusion, CSCs are an important player in carcinogenesis and represent a valid target for therapy in RCC patients.
Simultaneous Minimally Invasive Treatment of Colorectal Neoplasm with Synchronous Liver Metastasis
Authors: Garritano Stefano , Selvaggi Federico , Spampinato Marcello Giuseppe
Published: May 2016

Purpose. To analyse perioperative and oncological outcomes of minimally invasive simultaneous resection of primary colorectal neoplasm with synchronous liver metastases.Methods. A Medline revision of the current published literature on laparoscopic and robotic-assisted combined colectomy with hepatectomy for synchronous liver metastatic colorectal neoplasm was performed until February 2015. The specific search terms were “liver metastases”, “hepatic metastases”, “colorectal”, “colon”, “rectal”, “minimally invasive”, “laparoscopy”, “robotic-assisted”, “robotic colorectal and liver resection”, “synchronous”, and “simultaneous”.Results. 20 clinical reports including 150 patients who underwent minimally invasive one-stage procedure were retrospectively analysed. No randomized trials were found. The approach was laparoscopic in 139 patients (92.7%) and robotic in 11 cases (7.3%). The rectum was the most resected site of primary neoplasm (52.7%) and combined liver procedure was in 89% of cases a minor liver resection. One patient (0.7%) required conversion to open surgery. The overall morbidity and mortality rate were 18% and 1.3%, respectively. The most common complication was colorectal anastomotic leakage. Data concerning oncologic outcomes were too heterogeneous in order to gather definitive results.Conclusion. Although no prospective randomized trials are available, one-stage minimally invasive approach seems to show advantages over conventional surgery in terms of postoperative short-term course. On the contrary, more studies are required to define the oncologic values of the minimally invasive combined treatment.
Exercise-Induced Dose-Response Alterations in Adiponectin and Leptin Levels Are Dependent on Body Fat Changes in Women at Risk for Breast Cancer
Authors: Sturgeon Kathleen , Digiovanni Laura , Good Jerene , Salvatore Domenick , Fenderson Desiré , Domchek Susan , Stopfer Jill , Galantino Mary Lou , Bryan Cathy , Hwang Wei-Ting , Schmitz Kathryn
Published: May 2016

Background: Dysregulation of adipokines, such as adiponectin and leptin, is associated with a variety of chronic diseases, including cancer. Physical activity protects against breast cancer and one of the mechanisms which may underlie this association is exercise-induced changes in adipokine levels. The WISER Sister Trial was a three-armed randomized controlled trial in premenopausal women (n = 137) with an elevated risk for breast cancer.

Methods: A 5-menstrual-cycle-long dosed aerobic exercise intervention compared low-dose exercise (150 min/wk; n = 44) or high-dose exercise (300 min/wk; n = 48) with a control group asked to maintain usual activity levels (n = 45). Exercise intensity progressed to and was maintained at 70% to 80% of age predicted heart rate max. Body composition and adipokine levels were measured at baseline and follow-up.

Results: We observed significant linear trends for increased fitness capacity (Δ%: −2.0% control, 10.1% low dose, 13.1% high dose), decreased fat tissue-to-total tissue mass (Δ%: 0.7% control, −2.9% low dose, −3.7% high dose), increased body fat adjusted adiponectin (Δ%: −0.6% control, 0.6% low dose, 0.9% high dose), and decreased body fat adjusted leptin (Δ%: 0.7% control, −8.2% low dose, −10.2% high dose).

Conclusions: In this randomized clinical trial of premenopausal women at risk for breast cancer, we demonstrate a dose–response effect of exercise on adiponectin and leptin and that dose response is dependent on changes in body fat.

Impact: Improved adipokine levels, achieved by aerobic exercise training-induced decreases in body fat, may decrease breast cancer risk for high-risk premenopausal women. Cancer Epidemiol Biomarkers Prev; 25(8); 1195–200. ©2016 AACR.
Phase I Study of the Investigational Anti-Guanylyl Cyclase Antibody–Drug Conjugate TAK-264 (MLN0264) in Adult Patients with Advanced Gastrointestinal Malignancies
Authors: Almhanna Khaldoun , Kalebic Thea , Cruz Cristina , Faris Jason E. , Ryan David P. , Jung JungAh , Wyant Tim , Fasanmade Adedigbo A. , Messersmith Wells , Rodon Jordi
Published: May 2016

Purpose: To assess the safety, tolerability, and preliminary antitumor activity of the investigational anti–guanylyl cyclase C (GCC) antibody–drug conjugate TAK-264 (formerly MLN0264) in adult patients with advanced gastrointestinal malignancies.

Experimental Design: Adult patients with GCC-expressing gastrointestinal malignancies (H-score ≥ 10) were eligible for inclusion. TAK-264 was administered as a 30-minute intravenous infusion once every 3 weeks for up to 17 cycles. Dose escalation proceeded using a Bayesian continual reassessment method. At the maximum tolerated dose (MTD), 25 patients with metastatic colorectal cancer were enrolled in a prespecified dose expansion cohort.

Results: Forty-one patients were enrolled, including 35 (85%) with metastatic colorectal cancer. During dose escalation (0.3–2.4 mg/kg), four of 19 patients experienced dose-limiting toxicities of grade 4 neutropenia; the MTD was determined as 1.8 mg/kg. Patients received a median of two cycles of TAK-264 (range, 1–12); nine received ≥four cycles. Common drug-related adverse events (AEs) included nausea and decreased appetite (each 41%), fatigue (32%), diarrhea, anemia, alopecia, and neutropenia (each 27%); grade ≥3 AEs included neutropenia (22%), hypokalemia, and febrile neutropenia (each 7%). Peripheral neuropathy was reported in four (10%) patients. Pharmacokinetic data showed approximately dose proportional systemic exposure and a mean plasma half-life of around 4 days, supporting the dosing schedule. Overall, 39 patients were response-evaluable; three experienced durable stable disease; and one with gastric adenocarcinoma had a partial response. GCC expression did not appear to correlate with treatment duration.

Conclusions: These findings suggest that TAK-264 has a manageable safety profile, with preliminary evidence of potential antitumor activity in specific gastrointestinal malignancies. Further investigation is underway. Clin Cancer Res; 22(20); 5049–57. ©2016 AACR.
PAK1 Is a Novel Therapeutic Target in Tyrosine Kinase Inhibitor–Resistant Lung Adenocarcinoma Activated by the PI3K/AKT Signaling Regardless of EGFR Mutation
Authors: Wu De-Wei , Wu Tzu-Chin , Chen Chih-Yi , Lee Huei
Published: May 2016

Purpose: EGFR mutation as a biomarker has documented that EGFR-mutant patients will derive clinical benefit from tyrosine kinase inhibitor (TKI) treatment. Unfortunately, most patients show TKI resistance and tumor recurrence after therapy. Therefore, we expected that an adjuvant biomarker other than EGFR mutation is needed for predicting TKI resistance.

Experimental Design: Molecular manipulations were performed to verify whether TKI resistance mediated by p21-activated kinase (PAK1) could be through increasing Mcl-1 protein stability via the PI3K/AKT/C/EBP-β/miR-145 cascade. Xenograft mouse models were used to confirm the mechanistic action of PAK1 on TKI resistance. Forty-six tumor tissues from patients with lung adenocarcinoma who received TKI therapy were collected to evaluate PAK1 and E-cadherin mRNA expressions by real-time PCR. The association of PAK1 and E-cadherin mRNA expressions with tumor response to TKI treatment and outcomes was evaluated.

Results: We demonstrate that PAK1 confers TKI resistance in EGFR-mutant cells as well as in EGFR–wild-type cells. Mechanistically, the positive feedback loop of PAK1/PI3K/AKT/C/EBP-β/miR-145 cascades persistently activates the PI3K/AKT signaling pathway to protect Mcl-1 degradation by Fbw7, which results, in turn, in TKI resistance and cell invasion via epithelial-to-mesenchymal transition due to a decrease in E-cadherin expression. The mechanism underlying the cell model is further confirmed in xenograft tumors. Among patients, high-PAK1 or low–E-cadherin tumors more commonly exhibited an unfavorable response to TKI and poorer outcome compared with low-PAK1 or low–E-cadherin tumors.

Conclusions: The combination of TKI with AKT inhibitor might confer TKI sensitivity and in turn improve outcomes in patients with lung adenocarcinoma who harbored high PAK1 mRNA–expressing tumors. Clin Cancer Res; 22(21); 5370–82. ©2016 AACR.
Immune-Derived PD-L1 Gene Expression Defines a Subgroup of Stage II/III Colorectal Cancer Patients with Favorable Prognosis Who May Be Harmed by Adjuvant Chemotherapy
Authors: Dunne Philip D. , McArt Darragh G. , O'Reilly Paul G. , Coleman Helen G. , Allen Wendy L. , Loughrey Maurice , Van Schaeybroeck Sandra , McDade Simon , Salto-Tellez Manuel , Longley Daniel B. , Lawler Mark , Johnston Patrick G.
Published: May 2016

A recent phase II study of patients with metastatic colorectal carcinoma showed that mismatch repair gene status was predictive of clinical response to PD-1–targeting immune checkpoint blockade. Further examination revealed strong correlation between PD-L1 protein expression and microsatellite instability (MSI) in stage IV colorectal carcinoma, suggesting that the amount of PD-L1 protein expression could identify late-stage patients who might benefit from immunotherapy. To assess whether the clinical associations between PD-L1 gene expression and MSI identified in metastatic colorectal carcinoma are also present in stage II/III colorectal carcinoma, we used in silico analysis to elucidate the cell types expressing the PD-L1 gene. We found a statistically significant association of PD-L1 gene expression with MSI in early-stage colorectal carcinoma (P < 0.001) and show that, unlike in non–colorectal carcinoma tumors, PD-L1 is derived predominantly from the immune infiltrate. We demonstrate that PD-L1 gene expression has positive prognostic value in the adjuvant disease setting (PD-L1low vs. PD-L1high HR = 9.09; CI, 2.11–39.10). PD-L1 gene expression had predictive value, as patients with high PD-L1 expression appear to be harmed by standard-of-care treatment (HR = 4.95; CI, 1.10–22.35). Building on the promising results from the metastatic colorectal carcinoma PD-1–targeting trial, we provide compelling evidence that patients with PD-L1high/MSI/immunehigh stage II/III colorectal carcinoma should not receive standard chemotherapy. This conclusion supports the rationale to clinically evaluate this patient subgroup for PD-1 blockade treatment. Cancer Immunol Res; 4(7); 582–91. ©2016 AACR.
Obstructive Sleep Apnea and Cardiovascular Events After Percutaneous Coronary Intervention
Authors: Lee Chi-Hang , Sethi Rishi , Li Ruogu , Ho Hee-Hwa , Hein Thet , Jim Man-Hong , Loo Germaine , Koo Chieh-Yang , Gao Xiao-Fei , Chandra Sharad , Yang Xiao-Xiao , Furlan Sofia F. , Ge Zhen , Mundhekar Ajeya , Zhang Wei-Wei , Uchôa Carlos Henrique G. , Kharwar Rajiv Bharat , Chan Po-Fun , Chen Shao-Liang , Chan Mark Y. , Richards Arthur Mark , Tan Huay-Cheem , Ong Thun-How , Roldan Glenn , Tai Bee-Choo , Drager Luciano F. , Zhang Jun-Jie
Published: May 2016

Background—

There is a paucity of data from large cohort studies examining the prognostic significance of obstructive sleep apnea (OSA) in patients with coronary artery disease. We hypothesized that OSA predicts subsequent major adverse cardiac and cerebrovascular events (MACCEs) in patients undergoing percutaneous coronary intervention.

Methods and Results—

The Sleep and Stent Study was a prospective, multicenter registry of patients successfully treated with percutaneous coronary intervention in 5 countries. Between December 2011 and April 2014, 1748 eligible patients were prospectively enrolled. The 1311 patients who completed a sleep study within 7 days of percutaneous coronary intervention formed the cohort for this analysis. Drug-eluting stents were used in 80.1% and bioresorbable vascular scaffolds in 6.3% of the patients, and OSA, defined as an apnea-hypopnea index of ≥15 events per hour, was found in 45.3%. MACCEs, a composite of cardiovascular mortality, nonfatal myocardial infarction, nonfatal stroke, and unplanned revascularization, occurred in 141 patients during the median follow-up of 1.9 years (interquartile range, 0.8 years). The crude incidence of an MACCEs was higher in the OSA than the non-OSA group (3-year estimate, 18.9% versus 14.0%;
p
=0.001). Multivariate Cox regression analysis indicated that OSA was a predictor of MACCEs, with an adjusted hazard ratio of 1.57 (95% confidence interval, 1.10–2.24;
P
=0.013), independently of age, sex, ethnicity, body mass index, diabetes mellitus, and hypertension.

Conclusions—

OSA is independently associated with subsequent MACCEs in patients undergoing percutaneous coronary intervention. Evaluation of therapeutic approaches to mitigate OSA-associated risk is warranted.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01306526.
Galectin‐3 and Risk of Heart Failure and Death in Blacks and Whites
Authors: McEvoy John W. , Chen Yuan , Halushka Marc K. , Christenson Eric , Ballantyne Christie M. , Blumenthal Roger S. , Christenson Robert H. , Selvin Elizabeth
Published: May 2016

Background

The association between galectin‐3 and heart failure (
HF
) or death is well established for white, but not for black, adults.

Methods and Results

Galectin‐3 was measured in 1809 participants (1375 white, 434 black), enrolled in a substudy of the Atherosclerosis Risk in Communities (
ARIC
) observational cohort during 2004–2005. We used Cox proportional hazard models to estimate the adjusted association between galectin‐3 and outcomes. Analyses were conducted overall and by race category. Median (interquartile range) galectin‐3 levels were 13.4 (11.2–16.4) and 14.8 (12–17.6) ng/mL, in white and black participants, respectively. In the sample overall, galectin‐3 was not independently associated with
HF
or death over a maximum of 7.9 years. However, in race‐stratified analyses, galectin‐3 was independently associated with a composite of
HF
or death among whites (eg, hazard ratio 2.2, 95%
CI
1.2–3.9, comparing Q4 versus Q1); but not among blacks (hazard ratio of 0.8 [0.4–1.8] for Q4 versus Q1, race interaction
P
=0.03). Associations between galectin‐3 and both outcomes analyzed individually also demonstrated similar racial differences. Furthermore, results were qualitatively similar with galectin‐3 modeled as a continuous exposure. In addition, galectin‐3 improved discrimination for the composite of
HF
or death among whites (increase in Harrell's C statistic from 0.729 to 0.735 [difference of +0.006],
P
=0.049), but not among blacks (0.696 to 0.695 [difference of −0.001],
P
=0.814).

Conclusions

In contrast to whites, galectin‐3 may have limited prognostic utility for predicting
HF
and death in blacks. While our results require replication, they could reflect racial differences in the processes by which galectin‐3 mediates disease.
Science–Policy Interplay: Improvement of Air Quality from 2008 to 2014 in Beijing and the Scientific Approach to Achieve APEC Blue
Authors: Wang Zhanshan , Li Yunting , Chen Tian , Zhang Dawei , Li Lingjun , Liu Baoxian , Li Jinxiang , Sun Feng , Pan Libo
Published: May 2016

The Beijing government has made great effort to solve the air pollution problem in recent years. In this paper, the major air pollution control measures and the air quality improvement from 2008 to 2014 in Beijing were represented. With the implementation of a series of unconventional and high–air pollutant reduction measures in Beijing and the surrounding area, good air quality during both the 2008 Olympic Games and the 2014 Asia–Pacific Economic Cooperation (APEC) conference was guaranteed. Notably, a new scientific approach was applied to formulate air pollution control policy during the APEC conference. In addition to the established measures, two periods of enhanced and targeted reduction measures were implemented according to the forecast in advance. Finally, suggestions for improving air quality in Beijing were offered on the basis of the monitoring results and analyses during the APEC conference.
Single-Center Experience Following the Introduction of a Percutaneous Endovascular Aneurysm Repair First Approach
Authors: Ashrafi Mohammed , Al-Jarrah Qusai , Anandarajah Mayooreshan , Ashleigh Ray , Welch Mark , Baguneid Mohamed
Published: May 2016

We evaluated our experience following the introduction of a percutaneous endovascular aneurysm repair (pEVAR) first approach using Perclose Proglide assessing efficacy, complications, and identification of factors that could predict failure. A retrospective cohort study on patients over a 2-year period following the introduction of a pEVAR first approach was performed. The primary end point was defined as successful deployment and access site hemostasis. Percutaneous EVAR was technically successful in 41 (77.4%) of 53 patients and 83 (86.5%) of 96 access sites. Factors associated with failure were smaller common femoral artery (CFA) diameter ( P = .045) and CFA circumferential calcification of greater than 50% ( P = .0001). The incidence of access site infection was significantly higher in the failure group ( P = .008) as was procedure duration ( P = .026). Percutaneous EVAR first approach must be introduced with caution. Percutaneous EVAR failure occurs more often in patients with unfavorable access site anatomy. Success rate can be improved with careful patient selection.
Admission Endocan Level may be a Useful Predictor for In-Hospital Mortality and Coronary Severity Index in Patients With ST-Segment Elevation Myocardial Infarction
Authors: Kundi Harun , Balun Ahmet , Cicekcioglu Hulya , Karayigit Orhan , Topcuoglu Canan , Kilinckaya Muhammed Fevzi , Kiziltunc Emrullah , Cetin Mustafa , Ornek Ender
Published: May 2016

We assessed the prognostic role of serum endocan level in patients with ST-segment elevation myocardial infarction (STEMI) and compared the results with a normal coronary angiography group. A total of 133 patients were included in the study (88 patients with STEMI and 45 patients with normal coronary arteries). The SYNTAX score was determined based on the baseline coronary angiogram. Multivariate logistic regression analysis indicated that endocan independently correlated with the presence of STEMI. Moreover, high-sensitivity C-reactive protein (hsCRP), peak troponin I, and left ventricular ejection fraction (LVEF) were found to be independently associated with STEMI. Endocan level correlated significantly with hsCRP and SYNTAX score. We analyzed the discriminatory capability of endocan level for the presence of STEMI using a receiver–operating characteristics curve. A cutoff endocan level of 1.7 (ng/mL) predicted the presence of STEMI with a sensitivity of 76.1% and specificity of 73.6%. In conclusion, a high endocan level on hospital admission is an independent predictor of a worse cardiovascular outcome and a high SYNTAX score in patients with STEMI.
Color Doppler Ultrasound Imaging in the Assessment of Iliac Endofibrosis
Authors: D’Abate Fabrizio , Paraskevas Kosmas I. , Oates Crispian , Palfreeman Roger , Hinchliffe Robert J.
Published: May 2016

Endofibrosis (EF) of the iliac arteries is a flow-limiting condition typically seen in highly trained endurance athletes. Thirty-seven athletes (74 limbs) were referred to our department with suspected EF. All patients had a pre- and postexercise color Doppler ultrasound (CDU) of the iliac arteries. Doppler waveform and peak systolic velocity (PSV) and end-diastolic velocity (EDV) were assessed pre- and postexercise. Endofibrosis was diagnosed with CDU in 24 athletes (29 limbs). Arterial wall and course abnormalities were detected at rest in 20 (67%) symptomatic limbs of athletes with and 4 (22%) symptomatic limbs of athletes without EF. Postexercise abnormal waveforms of the stenotic/damped type were seen in the iliac arteries in all 29 limbs of athletes diagnosed with EF. These waveform changes were accompanied by high PSV (>350 cm/s) and EDV (>150 cm/s), with (n = 10; 34%) or without (n = 19; 66%) the evidence of reduced arterial lumen caliber. Color Doppler ultrasound can be used to detect EF.
The Relationship Between Resting Heart Rate and SYNTAX Score in Patients With Stable Coronary Artery Disease
Authors: Yilmaz Samet , Sen Fatih , Akboga Mehmet K. , Balci Kevser G. , Aras Dursun , Temizhan Ahmet , Aydogdu Sinan
Published: May 2016

We investigated the relationship between resting heart rate (HR) and The Synergy between percutaneous coronary intervention with Taxus and cardiac surgery (SYNTAX) score in patients with stable coronary artery disease (SCAD). A total of 420 patients who were admitted to our outpatient clinic for stable angina pectoris with sinus rhythm and had at least 50% narrowing in at least 1 coronary artery after coronary angiography were included in the study. Patients were divided into 3 tertiles based on the resting HR: HR of tertile 1 was ≤65 (n = 138), tertile 2 was between 66 and 76 (n = 139), and tertile 3 was ≥77 beats/min (n = 143). The SYNTAX score (7.6 ± 4.6, 12.4 ± 5.6, 20.3 ± 8.1; P < .001) was significantly higher for those in tertile 3 than for those in tertiles 1 and 2. Leukocyte count (7.8 ± 2.2, 7.9 ± 2.2, 8.4 ± 2.3 × 109/L; P = .035) and C-reactive protein (CRP) levels (2.4 ± 0.5, 3.2 ± 0.7, 4.5 ± 1.2 mg/L, P < .001) were increasing from the lowest to the highest tertile. Using multiple logistic regression analysis, CRP (odds ratio [OR] 1.54 [1.17-2.11], P = .001) and resting HR (OR 1.67 [1.25-2.19], P < .001) emerged as independent predictors of SYNTAX score. Resting HR is related to SYNTAX score in patients with SCAD.
Is Board Gender Diversity Linked to Financial Performance? The Mediating Mechanism of CSR
Authors: Galbreath Jeremy
Published: May 2016

The evidence for a positive, direct link between the representation of women on boards of directors and financial performance is tenuous. Given the importance of the gender diversity–financial performance debate, researchers are left to examine how, if at all, the two are linked. The present study takes the position that the link is indirect. Specifically, following stakeholder theory, an argument is made that women on boards’ attunement to stakeholder interests leads them to influence firms’ prosocial actions, which results in higher levels of corporate social responsibility (CSR). In turn, following the extant literature, CSR is expected to be positively linked to financial performance. Relying on a sample of Australia’s largest publicly traded firms, the results demonstrate that women on boards are linked to CSR and that CSR is linked to financial performance. However, in the mediation test, CSR appears to fully mediate the link between women on boards and financial performance. The results are discussed along with limitations and future research directions.
Managing Physical Impacts of Climate Change: An Attentional Perspective on Corporate Adaptation
Authors: Pinkse Jonatan , Gasbarro Federica
Published: May 2016

Based on a study of the oil and gas industry, this article examines how physical impacts of climate change become events that firms notice and interpret in a way that leads to an active response to adapt to these impacts. Theoretically, the study draws on the attention-based view to highlight the potential biases that might occur as a consequence of firms’ preconceptions as well as organizational structure and context. In the empirical analysis, the article derives a model that explains the influence of the attentional process on how awareness and perceived vulnerability lead firms to adopt either routine or non-routine measures to adapt to climate change. The article also explores the relevant underlying factors of awareness and perceived vulnerability. The findings suggest that how firms channel attention to climate events has a distinctive influence on the measures firms take to cope with physical impacts. The article concludes with implications for research, management practice, and policy makers.
Self-rated confidence and on-road driving performance among older adults
Authors: Riendeau Julie A. , Maxwell Hillary , Patterson Loretta , Weaver Bruce , Bédard Michel
Published: May 2016

Background.

Driver confidence can be measured through concepts such as driving frequency, situational avoidance, and self-perceptions. However, it is not clear how well confidence aligns with actual driving performance.

Purpose.

We examined the relationship between subjective measures of confidence in driving ability and on-road performance.

Method.

We report findings from two studies. The first compared scores from the Older and Wiser Driver Questionnaire to an on-road driving evaluation. The second looked at the Day and Night Driving Comfort Scales and Driving Habits and Intentions Questionnaire in relation to an on-road driving evaluation.

Findings.

No measures of confidence in driving ability were related to on-road driving performance.

Implications.

Confidence in driving ability bears little relationship to on-road performance. Future research should examine approaches to foster a better match between self-assessments and actual abilities among drivers.
Patient and Caregiver Perspectives on Transition and Transfer
Authors: Maddux Michele Herzer , Ricks Shawna , Bass Julie
Published: May 2016

Little is known about the needs of adolescents with inflammatory bowel disease (IBD) with regard to transition, and how well those needs align with guidelines put forth by the American Academy of Pediatrics (AAP). This study examines perspectives on transition among young IBD patients and their caregivers. Surveys were mailed to 370 adolescent IBD patients, aged 12 years and older, and their caregivers. Most respondents endorsed ages 16 to 17 years as the best age to initiate discussions about transition, and age 18 years or older as the best age to transfer care. Independent self-management by patients was selected as the primary marker of transition readiness, while worry of starting over with a new provider was a primary barrier to successful transfer. Overall, the needs of youth with IBD and their caregivers are largely aligned with AAP best practice recommendations for transition. Further examination into patient needs is essential to inform transition planning efforts and identify targets of intervention.