bluuebunny/crossref_metadata_2025 huggingface dataset:
Document-based and term-based linear methods for pseudo-relevance feedback
Authors: Valcarce Daniel , Parapar Javier , Barreiro Álvaro
Published: January 2019

Query expansion is a successful approach for improving Information Retrieval effectiveness. This work focuses on pseudo-relevance feedback (PRF) which provides an automatic method for expanding queries without explicit user feedback. These techniques perform an initial retrieval with the original query and select expansion terms from the top retrieved documents. We propose two linear methods for pseudo-relevance feedback, one document-based and another term-based, that models the PRF task as a matrix decomposition problem. These factorizations involve the computation of an inter-document or inter-term similarity matrix which is used for expanding the original query. These decompositions can be computed by solving a least squares regression problem with regularization and a non-negativity constraint. We evaluate our proposals on five collections against state-of-the-art baselines. We found that the term-based formulation provides high figures of MAP, nDCG and robustness index whereas the document-based formulation provides very cheap computation at the cost of a slight decrease in effectiveness.
Loss of Nmp4 optimizes osteogenic metabolism and secretion to enhance bone quality
Authors: Shao Yu , Wichern Emily , Childress Paul J. , Adaway Michele , Misra Jagannath , Klunk Angela , Burr David B. , Wek Ronald C. , Mosley Amber L. , Liu Yunlong , Robling Alexander G. , Brustovetsky Nickolay , Hamilton James , Jacobs Kylie , Vashishth Deepak , Stayrook Keith R. , Allen Matthew R. , Wallace Joseph M. , Bidwell Joseph P.
Published: January 2019

A goal of osteoporosis therapy is to restore lost bone with structurally sound tissue. Mice lacking the transcription factor nuclear matrix protein 4 ( Nmp4, Zfp384, Ciz, ZNF384) respond to several classes of osteoporosis drugs with enhanced bone formation compared with wild-type (WT) animals. Nmp4−/− mesenchymal stem/progenitor cells (MSPCs) exhibit an accelerated and enhanced mineralization during osteoblast differentiation. To address the mechanisms underlying this hyperanabolic phenotype, we carried out RNA-sequencing and molecular and cellular analyses of WT and Nmp4−/− MSPCs during osteogenesis to define pathways and mechanisms associated with elevated matrix production. We determined that Nmp4 has a broad impact on the transcriptome during osteogenic differentiation, contributing to the expression of over 5,000 genes. Phenotypic anchoring of transcriptional data was performed for the hypothesis-testing arm through analysis of cell metabolism, protein synthesis and secretion, and bone material properties. Mechanistic studies confirmed that Nmp4−/− MSPCs exhibited an enhanced capacity for glycolytic conversion: a key step in bone anabolism. Nmp4−/− cells showed elevated collagen translation and secretion. The expression of matrix genes that contribute to bone material-level mechanical properties was elevated in Nmp4−/− cells, an observation that was supported by biomechanical testing of bone samples from Nmp4−/− and WT mice. We conclude that loss of Nmp4 increases the magnitude of glycolysis upon the metabolic switch, which fuels the conversion of the osteoblast into a super-secretor of matrix resulting in more bone with improvements in intrinsic quality.
Dietary feeding pattern does not modulate the loss of muscle mass or the decline in metabolic health during short-term bed rest
Authors: Dirks Marlou L. , Smeets Joey S. J. , Holwerda Andrew M. , Kouw Imre W. K. , Marzuca-Nassr Gabriel N. , Gijsen Annemie P. , Holloway Graham P. , Verdijk Lex B. , van Loon Luc J. C.
Published: January 2019

Short periods of bed rest lead to the loss of muscle mass and quality. It has been speculated that dietary feeding pattern may have an impact upon muscle protein synthesis rates and, therefore, modulate the loss of muscle mass and quality. We subjected 20 healthy men (age: 25 ± 1 yr, body mass index: 23.8 ± 0.8 kg/m2) to 1 wk of strict bed rest with intermittent (4 meals/day) or continuous (24 h/day) enteral tube feeding. Participants consumed deuterium oxide for 7 days before bed rest and throughout the 7-day bed rest period. Prior to and immediately after bed rest, lean body mass (dual energy X-ray absorptiometry), quadriceps cross-sectional area (CSA; CT), maximal oxygen uptake capacity (V̇o2peak), and whole body insulin sensitivity (hyperinsulinemic-euglycemic clamp) were assessed. Muscle biopsies were collected 7 days before, 1 day before, and immediately after bed rest to assess muscle tracer incorporation. Bed rest resulted in 0.3 ± 0.3 vs. 0.7 ± 0.4 kg lean tissue loss and a 1.1 ± 0.6 vs. 0.8 ± 0.5% decline in quadriceps CSA in the intermittent vs. continuous feeding group, respectively (both P < 0.05), with no differences between groups (both P > 0.05). Moreover, feeding pattern did not modulate the bed rest-induced decline in insulin sensitivity (−46 ± 3% vs. 39 ± 3%; P < 0.001) or V̇o2peak(−2.5 ± 2.2 vs. −8.6 ± 2.2%; P < 0.010) (both P > 0.05). Myofibrillar protein synthesis rates during bed rest did not differ between the intermittent and continuous feeding group (1.33 ± 0.07 vs. 1.50 ± 0.13%/day, respectively; P > 0.05). In conclusion, dietary feeding pattern does not modulate the loss of muscle mass or the decline in metabolic health during 1 wk of bed rest in healthy men.
Impact of Hydrogen Peroxide on the UVC Photolysis of Diclofenac and Toxicity of the Phototransformation Products
Authors: Ledakowicz Stanisław , Drozdek Emilia , Boruta Tomasz , Foszpańczyk Magdalena , Olak-Kucharczyk Magdalena , Żyłła Renata , Gmurek Marta
Published: January 2019

The aim of this study was to investigate the effect of hydrogen peroxide on the UVC photolysis of diclofenac (DCF) in aqueous solution. The experimental results confirmed very high effectivity of UVC direct photolysis of diclofenac. Moreover, it was found that H2O2/UV only slightly improved photodegradation; however, the addition of hydrogen peroxide into the reaction system affected the mechanism of DCF decomposition. Kinetics of the DCF reaction with ⋅OH radicals in the UV/H2O2 process was determined. For both processes, namely, photolysis and UV/H2O2, an in-depth analysis focused on the formation of phototransformation products of DCF (TPs) was performed. To the best of our knowledge, such comprehensive comparison of diclofenac photodegradation via UVC photolysis and UV/H2O2 has not been presented so far. Although there were no significant differences with regard to the rate of diclofenac degradation by photolysis and UV/H2O2, different oxidation products were found to be associated with the two considered processes. Furthermore, the H2O2/UV treatment increased toxicity towards Vibrio fischeri, while direct UVC photolysis had no significant effect on toxicity. The increase in toxicity can be attributed to the breakdown of DCF and formation of much more toxic TPs in the course of the H2O2/UVC process.
Correlates of and Body Composition Measures Associated with Metabolically Healthy Obesity Phenotype in Hispanic/Latino Women and Men: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL)
Authors: Estrella Mayra L. , Pirzada Amber , Durazo-Arvizu Ramon A. , Cai Jianwen , Giachello Aida L. , Espinoza Gacinto Rebeca , Siega-Riz Anna Maria , Daviglus Martha L.
Published: January 2019

Background. Individuals with “metabolically healthy obesity” (MHO) phenotype (i.e., obesity and absence of cardiometabolic abnormalities: favorable levels of blood pressure, lipids, and glucose) experience lower risk of cardiovascular disease compared with those with “metabolically at-risk obesity” (MAO) phenotype (i.e., obesity with concurrent cardiometabolic abnormalities). Among Hispanic/Latino women and men with obesity, limited data exist on the correlates of and body composition measures associated with obesity phenotypes. Methods. Data from the Hispanic Community Health Study/Study of Latinos (2008–2011) were used to estimate the age-adjusted distribution of obesity phenotypes among 5,426 women and men (aged 20–74 years) with obesity (BMI ≥ 30 kg/m2) and to compare characteristics between individuals with MHO and MAO phenotypes. Weighted Poisson regression models were used to examine cross-sectional associations between 1-standard deviation (SD) increase in body composition measures (i.e., body fat percentage, waist circumference, and body lean mass) and MHO phenotype prevalence. Results. The age-adjusted proportion of the MHO phenotype was low (i.e., 12.5% in women and 6.5% in men). In bivariate analyses, women and men with the MHO phenotype were more likely to be younger, have higher education and acculturation levels, report lower lifetime cigarette use, and have fasting insulin and waist circumference levels than MAO. Adjusting for sociodemographic and lifestyle factors, among women, each 1-SD increase in body fat percentage, waist circumference, and lean body mass was, respectively, associated with a 21%, 33%, and 31% lower prevalence of the MHO phenotype. Among men, each 1-SD increase in waist circumference and lean body mass was, respectively, associated with a 20% and 15% lower prevalence of the MHO phenotype. Conclusions. We demonstrated that higher waist circumference and higher lean body mass were independently associated with a lower proportion of the MHO phenotype in Hispanic/Latino women and men. Findings support the need for weight reduction interventions to manage cardiometabolic health among Hispanics/Latinos.
How Early Experience Shapes Human Development: The Case of Psychosocial Deprivation
Authors: Nelson Charles A. , Zeanah Charles H. , Fox Nathan A.
Published: January 2019

Experience plays an essential role in building brain architecture after birth. The question we address in this paper is what happens to brain and behavior when a young child is deprived of key experiences during critical periods of brain development. We focus in particular on the consequences of institutional rearing, with implication for the tens of millions of children around the world who from an early age experience profound psychosocial deprivation. Evidence is clear that deprivation can lead to a host of both short- and long-term consequences, including perturbations in brain structure and function, changes at cellular and molecular levels, and a plethora of psychological and behavioral impairments.
Prevalence of Depression and Associated Factors among Diabetic Patients in an Outpatient Diabetes Clinic
Authors: Khan Zahra D. , Lutale Janet , Moledina Sibtain M.
Published: January 2019

Despite adequate treatment for diabetes, it is estimated that 15%- 20% of people with diabetes are struggling with a moderate to severe form of depression daily. Little is known about depression in diabetes in East Africa, particularly in Tanzania. The study is aimed at determining the prevalence of depression and associated factors among patients with diabetes. A descriptive cross-sectional study was carried out at the diabetes clinic of Muhimbili National Hospital. The 9-item Patient Health Questionnaire (PHQ 9) scale was used to assess presence of depressive symptoms among diabetes patients at the clinic. In addition, patient’s sociodemographic and clinical characteristics were obtained and analysed for their association with depression. A total of 353 participants were recruited, of whom 229 (64.9%) patients were female and 156 (44.2%) were aged between 41 and 60 years. The overall prevalence of depression among diabetes patients at the diabetes clinic was 87%. Most (56.7%) had minimal depression, 22.1% had mild depression, and 8.2% had moderate depression. None had severe depression. Factors independently associated with a diagnosis of mild to moderate depression were being on insulin therapy and being a current smoker. There was a high prevalence of depression in this diabetic population. Majority of patients had minimal depression but about 30% had either mild or moderate depression. A holistic approach that focuses on the identification and management of depression among patients with diabetes is recommended.
ENA-78 Is a Novel Predictor of Wound Healing in Patients with Diabetic Foot Ulcers
Authors: Li Ju-yi , Wang Zhong-jing , Deng Ai-ping , Li Yu-ming
Published: January 2019

Objectives. Chronic foot ulceration is a severe complication of diabetes, driving morbidity and mortality. The aim of our study was to identify novel biomarkers of impaired wound healing in diabetic foot ulcers. Methods. 109 patients with neuropathic diabetic foot ulcers and 30 burn victims otherwise healthy participated. Antibody-coated glass slide arrays were used to determine the levels of 80 human cytokines in pooled plasma or pooled wound exudate of diabetic foot ulcers with rapidly healing (RH, n=12) and matched nonhealing (NH, n=12) patients. Potential biomarkers were confirmed in an independent cohort by enzyme-linked immunosorbent assay (ELISA). Results. Protein array profiling identified 27 proteins or 15 proteins significantly altered in protein profiling of pooled plasma or pooled wound exudate of 12 RH patients compared with 12 matched NH patients, respectively. In an independent cohort, quantitative ELISA validation confirmed a decrease in MCP-2 and ENA-78 levels in NH patients versus RH patients or burn victims. After adjusting for the traditional risk factors (sex, age, body mass index, fasting plasma glucose, ulcer area, HbA1C, diabetes duration, hyperlipidemia, and antibiotic therapy), only wound exudate level of ENA-78 remained having a significant association with an increased odds ratio (OR) for wound healing by binary logistic regression analysis (P<0.05). Conclusion. Decreased wound exudate ENA-78 was independently associated with wound healing of patients with diabetic foot. Exudate ENA-78 level is implicated as a novel predictor of wound healing in patients with diabetic foot ulcers.
Acute Interstitial Nephritis in a Patient with Non-Small Cell Lung Cancer under Immunotherapy with Nivolumab
Authors: Georgianos Panagiotis I. , Vaios Vasilios , Leontaridou Eleni , Karayannopoulou Georgia , Koletsa Triantafyllia , Sioulis Athanasios , Balaskas Elias V. , Zebekakis Pantelis E.
Published: January 2019

Immune-checkpoint-inhibitors (ICPIs) represent a novel class of immunotherapy against several malignancies. These agents are associated with several “immune-mediated” adverse effects, but the reported renal toxicity of ICPIs is less well defined. We present the case of a 60-year-old man with a history of non-small cell lung cancer, who developed acute kidney injury (AKI) approximately 3.5 months after initiation of immunotherapy with nivolumab. Urinalysis revealed sterile pyuria, without microscopic hematuria or proteinuria. Immunological examination was negative. A renal biopsy showed severe interstitial inflammatory infiltration of T-cells, monocytes, and eosinophils without interstitial granulomas and normal appearance of glomeruli, indicating acute interstitial nephritis (AIN) as the cause of AKI. After a short-term course of corticosteroids and permanent nivolumab discontinuation, partial recovery of renal function was noted. AIN is a rare adverse effect of ICPIs that mandates the close monitoring of renal function in patients under immunotherapy with these agents.
Effect of Propolis Preparations on Transepithelial Electrical Potential, Resistance, and Ion Transport in In Vitro Study
Authors: Smyk Paulina , Hołyńska-Iwan Iga , Olszewska-Słonina Dorota
Published: January 2019

Background. Propolis and its ethanol extract show positive germicidal, bacteriostatic, and anti-inflammatory antioxidants and regenerative properties after use on the surface of the skin. Propolis is in common use in production of cosmetics and in folk medicine. The influence of this resinous mixture on ion channels, channels located in skin cells membranes and skin electrical resistance, was not explained. Objective. The main aim of the study was the evaluation of electrophysiological skin parameters during mechanical and chemical-mechanical stimulation after use of ethanol extract of propolis and propolis ointment in comparison with iso-osmotic Ringer solution. Methods. Skin fragments were taken from white New Zealand rabbits and distributed into three experimental groups which were incubated in ethanol extract of propolis (EEP), propolis ointment, and Ringer solution. Then they were placed in a Ussing chamber to measure electrophysiological parameters values. Results. In this study the influence of EEP on changes in value of electrical potential during block of chloride ions transport at the same time was observed. Ethanol propolis extract dissolved in water increases the transepidermal sodium ions transport in contrast to propolis ointment. Conclusion. The way of preparation cosmetics, which contain propolis, has effects on transepidermal ions transport in the rabbit’s skin. The value of skin electrical resistance is changing with penetration depth of active propolis substances contained in cosmetics.
Modeling and Speed Control of the Underwater Wheeled Vehicle Flexible Towing System
Authors: Liu Gang , Xu Guohua , Wang Guanxue , Yuan Guoqiang , Liu Jiajia
Published: January 2019

In this paper, the research contents are mainly focused on the technology of the underwater wheeled vehicle speed control. For providing a passive towed underwater wheeled vehicle with accelerating, uniform motion and decelerating capability which can simulate an underwater navigation environment for the carried unit, we devised a novel open‐type hydraulic flexible towing system. Combining the hydrodynamic model of the vehicle and the hydraulic mechanism model, the dynamic characteristics of the novel towing system are studied by computing simulation. Aiming at the force coupling character of double driving hydraulic winches, a master‐slave synchronization control strategy is proposed. Then, in view of the flexible towing system features, i.e., strong coupling, nonlinear, time‐varying load, and environmental constraints, a real speed controller based on fast terminal sliding mode control theory is designed and manufactured. To verify the effectiveness of the controller, a hardware‐in‐the‐loop simulation test is carried out on the strength of a semiphysical simulation platform based on Matlab/Simulink and VxWorks real‐time system. The experiment results show that the speed controller based on fast terminal sliding mode control has excellent effect on rapidity, stability, and anti‐interference characteristics.
Measuring Surface Area of Skin Lesions with 2D and 3D Algorithms
Authors: Mirzaalian Dastjerdi Houman , Töpfer Dominique , Rupitsch Stefan J. , Maier Andreas
Published: January 2019

Purpose. The treatment of skin lesions of various kinds is a common task in clinical routine. Apart from wound care, the assessment of treatment efficacy plays an important role. In this paper, we present a new approach to measure the skin lesion surface in two and three dimensions. Methods. For the 2D approach, a single photo containing a flexible paper ruler is taken. After semi-automatic segmentation of the lesion, evaluation is based on local scale estimation using the ruler. For the 3D approach, reconstruction is based on Structure from Motion. Roughly outlining the region of interest around the lesion is required for both methods. Results. The measurement evaluation was performed on 117 phantom images and five phantom videos for 2D and 3D approach, respectively. We found an absolute error of 0.99±1.18  cm2 and a relative error 9.89± 9.31% for 2D. These errors are <1  cm2 and <5% for five test phantoms in our 3D case. As expected, the error of 2D surface area measurement increased by approximately 10% for wounds on the bent surface compared to wounds on the flat surface. Using our method, the only user interaction is to roughly outline the region of interest around the lesion. Conclusions. We developed a new wound segmentation and surface area measurement technique for skin lesions even on a bent surface. The 2D technique provides the user with a fast, user-friendly segmentation and measurement tool with reasonable accuracy for home care assessment of treatment. For 3D only preliminary results could be provided. Measurements were only based on phantoms and have to be repeated with real clinical data.
Effective Hybrid Algorithm of Taguchi Method, FEM, RSM, and Teaching Learning‐Based Optimization for Multiobjective Optimization Design of a Compliant Rotary Positioning Stage for Nanoindentation Tester
Authors: Dang Minh Phung , Dao Thanh-Phong , Chau Ngoc Le , Le Hieu Giang
Published: January 2019

This paper proposes an effective hybrid optimization algorithm for multiobjective optimization design of a compliant rotary positioning stage for indentation tester. The stage is created with respect to the Beetle’s profile. To meet practical demands of the stage, the geometric parameters are optimized so as to find the best performances. In the present work, the Taguchi method is employed to lay out the number of numerical experiments. Subsequently, the finite element method is built to retrieve the numerical data. The mathematical models are then established based on the response surface method. Before conducting the optimization implementation, the weight factor of each response is calculated exactly. Based on the well‐established models, the multiple performances are simultaneously optimized utilizing the teaching learning‐based optimization. The results found that the weight factors of safety factor and displacement are 0.5995 (59.95%) and 0.4005 (40.05%), respectively. The results revealed that the optimal safety factor is about 1.558 and the optimal displacement is 2.096 mm. The validations are in good agreement with the predicted results. Sensitivity analysis is carried out to identify the effects of variables on the responses. Using the Wilcoxon’s rank signed test and Friedman test, the effectiveness of the proposed hybrid approach is better than that of other evolutionary algorithms. It ensures a good effectiveness to solve a complex multiobjective optimization problem.
Untreated Giant Macroprolactinoma with Chronic Cerebrospinal Fluid Leakage: An Unusual Complication
Authors: Mad Naser Mohamad Nazrulhisham , Aziz Nor Azizah , Karim Noor Khairiah A.
Published: January 2019

Macroprolactinoma has the potential to cause base of skull erosion and often extends into the sphenoid sinus. Rapid shrinkage of this invasive tumor following dopamine agonist therapy has been postulated to cause unplugging of the eroded area, leading to cerebrospinal fluid leakage. To the best of our knowledge, the occurrence of spontaneous cerebrospinal fluid leak in treatment-naive prolactinomas is very rare, the majority of which involve undiagnosed macroprolactinomas. We describe here a lady presented late with giant macroprolactinoma, complicated by cerebrospinal fluid leakage. This case raised the dilemma in the management pertaining to the role of either pharmacotherapy or surgical intervention, or combination of both. As she strictly refused surgery, she was treated with bromocriptine which was later changed to cabergoline. On follow-up, there was cessation of cerebrospinal fluid leak, marked reduction of serum prolactin level, and imaging evidence of tumor shrinkage. The majority of patients with medically induced cerebrospinal fluid leakage will require surgical procedures to overcome this complication; however, there are isolated cases of leakage resolution on continuing dopamine agonist therapy while awaiting surgery. The use of dopamine agonist does not necessarily cause worsening of cerebrospinal fluid leakage and instead may produce spontaneous resolution as in this case.
Serum-Free Manufacturing of Mesenchymal Stem Cell Tissue Rings Using Human-Induced Pluripotent Stem Cells
Authors: Winston Tackla S. , Suddhapas Kantaphon , Wang Chenyan , Ramos Rafael , Soman Pranav , Ma Zhen
Published: January 2019

Combination of stem cell technology and 3D biofabrication approaches provides physiological similarity to in vivo tissues and the capability of repairing and regenerating damaged human tissues. Mesenchymal stem cells (MSCs) have been widely used for regenerative medicine applications because of their immunosuppressive properties and multipotent potentials. To obtain large amount of high-quality MSCs without patient donation and invasive procedures, we differentiated MSCs from human-induced pluripotent stem cells (hiPSC-MSCs) using serum-free E6 media supplemented with only one growth factor (bFGF) and two small molecules (SB431542 and CHIR99021). The differentiated cells showed a high expression of common MSC-specific surface markers (CD90, CD73, CD105, CD106, CD146, and CD166) and a high potency for osteogenic and chondrogenic differentiation. With these cells, we have been able to manufacture MSC tissue rings with high consistency and robustness in pluronic-coated reusable PDMS devices. The MSC tissue rings were characterized based on inner diameter and outer ring diameter and observed cell-type-dependent tissue contraction induced by cell-matrix interaction. Our approach of simplified hiPSC-MSC differentiation, modular fabrication procedure, and serum-free culture conditions has a great potential for scalable manufacturing of MSC tissue rings for different regenerative medicine applications.
Cold at the Core: Osborn Waves in Neurosarcoidosis-Induced Central Hypothermia
Authors: Troutman Gregory Scott , Salamon Jason , Scharf Matthew , Mazurek Jeremy A.
Published: January 2019

Osborn waves, or J waves, initially described by John Osborn in 1953 in hypothermic dog experiments, are highly sensitive and specific for hypothermia. Initially thought to be secondary to a hypothermia-induced “injury current,” they have more recently been attributed to a voltage differential between epicardial and endocardial potassium (Ito) currents. While the exact conditions required to induce such waves have been debated, numerous clinical scenarios of environmental and iatrogenic hypothermia have been described. Below, we report a novel case of hypothermia—that of neurosarcoidosis-induced central hypothermia with resultant Osborn waves and other associated findings found on electrocardiogram (ECG).
Thyroid Diagnosis from SPECT Images Using Convolutional Neural Network with Optimization
Authors: Ma Liyong , Ma Chengkuan , Liu Yuejun , Wang Xuguang
Published: January 2019

Thyroid disease has now become the second largest disease in the endocrine field; SPECT imaging is particularly important for the clinical diagnosis of thyroid diseases. However, there is little research on the application of SPECT images in the computer-aided diagnosis of thyroid diseases based on machine learning methods. A convolutional neural network with optimization-based computer-aided diagnosis of thyroid diseases using SPECT images is developed. Three categories of diseases are considered, and they are Graves’ disease, Hashimoto disease, and subacute thyroiditis. A modified DenseNet architecture of convolutional neural network is employed, and the training method is improved. The architecture is modified by adding the trainable weight parameters to each skip connection in DenseNet. And the training method is improved by optimizing the learning rate with flower pollination algorithm for network training. Experimental results demonstrate that the proposed method of convolutional neural network is efficient for the diagnosis of thyroid diseases with SPECT images, and it has superior performance than other CNN methods.
Growth Kinetics and Sensing Features of Colloidal Silver Nanoplates
Authors: Compagnini Giuseppe , Condorelli Marcello , Fragalà Maria E. , Scardaci Vittorio , Tinnirello Ilaria , Puglisi Orazio , Neri Fortunato , Fazio Enza
Published: January 2019

This paper presents the growth mechanisms and the plasmon sensing features for a large class of silver nanoplates obtained in the colloidal form. The synthesis is conducted by seed-mediated growth and leads to plates with aspect ratios as large as 20, having localized surface plasmon resonances extending deeply into the infrared spectral region (1000 nm and above). We measure plasmon sensitivity by varying the colloidal local refractive index, and Δλ/Δn sensitivity values up to 500 nm/RIU are obtained. Theoretical considerations regarding the correlation between the refractive index sensitivity and the position of the main localized plasmon resonance band demonstrate that plasmon sensitivity does not depend directly on the nanoparticle shape and aspect ratio.
Auricular Plaster Therapy for Comorbid Insomnia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Zhao Huimin , Li Dan , Yang Ying , Liu Yueting , Li Jie , Mao Jing
Published: January 2019

Background. Although the effectiveness of auricular plaster therapy (APT) on primary insomnia has been systematically reviewed, no systematic review of studies has focused on the effect on comorbid insomnia. Objective. To evaluate the efficacy and safety of APT for comorbid insomnia. Methods. Fifteen databases were searched from inception to July 2018. Randomized controlled trials (RCTs) of APT as an exclusive intervention for comorbid insomnia against Western medications, sham APT or no treatment were identified. Results. Fourteen studies involving 928 participants were identified. The pooled outcomes revealed that APT was superior to control conditions for the global score on PSQI (SMD = -1.13, and 95% CI = -1.48—-0.78) and the effective rate (RR = 1.24, 95% CI = 1.13—1.36, NNT = 5, and 95% CI =4—7). Furthermore, the results of subgroup analyses were similar to the pooled results. Additionally, the pooled results were verified to be stable by sensitivity analyses. Regarding safety, no significant difference was identified between APT and Western medications. Conclusions. APT appears to be an effective and safe treatment for comorbid insomnia. However, the benefits of APT for comorbid insomnia could not be ascertained due to the paucity of the quantity and quality of the included studies. Large-scale studies using proper methodology are needed to yield a firm conclusion.
Adaptive Asymmetric Real Laplace Wavelet Filtering and Its Application on Rolling Bearing Early Fault Diagnosis
Authors: Wan Shuting , Peng Bo
Published: January 2019

The early fault of rolling bearing is weak and may not be readily detected. To overcome this issue, the present paper comes up with a rolling bearing fault‐diagnosing approach based on adaptive asymmetric real Laplace wavelet (ARLW) filtering, which is on the strength of water cycle optimization algorithm (WCA). Firstly, ARLW is introduced to filter the initial vibration signal since its waveform has the same asymmetric structure as the fault impact. Secondly, the optimum center frequency and bandwidth of ARLW is found out adaptively by applying the WCA through the proposed square envelope fault energy ratio (SEFER). Finally, envelope analysis is conducted to the narrowband signal obtained by the optimum ARLW filtering, and its envelope spectrum presents the rolling bearing fault characteristic frequency apparently. The proposed approach and two existing approaches are all tested in four signal analysis cases. The results are analyzed, and the conclusion is that the approach proposed by the present paper can detect the early fault of rolling bearing more accurately. The present research is valuable for diagnosing the early fault of rolling bearing.
The Impact of EGDT on Sepsis Mortality in a Single Tertiary Care Center in Lebanon
Authors: El Khuri Christopher , Abou Dagher Gilbert , Chami Ali , Bou Chebl Ralph , Amoun Tarek , Bachir Rana , Jaafar Batoul , Rizk Nesrine
Published: January 2019

Background. EGDT (Early Goal Directed Therapy) or some portion of EGDT has been shown to decrease mortality secondary to sepsis and septic shock.Objective. Our study aims to assess the effect of adopting this approach in the emergency department on in-hospital mortality secondary to sepsis/septic shock in Lebanon.Hypothesis. Implementation of the EGDT protocol of sepsis in ED will decrease in-hospital mortality.Methods. Our retrospective study included 290 adult patients presenting to the ED of a tertiary center in Lebanon with severe sepsis and/or septic shock. 145 patients between years 2013 and 2014 who received protocol care were compared to 145 patients treated by standard care between 2010 and 2012. Data from the EHR were retrieved about patients’ demographics, medical comorbidities, and periresuscitation parameters. A multivariate analysis using logistic regression for the outcome in-hospital mortality after adjusting for protocol use and other confounders was done and AOR was obtained for the protocol use. 28-day mortality, ED, and hospital length of stay were compared between the two groups.Results. The most common infection site in the protocol arm was the lower respiratory tract (42.1%), and controls suffered more from UTIs (33.8%). Patients on protocol care had lower in-hospital mortality than that receiving usual care, 31.7% versus 47.6% (p=0.006) with an AOR of 0.429 (p =0.018). Protocol patients received more fluids at 6 and 24 hours (3.8 ± 1.7 L and 6.1 ± 2.1 L) compared to the control group (2.7 ± 2.0 L and 4.9 ± 2.8 L p=<0.001). Time to and duration of vasopressor use, choice of appropriate antibiotics, and length of ED stay were not significantly different between the two groups.Conclusion. EGDT- (Early Goal Directed Therapy-) based sepsis protocol implementation in EDs decreases in-hospital mortality in developing countries. Adopting this approach in facilities with limited resources, ICU capabilities, and prehospital systems may have a pronounced benefit.
HPVE6/E7,hTERT, andKi67mRNA RT-qPCR Assay for Detecting High-Grade Cervical Lesion with Microscope Slides
Authors: Kim Geehyuk , Taye Jemberu , Yu Kwangmin , Park Sunyoung , Kim Jungho , Kim Sunghyun , Lee Dongsup , Wang Hye-young , Park Kwang Hwa , Lee Hyeyoung
Published: January 2019

After breast and colon cancer, cervical cancer is the third most common cancer of women worldwide. Since human papillomavirus (HPV) infection is known to be the predominant cause of cervical cancer, molecular HPV screening is currently used along with cytological and histological examination methods for precancer diagnosis. Nevertheless, the sensitivity of the current HPV test is less than 80%; thus, many cervical cancer cases are not able to be diagnosed by HPV screening alone, and likewise, patients with cervical cancer are often determined to be HPV-negative by the current screening methods. Therefore, human telomerase reverse transcriptase (hTERT) andKi67previously identified as cancer markers were attempted. And cervical exfoliated cells of high-grade squamous intraepithelial lesion (HSIL), the most severe precancerous lesion of cancer, were used in the study. However, it takes a long time to collect enough specimens to conduct statistical analysis. Therefore, in the present study, microscope slides, cervical exfoliated cells on glass slides, were attempted. The results of the analysis demonstrated thathTERTandKi67expression levels were useful in distinguishing between cancerous and normal specimens, exhibiting a higher sensitivity and specificity than conventional HPVE6/E7testing. And the study suggests clinical slide cell samples could be effectively used in the context of retrospective studies to identify novel biomarkers.
Endoscopic Sphincterotomy before Fully Covered Metal Stent Placement Is Not Required for Distal Malignant Biliary Stricture due to a Pancreatic Head Tumor
Authors: Nakahara Kazunari , Michikawa Yosuke , Morita Ryo , Suetani Keigo , Morita Nozomi , Sato Junya , Tsuji Kensuke , Ikeda Hiroki , Matsunaga Kotaro , Watanabe Tsunamasa , Matsumoto Nobuyuki , Kobayashi Shinjiro , Otsubo Takehito , Itoh Fumio
Published: January 2019

Background/Aims. Endoscopic sphincterotomy (EST) is often performed before fully covered self-expandable metal stent (FCSEMS) placement in order to prevent pancreatitis. However, it is not clear whether EST prevents pancreatitis or affects other adverse events (AEs). This study is conducted to evaluate the necessity of EST before FCSEMS placement for distal malignant biliary strictures due to a pancreatic head tumor. Methods. This study included 68 patients who underwent FCSEMS placement for distal malignant biliary stricture due to a pancreatic head tumor. Treatment outcomes and AEs were retrospectively compared between 32 patients with EST before FCSEMS placement (EST group) and 36 patients without EST (non-EST group). Results. The success rates of drainage for the EST and non-EST groups were 100% and 97.2%, respectively (P=0.95). The incidence of pancreatitis in the EST and non-EST groups was 3.1% and 0%, respectively (P=0.95). The incidence of hyperamylasemia in the EST and non-EST groups was 12.5% and 13.9%, respectively (P=0.85). The incidence of all AEs in the EST and non-EST groups was 15.6% (pancreatitis: 1, cholecystitis: 2, and stent migration: 2) and 13.9% (cholecystitis: 3, stent migration: 2), respectively (P=0.89). Conclusions. EST before FCSEMS placement for distal malignant biliary stricture due to a pancreatic head tumor does not affect the successful drainage and incidence of adverse events. The necessity of EST to prevent pancreatitis before FCSEMS placement was deemed low.
Acetylation of CCAR2 Establishes a BET/BRD9 Acetyl Switch in Response to Combined Deacetylase and Bromodomain Inhibition
Authors: Rajendran Praveen , Johnson Gavin , Li Li , Chen Ying-Shiuan , Dashwood Mohaiza , Nguyen Nhung , Ulusan Ahmet , Ertem Furkan , Zhang Mutian , Li Jia , Sun Deqiang , Huang Yun , Wang Shan , Leung Hon-Chiu , Lieberman David , Beaver Laura , Ho Emily , Bedford Mark , Chang Kyle , Vilar Eduardo , Dashwood Roderick
Published: January 2019

There continues to be interest in targeting epigenetic “readers, writers, and erasers” for the treatment of cancer and other pathologies. However, a mechanistic understanding is frequently lacking for the synergy observed when combining deacetylase and bromodomain inhibitors. Here we identify cell cycle and apoptosis regulator 2 (CCAR2) as an early target for acetylation in colon cancer cells treated with sulforaphane. N-terminal acetylation of CCAR2 diminished its interactions with histone deacetylase 3 and β-catenin, interfering with Wnt coactivator functions of CCAR2, including in cells harboring genetically encoded CCAR2 acetylation. Protein domain arrays and pull-down assays identified acetyl “reader” proteins that recognized CCAR2 acetylation sites, including BRD9 and members of the bromodomain and extraterminal domain (BET) family. Treatment with the BET inhibitor JQ1 synergized with sulforaphane in colon cancer cells and suppressed tumor development effectively in a preclinical model of colorectal cancer. Studies with sulforaphane+JQ1 in combination implicated a BET/BRD9 acetyl switch and a shift in the pool of acetyl “reader” proteins in favor of BRD9-regulated target genes.

Significance:

These results highlight the competition that exists among the “readers” of acetylated histone and nonhistone proteins and provide a mechanistic basis for potential new therapeutic avenues involving epigenetic combination treatments.
Colorectal Carcinomas Containing Hypermethylated MLH1 Promoter and Wild-Type BRAF/KRAS Are Enriched for Targetable Kinase Fusions
Authors: Cocco Emiliano , Benhamida Jamal , Middha Sumit , Zehir Ahmet , Mullaney Kerry , Shia Jinru , Yaeger Rona , Zhang Liying , Wong Donna , Villafania Liliana , Nafa Khedoudja , Scaltriti Maurizio , Drilon Alexander , Saltz Leonard , Schram Alison M. , Stadler Zsofia K. , Hyman David M. , Benayed Ryma , Ladanyi Marc , Hechtman Jaclyn F.
Published: January 2019

Kinase fusions are rare and poorly characterized in colorectal carcinoma, yet they present unique opportunities for targeted therapy. In this study, we characterized kinase fusions from patients with advanced colorectal carcinoma who had MSK-IMPACT testing of their tumors between January 2014 and June 2018. Patients were analyzed for the presence of fusions, microsatellite instability (MSI), and RAS/BRAF mutations. Mismatch repair (MMR), IHC, and promoter hypermethylation status of MLH1 (MLH1ph) in microsatellite instability-high (MSI-H) colorectal carcinoma with fusions were investigated. Fusion transcripts were confirmed using a targeted RNA-seq panel assay. Of 2,314 colorectal carcinomas with MSK-IMPACT testing, 21 harbored kinase fusions. Overall 57% (12/21) of colorectal carcinoma fusions were MSI-H/MMR-D. Loss of MLH1 and MLH1ph was confirmed in all 12 and all 10 cases with available material, respectively. Fusions were present in 5% of MSI-H/MMR-D colorectal carcinoma compared with 0.4% of MSS/MMR-P colorectal carcinoma (P < 0.001) and 15% of MSI-H/MMR-D colorectal carcinoma with wild-type RAS/BRAF. Of 24 total MLH1-deficient colorectal carcinomas with MLH1ph and wild-type RAS/BRAF, 10 (42%) harbored kinase fusions. Kinase fusions in MSI-H colorectal carcinoma were associated with sporadic MLH1ph rather than with Lynch syndrome, and these patients may be eligible for kinase inhibitors, particularly following resistance or toxicity in response to immunotherapy. These findings identify a molecular subset of colorectal carcinoma with kinase fusions that may be responsive to kinase inhibitors.

Significance: A high frequency of targetable kinase fusions in BRAF/RAS wild-type, MSI-H colorectal carcinoma offers a rationale for routine screening to identify patients with colorectal carcinoma with kinase fusions that may be responsive to kinase inhibitors.

See related commentary by Valeri, p. 1041
Particulate Matter and Traffic-Related Exposures in Relation to Breast Cancer Survival
Authors: DuPré Natalie C. , Hart Jaime E. , Holmes Michelle D. , Poole Elizabeth M. , James Peter , Kraft Peter , Laden Francine , Tamimi Rulla M.
Published: January 2019

Background:

Although particulate matter (PM) has not been consistently associated with breast cancer risk, two studies have reported harmful associations for breast cancer survival. We examined PM exposures and breast cancer survival in two U.S.-based prospective cohort studies.

Methods:

The Nurses' Health Study (NHS) and NHSII are cohorts with detailed data on medical history, lifestyle factors, and causes of death. Women with Stage I–III breast cancer (n = 8,936) were followed through June 2014. Residential PM was estimated using spatio-temporal models. We performed Cox regression to estimate hazard ratios (HR) of breast cancer–specific mortality and all-cause mortality for 10 μg/m3 increases in post-diagnosis PM.

Results:

There were 1,211 breast cancer–specific deaths. Overall, PM was not associated with breast cancer–specific mortality [PM2.5: HR, 1.09; 95% confidence interval (CI), 0.87–1.36; PM2.5-10: HR, 1.03; 95% CI, 0.85–1.24; PM10: HR, 1.05; 95% CI, 0.89–1.24], but was associated with modest increases in all-cause mortality (PM2.5: HR, 1.12; 95% CI, 0.96–1.30; PM2.5-10: HR, 1.12; 95% CI, 1.00–1.24; PM10: HR, 1.09; 95% CI, 1.01–1.18). However, among participants with Stage I disease, PM2.5 was associated with higher breast cancer–specific mortality (HR, 1.64; 95% CI, 1.11–2.43).

Conclusions:

PM was not associated with breast cancer–specific death overall; however, higher PM was associated with all-cause mortality. Higher PM2.5 was associated with higher breast cancer–specific mortality among patients with Stage I breast cancer even after adjustment.

Impact:

Studies on ambient PM and breast cancer survival demonstrate that PM2.5 may have broader health effects than previously recognized and warrants further research on breast tumor progression.
Induction of Peripheral Effector CD8 T-cell Proliferation by Combination of Paclitaxel, Carboplatin, and Bevacizumab in Non–small Cell Lung Cancer Patients
Authors: de Goeje Pauline L. , Poncin Myrthe , Bezemer Koen , Kaijen-Lambers Margaretha E.H. , Groen Harry J.M. , Smit Egbert F. , Dingemans Anne-Marie C. , Kunert André , Hendriks Rudi W. , Aerts Joachim G.J.V.
Published: January 2019

Purpose:

Chemotherapy has long been the standard treatment for advanced stage non–small cell lung cancer (NSCLC), but checkpoint inhibitors are now approved for use in several patient groups and combinations. To design optimal combination strategies, a better understanding of the immune-modulatory capacities of conventional treatments is needed. Therefore, we investigated the immune-modulatory effects of paclitaxel/carboplatin/bevacizumab (PCB), focusing on the immune populations associated with the response to checkpoint inhibitors in peripheral blood.

Experimental Design:

A total of 223 patients with stage IV NSCLC, enrolled in the NVALT12 study, received PCB, with or without nitroglycerin patch. Peripheral blood was collected at baseline and after the first and second treatment cycle, proportions of T cells, B cells, and monocytes were determined by flow cytometry. Furthermore, several subsets of T cells and the expression of Ki67 and coinhibitory receptors on these subsets were determined.

Results:

Although proliferation of CD4 T cells remained stable following treatment, proliferation of peripheral blood CD8 T cells was significantly increased, particularly in the effector memory and CD45RA+ effector subsets. The proliferating CD8 T cells more highly expressed programmed death receptor (PD)-1 and cytotoxic T-lymphocyte–associated antigen-4 (CTLA-4) compared with nonproliferating CD8 T cells. Immunologic responders (iR; >2 fold increased proliferation after treatment) did not show an improved progression-free (PFS) or overall survival (OS).

Conclusions:

Paclitaxel/carboplatin/bevacizumab induces proliferation of CD8 T cells, consisting of effector cells expressing coinhibitory checkpoint molecules. Induction of proliferation was not correlated to clinical outcome in the current clinical setting. Our findings provide a rationale for combining PCB with checkpoint inhibition in lung cancer.
The Rolipram–Perillyl Alcohol Conjugate (NEO214) Is A Mediator of Cell Death through the Death Receptor Pathway
Authors: Cho Hee-Yeon , Thein Thu Zan , Wang Weijun , Swenson Stephen D. , Fayngor Rochelle A. , Ou Mengting , Marín-Ramos Nagore I. , Schönthal Axel H. , Hofman Florence M. , Chen Thomas C.
Published: January 2019

Glioblastoma (GBM) is a highly aggressive primary brain tumor with a poor prognosis. Treatment with temozolomide, standard of care for gliomas, usually results in drug resistance and tumor recurrence. Therefore, there is a great need for drugs that target GBM. NEO214 was generated by covalently linking rolipram to perillyl alcohol (POH) via a carbamate bond to form the rolipram–perillyl alcohol conjugate. We show here that NEO214 is effective against both temozolomide-sensitive and temozolomide-resistant glioma cells. Furthermore, NEO214 is effective for different mechanisms of temozolomide resistance: overexpression of MGMT (O6-methylguanine methyl-transferase); deficiency in specific mismatch repair proteins; and overexpression of base excision repair (BER) proteins. NEO214-induced cytotoxicity involves apoptosis triggered by endoplasmic reticulum (ER) stress, as well as activating the Death Receptor 5 (DR5)/TNF-related apoptosis-inducing ligand (TRAIL/Apo2L) pathway. In vitro studies show that glioma cells treated with NEO214 express DR5 and exhibit cell death in the presence of recombinant TRAIL, a growth factor constitutively produced by astrocytes. Our in vitro 3D coculture data show that induction of DR5 in glioma cells with NEO214 and TRAIL cause tumor cell death very effectively and specifically for glioma cells. In vivo studies show that NEO214 has antitumor efficacy in orthotropic syngeneic rodent tumor models. Furthermore, NEO214 has therapeutic potential especially for brain tumors because this drug can cross the blood–brain barrier (BBB), and is effective in the TRAIL-rich astrocyte microenvironment. NEO214 is a strong candidate for use in the treatment of GBMs.