bluuebunny/crossref_metadata_2025 huggingface dataset:
Paillier Cryptosystem based Mean Value Computation for Encrypted Domain Image Processing Operations
Authors: Shah Mohsin , Zhang Weiming , Hu Honggang , Yu Nenghai
Published: September 2019

Due to its large storage facility and high-end computing capability, cloud computing has received great attention as a huge amount of personal multimedia data and computationally expensive tasks can be outsourced to the cloud. However, the cloud being third-party semi-trusted, is prone to information leakage, raising privacy risks. Signal processing in the encrypted domain has emerged as a new research paradigm on privacy-preserving processing over outsourced data by semi-trusted cloud. In this article, we propose a solution for non-integer mean value computation in the homomorphic encrypted domain without any interactive protocol between the client and the service provider. Using the proposed solution, various image processing operations, such as local smoothing filter, un-sharp masking, and histogram equalization, can be performed in the encrypted domain at the cloud server without any privacy concerns. Our experimental results from standard test images reveal that these image processing operations can be performed without pre-processing, without client-server interactive protocol, and without any error between the encrypted domain and the plain domain.
Designing a Controller with Image-based Pipelined Sensing and Additive Uncertainties
Authors: Medina Róbinson , Valencia Juan , Stuijk Sander , Goswami Dip , Basten Twan
Published: September 2019

Pipelined image-based control uses parallel instances of its image-processing algorithm in a pipelined fashion to improve the quality of control. A performance-oriented control design improves the controller settling time with each additional processing resource, which creates a resources-performance trade-off. In real-life applications, it is common to have a continuous-time model with additive uncertainties in one or more parameters that may affect the controller performance and the aforementioned trade-off. We present a robustness analysis framework for performance-oriented pipelined controllers with additive model uncertainties. We present a technique to obtain discrete-time uncertainties based on the continuous-time uncertainties for given uncertainty bounds. To benchmark such uncertainty bounds for a real system, we consider uncertainties in one element of the system, potentially caused by multiple uncertain parameters in the model. Robustness and its impact in the trade-off analysis are studied. We also provide a robustness-oriented pipelined controller design that takes into account the benchmarked uncertainties. Our results show that in performance-oriented designs, the tolerable uncertainties for a pipelined controller decrease when increasing the number of pipes. In robustness-oriented designs, the controller robustness is enhanced with each newly added pipe. We show the feasibility of our technique by implementing a realistic example in a Hardware-in-the-Loop simulation.
Typing Messages for Free in Security Protocols
Authors: Chrétien Rémy , Cortier Véronique , Dallon Antoine , Delaune Stéphanie
Published: September 2019

Security properties of cryptographic protocols are typically expressed as reachability or equivalence properties. Secrecy and authentication are examples of reachability properties, while privacy properties such as untraceability, vote secrecy, or anonymity are generally expressed as behavioral equivalence in a process algebra that models security protocols.

Our main contribution is to reduce the search space for attacks for reachability as well as equivalence properties. Specifically, we show that if there is an attack then there is one that is well-typed. Our result holds for a large class of typing systems, a family of equational theories that encompasses all standard primitives, and protocols without else branches. For many standard protocols, we deduce that it is sufficient to look for attacks that follow the format of the messages expected in an honest execution, therefore considerably reducing the search space.
Antiviral immunity is impaired in COPD patients with frequent exacerbations
Authors: Singanayagam Aran , Loo Su-Ling , Calderazzo Maria , Finney Lydia J. , Trujillo Torralbo Maria-Belen , Bakhsoliani Eteri , Girkin Jason , Veerati Punnam , Pathinayake Prabuddha S. , Nichol Kristy S. , Reid Andrew , Footitt Joseph , Wark Peter A. B. , Grainge Christopher L. , Johnston Sebastian L. , Bartlett Nathan W. , Mallia Patrick
Published: September 2019

Patients with frequent exacerbations represent a chronic obstructive pulmonary disease (COPD) subgroup requiring better treatment options. The aim of this study was to determine the innate immune mechanisms that underlie susceptibility to frequent exacerbations in COPD. We measured sputum expression of immune mediators and bacterial loads in samples from patients with COPD at stable state and during virus-associated exacerbations. In vitro immune responses to rhinovirus infection in differentiated primary bronchial epithelial cells (BECs) sampled from patients with COPD were additionally evaluated. Patients were stratified as frequent exacerbators (≥2 exacerbations in the preceding year) or infrequent exacerbators (<2 exacerbations in the preceding year) with comparisons made between these groups. Frequent exacerbators had reduced sputum cell mRNA expression of the antiviral immune mediators type I and III interferons and reduced interferon-stimulated gene (ISG) expression when clinically stable and during virus-associated exacerbation. A role for epithelial cell-intrinsic innate immune dysregulation was identified: induction of interferons and ISGs during in vitro rhinovirus (RV) infection was also impaired in differentiated BECs from frequent exacerbators. Frequent exacerbators additionally had increased sputum bacterial loads at 2 wk following virus-associated exacerbation onset. These data implicate deficient airway innate immunity involving epithelial cells in the increased propensity to exacerbations observed in some patients with COPD. Therapeutic approaches to boost innate antimicrobial immunity in the lung could be a viable strategy for prevention and treatment of frequent exacerbations.
Pharmacological attenuation of group III/IV muscle afferents improves endurance performance when oxygen delivery to locomotor muscles is preserved
Authors: Hureau Thomas J. , Weavil Joshua C. , Thurston Taylor S. , Wan Hsuan-Yu , Gifford Jayson R. , Jessop Jacob E. , Buys Michael J. , Richardson Russell S. , Amann Markus
Published: September 2019

We sought to investigate the role of group III/IV muscle afferents in limiting endurance exercise performance, independently of their role in optimizing locomotor muscle O2 delivery. While breathing 100% O2 to ensure a similar arterial O2 content ([Formula: see text]) in both trials, eight male cyclists performed 5-km time trials under control conditions (HCTRL) and with lumbar intrathecal fentanyl (HFENT) impairing neural feedback from the lower limbs. After each time trial, common femoral artery blood flow (FBF) was quantified (Doppler ultrasound) during constant-load cycling performed at the average power of the preceding time trial. The assessment of end-tidal gases, hemoglobin content and saturation, and FBF facilitated the calculation of leg O2 delivery. Locomotor muscle activation during cycling was estimated from vastus lateralis EMG. With electrical femoral nerve stimulation, peripheral and central fatigue were quantified by pre- to postexercise decreases in quadriceps twitch torque (ΔQtw) and voluntary activation (ΔVA), respectively. FBF (~16 mL·min−1·W−1; P = 0.6), [Formula: see text] (~24 mL O2/dL; P = 0.9), and leg O2 delivery (~0.38 mL O2·min−1·W−1; P = 0.9) were not different during HCTRL and HFENT. Mean power output and time to completion were significantly improved by 9% (~310 W vs. ~288 W) and 3% (~479 s vs. ~463 s), respectively, during HFENT compared with HCTRL. Quadriceps muscle activation was 9 ± 7% higher during HFENT compared with HCTRL ( P < 0.05). ΔQtw was significantly greater in HFENT compared with HCTRL (54 ± 8% vs. 39 ± 9%), whereas ΔVA was not different (~5%; P = 0.3) in both trials. These findings reveal that group III/IV muscle afferent feedback limits whole body endurance exercise performance and peripheral fatigue by restricting neural activation of locomotor muscle.

NEW & NOTEWORTHY Group III/IV muscle afferent feedback facilitates endurance performance by optimizing locomotor muscle O2 delivery but also limits performance by restricting neural drive to locomotor muscle. To isolate the performance-limiting effect of these sensory neurons, we pharmacologically attenuated their central projection during a cycling time trial while controlling for locomotor muscle O2 delivery. With no difference in leg O2 delivery, afferent blockade attenuated the centrally mediated restriction in motoneuronal output and improved cycling performance.
Women Hospitalized for Acute on Chronic Decompensated Systolic Heart Failure Receive Less Furosemide Compared to Men
Authors: Rasmussen Tyler P. , Williford Noah N. , DeZorzi Christopher , Hammoud Aziz , Boyle Brenden J. , Zhou Yunshu , Ten Eyck Patrick , Gebska Milena A.
Published: September 2019

The cumulative incidence of systolic heart failure is similar in men and women. However, major prognostic differences exist between genders. We sought to measure gender differences in furosemide prescribing patterns for patients with preexisting heart failure with reduced ejection fraction (HFrEF) admitted with Stage C acute decompensation, regardless of the underlying cause. We conducted a single-center retrospective analysis of patients admitted between 2015 and 2018 for acute on chronic decompensated HFrEF. Primary outcomes were differences in initial furosemide dose, total dose over the first 24 hours of hospitalization, and total dose during the entire hospitalization between women and men. Secondary outcomes included acute kidney injury (AKI), intubation, noninvasive ventilation (NIV), and in-hospital 30-day and 1-year mortality. We studied 434 patients (31% female) with similar baseline characteristics. Females received significantly less furosemide compared to men for the initial dose, over the first 24 hours, and throughout their hospitalization. However, AKI was more prevalent in women versus men (p=0.008). Females admitted for acute on chronic decompensated HFrEF receive significantly less furosemide when compared to men, but developed more AKI prior to discharge.
A Mathematical Approach with Fractional Calculus for the Modelling of Children’s Physical Development
Authors: Önal Nisa Özge , Karaçuha Kamil , Erdinç Göksu Hazar , Karaçuha Banu Bahar , Karaçuha Ertuğrul
Published: September 2019

From birth to now, it is getting more and more important to keep track of the children development, because knowing and determining the factors related to the physical development of the children would provide better and reliable results for children care. In this study, we developed a mathematical approach to have the ability of analysing and examining factors such as weight, height, and body mass index with respect to the age. We used 7 groups for weight, height, and body mass index in Percentage Chart of Turkey. We developed a continuous curve which is valid for any time interval by using discrete weight, height, and body mass index data of 0–18 years old children and the least squares method. By doing so, it became possible to find the percentage and location of the children in Percentage Chart. We advanced a new mathematical model with the help of fractional calculus theory. The results are quite successful and better compared to linear and Polynomial Model analysis. The method provides the opportunity to predict expected values of the children for the future by using previous data obtained in the development of the children.
Pancreatic Cysts: Diagnostic Role of EUS-Guided Microforceps Biopsy and Confocal Laser Endomicroscopy
Authors: Kohoutova Darina , Zar Sameer , Repak Rudolf , Vlavianos Panagiotis , Bures Jan
Published: September 2019

Frequent use of high-quality cross-sectional imaging has led to a significant rise in diagnosis of pancreatic cystic lesions (PCLs). Despite the fact that enormous effort has been put into the research of PCLs within the last two decades and multiple guidelines have been developed, our clinical decision-making especially in regard to mucinous lesions remains limited. Currently, clinical assessment, cross-sectional imaging and EUS with fluid analysis (if appropriate) belong to the standard care in patients with PCLs. For differentiation of mucinous from nonmucinous cysts, the sensitivity of cytological investigation and CEA in the cyst fluid is 42% and 52-79%, respectively. Due to the limited accuracy, further diagnostic tools are warranted. Two EUS-guided approaches have been introduced recently. Through-the-(19-gauge EUS) needle Moray microforceps have been developed, and several studies have acknowledged their contribution to the correct diagnosis as they help to overcome limited cellularity of the EUS-guided cyst fluid aspiration and traditional cytology. Confocal laser endomicroscopy offers real-time images and seems to be a promising method for the diagnosis and differential diagnosis of pancreatic PCLs. Example images of the needle-based confocal laser endomicroscopy criteria for the diagnosis of PCLs have been suggested recently. Before both, Moray microforceps and confocal laser endomicroscopy can be widely accepted, further studies are necessary to determine the real diagnostic yield and the clinical efficacy.
Compuflo®-Assisted Training vs Conventional Training for the Identification of the Ligamentum Flavum with an Epidural Simulator: A Brief Report
Authors: Capogna Emanuele , Coccoluto Alessandra , Gibiino Giovanni , Del Vecchio Angelica
Published: September 2019

The ability of recognizing the ligamentum flavum is the first, crucial, important skill to teach novices when they are learning the epidural technique. The aim of this preliminary prospective study was to evaluate whether the Compuflo® Epidural instrument may help inexperienced trainees to better identify the ligamentum flavum during an epidural simulator training session. Compuflo® reduced the total number of attempts to identify the ligamentum flavum and increased three fold the chance to identify it at the first attempt during a simulator-assisted training module, making this identification easier for inexperienced trainees. This trial is registered with NCT03812926.
Altered Toll-Like Receptor Signalling in Children with Down Syndrome
Authors: Huggard Dean , Koay W. J. , Kelly Lynne , McGrane Fiona , Ryan Emer , Lagan Niamh , Roche Edna , Balfe Joanne , Leahy T. Ronan , Franklin Orla , Moreno-Oliveira Ana , Melo Ashanty M. , Doherty Derek G. , Molloy Eleanor J.
Published: September 2019

Toll-like receptors (TLRs) are the key in initiating innate immune responses. TLR2 is crucial in recognising lipopeptides from gram-positive bacteria and is implicated in chronic inflammation. Children with Down syndrome (DS) are prone to infections from these pathogens and have an increased risk of autoimmunity. Sparstolonin B (SsnB) is a TLR antagonist which attenuates cytokine production and improves outcomes in sepsis. We hypothesised that TLR signalling may be abnormal in children with DS and contribute to their clinical phenotype. We evaluated TLR pathways in 3 ways: determining the expression of TLR2 on the surface of neutrophils and monocytes by flow cytometry, examining the gene expression of key regulatory proteins involved in TLR signal propagation, MyD88, IRAK4, and TRIF, by quantitative PCR, and lastly determining the cytokine production by ELISA following immunomodulation with proinflammatory stimuli (lipopolysaccharide (LPS), Pam3Csk4) and the anti-inflammatory agent SsnB. We report TLR2 expression being significantly increased on neutrophils, total monocytes, and intermediate and nonclassical monocytes in children with DS (n=20,mean age 8.8±SD 5.3years, femalen=11) compared to controls (n=15,mean age 6.2±4.2years, femalen=5). At baseline, the expression of MyD88 was significantly lower, and TRIF significantly raised in children with DS. The TLR antagonist SsnB was effective in reducing TLR2 and CD11b expression and abrogating cytokine production in both cohorts. We conclude that TLR signalling and the TLR2 pathway are dysregulated in DS, and this disparate innate immunity may contribute to chronic inflammation in DS. SsnB attenuates proinflammatory mediators and may be of therapeutic benefit.
Anti-Inflammatory Effects of Licania macrocarpa Cuatrec Methanol Extract Target Src- and TAK1-Mediated Pathways
Authors: Shin Kon Kuk , Park Jae Gwang , Hong Yo Han , Aziz Nur , Park Sang Hee , Kim Sunggyu , Kim Eunji , Cho Jae Youl
Published: September 2019

In this study, we investigated the anti-inflammatory effects of Licania macrocarpa Cuatrec methanol extract (Lm-ME) in vitro and in vivo and found pharmacological target proteins of Lm-ME in TLR4-mediated inflammatory signaling. This extract reduced NO production and mRNA expression of inflammatory cytokines such as iNOS, COX-2, IL-6, and IL-1β. In the NF-κB- and AP-1-mediated luciferase reporter gene assay, transcription factor activities decreased under cotransfection with MyD88 or TRIF. Phosphorylated protein levels of Src, PI3K, IKKα/β, and IκBα as well as p50 and p65 in the NF-κB signal pathway were downregulated, and phosphorylation of TAK1, MEK1/2, MKK4/7, and MKK3/6 as well as ERK, JNK, and p38 was decreased in the AP-1 signal pathway. Through overexpression of HA-Src and HA-TAK1, respectively, Lm-ME inhibited autophosphorylation of overexpressed proteins and thereby activated fewer downstream signaling molecules. Lm-ME also attenuated stomach ulcers in an HCl/EtOH-induced acute gastritis model mice, and COX-2 mRNA expression and phosphorylated TAK1 levels in gastric tissues were diminished. The flavonoids kaempferol and quercetin were identified in the HPLC analysis of Lm-ME; both are actively anti-inflammatory. Therefore, these results suggest that Lm-ME can be used for anti-inflammatory remedy by targeting Src and TAK1.
Vehicular Channel in Urban Environments at 23 GHz for Flexible Access Common Spectrum Application
Authors: Wang Longhe , Ai Bo , Yang Jingya , Qiu Hao , Wang Wanqiao , Guan Ke
Published: September 2019

With the development of the vehicular network, new radio technologies have been in the spotlight for maximizing the utilization of the limited radio spectrum resource while accommodating the increasing amount of services and applications in the wireless mobile networks. New spectrum policies based on dynamic spectrum access technology such as flexible access common spectrum (FACS) have been adopted by the Korea Communications Commission (KCC). 23 GHz bands have been allocated to FACS bands by the KCC, which is expected extensively for vehicular communications. The comprehensive knowledge on the radio channel is essential to effectively support the design, simulation, and development of such radio technologies. In this paper, the characteristics of 23 GHz vehicle-to-infrastructure (V2I) channels are simulated and extracted for the urban environment in Seoul. The path loss, shadow factor, Ricean K-factor, root-mean-square (RMS) delay spread, and angular spreads are characterized from the calibrated ray-tracing simulation results, and it can help researchers have a better understanding of the propagation channel for designing vehicular radio technologies and a communication system in a similar environment.
Sanbai Melon Seed Oil Exerts Its Protective Effects in a Diabetes Mellitus Model via the Akt/GSK-3β/Nrf2 Pathway
Authors: Wang Fang , Xi Yuanhang , Liu Wenzhe , Li Jie , Zhang Ya , Jia Min , He Qiaoyan , Zhao Hongsheng , Wang Siwang
Published: September 2019

Traditional Chinese medicine (TCM) plays an important role in the treatment of type 2 diabetes mellitus (T2DM). However, the lack of adequate and scientifically rigorous evidence has limited its application in this disorder. Sanbai melon seed oil (SMSO) is used in folk medicine to treat DM; however, only few literature reports exist regarding its mechanism. Herein, we aimed to confirm the antidiabetic activity of SMSO in a T2DM model and further elucidate its possible mechanisms. The T2DM rat model was induced by high-fat and sugar diet and streptozocin (STZ, 40 mg/kg). SMSO was administered at doses of 0.7 g/kg, 1.4 g/kg, and 2.8 g/kg. Several biochemical parameters and antioxidant protein levels were measured to evaluate the hyperglycemic and antioxidant activities of SMSO. Western blotting was performed to determine its potential mechanism. Based on the results, SMSO treatment significantly reduced blood glucose levels, increased plasma insulin, and repaired islet tissue injury in diabetic rats (P<0.05). To add, it markedly reduced MDA levels and increased that of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px). Western blot results showed that SMSO induced n-Nrf2 and HO-1 expression and Akt and GSK-3β phosphorylation in a dose-dependent manner. Further studies showed that LY294002, aPI3K inhibitor, abolished the effects of SMSO on GSK-3β phosphorylation and Nrf2 nuclear translocation as well as the protective effects on pancreatic β cells. Together, these results suggest that SMSO regulates the Akt/GSK-3β/Nrf2 pathway and induces the expression of antioxidant proteins to impede oxidative stress in rats with T2DM.
Exploring Pharmacological Mechanisms of Xiang Ju Tablets in the Treatment of Allergic Rhinitis via a Network Pharmacology Approach
Authors: Hu Kun xia , Duan Xi , Han Li zhu , Ju Hong ye , Wang Bin , Tang Zhi shu , Song Xiao
Published: September 2019

In this study, allergic rhinitis (AR) disease targets and Xiang Ju tablet-associated targets were determined through the use of databases for the identification of putative therapeutic targets and then combined. After the production of a putative therapeutic target interaction network for Xiang Ju tablets against AR, topological analysis was used to determine the core targets of Xiang Ju tablets in AR treatment. For all putative therapeutic targets, analyses of biological function and pathway enrichment were performed to optimize the biological processes and key signaling pathways of Xiang Ju tablets in AR treatment. The top 5 therapeutic targets of Xiang Ju tablets in AR treatment were identified and included CXCL8, IL1B, IL6, IL10, and TNF. The biological processes, molecular functions, and cell composition related to the use of Xiang Ju tablets in AR treatment were predominantly associated with cytokine production, regulation of protein secretion, and regulation of peptide secretion; cytokine activity, cytokine receptor binding, and receptor ligand activity; and platelet alpha granule lumen, collagen-containing extracellular matrix, and platelet alpha granule. In addition, the top 64 key signaling pathways were identified.
Prediction of Small‐Strain Dynamic Properties on Granulated Spherical Glass Bead‐Polyurethane Mixtures
Authors: Kang Gyeong-o , Choi Woong , Lee Changho
Published: September 2019

This paper aims to propose predictive equations for the small‐strain shear modulus (Gmax) and small‐strain damping ratio (Dmin) of a granulated mixture with plastic and nonplastic materials to reduce the dynamic energy of the ground. Polyurethane bead (PB) and glass bead (GB) were used as the plastic and nonplastic materials, respectively. 180 resonant‐column tests were conducted with various conditions affecting the dynamic properties, such as nonplastic particle content (PC), void ratio (e), particle‐size ratio (sr), and mean effective confining pressure (). The results showed that Gmax and Dmin, respectively, increased and decreased as e decreased with increasing of material mixtures. In addition, Gmax decreased with an increase in PC, whereas Dmin increased. It was also found that sr of materials affected the changes in Gmax and Dmin. With an increase in sr, Gmax increased while Dmin decreased because small particles do not hinder the behavior of large particles as the size of larger particles increases. Finally, based on the results, new equations for estimating Gmax and Dmin of a granulated mixture with PB and GB were proposed as functions of PC, e, median grain size (D50), and .
Dynamic Behavior of Self-Piercing Riveted and Mechanical Clinched Joints of Dissimilar Materials: An Experimental Comparative Investigation
Authors: Ge Yulong , Xia Yong
Published: September 2019

The present work compares the dynamic effect of a self-piercing riveted (SPR) joint with that of a mechanical clinched joint having the dissimilar materials combination. The substrates used in this investigation are aluminum alloy AA5182-O and deep drawing steel DX51D+Z. The static and dynamic behaviors and the failure modes of the SPR and clinching joints are characterized by lap-shear, cross-tension, and coach-peel tests. The influence of the strain-rate-dependent mechanical behavior of the substrates on the joints is examined; this can help improve prediction of the energy absorption of the joints under impact loading. Considering the realistic baking process in a painting shop, the deforming and hardening effects on the SPR and the clinched joints induced by baking are also studied. The specimens are heated to 180°C for 30 min in an oven and then cooled down in air. The SPR and the clinched joints before and after the baking process are compared in terms of the mechanical behavior.
Genetic Association betweenNFKBIAandNFKB1Gene Polymorphisms and the Susceptibility to Head and Neck Cancer: A Meta-Analysis
Authors: Li Lin , Zhang Zhong-Ti
Published: September 2019

Background. The role of theNFKB1gene rs28362491 polymorphism andNFKBIAgene rs2233406 polymorphism in the development of head and neck cancer (HNC) remains controversial. This meta-analysis was performed to assess the relationship between the gene polymorphisms and HNC quantitatively.Methods. PubMed, Embase, Web of Science, WanFang Data, and China National Knowledge databases were used to search for eligible articles. The relationship was evaluated by STATA 11.0.Results. Eight eligible articles were included in our study. Nine case-control studies from the eight included articles were correlated with rs28362491 polymorphism. Four articles were related to rs2233406 polymorphism. Overall, a significant correlation was observed between the rs28362491 polymorphism and a decreased risk of HNCs (OR=0.76,95%CI=0.60‐0.97for DD vs. II;OR=0.80,95%CI=0.68‐0.95for DD vs. DI+II). In subgroup analyses, the rs28362491 polymorphism was associated with the risk of nasopharyngeal carcinoma (NC), but not with oral cancer (OC). In addition, no statistical correlation was found between the polymorphism of rs2233406 and HNCs.Conclusion. rs28362491 polymorphism was significantly associated with the risk of HNCs, especially with NC. Additionally, our results showed that no association was discovered between rs2233406 polymorphism and HNCs.
The Relationship between Self-Perceived Burden and Posttraumatic Growth among Colorectal Cancer Patients: The Mediating Effects of Resilience
Authors: Zhang Chengshuai , Gao Ruitong , Tai Jiandong , Li Yuewei , Chen Si , Chen Lei , Cao Xiaobai , Wang Li , Jia Minghua , Li Feng
Published: September 2019

At present, the influence factors of posttraumatic growth (PTG) in colorectal cancer (CRC) patients and the relationship between PTG, self-perceived burden (SPB), and resilience are not completely clear. Thus, the present study examined whether resilience and SPB could predict PTG in CRC patients. The role of resilience as a potential mediator was also assessed. Using a cross-sectional design, a convenience sample of 157 CRC patients was selected as subjects, from July to December 2016 in a third-grade hospital. It was found that the main influencing factors for the total PTG score of CRC patients included work status, affordability for medical expenses, and duration of illness. Resilience was positively correlated with PTG, SPB was negatively correlated with PTG, and resilience played an intermediary role. Our findings remind clinicians to treat the psychosocial response of CRC patients from multiple perspectives, with a focus on their positive aspects. By increasing resilience and reducing the patient’s SPB, clinicians might enhance the patient’s PTG and quality of life.
Study of GLR and Inlet Velocity on Hydrocyclone for Fracturing Flow‐Back Fluids
Authors: Liu Bing , Wang Huajian , Li Luncao , Zhao Zhenjiang , Xu Liping , Xue Jianliang
Published: September 2019

In this work, based on the Reynolds stress model (RSM) of the computational fluid dynamics (CFD) software Fluent and experimental method, the velocity field, pressure characteristics, split ratio, and separation efficiency of the hydrocyclone are analyzed under different gas‐liquid ratios (GLRs). For the inlet velocity, the lower limit is ascertained by the flow field stability, the upper limit is largely determined by the energy consumption, and the optimum range is 4 m/s to 10 m/s. Within the optimum range, the peak value of tangential velocity increases while the GLR increases, whereas the pressure and pressure drop decrease. With the increase in the GLR, the axial velocity decreases, and the locus of zero vertical velocity shifts inward. The increase in the GLR causes more gas to collect at the vortex finder, which hinders the discharge of the solid‐liquid mixture from the overflow, and the larger the GLR, the faster the decrease in the split ratio. The separation efficiency of particles with a particle size of 15 μm is increased by 6.75%, and the separation efficiency of particles with a particle size of 30 μm is increased by 0.57%. Meanwhile, the separation efficiency is increased by 2.43%, and the cut size (d50) is reduced as the GLR increases.
Biodentine™ Partial Pulpotomy of a Young Permanent Molar with Signs and Symptoms Indicative of Irreversible Pulpitis and Periapical Lesion: A Case Report of a Five-Year Follow-Up
Authors: Chinadet W. , Sutharaphan T. , Chompu-inwai P.
Published: September 2019

The purpose of this paper was to report the five-year success of Biodentine™ partial pulpotomy in a young permanent molar, with signs and symptoms indicative of irreversible pulpitis and periapical lesion, in a nine-year-old girl. Preoperative clinical examination revealed a large carious lesion of the left mandibular permanent first molar. The patient reported pain on percussion. The tooth responded positively to the electric pulp test and had lingering pain after cold testing. A periapical radiograph showed a deep carious lesion and periapical lesion. Based on the clinical and radiographical examination, the tooth had signs and symptoms indicative of irreversible pulpitis and periapical lesion. During caries removal, pulp exposure occurred, and 2-3 mm in depth of pulp tissue at the exposure site was removed. Haemorrhage was controlled within four minutes with 2.5% sodium hypochlorite-moistened cotton pellets. Biodentine™ was then applied as both a pulp dressing and a temporary restoration. At the following visit, composite resin was placed over the Biodentine™ as a final restoration. During a five-year follow-up, the tooth was asymptomatic, had positive responses to sensibility tests, and had no discolouration. Follow-up radiographs showed a dentine bridge and periapical healing.
miR-154-5p Functions as an Important Regulator of Angiotensin II-Mediated Heart Remodeling
Authors: Wang Que , Yu Xiaoxue , Dou Lin , Huang Xiuqing , Zhu Kaiyi , Guo Jun , Yan Mingjing , Wang Siming , Man Yong , Tang Weiqing , Shen Tao , Li Jian
Published: September 2019

Chronic hypertension, valvular heart disease, and heart infarction cause cardiac remodeling and potentially lead to a series of pathological and structural changes in the left ventricular myocardium and a progressive decrease in heart function. Angiotensin II (AngII) plays a key role in the onset and development of cardiac remodeling. Many microRNAs (miRNAs), including miR-154-5p, may be involved in the development of cardiac remolding, but the underlying molecular mechanisms remain unclear. We aimed to characterize the function of miR-154-5p and reveal its mechanisms in cardiac remodeling induced by AngII. First, angiotensin II led to concurrent increases in miR-154-5p expression and cardiac remodeling in adult C57BL/6J mice. Second, overexpression of miR-154-5p to a level similar to that induced by AngII was sufficient to trigger cardiomyocyte hypertrophy and apoptosis, which is associated with profound activation of oxidative stress and inflammation. Treatment with a miR-154-5p inhibitor noticeably reversed these changes. Third, miR-154-5p directly inhibited arylsulfatase B (Arsb) expression by interacting with its 3′-UTR and promoted cardiomyocyte hypertrophy and apoptosis. Lastly, the angiotensin type 1 receptor blocker telmisartan attenuated AngII-induced cardiac hypertrophy, apoptosis, and fibrosis by blocking the increase in miR-154-5p expression. Moreover, upon miR-154-5p overexpression in isolated cardiomyocytes, the protective effect of telmisartan was partially abolished. Based on these results, increased cardiac miR-154-5p expression is both necessary and sufficient for AngII-induced cardiomyocyte hypertrophy and apoptosis, suggesting that the upregulation of miR-154-5p may be a crucial pathological factor and a potential therapeutic target for cardiac remodeling.
Combination of TMB and CNA Stratifies Prognostic and Predictive Responses to Immunotherapy Across Metastatic Cancer
Authors: Liu Li , Bai Xue , Wang Jian , Tang Xin-Ran , Wu De-Hua , Du Sha-Sha , Du Xiu-Ju , Zhang Yao-Wei , Zhu Hong-Bo , Fang Yuan , Guo Ze-Qin , Zeng Qin , Guo Xue-Jun , Liu Zhu , Dong Zhong-Yi
Published: September 2019

Purpose:

Although tumor mutation burden (TMB) has been well known to predict the response to immune checkpoint inhibitors (ICI), lack of randomized clinical trial data has restricted its clinical application. This study aimed to explore the significance and feasibility of biomarker combination based on TMB and copy-number alteration (CNA) for the prognosis of each tumor and prediction for ICI therapy in metastatic pan-cancer milieu.

Experimental Design:

Non-ICI–treated MSK pan-cancer cohort was used for prognosis analysis. Three independent immunotherapy cohorts, including non–small cell lung cancer (n = 240), skin cutaneous melanoma (n = 174), and mixed cancer (Dana-Farber, n = 98) patients from previous studies, were analyzed for efficacy of ICI therapy.

Results:

TMB and CNA showed optimized combination for the prognosis of most metastatic cancer types, and patients with TMBlowCNAlow showed better survival. In the predictive analysis, both TMB and CNA were independent predictive factors for ICI therapy. Remarkably, when TMB and CNA were jointly analyzed, those with TMBhighCNAlow showed favorable responses to ICI therapy. Meanwhile, TMBhighCNAlow as a new biomarker showed better prediction for ICI efficacy compared with either TMB-high or CNA-low alone. Furthermore, analysis of the non-ICI–treated MSK pan-cancer cohort supported that the joint stratification of TMB and CNA can be used to categorize tumors into distinct sensitivity to ICI therapy across pan-tumors.

Conclusions:

The combination of TMB and CNA can jointly stratify multiple metastatic tumors into groups with different prognosis and heterogeneous clinical responses to ICI treatment. Patients with TMBhighCNAlow cancer can be an optimal subgroup for ICI therapy.
Metastatic Breast Carcinoma–Associated Fibroblasts Have Enhanced Protumorigenic Properties Related to Increased IGF2 Expression
Authors: Gui Yirui , Aguilar-Mahecha Adriana , Krzemien Urszula , Hosein Abdel , Buchanan Marguerite , Lafleur Josiane , Pollak Michael , Ferrario Cristiano , Basik Mark
Published: September 2019

Purpose:

The microenvironment of metastatic breast cancer is incompletely characterized, despite prior evidence that it plays a key role in the biology of metastasis. A major component of the tumor stroma is the carcinoma-associated fibroblast (CAF), which has been shown to communicate with other stromal and cancer cells to create a protumorigenic milieu. Our study was designed to characterize human CAFs from different metastatic sites.

Experimental Design:

We collected eight carcinoma-associated fibroblasts (mCAFs) from different metastatic sites and compared them with CAFs from primary tumors (pCAFs) and with normal breast fibroblasts (NFs). Molecular profiles and effects on breast cancer cell growth, on response to doxorubicin and on T-cell proliferation were compared.

Results:

We observed marked differences in mCAFs compared with pCAFs and NFs with respect to in vitro proliferation and effects on breast cancer cell migration, spheroid growth, invasion, response to doxorubicin, and in vivo tumor growth. We found marked transcriptomic differences between mCAFs and pCAFs, including increased expression of IFN-related genes and IGF2 in the former. Cluster analysis revealed two groups of mCAFs, with the liver mCAFs clustering together, with increased PDGFA expression. Treatment with an antibody against insulin-like growth factors (BI836845) inhibited growth of mixed mCAF-tumor cell xenografts in vivo. Also, mCAFs had a suppressive effect on T-cell proliferation.

Conclusions:

This is the first comparative analysis of a set of CAFs from metastatic sites in breast cancer. It revealed a marked protumorigenic effect in these mCAFs, which occurs in part through increased expression of IGF2.
Transcriptomic Heterogeneity of Androgen Receptor Activity Defines a de novo low AR-Active Subclass in Treatment Naïve Primary Prostate Cancer
Authors: Spratt Daniel E. , Alshalalfa Mohammed , Fishbane Nick , Weiner Adam B. , Mehra Rohit , Mahal Brandon A. , Lehrer Jonathan , Liu Yang , Zhao Shuang G. , Speers Corey , Morgan Todd M. , Dicker Adam P. , Freedland Stephen J. , Karnes R. Jeffery , Weinmann Sheila , Davicioni Elai , Ross Ashley E. , Den Robert B. , Nguyen Paul L. , Feng Felix Y. , Lotan Tamara L. , Chinnaiyan Arul M. , Schaeffer Edward M.
Published: September 2019

Purpose:

The heterogeneity of androgen receptor (AR)-activity (AR-A) is well-characterized in heavily treated metastatic castration-resistant prostate cancer (mCRPC). However, the diversity and clinical implications of AR-A in treatment-naïve primary prostate cancer is largely unknown. We sought to characterize AR-A in localized prostate cancer and understand its molecular and clinical implications.

Experimental Design:

Genome-wide expression profiles from prostatectomy or biopsy samples from 19,470 patients were used, all with independent pathology review. This was comprised of prospective discovery (n = 5,239) and validation (n = 12,728) cohorts, six retrospective institutional cohorts with long-term clinical outcomes data (n = 1,170), and The Cancer Genome Atlas (n = 333).

Results:

A low AR-active subclass was identified, which comprised 9%–11% of each cohort, and was characterized by increased immune signaling, neuroendocrine expression, and decreased DNA repair. These tumors were predominantly ERG and basal subtype. Low AR-active tumors had significantly more rapid development of recurrence or metastatic disease across cohorts, which was maintained on multivariable analysis [HR, 2.61; 95% confidence interval (CI), 1.22–5.60; P = 0.014]. Low AR-active tumors were predicted to be more sensitive to PARP inhibition, platinum chemotherapy, and radiotherapy, and less sensitive to docetaxel and androgen-deprivation therapy. This was validated clinically, in that low AR-active tumors were less sensitive to androgen-deprivation therapy (OR, 0.41; 95% CI, 0.21–0.80; P = 0.008).

Conclusions:

Leveraging large-scale transcriptomic data allowed the identification of an aggressive subtype of treatment-naïve primary prostate cancer that harbors molecular features more analogous to mCRPC. This suggests that a preexisting subgroup of patients may have tumors that are predisposed to fail multiple current standard-of-care therapies and warrant dedicated therapeutic investigation.
Utility of the RIG-I Agonist Triphosphate RNA for Melanoma Therapy
Authors: Helms Mike W. , Jahn-Hofmann Kerstin , Gnerlich Felix , Metz-Weidmann Christiane , Braun Monika , Dietert Gabriele , Scherer Petra , Grandien Kaj , Theilhaber Joachim , Cao Hui , Wagenaar Timothy R. , Schnurr Max M. , Endres Stefan , Wiederschain Dmitri , Scheidler Sabine , Rothenfußer Simon , Brunner Bodo , König Lars M.
Published: September 2019

The pattern recognition receptor RIG-I plays an important role in the recognition of nonself RNA and antiviral immunity. RIG-I's natural ligand, triphosphate RNA (ppp-RNA), is proposed to be a valuable addition to the growing arsenal of cancer immunotherapy treatment options. In this study, we present comprehensive data validating the concept and utility of treatment with synthetic RIG-I agonist ppp-RNA for the therapy of human cancer, with melanoma as potential entry indication amenable to intratumoral treatment. Using mRNA expression data of human tumors, we demonstrate that RIG-I expression is closely correlated to cellular and cytokine immune activation in a wide variety of tumor types. Furthermore, we confirm susceptibility of cancer cells to ppp-RNA treatment in different cellular models of human melanoma, revealing unexpected heterogeneity between cell lines in their susceptibility to RNA agonist features, including sequence, secondary structures, and presence of triphosphate. Cellular responses to RNA treatment (induction of type I IFN, FasR, MHC-I, and cytotoxicity) were demonstrated to be RIG-I dependent using KO cells. Following ppp-RNA treatment of a mouse melanoma model, we observed significant local and systemic antitumor effects and survival benefits. These were associated with type I IFN response, tumor cell apoptosis, and innate and adaptive immune cell activation. For the first time, we demonstrate systemic presence of tumor antigen–specific CTLs following treatment with RIG-I agonists. Despite potential challenges in the generation and formulation of potent RIG-I agonists, ppp-RNA or analogues thereof have the potential to play an important role for cancer treatment in the next wave of immunotherapy.
Morin Inhibits Proliferation and Induces Apoptosis by Modulating the miR-188-5p/PTEN/AKT Regulatory Pathway in CML Cells
Authors: Nie Zi-Yuan , Yang Lin , Liu Xiao-Jun , Yang Zhan , Yang Gao-Shan , Zhou Jing , Qin Yan , Yu Jing , Jiang Ling-Ling , Wen Jin-Kun , Luo Jian-Min
Published: September 2019

Increased activity of the PI3K/AKT/mTOR pathway has been observed in chronic myeloid leukemia (CML). Morin, a kind of flavonoid, exhibits a significant anticancer activity by suppressing the PI3K/AKT signaling pathway. However, the effect of morin on CML and its underlying mechanisms is poorly understood. Here, we found that morin dose dependently inhibited the proliferation of CML cell lines K562 and KCL22 and induced their apoptosis, with a significant increase in cell apoptosis upon exposure of cells to 50 μmol/L morin. Moreover, morin significantly reduced CML xenograft growth in nude mice. Mechanically, morin attenuated phosphorylated AKT level by upregulating PTEN expression, thus leading to the inhibition of AKT signaling. Knockdown of PTEN by its siRNA completely abrogated morin-induced cell apoptosis, indicating that PTEN mediates the inductive effect of morin on CML cell apoptosis. More importantly, we found that miR-188-5p was significantly upregulated in CML patients and CML cell lines. Treating CML cells with morin markedly downregulated the miR-188-5p expression level. Further, we demonstrated that miR-188-5p repressed PTEN expression by directly targeting its 3′-UTR. miR-188-5p downregulation induced by morin enhanced CML cell apoptosis by relieving miR-188-5p repression of PTEN expression. In summary, morin exerts significant anticancer efficacy in CML by regulating the miR-188-5p/PTEN axis and thus repressing the PI3K/AKT signaling.
Association between Deep Gray Matter Changes and Neurocognitive Function in Mild Cognitive Impairment and Alzheimer’s Disease: A Tensor-Based Morphometric MRI Study
Authors: Tuokkola Terhi , Karrasch Mira , Koikkalainen Juha , Parkkola Riitta , Lötjönen Jyrki , Löyttyniemi Eliisa , Hurme Saija , Rinne Juha Olavi
Published: September 2019

Background: Atrophy of the deep gray matter (DGM) has been associated with a risk of conversion from mild cognitive impairment (MCI) to Alzheimer’s disease (AD) and the degree of cognitive impairment. However, specific knowledge of the associations between degenerative DGM changes and neurocognitive functions remains limited. Objective: To examine degenerative DGM changes and evaluate their association with neurocognitive functions. Method: We examined DGM volume changes with tensor-based morphometry (TBM) and analyzed the relationships between DGM changes and neurocognitive functions in control (n = 58), MCI (n = 38), and AD (n = 58) groups with multiple linear regression analyses. Results: In all DGM areas, the AD group had the largest changes in TBM volume. The differences in TBM volume changes were larger between the control group and the AD group than between the other pairs of groups. In the AD group, volume changes of the right thalamus were significantly associated with episodic memory, learning, and semantic processing. Significant or trend-level associations were identified between bilateral caudate nucleus changes and episodic memory as well as semantic processing. In the control and MCI groups, very few significant associations emerged. Conclusions: Atrophy of the DGM structures, especially the thalamus and caudate nucleus, is related to cognitive impairment in AD. DGM atrophy is associated with tests reflecting both subcortical and cortical cognitive functions.
Protective Effects of Prunasin A against the Differentiation of Osteoclasts and Destruction of Cartilage via the Receptor Activator of Nuclear Factor-Kappa-Β Ligand/Mitogen-Activated Protein Kinase/Osteoprotegerin Pathway in a Rat Model of Arthritis
Authors: Chen Tong , Zhang Bo , Lin Yuan , Pan Jiang , Zhao Xiao-Xiong , Ren Shi-Xiang
Published: September 2019

The present study evaluated the protective effects of pseurotin A against inflammation and the destruction of cartilage in a rat model of rheumatoid arthritis (RA). RA was induced by intradermal injections of Freund’s complete adjuvant (1 mg/mL), and the treatment with pseurotin A (50 and 100 mg/kg, p.o.) was administered over 1 week. The effects of pseurotin A were assessed by estimating hind paw volume (HPV) and determining the levels of inflammatory mediators in the serum and synovial fluid of collagen-induced arthritis (CIA)-induced RA rats. Western blot and histopathological assays were performed to assess changes in synovial tissues. Additionally, in vitro analyses of receptor activator of nuclear factor-kappa-Β ligand (RANKL)-stimulated RAW264.7 cells treated with pseurotin A at different concentrations (1, 10, and 100 µg/mL) were conducted to assess the effects of pseurotin A on apoptosis ratio, real-time polymerase chain reaction data, and tartrate-resistant acid phosphatase staining. Compared to the RA group, treatment with pseurotin A significantly decreased HPV and reduced the levels of inflammatory mediators in the synovial fluid and blood. Additionally, pseurotin A ameliorated the protein expressions of osteoprotegerin, nuclear factor of activated T-cells, nuclear factor-kappa beta (NF-κB), IκBα, extracellular signal regulated kinase, and P38 as well as histopathological changes in the synovial tissue of CIA-induced RA rats. The in vitro findings revealed that pseurotin A treatment did not alter the apoptosis ratio in RANKL-stimulated RAW264.7 cells but significantly reduced the mRNA expressions of calcitonin receptor, NF-κB, and matrix metallopeptidase-9. The present findings suggest that pseurotin A ameliorated the differentiation of osteoclasts and the destruction of cartilage in RA rats via regulation of the mitogen-activated protein kinase/RANKL/NF-kB pathway.