bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex differences in sympathetic vasoconstrictor responsiveness and sympatholysis
Authors: Just Timothy P. , DeLorey Darren S.
Published: May 2017

Sex differences in the neurovascular control of blood pressure and vascular resistance have been reported. However, the mechanisms underlying the modulatory influence of sex have not been fully elucidated. Nitric oxide (NO) has been shown to inhibit sympathetic vasoconstriction in resting and contracting skeletal muscle, and estrogen modulates NO synthase (NOS) expression and NO bioavailability. Therefore NO-mediated inhibition of sympathetic vasoconstriction may be enhanced in females. Thus the purpose of the present study was to investigate the hypothesis that sympathetic vasoconstrictor responsiveness would be blunted and NO-mediated inhibition of sympathetic vasoconstriction would be enhanced in females compared with males. Male (M; n = 8) and female (F; n = 10) Sprague-Dawley rats were anesthetized and surgically instrumented for measurement of arterial blood pressure and femoral artery blood flow and stimulation of the lumbar sympathetic chain. The percentage change of femoral vascular conductance in response to sympathetic chain stimulation delivered at 2 and 5 Hz was determined at rest and during triceps surae muscle contraction before (control) and after NOS blockade [ Nω-nitro-l-arginine methyl ester (l-NAME), 10 mg/kg iv]. At rest, sympathetic vasoconstrictor responsiveness was augmented ( P < 0.05) in female compared with male rats at 2 Hz [F: −33 ± 8% (SD); M: −26 ± 6%] but was not different at 5 Hz (F: −55 ± 7%; M: −47 ± 7%). During muscle contraction, evoked vasoconstriction was similar ( P > 0.05) in females and males at 2 Hz (F: −12 ± 5%; M: −13 ± 5%) but was blunted ( P < 0.05) in females compared with males at 5 Hz (F: −24 ± 5%; M: −34 ± 8%). l-NAME increased ( P < 0.05) sympathetic vasoconstrictor responsiveness in both groups at rest and during contraction. Contraction-mediated inhibition of vasoconstriction (sympatholysis) was enhanced ( P < 0.05) in females compared with males; however, sympatholysis was not different ( P > 0.05) between males and females in the presence of NOS blockade, indicating that NO-mediated sympatholysis was augmented in female rats. These data suggest that sex modulates sympathetic vascular control in resting and contracting skeletal muscle and that a portion of the enhanced sympatholysis in female rats was NO dependent.

NEW & NOTEWORTHY Sex differences in the neurovascular regulation of blood pressure and vascular resistance have been documented. However, our understanding of the underlying mechanisms that mediate these differences is incomplete. The present study demonstrates that female rats have an enhanced capacity to inhibit sympathetic vasoconstriction during exercise (sympatholysis) and that NO mediates a portion of the enhanced sympatholysis.
Evidence for β-adrenergic modulation of sweating during incremental exercise in habitually trained males
Authors: Amano Tatsuro , Shitara Yosuke , Fujii Naoto , Inoue Yoshimitsu , Kondo Narihiko
Published: May 2017

The aim of the present study was to determine the β-adrenergic contribution to sweating during incremental exercise in habitually trained males. Nine habitually trained and 11 untrained males performed incremental cycling until exhaustion (20 W/min). Bilateral forearm sweat rates (ventilated capsule) were measured at two skin sites that were transdermally administered via iontophoresis with either 1% propranolol (Propranolol, a nonselective β-adrenergic receptor antagonist) or saline (Control). The sweat rate was evaluated as a function of both relative (percentage of maximum workload) and absolute exercise intensities. The sweat rate at the Propranolol site was lower than the control during exercise at 80 (0.57 ± 0.21 and 0.45 ± 0.19 mg·cm−2·min−1 for Control and Propranolol, respectively) and 90% (0.74 ± 0.22 and 0.65 ± 0.17 mg·cm−2·min−1, respectively) of maximum workload in trained males (all P < 0.05). By contrast, no between-site differences in sweat rates were observed in untrained counterparts (all P > 0.05). At the same absolute intensity, higher sweat rates on the control site were observed in trained males relative to the untrained during exercise at 160 (0.23 ± 0.20 and 0.04 ± 0.05 mg·cm−2·min−1 for trained and untrained, respectively) and 180 W (0.40 ± 0.20 and 0.13 ± 0.13 mg·cm−2·min−1, respectively) (all P < 0.05), whereas this between-group difference was not observed at the Propranolol site (all P > 0.05). We show that the β-adrenergic mechanism does modulate sweating during exercise at a submaximal high relative intensity in habitually trained males. The β-adrenergic mechanism may in part contribute to the greater sweat production in habitually trained males than in untrained counterparts during exercise.

NEW & NOTEWORTHY We demonstrated for the first time that the β-adrenergic mechanism does modulate sweating (i.e., β-adrenergic sweating) during exercise using a localized β-adrenoceptor blockade in humans in vivo. β-Adrenergic sweating was evident in habitually trained individuals during exercise at a submaximal high relative intensity (80–90% maximal work). This observation advances our understanding of human thermoregulation during exercise and of the mechanism that underlies sweat gland adaptation to habitual exercise training.
Lower limb explosive strength capacity in elderly women: effects of resistance training and healthy diet
Authors: Edholm Peter , Strandberg Emelie , Kadi Fawzi
Published: May 2017

The effects of 24 wk of resistance training combined with a healthy diet on lower limb explosive strength capacity were investigated in a population of healthy elderly women. Participants ( n = 63; 67.5 ± 0.4 yr) were randomized into three groups; resistance training (RT), resistance training and healthy diet (RT-HD), and control (CON). Progressive resistance training was performed at a load of 75–85% one-repetition maximum. A major adjustment in the healthy dietary approach was an n-6/n-3 polyunsaturated fatty acid (PUFA) ratio below 2. Lower limb maximal strength, explosive force capacity during dynamic and isometric movements, whole body lean mass, and physical function were assessed. Whole body lean mass significantly increased by 1.5 ± 0.5% in RT-HD only. Isometric strength performance during knee extension as well as the performance in the five sit-to-stand and single-leg-stance tests increased similarly in RT and RT-HD. Improvements in dynamic peak power and time to reach peak power (i.e shorter time) during knee extension occurred in both RT (+15.7 ± 2.6 and −11.0 ± 3.8%, respectively) and RT-HD (+24.6 ± 2.6 and −20.3 ± 2.7%, respectively); however, changes were significantly larger in RT-HD. Similarly, changes in peak force and rate of force development during squat jump were higher in RT-HD (+58.5 ± 8.4 and +185.4 ± 32.9%, respectively) compared with RT (+35.7 ± 6.9 and +105.4 ± 22.4%, respectively). In conclusion, a healthy diet rich in n-3 PUFA can optimize the effects of resistance training on dynamic explosive strength capacity during isolated lower limb movements and multijoint exercises in healthy elderly women.

NEW & NOTEWORTHY Age-related decline in lower limb explosive strength leads to impaired ability to perform daily living tasks. The present randomized controlled trial demonstrates that a healthy diet rich in n-3 polyunsaturated fatty acid (n-3 PUFA) enhances resistance training-induced gains in dynamic explosive strength capacity during isolated lower limb movements and multijoint exercises in healthy elderly women. This supports the use of strategies combining resistance training and dietary changes to mitigate the decline in explosive strength capacity in older adults.
Little Fish, Big Data: Zebrafish as a Model for Cardiovascular and Metabolic Disease
Authors: Gut Philipp , Reischauer Sven , Stainier Didier Y. R. , Arnaout Rima
Published: May 2017

The burden of cardiovascular and metabolic diseases worldwide is staggering. The emergence of systems approaches in biology promises new therapies, faster and cheaper diagnostics, and personalized medicine. However, a profound understanding of pathogenic mechanisms at the cellular and molecular levels remains a fundamental requirement for discovery and therapeutics. Animal models of human disease are cornerstones of drug discovery as they allow identification of novel pharmacological targets by linking gene function with pathogenesis. The zebrafish model has been used for decades to study development and pathophysiology. More than ever, the specific strengths of the zebrafish model make it a prime partner in an age of discovery transformed by big-data approaches to genomics and disease. Zebrafish share a largely conserved physiology and anatomy with mammals. They allow a wide range of genetic manipulations, including the latest genome engineering approaches. They can be bred and studied with remarkable speed, enabling a range of large-scale phenotypic screens. Finally, zebrafish demonstrate an impressive regenerative capacity scientists hope to unlock in humans. Here, we provide a comprehensive guide on applications of zebrafish to investigate cardiovascular and metabolic diseases. We delineate advantages and limitations of zebrafish models of human disease and summarize their most significant contributions to understanding disease progression to date.
Kingella kingaeKeratitis in a Child with Underlying Vernal Keratoconjunctivitis
Authors: Nurul-Laila Salim , Chai Khai-Siang , Liza-Sharmini Ahmad Tajudin , Shatriah Ismail
Published: May 2017

Kingella kingaehad rarely been reported as a causative organism for corneal ulcer and had not been described before in vernal keratoconjunctivitis (VKC). Generally regarded as commensals of respiratory tract particularly in young children, it had however been isolated from the corneal ulcer scraping of both adult and children. We report a case of bacterial ulcer with isolation ofKingella kingaefrom the corneal scraping in a young child with underlying VKC.
A Novel Preferential Diffusion Recommendation Algorithm Based on User’s Nearest Neighbors
Authors: Zhang Fuguo , Liu Yehuan , Xiong Qinqiao
Published: May 2017

Recommender system is a very efficient way to deal with the problem of information overload for online users. In recent years, network based recommendation algorithms have demonstrated much better performance than the standard collaborative filtering methods. However, most of network based algorithms do not give a high enough weight to the influence of the target user’s nearest neighbors in the resource diffusion process, while a user or an object with high degree will obtain larger influence in the standard mass diffusion algorithm. In this paper, we propose a novel preferential diffusion recommendation algorithm considering the significance of the target user’s nearest neighbors and evaluate it in the three real-world data sets: MovieLens 100k, MovieLens 1M, and Epinions. Experiments results demonstrate that the novel preferential diffusion recommendation algorithm based on user’s nearest neighbors can significantly improve the recommendation accuracy and diversity.
A Downmodulated MicroRNA Profiling in Patients with Gastric Cancer
Authors: Zhang Tao , Liu Chang , Huang Shi , Ma Yuanping , Fang Jiansong , Chen Yuanneng
Published: May 2017

Objective. Here, we aim to investigate the microRNA (miR) profiling in human gastric cancer (GC). Methods. Tumoral and matched peritumoral gastric specimens were collected from 12 GC patients who underwent routine surgery. A high-throughput miR sequencing method was applied to detect the aberrantly expressed miRs in a subset of 6 paired samples. The stem-loop quantitative real-time polymerase chain reaction (qRT-PCR) assay was subsequently performed to confirm the sequencing results in the remaining 6 paired samples. The profiling results were also validated in vitro in three human GC cell lines (BGC-823, MGC-803, and GTL-16) and a normal gastric epithelial cell line (GES-1). Results. The miR sequencing approach detected 5 differentially expressed miRs, hsa-miR-132-3p, hsa-miR-155-5p, hsa-miR-19b-3p, hsa-miR-204-5p, and hsa-miR-30a-3p, which were significantly downmodulated between the tumoral and peritumoral GC tissues. Most of the results were further confirmed by qRT-PCR, while no change was observed for hsa-miR-30a-3p. The in vitro finding also agreed with the results of both miR sequencing and qRT-PCR for hsa-miR-204-5p, hsa-miR-155-5p, and hsa-miR-132-3p. Conclusion. Together, our findings may serve to identify new molecular alterations as well as to enrich the miR profiling in human GC.
Sinonasal Characteristics in Patients with Obstructive Sleep Apnea Compared to Healthy Controls
Authors: Moxness Mads Henrik Strand , Bugten Vegard , Thorstensen Wenche Moe , Nordgård Ståle
Published: May 2017

Background. The difference in nasal obstruction between OSA patients and healthy individuals is not adequately documented. Our aim was to describe the sinonasal quality of life and nasal function in OSA patients and healthy controls using the sinonasal outcome test-20 (SNOT-20), nasal obstruction visual analog scale (NO-VAS), and peak nasal inspiratory flow (PNIF). Methodology and Principal. Ninety-three OSA patients and 92 controls were included in a case-control study from 2010 to 2015. Results. Mean SNOT-20 score in the OSA group was 1.69 (SD 0.84) compared to 0.55 (SD 0.69) in controls (p<0.001, 95% CI [0.9, 1.4]). The mean NO-VAS score was 41.3 (SD 12.8) and 14.7 (SD 14.4) in the OSA group and controls, respectively, (p<0.001, 95% CI [22.7, 30.6]). PNIF measured 105 litres/minute in the OSA group and 117 litres/minute in controls (p<0.01, 95% CI [−21.8, −3.71]). There was a positive correlation between subjective nasal obstruction and change in PNIF after decongestion in the control group alone. Conclusions. OSA patients have a reduced sinonasal QoL and lower peak nasal inspiratory flow compared to controls. Treatment of nasal obstruction in OSA patients should be made a priority along with treatment of the ailment itself.
New Caffeic Acid Phenylethyl Ester Analogs Bearing Substituted Triazole: Synthesis and Structure-Activity Relationship Study towards 5-Lipoxygenase Inhibition
Authors: Roy Pierre-Philipe , Faye Diene , Blanchard Sébastien , Cormier Marc , Doiron Jérémie A. , Surette Marc E. , Touaibia Mohamed
Published: May 2017

Leukotrienes are biosynthesized by the conversion of arachidonic acid by 5-Lipoxygenase and play a key role in many inflammatory disorders. Inspired by caffeic acid phenylethyl ester (CAPE) (2) and an analog carrying a triazole substituted by cinnamoyl and 5-LO inhibitors recently reported by our team, sixteen new CAPE analogs bearing substituted triazole were synthesized by copper catalyzed Huisgen 1,3-dipolar cycloaddition. Compound10e, an analog bearingp-CF3 phenethyl substituted triazole, was equivalent to CAPE (2) but clearly surpassed Zileuton (2), the only approved 5-LO inhibitor. Substitution of the phenethyl moiety by cyclohexylethyl, as with12g, clearly increased 5-LO inhibition which confirms the importance of hydrophobic interactions. Molecular docking revealed new hydrogen bonds andπ-πinteractions between the enzyme and some of the investigated compounds. Overall, this work highlights the relevance of exploring polyphenolic compounds as leukotrienes biosynthesis inhibitors.
Recent Advances of Curcumin in the Prevention and Treatment of Renal Fibrosis
Authors: Sun Xuejiao , Liu Yi , Li Cheng , Wang Xiting , Zhu Ruyuan , Liu Chenyue , Liu Haixia , Wang Lili , Ma Rufeng , Fu Min , Zhang Dongwei , Li Yu
Published: May 2017

Curcumin, a polyphenol derived from the turmeric, has received attention as a potential treatment for renal fibrosis primarily because it is a relatively safe and inexpensive compound that contributes to kidney health. Here, we review the literatures on the applications of curcumin in resolving renal fibrosis in animal models and summarize the mechanisms of curcumin and its analogs (C66 and (1E,4E)-1,5-bis(2-bromophenyl) penta-1,4-dien-3-one(B06)) in preventing inflammatory molecules release and reducing the deposition of extracellular matrix at the priming and activation stage of renal fibrosis in animal models by consulting PubMed and Cnki databases over the past 15 years. Curcumin exerts antifibrotic effect through reducing inflammation related factors (MCP-1, NF-κB, TNF-α, IL-1β, COX-2, and cav-1) and inducing the expression of anti-inflammation factors (HO-1, M6PRBP1, and NEDD4) as well as targeting TGF-β/Smads, MAPK/ERK, and PPAR-γ pathways in animal models. As a food derived compound, curcumin is becoming a promising drug candidate for improving renal health.
Experimental Research and Finite Element Analysis on Mechanical Property of SFRC T-Beam
Authors: Sun Min , Zhu Jiapeng , Li Ning , Fu C. C.
Published: May 2017

Research on mechanical property of SFRC was done through experiments of two SFRC T-beams and one concrete T-beam, while the influences of different volume fractions of steel fibers on integral rigidity, ultimate shear capacity, and the crack distribution characteristics were analyzed. ANSYS finite element software was used to simulate the tests and it was found that there was good conformation between the results of ANSYS simulation and tests. The test results and finite element software simulation both showed that the incorporation of steel fibers in the concrete can increase the integral rigidity and ultimate shear capacity, while partially reducing the propagation of cracks effectively. It was also proved that it is reliable to simulate SFRC T-beam by ANSYS software.
Improving Classification Performance through an Advanced Ensemble Based Heterogeneous Extreme Learning Machines
Authors: Abuassba Adnan O. M. , Zhang Dezheng , Luo Xiong , Shaheryar Ahmad , Ali Hazrat
Published: May 2017

Extreme Learning Machine (ELM) is a fast-learning algorithm for a single-hidden layer feedforward neural network (SLFN). It often has good generalization performance. However, there are chances that it might overfit the training data due to having more hidden nodes than needed. To address the generalization performance, we use a heterogeneous ensemble approach. We propose an Advanced ELM Ensemble (AELME) for classification, which includes Regularized-ELM, L2-norm-optimized ELM (ELML2), and Kernel-ELM. The ensemble is constructed by training a randomly chosen ELM classifier on a subset of training data selected through random resampling. The proposed AELM-Ensemble is evolved by employing an objective function of increasing diversity and accuracy among the final ensemble. Finally, the class label of unseen data is predicted using majority vote approach. Splitting the training data into subsets and incorporation of heterogeneous ELM classifiers result in higher prediction accuracy, better generalization, and a lower number of base classifiers, as compared to other models (Adaboost, Bagging, Dynamic ELM ensemble, data splitting ELM ensemble, and ELM ensemble). The validity of AELME is confirmed through classification on several real-world benchmark datasets.
Application of the Initial Rate Method in Anaerobic Digestion of Kitchen Waste
Authors: Feng Lei , Gao Yuan , Kou Wei , Lang Xianming , Liu Yiwei , Li Rundong , Yu Meiling , Shao Lijie , Wang Xiaoming
Published: May 2017

This article proposes a methane production approach through sequenced anaerobic digestion of kitchen waste, determines the hydrolysis constants and reaction orders at both low total solid (TS) concentrations and high TS concentrations using the initial rate method, and examines the population growth model and first-order hydrolysis model. The findings indicate that the first-order hydrolysis model better reflects the kinetic process of gas production. During the experiment, all the influential factors of anaerobic fermentation retained their optimal values. The hydrolysis constants and reaction orders at low TS concentrations are then employed to demonstrate that the first-order gas production model can describe the kinetics of the gas production process. At low TS concentrations, the hydrolysis constants and reaction orders demonstrated opposite trends, with both stabilizing after 24 days at 0.99 and 1.1252, respectively. At high TS concentrations, the hydrolysis constants and the reaction orders stabilized at 0.98 (after 18 days) and 0.3507 (after 14 days), respectively. Given sufficient reaction time, the hydrolysis involved in anaerobic fermentation of kitchen waste can be regarded as a first-order reaction in terms of reaction kinetics. This study serves as a good reference for future studies regarding the kinetics of anaerobic digestion of kitchen waste.
A Case of Urachal Carcinoma of the Abdominal Wall in a Kidney Transplant Recipient
Authors: Yamazaki Takuya , Nagaba Yasushi , Shimada Yoshitaka , Taoka Yoshinori , Minamida Satoru , Koguchi Dai , Hagiwara Masahiro , Watanuki Sho , Nagaba Hide , Yoshida Kazunari , Takeuchi Yasuo
Published: May 2017

Urachal carcinoma is an extremely rare malignant tumor arising from the urachus in the fetus. We report a patient who developed urachal carcinoma 18 years after kidney transplantation. A 59-year-old man was admitted because of abdominal pain and massive ascites. He had undergone kidney transplantation 18 years earlier and had end-stage renal disease requiring dialysis. Abdominal CT showed massive ascites and an abdominal wall cystic mass separated from the peritoneal cavity. Hemodialysis was started, and paralytic ileus was diagnosed and treated. His ileus symptoms improved temporarily, but he died of myocardial infarction. An autopsy was performed, which revealed cystadenocarcinoma in the abdominal wall mass, leading to a diagnosis of urachal carcinoma.
Preclinical and Clinical Studies Demonstrate That the Proprietary Herbal Extract DA‐5512 Effectively Stimulates Hair Growth and Promotes Hair Health
Authors: Yu Jae Young , Gupta Biki , Park Hyoung Geun , Son Miwon , Jun Joon-Ho , Yong Chul Soon , Kim Jeong Ah , Kim Jong Oh
Published: May 2017

The proprietary DA‐5512 formulation comprises six herbal extracts from traditional oriental plants historically associated with therapeutic and other applications related to hair. Here, we investigated the effects of DA‐5512 on the proliferation of human dermal papilla cells (hDPCs) in vitro and on hair growth in C57BL/6 mice and conducted a clinical study to evaluate the efficacy and safety of DA‐5512. DA‐5512 significantly enhanced the viability of hDPCs in a dose‐dependent manner (p < 0.05), and 100 ppm of DA‐5512 and 1 μM minoxidil (MXD) significantly increased the number of Ki‐67‐positive cells, compared with the control group (p < 0.05). MXD (3%) and DA‐5512 (1%, 5%) significantly stimulated hair growth and increased the number and length of hair follicles (HFs) versus the controls (each p < 0.05). The groups treated with DA‐5512 exhibited hair growth comparable to that induced by MXD. In clinical study, we detected a statistically significant increase in the efficacy of DA‐5512 after 16 weeks compared with the groups treated with placebo or 3% MXD (p < 0.05). In conclusion, DA‐5512 might promote hair growth and enhance hair health and can therefore be considered an effective option for treating hair loss.
Role of Adult Asthma Education in Improving Asthma Control and Reducing Emergency Room Utilization and Hospital Admissions in an Inner City Hospital
Authors: Mishra Rashmi , Kashif Muhammad , Venkatram Sindhaghatta , George Teresa , Luo Kristina , Diaz-Fuentes Gilda
Published: May 2017

Objective. Asthma education programs have been shown to decrease healthcare utilization and improve disease control and management. The purpose of our study was to evaluate the impact of an outpatient adult asthma education program in an inner city hospital caring for patients with low socioeconomic and educational status. Methods. An asthma education program was implemented in September 2014. Patients who received education from September 2014 to July 2015 were evaluated. Outcomes were compared for the same group of patients before and after education. Primary outcomes were emergency room (ER) visits and hospital admissions. Secondary outcomes were change in Asthma Control Test (ACT) score and number of pulmonary clinic visits. Results. Asthma education significantly decreased number of patients requiring ER visits and hospital admissions (p = 0.0005 and p = 0.0015, resp.). Asthma control as per ACT score ≥ 20 improved with education (p = 0.0001) with an increase in clinic visits (p = 0.0185). Conclusions. Our study suggests that implementation of a structured asthma education program in an inner city community hospital has a positive impact on reduction of ER visits and hospital admissions with improvement in asthma control. Institutional Review Board Clinical Study registration number is 01081507.
Haematological Malignancies in Systemic Sclerosis Patients: Case Reports and Review of the World Literature
Authors: Colaci M. , Giuggioli D. , Vacchi C. , Ferri C.
Published: May 2017

Background. The association of systemic sclerosis (SSc) and haematological cancers was reported in a large number of case reports and cohort studies, describing SSc patients with highly heterogeneous clinical pictures.Objective. We reviewed the literature to better describe SSc patients with haematological malignancies.Methods. SSc cases complicated by haematological malignancies described in the world literature were collected; other 2 cases referred to our centre were reported.Results. One hundred-thirty SSc subjects were collected from 1954 up to date. The mean age of patients at cancer diagnosis was 56.1 ± 16.7 years; 72% of patients were females. In 60% of cases, the diagnosis of haematological malignancy was described within 5 years of SSc diagnosis. In 7.8% of cases, coexistence of Sjögren’s syndrome or other autoimmune disorders was cited. Sixty-six cases with lymphoma (in the majority of cases B-cell neoplasms), 28 with leukaemia (chronic lymphocytic form in 9), 14 with multiple myeloma plus one solitary IgM plasmocytoma, and 16 with myeloproliferative disorders were found. No specific SSc subsets seem to be related to haematological malignancies.Conclusions. We remarked the importance of clinical work-up in SSc, in order to early diagnose and treat eventual occult haematological malignancies, especially during the first years of the disease.
Sulfate and Calcium Chloride Resistance of Steel/Glass Fiber-Reinforced Polymer Hybrid Panel for Improved Movable Weir Application
Authors: Lee S.-K. , Yoo S.-Y. , Park C.-G.
Published: May 2017

This study evaluated the performance of a hybrid panel that can overcome the current problem of corrosion of the steel panels of improved movable weirs when they are exposed to a sulfate and calcium chloride environment such as sea water. A hybrid panel with glass fiber-reinforced polymer (GFRP) layers on both sides of a steel panel means that the central panel is not exposed to the external elements, which can avoid corrosion problems. In this study, to maximize the hybrid panel’s strength and durability, the moisture absorption characteristics and the durability in an accelerated environment were evaluated. The test results were considered to indicate no durability issues as the final absorption ratio was approximately 2.0% or less in all environments. Also, from the accelerated deterioration test results when the steel panel processed by sand blasting was applied in all accelerated deterioration environments, it satisfied the residual strength level of 65% or more. However, in the case without surface processing, upon exposure to MgSO4 solution, it did not satisfy the standard residual strength level of 65%. These results show that sand blasting on the surface of a steel panel is adequate for hybrid panels for improved movable weirs.
Ensemble Learning for Short-Term Traffic Prediction Based on Gradient Boosting Machine
Authors: Yang Senyan , Wu Jianping , Du Yiman , He Yingqi , Chen Xu
Published: May 2017

Short-term traffic prediction is vital for intelligent traffic systems and influenced by neighboring traffic condition. Gradient boosting decision trees (GBDT), an ensemble learning method, is proposed to make short-term traffic prediction based on the traffic volume data collected by loop detectors on the freeway. Each new simple decision tree is sequentially added and trained with the error of the previous whole ensemble model at each iteration. The relative importance of variables can be quantified in the training process of GBDT, indicating the interaction between input variables and response. The influence of neighboring traffic condition on prediction performance is identified through combining the traffic volume data collected by different upstream and downstream detectors as the input, which can also improve prediction performance. The relative importance of input variables for 15 GBDT models is different, and the impact of upstream traffic condition is not balanced with that of downstream. The prediction accuracy of GBDT is generally higher than SVM and BPNN for different steps ahead, and the accuracy of multi-step-ahead models is lower than 1-step-ahead models. For 1-step-ahead models, the prediction errors of GBDT are smaller than SVM and BPNN for both peak and nonpeak hours.
The Impact of Different Lactic Acid Bacteria Sourdoughs on the Quality Characteristics of Toast Bread
Authors: Hadaegh H. , Seyyedain Ardabili S. M. , Tajabadi Ebrahimi M. , Chamani M. , Azizi Nezhad R.
Published: May 2017

The effect of sourdough inoculated with three novel single strains of lactic acid bacteria (LAB) (Lactobacillus casei jQ412732, Lactobacillus plantarum jQ301799, and Lactobacillus brevis IBRC-M10790) as well as mixed strains was evaluated on the quality characteristics of Toast bread. Antifungal properties of sourdoughs due to organic acid production were measured by HPLC, and storability was evaluated by thermal and textural analysis in days 1, 3, and 6. Despite the impact of sourdough concentration on microbial preservation, no significant effect was observed in the case of enthalpy reduction. Mixed LAB strains showed the best results in reducing the enthalpy and hardness of bread as well as better microbial preservation by producing the highest amount of organic acids, justified by sensory panelists. Among single strains, L. casei gave better results in reducing hardness and staling rate of bread. Scanning Electron Microscopy micrographs of bread also showed the differences.
Discovery and Characterization of Novel Nonsubstrate and Substrate NAMPT Inhibitors
Authors: Wilsbacher Julie L. , Cheng Min , Cheng Dong , Trammell Samuel A.J. , Shi Yan , Guo Jun , Koeniger Stormy L. , Kovar Peter J. , He Yupeng , Selvaraju Sujatha , Heyman H. Robin , Sorensen Bryan K. , Clark Richard F. , Hansen T. Matthew , Longenecker Kenton L. , Raich Diana , Korepanova Alla V. , Cepa Steven , Towne Danli L. , Abraham Vivek C. , Tang Hua , Richardson Paul L. , McLoughlin Shaun M. , Badagnani Ilaria , Curtin Michael L. , Michaelides Michael R. , Maag David , Buchanan F. Gregory , Chiang Gary G. , Gao Wenqing , Rosenberg Saul H. , Brenner Charles , Tse Chris
Published: May 2017

Cancer cells are highly reliant on NAD+-dependent processes, including glucose metabolism, calcium signaling, DNA repair, and regulation of gene expression. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme for NAD+ salvage from nicotinamide, has been investigated as a target for anticancer therapy. Known NAMPT inhibitors with potent cell activity are composed of a nitrogen-containing aromatic group, which is phosphoribosylated by the enzyme. Here, we identified two novel types of NAM-competitive NAMPT inhibitors, only one of which contains a modifiable, aromatic nitrogen that could be a phosphoribosyl acceptor. Both types of compound effectively deplete cellular NAD+, and subsequently ATP, and produce cell death when NAMPT is inhibited in cultured cells for more than 48 hours. Careful characterization of the kinetics of NAMPT inhibition in vivo allowed us to optimize dosing to produce sufficient NAD+ depletion over time that resulted in efficacy in an HCT116 xenograft model. Our data demonstrate that direct phosphoribosylation of competitive inhibitors by the NAMPT enzyme is not required for potent in vitro cellular activity or in vivo antitumor efficacy. Mol Cancer Ther; 16(7); 1236–45. ©2017 AACR.
RIG-I Resists Hypoxia-Induced Immunosuppression and Dedifferentiation
Authors: Engel Christina , Brügmann Grethe , Lambing Silke , Mühlenbeck Larissa H. , Marx Samira , Hagen Christian , Horváth Dorottya , Goldeck Marion , Ludwig Janos , Herzner Anna-Maria , Drijfhout Jan W. , Wenzel Daniela , Coch Christoph , Tüting Thomas , Schlee Martin , Hornung Veit , Hartmann Gunther , Van den Boorn Jasper G.
Published: May 2017

A hypoxic tumor microenvironment is linked to poor prognosis. It promotes tumor cell dedifferentiation and metastasis and desensitizes tumor cells to type-I IFN, chemotherapy, and irradiation. The cytoplasmic immunoreceptor retinoic acid-inducible gene-I (RIG-I) is ubiquitously expressed in tumor cells and upon activation by 5′-triphosphate RNA (3pRNA) drives the induction of type I IFN and immunogenic cell death. Here, we analyzed the impact of hypoxia on the expression of RIG-I in various human and murine tumor and nonmalignant cell types and further investigated its function in hypoxic murine melanoma. 3pRNA-inducible RIG-I–expression was reduced in hypoxic melanoma cells compared with normoxic controls, a phenomenon that depended on the hypoxia-associated transcription factor HIF1α. Still, RIG-I functionality was conserved in hypoxic melanoma cells, whereas responsiveness to recombinant type-I IFN was abolished, due to hypoxia-induced loss of type I IFN receptor expression. Likewise, RIG-I activation in hypoxic melanoma cells, but not exposure to recombinant IFNα, provoked melanocyte antigen-specific CD8+ T-cell and NK-cell attack. Scavenging of hypoxia-induced reactive oxygen species by vitamin C restored the inducible expression of RIG-I under hypoxia in vitro, boosted in vitro anti-melanoma NK- and CD8+ T-cell attack, and augmented 3pRNA antitumor efficacy in vivo. These results demonstrate that RIG-I remains operational under hypoxia and that RIG-I function is largely insensitive to lower cell surface expression of the IFNα receptor. RIG-I function could be fortified under hypoxia by the combined use of 3pRNA with antioxidants. Cancer Immunol Res; 5(6); 455–67. ©2017 AACR.
Tumor-Derived α-Fetoprotein Directly Drives Human Natural Killer–Cell Activation and Subsequent Cell Death
Authors: Vujanovic Lazar , Stahl Elizabeth C. , Pardee Angela D. , Geller David A. , Tsung Allan , Watkins Simon C. , Gibson Gregory A. , Storkus Walter J. , Butterfield Lisa H.
Published: May 2017

Hepatocellular carcinoma (HCC) patients with reduced natural killer (NK)–cell numbers and function have been shown to have a poor disease outcome. Mechanisms underlying NK-cell deficiency and dysfunction in HCC patients remain largely unresolved. α-Fetoprotein (AFP) is an oncofetal antigen produced by HCC. Previous studies demonstrated that tumor-derived AFP (tAFP) can indirectly impair NK-cell activity by suppressing dendritic cell function. However, a direct tAFP effect on NK cells remains unexplored. The purpose of this study was to examine the ability of cord blood-derived AFP (nAFP) and that of tAFP to directly modulate human NK-cell activity and longevity in vitro. Short-term exposure to tAFP and, especially, nAFP proteins induced a unique proinflammatory, IL2-hyperresponsive phenotype in NK cells as measured by IL1β, IL6, and TNF secretion, CD69 upregulation, and enhanced tumor cell killing. In contrast, extended coculture with tAFP, but not nAFP, negatively affected long-term NK-cell viability. NK-cell activation was directly mediated by the AFP protein itself, whereas their viability was affected by hydrophilic components within the low molecular mass cargo that copurified with tAFP. Identification of the distinct impact of circulating tAFP on NK-cell function and viability may be crucial to developing a strategy to ameliorate HCC patient NK-cell functional deficits. Cancer Immunol Res; 5(6); 493–502. ©2017 AACR.
Remote Ischaemic Preconditioning and Sevoflurane Postconditioning Synergistically Protect Rats from Myocardial Injury Induced by Ischemia and Reperfusion Partly via Inhibition TLR4/MyD88/NF-κB Signaling Pathway
Authors: Zhang Jiru , Zhang Jing , Yu Peng , Chen Min , Peng Qingfeng , Wang Zhiqiang , Dong Nan
Published: May 2017

Background/Aims: A combination sevoflurane postconditioning (SPC) and remote ischemic preconditioning (RIPC) is proved effective in an ex vivo rat heart perfusion model. However, the combined effect of those two interventions is not tested in rat myocardial ischemia/reperfusion (I/R) model, and the underlying mechanisms remain to be elucidated. This study aimed to investigate the effect in vivo using a rat myocardial I/R model and illuminate the related mechanisms. Methods: Forty male Sprague-Dawley rats were randomly divided into the following 5 groups: i) sham-operated control; ii) I/R; iii) I/R + RIPC; iv) I/R + SPC; v) I/R + RIPC + SPC. The hemodynamic parameters were recorded at the end of reperfusion. The histological changes including the infarct size were assessed using Triphenyltetrazolium chloride (TTC) staining and H&E staining. In addition, the circulating levels of cardiac enzymes (CK-MB, hs-cTnT, and cTnT) inflammatory cytokines (IL-6, IL-8, and TNF-α) were detected. The expression levels of apoptosis-related proteins (C-Caspase 3, PARP, Bax, and Bcl-2), proinflammatory factors (TLR4, HMGB-1, MyD88, and p65), and IKB-α were measured by Western blot analysis. Real-time PCR was performed to detect mRNA levels of the proinflammatory factors. Results: Both SPC and RIPC significantly reduced the infarct size, cardiac enzyme release, inflammatory cytokine secretion, and proinflammatory factor expression, and increased IKB-α expression compared to I/R group. Furthermore, the combination of those two strategies had synergic infarct size limiting and anti-inflammatory effects. Conclusions: The finding of this study suggested that the combination of SPC and RIPC had a potentially cardioprotective effect through inhibiting TLR4/MyD88/NF-κB signaling.
Next-Generation Sequencing Reveals a Nonsense Mutation (p.Arg364Ter) in MRE11A Gene in an Indian Patient with Familial Breast Cancer
Authors: Sharma Bhai Pratibha , Sharma Deepak , Saxena Renu , Verma Ishwar C.
Published: May 2017

Background: The MRN complex consisting of MRE11A-RAD50-NBS1 proteins is involved in the repair of double-strand breaks, and mutations in genes coding for the MRN complex have been identified in families with breast and ovarian cancer. Case Report: In a BRCA-negative family with positive history of breast and endometrial cancer, next-generation sequencing-based panel testing identified a mutation in the MRE11A gene (NM_005590 c.1090C>T: p.Arg364Ter). This mutation results in a shorter mutated protein lacking 2 DNA binding domains (the GAR domain and the RAD50 binding site), abolishing the function of protein. Conclusion: This case provides insight into the role of the MRE11A gene in causing breast cancer susceptibility in families, and supports the use of multigene panel testing in cases with hereditary predisposition to breast cancer.
Occult Hepatitis Infection in Transfusion Medicine: Screening Policy and Assessment of Current Use of Anti-HBc Testing
Authors: Esposito Antonella , Sabia Chiara , Iannone Carmela , Nicoletti Giovanni F. , Sommese Linda , Napoli Claudio
Published: May 2017

HBV still represents a global risk factor in transfusion medicine. The residual risk of HBV is not limited to pre-seroconversion window period but it extends to donors with occult HBV infection (OBI) characterized by the presence of HBV DNA in liver and by the absence of the virus surface antigen. Each country developed an appropriate blood screening policy according to local HBV prevalence, yields of infectious units per different screening methods and cost-effectiveness. We underline the need of maintaining a high level of attention for OBI carrier identification in all blood banks worldwide where the screening procedures are generally based on a combination of both serological markers and nucleic acid amplification test. In this context, markers such as hepatitis B surface antibodies and hepatitis B core antibodies (anti-HBc) might be useful, although the use of this latter is highly debated and still controversial. Our aim is to give an overview on the relevant diagnostic approaches for the routine screening for HBV focusing on the feasibility of anti-HBc testing as precautionary measure in preventing OBI transmission worldwide. In our tailored algorithm, the loss of about 1% of ‘anti-HBc only' donors, does not significantly affect the blood supply while improving recipient safety.
Clinical Features and Treatment Outcome of Malignant Pleural Mesothelioma
Authors: Mencoboni Manlio , Filiberti Rosa A. , Taveggia Paola , Grosso Federica , Pasello Giulia , Del Corso Lisette , Muzio Alberto , Polo Valentina , Zucali Paolo , Ceresoli Giovanni L. , Soto Parra Hector J. , Auriati Laura , Simonassi Claudio
Published: May 2017

Background: Malignant pleural mesothelioma is a problematic condition due to poor prognosis and difficulties in management. We evaluated the treatment and outcome of 378 mesothelioma patients referred to 6 Italian Oncology Departments. Methods: Demographic and clinical data were collected. Treatment was assessed in terms of chemotherapy (line of treatment, pemetrexed-based regimen, other therapies), surgery, and radiotherapy. Response to therapy, progression-free survival, and overall survival were evaluated. Results: 36 and 342 patients received best supportive care and active treatment, respectively; 86 patients underwent surgery, and 26 received trimodal therapy. Disease control after first-line chemotherapy was achieved in 74.2% of patients (75.7% in patients treated with pemetrexed combined with other drugs and 69% with pemetrexed as monotherapy). The disease control rate was 82.6% in pemetrexed re-challenged individuals. Median survival time was 11.6 months with supportive care, 16.2 months with chemotherapy only, 32.4 months with surgery plus chemotherapy, and 47.2 months with trimodal therapy. A more favorable prognosis was observed in responders to first-line therapy who were then actively treated with second-line (24.8 vs. 11.8 months in non-responders, p < 0.001) and third-line chemotherapy (28.9 vs. 17.8 months in non-responders, p = 0.005). Conclusion: Mesothelioma patients benefited from chemotherapy alone only when retreated in the second line after response to first-line therapy.
Developmental Changes in Expression of GABAA Receptor Subunits α1, α2, and α3 in the Pig Brain
Authors: Miller Stephanie M. , Kalanjati Viskasari P. , Colditz Paul B. , Björkman Stella Tracey
Published: May 2017

GABA is a major neurotransmitter in the mammalian brain. In the mature brain GABA exerts inhibitory actions via the GABAA receptor (GABAAR); however, in the immature brain GABA provides much of the excitatory drive. We examined the expression of 3 predominant GABAA α-subunit proteins in the pig brain at various pre- and postnatal ages. Brain tissue was collected from piglets born via caesarean section at preterm ages 91, 97, 100, and 104 days' gestational age (GA), at term equivalent (114 days' GA, caesarean section) and at term, postnatal day 0 (P0) (spontaneous delivery, term = 115 days). Tissue was obtained from piglets at P4 and P7. Adult tissue from sows was collected postmortem after caesarean section. In all cortical regions and basal ganglia (1) α3 exhibited a significant increase in protein expression at 100 days' GA, (2) α3 expression decreased with age after 100 days' GA, (3) α1 increased with age, with peak expression at P7 in cortices, hippocampus, and thalamus, and (4) α2 protein expression remained relatively constant across the ages examined. The subunit expression of α3 was most abundant at preterm ages, with α1 the predominant subunit expressed postnatally. Immunofluorescent labelling revealed α1 expression on the somatic membranes of pyramidal cells in the cortex and hippocampus, and in the cerebellar Purkinje cells. Positive α3 labelling was apparent on interneurones in the cortex and hippocampus. The switch between dominant α-subunits may coincide with the functional change in GABAergic neurotransmission from excitation to inhibition. Brain growth in the pig closely reflects that in the term human, making the pig a valuable non-primate model for studying development and the effects of insults on the perinatal brain.
Significance of Tumor-Infiltrating Lymphocytes and the Expression of Topoisomerase IIα in the Prediction of the Clinical Outcome of Patients with Triple-Negative Breast Cancer after Taxane-Anthracycline-Based Neoadjuvant Chemotherapy
Authors: Rao Nanyan , Qiu Jiayin , Wu Jiannan , Zeng Hong , Su Fengxi , Qiu Kaifeng , Wu Junyan , Yao Herui
Published: May 2017

Purpose: The aim of this study was to determine factors able to predict chemotherapeutic responses and clinical outcomes in patients with triple-negative breast cancer (TNBC) after neoadjuvant chemotherapy (NAC). Methods: Fifty-two TNBC patients on taxane-anthracycline-based NAC were included. The expression of Ki67, topoisomerase IIα (TOPOIIα), and p53, as well as the presence of CD4+ tumor-infiltrating lymphocytes (TILs) and CD8+ TILs were evaluated in biopsy specimens by immunohistochemistry. The expression of Ki67, TOPOIIα, and p53, as well as CD4 and CD8 in TILs was calculated according to the pathological response to NAC, disease-free survival (DFS), and overall survival (OS). Results: Fourteen (26.9%) TNBC patients demonstrated a pathological complete response (pCR). According to univariate analyses, significant factors associated with pCR were high infiltration of CD4+ TILs (p = 0.004), high infiltration of CD8+ TILs (p = 0.010), and high expression of topoisomerase IIα (TOPOIIα) (p = 0.006). CD4+ TILs and TOPOIIα were significantly positively correlated with CD8+ TILs. Multivariate analyses indicated that TOPOIIα was an independent predictor of pCR. Although TNBC patients with high infiltration of CD4+ TILs, CD8+ TILs, or with high expression of TOPOIIα exhibited a significantly good 5-year DFS, only TNBC patients with a high infiltration of CD8+ TILs exhibited significantly positive 5-year OS probabilities. Conclusion: Our study demonstrated that CD4+ TILs and TOPOIIα in pretreated cancer tissues were significantly correlated with CD8+ TILs. CD4+ TILs, CD8+ TILs, and TOPOIIα expression were predictors of pCR and 5-year DFS of TNBC patients who were treated with NAC, and TOPOIIα was an independent predictor of pCR. CD8+ TILs were a key factor in the prediction of good 5-year OS rates of TNBC patients after taxane-anthracycline-based NAC.