bluuebunny/crossref_metadata_2025 huggingface dataset:
Microbiota-Based Therapies for Clostridium difficile and Antibiotic-Resistant Enteric Infections
Authors: Lewis Brittany B. , Pamer Eric G.
Published: June 2017

Bacterial pathogens are increasingly antibiotic resistant, and development of clinically effective antibiotics is lagging. Curing infections increasingly requires antimicrobials that are broader spectrum, more toxic, and more expensive, and mortality attributable to antibiotic-resistant pathogens is rising. The commensal microbiota, comprising microbes that colonize the mammalian gastrointestinal tract, can provide high levels of resistance to infection, and the contributions of specific bacterial species to resistance are being discovered and characterized. Microbiota-mediated mechanisms of colonization resistance and pathogen clearance include bactericidal activity, nutrient depletion, immune activation, and manipulation of the gut's chemical environment. Current research is focusing on development of microbiota-based therapies to reduce intestinal colonization with antibiotic-resistant pathogens, with the goal of reducing pathogen transmission and systemic dissemination.
Function, Discovery, and Exploitation of Plant Pattern Recognition Receptors for Broad-Spectrum Disease Resistance
Authors: Boutrot Freddy , Zipfel Cyril
Published: June 2017

Plants are constantly exposed to would-be pathogens and pests, and thus have a sophisticated immune system to ward off these threats, which otherwise can have devastating ecological and economic consequences on ecosystems and agriculture. Plants employ receptor kinases (RKs) and receptor-like proteins (RLPs) as pattern recognition receptors (PRRs) to monitor their apoplastic environment and detect non-self and damaged-self patterns as signs of potential danger. Plant PRRs contribute to both basal and non-host resistances, and treatment with pathogen-/microbe-associated molecular patterns (PAMPs/MAMPs) or damage-associated molecular patterns (DAMPs) recognized by plant PRRs induces both local and systemic immunity. Here, we comprehensively review known PAMPs/DAMPs recognized by plants as well as the plant PRRs described to date. In particular, we describe the different methods that can be used to identify PAMPs/DAMPs and PRRs. Finally, we emphasize the emerging biotechnological potential use of PRRs to improve broad-spectrum, and potentially durable, disease resistance in crops.
Consumption of a high-iron diet disrupts homeostatic regulation of intestinal copper absorption in adolescent mice
Authors: Ha Jung-Heun , Doguer Caglar , Collins James F.
Published: June 2017

High-iron feeding of rodents has been commonly used to model human iron-overload disorders. We recently noted that high-iron consumption impaired growth and caused severe systemic copper deficiency in growing rats, but the mechanism by which this occurred could not be determined due to technical limitations. In the current investigation, we thus utilized mice; first to determine if the same phenomenon occurred in another mammalian species, and second since we could assess in vivo copper absorption in mice. We hypothesized that excessive dietary iron impaired intestinal copper absorption. Weanling, male mice were thus fed AIN-93G-based diets containing high (HFe) (~8,800 ppm) or adequate (AdFe) (~80 ppm) iron in combination with low (~0.9 ppm), adequate (~9 ppm), or high (~180 ppm) copper for several weeks. Iron and copper homeostasis was subsequently assessed. Mice consuming the HFe diets grew slower, were anemic, and had lower hepatic copper levels and serum ceruloplasmin activity. These physiological perturbations were all prevented by higher dietary copper, demonstrating that copper depletion was the underlying cause. Furthermore, homeostatic regulation of copper absorption was noted in the mice consuming the AdFe diets, with absorption increasing as dietary copper decreased. HFe-fed mice did not have impaired copper absorption (disproving our hypothesis), but homeostatic control of absorption was disrupted. There were also noted perturbations in the tissue distribution of copper in the HFe-fed mice, suggesting that altered storage and thus bioavailability contributed to the noted copper deficiency. Dietary iron loading thus antagonizes copper homeostasis leading to pathological symptoms of severe copper depletion.

NEW & NOTEWORTHY High-iron feeding is a common experimental method to model human iron-overload disorders in rodents. Here, we show that dietary iron loading causes severe copper deficiency due to perturbations in the homeostatic regulation of intestinal copper absorption and tissue distribution, which may decrease the bioavailability of copper for use in cuproenzyme synthesis. Whether high-dose iron supplementation in humans antagonizes copper homeostasis is worthy of consideration.
Impaired TNF/TNFR2 signaling enhances Th2 and Th17 polarization and aggravates allergic airway inflammation
Authors: Li Xiao-Ming , Chen Xi , Gu Wen , Guo Yi-Jia , Cheng Yi , Peng Juan , Guo Xue-Jun
Published: June 2017

CD4+ T-cell differentiation plays an important role in allergic airway diseases. Tumor necrosis factor receptor 2 (TNFR2) has been shown to regulate CD4+ T-lymphocyte differentiation, but its role in allergic airway inflammation is not clear. Here, we investigated the role of TNFR2 in allergic airway inflammation. The mouse model was generated by immunization with ovalbumin and intranasal administration of TNFR2 antibody. Airway inflammation and CD4+ T-cell differentiation were measured in vivo and in vitro. Inhibited TNFR2 signaling aggravated airway inflammation and increased the expression of inflammatory cytokines (IL-4, IL-5, IL-17, and TNF-α) in serum and bronchoalveolar lavage fluid. Impaired TNFR2 signaling promoted Th2 and Th17 polarization but inhibited Th1 and CD4+CD25+ T-cell differentiation in vivo. Furthermore, TNFR2 signaling inhibition promoted Th2 and Th17 polarization in vitro, which may occur through the activation of TNF receptor-associated factor 2 and NF-κB signaling. Therefore, our findings indicate that impaired TNF/TNFR2 signaling enhances Th2 and Th17 polarization and aggravates allergic airway inflammation.
Src family kinases in chronic kidney disease
Authors: Wang Jun , Zhuang Shougang
Published: June 2017

Src family kinases (SFKs) belong to nonreceptor protein tyrosine kinases and have been implicated in the regulation of numerous cellular processes, including cell proliferation, differentiation, migration and invasion, and angiogenesis. The role and mechanisms of SFKs in tumorgenesis have been extensively investigated, and some SFK inhibitors are currently under clinical trials for tumor treatment. Recent studies have also demonstrated the importance of SFKs in regulating the development of various fibrosis-related chronic diseases (e.g., idiopathic pulmonary fibrosis, liver fibrosis, renal fibrosis, and systemic sclerosis). In this article, we summarize the roles of SFKs in various chronic kidney diseases, including glomerulonephritis, diabetic nephropathy, human immunodeficiency virus-associated nephropathy, autosomal dominant form of polycystic kidney disease, and obesity-associated kidney disease, and discuss the mechanisms involved.
Lithium-induced NDI: acetazolamide reduces polyuria but does not improve urine concentrating ability
Authors: de Groot Theun , Doornebal Joan , Christensen Birgitte M. , Cockx Simone , Sinke Anne P. , Baumgarten Ruben , Bedford Jennifer J. , Walker Robert J. , Wetzels Jack F. M. , Deen Peter M. T.
Published: June 2017

Lithium is the mainstay treatment for patients with bipolar disorder, but it generally causes nephrogenic diabetes insipidus (NDI), a disorder in which the renal urine concentrating ability has become vasopressin insensitive. Li-NDI is caused by lithium uptake by collecting duct principal cells and downregulation of aquaporin-2 (AQP2) water channels, which are essential for water uptake from tubular urine. Recently, we found that the prophylactic administration of acetazolamide to mice effectively attenuated Li-NDI. To evaluate whether acetazolamide might benefit lithium-treated patients, we administered acetazolamide to mice with established Li-NDI and six patients with a lithium-induced urinary concentrating defect. In mice, acetazolamide partially reversed lithium-induced polyuria and increased urine osmolality, which, however, did not coincide with increased AQP2 abundances. In patients, acetazolamide led to the withdrawal of two patients from the study due to side effects. In the four remaining patients acetazolamide did not lead to clinically relevant changes in maximal urine osmolality. Urine output was also not affected, although none of these patients demonstrated overt lithium-induced polyuria. In three out of four patients, acetazolamide treatment increased serum creatinine levels, indicating a decreased glomerular filtration rate (GFR). Strikingly, these three patients also showed a decrease in systemic blood pressure. All together, our data reveal that acetazolamide does not improve the urinary concentrating defect caused by lithium, but it lowers the GFR, likely explaining the reduced urine output in our mice and in a recently reported patient with lithium-induced polyuria. The reduced GFR in patients prone to chronic kidney disease development, however, warrants against application of acetazolamide in Li-NDI patients without long-term (pre)clinical studies.
An assessment of the autonomic nervous system in the electrohypersensitive population: a heart rate variability and skin conductance study
Authors: Andrianome Soafara , Gobert Jonathan , Hugueville Laurent , Stéphan-Blanchard Erwan , Telliez Frederic , Selmaoui Brahim
Published: June 2017

The aim of the study was twofold: first, to compare the activity of the autonomic nervous system (ANS) between the population self-declared as electrohypersensitive (EHS) and their matched control individuals without intended exposure to electromagnetic fields (EMF). The second objective was to determine whether acute exposure to different radiofrequency signals modifies ANS activity in EHS. For that purpose, two different experiments were undertaken, in which ANS activity was assessed through heart rate variability (HRV) and skin conductance (SC). In the first experiment, a comparison between the EHS group ( n = 30) and the control group ( n = 25) showed that the EHS has an increased number of responses to auditory stimuli as measured by skin conductance activity, and that none of the short-term heart rate variability parameters differ between the two matched study groups. The second experiment, performed in a shielded chamber, involved 10 EHS from the first experiment. The volunteers participated in two different sessions (sham and exposure). The participants were consecutively exposed to four EMF signals (GSM 900, GSM 1800, DECT, and Wi-Fi) at environmental level (1 V/m). The experiment was double blinded and counterbalanced. The HRV variables studied did not differ between the two sessions. Concerning electrodermal activity, the data issued from skin conductance and tonic activity did not differ between the sessions, but showed a time variability. In conclusion, the HRV and SC profiles did not significantly differ between the EHS and control populations under no exposure. Exposure did not have an effect on the ANS parameters we have explored.

NEW & NOTEWORTHY This study provided analysis on the skin conductance parameters using a newly developed method (peak/min, extraction of skin conductance responses) that had not been performed previously. Additionally, the skin conductance signal was decomposed, considering tonic and phasic activities to be a distinct compound. Moreover, this is the first time a study has been designed into two steps to understand whether the autonomic nervous system is disturbed in the EHS population.
Low-Density Lipoprotein Receptor-Related Proteins in Skeletal Development and Disease
Authors: Yang Tao , Williams Bart O.
Published: June 2017

The identification of the low-density lipoprotein receptor (LDLR) provided a foundation for subsequent studies in lipoprotein metabolism, receptor-mediated endocytosis, and many other fundamental biological functions. The importance of the LDLR led to numerous studies that identified homologous molecules and ultimately resulted in the description of the LDL-receptor superfamily, a group of proteins that contain domains also found in the LDLR. Subsequent studies have revealed that members of the LDLR-related protein family play roles in regulating many aspects of signal transduction. This review is focused on the roles of selected members of this protein family in skeletal development and disease. We present background on the identification of this subgroup of receptors, discuss the phenotypes associated with alterations in their function in human patients and mouse models, and describe the current efforts to therapeutically target these proteins to treat human skeletal disease.
Upper Limb Rehabilitation Robot Powered by PAMs Cooperates with FES Arrays to Realize Reach-to-Grasp Trainings
Authors: Tu Xikai , Han Hualin , Huang Jian , Li Jian , Su Chen , Jiang Xiaobo , He Jiping
Published: June 2017

The reach-to-grasp activities play an important role in our daily lives. The developed RUPERT for stroke patients with high stiffness in arm flexor muscles is a low-cost lightweight portable exoskeleton rehabilitation robot whose joints are unidirectionally actuated by pneumatic artificial muscles (PAMs). In order to expand the useful range of RUPERT especially for patients with flaccid paralysis, functional electrical stimulation (FES) is taken to activate paralyzed arm muscles. As both the exoskeleton robot driven by PAMs and the neuromuscular skeletal system under FES possess the highly nonlinear and time-varying characteristics, iterative learning control (ILC) is studied and is taken to control this newly designed hybrid rehabilitation system for reaching trainings. Hand function rehabilitation refers to grasping. Because of tiny finger muscles, grasping and releasing are realized by FES array electrodes and matrix scan method. By using the surface electromyography (EMG) technique, the subject’s active intent is identified. The upper limb rehabilitation robot powered by PAMs cooperates with FES arrays to realize active reach-to-grasp trainings, which was verified through experiments.
Design and Implementation of a Cloud-Based Platform for Unleashing the Personal and Communal Internet of Things
Authors: Elicegui Ignacio , López Carmen , Sánchez Luis , Lanza Jorge , Muñoz Luis , Pintus Antonio , Manchinu Andrea , Serra Alberto
Published: June 2017

Internet of Things (IoT) concept has attracted a lot of attention in recent years and it is foreseen as one of the technologies that will leverage the Future Internet. It is seen as a major enabler of novel applications and services that will foster efficiency and will ease every day’s life. However, current IoT solutions are mainly focusing on the development of centralized solutions that do not promote the democratization of the IoT but rather concentrate the IoT around a set of cloud-based platforms which pretend to be open but limit the capacity of the people to tailor their Personal and Communal IoT. This paper describes a software platform based on available generic enablers as defined by the FIWARE initiative. It extends the existing architecture models to accommodate the requirements stemming from the vision of people-sourced IoT devices which are shared to create applications and services in smart communities where the owners of the shared devices are always empowered to control who, and in which circumstances, has access to the shared information.
Synthesis and Experimental Validation of New PDI Inhibitors with Antiproliferative Activity
Authors: Badolato Mariateresa , Carullo Gabriele , Aiello Francesca , Garofalo Antonio
Published: June 2017

Protein disulfide isomerase (PDI) is a member of the thioredoxin superfamily of redox enzymes. PDI is a multifunctional protein that catalyzes disulfide bond formation, cleavage, and rearrangement in unfolded or misfolded proteins and functions as a chaperone in the endoplasmic reticulum. Besides acting as a protein folding catalyst, several evidences have suggested that PDI can bind small molecules containing, for example, a phenolic structure, which includes the estrogenic one. Increasing studies indicate that PDI is involved in both physiology and pathophysiology of cells and tissues and is involved in the survival and proliferation of different cancers. Propionic acid carbamoyl methyl amides (PACMAs) showed anticancer activity in human ovarian cancer, both in vitro and in vivo, by inhibiting PDI. The inhibition of PDI’s activity may have a therapeutic role, in various diseases, including cancer. In the present study, we designed and synthesized a diversified small library of compounds with the aim of identifying a new class of PDI inhibitors. Most of synthesized compounds showed a good inhibitory potency against PDI and particularly 4-methyl substituted 2,6-di-tert-butylphenol derivatives (8–10) presented an antiproliferative activity in a wide panel of human cancer cell lines, including ovarian ones.
Diagnostic MicroRNA Biomarker Discovery for Non-Small-Cell Lung Cancer Adenocarcinoma by Integrative Bioinformatics Analysis
Authors: Shao Yang , Liang Bin , Long Fei , Jiang Shu-Juan
Published: June 2017

Lung cancer is the leading cause of cancer death and its incidence is ranked high in men and women worldwide. Non-small-cell lung cancer (NSCLC) adenocarcinoma is one of the most frequent histological subtypes of lung cancer. The aberration profile and the molecular mechanism driving its progression are the key for precision therapy of lung cancer, while the screening of biomarkers is essential to the precision early diagnosis and treatment of the cancer. In this work, we applied a bioinformatics method to analyze the dysregulated interaction network of microRNA-mRNA in NSCLC, based on both the gene expression data and the microRNA-gene regulation network. Considering the properties of the substructure and their biological functions, we identified the putative diagnostic biomarker microRNAs, some of which have been reported on the PubMed citations while the rest, that is, miR-204-5p, miR-567, miR-454-3p, miR-338-3p, and miR-139-5p, were predicted as the putative novel microRNA biomarker for the diagnosis of NSCLC adenocarcinoma. They were further validated by functional enrichment analysis of their target genes. These findings deserve further experimental validations for future clinical application.
Investigating Visible-Photocatalytic Activity of MoS2/TiO2 Heterostructure Thin Films at Various MoS2 Deposition Times
Authors: Phung Hang Nguyen Thai , Tran Van Nguyen Khanh , Nguyen Lam Thanh , Phan Loan Kieu Thi , Duong Phuong Ai , Le Hung Vu Tuan
Published: June 2017

MoS2/TiO2 heterostructure thin films were fabricated by sol-gel and chemical bath deposition methods. Crystal structure, surface morphology, chemical states of all elements, and optical property of the obtained thin films were characterized by using X-ray diffraction, scanning electron microscopy, X-ray photoelectron spectroscopy, and UV-Vis spectroscopy techniques, respectively. Photocatalytic activity of all thin films was evaluated by measuring decomposition rate of methylene blue solution under visible light irradiation. The results indicate that ultrathin MoS2 film on TiO2-glass substrate improves photocatalytic activity of TiO2 in the visible light due to the efficient absorption of visible photon of MoS2 few layers and the transfer of electrons from MoS2 to TiO2. All MoS2/TiO2 heterostructure thin films exhibit higher visible light photocatalytic activity than that of pure MoS2 and TiO2 counterparts. The best MoS2/TiO2 heterostructure thin film at MoS2 layer deposition time of 45 minutes can decompose about 60% MB solution after 150 minutes under visible light irradiation. The mechanism of the enhancement for visible-photocatalytic activity of MoS2/TiO2 heterostructure thin film was also discussed.
Optimisation of Scanning Difference Pattern and Monopulse Feed
Authors: Khan Asim Ali , Brown Anthony Keith
Published: June 2017

Certain radar applications may require maintaining the difference pattern slope and twin beam shape, while main null is scanning in the presence of mutual coupling. It is also desirable in monopulse radar applications to be able to generate acceptable sum and difference patterns using single simplified feed structure. This paper focuses on these problems and provides a solution based on Intelligent z-Plane Boundary Condition-Particle Swarm Optimiser (IzBC-PSO) to compensate for the difference pattern degradation while scanning a small coupled array (N=8). In second case, a simplified feed is proposed that only requires phase flip for 50% of elements to produce sum and difference patterns for the monopulse array, consisting of isotropic elements.
Dynamics and Stability of Permanent‐Magnet Synchronous Motor
Authors: He Ren , Han Qingzhen
Published: June 2017

The aim of this article is to explore the dynamic characteristics and stability of the permanent‐magnet synchronous motor (PMSM). PMSM equilibrium local stability condition and Hopf  bifurcation condition, pitchfork bifurcation condition, and fold bifurcation condition have been derived by using the Routh‐Hurwitz criterion and the bifurcation theory, respectively. Bifurcation curves of the equilibrium with single and double parameters are obtained by continuation method. Numerical simulations not only confirm the theoretical analysis results but also show one kind of codimension‐two‐bifurcation points of the equilibrium. PMSM, with or without external load, can exhibit rich dynamic behaviors in different parameters regions. It is shown that if unstable equilibrium appears in the parameters regions, the PMSM may not be able to work stably. To ensure the PMSMs work stably, the inherent parameters should be designed in the region which has only one stable equilibrium.
Characteristics and Clinical Outcomes in Overhead Sports Athletes after Rotator Cuff Repair
Authors: Muto Tomoyuki , Inui Hiroaki , Ninomiya Hiroki , Tanaka Hiroshi , Nobuhara Katsuya
Published: June 2017

Rotator cuff tears in young overhead sports athletes are rare. The pathomechanism causing rotator cuff tears in young overhead athletes is different from that in aged patients. The purpose of this study was to investigate rotator cuff tear characteristics in young overhead sports athletes to reveal the pathomechanism causing these injuries. This study included 25 overhead sports athletes less than 30 years old with atraumatic rotator cuff tears necessitating repair. Rotator cuff tear characteristics were evaluated intraoperatively, including rotator cuff tear shape and injured rotator cuff tendon. Clinical outcome measures were assessed before surgery and at the final follow-up. In this study, 22 patients reported minimal to no shoulder pain and returned to sports without significant complaints at last follow-up. The isolated infraspinatus tendon was most often injured; the incidence rate of the tear at this site was 32% (8 cases). In the deceleration phase of overhead motion, the eccentric contraction force of the ISP (infraspinatus) tendon peaks and the increased load leads to injury at the ISP tendon. The pathomechanism of rotator cuff injuries in young overhead athletes might be not only internal or subacromial impingement, but also these mechanisms.
An Efficient K2CO3-Promoted Synthesis of 1-Bromo-2-aryloxyethane Derivatives and Evaluation of Larval Mortality against Aedes aegypti
Authors: Pájaro Yina , Sathicq Ángel , Puello-Polo Esneyder , Pérez Astrid , Romanelli Gustavo , Trilleras Jorge
Published: June 2017

The influences of reaction parameters on the etherification of phenols to obtain 1-bromo-2-aryloxyethane derivatives were evaluated. The compounds were prepared by direct etherification of phenols with 1,2-dibromoethane using anhydrous K2CO3 and acetonitrile as solvent reaction, at 80°C, in a reaction time of 6 h. Under these conditions, excellent yields (71%–94%) were obtained, with low yields of secondary products. The anhydrous K2CO3 was recycled by simple filtration, dried in vacuum, and reused. The compounds were characterized by conventional spectral data (MS and NMR). Larvicidal activity results showed a 100% larval mortality after 24-hour exposure to the compound 1-(2-bromoethoxy)-2-phenylbenzene.
Marker-Negative Pheochromocytoma Associated with Inferior Vena Cava Thrombosis
Authors: Poudyal S. , Pradhan M. , Chapagain S. , Luitel B. R. , Chalise P. R. , Sharma U. K. , Gyawali P. R.
Published: June 2017

Pheochromocytoma associated with inferior vena cava (IVC) thrombosis is very rare. A 27-year-old female presented with right flank pain and hypertensive urgency. Contrast-enhanced CT abdomen and gadolinium-contrast MRI abdomen revealed right adrenal mass suspicious of malignancy with invasion and compression to the right IVC wall along with IVC thrombus extending from the level of renal veins to the level of confluence with hepatic veins. Her routine laboratory investigations including 24-hour urine fractionated metanephrines, vanillylmandelic acid, and cortisol were normal. Right adrenalectomy with IVC thrombectomy was done. Perioperative period was uneventful. Histopathology of the mass turned out to be pheochromocytoma with thrombus revealing fibroadipose tissue with fibrin. Pheochromocytoma may present with IVC thrombus as well as normal serum and urinary markers. Thus, clinical suspicion is imperative in perioperative management of adrenal mass.
Prevalence and Risk Factors of Mortality among Adult HIV Patients Initiating ART in Rural Setting of HIV Care and Treatment Services in North Western Tanzania: A Retrospective Cohort Study
Authors: Gunda Daniel Wilfred , Nkandala Igembe , Kilonzo Semvua Bukheti , Kilangi Boniface Bartholomew , Mpondo Bonaventura Cornel
Published: June 2017

Introduction. HIV still causes high mortality despite use of ART. This study was designed to determine the prevalence and risk factors of mortality among HIV patients receiving ART in northwestern rural Tanzania. Methods. A retrospective study of HIV patients on ART was done at Sengerema in Mwanza, Tanzania. The data on demography, date of HIV diagnosis, WHO stage, opportunistic infections, CD4, hemoglobin, ART regimen, and time and outcome on treatment as dead or alive were collected and analyzed using STATA version 11. Results. In total, 740 patients were studied. The median age was 35 (27–42) years with female predominance of 465 (62.8%). Of the participants, 261 (35.3%) had WHO stages 3 and 4 diseases. Most participants, 258 (34.9%), had baseline CD4 counts <200 cells/μl. Deaths occurred in 86 (11.6%) patients which were independently associated with male gender (16.0% versus 9.0%, p=0.015), being divorced (OR = 2.7, p<0.001), WHO stages 3 and 4 (OR = 2.3, p=0.05), CD4 <200 cells/μl (OR = 3.4, p<0.001), and severe anemia (OR = 6.6, p<0.001). Conclusions. The mortality is high among HIV patients receiving ART in northwestern rural Tanzania. Universal testing could increase early diagnosis and treatment. A close follow-up of at-risk patients within the first year of ART could reduce the mortality of this subgroup of patients.
Optimal Piezoelectric Actuators and Sensors Configuration for Vibration Suppression of Aircraft Framework Using Particle Swarm Algorithm
Authors: Huang Quanzhen , Chen Suxia , Pu Huayan , Zhang Ning
Published: June 2017

Numbers and locations of sensors and actuators play an important role in cost and control performance for active vibration control system of piezoelectric smart structure. This may lead to a diverse control system if sensors and actuators were not configured properly. An optimal location method of piezoelectric actuators and sensors is proposed in this paper based on particle swarm algorithm (PSA). Due to the complexity of the frame structure, it can be taken as a combination of many piezoelectric intelligent beams and L‐type structures. Firstly, an optimal criterion of sensors and actuators is proposed with an optimal objective function. Secondly, each order natural frequency and modal strain are calculated and substituted into the optimal objective function. Preliminary optimal allocation is done using the particle swarm algorithm, based on the similar optimization method and the combination of the vibration stress and strain distribution at the lower modal frequency. Finally, the optimal location is given. An experimental platform was established and the experimental results indirectly verified the feasibility and effectiveness of the proposed method.
Ethyl Caffeate Ameliorates Collagen-Induced Arthritis by Suppressing Th1 Immune Response
Authors: Xu Shikui , Zuo Aixue , Guo Zengjun , Wan Chunping
Published: June 2017

The present study was designed to assess the antiarthritic potential of ECF in collagen-induced arthritis (CIA) and explore its underlying mechanism.Methods.In vitro, lymphocyte proliferation assay was measured by CCK-8 kit. In vivo, the therapeutic potential of ECF on CIA was investigated; surface marker, Treg cell, and intracellular cytokines (IL-17A and IFN-γ) were detected by flow cytometry. Th1 cell differentiation assay was performed, and mRNA expression in interferon-γ-related signaling was examined by q-PCR analysis.Results.In vitro, ECF markedly inhibited the proliferation of splenocytes in response to ConA and anti-CD3. In vivo, ECF treatment reduced the severity of CIA, inhibited IFN-γand IL-6 secretion, and decreased the proportion of CD11b+Gr-1+ splenic neutrophil. Meanwhile, ECF treatment significantly inhibited the IFN-γexpression in CD4+T cell without obviously influencing the development of Th17 cells and T regulatory cells. In vitro, ECF suppressed the differentiation of naive CD4+ T cells into Th1. Furthermore, ECF intensely blocked the transcriptional expression in interferon-γ-related signaling, including IFN-γ, T-bet, STAT1, and STAT4.Conclusion.Our results indicated that ECF exerted antiarthritic potential in collagen-induced arthritis by suppressing Th1 immune response and interferon-γ-related signaling.
Bacterial Community Profile of the Gut Microbiota Differs between Hypercholesterolemic Subjects and Controls
Authors: Rebolledo Camilo , Cuevas Alejandro , Zambrano Tomás , Acuña Jacquelinne J. , Jorquera Milko A. , Saavedra Kathleen , Martínez Claudia , Lanas Fernando , Serón Pamela , Salazar Luis A. , Saavedra Nicolás
Published: June 2017

The role of gut microbiota in the development of metabolic illnesses has been abundantly demonstrated. Recent studies suggest that gut microbiota alterations may also be related to the development of hypercholesterolemia. Therefore, we aimed to assess differences in the gut bacterial community profiles between hypercholesterolemic subjects and controls. Thirty cases diagnosed with hypercholesterolemia and 27 normocholesterolemic controls were included. A fasting whole blood sample was obtained to determine the lipid profile. In parallel, stool samples were collected and total DNA was isolated to assess the bacterial community profiles by denaturing gradient gel electrophoresis (DGGE). In addition, the Richness, Shannon-Weaver, and Simpson indexes were used to evaluate the richness and diversity of bacterial communities. As expected, serum concentrations of total cholesterol, triglycerides, and LDL-cholesterol were significantly higher in the cases compared with controls. Moreover, DGGE analysis showed a lower richness and diversity of bacterial communities in hypercholesterolemic subjects. In conclusion, our results showed differences in the profiles of bacterial communities between hypercholesterolemic subjects and controls, suggesting a possible role of the gut microbiota in the development of hypercholesterolemia.
Risperidone‐Induced Renal Damage and Metabolic Side Effects: The Protective Effect of Resveratrol
Authors: Bilgiç Sedat , Korkmaz Deniz Taştemir , Azirak Sebile , Güvenç Ayşe Nilay , Kocaman Nevin , Özer Mehmet Kaya
Published: June 2017

Objective. The aim of the study was to investigate the possible protective qualities of resveratrol (RSV) against the side effects of risperidone (RIS) in an experimental model in rat kidneys with histologic and biochemical assessments. Materials and Methods. Experimental procedures were performed on 35 female Sprague Dawley rats. Rats were randomly divided into five groups: control, untreated rats (n = 7) were in group 1; group 2 was given 2 mg/kg/day RIS (n = 7); group 3 was treated with 2 mg/kg/day RIS and 20 mg/kg/day RSV (n = 7); group 4 was treated with 2 mg/kg/day RIS and 40 mg/kg/day RSV (n = 7); and group 5 was treated with 2 mg/kg/day RIS and 80 mg/kg/day RSV (n = 7). All treatments were administered for two weeks by gavage. On treatment day 15, kidney tissues were removed for analysis. Results. The results showed that RSV treatment reduced weight gain induced by RIS. In addition, RSV increased the total antioxidant status (TAS) and decreased serum creatinine (Cr), blood urea nitrogen (BUN), oxidative stress index (OSI), and total oxidant status (TOS) levels significantly (p < 0.05). Conclusion. This study revealed that treatment with RSV might protect kidney tissues against the side effects of RIS. RSV could be an effective course of therapy to enhance therapeutic efficacy.
The Influence of Nanohydroxyapatite on the Thermal, Mechanical, and Tribological Properties of Polyoxymethylene Nanocomposites
Authors: Pielichowska Kinga , Bieliński Dariusz , Dworak Michał , Kilian Ewelina , Macherzyńska Beata , Błażewicz Stanisław
Published: June 2017

The influence of nanohydroxyapatite on the glass transition region and its activation energy, as well as on the tribological and mechanical properties of polyoxymethylene nanocomposites, was investigated using DMA, TOPEM DSC, nanoindentation, and nondestructive ultrasonic methods. It was found that the glass transition for unmodified POM was in the lower temperature range than in POM/HAp nanocomposites. Moreover,ΔCpand activation energy were larger for POM/HAp nanocomposites. Friction coefficient was higher for POM/HAp nanocomposites in comparison to both POM homopolymer and POM copolymer. Simultaneously, the indentation test results show that microhardness is also higher for POM/HAp nanocomposites than for POM. From ultrasonic investigations it was found that the highest values of both longitudinal and transverse propagation waves and Young’s and shear modulus for POM homopolymer (DH) and POM copolymer T2H and their nanocomposites can be attributed to their higher degree of crystallinity in comparison to UH copolymer. Moreover, for POM/HAp nanocomposites with 5% of HAp, ultrasonic longitudinal wave velocity was almost constant even after 1000000 mechanical loading cycles, evidencing an enhancement of mechanical properties by HAp nanoparticles.
An Open-Structure Treadmill Gait Trainer: From Research to Application
Authors: Li Jian , Chen Diansheng , Fan Yubo
Published: June 2017

Lower limb rehabilitation robots are designed to enhance gait function in individuals with motor impairments. Although numerous rehabilitation robots have been developed, only few of these robots have been used in practical health care, particularly in China. The objective of this study is to construct a lower limb rehabilitation robot and bridge the gap between research and application. Open structure to facilitate practical application was created for the whole robot. Three typical movement patterns of a single leg were adopted in designing the exoskeletons, and force models for patient training were established and analyzed under three different conditions, respectively, and then a control system and security strategy were introduced. After establishing the robot, a preliminary experiment on the actual use of a prototype by patients was conducted to validate the functionality of the robot. The experiment showed that different patients and stages displayed different performances, and results on the trend variations across patients and across stages confirmed the validity of the robot and suggested that the design may lead to a system that could be successful in the treatment of patients with walking disorders in China. Furthermore, this study could provide a reference for a similar application design.
Common Genetic Variation and Susceptibility to Ovarian Cancer: Current Insights and Future Directions
Authors: Kar Siddhartha P. , Berchuck Andrew , Gayther Simon A. , Goode Ellen L. , Moysich Kirsten B. , Pearce Celeste Leigh , Ramus Susan J. , Schildkraut Joellen M. , Sellers Thomas A. , Pharoah Paul D.P.
Published: June 2017

In this review, we summarize current progress in the genetic epidemiology of epithelial ovarian cancer (EOC), focusing exclusively on elucidating the role of common germline genetic variation in conferring susceptibility to EOC. We provide an overview of the more than 30 EOC risk loci identified to date by genome-wide association studies (GWAS) and describe the contribution of large-scale, cross-cancer type, custom genotyping projects, such as the OncoArray and the Collaborative Oncological Gene-Environment Study, to locus discovery and replication. We discuss the histotype-specific nature of these EOC risk loci, pleiotropy, or overlapping genetic effects between EOC and other hormone-related cancer types, and the application of findings to polygenic risk prediction for EOC. The second part of the article offers a concise review of primarily laboratory-based studies that have led to the identification of several putative EOC susceptibility genes using common variants at the known EOC risk loci as starting points. More global biological insights emerging from network- and pathway-based analyses of GWAS for EOC susceptibility are also highlighted. Finally, we delve into potential future directions, including the need to identify EOC risk loci in non-European populations and the next generation of GWAS functional studies that are likely to involve genome editing to establish the cell type–specific carcinogenic effects of EOC risk variants Cancer Epidemiol Biomarkers Prev; 27(4); 395–404. ©2018 AACR.

See all articles in this CEBP Focus section, “Genome-Wide Association Studies in Cancer.”
Von Hippel–Lindau and Hereditary Pheochromocytoma/Paraganglioma Syndromes: Clinical Features, Genetics, and Surveillance Recommendations in Childhood
Authors: Rednam Surya P. , Erez Ayelet , Druker Harriet , Janeway Katherine A. , Kamihara Junne , Kohlmann Wendy K. , Nathanson Katherine L. , States Lisa J. , Tomlinson Gail E. , Villani Anita , Voss Stephan D. , Schiffman Joshua D. , Wasserman Jonathan D.
Published: June 2017

Von Hippel–Lindau disease (vHL) is a hereditary tumor predisposition syndrome that places affected individuals at risk for multiple tumors, which are predominantly benign and generally occur in the central nervous system or abdomen. Although the majority of tumors occur in adults, children and adolescents with the condition develop a significant proportion of vHL manifestations and are vulnerable to delayed tumor detection and their sequelae. Although multiple tumor screening paradigms are currently being utilized for patients with vHL, surveillance should be reassessed as the available relevant clinical information continues to expand. We propose a new vHL screening paradigm similar to existing approaches, with important modifications for some tumor types, placing an emphasis on risks in childhood. This includes advancement in the timing of surveillance initiation and increased frequency of screening evaluations. Another neuroendocrine-related familial condition is the rapidly expanding hereditary paraganglioma and pheochromocytoma syndrome (HPP). The tumor spectrum for patients with HPP syndrome includes paragangliomas, pheochromocytomas, renal cancer, and gastrointestinal stromal tumors. The majority of patients with HPP syndrome harbor an underlying variant in one of the SHDx genes (SDHA, SDHB, SDHC, SDHD, SDHA, and SDHAF2), although other genes also have been described (MAX and TMEM127). Annual screening for elevated plasma or urine markers along with complete blood count and biennial whole-body MRI accompanied by focal neck MRI is recommended for older children and adults with HPP syndrome to detect tumors early and to decrease morbidity and mortality from HPP-related tumors. Clin Cancer Res; 23(12); e68–e75. ©2017 AACR.

See all articles in the online-only CCR Pediatric Oncology Series.
Cancer and Central Nervous System Tumor Surveillance in Pediatric Neurofibromatosis 2 and Related Disorders
Authors: Evans D. Gareth R. , Salvador Hector , Chang Vivian Y. , Erez Ayelet , Voss Stephan D. , Druker Harriet , Scott Hamish S. , Tabori Uri
Published: June 2017

The neurofibromatoses consist of at least three autosomal-dominant inherited disorders: neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis. For over 80 years, these conditions were inextricably tied together under generalized neurofibromatosis. In 1987, the localization of NF1 to chromosome 17q and NF2 (bilateral vestibular schwannoma) to 22q led to a consensus conference at Bethesda, Maryland. The two main neurofibromatoses, NF1 and NF2, were formally separated. More recently, the SMARCB1 and LZTR1 genes on 22q have been confirmed as causing a subset of schwannomatosis. The last 26 years have seen a great improvement in understanding of the clinical and molecular features of these conditions as well as insights into management. Childhood presentation of NF2 (often with meningioma) in particular predicts a severe multitumor disease course. Malignancy is rare in NF2, particularly in childhood; however, there are substantial risks from benign and low-grade central nervous system (CNS) tumors necessitating MRI surveillance to optimize management. At least annual brain MRI, including high-resolution images through the auditory meatus, and a clinical examination and auditory assessment are required from diagnosis or from around 10 to 12 years of age if asymptomatic. Spinal imaging at baseline and every 2 to 3 years is advised with more frequent imaging if warranted on the basis of sites of tumor involvement. The malignancy risk in schwannomatosis is not well defined but may include an increased risk of malignant peripheral nerve sheath tumor in SMARCB1. Imaging protocols are also proposed for SMARCB1 and LZTR1 schwannomatosis and SMARCE1-related meningioma predisposition. Clin Cancer Res; 23(12); e54–e61. ©2017 AACR.

See all articles in the online-only CCR Pediatric Oncology Series.
Disruption of Aneuploidy and Senescence Induced by Aurora Inhibition Promotes Intrinsic Apoptosis in Double Hit or Double Expressor Diffuse Large B-cell Lymphomas
Authors: Islam Shariful , Qi Wenqing , Morales Carla , Cooke Laurence , Spier Catherine , Weterings Eric , Mahadevan Daruka
Published: June 2017

Double hit (DH) or double expressor (DE) diffuse large B-cell lymphomas (DLBCL) are aggressive non-Hodgkin's lymphomas (NHL) with translocations and/or overexpressions of MYC and BCL-2, which are difficult to treat. Aurora kinase (AK) inhibition with alisertib in DH/DE-DLBCL induces cell death in ∼30%, while ∼70% are aneuploid and senescent cells (AASC), a mitotic escape mechanism contributing to drug resistance. These AASCs elaborated a high metabolic rate by increased AKT/mTOR and ERK/MAPK activity via BTK signaling through the chronic active B-cell receptor (BCR) pathway. Combinations of alisertib + ibrutinib or alisertib + ibrutinib + rituximab significantly reduced AASCs with enhanced intrinsic cell death. Inhibition of AK + BTK reduced phosphorylation of AKT/mTOR and ERK-1/2, upregulated phospho-H2A-X and Chk-2 (DNA damage), reduced Bcl-6, and decreased Bcl-2 and Bcl-xL and induced apoptosis by PARP cleavage. In a DE-DLBCL SCID mouse xenograft model, ibrutinib alone was inactive, while alisertib + ibrutinib was additive with a tumor growth inhibition (TGI) rate of ∼25%. However, TGI for ibrutinib + rituximab was ∼50% to 60%. In contrast, triple therapy showed a TGI rate of >90%. Kaplan–Meier survival analysis showed that 67% of mice were alive at day 89 with triple therapy versus 20% with ibrutinib + rituximab. All treatments were well tolerated with no changes in body weights. A novel triple therapy consisting of alisertib + ibrutinib + rituximab inhibits AASCs induced by AK inhibition in DH/DE-DLBCL leading to a significant antiproliferative signal, enhanced intrinsic apoptosis and may be of therapeutic potential in these lymphomas. Mol Cancer Ther; 16(10); 2083–93. ©2017 AACR.
Antitumor Effects of Epidrug/IFNα Combination Driven by Modulated Gene Signatures in Both Colorectal Cancer and Dendritic Cells
Authors: Fragale Alessandra , Romagnoli Giulia , Licursi Valerio , Buoncervello Maria , Del Vecchio Giorgia , Giuliani Caterina , Parlato Stefania , Leone Celeste , De Angelis Marta , Canini Irene , Toschi Elena , Belardelli Filippo , Negri Rodolfo , Capone Imerio , Presutti Carlo , Gabriele Lucia
Published: June 2017

Colorectal cancer results from the progressive accumulation of genetic and epigenetic alterations. IFN signaling defects play an important role in the carcinogenesis process, in which the inability of IFN transcription regulatory factors (IRF) to access regulatory sequences in IFN-stimulated genes (ISG) in tumors and in immune cells may be pivotal. We reported that low-dose combination of two FDA-approved epidrugs, azacytidine (A) and romidepsin (R), with IFNα2 (ARI) hampers the aggressiveness of both colorectal cancer metastatic and stem cells in vivo and triggers immunogenic cell death signals that stimulate dendritic cell (DC) function. Here, we investigated the molecular signals induced by ARI treatment and found that this drug combination increased the accessibility to regulatory sequences of ISGs and IRFs that were epigenetically silenced in both colorectal cancer cells and DCs. Likewise, specific ARI-induced histone methylation and acetylation changes marked epigenetically affected ISG promoters in both metastatic cancer cells and DCs. Analysis by ChIP-seq confirmed such ARI-induced epigenetically regulated IFN signature. The activation of this signal endowed DCs with a marked migratory capability. Our results establish a direct correlation between reexpression of silenced ISGs by epigenetic control and ARI anticancer activity and provide new knowledge for the development of innovative combined therapeutic strategies for colorectal cancer. Cancer Immunol Res; 5(7); 604–16. ©2017 AACR.
An Analysis of Outcome of Endoscopic Fenestration of Cavum Septum Pellucidum Cyst - More Grey than Black and White?
Authors: Udayakumaran Suhas , Onyia Chiazor U. , Cherkil Sandhya
Published: June 2017

Background: Cavum septum pellucidum (CSP) and cavum vergae are actually fluid-filled, generally communicating midline cavities located between the third ventricle and corpus callosum. There have been various reports of their association with many behavioral and psychiatric disorders. Infrequently, they have been associated with an obstructive hydrocephalus-like picture. Although the structure and management of CSP has long been known, it has been an enigma as far as functional significance and management indications are concerned. The authors of this article try to analyze the significance of a persistent cavum and involvement of the same entity in varied presentations ranging from an incidental imaging finding to acute hydrocephalus, and propose a possible implication on the present surgical intervention paradigm. Purpose: To assess the surgical outcome of fenestration of a CSP cyst. Methods: Retrospective analysis of 3 patients who underwent endoscopic fenestration for CSP with obstructive hydrocephalus between 2012 and 2014 was done, and data were analyzed for symptomatic clinical improvement in particular behavior. Results: Pre- and postoperative brain MRI showed a significant decrease in the size of the cyst as well as the ventricles. There were no recurrences during follow-up. All of the patients improved. Conclusions: (1) Endoscopic fenestration of symptomatic CSP cysts is a safe treatment option. (2) Neurocognitive assessment is essential in the evaluation and outcome assessment of CSP.