bluuebunny/crossref_metadata_2025 huggingface dataset:
A SVDD and K‐Means Based Early Warning Method for Dual‐Rotor Equipment under Time‐Varying Operating Conditions
Authors: Jiang Zhinong , Hu Minghui , Feng Kun , Wang Hao
Published: January 2018

Under frequently time‐varying operating conditions, equipment with dual rotors like gas turbines is influenced by two rotors with different rotating speeds. Alarm methods of fixed threshold are unable to consider the influences of time‐varying operating conditions. Hence, those methods are not suitable for monitoring dual‐rotor equipment. An early warning method for dual‐rotor equipment under time‐varying operating conditions is proposed in this paper. The influences of time‐varying rotating speeds of dual rotors on alarm thresholds have been considered. Firstly, the operating conditions are divided into several limited intervals according to rotating speeds of dual rotors. Secondly, the train data within each interval is processed by SVDD and the allowable ranges (i.e., the alarm threshold) of the vibration are determined. The alarm threshold of each interval of operating conditions is obtained. The alarm threshold can be expressed as a sphere, whose controlling parameters are the coordinate of the center and the radius. Then, the cluster center of the test data, whose alarm state is to be judged, can be extracted through K‐means. Finally, the alarm state can be obtained by comparing the cluster center with the corresponding sphere. Experiments are conducted to validate the proposed method.
A SA‐ANN‐Based Modeling Method for Human Cognition Mechanism and the PSACO Cognition Algorithm
Authors: Chen Shuting , Tan Dapeng
Published: January 2018

Artificial neural networks (ANNs) are the important approaches for researching human cognition process. However, current ANNs‐based cognition methods cannot address the problems of complex information understanding and fault‐tolerant learning. Here we present a modeling method for cognition mechanism based on a simulated annealing–artificial neural network (SA‐ANN). Firstly, the relationship between SA processing procedure and cognition knowledge evolution is analyzed, and a SA‐ANN‐based inference model is set up. Then, based on the inference model, a Powell SA with combinatorial optimization (PSACO) algorithm is proposed to improve the clustering efficiency and recognition accuracy for the cognition process. Finally, three groups of numerical instances for knowledge clustering are provided, and three comparative experiments are performed by self‐developed cognition software. The simulated results show that the proposed method can increase the convergence rate by more than 20%, compared with the back‐propagation (BP), SA, and restricted Boltzmann machines based extreme learning machine (RBM‐ELM) algorithms. The comparative cognition experiments prove that the method can obtain better performances of information understanding and fault‐tolerant learning, and the cognition accuracies for original sample, damaged sample, and transformed sample can reach 99.6%, 99.2%, and 97.1%, respectively.
Therapeutic Effectiveness and Safety of Mesotherapy in Patients with Osteoarthritis of the Knee
Authors: Chen Liang , Li Dongqing , Zhong Jun , Qiu Bo , Wu Xianglei
Published: January 2018

Objective. To evaluate the therapeutic effectiveness and safety of mesotherapy by comparing it with the classic systematic therapy in patients with osteoarthritis (OA). Methods. Sixty patients were included and classified into two groups based on the existence of contraindications for nonsteroidal anti‐inflammatory drugs (NSAIDs). These patients were treated with oral NSAIDs (Group A) or mesotherapy (Group B). After completing the treatment, the patients were followed up for 6 months. Their clinical features, laboratory results, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores were evaluated. Results. A total of 50 patients completed treatment and follow‐up. The patients in Group B had significantly fewer gastric acid‐related complaints and requested less supplementary treatment for recurrent pain (p < 0.05). The patients in both groups exhibited decreased blood viscosity after treatment (p < 0.05). WOMAC scores, specifically those for pain and stiffness, were found to be significantly improved after either type of treatment (p < 0.05). Mesotherapy also ameliorated physical function (p < 0.05). Furthermore, Group B presented with better outcomes than Group A (p < 0.05 or p < 0.01). Conclusion. Our results suggest that mesotherapy is an effective and safe treatment for patients with OA. Clinicians should consider mesotherapy as an alternative therapy for patients with contraindications for NSAID use.
A Decision for Predicting Successful Extubation of Patients in Intensive Care Unit
Authors: Tu Chang-Shu , Chang Chih-Hao , Chang Shu-Chin , Lee Chung-Shu , Chang Ching-Ter
Published: January 2018

Approximately 40% of patients admitted to the medical intensive care unit (ICU) require mechanical ventilation. An accurate prediction of successful extubation in patients is a key clinical problem in ICU due to the fact that the successful extubation is highly associated with prolonged ICU stay. The prolonged ICU stay is also associated with increasing cost and mortality rate in healthcare system. This study is retrospective in the aspect of ICU. Hence, a total of 41 patients were selected from the largest academic medical center in Taiwan. Our experimental results show that predicting successful rate of 87.8% is obtained from the proposed predicting function. Based on several types of statistics analysis, including logistic regression analysis, discriminant analysis, and bootstrap method, three major successful extubation predictors, namely, rapid shallow breathing index, respiratory rate, and minute ventilation, are revealed. The prediction of successful extubation function is proposed for patients, ICU, physicians, and hospital for reference.
Channel Access and Power Control for Mobile Crowdsourcing in Device‐to‐Device Underlaid Cellular Networks
Authors: Ma Yue , Zhou Li , Gu Zhenghua , Song Yang , Wang Bin
Published: January 2018

With the access of a myriad of smart handheld devices in cellular networks, mobile crowdsourcing becomes increasingly popular, which can leverage omnipresent mobile devices to promote the complicated crowdsourcing tasks. Device‐to‐device (D2D) communication is highly desired in mobile crowdsourcing when cellular communications are costly. The D2D cellular network is more preferable for mobile crowdsourcing than conventional cellular network. Therefore, this paper addresses the channel access and power control problem in the D2D underlaid cellular networks. We propose a novel semidistributed network‐assisted power and a channel access control scheme for D2D user equipment (DUE) pieces. It can control the interference from DUE pieces to the cellular user accurately and has low information feedback overhead. For the proposed scheme, the stochastic geometry tool is employed and analytic expressions are derived for the coverage probabilities of both the cellular link and D2D links. We analyze the impact of key system parameters on the proposed scheme. The Pareto optimal access threshold maximizing the total area spectral efficiency is obtained. Unlike the existing works, the performances of the cellular link and D2D links are both considered. Simulation results show that the proposed method can improve the total area spectral efficiency significantly compared to existing schemes.
Axial Force Analysis and Roll Contour Configuration of Four-High CVC Mill
Authors: Liu Guang-ming , Li Yu-gui , Huang Qing-xue , Yang Xia
Published: January 2018

In order to analyze the influence of technical parameters on work roll axial force of four-high continuous variable crown (CVC) mill, the deformation analyzing model with top roll system and strip was established based on influence function method. Then a CVC work roll curve designing scheme was proposed and it was carried out on some cold rolling mill considering the requirement of comprehensive work roll axial force minimization. The status of comprehensive work roll axial force is improved considering the rolling schedule that is beneficial to the roller bearing. Corresponding to the newly designed work roll contour, the backup roll end chamfer was designed considering comprehensive performance of interroll stress concentration, comprehensive work roll axial force, and strip shape control ability. The distribution of roll wear with newly designed backup roll contour is more even according to the field application data. The newly established roll configuration scheme is beneficial to four-high CVC mill.
Traditional Chinese Medicine for Refractory Nephrotic Syndrome: Strategies and Promising Treatments
Authors: Wang Xiao-Qin , Wang Lan , Tu Yuan-Chao , Zhang Yuan Clare
Published: January 2018

Refractory nephrotic syndrome (RNS) is an immune‐related kidney disease with poor clinical outcomes. Standard treatments include corticosteroids as the initial therapy and other immunosuppressants as second‐line options. A substantial proportion of patients with RNS are resistant to or dependent on immunosuppressive drugs and often experience unremitting edema and proteinuria, cycles of remission and relapse, and/or serious adverse events due to long‐term immunosuppression. Traditional Chinese medicine has a long history of treating complicated kidney diseases and holds great potential for providing effective treatments for RNS. This review describes the Chinese medical theories relating to the pathogenesis of RNS and discusses the strategies and treatment options using Chinese herbal medicine. Available preclinical and clinical evidence strongly supports the integration of traditional Chinese medicine and Western medicine for improving the outcome of RNS. Herbal medicine such as Astragalus membranaceus, Stephania tetrandra S. Moore, and Tripterygium wilfordii Hook F can serve as the alternative therapy when patients fail to respond to immunosuppression or as the complementary therapy to improve therapeutic efficacy and reduce side effects of immunosuppressive agents. Wuzhi capsules (Schisandra sphenanthera extract) with tacrolimus and tetrandrine with corticosteroids are two herb‐drug combinations that have shown great promise and warrant further studies.
Enhancement of Capacitive Performance in Titania Nanotubes Modified by an Electrochemical Reduction Method
Authors: Samsudin Nurul Asma , Zainal Zulkarnain , Lim Hong Ngee , Sulaiman Yusran , Chang Sook-Keng , Lim Ying-Chin , Mohd Amin Wardatun Nadrah
Published: January 2018

Highly ordered titania nanotubes (TNTs) were synthesised by an electrochemical anodization method for supercapacitor applications. However, the capacitive performance of the TNTs was relatively low and comparable to the conventional capacitor. Therefore, in order to improve the capacitive performance of the TNTs, a fast and facile electrochemical reduction method was applied to modify the TNTs (R-TNTs) by introducing oxygen vacancies into the lattice. X-ray photoelectron spectroscopy (XPS) data confirmed the presence of oxygen vacancies in the R-TNTs lattice upon the reduction of Ti4+ to Ti3+. Electrochemical reduction parameters such as applied voltage and reduction time were varied to optimize the best conditions for the modification process. The electrochemical performance of the samples was analyzed in a three-electrode configuration cell. The cyclic voltammogram recorded at 200 mV s−1 showed a perfect square-shaped voltammogram indicating the excellent electrochemical performance of R-TNTs prepared at 5 V for 30 s. The total area of the R-TNTs voltammogram was 3 times larger than the unmodified TNTs. A specific capacitance of 11.12 mF cm−2 at a current density of 20 μA cm−2 was obtained from constant current charge-discharge measurements, which was approximately 57 times higher than that of unmodified TNTs. R-TNTs also displayed outstanding cycle stability with 99% capacity retention after 1000 cycles.
Improvement of Endovascular Stroke Treatment: A 24-Hour Neuroradiological On-Site Service Is Not Enough
Authors: Nikoubashman Omid , Schürmann Kolja , Othman Ahmed E. , Bach Jan-Philipp , Wiesmann Martin , Reich Arno
Published: January 2018

Background and Purpose. With the advent of endovascular stroke treatment (EST) with mechanical thrombectomy, stroke treatment has also become more challenging. Purpose of this study was to investigate whether a fulltime neuroradiological on-site service and workflow optimization with a structured documentation of the interdisciplinary stroke workflow resulted in improved procedural times. Material and Methods. Procedural times of 322 consecutive patients, who received EST (1) before (n=96) and (2) after (n=126) establishing a 24-hour neuroradiological on-site service as well as (3) after implementation of a structured interdisciplinary workflow documentation (“Stroke Check”) (n=100), were analysed. Results. A fulltime neuroradiological on-site service resulted in a nonsignificant improvement of procedural times during out-of-hours admissions (p≥0.204). Working hours and out-of-hours procedural times improved significantly, if additional workflow optimization was realized (p≤0.026). Conclusions. A 24-hour interventional on-site service is a major prerequisite to adequately provide modern reperfusion therapies in patients with acute ischemic stroke. However, simple measures like standardized and focused documentation that affect the entire interdisciplinary pre- and intrahospital stroke rescue chain seem to be important.
Efficacy, Safety, and Pharmacokinetics of Axitinib in Nasopharyngeal Carcinoma: A Preclinical and Phase II Correlative Study
Authors: Hui Edwin P. , Ma Brigette B. Y. , Loong Herbert H. F. , Mo Frankie , Li Leung , King Ann D. , Wang Ki , Ahuja Anil T. , Chan Charles M. L. , Hui Connie W. C. , Wong Chi H. , Chan Anthony T. C.
Published: January 2018

Purpose: We hypothesized that axitinib is active with an improved safety profile in nasopharyngeal carcinoma (NPC).

Experimental Design: We evaluated axitinib in preclinical models of NPC and studied its efficacy in a phase II clinical trial in recurrent or metastatic NPC patients who progressed after at least one line of prior platinum-based chemotherapy. We excluded patients with local recurrence or vascular invasion. Axitinib was started at 5 mg twice daily in continuous 4-week cycles. Primary endpoint was clinical benefit rate (CBR), defined as the percentage of patients achieving complete response, partial response, or stable disease by RECIST criteria for more than 3 months.

Results: We recruited 40 patients, who received a median of 3 lines of prior chemotherapy. Axitinib was administered for a mean of 5.6 cycles, with 16 patients (40%) receiving ≥6 cycles. Of 37 patients evaluable for response, CBR was 78.4% (95% CI, 65.6%–91.2%) at 3 months and 43.2% (30.4%–56.1%) at 6 months. Grade 3/4 toxicities were uncommon, including hypertension (8%), diarrhea (5%), weight loss (5%), and pain (5%). All hemorrhagic events were grade 1 (15%) or grade 2 (3%). Elevated diastolic blood pressure during the first 3 months of axitinib treatment was significantly associated with improved overall survival (HR, 0.29; 95% CI, 0.13–0.64, P = 0.0012). Patient-reported fatigue symptom was associated with hypothyroidism (P = 0.039). Axitinib PK parameters (Cmax and AUC(0-t)) were significantly correlated with tumor response, toxicity, and serum thyroid-stimulating hormone changes.

Conclusions: Axitinib achieved durable disease control with a favorable safety profile in heavily pretreated NPC patients. Clin Cancer Res; 24(5); 1030–7. ©2018 AACR.
A Randomized in situ Clinical Study of Fluoride Dentifrices on Enamel Remineralization and Resistance to Demineralization: Effects of Zinc
Authors: Creeth Jonathan E. , Karwal Ritu , Hara Anderson T. , Zero Domenick T.
Published: January 2018

This study aimed to determine the effect of zinc ions and F concentration in a dentifrice on remineralization of early caries lesions in situ and on resistance to subsequent demineralization. This was a single-center, 6-period, 6-product, blinded (examiner, subject, analyst), randomized (n = 62), crossover study. Products (all NaF) were: 0, 250, 1,150 and 1,426 ppm F (dose-response controls), “Zn-A” (0.3% ZnCl2, 1,426 ppm F), and “Zn-B” (as Zn-A, with high-foaming surfactants) in a conventional silica base. Subjects wore palatal appliances holding partially demineralized bovine enamel specimens. They brushed their teeth with 1.5 g test dentifrice (25 s), then swished the slurry ensuring even exposure of specimens (95 s), expectorated, and rinsed (15 mL water, 10 s). After 4 h intraoral remineralization, specimens were removed and acid-challenged in vitro. Surface microhardness (SMH), measured pre-experimental, post-initial acid exposure, post-remineralization, and post-second acid exposure, was used to calculate recovery (SMHR), net acid resistance (NAR), and a new, specifically demineralization-focused calculation, “comparative acid resistance” (CAR). Enamel fluoride uptake (EFU) was also measured. For the F dose-response controls, all measures showed significant relationships with dentifrice F concentration (p < 0.0001). The presence of zinc counteracted the ability of F to promote remineralization in this model. Compared to the 1,426 ppm F control, the zinc formulations gave reduced SMHR, EFU, and NAR (all p < 0.0001); however, they showed evidence of increased CAR (Zn-A: p = 0.0040; Zn-B: p = 0.0846). Products were generally well tolerated. In this study, increasing dentifrice F concentration progressively increased in situ remineralization and demineralization resistance of early caries enamel lesions. Zinc ions reduced remineralization but could increase demineralization resistance.
Features and Outcomes of Patients with Calcified Nodules at Culprit Lesions of Acute Coronary Syndrome: An Optical Coherence Tomography Study
Authors: Kobayashi Nobuaki , Takano Masamichi , Tsurumi Masafumi , Shibata Yusaku , Nishigoori Suguru , Uchiyama Saori , Okazaki Hirotake , Shirakabe Akihiro , Seino Yoshihiko , Hata Noritake , Shimizu Wataru
Published: January 2018

Objectives: We sought to clarify clinical features and outcomes related to calcified nodules (CN) compared with plaque rupture (PR) and plaque erosion (PE) detected by optical coherence tomography (OCT) at the culprit lesions in patients with acute coronary syndrome (ACS). Methods: Based on OCT findings for culprit lesion plaque morphologies, ACS patients with analyzable OCT images (n = 362) were classified as CN, PR, PE, and other. Results: The prevalence of CN, PR, and PE was 6% (n = 21), 45% (n = 163), and 41% (n = 149), respectively. Patients with CN were older (median 71 vs. 65 years, p = 0.03) and more diabetic (71 vs. 35%, p = 0.002) than those without CN. In OCT findings, the distal reference lumen cross-sectional area (median 4.2 vs. 5.2 mm2, p = 0.048) and the postintervention minimum lumen cross-sectional area (median 4.5 vs. 5.3 mm2, p = 0.04) were smaller in lesions with CN than in those without. Kaplan-Meier estimate survival curves showed that the 500-day survival without target lesion revascularization (TLR) was lower (p = 0.011) for patients with CN (72.9%) than for those with PR (89.3%) or PE (94.8%). Conclusions: ACS patients with CN at the culprit lesion had more TLR compared to those with PR or PE.
Reduced Protein C Global Assay Levels in Infertile Women with in vitro Fertilization Failure: A Pilot Study
Authors: El Masry Sally , Azzam Hanan , Youssef Hamed , Othman Maha , Awad Mohamed
Published: January 2018

Protein C global is a global dotting assay that evaluates abnormalities in the protein C anticoagulant pathway. A few studies have examined this assay in relation to assisted reproductive technology (ART), but its role in infertile women with in vitro fertilization (IVF) failure remains unclear. In this study, we assessed protein C in infertile women with a history of IVF failure who were undergoing ART. We examined 45 healthy fertile women who conceived naturally, and 45 infertile women with 2 or more implantation failures undergoing ART. Both protein C and activated protein C resistance (APC-R) were evaluated. The results showed that mean protein C expressed as a normalized ratio (PCAT-NR) was significantly lower in the study group compared to the control group (0.76 ± 0.15 vs. 0.91 ± 0.14, respectively; p = 0.0001). Follow-up on ART outcomes showed that women who failed ART had significantly lower PCAT-NR compared to successful cases. PCAT-NR did not correlate with APC-R levels in the study (r = 0.125, p < 0.5) or failed ART subgroups. Using logistic regression analysis, patients with lower PCAT-NR levels showed an elevated risk of implantation failure (p = 0.04, OR 0.50, 95% CI 0.26-0.84). In conclusion, protein C global assay may play a role in the etiology of IVF failure, which might be independent of APC-R. Larger studies are encouraged to validate these findings and explore the underlying pathophysiological mechanisms.
Suprachiasmatic Nucleus and Subordinate Brain Oscillators: Clock Gene Desynchronization by Neuroinflammation
Authors: Guissoni Campos Leila Maria , Buchaim Rogerio Leone , da Silva Nathani Cristina , Spilla Caio Sergio Galina , Hataka Alessandre , Pinato Luciana
Published: January 2018

Objective: The clock genes Period (per) 1 and 2 are essential components in the generation and adjustment of biological circadian rhythms by the suprachiasmatic nucleus (SCN). Both genes are also rhythmically present in extrahypothalamic areas such as the hippocampus and cerebellum, considered subordinate oscillators. Several pathological conditions alter rhythmic biological phenomena, but the mechanisms behind these changes involving the clock genes are not well defined. The current study investigated changes in PER1 and PER2 immunoreactivity in the SCN, hippocampus, and cerebellum in a neuroinflammation model. Methods: Wistar rats received lipopolysaccharide (LPS) or vehicle intracerebroventricularly. The melatonin plasmatic content was quantified by ELISA to confirm the alterations in biological rhythms, and PER1 and PER2 immunoreactivities were analyzed in brain sections by immunohistochemistry. Results: In the SCN, intracerebroventricular LPS changed PER1 expression, increasing the number of PER1-immunoreactive (IR) cells at zeitgeber time (ZT) 15, decreasing it at ZT5 and ZT20 and not changing it at ZT10. LPS also induced a decrease in PER2-IR cells at ZT5, ZT10, and ZT15 but not at ZT20 in the SCN. In the hippocampus, LPS induced a decrease in PER1-IR and PER2-IR cells at both ZTs (ZT10 and ZT15). In the cerebellum, LPS increased the number of PER1-IR cells at ZT10 and decreased it at ZT15, while the number of PER2-IR cells was reduced at both ZTs. Conclusions: These results indicate that a neuroinflammatory condition leads to desynchronization of primary and subordinate brain oscillators, supporting the existence of the integration between the immune and the circadian system.
A Patient with Advanced Gastric Cancer Who Achieved a Long-Term Prognosis by Early Diagnosis of Sister Mary Joseph’s Nodule
Authors: Ota Shuji , Haruyama Terunobu , Ishihara Masashi , Natsume Maika , Fukasawa Yoko , Sakamoto Takahiko , Tanzawa Shigeru , Usui Ryo , Honda Takeshi , Ichikawa Yasuko , Watanabe Kiyotaka , Sasajima Yuko , Seki Nobuhiko
Published: January 2018

The patient was a 66-year-old woman. An induration of approximately 15 mm in size that accompanied redness was palpable in the umbilical fossa. She did not respond to 1-month antibiotic treatment provided by the previous physician. For this reason, a biopsy of the site was performed with the possibility of neoplastic disease in mind, resulting in the detection of adenocarcinoma. Subsequent detailed whole-body examination revealed advanced gastric cancer and peritoneal dissemination, and the induration in the umbilical fossa was diagnosed as a direct infiltration from the peritoneal dissemination. Metastasis or infiltration of malignant tumor to the umbilicus is called Sister Mary Joseph’s nodule (SMJN), and considered as a sign of poor prognosis. However, this case was successfully treated and achieved a long-term prognosis by the early diagnosis of SMJN. In routine clinical practice, it is considered necessary to examine patients carefully, as not to overlook SMJN.
Safety of Outpatient Kidney Biopsies
Authors: Šimunov Bojana , Gunjača Mihaela , Čingel Branislav , Škegro Dinko , Knotek Mladen
Published: January 2018

Background: Kidney biopsy is frequently performed in our centre as an outpatient procedure. The aim of this study was to evaluate the safety of biopsy in the outpatient setting. Methods: We analysed kidney biopsies performed from March 2013 to February 2017. Seven hundred twenty-five biopsies performed in the outpatient setting were identified: There were 592 transplant and 133 native biopsies including 3 solitary kidney biopsies. All were performed under ultrasound guidance using a 16G or 18G needle, with freehand technique. In all patients with estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 desmopressin was administered. Patients were observed for 6h before discharge, with a complete blood count and urine test after 4 h. Major complications were haemorrhage requiring therapeutic intervention or transfusion. Minor complications were significant reduction in haemoglobin (Hb) levels (>10%), without need for transfusion or intervention and macrohaematuria. Results: There were 506 (69.8%) male patients. Average age was 50.3 ± 12.7 years. Indications for native kidney biopsy included nephrotic syndrome (39.8%), nephritic syndrome (42.9%), follow-up biopsy (15.8%), and other (1.5%). There were no major complications. A decline in Hb was observed in 72% of patients. Average Hb decline was 4.2 ± 6.3 g/L. In 10.1% patients there was >10% reduction in Hb level, with no evident bleeding, including by ultrasonography. In 2.5% of patients, macrohaematuria was present. In a multivariate analysis, male gender, lower eGFR, higher pre-biopsy Hb and native kidney biopsy were predictive for Hb decline. No therapeutic interventions were required. Conclusion: We found that kidney biopsy performed in an outpatient setting in select patients is only rarely associated with adverse events and is a safe procedure.
A Rare Case of Glossopharyngeal Neuralgia due to Neurovascular Conflict
Authors: Vecchi Marc , Pereira Mestre Ricardo , Thiekalamuriyil S. Luciamma , Cartolari Roberto
Published: January 2018

In the context of painful cranial neuropathies, a very rare cause is represented by the irritation of the glossopharyngeal nerve due to various aetiologic factors. Here, we present a case of neuralgia of the ninth right cranial nerve due to a compression of its nerve root upon the kinking of the homolateral vertebral artery, resulting in a disabling clinical overview for the patient. Our objective was to focus the reader’s attention on the clinical manifestation, which alone could lead to an immediate diagnosis. The imaging and laboratory studies proved to be fundamental in diagnosing the causes, yet the knowledge of the symptoms and the signs of this rare clinical entity can prevent misdiagnosis, mismanagement and consequent economic expenditure as occurred in the case described here.
Associations of Fibroblast Growth Factor 23 with Markers of Inflammation and Leukocyte Transmigration in Chronic Kidney Disease
Authors: Wallquist Carin , Mansouri Ladan , Norrbäck Mattias , Hylander Britta , Jacobson Stefan H. , Larsson Tobias E. , Lundahl Joachim
Published: January 2018

Background: Patients with chronic kidney disease (CKD) show elevated levels of inflammatory markers and have an increased risk of infections as well as cardiovascular morbidity. Recent studies have implied effects of fibroblast growth factor 23 (FGF23) on inflammation in CKD. We analyzed potential correlations between levels of FGF23 with pro-inflammatory chemokines and markers of leukocyte transmigration in CKD patients. Methods: One hundred three patients with CKD 2–5ND and 54 healthy controls, had biochemical markers in blood and urine analyzed according to routine protocol. Pro-inflammatory cytokines were analyzed by Milliplex technique and leukocyte CD11b adhesion molecule expression was measured by flow cytometry. FGF23 levels were measured with ELISA technique. Treatment of leukocytes from healthy blood donors with FGF23 was performed in vitro and effects analyzed by flow cytometry. Results: Tumor necrosis factor-alpha, RANTES and interleukin (IL)-12 levels were significantly higher (p = 0.001, p < 0.001, and p < 0.001) in patients with CKD. Elevated FGF23 levels in the CKD group correlated to glomerular filtration rate, parathyroid hormone, urinary albumin excretion and phosphate as well as to IL-12 and RANTES. CD11b expression on resting granulocytes and monocytes, and on activated monocytes, was associated with FGF23. In vitro treatment of leukocytes with FGF23 reduced CD11b expression in resting as well as in formyl-methyinoyl-leucyl-phenylalanine-stimulated granulocytes (p = 0.03). Conclusion: FGF23 levels are associated with various inflammatory markers such as pro-inflammatory cytokines and adhesion molecules on innate immune cells. However, further studies are warranted to define the direct role of FGF23 in modulation of the innate immune system in CKD.
Case Report of a Family Affected by Stickler Syndrome in Which Rhegmatogenous Retinal Detachment Occurred in Five Eyes of Three Siblings
Authors: Kimura Daisaku , Sato Takaki , Oosuka Shou , Kohmoto Ryohsuke , Fukumoto Masanori , Mimura Masashi , Tajiri Kensuke , Kobayashi Takatoshi , Kida Teruyo , Ikeda Tsunehiko
Published: January 2018

Purpose: Stickler syndrome is an autosomal dominant inherited disorder that is well known to be highly associated with the development of rhegmatogenous retinal detachment. In this study, we report the case of a family affected by Stickler syndrome in which rhegmatogenous retinal detachment developed in 5 eyes of 3 siblings. Case Series: For treatment, we performed vitreous surgery on 1 eye of the eldest son, and bilateral scleral buckling surgery on the 2 younger children. A good postoperative outcome was obtained on the 4 eyes that underwent scleral buckling surgery, yet the prognosis was poor on the 1 eye that underwent vitrectomy due to redetachment of the retina and corneal complication. Since vitreous surgery was quite difficult due to strong vitreoretinal adhesion, we created an artificial posterior vitreous detachment via the bimanual technique combined with encircling. For the scleral buckling surgery, broad scleral extrusion was needed to seal multiple retinal breaks. Conclusions: The findings of this study showed a high prevalence of rhegmatogenous retinal detachment in a single family with Stickler syndrome. In these cases, scleral buckling surgery was effective for treating the detached retina, and some prophylactic treatment, such as laser photocoagulation to prevent the occurrence of rhegmatogenous retinal detachment, should be considered for such cases in the future.
Successful Treatment of Refractory Squamous Cell Cancer of the Head and Neck with Nivolumab and Ipilimumab
Authors: Schwab Katjana S. , Kristiansen Glenn , Schild Hans H. , Held Stefanie E.A. , Heine Annkristin , Brossart Peter
Published: January 2018

Treatment options for patients with platinum-refractory, recurrent, metastatic head and neck squamous cell carcinoma (HNSCC) are limited, and prognosis is poor. Nivolumab (Opdivo) has been approved by the US Food and Drug Administration (FDA) for the treatment of patients with recurrent or metastatic HNSCC who have disease progression on or after platinum-based therapy. Recently, in patients with metastatic malignant melanoma a significant improvement of outcome and response was achieved with the combination of ipilimumab (CTLA4 antibody) and the programmed death (PD)-1 inhibitor nivolumab compared with monotherapy. Based on these results, the combination of nivolumab and ipilimumab has been approved by the FDA for the treatment of patients with unresectable or metastatic melanoma. So far, there have been no data concerning the combination of nivolumab and ipilimumab in squamous cell head and neck cancer. We here present the case of a 46-year-old male with refractory squamous cell head and neck cancer, who was successfully treated with the PD-1 inhibitor nivolumab in combination with the anti-CTLA4 antibody ipilimumab.
Consideration of Sex Differences in Design and Reporting of Experimental Arterial Pathology Studies—Statement From ATVB Council
Authors: Robinet Peggy , Milewicz Dianna M. , Cassis Lisa A. , Leeper Nicholas J. , Lu Hong S. , Smith Jonathan D.
Published: January 2018

There are many differences in arterial diseases between men and women, including prevalence, clinical manifestations, treatments, and prognosis. The new policy of the National Institutes of Health, which requires the inclusion of sex as a biological variable for preclinical studies, aims to foster new mechanistic insights and to enhance our understanding of sex differences in human diseases. The purpose of this statement is to suggest guidelines for designing and reporting sex as a biological variable in animal models of atherosclerosis, thoracic and abdominal aortic aneurysms, and peripheral arterial disease. We briefly review sex differences of these human diseases and their animal models, followed by suggestions on experimental design and reporting of animal studies for these vascular pathologies.
Akt2 (Protein Kinase B Beta) Stabilizes ATP7A, a Copper Transporter for Extracellular Superoxide Dismutase, in Vascular Smooth Muscle
Authors: Sudhahar Varadarajan , Okur Mustafa Nazir , Bagi Zsolt , O’Bryan John P. , Hay Nissim , Makino Ayako , Patel Vijay S. , Phillips Shane A. , Stepp David , Ushio-Fukai Masuko , Fukai Tohru
Published: January 2018

Objective—

Copper transporter ATP7A (copper-transporting/ATPase) is required for full activation of SOD3 (extracellular superoxide dismutase), which is secreted from vascular smooth muscle cells (VSMCs) and anchors to endothelial cell surface to preserve endothelial function by scavenging extracellular superoxide. We reported that ATP7A protein expression and SOD3 activity are decreased in insulin-deficient type 1 diabetes mellitus vessels, thereby, inducing superoxide-mediated endothelial dysfunction, which are rescued by insulin treatment. However, it is unknown regarding the mechanism by which insulin increases ATP7A expression in VSMCs and whether ATP7A downregulation is observed in T2DM (type2 diabetes mellitus) mice and human in which insulin–Akt (protein kinase B) pathway is selectively impaired.

Approach and Results—

Here we show that ATP7A protein is markedly downregulated in vessels isolated from T2DM patients, as well as those from high-fat diet–induced or db/db T2DM mice. Akt2 (protein kinase B beta) activated by insulin promotes ATP7A stabilization via preventing ubiquitination/degradation as well as translocation to plasma membrane in VSMCs, which contributes to activation of SOD3 that protects against T2DM-induced endothelial dysfunction. Downregulation of ATP7A in T2DM vessels is restored by constitutive active Akt or PTP1B
−/−
(protein-tyrosine phosphatase 1B-deficient) T2DM mice, which enhance insulin–Akt signaling. Immunoprecipitation, in vitro kinase assay, and mass spectrometry analysis reveal that insulin stimulates Akt2 binding to ATP7A to induce phosphorylation at Ser1424/1463/1466. Furthermore, SOD3 activity is reduced in Akt2
−/−
vessels or VSMCs, which is rescued by ATP7A overexpression.

Conclusion—

Akt2 plays a critical role in ATP7A protein stabilization and translocation to plasma membrane in VSMCs, which contributes to full activation of vascular SOD3 that protects against endothelial dysfunction in T2DM.
TRPV4 (Transient Receptor Potential Vanilloid 4) Channel–Dependent Negative Feedback Mechanism Regulates G
q
Protein–Coupled Receptor–Induced Vasoconstriction
Authors: Hong Kwangseok , Cope Eric L. , DeLalio Leon J. , Marziano Corina , Isakson Brant E. , Sonkusare Swapnil K.
Published: January 2018

Objective—

Several physiological stimuli activate smooth muscle cell (SMC) G
q
PCRs (G
q
protein–coupled receptors) to cause vasoconstriction. As a protective mechanism against excessive vasoconstriction, SMC G
q
PCR stimulation invokes endothelial cell vasodilatory signaling. Whether Ca
2+
influx in endothelial cells contributes to the regulation of G
q
PCR-induced vasoconstriction remains unknown. Ca
2+
influx through TRPV4 (transient receptor potential vanilloid 4) channels is a key regulator of endothelium-dependent vasodilation. We hypothesized that SMC G
q
PCR stimulation engages endothelial TRPV4 channels to limit vasoconstriction.

Approach and Results—

Using high-speed confocal microscopy to record unitary Ca
2+
influx events through TRPV4 channels (TRPV4 sparklets), we report that activation of SMC α
1
ARs (alpha
1
-adrenergic receptors) with phenylephrine or thromboxane A
2
receptors with U46619 stimulated TRPV4 sparklets in the native endothelium from mesenteric arteries. Activation of endothelial TRPV4 channels did not require an increase in Ca
2+
as indicated by the lack of effect of L-type Ca
2+
channel activator or chelator of intracellular Ca
2+
EGTA-AM. However, gap junction communication between SMCs and endothelial cells was required for phenylephrine activation or U46619 activation of endothelial TRPV4 channels. Lowering inositol 1,4,5-trisphosphate levels with phospholipase C inhibitor or lithium chloride suppressed phenylephrine activation of endothelial TRPV4 sparklets. Moreover, uncaging inositol 1,4,5-trisphosphate profoundly increased TRPV4 sparklet activity. In pressurized arteries, phenylephrine-induced vasoconstriction was followed by a slow, TRPV4-dependent vasodilation, reflecting activation of negative regulatory mechanism. Consistent with these data, phenylephrine induced a significantly higher increase in blood pressure in TRPV4
−/−
mice.

Conclusions—

These results demonstrate that SMC G
q
PCR stimulation triggers inositol 1,4,5-trisphosphate–dependent activation of endothelial TRPV4 channels to limit vasoconstriction.
Long Noncoding RNA Discovery in Cardiovascular Disease
Authors: Sallam Tamer , Sandhu Jaspreet , Tontonoz Peter
Published: January 2018

Despite significant improvements during the past 3 decades, cardiovascular disease remains a leading worldwide health epidemic. The recent identification of a fascinating group of mediators known as long noncoding RNAs (lncRNAs) has provided a wealth of new biology to explore for cardiovascular risk mitigation. lncRNAs are expressed in a highly context-specific fashion, and multiple lines of evidence implicated them in diverse biological processes. Indeed, abnormalities of lncRNAs have been directly linked with human ailments, including cardiovascular biology and disease. Of particular interest to the cardiovascular research community, dysregulation in lncRNA regulatory circuits have been associated with cardiac pathological hypertrophy, vascular disease, cell fate programming and development, atherosclerosis, dyslipidemia, and metabolic syndrome. Although techniques in interrogating noncoding RNAs are rapidly evolving, a major challenge in studying lncRNAs remains navigating through multiple technical constraints. In this review, we provide a road map for lncRNA discovery and interrogation in biological systems relevant to cardiovascular disease and highlight approaches to decipher their modes of action.
Intracranial Aneurysm–Associated Single-Nucleotide Polymorphisms Alter Regulatory DNA in the Human Circle of Willis
Authors: Laarman Melanie D. , Vermunt Marit W. , Kleinloog Rachel , de Boer-Bergsma Jelkje J. , Brain Bank Netherlands , Rinkel Gabriël J.E. , Creyghton Menno P. , Mokry Michal , Bakkers Jeroen , Ruigrok Ynte M.
Published: January 2018

Background and Purpose—

Genome-wide association studies significantly link intracranial aneurysm (IA) to single-nucleotide polymorphisms (SNPs) in 6 genomic loci. To gain insight into the relevance of these IA-associated SNPs, we aimed to identify regulatory regions and analyze overall gene expression in the human circle of Willis (CoW), on which these aneurysms develop.

Methods—

We performed chromatin immunoprecipitation and sequencing for histone modifications H3K4me1 and H3K27ac to identify regulatory regions, including distal enhancers and active promoters, in postmortem specimens of the human CoW. These experiments were complemented with RNA sequencing on the same specimens. We determined whether these regulatory regions overlap with IA-associated SNPs, using computational methods. By combining our results with publicly available data, we investigated the effect of IA-associated SNPs on the newly identified regulatory regions and linked them to potential target genes.

Results—

We find that IA-associated SNPs are significantly enriched in CoW regulatory regions. Some of the IA-associated SNPs that overlap with a regulatory region are likely to alter transcription factor binding, and in proximity to these regulatory regions are 102 genes that are expressed in the CoW. In addition, gene expression in the CoW is enriched for genes related to cell adhesion and the extracellular matrix.

Conclusions—

CoW regulatory regions link IA-associated SNPs to genes with a potential role in the development of IAs. Our data refine previous predictions on SNPs associated with IA and provide a substantial resource from which candidates for follow-up studies can be prioritized.
Reassessment of the species Stigeoclonium polyrhizum (Chaetophoraceae, Chaetophorales) based on morphological and molecular data
Authors: LIU BENWEN , LIU XUDONG , WANG QINGHUA , HU ZHENGYU , LIU GUOXIANG
Published: January 2018

Four specimens of Stigeoclonium spp., sampled in China between 2015 and 2016, were identified as the species Stigeoclonium polyrhizum (Chaetophoraceae, Chaetophorales) due to their unique morphology. A large part of the main filament and branches was tightly enclosed by numerous rhizoidal branches, which extended downward to the base of the plant to form an expanded holdfast. S. polyrhizum has previously been regarded as a synonym of S. longipilum or other related species by most phycologists. Therefore, a reassessment of S. polyrhizum based on morphological and molecular data was conducted. Rhizoidal branch development of S. polyrhizum was also described, showing the abundant rhizoidal branches present from the juvenile stage to the mature stage under controlled culture conditions. Phylogenetic evidence, using nuclear-encoded SSU rDNA data, clearly revealed that the Chaetophoraceae diverged into two well-supported sister clades: the Chaetophora-clade and the Fritschiella-clade. S. polyrhizum was included in the Fritschiella-clade instead of the Chaetophora-clade where Chaetophora draparnaldioides (S. longipilum) was found. The morphological and molecular data unambiguously show that S. polyrhizum is a valid species rather than a synonym of S. longipilum or other related species. Thylakoid bands appressed to the periphery of the pyrenoid matrix of S. polyrhizum was also described.
A new species of Aspidosperma (Apocynaceae) from the Brazilian Cerrado
Authors: SCUDELER ANA LAURA , DEVIDES CASTELLO ANA CAROLINA , DE SOUZA PEREIRA ANDREZA STEPHANIE , KOCH INGRID
Published: January 2018

Aspidosperma rizzoanum is a new species of Cerrado from Goiás and Tocantins states, Brazil. Here we provide the description and illustration of this new species and, besides that, a comparative table and an identification key to the species occurring in the Cerrado of Goiás and Tocatins.
Epimeria cleo sp. nov., a new crested amphipod from the Ross Sea, Antarctica, with notes on its phylogenetic affinities (Crustacea, Amphipoda, Eusiroidea, Epimeriidae)
Authors: VERHEYE MARIE L. , LÖRZ ANNE-NINA , D‘ACOZ CÉDRIC D’UDEKEM
Published: January 2018

A new crested amphipod, Epimeria cleo sp. nov., is described after specimens collected in the western Ross Sea, Southern Ocean, at 151–409 m depth. This increases the number of Epimeria species known from the Ross Sea to eleven. This new species belongs to the subgenus Drakepimeria d'Udekem d'Acoz & Verheye, 2017. E. cleo sp. nov. has very robust walking pereiopods, no mid-dorsal tooth or bump on pereonites 1–2, no lateral tooth or angle on the lateral carina of coxa 4 and no pair of small teeth pointing upwards on urosomite 2. It is morphologically very similar to Epimeria leukhoplites d'Udekem d'Acoz & Verheye, 2017, E. reoproi Lörz & Coleman, 2001 and E. vaderi Coleman, 1998, the latter three species being known only from the Antarctic Peninsula and South Shetland Islands. Epimeria cleo sp. nov. can be distinguished from them by the following combination of characters: flexed rostrum, narrow coxa 3, long ventral tooth on coxa 4 and non-duplicate lateral tooth on pleonites 1–2. The phylogenetic relationships between E. cleo sp. nov. and other Epimeria of the subgenus Drakepimeria, for which DNA sequences are available, are briefly outlined based on a phylogenetic analysis of 28S rDNA fragments.
Syllidae (Annelida: Phyllodocida) from the deep Mediterranean Sea, with the description of three new species
Authors: LANGENECK JOACHIM , MUSCO LUIGI , BUSONI GIULIO , CONESE ILARIA , ALIANI STEFANO , CASTELLI ALBERTO
Published: January 2018

Despite almost two centuries of research, the diversity of Mediterranean deep-sea environments remain still largely unexplored. This is particularly true for the polychaete family Syllidae. We report herein 14 species; among them, we describe Erinaceusyllis barbarae n. sp., Exogone sophiae n. sp. and Prosphaerosyllis danovaroi n. sp. and report Parexogone wolfi San Martín, 1991, Exogone lopezi San Martín, Ceberio & Aguirrezabalaga, 1996 and Anguillosyllis Day, 1963 for the first time from the Western Mediterranean, the latter based on a single individual likely belonging to an undescribed species. Moreover, we re-establish Syllis profunda Cognetti, 1955 based on type and new material. Present data, along with a critical analysis of available literature, show that Syllidae are highly diverse in deep Mediterranean environments, even though they are rarely reported, probably due to the scarce number of studies devoted to the size-fraction of benthos including deep-sea syllids. Most deep-sea Syllidae have wide distributions, which do not include shallow-waters. 100 m depth apparently represents the boundary between the assemblages dominated by generalist shallow water syllids like Exogone naidina Ørsted, 1843 and Syllis parapari San Martín & López, 2000, and those deep-water assemblages characterised by strictly deep-water species like Parexogone campoyi San Martín, Ceberio & Aguirrezabalaga, 1996, Parexogone wolfi San Martín, 1991 and Syllis sp. 1 (= Langerhansia caeca Katzmann, 1973).
Systematics of the combtooth blenny clade Omobranchus (Blenniidae: Omobranchini), with notes on early life history stages
Authors: GIBBS SEAN , HUNDT PETER J. , NELSON ANDREA , EGAN JOSHUA P. , TONGNUNUI PRASERT , SIMONS ANDREW M.
Published: January 2018

The combtooth blenny (Blenniidae) genus Omobranchus contains small, cryptobenthic fishes common to nearshore habitats throughout the Indo-West Pacific. Recent molecular systematic studies have resolved Omobranchus as monophyletic but little research has been done to resolve species-level relationships. Herein, phylogenetic analyses of one mitochondrial (CO1) and four nuclear (ENC1, myh6, sreb2, and tbr1) genes provide evidence for the monophyly of Omobranchus and support for the elongatus and banditus species group. Sampling of multiple individuals from widespread species (O. ferox, O. punctatus, and O. elongatus) suggested that the Thai-Malay Peninsula is a phylogeographic break that may be a historic barrier to gene flow. Additionally, common meristics and other morphological characters are used to describe an early life history stage of O. ferox and O. punctatus.