bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pectolinarigenin prevents bone loss in ovariectomized mice and inhibits RANKL‐induced osteoclastogenesis via blocking activation of MAPK and NFATc1 signaling
Authors: Xiao Yu , Li Kai , Wang Ziyi , Fu Fangsheng , Shao Siyuan , Song Fangming , Zhao Jinmin , Chen Weiwei , Liu Qian , Xu Jiake 
Published: January 2019

AbstractOsteoporosis (OP) is a metabolic disease caused by multiple factors, which is characterized by a reduction of bone mass per unit volume and destruction of bone microstructure. Aberrant osteoclast function is the main cause of OP, therefore, regulating the differentiation and function of osteoclast is one of the treatment strategies for OP. Pectolinarigenin (PEC) is a medicinal implant isolated from Fragrant Eupatorium. Our experimental data showed that PEC was able to inhibit receptor activator of nuclear factor‐κB ligand (RANKL)‐induced osteoclastogenesis in vitro, by tartrate‐resistant acid phosphatase (TRAcP) staining, Fibrous actin ring formation, and hydroxyapatite resorption assays. In terms of mechanism, PEC inhibited the expression of the osteoclastogenesis‐related gene, including cathepsin K (Ctsk), matrix metalloproteinase 9 (Mmp9), and TRAcP (Acp5). Western blot analysis demonstrated that PEC could significantly block the activation of RANKL‐induced mitogen‐activated protein kinase signaling cascades and was able to suppress the protein expression of nuclear factor of activated T‐cells and c‐Fos. Meanwhile, the intracellular reactive oxygen species levels were also reduced by PEC in a concentration‐dependent manner. Further, PEC could prevent the ovariectomy‐induced bone loss in vivo. Summarizing all, our data suggested that PEC inhibits osteoclast formation and function and RANKL signaling pathways, and thus could potentially be used in the treatment the osteoclast‐related bone loss diseases.
LncRNA UCA1 sponges miR‐206 to exacerbate oxidative stress and apoptosis induced by ox‐LDL in human macrophages
Authors: Hu Xiaorong , Ma Ruisong , Fu Wenwen , Zhang Changjiang , Du Xianjin 
Published: January 2019

AbstractLong noncoding RNA UCA1 has exerted a significant effect in cardiovascular disease. The biological role of UCA1 in atherosclerosis is unclear. Our study was to identify the potential mechanisms in the progression of atherosclerosis. Here, we observed that ox‐LDL increased UCA1 expression greatly in THP‐1 cells. Knockdown of UCA1 greatly inhibited CD36 expression, a crucial biomarker in atherosclerosis. Meanwhile, 20 μg/ml ox‐LDL induced foam cell formation, which can be reversed by downregulation of UCA1. In addition, TC and TG levels induced by ox‐LDL was rescued by UCA1 small interfering RNA. Accumulating studies have indicated that oxidative stress contributes to atherosclerosis progression. Here, we also found that reactive oxygen species, MDA, and THP‐1 cell apoptosis were restrained by decreased of UCA1 with an increase of the superoxide dismutase activity. Moreover, miR‐206 was predicted as a target of UCA1 and knockdown of UCA1 was able to repress miR‐206 expression. Furthermore, overexpression of miR‐206 inhibited oxidative stress process and it was reversed by UCA1 upregulation in vitro. In conclusion, we indicated that UCA1 sponged miR‐206 to exacerbate atherosclerosis events induced by ox‐LDL in THP‐1 cells.
Characterization of the Effect of Renal Impairment on Upadacitinib Pharmacokinetics
Authors: Mohamed Mohamed‐Eslam F. , Trueman Sheryl , Feng Tian , Anderson Jaclyn , Marbury Thomas C. , Othman Ahmed A. 
Published: January 2019

AbstractUpadacitinib is a novel selective Janus kinase 1 inhibitor developed for treatment of rheumatoid arthritis and other autoimmune diseases. The objective of this study was to assess the pharmacokinetics and safety of a single upadacitinib dose in subjects with normal renal function and in subjects with renal impairment. A total of 24 subjects between the ages of 18 and 75 years were assigned to 1 of 4 renal function groups based on estimated glomerular filtration rate (normal, mild, moderate, severe; N = 6/group). A single 15‐mg dose of upadacitinib extended‐release formulation was administered under fasting conditions. Serial plasma and urine samples were assayed to evaluate the effect of renal impairment on upadacitinib exposure through regression analysis and analysis of covariance. The primary analysis was the regression analysis of upadacitinib exposures versus estimated glomerular filtration rate. The point estimates for upadacitinib plasma exposure ratios (90% confidence interval [CI]) in subjects with mild, moderate, and severe renal impairment were 1.18 (90%CI, 1.06–1.32), 1.33 (90%CI, 1.11–1.59), and 1.44 (90%CI, 1.14–1.82) for area under the plasma concentration–time curve and 1.06 (90%CI, 0.92–1.23), 1.11 (90%CI, 0.88–1.40), and 1.14 (90%CI, 0.84–1.56) for maximum observed plasma concentration, respectively, relative to subjects with normal renal function based on the regression analysis. The analysis of covariance categorical analysis provided consistent results. Upadacitinib was well tolerated by all subjects, and no safety issues were identified in subjects with renal impairment. Renal impairment has a limited effect on upadacitinib pharmacokinetics. This is in agreement with the known limited role of urinary excretion in upadacitinib elimination. Based on the limited impact on exposure, no dose adjustment is necessary for upadacitinib in subjects with impaired renal function.
Pharmacokinetic Evaluation of Nimotuzumab in Patients With Autosomal Dominant Polycystic Kidney Disease
Authors: de Castro‐Suárez Niurys , Rodríguez‐Vera Leyanis , Villegas Carlos , Dávalos‐Iglesias José M. , Bacallao‐Mendez Raymed , Llerena‐Ferrer Betsy , Leyva‐de la Torre Christian , Lorenzo‐ Luaces Patricia , Troche‐Concepción Mayelin , Ramos‐Suzarte Mayra 
Published: January 2019

AbstractAutosomal dominant polycystic kidney disease (ADPKD) is a genetic disease characterized by an overexpression and mislocalization of epidermal growth factor receptor (EGFR) to the apical membranes of cystic epithelial cells. Nimotuzumab is a humanized antibody that recognizes an extracellular domain III of human EGFR. The aim of this study was to assess the pharmacokinetic behavior of nimotuzumab in patients with ADPKD given as a single dose. A phase I, single‐center, and noncontrolled open clinical study was conducted. Five patients were enrolled at each of the following fixed‐dose levels: 50, 100, 200, and 400 mg. Intravenous continuous infusions of nimotuzumab were administered every 14 days during a year, except the first administration, when blood samples were drawn during 28 days for pharmacokinetic assessments. Subjects were closely monitored during the trial and at completion of the administration of nimotuzumab, including the anti‐idiotypic response. For the first time, nimotuzumab was used for treating a nononcological disease. The administration of nimotuzumab showed dose‐dependent kinetics. Nimotuzumab does not develop anti‐idiotypic response against the murine portion present in the hypervariable region of the antibody present in the serum of the patients treated. No significant differences were found in the systemic clearance between the 100‐ and 400‐mg dose, which indicates that the optimal biological dose is in this range of dose.
Design and Synthesis of Novel C4‐Linked Substituted 2H‐Chromen‐2‐one‐hypoxanthine Hybrids as Potential Antimicrobial Agents: An Approach to Molecular Docking Studies
Authors: Naik Soniya D. , Hosamani Kallappa M. 
Published: January 2019

We present here design and synthesis of very efficient, high‐yielded and simple approach of a series of C4‐linked coumarin–hypoxanthine pharmacophores 1(a–j) with moderate to excellent in vitro antimicrobial activity. According to earlier studies, potential modification at C4‐position of coumarin ring provided excellent bioactive molecules. All the titled compounds were characterized by spectroscopic and elemental analyses. Titled compounds have been developed via systematic tuning of coumarin ring substitutions, which are prepared from the well‐known Pechmann condensation reaction. The addition of a pendent nucleobase in hypoxanthine group improved the in vitro antimicrobial activity. Computational studies were also mimicking the potent biomolecules. A good pharmacokinetic profile is suggested by theoretical calculation of absorption, distribution, metabolism, and excretion properties. Therefore, synthesis of these titled compounds provided an insight towards better antimicrobial agents.
Sex‐based outcomes in type I thyroplasty for nonparalytic glottic incompetence
Authors: Farzal Zainab , Overton Lewis J. , Farquhar Douglas R. , Stephenson Elizabeth D. , Shah Rupali N. , Buckmire Robert A. 
Published: January 2019

ObjectiveClinical outcomes for type I Gore‐Tex thyroplasty (GMT) for nonparalytic glottic incompetence (GI) have been reported in the literature. Given differences in male and female laryngeal anatomy, sex‐based outcomes should also be evaluated. We endeavored to evaluate sex‐specific post‐GMT voice outcomes.MethodsWe performed a retrospective review of patients undergoing GMT for nonparalytic GI. Multidimensional voice outcome measures including voice‐related quality of life (VRQOL), Glottal Function Index (GFI), and grade/roughness/breathiness/asthenia/strain (GRBAS) were analyzed at postoperative time frames: 0 to 3 months, 3 to 9 months, and 9 to 18 months.ResultsEighty‐five subjects (43 females, 42 males) with mean age 53.5 undergoing GMT for nonparalytic GI from 2005 to 2017 met inclusion criteria. Etiologies included vocal fold hypomobility (N = 36, 42%), paresis (N = 18, 21%), vocal fold atrophy (N = 17, 20%), and scarring (N = 14, 17%). Females had significantly greater improvement on VRQOL at 0 to 3 months and 9 to 18 months timeframes compared to males, with mean change in VRQOL: 41.3 versus 22.4 (P = 0.0002) and 42.5 versus 20.8 (P = 0.002), respectively. Similarly, women had significantly greater improvement in GFI at 0 to 3 months follow‐up (mean difference − 10.8 vs. −4.9, respectively, P = 0.0002). There was no statistically significant sex difference in GRBAS at any follow‐up interval.ConclusionFollowing GMT, females had greater improvement in patient‐reported voice outcomes in the early postoperative period. No significant difference between sexes was noted in perceptual measures (GRBAS). Sex‐specific outcomes should be evaluated for clinical interventions to improve specificity of preoperative counseling.Level of Evidence4. Laryngoscope, 129:2543–2548, 2019
Basaloid nasopharyngeal carcinoma: A population‐based analysis of a rare tumor
Authors: Unsal Aykut A. , Booth J. Renee , Rossi Nicholas A. , Byrd J. Kenneth , Kountakis Stilianos E. 
Published: January 2019

ObjectivesBasaloid nasopharyngeal carcinoma (BNPC) is an extremely rare malignancy with a paucity of cases reported in the literature. This analysis represents the largest cohort of BNPC to date.Study DesignRetrospective population‐based analysis.MethodsThe Surveillance, Epidemiology, and End Results registry from 2001 to 2015 was utilized to extract a total of 82 cases of BNPC. Data were analyzed for incidence trends, demographic, and tumor characteristics, as well as potential outcome prognosticators.ResultsWhite male patients between the ages of 40 to 79 years were most commonly affected. The incidence was measured at 0.06 per 100 thousand people. The majority of tumors were considered high grade (grade III/IV; 92.2%). At presentation, patients were most commonly advanced stage (American Joint Committee on Cancer [AJCC] stage IV) at 29.3%, followed by AJCC stages II and III (20.7%, respectively). T2 tumors were most common at 28.8%. Cervical node involvement and distant metastasis were measured at 53.7% and 10.4%, respectively. One‐year, 5‐year, and 10‐year disease‐specific survival was 87.7%, 60.7%, and 29.8%, respectively. No prognostic factors were identified in this study.ConclusionBasaloid squamous cell carcinoma represents a histologic subtype of nasopharyngeal carcinoma with excellent short‐term outcomes but poor survival at 10 years when compared to conventional squamous cell carcinomas.Level of EvidenceNA Laryngoscope, 129:2727–2732, 2019
Outcomes of transmastoid resurfacing for superior canal dehiscence using a cartilage overlay technique
Authors: Al Afif Ayham , Farmer Robert , Bance Manohar 
Published: January 2019

ObjectiveSuperior semicircular canal dehiscence is a well‐described syndrome with potentially debilitating symptoms. We report on the audiologic and long‐term symptom outcomes of 10 patients (12 ears) undergoing a cartilage overlay transmastoid resurfacing technique.MethodsRetrospective chart review and cross‐sectional outcomes recall survey were used. A mailed questionnaire quantifying the effect of surgery on symptom severity and patient satisfaction were used. Nonlinear regression curves of pre‐/postoperative air and bone pure‐tone audiometric data were used to evaluate postoperative changes in hearing. Surgical failure was defined as requiring revision surgery, and rates were estimated over time using a Kaplan‐Meier analysis.ResultsMost patients reported improved symptoms postoperatively and were satisfied overall with the surgical outcomes. However, four of 12 ears (33%) had a second (revision) surgery before achieving these results. Postoperatively, hearing through air and bone conduction tended to decrease at frequencies greater than 2500 Hz. The chance of avoiding a re‐operation at 36 months (and up to 120 months) was estimated to be 57.1% (95% confidence interval [confidence interval]: 100%, 32.6%). The most common surgical complication was intraoperative cerebrospinal fluid (CSF) leak, encountered exclusively during dural elevation, seen in four of 12 ears (33%).ConclusionAlthough subjectively successful at reducing symptoms, in our small sample this surgical approach did not provide a long‐term stable repair and was frequently associated with intraoperative CSF leak. Offering transmastoid resurfacing to patients should involve a detailed discussion on the potential for revision surgery and risks of diminished hearing and CSF leak.Level of Evidence4Laryngoscope, 129:2164–2169, 2019
Electronically Tunable Distributed Feedback (DFB) Laser on Silicon
Authors: Dhoore Sören , Köninger Anna , Meyer Ralf , Roelkens Gunther , Morthier Geert 
Published: January 2019

AbstractAn electronically tunable distributed feedback (DFB) laser heterogeneously integrated on a silicon photonics platform is experimentally demonstrated. Tuning is achieved through carrier injection into the tuning layer of a tunable twin‐guide III–V membrane on silicon. A 2 nm continuous tuning range is achieved with a single tuning current. Continuous‐wave single‐mode laser operation with a side‐mode suppression ratio larger than 44 dB across the tuning range is obtained. Measured wavelength switching times are on the order of 3 ns and non‐return‐to‐zero on‐off keying direct modulation at 12.5 Gbit s−1 is readily achieved. This work can be a major advance toward the realization of optical burst or packet switching systems for future data center networks.
Deep brain stimulation for pantothenate kinase‐associated neurodegeneration: A meta‐analysis
Authors: De Vloo Philippe , Lee Darrin J. , Dallapiazza Robert F. , Rohani Mohammad , Fasano Alfonso , Munhoz Renato P. , Ibrahim George M. , Hodaie Mojgan , Lozano Andres M. , Kalia Suneil K. 
Published: January 2019

AbstractBackgroundPantothenate kinase‐associated neurodegeneration is a rare autosomal‐recessive disorder, characterized by progressive neurodegeneration associated with brain iron accumulation. DBS has been trialed to treat related movement disorders, particularly dystonia. The objective of this study was to determine the outcome and safety of DBS for pantothenate kinase‐associated neurodegeneration.MethodsWe performed a meta‐analysis using independent participant data (n = 99) from 38 articles. Primary outcome was change in movement and disability scores of the Burke‐Fahn‐Marsden Dystonia Rating Scale 1 year postoperatively. Secondary outcomes were response rate and complications.ResultsPatients with classic‐type (n = 58) and atypical‐type (n = 15) pantothenate kinase‐associated neurodegeneration were operated on at a median age of 11 and 31 years, respectively (P < 0.001). GPi was primarily targeted (n = 87). Mean dystonia movement score improved 1 year following GPi‐DBS (‐26%; 95% confidence interval, ‐37% to ‐15%), particularly in atypical versus classic cases (‐45% vs ‐16%; P < 0.001). At least 30% improvement was observed in 34% of classic versus 73% of atypical cases (P = 0.04). Higher preoperative score and atypical type predicted larger improvement. GPi‐DBS improved dystonia disability score in atypical (‐31%; 95% confidence interval, ‐49% to ‐13%) but not classic (‐5%; 95% confidence interval, ‐17% to 8%) cases. Prevalence of surgical infections (6%) and hardware failure (7%) was similar to other dystonia etiologies. Two patients died within 3 months. There was insufficient data to describe outcome > 1 year following GPi‐DBS or with other DBS targets. Overall, small sample sizes limited generalizability.ConclusionsThis meta‐analysis provides level 4 evidence that GPi‐DBS for pantothenate kinase‐associated neurodegeneration may improve dystonia movement scores in classic type and atypical type and disability scores in atypical type 1 year postoperatively. © 2019 International Parkinson and Movement Disorder Society
An Approach to Identify New Insecticides Against Myzus Persicae. In silico Study Based on Linear and Non‐linear Regression Techniques
Authors: Crisan Luminita , Borota Ana , Suzuki Takahiro , Funar‐Timofei Simona 
Published: January 2019

AbstractNeonicotinoids are known to have high insecticidal potency, low mammalian toxicity and relatively tough activity for the development of resistance against aphids. A series of guadipyr insecticides, active against Myzus persicae was engaged in silico studies, based on Multiple Linear Regression (MLR), Partial Least Squares regression (PLS), Artificial Neural Networks (ANN), Support Vector Machine (SVM) and Pharmacophore modeling. Robust and predictive models were built using correlations between the insecticidal profile, expressed by experimental pLC50 values, and molecular descriptors, calculated from the energy optimized structures. Four new potential insecticides active against Myzus persicae and their predicted pLC50 toxicity values were reported for the first time. The models presented here can be used as an approach in the screening and prioritization of chemicals in a scientific and regulatory frame and for toxicity prediction.
Fish Oil Protects Wild Type and Uncoupling Protein 1‐Deficient Mice from Obesity and Glucose Intolerance by Increasing Energy Expenditure
Authors: Oliveira Tiago E. , Castro Érique , Belchior Thiago , Andrade Maynara L. , Chaves‐Filho Adriano B. , Peixoto Albert S. , Moreno Mayara F. , Ortiz‐Silva Milene , Moreira Rafael J. , Inague Alex , Yoshinaga Marcos Y. , Miyamoto Sayuri , Moustaid‐Moussa Naima , Festuccia William T. 
Published: January 2019

ScopeThe mechanisms and involvement of uncoupling protein 1 (UCP1) in the protection from obesity and insulin resistance induced by intake of a high‐fat diet rich in omega‐3 (n‐3) fatty acids are investigated.Methods and resultsC57BL/6J mice are fed either a low‐fat (control group) or one of two isocaloric high‐fat diets containing either lard (HFD) or fish oil (HFN3) as fat source and evaluated for body weight, adiposity, energy expenditure, glucose homeostasis, and inguinal white and interscapular brown adipose tissue (iWAT and iBAT, respectively) gene expression, lipidome, and mitochondrial bioenergetics. HFN3 intake protected from obesity, glucose and insulin intolerances, and hyperinsulinemia. This is associated with increased energy expenditure, iWAT UCP1 expression, and incorporation of n‐3 eicosapentaenoic and docosahexaenoic fatty acids in iWAT and iBAT triacylglycerol. Importantly, HFN3 is equally effective in reducing body weight gain, adiposity, and glucose intolerance and increasing energy expenditure in wild‐type and UCP1‐deficient mice without recruiting other thermogenic processes in iWAT and iBAT, such as mitochondrial uncoupling and SERCA‐mediated calcium and creatine‐driven substrate cyclings.ConclusionIntake of a high‐fat diet rich in omega‐3 fatty acids protects both wild‐type and UCP1‐deficient mice from obesity and insulin resistance by increasing energy expenditure through unknown mechanisms.
ChebStaBlkCG: A block variant of ChebFilterCG
Authors: Sadkane Miloud , Touhami Ahmed 
Published: January 2019

SummaryThe behavior of ChebFilterCG (an algorithm that combines the Chebyshev filter and Conjugate Gradient) applied to systems with unfavorable eigenvalue distribution is examined. To improve the convergence, a hybrid approach combining a stabilized version of the block conjugated gradient with Chebyshev polynomials as preconditioners (ChebStaBlkCG) is proposed. The performance of ChebStaBlkCG is illustrated and validated on a set of linear systems. It is shown how ChebStaBlkCG can be used to accelerate the block Cimmino method and to solve linear systems with multiple right‐hand sides.
35 years of photovoltaics: Analysis of the TISO‐10‐kW solar plant, lessons learnt in safety and performance—Part 1
Authors: Virtuani Alessandro , Caccivio Mauro , Annigoni Eleonora , Friesen Gabi , Chianese Domenico , Ballif Christophe , Sample Tony 
Published: January 2019

AbstractThe TISO‐10‐kW solar plant, connected to the grid in 1982, is the oldest installation of this kind in Europe. Its history is well documented, and the full set of modules has been tested indoors at regular intervals over the years. After 35 years of operation, we observe an increase in the degradation rates and that the distributions of modules' performances are drastically changing compared with previous years. Two groups of modules can be observed: (a) group 1: 21.5% of the modules show a very modest degradation, described by a Gaussian distribution with mean yearly power degradation of only −0.2%/y. (b) Group 2: 72.9% of the modules form a negatively skewed distribution with a long tail described by mode (−0.54%/y), median (−0.62%/y), and mean (−0.69%/y) values. In earlier years, decreases in performances could strongly be correlated to losses in fill factor (FF). After 35 years, the situation changes and, for a subset of modules, losses in the current (Isc) are superimposed to losses in FF. The reasons for this will become clearer in part 2, where we will present results of a detailed visual inspection on the whole set of modules and will focus on safety aspect too. We conclude that, after 35 years of operation in a temperate climate, approximately 60% (~70% if considering a ± 3% measurement uncertainty) of the modules would still satisfy a warranty criteria that module manufacturers are presently considering to apply to the technology of tomorrow: 35 years of operation with a performance threshold set at 80% of the initial value.