bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacodynamic and pharmacokinetic profile of SM‐1, a triple‐drug combination to increase total sleep time
Authors: Dahl Thomas , Chen Lan Bo , Scheinin Mika , Suopanki‐Lalowski Jaana , Valge Marju , Puhakka Antti , Mikola Hannu , Lovró Zsófia , Meierjohann Axel , Vuorilehto Lauri , Roth Thomas 
Published: December 2019

AbstractObjectiveThe primary objective was to characterize the pharmacokinetics and pharmacodynamics of SM‐1 after administration of a single oral dose to healthy volunteers in a placebo‐controlled double‐blind trial of daytime sedation. Secondary objectives were to determine the onset, duration, and offset of the sedative effects using subjective and objective measures of sedation. Safety and tolerability of SM‐1 were also investigated.MethodsMales and females 18–45 years of age received SM‐1, a combination drug product comprised of diphenhydramine, zolpidem (delayed release), and lorazepam (delayed release). The pharmacokinetic profile of each drug was determined from blood samples. Sedative effects were assessed by visual analog scale, digit symbol substitution test, memory test, and quantitative electroencephalography.ResultsSimilar number and severity of adverse events were observed following administration of SM‐1 and placebo. Onset of sedation, as determined by subjective, performance, and electroencephalography measures, occurred 0.5–1 hr postdose, lasting about 7–7.5 hr. Plasma concentration curves for the two delayed‐release components were altered compared with published data for unmodified drugs. Exposure values obtained with the combination product were in good agreement with published values of the drugs given individually.ConclusionsSM‐1 was well tolerated and has pharmacologic activity starting within an hour of ingestion, lasting approximately 7–8 hr. Sedative activity was seen with subjective, psychomotor, and electroencephalography assays.
SANITARY QUALITY OF IRRIGATED VEGETABLES IN THE SWAMPY LOWLANDS OF DSCHANG CITY, CAMEROON
Authors: Ntangmo Tsafack Honorine , Temgoua Emile , Njine Thomas 
Published: December 2019

AbstractIn Dschang City, as in Cameroon's secondary cities, waterborne diseases are increasing. Stream waters are used for watering crops. The purpose of this work was to evaluate the health risk of irrigating vegetables (lettuce, carrots and eggplants) in the Dschang lowlands. Escherichia coli, Entamoeba spp. cysts, Ascaris lumbricoides eggs, major elements and trace elements were looked for in the vegetables collected from 18 plots. The results show that market gardening is practised mainly in the lowlands that receive all the untreated waste from the city. Stream waters used for spraying crops contains approximately 4.2 Log (CFU of E. coli) in 100 ml, regardless of the season. Eggs and parasite cysts were detected. The vegetables analysed have a low and acceptable chemical content. Regardless of the season, E. coli found on crops was far above the standards (103 UFCg−1 DM), 5–58 times above. Eggs and parasite cysts were also detected. These parasites and bacteria represent a real risk to consumers and would be partly responsible for the upsurge of waterborne diseases in Dschang City. © 2019 John Wiley & Sons, Ltd.
Systematic in vitro biocompatibility studies of multimodal cellulose nanocrystal and lignin nanoparticles
Authors: Imlimthan Surachet , Correia Alexandra , Figueiredo Patrícia , Lintinen Kalle , Balasubramanian Vimalkumar , Airaksinen Anu J. , Kostiainen Mauri A. , Santos Hélder A. , Sarparanta Mirkka 
Published: December 2019

AbstractNatural biopolymer nanoparticles (NPs), including nanocrystalline cellulose (CNC) and lignin, have shown potential as scaffolds for targeted drug delivery systems due to their wide availability, cost‐efficient preparation, and anticipated biocompatibility. As both CNC and lignin can potentially cause complications in cell viability assays because of their ability to scatter the emitted light and absorb the assay reagents, we investigated the response of bioluminescent (CellTiter‐Glo®), colorimetric (MTT® and AlamarBlue®), and fluorometric (LIVE/DEAD®) assays for the determination of the biocompatibility of the multimodal CNC and lignin constructs in murine RAW 264.7 macrophages and 4T1 breast adenocarcinoma cell lines. Here, we have developed multimodal CNC and lignin NPs harboring the radiometal chelator 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid and the fluorescent dye cyanine 5 for the investigation of nanomaterial biodistribution in vivo with nuclear and optical imaging, which were then used as the model CNC and lignin nanosystems in the cell viability assay comparison. CellTiter‐Glo® based on the detection of ATP‐dependent luminescence in viable cells revealed to be the best assay for both nanoconstructs for its robust linear response to increasing NP concentration and lack of interference from either of the NP types. Both multimodal CNC and lignin NPs displayed low cytotoxicity and favorable interactions with the cell lines, suggesting that they are good candidates for nanosystem development for targeted drug delivery in breast cancer and for theranostic applications. Our results provide useful guidance for cell viability assay compatibility for CNC and lignin NPs and facilitate the future translation of the materials for in vivo applications.
Loss-of-Function Mutations in the ALPL Gene Presenting with Adult Onset Osteoporosis and Low Serum Concentrations of Total Alkaline Phosphatase
Authors: Alonso Nerea , Larraz-Prieto Beatriz , Berg Kathryn , Lambert Zoe , Redmond Paul , Harris Sarah E , Deary Ian J , Pugh Carys , Prendergast James , Ralston Stuart H 
Published: December 2019

ABSTRACT
Hypophosphatasia (HPP) is a rare inherited disorder characterized by rickets and low circulating concentrations of total alkaline phosphatase (ALP) caused by mutations in ALPL. Severe HPP presents in childhood but milder forms can present in adulthood. The prevalence and clinical features of adult HPP are poorly defined. The aim of this study was to evaluate the prevalence and clinical significance of low serum total alkaline phosphatase (ALP) levels in a clinic-based population of adult osteoporotic patients. We searched for patients with low ALP in a cohort of 3285 patients referred to an osteoporosis clinic over a 10-year period and performed mutation screening of ALPL in those with low ALP (≤40 U/L) on two or more occasions. These individuals were matched with four clinic controls with a normal ALP. We also evaluated the prevalence of low ALP and ALPL mutations in 639 individuals from the general population from the same region. We identified 16/3285 (0.49%) clinic patients with low ALP and 14 (87.5%) had potentially pathogenic variants in ALPL. Eight of these individuals were heterozygous for mutations previously described in HPP and 2 were heterozygous for novel mutations (p.Arg301Trp and p.Tyr101X). These mutations were not found in clinic controls or in the general population. Eight patients with low ALP, including 4 with ALPL mutations, were treated with bisphosphonates for an average of 6.5 years. In these individuals, the rate of fractures during treatment was comparable to that in normal ALP clinic controls who were treated with bisphosphonates. We conclude that heterozygous loss-of-function mutations in ALPL are common in osteoporosis patients with low ALP. Further studies are required to determine how best these individuals should be treated. © 2019 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.
Aberrant expression of ADAM9 in ovarian cancer and its clinical significance
Authors: Guo Ting , Yuan Donglan , Lin Mei , Zhu Dandan , Xu Ning , Wang Jun 
Published: December 2019

AbstractBackgroundThe oncogene a disintegrin and metalloproteinase 9 (ADAM9) was up‐regulated in ovarian cancer tissues, and the present study aims to explore the potential diagnostic and prognostic value of ADAM9 in ovarian cancer (OC).MethodsA total of 30 paired fresh OC tumor tissues and the paired‐adjacent normal tissue, and 90 formalin‐fixed paraffin‐embedded (FFPE) OC samples and adjacent normal tissue were collected. The expression of OC in FFPE samples was examined by immunohistochemical methods, and the mRNA expression of ADAM9 in fresh tumor samples was examined by RT‐qPCR methods. Receiver operating characteristics curve was drawn to analyze the potential diagnostic value of ADAM9. Kaplan‐Meier survival analysis was performed to compare the overall survival (OS) and disease‐free survival (DFS) of the ADAM9 positive and negative OC patients.ResultsThe positive rate of ADAM9 in FFPE OC tumor tissue was markedly higher than in the non‐tumorous tissue (61/90 vs 47/90), and increased expression level of ADAM9 may associate with higher histological grade, advanced Figo stage and increased risk of metastasis; moreover, the mRNA expression of ADAM9 was also increased in OC tissue compared with the normal tissue (P < .001), and results of ROC analysis suggested that ADAM9 is a sensitive marker for the diagnosis of OC( AUC 0.8389, 95% confidence interval 0.7333 to 0.9445); finally, increased expression of ADAM9 may indicate decreased OS (P = .004) and DFS (P = .014) of the patients.ConclusionA disintegrin and metalloproteinase 9 was up‐regulated in OC, and ADAM9 may serve as potential diagnostic and prognostic marker for the diagnosis and treatment of OC.
Extraction and purification of violacein from Yarrowia lipolytica cells using aqueous solutions of surfactants
Authors: Kholany Mariam , Trébulle Pauline , Martins Margarida , Ventura Sónia PM , Nicaud Jean‐Marc , Coutinho João AP 
Published: December 2019

AbstractBACKGROUNDThe demand for colorants from natural bio‐based sources is increasing. Violacein is a natural purple‐blue hydrophobic pigment with interesting bioactivity whose expression in genetically modified Yarrowia lipolytica production was successfully achieved.RESULTSIn this work, several surfactants were tested in the extraction of violacein from Y. lipolytica cells, and the operational conditions were optimized to maximize the extraction yield. After the optimization, the purification of violacein using aqueous biphasic systems (ABS) composed of Tween 20 and cholinium‐based ionic liquids (ILs) was pursued. The ABS were characterized and applied in the separation of violacein from contaminant proteins, reaching a maximum selectivity of 155 with violacein being fully concentrated in the Tween 20‐rich phase, with 80% of the contaminant proteins present in the extract being removed.CONCLUSIONThis work led to a conceptual downstream process based on a first step of (solid–liquid) extraction and a second step addressing the separation of violacein from contaminant proteins using ABS. © 2019 Society of Chemical Industry
Impact of additional polishing method on physical, micromorphological, and microtopographical properties of conventional composites and bulk fill
Authors: de Fátima Alves da Costa Giovanna , Melo Ana Margarida dos Santos , de Assunção Isauremi Vieira , Borges Boniek Castillo Dutra 
Published: December 2019

AbstractThe objective of this study was to evaluate the surface roughness (SR), contact angle (CA), depth distribution of the charge particles (DDCP), mapping of chemical elements, 3D microtopography (3DM), and the micromorphology of the composites (MOR) of conventional and bulk fill after additional polishing. The specimens were prepared from Filtek Bulk Fill (FBF), Tetric N‐Ceram Bulk Fill (TNCBF), Opus Bulk Fill (OBF), X‐tra Fil (XTFL), Filtek Z250 XT (XT), Grandioso (GRA), Tetric N‐Ceram (TNC), Vittra APS (VT), according to three additional techniques (n = 10): without finishing and polishing, finishing and polishing with abrasive rubbers (Astropol), finishing and polishing with Astropol plus additional polishing with silicon carbide brush. The SR and CA were measured using a profilometer and adapted goniometer, respectively; 3DM used atomic force microscopy (AFM); the micromorphology and DDCP by scanning electron microscopy (SEM) and the MOR by means of X‐ray dispersive energy spectroscopy (EDS). The SR and CA were analyzed by ANOVA‐two factors and Tukey test (p < .05); the others data were analyzed descriptively. The DDCP of all the resins had an organic matrix rich surface layer and a particulate rich subsurface layer of smaller dimensions. Additional polishing: reduced SR of FBF, VT, TNCBF, and XTFL resins; increased the CA value of the XTFL and decreased of XT. In the analyzes for 3DM, smoother and more uniform surfaces were observed in all a resins. The elements: carbon (predominant), oxygen, silicon, zirconia, and aluminum were present in all composite resins. Therefore, additional polishing improved the surface properties of the resins studied.
Relative Enhanced Diffusivity in Prostate Cancer: Protocol Optimization and Diagnostic Potential
Authors: Billdal Daniel C. , While Peter T. , Selnæs Kirsten M. , Sunoqrot Mohammed R. S. , Langørgen Sverre , Bertilsson Helena , Bathen Tone F. , Elschot Mattijs 
Published: December 2019

BackgroundRelative enhanced diffusivity (RED) is a potential biomarker for indirectly measuring perfusion in tissue using diffusion‐weighted magnetic resonance imaging (MRI) with 3 b values.PurposeTo optimize the RED MRI protocol for the prostate, and to investigate its potential for prostate cancer (PCa) diagnosis.Study TypeProspective.PopulationTen asymptomatic healthy volunteers and 35 patients with clinical suspicion of PCa.Sequence3T T2‐ and diffusion‐weighted MRI with b values: b = 0, 50, [100], 150, [200], 250, [300], 400, 800 s/mm2 (values in brackets were only used for patients).AssessmentMonte Carlo simulations were performed to assess noise sensitivity of RED as a function of intermediate b value. Volunteers were scanned 3 times to assess repeatability of RED. Patient data were used to investigate RED's potential for discriminating between biopsy‐confirmed cancer and healthy tissue, and between true and false positive radiological findings.Statistical TestsWithin‐subject coefficient of variation (WCV) to assess repeatability and receiver‐operating characteristic curve analysis and logistic regression to assess diagnostic performance of RED.ResultsThe repeatability was acceptable (WCV = 0.2‐0.3) for all intermediate b values tested, apart from b = 50 s/mm2 (WCV = 0.3‐0.4). The simulated RED values agreed well with the experimental data, showing that an intermediate b value between 150‐250 s/mm2 minimizes noise sensitivity in both peripheral zone (PZ) and transition zone (TZ). RED calculated with the b values 0, 150 and 800 s/mm2 was significantly higher in tumors than in healthy tissue in both PZ (P < 0.001, area under the curve [AUC] = 0.85) and PZ + TZ (P < 0.001, AUC = 0.84). RED was shown to aid apparent diffusion coefficient (ADC) in differentiating between false‐positive findings and true‐positive PCa in the PZ (AUC; RED = 0.71, ADC = 0.74, RED+ADC = 0.77).Data ConclusionRED is a repeatable biomarker that may have value for prostate cancer diagnosis. An intermediate b value in the range of 150‐250 s/mm2 minimizes the influence of noise and maximizes repeatability.Level of Evidence: 2Technical Efficacy Stage: 1J. Magn. Reson. Imaging 2020;51:1900–1910.
Preconditioning of the precipitation interannual variability in southern Mexico and Central America by oceanic and atmospheric anomalies
Authors: Straffon Alejandra , Zavala‐Hidalgo Jorge , Estrada Francisco 
Published: December 2019

AbstractThe interannual variability of precipitation in southern Mexico, northwestern Central America, and part of the northeastern tropical Pacific and its relation with previous oceanic and atmospheric anomalies are studied using the National Centers for Environmental Prediction Climate Forecast System Reanalysis data for 1979–2015. The rainy season over the study region was divided into three intraseasonal phases: before, during, and after the mid‐summer drought. The interannual precipitation anomalies between the three phases are significantly correlated with each other, although there are years in which the precipitation anomalies for different phases differ in their sign. The interannual variability of the precipitation in this region is closely related with previous oceanic and atmospheric anomalies that occurred in the 60–31 days before the beginning of each phase. Multilinear regression models, between precipitation anomalies and previous anomalies of oceanic and atmospheric variables, explain 49, 60, and 55% of the variance of the precipitation interannual variability for the respective phase. Within a phase, in more than 76% of the cases, the estimated precipitation anomalies had the correct sign but in most cases their amplitude, irrespective of sign, were underestimated, as is expected from a regression model which aims to estimate the conditional mean. The more relevant processes associated with the interannual variability of precipitation in the study area are the westward displacement and strengthening of the North Atlantic Subtropical High, the meridional displacement of the Intertropical Convergence Zone and the strength of the Caribbean Low‐Level Jet. In general, the mechanisms that explain interannual variability of precipitation are the same through the phases. However, the magnitude of the anomalies and the size of the regions evolve in time in a particular way for each variable.
Ultra‐small and abundant: Candidate phyla radiation bacteria are potential catalysts of carbon transformation in a thermokarst lake ecosystem
Authors: Vigneron Adrien , Cruaud Perrine , Langlois Valérie , Lovejoy Connie , Culley Alexander I. , Vincent Warwick F. 
Published: December 2019

AbstractThe candidate phyla radiation (CPR) is a diverse group of uncultured bacterial lineages with poorly understood metabolic functions. CPR bacteria can represent a large proportion of the total planktonic microbial community in subarctic thermokarst lakes, but their functional roles remain unexplored. We applied sequential water filtration and metagenomic shotgun sequencing to a peatland permafrost thaw lake, and found high proportions of CPR bacteria in both summer and winter (> 40% of 16S rRNA reads in the 0.02–0.22 μm pore‐size fraction). The metagenome‐assembled genomes of CPR bacteria representatives showed capacities to degrade and ferment permafrost‐ and peatland‐derived organic matter. Potential products of their metabolic activities included acetate, CO2, and hydrogen, implying a syntrophic relationship with other community members, including methanogens and methanotrophs. The results indicate biogeochemical interdependencies in organic matter utilization within thermokarst microbial communities, with CPR members playing a key intermediate role in carbon and methane cycling.
Segmental uniparental disomy of chromosome 4 in a patient with methylmalonic acidemia
Authors: Chen Min , Hao Hu , Xiong Hui , Cai Yao , Ma Fei , Shi Congcong , Xiao Xin , Li Sitao 
Published: December 2019

AbstractBackgroundMethylmalonic acidemia (MMA) is an autosomal recessive genetic disorder involving the metabolism of organic acids.MethodsHere, we report the case of a patient who developed acute metabolic crisis after vaccination and was diagnosed with cblA type MMA after hospitalization.ResultsFurther examination revealed a homozygous pathogenic variant in the MMAA gene that caused the disease in the patient but did not conform to Mendelian inheritance. Using chromosomal microarray analysis, maternal uniparental disomy (UPD) was found on chromosome 4q26‐q35.2 of the patient. The MMAA gene of the patient was inherited only from the mother and carried the same pathogenic variant on both alleles of chromosome 4. MMAA gene expression levels in whole blood were detected by real‐time PCR.ConclusionThe nonsense pathogenic variant, NM_172250.2:c.742C>T (p.Gln248*), carried by the patient leads to a premature termination of transcription of the gene, thereby resulting in partial loss of protein function while retaining some others. Segmental UPD 4 is rare, and to our knowledge, has not been reported previously.
A novel lightweight and low‐loss stripline with embedded air cavity
Authors: Cong You‐Ji , Chang De‐Jie , Cheng Hai‐Rong , Li Jiang , Wu Shao‐Peng 
Published: December 2019

AbstractThis article presents a novel structure of stripline which is made of sandwich structure composed of printed circuit board (PCB) and polymethacrylimide foam, and a loss reduction design is carried out. Compared with the traditional air stripline structure, the weight of proposed structure is reduced by more than 80% with the transmission loss slightly increases. The transmission loss of this stripline structure is significantly lower than that of PCB and low‐temperature cofired ceramic stripline structure. A section of transmission line is fabricated and measured for verification; the measured results are in good agreement with the theoretical simulation, and it shows about 0.1 dB per 100 mm of transmission loss at C band.
Comparison of MRI and motor evoked potential with triple stimulation technique for the detection of brachial plexus abnormalities in multifocal motor neuropathy
Authors: Corazza Giovanni , Le Corroller Thomas , Grapperon Aude‐Marie , Salort‐Campana Emmanuelle , Verschueren Annie , Attarian Shahram , Delmont Emilien 
Published: December 2019

AbstractBackgroundConduction blocks (CB) are the diagnostic hallmark of multifocal motor neuropathy (MMN). Conventional nerve conduction studies cannot detect CB above Erb's point. Our purpose was to compare the performance of the motor evoked potential with triple stimulation technique (MEP‐TST) and MRI in the detection of abnormalities of the brachial plexus.MethodsExaminations were performed on 26 patients with MMN (11 definite, 6 probable, 9 possible), of whom 7 had no CB.ResultsMEP‐TST detected proximal CB in 19/26 patients. Plexus MRI showed T2 hyperintensity in 18/26 patients, with nerve enlargement in 14/18. A combination of both techniques increased the detection rate of brachial plexus abnormalities to 96% of patients (25/26).ConclusionsMEP‐TST and MRI have high sensitivities for detecting brachial plexus abnormalities. A combination of the two techniques increases the detection rate of supportive criteria for the diagnosis of MMN.