bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and clinical applications of the dried blood spot method for therapeutic drug monitoring of anti‐epileptic drugs
Authors: Min Kyoung Lok , Ryu Jae Yeoul , Chang Min Jung 
Published: June 2019

AbstractAnti‐epileptic drugs (AEDs) have various pharmacokinetic profiles, inter‐individual variabilities, high possibilities of drug‐drug interactions and narrow therapeutic indices. To provide optimal treatment for patients, therapeutic drug monitoring (TDM) is necessary. However, TDM requires sufficient quantities of blood samples to measure drug concentrations. Therefore, TDM could be a burden, particularly in paediatric cases. A good alternative that overcomes these disadvantages is the dried blood spot (DBS) method, which is simple, convenient to use and less invasive, requiring a lower quantity of blood than traditional blood sampling methods. However, the DBS method is affected by haematocrit (Hct) levels to varying extents depending on the drug properties. In addition, different papers with varying characteristics are available for use when applying the DBS method. Therefore, it has not yet been applied to TDM in clinical practice. To achieve this, several steps are required, including method development, method validation and clinical validation. Currently, the development status of the DBS method is different for each AED and unclear. Therefore, we assessed the development status of the following 19 AEDs in 26 studies: lamotrigine, valproic acid, levetiracetam, phenytoin, topiramate, carbamazepine, carbamazepine epoxide, gabapentin, phenobarbital, pregabalin, clobazam, clonazepam, ethosuximide, felbamate, monohydroxycarbamazepine, nitrazepam, rufinamide, vigabatrin and zonisamide. Among them, carbamazepine, lamotrigine, topiramate and valproic acid have been developed such that they are nearly available for TDM. In addition, Whatman 903 Protein Saver Cards and concentration analysis by liquid chromatography with triple quadrupole mass spectrometer were used most often.
The use of freeze‐dried retronasal stimuli to assess olfactory function
Authors: Pal Pooja , Shepherd Daniel , Hamid Nazimah , Hautus Michael J. 
Published: June 2019

AbstractObjectivesTo evaluate a test of olfactory perception that uses freeze‐dried stimuli developed to rapidly release aromas capable of migrating to the olfactory mucosa retronasally.DesignValidation study.SettingPsychology and Chemistry Departments.ParticipantsFirst, 15 participants provided data for psychometric functions. Second, 70 participants made perceptual judgments of retronasal stimuli. Inclusion criterion included informed consent and a satisfactory Nasal Obstruction Symptom Evaluation result.Main outcome measuresFirst, psychometric functions were generated for two types of freeze‐dried stimuli (coffee and orange) using the Single‐Interval Adjustment Matrix method. Second, participants provided ratings of pleasantness, intensity, and familiarity and performed a standardised identification test using seven retronasally presented aromas alongside the previously validated Sniffin’ Sticks orthonasal olfactory test.ResultsPsychometric functions indicated a dose‐response relationship between aroma concentration and probability of detection. Test‐retest reliability of the retronasal stimuli was acceptable (r70 = 0.72, P < 0.001), and identification scores were not dependent on testing method (ie, retronasal vs Sniffin’ Sticks). Stimuli delivered using the Sniffin’ Sticks test were rated more pleasant than their retronasal counterparts.ConclusionsFreeze‐dried retronasal stimuli offer an easy‐to‐use and rapid means to test olfaction function and are arguably well suited for clinical practice, but require further development and trialing prior to the adoption in the clinical context.
Identifying biomarker candidates of influenza infection based on scalable time‐course big data of gene expression
Authors: Zhang Yuan , Zhang Jin , Ju Shan , Qiu Lu 
Published: June 2019

AbstractLarge‐scale biological data processing is an important topic in computational biology, which gives the promotion of many biomedical research. For example, a huge volume of gene expression data can help us achieve potentially useful medical knowledge and identify disease biomarker candidates. Nevertheless, a great deal of attention has been paid to unscalable single‐time‐point expression data after disease symptoms appear (outbreak period) and there have been few investigations into scalable time‐course expression data before disease symptoms appear (incubation) for each sample. By exploiting such dynamic big data in the incubation, we can easily catch early signals of disease states and prevent illness in the first place. In this study, we apply a new mathematical model on biological data of given incubations and identify biomarker candidates using an intellectualized method. The model narrows a large number of alternative genes into a few ones (top genes), which facilitate the discovery of genes related to disease. The aim of our work is to propose a powerful biomarker‐detecting tool, which helps people to aid early diagnosis or identify effective drug targets before the appearance of clinical symptoms.
Circ‐SERPINE2 promotes the development of gastric carcinoma by sponging miR‐375 and modulating YWHAZ
Authors: Liu Jianing , Song Suzhen , Lin Sen , Zhang Mingbao , Du Yating , Zhang Dongdong , Xu Weihua , Wang Hongbo 
Published: June 2019

AbstractObjectivesCircular RNAs (circRNAs) exist extensively in the eukaryotic genome. The study aimed to identify the role of hsa_circ_0008365 (Circ‐SERPINE2) in gastric carcinoma (GC) cells and its downstream mechanisms.Materials and methodsGene Expression Omnibus (GEO) database was applied to screen differentially expressed circRNAs. CircInteractome, TargetScan and miRecords websites were used to predict target relationships. qRT‐PCR and RNase R treatment were utilised to detect molecule expression and confirm the existence of circ‐SERPINE2. RNA pull‐down assay and dual‐luciferase reporter assay were performed for interaction between circRNA and miRNA or mRNA. EdU assay, colony formation assay, and flow cytometry for apoptosis and cell cycle detections were utilised to assess cell function. Western blot and immunohistochemistry (IHC) assays were applied for detection of proteins in tissues or cells.ResultsCirc‐SERPINE2 and YWHAZ were upregulated, and miR‐375 was downregulated in GC tissues and cells. Circ‐SERPINE2 and YWHAZ targetedly bound to miR‐375. Circ‐SERPINE2 promoted cell proliferation and cell cycle progress and inhibited cell apoptosis by sponging miR‐375 and regulating YWHAZ expression in vitro. Circ‐SERPINE2 repressed solid tumour growth through enhancing miR‐375 expression and reducing YWHAZ expression in vivo.ConclusionsCirc‐SERPINE2 is a novel proliferative promoter through the regulation of miR‐375/YWHAZ. Circ‐SERPINE2/miR‐375/YWHAZ axis might provide a novel therapeutic target of GC.
Conservation implications of sex‐specific landscape suitability for a large generalist carnivore
Authors: Gantchoff Mariela , Conlee Laura , Belant Jerrold 
Published: June 2019

AbstractAimTerrestrial mammal distribution models typically do not differentiate between sexes when making spatial predictions, which could have important conservation implications. As male carnivores are usually more risk tolerant and travel longer distances, male potential range should be larger and include more human‐modified areas than female range. To evaluate if differences between females and males could influence their conservation planning, we quantified sex‐specific suitable range for a recolonizing population of American black bears (Ursus americanus).LocationWe applied this method in Missouri, USA.MethodsWe collected telemetry data from 57 females and 43 male bears from 2010 to 2018. We used three machine‐learning methods (generalized boosted regression, random forest and maximum entropy) to develop sex‐specific distribution models, which were combined into a weighted average ensemble model and converted into a binary (presence/absence) model using an optimized threshold. We used 80% of individuals for each sex as training data, and 20% as evaluation data.ResultsAll models had high predictive performance; the greatest uncertainty in model predictions corresponded with the periphery of the distributions, whereas there was high agreement in the core distribution. Male suitable range was 66% larger than female range, and males were predicted to occur in more human‐modified areas and more likely to be present in developed land and agriculture.Main conclusionsDistribution models based on data from both sexes, or that is male‐biased, could overestimate the female (i.e., reproductive) range and potentially misrepresent the biologically relevant species distribution. This bias can potentially lead to misguided decisions and suboptimal use of resources. By improving models when sex‐specific data are available, we can better focus resources in areas where there is reproductive potential, leading to more accurate assessments of species' conservation status and better identifying areas vital for species persistence.
Situated Comparison: A Methodological Response to an Epistemological Dilemma
Authors: Flood David , Starr Julie 
Published: June 2019

AbstractEthnographic knowledge production exists in implicit tension with the tenets of a critical disciplinary politics normalized in the reflexive critiques of the late 20th century. Anthropologists have responded with numerous theoretical ‘turns,’ which in different ways attempt to reconcile the conflicting imperatives of critical attention to histories of power and inequality, with rich and nuanced accounts of cultural worlds and peoples’ agentive roles in them. This article proposes Situated Comparison as one possible methodological approach to this epistemological dilemma. We propose explicit attention to multiple local understandings of categorical social differentiation, which we compare on a plane of epistemic equality with academic theories of those same boundaries. Examples from two disparate fieldwork contexts—classed ideas of ethical sociality in the rural American South; and guanxi and social intimacy in Shanghai, China—demonstrate the potential of this methodology for reflexive engagement with ideas of personhood and self across lines of difference.
Advanced magnetic resonance imaging of cartilage components in haemophilic joints reveals that cartilage hemosiderin correlates with joint deterioration
Authors: von Drygalski Annette , Barnes Richard F. W. , Jang Hyungseok , Ma Yajun , Wong Jonathan H. , Berman Zachary , Du Jiang , Chang Eric Y. 
Published: June 2019

AbstractIntroductionEvidence suggests that toxic iron is involved in haemophilic joint destruction.AimTo determine whether joint iron deposition is linked to clinical and imaging outcomes in order to optimize management of haemophilic joint disease.MethodsAdults with haemophilia A or haemophilia B (n = 23, ≥ age 21) of all severities were recruited prospectively to undergo assessment with Hemophilia Joint Health Scores (HJHS), pain scores (visual analogue scale [VAS]) and magnetic resonance imaging (MRI) at 3T using conventional MRI protocols and 4‐echo 3D‐UTE‐Cones sequences for one affected arthropathic joint. MRI was scored blinded by two musculoskeletal radiologists using the International Prophylaxis Study Group (IPSG) MRI scale. Additionally, UTE‐T2* values of cartilage were quantified. Correlations between parameters were performed using Spearman rank correlation. Two patients subsequently underwent knee arthroplasty, which permitted linking of histological findings (including Perl's reaction) with MRI results.ResultsMRI scores did not correlate with pain scores or HJHS. Sixteen joints had sufficient cartilage for UTE‐T2* analysis. T2* values for cartilage correlated inversely with HJHS (rs = −0.81, P < 0.001) and MRI scores (rs = −0.52, P = 0.037). This was unexpected since UTE‐T2* values decrease with better joint status in patients with osteoarthritis, suggesting that iron was present and responsible for the effects. Histological analysis of cartilage confirmed iron deposition within chondrocytes, associated with low UTE‐T2* values.ConclusionsIron accumulation can occur in cartilage (not only in synovium) and shows a clear association with joint health. Cartilage iron is a novel biomarker which, if quantifiable with innovative joint‐specific MRI T2* sequences, may guide treatment optimization.
Using peer effects to explain retention rates in a private university
Authors: Stinespring John R. , Kench Brian T. , Borja Karla 
Published: June 2019

AbstractThis study identifies factors associated with freshmen retention rates at a mid‐size private university. A key finding from our analysis is that roommates' academic efforts, residing on an honours floor and membership in co‐curricular groups increase retention. We also confirm many standard results in the literature regarding the impact on retention rates, such as student motivation and ability, and financial aid. We show that a timely housing application, closer proximity to home, a higher number of schools on a student's Free Application for Federal Student Aid and peer effects impact freshman retention. Our results suggest that a more sophisticated dormroom assignment algorithm matching students' abilities and interests could be considered to increase freshman retention rates among private institutions.
Steam radish sprout (Raphanus sativus L.): active substances, antioxidant activities and non‐targeted metabolomics analysis
Authors: Li Ru , Hao Rui , Zhu Yi 
Published: June 2019

SummaryVarious active substances, antioxidant activities and primary differential metabolite profiles were investigated to assess the nutritional quality of radish sprouts steamed for 0–300 s. The levels of flavonoids, total phenolic content and isothiocyanate in radish sprouts decreased with increased steaming time, and DPPH radical scavenging activity levels and superoxide dismutase levels also exhibited a downward trend (P < 0.05). By contrast, total phenolic acid, ferric‐reducing antioxidant power and reducing power levels exhibited significant increases in the early short‐term steaming process (P < 0.05). Steaming for 30 s promoted the accumulation of vitamin B2, whereas, steaming for 300 s promoted the accumulation of phospholipids and myristic acid to a greater extent than steaming for 30 s. Overall, there was a partial non‐decreased nutritional indicator in short‐term steaming of radish sprouts, and a longer steaming time positively affected the differential metabolites.
MiR‐34b‐3p represses cell proliferation, cell cycle progression and cell apoptosis in non‐small‐cell lung cancer (NSCLC) by targeting CDK4
Authors: Feng Hongxiang , Ge Feixiang , Du Lanfang , Zhang Zhenrong , Liu Deruo 
Published: June 2019

AbstractLung cancer is the most common incident cancer, with a high mortality worldwide, and non‐small‐cell lung cancer (NSCLC) accounts for approximately 85% of cases. Numerous studies have shown that the aberrant expression of microRNAs (miRNAs) is associated with the development and progression of cancers. However, the clinical significance and biological roles of most miRNAs in NSCLC remain elusive. In this study, we identified a novel miRNA, miR‐34b‐3p, that suppressed NSCLC cell growth and investigated the underlying mechanism. miR‐34b‐3p was down‐regulated in both NSCLC tumour tissues and lung cancer cell lines (H1299 and A549). The overexpression of miR‐34b‐3p suppressed lung cancer cell (H1299 and A549) growth, including proliferation inhibition, cell cycle arrest and increased apoptosis. Furthermore, luciferase reporter assays confirmed that miR‐34b‐3p could bind to the cyclin‐dependent kinase 4 (CDK4) mRNA 3′‐untranslated region (3′‐UTR) to suppress the expression of CDK4 in NSCLC cells. H1299 and A549 cell proliferation inhibition is mediated by cell cycle arrest and apoptosis with CDK4 interference. Moreover, CDK4 overexpression effectively reversed miR‐34‐3p‐repressed NSCLC cell growth. In conclusion, our findings reveal that miR‐34b‐3p might function as a tumour suppressor in NSCLC by targeting CDK4 and that miR‐34b‐3p may, therefore, serve as a biomarker for the diagnosis and treatment of NSCLC.
4‐O‐methylhonokiol protects against diabetic cardiomyopathy in type 2 diabetic mice by activation of AMPK‐mediated cardiac lipid metabolism improvement
Authors: Zheng Zongyu , Ma Tianjiao , Guo Hua , Kim Ki Soo , Kim Kyoung Tae , Bi Liqi , Zhang Zhiguo , Cai Lu 
Published: June 2019

AbstractDiabetic cardiomyopathy (DCM) is characterized by increased left ventricular mass and wall thickness, decreased systolic function, reduced ejection fraction (EF) and ultimately heart failure. The 4‐O‐methylhonokiol (MH) has been isolated mainly from the bark of the root and stem of Magnolia species. In this study, we aimed to elucidate whether MH can effectively prevent DCM in type 2 diabetic (T2D) mice and, if so, whether the protective response of MH is associated with its activation of AMPK‐mediated inhibition of lipid accumulation and inflammation. A total number of 40 mice were divided into four groups: Ctrl, Ctrl + MH, T2D, T2D + MH. Five mice from each group were sacrificed after 3‐month MH treatment. The remaining animals in each group were kept for additional 3 months without further MH treatment. In T2D mice, the typical DCM symptoms were induced as expected, reflected by decreased ejection fraction and lipotoxic effects inducing lipid accumulation, oxidative stress, inflammatory reactions, and final fibrosis. However, these typical DCM changes were significantly prevented by the MH treatment immediately or 3 months after the 3‐month MH treatment, suggesting MH‐induced cardiac protection from T2D had a memory effect. Mechanistically, MH cardiac protection from DCM may be associated with its lipid metabolism improvement by the activation of AMPK/CPT1‐mediated fatty acid oxidation. In addition, the MH treatment of DCM mice significantly improved their insulin resistance levels by activation of GSK‐3β. These results indicate that the treatment of T2D with MH effectively prevents DCM probably via AMPK‐dependent improvement of the lipid metabolism.
Description of a new small‐sizedSynodontisspecies (Siluriformes: Mochokidae) that is important for local subsistence fisheries in the middle Lufira (upper Congo River, DR Congo)
Authors: Kasongo Ilunga Micheline , Abwe Emmanuel , Decru Eva , Chocha Manda Auguste , Vreven Emmanuel 
Published: June 2019

AbstractSynodontis denticulatussp. nov. is an endemic from the middle Lufira Basin and its associated tributaries and lakes. The species shows close morphological resemblance toSynodontis greshoffiandSynodontis unicolor,which are widespread Congo Basin and Bangweulu‐Mweru endemic species, respectively. However, it differs from bothS. greshoffiandS. unicolorby its non‐villous skin (v. villous skin), strong and numerous serrations on the posterior margin of the dorsal spine (v. weak and fewer serrations), weak and few serrations on the posterior margin of the pectoral spine (v. strong and numerous serrations), relatively short maxillary barbels (v. long) and its small maximum standard length (89.1 mmLSv. 148.0 and 190.7 mmLSrespectively). A DNA barcoding study (coI, mtDNA) revealed thatS. denticulatusforms a distinct genetic clade with a genetic distance of 2.18% withS. greshoffiand 0.84% withS. unicolor.Synodontis denticulatusis caught regularly and abundantly as a by‐catch in the gillnet fisheries in the middle Lufira lakes. Owing to its small overall size and large bony head, the species has usually no real commercial value but is an important food fish for the fishermen's families.
Synergistic regulation of drought‐responsive genes by transcription factor OsbZIP23 and histone modification in rice
Authors: Zong Wei , Yang Jun , Fu Jie , Xiong Lizhong 
Published: June 2019

SummaryThousands of differentially expressed genes (DEGs) have been identified in rice under drought stress conditions. However, the regulatory mechanism of these DEGs remains largely unclear. Here, we report an interplay between histone H3K4me3 modification and transcription factor OsbZIP23 in the regulation of a dehydrin gene cluster under drought stress conditions in rice. When the H3K4me3 modification level was increased, the dehydrin gene expression levels were increased, and the binding levels of OsbZIP23 to the promoter of the dehydrin genes were also enhanced. Conversely, the H3K4me3 modification and dehydrin gene expression levels were downregulated in the osbzip23 mutant under drought stress conditions. Our study uncovers a collaboration between transcription factor and H3K4me3 modification in the regulation of drought‐responsive genes, which will help us to further understand the gene regulation mechanism under stress conditions in plants.
Chemerin inhibits vascular calcification through ChemR23 and is associated with lower coronary calcium in chronic kidney disease
Authors: Carracedo M. , Witasp A. , Qureshi A. R. , Laguna‐Fernandez A. , Brismar T. , Stenvinkel P. , Bäck M. 
Published: June 2019

AbstractBackgroundChemerin is an adipokine that signals through the G protein‐coupled receptor ChemR23 and is associated with inflammation, glucose homeostasis, lipid metabolism and renal function, all of which strongly influence cardiovascular risk. However, elevated chemerin provides a survival advantage in patients with chronic kidney disease (CKD), but how this relates to the cardiovascular phenotype is unknown.ObjectivesThe aim of the present study was to establish the association of chemerin with coronary calcification and to determine the effects of chemerin signalling, through ChemR23, in vascular smooth muscle cell (VSMC) calcification.MethodsPlasma chemerin was measured in 113 patients with CKD and 50 healthy controls. All patients underwent computed tomography to determine coronary artery calcium (CAC) score. VSMCs were isolated from wild‐type and ChemR23 knock‐out mice and treated with chemerin.ResultsMultivariate analyses established creatinine, cholesterol, body mass index and tumour necrosis factor as significant confounders for circulating chemerin levels. Despite these positive associations with renal function, cardiometabolic risk factors and inflammation, chemerin was inversely associated with CAC both in an age‐ and sex‐adjusted analysis and in a multivariate analysis adjusting for the aforementioned confounders. In addition, circulating chemerin levels were associated with the calcification inhibitors matrix gla protein (MGP) and fetuin‐A. Finally, chemerin significantly reduced phosphate‐induced calcification and increased MGP expression in VSMCs, whereas chemerin was devoid of these effects in VSMCs lacking ChemR23.ConclusionIn conclusion, these results suggest that chemerin signalling through ChemR23 in VSMCs protects against vascular calcification in CKD.