bluuebunny/crossref_metadata_2025_split huggingface dataset:
Magnetic-Dispersive Solid Phase Extraction Based on Graphene Oxide–Fe3O4 Nanocomposites Followed by High Performance Liquid Chromatography-Fluorescence for the Preconcentration and Determination of Terazosin Hydrochloride in Human Plasma
Authors: Pashaei Yaser , Daraei Bahram , Shekarchi Maryam 
Published: October 2019

Abstract
In the present study, a facile modified impregnation method was employed to synthesize superparamagnetic graphene oxide–Fe3O4 (GO–Fe3O4) nanocomposites. Based on the GO–Fe3O4 as adsorbent, a simple and fast magnetic-dispersive solid phase extraction followed by high performance liquid chromatography with fluorescence detection (M-dSPE–HPLC–FL) method was established and validated for the preconcentration and determination of terazosin hydrochloride (TRZ) in human plasma samples. The obtained nanomaterials were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, energy dispersive X-ray spectroscopy and vibrating sample magnetometry. Different parameters affecting the extraction efficiency, such as sample pH, amount of sorbent, extraction time, elution solvent and its volume and desorption time, were evaluated and optimized. The linearity of the proposed method was excellent over the range 0.3–50.0 ng mL−1 with an acceptable coefficient of determination (R2 = 0.9989). The limit of quantification and limit of detection were found to be 0.3 and 0.09 ng mL−1, respectively, and the preconcentration factor of 10 was achieved. Intra- and inter-day precision expressed as relative standard deviation (RSD %, n = 6) were between 2.2–3.8% and 4.7–6.4%, respectively. Accuracy, estimated by recovery assays, was 97.7–106.6% with RSD ≤ 5.2%. Ultimately, the applicability of the method was successfully confirmed by the extraction and determination of TRZ in human plasma samples.
A High-Performance Liquid Chromatographic Method for the Determination of Meropenem in Serum
Authors: Dincel Demet , Sagirli Olcay , Topcu Gulacti 
Published: October 2019

Abstract
In this study, a new, sensitive and selective high-performance liquid chromatographic method was developed for the determination of meropenem (MEM) in human serum. In the developed method, C18 column (3.9 × 150 mm, 5 μm) was selected as stationary phase at 30°C, and methanol: acetic acid solution mixture was used as mobile phase with gradient program. Chromatographic separation was carried out at a flow rate of 1 mL/min, and detection was performed at 300 nm with diode array detector. Doripenem was selected as an internal standard, and the analytes were extracted from serum using protein precipitation method with ortho-phosphoric acid: methanol. Detection wavelength was selected as 300 nm. The developed method was validated according to International Council for Harmonisation (ICH) guidelines. The calibration curve was linear over a concentration range of 4–240 μg/mL with correlation coefficient of 0.9985. The limit of detection and limit of quantification values were found as 0.057 and 0.192 μg/mL, respectively. The validated method was successfully applied for the determination of MEM in human serum samples collected from patient volunteers at different time intervals, and therapeutic drug monitoring of MEM has been investigated.
Detection of Anti-CagA Antibodies in Sera of Helicobacter pylori-Infected Patients Using an Immunochromatographic Test Strip
Authors: Karakus Cebrail , Ulupinar Zeynep , Akbas Fahri , Yazici Duygu 
Published: October 2019

Abstract
The cagA gene of Helicobacter pylori that encodes an immunodominant CagA protein provokes severe mucosal damage and acts as a risk factor for the development of peptic ulcer disease and gastric cancer. Our aim is to develop an immunochromatographic test strip (ICTS) using our previously developed recombinant CagA (rCagA) protein and anti-rCagA monoclonal antibody (Mab) for the detection of anti-CagA antibodies in sera of infected patients. The rCagA was firstly conjugated to gold nanoparticle and placed into the conjugate pad. A nonconjugated rCagA and anti-rCagA Mab (CK-02) were immobilized on the test line and control line, respectively. Biopsy and serum samples from 30 H. pylori-infected patients were used. The presence of cagA gene in biopsy samples was first detected by PCR (Polymerase Chain Reaction), and 22 patients were found positive while 8 were negative. When serum samples were tested by our developed ICTS, 21 were positive for anti-CagA antibodies while 9 were negative. The serum samples were also tested by a commercial ELISA (Enzyme Linked Immunosorbent Assay), and when compared to the ICTS a sensitivity of 95% and a specificity of 100% were obtained. The ICTS can be used for rapid detection of CagA-positive H. pylori infection instead of expensive, time consuming and laborious invasive approaches.
Network depth: identifying median and contours in complex networks
Authors: Bertagnolli Giulia , Agostinelli Claudio , De Domenico Manlio 
Published: October 2019

AbstractCentrality descriptors are widely used to rank nodes according to specific concept(s) of importance. Despite the large number of centrality measures available nowadays, it is still poorly understood how to identify the node which can be considered as the ‘centre’ of a complex network. In fact, this problem corresponds to finding the median of a complex network. The median is a non-parametric—or better, distribution-free—and robust estimator of the location parameter of a probability distribution. In this work, we present the statistical and most natural generalization of the concept of median to the realm of complex networks, discussing its advantages for defining the centre of the system and percentiles around that centre. To this aim, we introduce a new statistical data depth and we apply it to networks embedded in a geometric space induced by different metrics. The application of our framework to empirical networks allows us to identify central nodes which are socially or biologically relevant.
Benefits and challenges of Big Data in healthcare: an overview of the European initiatives
Authors: Pastorino Roberta , De Vito Corrado , Migliara Giuseppe , Glocker Katrin , Binenbaum Ilona , Ricciardi Walter , Boccia Stefania 
Published: October 2019

Abstract
Healthcare systems around the world are facing incredible challenges due to the ageing population and the related disability, and the increasing use of technologies and citizen’s expectations. Improving health outcomes while containing costs acts as a stumbling block. In this context, Big Data can help healthcare providers meet these goals in unprecedented ways. The potential of Big Data in healthcare relies on the ability to detect patterns and to turn high volumes of data into actionable knowledge for precision medicine and decision makers. In several contexts, the use of Big Data in healthcare is already offering solutions for the improvement of patient care and the generation of value in healthcare organizations. This approach requires, however, that all the relevant stakeholders collaborate and adapt the design and performance of their systems. They must build the technological infrastructure to house and converge the massive volume of healthcare data, and to invest in the human capital to guide citizens into this new frontier of human health and well-being. The present work reports an overview of best practice initiatives in Europe related to Big Data analytics in public health and oncology sectors, aimed to generate new knowledge, improve clinical care and streamline public health surveillance.
Implementation of the adverse childhood experiences conversation in primary care
Authors: Bodendorfer Victoria , Koball Afton M , Rasmussen Cary , Klevan Judy , Ramirez Luis , Olson-Dorff Denyse 
Published: October 2019

AbstractBackgroundResearch has focused on screening for adverse childhood experiences, rather than provision of education as a part of routine anticipatory guidance. An adverse childhood experiences ‘conversation’ is one method that has not been studied empirically but represents a complimentary or alternative approach to screening which could overcome many existing barriers.ObjectivesThis study aims to examine parent/guardian and provider acceptability/feasibility of the adverse childhood experiences conversation during well-child visits in primary care.MethodsProviders engaged in a conversation with parents/guardians of patients during well-child visits in a family medicine residency clinic. Parents/guardians and providers were surveyed following the visit to examine acceptability and feasibility. Quarterly assessments to further examine provider perspectives were completed. Data were collected for 1 year.ResultsIn total, 238 parent/guardian and 231 provider surveys were completed. Most parents/guardians felt positively (76%) about and comfortable (81%) with the information discussed and 97% felt that the conversation should be had with their primary care provider specifically. Most providers (71%) indicated that parents/guardians were receptive to the conversation, that the conversations took 1–2 minutes (60%) and that there were few disclosures of adversity (9%), none of which required mandatory reporting.ConclusionsResults suggest that the adverse childhood experiences conversation is well received by parents/guardians and providers and is feasible to implement into primary care. The conversation could be used as a complimentary or alternative method to screening to further spread knowledge of toxic stress and health, provide resources for families and promote resilience.
Discordance in the Epithelial Cell-Dendritic Cell Major Histocompatibility Complex Class II Immunoproteome: Implications for Chlamydia Vaccine Development
Authors: Karunakaran Karuna P , Yu Hong , Jiang Xiaozhou , Chan Queenie W T , Foster Leonard J , Johnson Raymond M , Brunham Robert C 
Published: October 2019

Abstract

Background
Chlamydia trachomatis and Chlamydia muridarum are intracellular bacterial pathogens of mucosal epithelial cells. CD4 T cells and major histocompatibility complex (MHC) class II molecules are essential for protective immunity against them. Antigens presented by dendritic cells (DCs) expand naive pathogen-specific T cells (inductive phase), whereas antigens presented by epithelial cells identify infected epithelial cells as targets during the effector phase. We previously showed that DCs infected by C trachomatis or C muridarum present epitopes from a limited spectrum of chlamydial proteins recognized by Chlamydia-specific CD4 T cells from immune mice.

Methods
We hypothesized that Chlamydia-infected DCs and epithelial cells present overlapping sets of Chlamydia-MHC class II epitopes to link inductive and effector phases to generate protective immunity. We tested that hypothesis by infecting an oviductal epithelial cell line with C muridarum, followed by immunoaffinity isolation and sequencing of MHC class I- and II-bound peptides.

Results
We identified 26 class I-bound and 4 class II-bound Chlamydia-derived peptides from infected epithelial cells. We were surprised to find that none of the epithelial cell class I- and class II-bound chlamydial peptides overlapped with peptides presented by DCs.

Conclusions
We suggest the discordance between the DC and epithelial cell immunoproteomes has implications for delayed clearance of Chlamydia and design of a Chlamydia vaccine.
A novel mechanism-based pharmacokinetic–pharmacodynamic (PKPD) model describing ceftazidime/avibactam efficacy against β-lactamase-producing Gram-negative bacteria
Authors: Kristoffersson Anders N , Bissantz Caterina , Okujava Rusudan , Haldimann Andreas , Walter Isabelle , Shi Tianlai , Zampaloni Claudia , Nielsen Elisabet I 
Published: October 2019

Abstract

Background
Diazabicyclooctanes (DBOs) are an increasingly important group of non β-lactam β-lactamase inhibitors, employed clinically in combinations such as ceftazidime/avibactam. The dose finding of such combinations is complicated using the traditional pharmacokinetic/pharmacodynamic (PK/PD) index approach, especially if the β-lactamase inhibitor has an antibiotic effect of its own.

Objectives
To develop a novel mechanism-based pharmacokinetic–pharmacodynamic (PKPD) model for ceftazidime/avibactam against Gram-negative pathogens, with the potential for combination dosage simulation.

Methods
Four β-lactamase-producing Enterobacteriaceae, covering Ambler classes A, B and D, were exposed to ceftazidime and avibactam, alone and in combination, in static time–kill experiments. A PKPD model was developed and evaluated using internal and external evaluation, and combined with a population PK model and applied in dosage simulations.

Results
The developed PKPD model included the effects of ceftazidime alone, avibactam alone and an ‘enhancer’ effect of avibactam on ceftazidime in addition to the β-lactamase inhibitory effect of avibactam. The model could describe an extensive external Pseudomonas aeruginosa data set with minor modifications to the enhancer effect, and the utility of the model for clinical dosage simulation was demonstrated by investigating the influence of the addition of avibactam.

Conclusions
A novel mechanism-based PKPD model for the DBO/β-lactam combination ceftazidime/avibactam was developed that enables future comparison of the effect of avibactam with other DBO/β-lactam inhibitors in simulations, and may be an aid in translating PKPD results from in vitro to animals and humans.
Bayesian clinical decision support-guided versus clinician-guided vancomycin dosing in attainment of targeted pharmacokinetic parameters in a paediatric population
Authors: Hughes David M , Goswami Srijib , Keizer Ron J , Hughes Maria-Stephanie A , Faldasz Jonathan D 
Published: October 2019

Abstract

Objectives
To compare a Bayesian clinical decision support (CDS) dose-optimizing software program with clinician judgement in individualizing vancomycin dosing regimens to achieve vancomycin pharmacokinetic (PK)/pharmacodynamic (PD) targets in a paediatric population.

Methods
A retrospective review combined with a model-based simulation of vancomycin dosing was performed on children aged 1 year to 18 years at the University of California, San Francisco Benioff Children’s Hospital Mission Bay. Dosing regimens recommended by the clinical pharmacists, ‘clinician-guided’, were compared with alternative ‘CDS-guided’ dosing regimens. The primary outcome was the percentage of occasions predicted to achieve steady-state trough levels within the target range of 10–15 mg/L, with a secondary outcome of predicted attainment of AUC24 ≥400 mg·h/L. Statistical comparison between approaches was performed using a standard t-test.

Results
A total of n = 144 patient occasions were included. CDS-guided regimens were predicted to achieve vancomycin steady-state troughs in the target range on 70.8% (102/144) of occasions, as compared with 37.5% (54/144) in the clinician-guided arm (P < 0.0001). An AUC24 of ≥400 mg·h/L was achieved on 93% (112/121) of occasions in the CDS-guided arm versus 72% (87/121) of occasions in the clinician-guided arm (P < 0.0001).

Conclusions
In a simulated analysis, the use of a Bayesian CDS tool was better than clinician judgement in recommending vancomycin dosing regimens in which PK/PD targets would be attained in children.
Best practices for data visualization: creating and evaluating a report for an evidence-based fall prevention program
Authors: Khasnabish Srijesa , Burns Zoe , Couch Madeline , Mullin Mary , Newmark Randall , Dykes Patricia C 
Published: October 2019

AbstractThis case report applied principles from the data visualization (DV) literature and feedback from nurses to develop an effective report to display adherence with an evidence-based fall prevention program. We tested the usability of the original and revised reports using a Health Information Technology Usability Evaluation Scale (Health-ITUES) customized for this project. Items were rated on a 5-point Likert scale, strongly disagree (1) to strongly agree (5). The literature emphasized that the ideal display maximizes the information communicated, minimizes the cognitive efforts involved with interpretation, and selects the correct type of display (eg, bar versus line graph). Semi-structured nurse interviews emphasized the value of simplified reports and meaningful data. The mean (standard deviation [SD]) Health-ITUES score for the original report was 3.86 (0.19) and increased to 4.29 (0.11) in the revised report (Mann Whitney U Test, z = −12.25, P &lt; 0.001). Lessons learned from this study can inform report development for clinicians in implementation science.
Thymic epithelial tumor treatment in Japan: analysis of hospital cancer registry and insurance claims data, 2012–2014
Authors: Kanemura Hiroaki , Tamura Tomohide , Nishimura Naoki , Kobayashi Daiki , Higashi Takahiro 
Published: October 2019

Abstract

Introduction
Thymic epithelial tumors are a rare type of neoplasm. Accordingly, it is difficult to perform phase III trials in patients with thymic epithelial tumors, and thus, no standard treatment has been established for these tumors. In this study, we aimed to investigate the current status of thymic epithelial tumor treatment in Japan.

Methods
This retrospective observational study enrolled patients with thymic epithelial tumor whose data were recorded in a nationwide Hospital-based Cancer Registry that was linked with health insurance claims data for the registered patients between 2012 and 2014. The patients’ treatment details were obtained from a health insurance claims database.

Results
A total of 813 patients with thymoma and 547 with thymic carcinoma were included in the analysis. Overall, 549 (67.5%) thymoma patients underwent surgical resection alone. Among patients with thymic carcinoma, 230 (42.0%) underwent initial surgery, and 124 (53.9%) received subsequent radiotherapy and chemotherapy. Chemotherapy regimens varied across the hospitals; overall, 21 and 22 regimens were used to treat thymoma and thymic carcinoma, respectively. Platinum-based combination regimens were predominantly selected for both diseases.

Conclusions
This study revealed the real-world patterns of thymic epithelial tumor treatment in Japan. Although the nature of this study did not enable the determination of optimal treatment strategies, the simultaneous analysis of nationwide registry, insurance, efficacy and prognostic data may contribute to the establishment of a standard treatment strategy for rarely occurring cancers such as thymic epithelial tumor.
Prevalence of zoonotic Bartonella among prairie rodents in Illinois
Authors: Beckmann Sean , Engelbrecht Malcolm , Chavez Fernanda , Rojas Gissel 
Published: October 2019

Abstract
Bartonella is a genus of gram-negative bacteria that includes a variety of human and veterinary pathogens. These pathogens are transmitted from reservoirs to secondary hosts through the bite of arthropod vectors including lice and fleas. Once in the secondary host, the bacteria cause a variety of pathologies including cat-scratch disease, endocarditis, and myocarditis. Reservoirs of these bacteria are numerous and include several species of large mammals, mesocarnivores, and small mammals. Research on reservoirs of these bacteria has focused on western North America, Europe, and Asia, with little focus on the eastern and central United States. We assessed the prevalence of zoonotic Bartonella species among prairie-dwelling rodent species in the midwestern United States. Tissue samples (n = 700) were collected between 2015 and 2017 from five rodent species and screened for the presence of Bartonella DNA via PCR and sequencing of two loci using Bartonella-specific primers. Bartonella were prevalent among all five species, with 13-lined ground squirrels (Ictidomys tridecemlineatus) serving as a likely reservoir of the pathogen B. washoensis, and other rodents serving as reservoirs of the pathogens B. grahamii and B. vinsonii subsp. arupensis. These results demonstrate the value of studies of disease ecology in grassland systems, particularly in the context of habitat restoration and human–vector interactions.
Evaluation of a New Clinical Endpoint for Moderate to Severe Influenza Disease in Children: A Prospective Cohort Study
Authors: Rao Suchitra , Yanni Emad , Moss Angela , Lamb Molly M , Schuind Anne , Bekkat-Berkani Rafik , Innis Bruce L , Cotter Jillian , Mistry Rakesh D , Asturias Edwin J 
Published: October 2019

Abstract

Background
A moderate to severe (M/S) influenza clinical endpoint has been proposed in children, defined as fever &gt;39°C, otitis media, lower respiratory tract infection, or serious extrapulmonary manifestations. The objective of the study was to evaluate the M/S measure against clinically relevant outcomes including hospitalization, emergency room visits, antimicrobial use, and child/parental absenteeism.

Methods
We conducted a prospective observational study of children aged 6 months–8 years at the Children’s Hospital Colorado emergency department (ED) and urgent care site during 2016–2017 and 2017–2018. Children with influenza-like illness (ILI) underwent influenza testing by polymerase chain reaction (PCR); children who tested positive and a subset of matched test-negative controls underwent follow-up at 2 weeks. The primary outcome was the proportion of children who were hospitalized. Secondary outcomes included recurrent ED visits, antimicrobial use, hospital charges, and child/parental absenteeism within 14 days.

Results
Among 1478 children enrolled with ILI, 411 (28%) tested positive for influenza by PCR. Of children with influenza illness, 313 (76%) met the M/S definition. Children with M/S influenza were younger (3.8 years vs 4.8 years), infected with influenza A (59% vs 44%), and more frequently hospitalized (unadjusted risk difference [RD], 6.3%; 95% confidence interval [CI], 2.1–10.4; P = .03) and treated with antibiotics (unadjusted RD, 13.3%; 95% CI, 4.3–22.4; P &lt; .01) compared to those with mild disease.

Conclusions
Children with M/S influenza have a higher risk of hospitalization and antibiotic use compared with mild disease. This proposed definition may be a useful clinical endpoint to study the public health and clinical impact of influenza interventions in children.

Clinical Trials Registration
NCT02979626.
Gene4Denovo: an integrated database and analytic platform for de novo mutations in humans
Authors: Zhao Guihu , Li Kuokuo , Li Bin , Wang Zheng , Fang Zhenghuan , Wang Xiaomeng , Zhang Yi , Luo Tengfei , Zhou Qiao , Wang Lin , Xie Yali , Wang Yijing , Chen Qian , Xia Lu , Tang Yu , Tang Beisha , Xia Kun , Li Jinchen 
Published: October 2019

AbstractDe novo mutations (DNMs) significantly contribute to sporadic diseases, particularly in neuropsychiatric disorders. Whole-exome sequencing (WES) and whole-genome sequencing (WGS) provide effective methods for detecting DNMs and prioritizing candidate genes. However, it remains a challenge for scientists, clinicians, and biologists to conveniently access and analyse data regarding DNMs and candidate genes from scattered publications. To fill the unmet need, we integrated 580 799 DNMs, including 30 060 coding DNMs detected by WES/WGS from 23 951 individuals across 24 phenotypes and prioritized a list of candidate genes with different degrees of statistical evidence, including 346 genes with false discovery rates <0.05. We then developed a database called Gene4Denovo (http://www.genemed.tech/gene4denovo/), which allowed these genetic data to be conveniently catalogued, searched, browsed, and analysed. In addition, Gene4Denovo integrated data from >60 genomic sources to provide comprehensive variant-level and gene-level annotation and information regarding the DNMs and candidate genes. Furthermore, Gene4Denovo provides end-users with limited bioinformatics skills to analyse their own genetic data, perform comprehensive annotation, and prioritize candidate genes using custom parameters. In conclusion, Gene4Denovo conveniently allows for the accelerated interpretation of DNM pathogenicity and the clinical implication of DNMs in humans.