bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapeutic Drug Monitoring of Biopharmaceuticals May Benefit From Pharmacokinetic and Pharmacokinetic–Pharmacodynamic Modeling
Authors: Passot Christophe , Pouw Mieke F. , Mulleman Denis , Bejan-Angoulvant Theodora , Paintaud Gilles , Dreesen Erwin , Ternant David 
Published: March 2017

Abstract:
Biopharmaceuticals, especially monoclonal antibodies, have been increasingly used to treat several chronic inflammatory diseases. Due to the complexity of their pharmacokinetics and concentration–effect relationship, therapeutic drug monitoring (TDM) has been used to optimize their dosing regimen. Up to date, several decisional algorithms have been developed to provide tools for monoclonal antibodies' therapeutic drug monitoring. However, these algorithms are unable to determine the individual optimal dosing scheme. The aim of this article is to deal with population pharmacokinetic (PK) and pharmacokinetic–pharmacodynamic (PK-PD) modeling. Allowing the quantification of the variability of the dose-concentration–response relationship, population pharmacokinetic–pharmacodynamic modeling may be a valuable tool to determine the optimal dosing scheme. Based on population modeling, Bayesian estimators may be developed to optimize dosing schemes for each patient using limited sampling strategies. These estimators may allow accurate dosing adjustment for each patient individually.
Drug Efficacy Monitoring in Pharmacotherapy of Multiple Sclerosis With Biological Agents
Authors: Caldano Marzia , Raoul William , Rispens Theo , Bertolotto Antonio 
Published: March 2017

Abstract:
Multiple sclerosis is a heterogenous disease. Although several EMA-approved disease-modifying treatments including biopharmaceuticals are available, their efficacy is limited, and a certain percentage of patients are always nonresponsive. Drug efficacy monitoring is an important tool to identify these nonresponsive patients early on. Currently, detection of antidrug antibodies and quantification of biological activity are used as methods of efficacy monitoring for interferon beta and natalizumab therapies. For natalizumab and alemtuzumab treatments, drug level quantification could be an essential component of the overall disease management. Thus, utilization and development of strategies to determine treatment response are vital aspects of multiple sclerosis management given the tremendous clinical and economic promise of this tool.
Comparison of Plasma, Saliva, and Hair Levetiracetam Concentrations
Authors: Karaś-Ruszczyk Katarzyna , Kuczyńska Julita , Sienkiewicz-Jarosz Halina , Kurkowska-Jastrzębska Iwona , Bienkowski Przemyslaw , Restel Magdalena , Samochowiec Jerzy , Mierzejewski Pawel 
Published: March 2017

Background:
Previous findings revealed high correlations between serum/plasma and saliva levetiracetam concentrations, indicating saliva as an alternative matrix for monitoring levetiracetam therapy. Levetiracetam concentration in the hair, which could reflect long-term drug exposure and patients' compliance, has not been systematically tested, as yet. The aim of this study was to determine the correlation between plasma, saliva, and hair levetiracetam concentrations in 47 patients with epilepsy.

Methods:
Plasma, saliva, and hair levetiracetam concentrations were measured by liquid chromatography–tandem mass spectrometry with positive ionization.

Results:
Levetiracetam saliva and plasma concentrations were highly correlated (r = 0.93). Plasma concentrations were not influenced by sex, age, and other concomitant antiepileptic drugs. Levetiracetam hair concentrations correlated with plasma concentrations (r = 0.36) but not daily dose (mg/kg). Drug hair concentrations were not influenced by hair color or treatment (dyed).

Conclusions:
The results tend to indicate that saliva may be a reliable alternative to plasma for monitoring levetiracetam concentrations. Levetiracetam can also be detected in human hair.
QUANTIFICATION OF RETINAL VESSEL TORTUOSITY IN DIABETIC RETINOPATHY USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY
Authors: Lee Hyungwoo , Lee Minsub , Chung Hyewon , Kim Hyung Chan 
Published: March 2017

Purpose:
To investigate the association of vessel tortuosity with severity of diabetic retinopathy (DR) using optical coherence tomography angiography.

Methods:
We retrospectively analyzed 30 healthy eyes and 121 eyes of diabetic subjects with no DR, mild nonproliferative DR (NPDR), moderate to severe NPDR and proliferative DR (PDR). Binarized images were used to quantify the vessel tortuosity, vessel density, foveal avascular zone (FAZ) area, and FAZ acircularity. The vessels were divided vertically as superficial retinal layer and deep retinal layer, and horizontally as circular areas with 3 mm and 1.5 mm diameters. Analysis of variance was performed for multiple comparisons. Correlation analysis evaluated the association between the quantified parameters.

Results:
Compared with healthy eyes, vessel tortuosity increased as DR severity was more in NPDR, but decreased in PDR (P = 0.033). The decrease in vessel density and the increase in both FAZ area and FAZ acircularity were consistent, while DR approached PDR. Among all parameters, statistically significant difference between no DR and mild NPDR was observed only in vessel tortuosity, especially within the 1.5 mm area of superficial retinal layer (P = 0.011). Correlations of vessel tortuosity with FAZ area and acircularity were confined to the 3 mm and 1.5 mm areas of superficial retinal layer (r = −0.185, P = 0.023 for FAZ area; r = 0.268, P = 0.001 for FAZ acircularity), while vessel density strongly correlated with FAZ parameters in the superficial retinal layer and deep retinal layer.

Conclusion:
Vessel tortuosity increased as the stage of NPDR was more severe, but decreased in PDR. The vessel tortuosity determined using optical coherence tomography angiography might be a useful parameter indicating the progression to PDR, circumventing the risk from invasive conventional angiography.
Effects of Corneal Scars and Their Treatment With Rigid Contact Lenses on Quality of Vision
Authors: de Jong Bram , van der Meulen Ivanka J. E. , van Vliet Johannes M. J. , Lapid-Gortzak Ruth , Nieuwendaal Carla P. , van den Berg Thomas J. T. P. 
Published: March 2017

Objectives:
To study the effects of corneal scars and the treatment of these scars with rigid gas-permeable (RGP) contact lenses on quality of vision including straylight. Visual effects were related to scar characteristics such as size and grade.

Methods:
Straylight and best-corrected visual acuity were measured in 23 patients with corneal scars during and after RGP contact lens wear. Contralateral eyes were used as controls, and age-normal values in case of bilateral scars. Straylight measurements were performed using the compensation comparison method of the Oculus C-Quant instrument.

Results:
Scarred eye straylight values were 1.53 log(s) without contact lens and 1.60 log(s) with contact lens (P=0.043). Healthy eyes without contact lens had a mean straylight value of 1.13 log(s), corresponding to age-normal values. Contact lens wear increased straylight in healthy eyes to 1.26 log(s) (P<0.001). Visual acuity improved from 0.66 logarithm of minimal angle of resolution (logMAR) to 0.19 logMAR with contact lens wear in eyes with a corneal scar (P<0.001).

Conclusions:
Corneal scars can have a strong effect on quality of vision by diminishing visual acuity and increasing straylight. The increase in straylight from corneal scars on its own can lead to a serious visual handicap. Contact lens treatment did not improve straylight, but showed a slight worsening. As the recovery of visual acuity with contact lens wear far exceeded straylight increase, contact lenses remain a clinically useful treatment option in most patients with corneal scars.
Mid-Term Follow-Up of Minimally Invasive Multivessel Coronary Artery Bypass Grafting
Authors: Rodriguez Maria Lorena , Lapierre Harry R. , Sohmer Benjamin , Glineur David , Ruel Marc 
Published: March 2017

Objective Minimally invasive coronary artery bypass grafting (MICS CABG) through a small left thoracotomy is a novel technique for surgical coronary revascularization, which is increasingly being adopted around the world. This study aimed to describe the characteristics and mid-term outcomes of a series of MICS CABG to identify areas for improvement. Methods A prospective longitudinal study was performed on the 306 MICS CABG patients operated on by a single surgeon from 2005 to 2015. Minimally invasive coronary artery bypass grafting used a small left thoracotomy to enable coronary revascularization with a similar configuration to an open sternotomy technique, with left internal thoracic artery harvesting, and hand-sewn proximal radial/saphenous and distal anastomoses, under direct visualization. We compared patients who were operated on during the first and second halves of the series to ascertain the impact of a learning curve on outcomes. Results The mean ± SD age was 62 ± 9 years, 87% were male, and 23% had three-vessel disease. Off-pump coronary artery bypass was performed in 80%, and the median number of grafts was 2 (range 1–4). Sternotomy conversion occurred in 3.3%, reoperation for bleeding in 2%, and unplanned, emergency CPB conversion in 1%. Superficial thoracotomy infection, atrial fibrillation, and left-sided pleural effusion requiring drainage were encountered in 2%, 1%, and 1%, respectively. There were no perioperative stroke, myocardial infarction, or death. At a mean ± SD follow-up of 2.8 ± 2.5 years, 97.4% of patients were free from major adverse cardiac and cerebrovascular events. Between the first and latter half of the series, there was a decrease in the rate of conversion to sternotomy (5.2%–1.3%, P = 0.05) and in the mid-term need for repeat revascularization (11% vs 2.6%, P = 0.03). Overall repeat revascularization rate was 2.5% per year. The intensive care unit and hospital lengths of stay (1.6 ± 1.5 vs 1.4 ± 0.9, P = 0.2, and 6.1 ± 2.6 vs 5.6 ± 1.8, P = 0.4) were not statistically different. Conclusions Minimally invasive coronary artery bypass grafting can be safely initiated as a minimally invasive, multivessel alternative to open surgical coronary revascularization, with excellent mid-term results. Learning phase effects were not observed with regard to overall procedural safety, but rather in terms of improved freedom from conversion to sternotomy and from repeat revascularization.
Development of the Irritable Bowel Syndrome Cognitive Affective Scale: a brief self-report measure for clinical and research settings
Authors: Ballou Sarah , Keefer Laurie 
Published: March 2017

Objectives
Measures of cognitive-affective processes believed to underlie Irritable Bowel Syndrome (IBS) symptom expression are used widely in both clinical and research settings. When combined, these measures can be time-consuming and it is not clear whether they evaluate distinct or overlapping constructs. With this study, we seek to identify the most critical cognitive-affective components contributing toward the expression of IBS and to identify which items in these constructs might be streamlined into a single, brief self-report measure.

Patients and methods
This measure was developed according to Food and Drug Administration guidelines for patient-reported outcome development. First, authors consolidated existing cognitive-affective measures (visceral sensitivity, anxiety sensitivity, and pain catastrophization) into a single questionnaire. Second, a principal components factor analysis was carried out on the basis of responses from a sample of participants with IBS. Third, on the basis of the results of the factor analysis, items were reduced to the final brief self-report measure and preliminary validity/reliability analyses (Cronbach’s α, correlation with other related constructs) were carried out.

Results
An initial, 44-item measure was created. In all, 179 patients with ROME-III IBS completed an online survey. Principal component analysis and item reduction yielded a 15-item scale with three factors: pain catastrophization, visceral hypervigilance, and extraintestinal hypervigilance. The final three factors showed comparable internal consistencies (α>0.90), concurrent validity, and predictive validity compared with the original 44 items.

Conclusion
Although more research is warranted, the 15 items identified appear to provide an accurate measure of two important cognitive-affective constructs in the IBS population.
MicroRNAs and lipid metabolism
Authors: Aryal Binod , Singh Abhishek K. , Rotllan Noemi , Price Nathan , Fernández-Hernando Carlos 
Published: March 2017

Purpose of review
Work over the past decade has identified the important role of microRNAs (miRNAS) in regulating lipoprotein metabolism and associated disorders including metabolic syndrome, obesity, and atherosclerosis. This review summarizes the most recent findings in the field, highlighting the contribution of miRNAs in controlling LDL-cholesterol (LDL-C) and HDL-cholesterol (HDL-C) metabolism.

Recent findings
A number of miRNAs have emerged as important regulators of lipid metabolism, including miR-122 and miR-33. Work over the past 2 years has identified additional functions of miR-33 including the regulation of macrophage activation and mitochondrial metabolism. Moreover, it has recently been shown that miR-33 regulates vascular homeostasis and cardiac adaptation in response to pressure overload. In addition to miR-33 and miR-122, recent GWAS have identified single-nucleotide polymorphisms in the proximity of miRNA genes associated with abnormal levels of circulating lipids in humans. Several of these miRNAs, such as miR-148a and miR-128-1, target important proteins that regulate cellular cholesterol metabolism, including the LDL receptor (LDLR) and the ATP-binding cassette A1 (ABCA1).

Summary
MicroRNAs have emerged as critical regulators of cholesterol metabolism and promising therapeutic targets for treating cardiometabolic disorders including atherosclerosis. Here, we discuss the recent findings in the field, highlighting the novel mechanisms by which miR-33 controls lipid metabolism and atherogenesis, and the identification of novel miRNAs that regulate LDL metabolism. Finally, we summarize the recent findings that identified miR-33 as an important noncoding RNA that controls cardiovascular homeostasis independent of its role in regulating lipid metabolism.
Pediatric intestinal failure-associated liver disease
Authors: Courtney Cathleen M. , Warner Brad W. 
Published: March 2017

Purpose of review
The goal of this review is to provide updates on the definition, pathophysiology, treatment, and prevention of intestinal failure-associated liver disease (IFALD) that are relevant to care of pediatric patients.

Recent findings
Current literature emphasizes the multifactorial nature of IFALD. The pathogenesis is still largely unknown; however, molecular pathways have been identified. Key to these pathways are proinflammatory cytokines involved in hepatic inflammation and bile acids synthesis such as Toll-like receptor 4 and farnesoid X receptor, respectively. Research for prevention and treatment is aimed at alleviating risk factors associated with IFALD, principally those associated with parental nutrition. Multiple nutrients and amino acids are relevant to the development of IFALD, but lipid composition has been the primary focus. Lipid emulsions with a lower ratio of omega-6-to-omega-3 polyunsaturated fatty acids (FAs) appear to improve bile flow and decrease intrahepatic inflammation. Long-term consequences of these alternative lipid emulsions are yet to be determined.

Summary
IFALD remains the greatest contributor of mortality in patients with intestinal failure. Many factors contribute to its development, namely, alterations in the gut microbiome, sepsis, and lack of enteral intake. Novel combinations of lipid formulations are promising alternatives to purely soy-based formulas to reduce cholestasis.
High-flow nasal cannula therapy beyond the perinatal period
Authors: Lee Michael , Nagler Joshua 
Published: March 2017

Purpose of review
High-flow nasal cannula (HFNC) is emerging as a means of oxygen delivery and respiratory support for a range of conditions outside the perinatal period. We aim to review the mechanisms of action and advantages of HFNC and to summarize current findings regarding clinical benefit in specific pediatric disease processes and in patients with significant respiratory distress.

Recent findings
Currently published studies outside the neonatal population demonstrate both safety and efficacy of this mode of respiratory support. Retrospective and prospective observational trials have shown improvements in oxygenation and respiratory distress, as well as reductions in the need for intubation in select patient populations. Randomized controlled trials are ongoing.

Summary
HFNC is emerging as a means of oxygen delivery and respiratory support across a wide range of pediatric conditions. Available data suggest that it is well tolerated by children and can have a favorable effect on clinical outcomes. Future research will better define optimal patient populations and best practices for use.
Pulmonary manifestations of rheumatologic diseases
Authors: Cidon Michal , Bansal Manvi , Hartl Dominik 
Published: March 2017

Purpose of review
The present review intends to provide an overview of the diversity and complexity of pulmonary manifestations of rheumatologic diseases and gaps in knowledge to effectively manage them.

Recent findings
Diffuse lung disease in children with rheumatologic diseases represents a heterogeneous group of autoimmune disorders. Despite their significant morbidity and mortality, we have limited understanding about their pathogenesis. Here, we provide an overview of the pathophysiology and current management approach of these disorders, highlighting tools which assist with diagnosis, risk stratification and therapy. In this context, we address the need to develop a standardized approach to diagnose at-risk patients with rheumatologic disease and to predict their progression and the need to develop robust studies which evaluate the factors and interventions that influence pulmonary disease outcome.

Summary
Diffuse lung disease in children with rheumatologic diseases represents a heterogeneous group of severe autoimmune disorders. By adopting a collaborative research approach among multicenters to help diagnose, risk stratify, and understand disease progression, effective management decisions can be optimized to improve clinical outcome.
Prevention of gastrointestinal side-effects in paediatric oncology: what are the guidelines?
Authors: Cheng Karis K.F. 
Published: March 2017

Purpose of review
Gastrointestinal side-effects, particularly with regard to alimentary tract mucositis and chemotherapy-induced nausea and vomiting (CINV), continue to be frequent and debilitating symptomatic conditions among children and adolescents receiving cytotoxic cancer therapy. Further avenues of progress for mucositis and CINV prevention in paediatric oncology setting are warranted.

Recent findings
The current article reviews the major guidelines and literature published in 2016 pertaining to the prevention of mucositis and CINV. Considerable professional organizational efforts have been made to develop consensus-based or evidence-based guidelines that periodically update to define basic standards of mucositis and CINV prevention. There are a few published works in 2016 that may contribute to the emerging evidence on prevention of mucositis and CINV in the paediatric setting for future guideline updates.

Summary
The concomitant use of 5-HT3 receptor antagonist and dexamethasone are effective to prevent acute and delayed CINV in children who are to receive highly or moderately emetogenic chemotherapy. Optimal control of acute and delayed CINV can prevent anticipatory CINV. Oral care protocols would be beneficial to prevent mucositis in children across all cancer treatment modalities. Cryotherapy or low-level light therapy may be applied to cooperative children undergoing chemotherapy or haematological stem cell transplant conditioning regimens with a high rate of mucositis.
Thermal decomposition of the amino acids glycine, cysteine, aspartic acid, asparagine, glutamic acid, glutamine, arginine and histidine
Authors: Weiss Ingrid M. , Muth Christina , Drumm Robert , Kirchner Helmut O.K. 
Published: March 2017

AbstractCalorimetry, thermogravimetry and mass spectrometry were used to follow the thermal decomposition of the eight amino acids G, C, D, N, E, Q, R and H between 185°C and 280°C. Endothermic heats of decomposition between 72 and 151 kJ/mol are needed to form 12 to 70%volatile products. This process is neither melting nor sublimation. With exception of cysteine they emit mainly H2O, some NH3 and no CO2. Cysteine produces CO2 and little else. The reactions are described by polynomials, AA ^ a (NH3) + b (H2O) + c (CO2) + d (H2S) + e (residue), with integer or half integer coefficients. The solid monomolecular residues are rich in peptide bonds.
Estimation of genomic prediction accuracy from reference populations with varying degrees of relationship
Authors: Hong Lee S. , Clark Sam , van der Werf Julius H.J. 
Published: March 2017

ABSTRACTGenomic prediction is emerging in a wide range of fields including animal and plant breeding, risk prediction in human precision medicine and forensic. It is desirable to establish a theoretical framework for genomic prediction accuracy when the reference data consists of information sources with varying degrees of relationship to the target individuals. A reference set can contain both close and distant relatives as well as ‘unrelated’ individuals from the wider population in the genomic prediction. The various sources of information were modeled as different populations with different effective population sizes (Ne). Both the effective number of chromosome segments (Me) andNeare considered to be a function of the data used for prediction. We validate our theory with analyses of simulated as well as real data, and illustrate that the variation in genomic relationships with the target is a predictor of the information content of the reference set. With a similar amount of data available for each source, we show that close relatives can have a substantially larger effect on genomic prediction accuracy than lesser related individuals. We also illustrate that when prediction relies on closer relatives, there is less improvement in prediction accuracy with an increase in training data or marker panel density. We release software that can estimate the expected prediction accuracy and power when combining different reference sources with various degrees of relationship to the target, which is useful when planning genomic prediction (before or after collecting data) in animal, plant and human genetics.
Toxicity of chlordane at early developmental stage of zebrafish
Authors: Xiong Jingxuan 
Published: March 2017

AbstractChlordane is highly toxic organochlorine pesticides that have been widely used throughout the world for decades and posing adverse effects on the environment. Contents detected in tissue and blood samples have resulted in a raising concern for their potential effects on wildlife and humans. In this study, we investigate the potential effect of chlordane on the development of zebrafish embryos. Zebrafish larvae were treated with different concentrations (0, 25, 50, 100, 200 ng/L) of chlordane from 12 hours postfertilization (hpf). Different early stage parameters were observed at 1, 2, 3 and 4 day post-fertilization (dpf). Chlordane-exposed zebrafish larvae appeared significant lower survival rate, developmental and hatching time delay and decreased embryo productivity. The heartbeat rate and blood flow were decreased in a dose dependent manner. These results suggested that exposure to real life of chlordane led to direct morphological and phenotypic changes and effects systems related to development and reproduction even in short-term manner.