bluuebunny/crossref_metadata_2025_split huggingface dataset:
Limited Ultrasound Protocol for Upper Extremity Peripherally Inserted Central Catheter Monitoring: A Pilot Study in the Neonatal Intensive Care Unit
Authors: Motz Patrick , Arnim Amelie von Saint Andre von , Likes Maggie , Chabra Shilpi , Traudt Christopher , Iyer Ramesh S. , Dighe Manjiri 
Published: September 2018

ObjectivesTo assess whether a limited ultrasound (US) scanning protocol to monitor the upper extremity peripherally inserted central catheter (PICC) location in neonates is feasible for experienced US operators.MethodsA radiologist, who was blinded to the PICC location on chest radiography, performed 14 US scans on 11 neonates with upper extremity PICCs. A US machine with 13–6‐MHz linear and 8–4‐MHz phased array transducers was used for the examinations.ResultsThe study population included 54% (n = 6) preterm infants, with 72% (n = 8) weighing less than 1500 g. The US location of the PICC was the same as the chest radiographic report in all 14 scans. A subclavicular long‐axis view of the anterior chest visualized all PICCs in the subclavian or brachiocephalic veins. A parasternal long‐axis right ventricular inflow view was able to visualize PICCs in the superior vena cava (SVC), and a subcostal long‐axis view evaluated PICCs in the lower SVC and heart. The scanning time was location dependent: less than 5 minutes for PICCs in the brachiocephalic or subclavian vein and 5 to 10 minutes for PICCs in the SVC or heart. There were no desaturations below 90%, increases in the fraction of inspired oxygen need, or hypotension episodes during scanning.ConclusionsA limited US scanning protocol to determine the upper extremity PICC location is feasible. Our protocol needs to be tested in neonatal providers before further dissemination.
Dynamic Changes of the Aspartate Aminotransferase‐to‐Platelet Ratio and Transient Elastography in Predicting a Histologic Response in Patients With Chronic Hepatitis B After Entecavir Treatment
Authors: Sun Jing , Li Yanfang , Sun Xuying , Yu Hong , Liu Youde 
Published: September 2018

ObjectivesTo evaluate the dynamic changes of the aspartate aminotransferase (AST)‐to‐platelet ratio and transient elastography (FibroScan; Echosens, Paris, France) in predicting a histologic response in patients with chronic hepatitis B (CHB) after entecavir treatment.MethodsA total of 148 patients with CHB were enrolled. Patient information was collected. All patients received liver biopsy and FibroScan before and after 96 weeks of entecavir treatment.ResultsBaseline liver biopsy results showed that there were 7 patients without liver fibrosis (fibrosis stage F0; 4.7%), 51 patients with mild liver fibrosis (F1; 34.5%), and 90 patients with advanced liver fibrosis (>F1; 60.9%). The liver stiffness value and AST‐to‐platelet ratio increased significantly as the METAVIR score of the patients increased from F0 to F4 (P < .001). After antiviral therapy for 96 weeks, the average liver stiffness value measured by FibroScan and the AST‐to‐platelet ratio showed a significant decrease. When we use a decreased liver stiffness value to predict a histologic response, the area under the receiver operating characteristic curve was 0.70 (95% confidence interval, 0.61–0.79; P < .001), and the sensitivity and specificity were 74.3% and 68.8%, respectively. The decrease of the AST‐to‐platelet ratio also could predict the histologic response of patients with CHB; the area under the receiver operating characteristic curve was 0.77 (95% confidence interval, 0.69–0.86; P < .001) with sensitivity of 76.2% and specificity of 70.2%. A multivariate analysis indicated that a high hepatitis B virus DNA viral load (odds ratio, 1.44; P = .04) and high METAVIR score (odds ratio, 1.38; P = .02) were independent risk factors for the histologic response.ConclusionsBoth the AST‐to‐platelet ratio and FibroScan value can effectively predict a histologic response in patients with CHB during entecavir treatment. Therefore, they can be used to monitor these patients during antiviral treatment to avoid multiple liver biopsies.
Secondary Imaging Findings Aid in Prenatal Diagnosis and Characterization of Congenital Diaphragmatic Hernia: Role of an Abnormal Orientation of Vascular Structures and Gallbladder Position
Authors: Didier Ryne A. , DeBari Suzanne E. , Oliver Edward R. , Gebb Juliana S. , Howell Lori J. , Hedrick Holly L. , Adzick N. Scott , Coleman Beverly G. 
Published: September 2018

ObjectivesTo determine whether an abnormal orientation of the abdominal or hepatic vasculature and an abnormal gallbladder position on prenatal ultrasound (US) imaging are associated with intrathoracic liver herniation and postnatal outcomes in cases of congenital diaphragmatic hernia (CDH).MethodsChildren who underwent prenatal US examinations and postnatal CDH repair at our institution were eligible. Prenatal US images were reviewed, and the orientation of the superior mesenteric artery (SMA) and hepatic veins as well as gallbladder position were recorded. Findings were correlated with prenatal US measurements (lung‐to‐head ratio and calculated observed‐to‐expected lung‐to‐head ratio) and postnatal outcomes, including intrathoracic liver herniation, an extracorporeal membrane oxygenation (ECMO) requirement, and mortality.ResultsA total of 175 patients met inclusion criteria. The SMA was shown in 168 cases and had a cephalad orientation in 95.4% (161 of 168), which was not associated with outcome measures and represented bowel herniation. A cephalad orientation of the hepatic veins was identified in 52.6% (90 of 171) and was associated with intrathoracic liver herniation, an ECMO requirement, and mortality (P < .01). In right‐sided CDH, the gallbladder was intrathoracic in 91.3% (21 of 23). In left‐sided CDH, an abnormal gallbladder position was seen in 51.3% (76/152) and was associated with intrathoracic liver herniation, an ECMO requirement, mortality, and lower lung‐to‐head ratio and observed‐to‐expected lung‐to‐head ratio values. When combined, abnormal hepatic vein and gallbladder positions showed good sensitivity and specificity in predicting intrathoracic liver herniation (area under the curve, 0.93).ConclusionsAbnormal SMA, hepatic vein, and gallbladder positions can be used to improve prenatal characterization of CDH. Accurate depiction of these structures on prenatal US images may aid in patient counseling and postnatal management.
Reproducibility of Liver‐to‐Thorax Area Ratio Ultrasound Measurements in Congenital Diaphragmatic Hernia
Authors: Novoa y Novoa Victoria Arruga , Sutton Laura F. , Neis Allan E. , Marroquin Amber M. , Coleman Tracey M. , Praska Kathleen A. , Freimund Tamara A. , Ruka Krystal L. , Warzala Vicki L. , Sangi‐Haghpeykar Haleh , Ruano Rodrigo 
Published: September 2018

ObjectivesThe aim of this study was to investigate the reproducibility of a standardized method to assess the ultrasound liver‐to‐thoracic area ratio in fetuses with congenital diaphragmatic hernia.MethodsWe selected 24 images of 9 fetuses diagnosed with left‐sided at our institution between January 2010 and December 2017. Eight operators (1 maternal‐fetal medicine specialist and 7 sonographers) reviewed the selected images and assessed the ultrasound liver‐to‐thoracic area ratio according to a standardized protocol. We evaluated the correlation between operators using the intraclass correlation coefficient and compared agreement between the sonographers and a physician with experience in measuring the ultrasound liver‐to‐thoracic area ratio using a Bland‐Altman analysis.ResultsGood intraoperator reproducibility was observed for the standardized ultrasound liver‐to‐thoracic area ratio (intraclass correlation coefficient, 0.78). Good agreement among sonographers and the physician was also observed for the standardized measurements (bias, 0.01; precision, 0.03; limits of agreement, –0.05 to + 0.07).ConclusionsWe demonstrated that good intraoperator and interoperator reproducibility of ultrasound liver‐to‐thoracic area ratio assessment is feasible after standardizing the method in our center.
Construction of Functional Hyperbranched Poly(phenyltriazolylcarboxylate)s by Metal‐Free Phenylpropiolate‐Azide Polycycloaddition
Authors: Chi Weiwen , Yuan Wei , Du Jun , Han Ting , Li Hongkun , Li Yongfang , Tang Ben Zhong 
Published: September 2018

AbstractThe 1,3‐dipolar cycloaddition of activated internal alkynes with azides has been developed into an efficient polymerization reaction for constructing functional linear 1,4,5‐trisubstitued polytriazoles. However, it is rarely employed for the synthesis of hyperbranched polymers. In this work, metal‐free polycycloadditions of tris(3‐phenylpropiolate)s (1) and tetraphenylethene‐containing diazides (2) are performed in dimethylformamide at 100 °C for 7 and 12 h, producing hyperbranched poly(phenyltriazolylcarboxylate)s (hb‐PPTCs) with high molecular weights and satisfactory regioregularities in good yields. The hb‐PPTCs have good solubility in common organic solvents and high thermal stability. They are non‐emissive in solutions, but emit intensively upon aggregation, showing an aggregation‐induced emission effect. Their aggregates can work as fluorescent sensors for explosive detection with high sensitivity. Furthermore, the polymers can be utilized for the fabrication of 2D fluorescent patterns with high resolution by UV irradiation through copper grid masks.
Optimal policies for inventory systems with concave ordering costs
Authors: Benjaafar Saif , Chen David , Yu Yimin 
Published: September 2018

AbstractIn this paper we study the structure of optimal policies for periodic review inventory systems with concave ordering costs and general demand distributions. By extending the Scarf () model to systems with piecewise linear concave ordering costs, we show that, except for a bounded region, the generalized (s, S) policy is optimal. We do so by (a) introducing the notion of c‐convexity and (b) proving a conditional monotonicity property for the optimal order‐up‐to levels. We also provide conditions under which the generalized (s, S) policy is optimal for all regions of the state space.
Risk of hospitalisation and death related to baclofen for alcohol use disorders: Comparison with nalmefene, acamprosate, and naltrexone in a cohort study of 165 334 patients between 2009 and 2015 in France
Authors: Chaignot Christophe , Zureik Mahmoud , Rey Grégoire , Dray‐Spira Rosemary , Coste Joël , Weill Alain 
Published: September 2018

AbstractPurposeBaclofen is widely used off‐label for alcohol use disorders (AUD) in France, despite its uncertain efficacy and safety, particularly at high doses. This study was designed to evaluate the safety of this off‐label use compared to the main approved drugs for AUD (acamprosate, naltrexone, nalmefene).MethodsThis cohort study from the French Health Insurance claims database included patients, aged 18 to 70 years, with no serious comorbidity (assessed by the Charlson score) initiating baclofen or approved drugs for AUD between 2009 and 2015. The risk of hospitalisation or death associated with baclofen, at variable doses over time (from low doses <30 mg/day to high doses ≥180 mg/day), compared to approved drugs, was evaluated by a Cox model adjusted to sociodemographic and medical characteristics.ResultsThe cohort included 165 334 patients, 47 614 of whom were exposed to baclofen. Patients exposed to baclofen differed from those treated with approved drugs in terms of sociodemographic and medical characteristics (more females, higher socioeconomic status, fewer hospitalisations for alcohol‐related problems), but these differences tended to fade at higher doses of baclofen. Baclofen exposure was significantly associated with hospitalisation (hazard ratio [HR] = 1.13 [95%CI: 1.09‐1.17]) and death (HR = 1.31 [95%CI: 1.08‐1.60]). The risk increased with dose, reaching 1.46 [1.28‐1.65] for hospitalisation and 2.27 [1.27‐4.07] for death at high doses. Similar results were in patients with a history of hospitalisation for alcohol‐related problems.ConclusionsThis study raises concerns about the safety of baclofen for AUD, particularly at high doses, with higher risks of hospitalisation and mortality than approved drugs.
The association between concerns toward adverse reactions during pre‐approval drug reviews and the post‐approval addition of clinically significant adverse reactions to package inserts: A retrospective analysis of pre‐approval drug review reports and safety updates
Authors: Watanabe Ko , Murakami Masayasu , Masuyama Koichi , Ishiguro Chieko , Matsuda Tsutomu 
Published: September 2018

AbstractPurposeTo determine if concerns toward adverse reactions (ARs) identified during the drug approval process are associated with their post‐approval addition to package inserts.MethodsPre‐approval concerns toward 24 target ARs were identified in the drug review reports and initial package inserts of 126 target drugs approved for use in Japan between April 2004 and March 2009. Each target drug was monitored for 5 years after approval for the addition of these ARs as clinically significant adverse reactions (CSARs) in the package inserts. Positive predictive values (PPVs) and negative predictive value (NPVs) were calculated. The odds ratios (ORs) and 95% confidence intervals (CIs) were also analyzed to test the association between pre‐approval concerns and post‐approval CSAR additions.ResultsTarget ARs with pre‐approval concerns were added as CSARs in 88 of 406 AR‐drug pairs (PPV: 21.7%). In contrast, target ARs without pre‐approval concerns were added as CSARs in 93 of 2304 drugs (NPV: 96.0%). Hypoglycemia had the highest PPV (100%), whereas hepatitis and myocardial infarction had the lowest PPVs (0.0%). Abnormal hepatic function had the lowest NPV (85.4%), whereas myocardial infarction and convulsions had the highest NPVs (100%). Pre‐approval concerns showed a significantly positive association with post‐approval CSAR additions (OR: 6.57, 95% CI: 4.74, 9.11; P < 0.001).ConclusionsThe significant association between pre‐approval concerns and post‐approval CSAR additions indicates that Japan's drug regulatory agency has generally conducted rigorous examination of the safety information available in the submitted data packages during drug review for approval.
Branched peptides as bioactive molecules for drug design
Authors: Brunetti Jlenia , Falciani Chiara , Bracci Luisa , Pini Alessandro 
Published: September 2018

AbstractPeptides are regarded as good candidates for new biotherapeutics in medicine. Several peptides have already completed clinical development, with more than 60 peptide‐based drugs already on the market, and a further 500 derivatives currently in developmental stages. Branched peptides are an emerging class of synthetic molecules being assessed for drug development. Here, we review possible clinical uses of branched peptides, considering major features such as stability, half‐life, toxicity, and efficacy compared to monomeric peptides, biodistribution, as well as modifications, encapsulation, and conjugation to improve delivery or bypass drug resistance. We focus in particular on the use of branched peptides in oncology and infectious diseases.
Protein engineering by chemical methods: Incorporation of nonnatural amino acids as a tool for studying protein folding, stability, and function
Authors: De Filippis Vincenzo , Pozzi Nicola , Acquasaliente Laura , Artusi Ilaria , Pontarollo Giulia , Peterle Daniele 
Published: September 2018

AbstractProteins are large complex biomolecules that act as the effectors of essentially all cell functions. Due to the intrinsic complexity of protein architecture at the microscopic level and the inadequacy of theoretical methods to predict protein reactivity (ie, folding, stability, and function), protein engineering has emerged as a valuable tool to investigate structure–stability–activity relationships in proteins and nowadays recombinant DNA technologies are the “gold standard” for site‐specifically manipulating a given protein chain. The usefulness of current mutagenesis techniques, however, is limited by the relatively poor chemical diversity of the 20 DNA‐coded amino acids, such that it is difficult to precisely assign the observed change of protein stability or function to the variation of a single physicochemical property at a protein site (ie, hydrophobicity, conformational propensity, polarizability, hydrogen bonding, etc). In this article, we report relevant examples from our laboratory showing that chemical methods, that is, enzyme‐catalyzed semisynthesis and stepwise solid‐phase synthesis, allow to conveniently incorporate non‐natural amino acids with “tailored” side chains into small proteins and thus effectively transfer the structure–activity relationship methodology, typical of the medicinal chemistry approach on small molecules, to the study of folding, stability, and molecular recognition in macromolecular protein systems.
CPProtectides: Rapid uptake of well‐folded β‐hairpin peptides with enhanced resistance to intracellular degradation
Authors: Safa Nora , Anderson Jeffery C. , Vaithiyanathan Manibarathi , Pettigrew Jacob H. , Pappas Gavin A. , Liu Dong , Gauthier Ted J. , Melvin Adam T. 
Published: September 2018

AbstractCell penetrating peptides (CPPs) have emerged as powerful tools for delivering bioactive cargoes, such as biosensors or drugs to intact cells. One limitation of CPPs is their rapid degradation by intracellular proteases. β‐hairpin “protectides” have previously been demonstrated to be long‐lived under cytosolic conditions due to their secondary structure. The goal of this work was to demonstrate that arginine‐rich β‐hairpin peptides function as both protectides and as CPPs. Peptides exhibiting a β‐hairpin motif were found to be rapidly internalized into cells with their uptake efficiency dependent on the number of arginine residues in the sequence. Cellular internalization of the β‐hairpin peptides was compared to unstructured, scrambled sequences and to commercially available, arginine‐rich CPPs. The unstructured peptides displayed greater uptake kinetics compared to the structured β‐hairpin sequences; however, intracellular stability studies revealed that the β‐hairpin peptides exhibited superior stability under cytosolic conditions with a 16‐fold increase in peptide half‐life. This study identifies a new class of long‐lived CPPs that can overcome the stability limitations of peptide‐based reporters or bioactive delivery mechanisms in intact cells.
The role of perceived dignity and control in the wish to hasten death among advanced cancer patients: A mediation model
Authors: Monforte‐Royo Cristina , Crespo Iris , Rodríguez‐Prat Andrea , Marimon Frederic , Porta‐Sales Josep , Balaguer Albert 
Published: September 2018

AbstractObjectiveThe objective of the study is to test a model in which perceived loss of dignity and control are proposed, along with symptoms of depression and functional impairment, as risk factors for the wish to hasten death (WTHD) in advanced cancer patients.MethodsThis was a cross‐sectional study of 193 patients in an oncology unit. Outcome measures included perceived control, performance status, symptoms of depression, perceived dignity, and the WTHD. Structural equation modeling was performed.ResultsStructural equation modeling showed that perceived loss of control (−0.402) and functional impairment (−0.21) were risk factors for perceived loss of dignity. Loss of control (−0.385) and functional impairment (−0.283) were also risk factors for symptoms of depression. Perceived loss of dignity and symptoms of depression were the most proximal determinants of the WTHD, on which they had a direct, positive, and significant effect (0.246 and 0.209, respectively). Therefore, both symptoms of depression and perceived loss of dignity independently predicted the WTHD and mediated the effects of perceived loss of control and functional impairment on this wish.ConclusionsThe hypothesized model provides evidence for the impact of the four aforementioned factors on the WTHD. Our results suggest that personalized care plans which are able to enhance the sense of dignity and control among advanced cancer patients could help to reduce the likelihood or intensity of a WTHD.
Sesquiterpene lactones‐enriched fraction of Inula helenium L. induces apoptosis through inhibition of signal transducers and activators of transcription 3 signaling pathway in MDA‐MB‐231 breast cancer cells
Authors: Chun Jaemoo , Song Kwangho , Kim Yeong Shik 
Published: September 2018

Inula helenium L., commonly known as Elecampane, has been extensively used for many countries in the folk medicine. Its root is a rich source of sesquiterpene lactones, which possess various pharmacological activities. To develop the phytomedicine including sesquiterpene lactones, we prepared hexane fraction from I. helenium (HFIH) and examined the inhibitory effect of HFIH on signal transducers and activators of transcription 3 (STAT3) activation in human breast cancer MDA‐MB‐231 cells. Additionally, detailed chemical investigation was done to pinpoint the most active sesquiterpene lactones responsible for its anticancer activity. HFIH selectively suppressed STAT3 phosphorylation at tyrosine 705, not affecting its upstream kinases. HFIH downregulated the expression of STAT3 target genes including cyclin D1, c‐myc, and bcl‐2 and induced caspase‐mediated apoptosis. Moreover, sesquiterpene lactones of HFIH clearly suppressed STAT3 activation. The in vivo results further supported that HFIH inhibits the growth of human breast xenograft tumors. Our results suggest that HFIH possesses potential anticancer activity, which is mainly mediated through STAT3 signaling pathway. These findings provide the potential of HFIH as a promising phytomedicine for the treatment and prevention of triple‐negative breast cancer.
Implications of the variation in biological 18O natural abundance in body water to inform use of Bayesian methods for modelling total energy expenditure when using doubly labelled water
Authors: Singh Priya A. , Orford Elise R. , Donkers Kevin , Bluck Leslie J.C. , Venables Michelle C. 
Published: September 2018

RationaleVariation in 18O natural abundance can lead to errors in the calculation of total energy expenditure (TEE) when using the doubly labelled water (DLW) method. The use of Bayesian statistics allows a distribution to be assigned to 18O natural abundance, thus allowing a best‐fit value to be used in the calculation. The aim of this study was to calculate within‐subject variation in 18O natural abundance and apply this to our original working model for TEE calculation.MethodsUrine samples from a cohort of 99 women, dosed with 50 g of 20% 2H2O, undertaking a 14‐day breast milk intake protocol, were analysed for 18O. The within‐subject variance was calculated and applied to a Bayesian model for the calculation of TEE in a separate cohort of 36 women. This cohort of 36 women had taken part in a DLW study and had been dosed with 80 mg/kg body weight 2H2O and 150 mg/kg body weight H218O.ResultsThe average change in the δ18O value from the 99 women was 1.14‰ (0.77) [0.99, 1.29], with the average within‐subject 18O natural abundance variance being 0.13‰2 (0.25) [0.08, 0.18]. There were no significant differences in TEE (9745 (1414), 9804 (1460) and 9789 (1455) kJ/day, non‐Bayesian, Bluck Bayesian and modified Bayesian models, respectively) between methods.ConclusionsOur findings demonstrate that using a reduced natural variation in 18O as calculated from a population does not impact significantly on the calculation of TEE in our model. It may therefore be more conservative to allow a larger variance to account for individual extremes.