bluuebunny/crossref_metadata_2025 huggingface dataset:
Mast cells at the crossroads of microbiota and IBD
Authors: De Zuani Marco , Dal Secco Chiara , Frossi Barbara
Published: November 2018

The human gut harbors a wide range of microorganisms that play a fundamental role in the well‐being of their host. A dysregulation of the microbial composition can lead to the development or exacerbation of gastrointestinal (GI) disorders. Emerging evidence supports the hypothesis that mast cells (MCs) play a role in host‐microbiota communication, modulating the mutual influence between the host and its microbiota through changes in their activation state. The ability of some bacteria to specifically affect MC functions and activation has been extensively studied, with different and sometimes conflicting results, while only little is known about MC–fungi interactions. In this review, the most recent advances in the field of MC–bacteria and MC–fungi interactions will be discussed, with a particular focus on the role of these interactions in the onset of GI disorders such as inflammatory bowel diseases (IBD). Moreover, the connection between some MC‐targeting drugs and IBD was discussed, suggesting probiotics as reasonable and promising therapy in the management of IBD patients.
One Pot Synthesis of Au_ZnO Core‐Shell Nanoparticles Using a Zn Complex Acting as ZnO Precursor, Capping and Reducing Agent During the Formation of Au NPs
Authors: Contino Annalinda , Maccarrone Giuseppe , Spitaleri Luca , Torrisi Lucia , Nicotra Giuseppe , Gulino Antonino
Published: November 2018

Invited for the cover of this issue is the group of Antonino Gulino at the University of Catania, Italy. The cover image shows the formation of Au_ZnO core‐shell nanoparticles using a Zn complex that acts as capping agent for the Au nanoparticles and as ZnO precursor. These Au_ZnO nanoparticles absorb both visible and UV light and behave as photocatalysts.
Sterically Congested Ester Formation from α‐Substituted Malononitrile and Alcohol by an Oxidative Method Using Molecular Oxygen
Authors: Hayashi Yujiro , Li Jing , Asano Hirotaka , Sakamoto Daisuke
Published: November 2018

A metal‐free oxidative esterification or thio‐esterification of readily available substituted malononitrile and alcohol or thiol has been developed by simply mixing α‐substituted malononitrile and alcohol or thiol in the presence of base under a molecular oxygen atmosphere. Sterically hindered ester or thioester can be prepared efficiently.
Rapid separation of post‐blast explosive residues on glass electrophoresis microchips
Authors: Pinheiro Kemilly M. P. , Moreira Roger C. , Rezende Kariolanda C. A. , Talhavini Márcio , Logrado Lucio P. L. , Baio José A. F. , Lanza Marcos R. V. , Coltro Wendell K. T.
Published: November 2018

This study describes the development of an analytical methodology based on the use of microchip electrophoresis (ME) devices integrated with capacitively coupled contactless conductivity detection (C4D) for the separation and detection of inorganic anions in post‐blast explosive residues. The best separation condition was achieved using a running buffer composed of 35 mmol/L lactic acid, 10 mmol/L histidine and 0.070 mmol/L cetyl(trimethyl ammonium) bromide. For C4D measurements, the highest sensitivity was obtained applying a 700 kHz sinusoidal wave with excitation voltage of 20 Vpp. The separation of Cl−, NO3−, NO2−, SO42−, ClO4− and ClO3− was performed within ca. 150 s with baseline resolution and efficiencies between 4.4 × 104 and 1.7 × 105 plates/m. The found limits of detection ranged between 2.5 and 9.5 μmol/L. Last, real samples of post‐blast explosive residues were analyzed on the ME‐C4D devices obtaining successfully the determination of Cl−, NO3− and SO42−. The achieved concentration values varied between 12.8–72.5 mg/L for Cl−, 1.7–293.1 mg/L for NO3− and 1.3–201.3 mg/L for SO42−. The data obtained using ME‐C4D devices were in good agreement with the concentrations found by ion chromatography. The approach reported herein has provided short analysis time, instrumental simplicity, good analytical performance and low cost. Furthermore, the ME‐C4D devices emerge as a powerful and portable analytical platform for on‐site analysis demonstrating to be a promising tool for the crime scene investigation.
Probabilistic models for structures with bilinear demand‐intensity relationships
Authors: O'Reilly Gerard J. , Monteiro Ricardo
Published: November 2018

An extension to the existing SAC/FEMA expressions to estimate mean annual frequency of exceedance (MAFE) for a given limit state is described. In specific, this study pertains to structural systems whose demand versus seismic intensity relationship cannot be reasonably represented by a linear fit in logspace, but rather a bilinear fit over the entire range of structural response. Using a predefined limiting intensity, the median demand is separated into two distinct zones of response. These expressions are derived using a second‐order polynomial hazard model fit and can be considered a further extension of the closed‐form expressions available in the literature. The steps in the derivation are described along with an example application of the proposed expressions. Comparing different models shows that the MAFE can be significantly misrepresented when using a linear demand‐intensity model for systems whose behaviour deviates from this assumption in logspace. Similarly, a logarithmic function demand‐intensity fit is examined and seen not to be suitable in the specific situations focused on here. Furthermore, significant underestimation or overestimation is observed when using local fits in the vicinity of the behaviour transition point, which highlights the need for such a bilinear model when assessing the structural performance at the transition point's vicinity. Adopting a bilinear model is shown to better represent structural systems with complex response characteristics, also allowing the use of a single demand model for the entire range of response. This is at the same time still compatible with the existing framework for performance‐based seismic design and assessment.
Assessing the time dependence of prognostic values of cytology and human papillomavirus testing in cervical cancer screening
Authors: Isidean Sandra D. , Wang Yishu , Mayrand Marie‐Hélène , Ratnam Sam , Coutlée François , Franco Eduardo L. , Abrahamowicz Michal ,   for the CCCaST Study Group
Published: November 2018

Accurate assessment of risks for developing cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) after a given set of screening test results is instrumental to reaching valid conclusions and informing cervical cancer screening recommendations. Using data from the Canadian Cervical Cancer Screening Trial (CCCaST), we assessed prognostic values of enrollment screening test results to predict CIN2+ among women attending routine cervical screening using multivariable Cox proportional hazards (PH) regression and its flexible extension during each of two follow‐up periods (protocol‐defined and extended). Nonproportional (time‐dependent (TD)) and/or nonlinear effects were modeled, as appropriate. Women with abnormal cytology had hazard ratios (HRs) for CIN2+ detection of 17.61 (95% CI: 11.25–27.57) and 10.46 (95% CI: 5.41–20.24) relative to women with normal cytology during the protocol‐defined and extended follow‐up periods, respectively. High‐risk human papillomavirus (HR‐HPV) positivity was an even stronger predictor of CIN2+ risk, with significant TD effects during both follow‐up periods (p<0.001 for both TD effects). Risks among women co‐testing HR‐HPV+ with and without abnormal cytology (relative to women co‐testing negative) were highest immediately after baseline, and decreased significantly thereafter (p<0.001 for both TD effects). HRs for HPV16+ and HPV18+ women (relative to those testing HR‐HPV‐) did not vary significantly over time (HR = 182.96; 95% CI: 95.16–351.77 and HR = 111.81; 95% CI: 44.60–280.31, respectively). Due to TD effects, conventional Cox model estimates considerably underestimated adjusted HRs associated with positive HR‐HPV testing results early on in the follow‐up periods.
Comprehensive analysis of HPV infection, EGFR exon 20 mutations and LINE1 hypomethylation as risk factors for malignant transformation of sinonasal‐inverted papilloma to squamous cell carcinoma
Authors: Sahnane Nora , Ottini Giorgia , Turri‐Zanoni Mario , Furlan Daniela , Battaglia Paolo , Karligkiotis Apostolos , Albeni Chiara , Cerutti Roberta , Mura Eleonora , Chiaravalli Anna Maria , Castelnuovo Paolo , Sessa Fausto , Facco Carla
Published: November 2018

Different risk factors are suspected to be involved in malignant transformation of sinonasal papillomas and include HPV infection, tobacco smoking, occupational exposure,EGFR/KRASmutations and DNA methylation alterations. In our study, 25 inverted sinonasal papillomas (ISPs), 5 oncocytic sinonasal papillomas (OSP) and 35 squamous cell carcinomas (SCCs) from 54 patients were genotyped for 10 genes involved inEGFRsignalling. HPV‐DNA detection was performed byin‐situhybridisation and LINE‐1 methylation was quantitatively determined by bisulphite‐pyrosequencing. High‐risk HPV was observed only in 13% of ISP‐associated SCC and in 8% ofde novo‐SCC patients.EGFRmutations occurred in 72% of ISPs, 30% of ISP‐associated SCCs and 17% ofde novo‐SCCs. At 5‐year follow‐up, SCC arose in only 30% (6/20) of patients withEGFR‐mutated ISPs compared to 76% (13/17) of patients withEGFR‐wild‐type ISP (p= 0.0044). LINE‐1 hypomethylation significantly increased from papilloma/early stage SCC to advanced stage SCC (p= 0.03) and was associated with occupational exposure (p= 0.01) and worse prognosis (p= 0.09). In conclusion, our results suggest that a small subset of these tumours could be related to HPV infection;EGFRmutations characterise those ISPs with a lower risk of developing into SCC; LINE‐1 hypomethylation is associated with occupational exposure and could identify more aggressive nasal SCC.
Comorbidities, age and period of diagnosis influence treatment and outcomes in early breast cancer
Authors: Minicozzi Pamela , Van Eycken Liesbet , Molinie Florence , Innos Kaire , Guevara Marcela , Marcos‐Gragera Rafael , Castro Clara , Rapiti Elisabetta , Katalinic Alexander , Torrella Ana , Žagar Tina , Bielska‐Lasota Magdalena , Giorgi Rossi Paolo , Larrañaga Nerea , Bastos Joana , Sánchez Maria José , Sant Milena ,   the European HR Working Group on breast cancer
Published: November 2018

Survival for breast cancer (BC) is lower in eastern than northern/central Europe, and in older than younger women. We analysed how comorbidities at diagnosis affected whether selected standard treatments (STs) were given, across Europe and over time, also assessing consequences for survival/relapse. We analysed 7581 stage I/IIA cases diagnosed in 9 European countries in 2009–2013, and 4 STs: surgery; breast‐conserving surgery plus radiotherapy (BCS + RT); reconstruction after mastectomy; and prompt treatment (≤6 weeks after diagnosis). Covariate‐adjusted models estimated odds of receiving STs and risks of death/relapse, according to comorbidities. Pearson's R assessed correlations between odds and risks. The z‐test assessed the significance of time‐trends. Most women received surgery: 72% BCS; 24% mastectomy. Mastectomied patients were older with more comorbidities than BCS patients (p < 0.001). Women given breast reconstruction (25% of mastectomies) were younger with fewer comorbidities than those without reconstruction (p < 0.001). Women treated promptly (45%) were younger than those treated later (p = 0.001), and more often without comorbidities (p < 0.001). Receiving surgery/BCS + RT correlated strongly (R = −0.9), but prompt treatment weakly (R = −0.01/−0.02), with reduced death/relapse risks. The proportion receiving BCS + RT increased significantly (p < 0.001) with time in most countries. This appears to be the first analysis of the influence of comorbidities on receiving STs, and of consequences for outcomes. Increase in BCS + RT with time is encouraging. Although women without comorbidities usually received STs, elderly patients often received non‐standard less prompt treatments, irrespective of comorbidities, with increased risk of mortality/relapse. All women, particularly the elderly, should receive ST wherever possible to maximise the benefits of modern evidence‐based treatments.
Evaluation of a validated methylation triage signature for human papillomavirus positive women in the HPV FOCAL cervical cancer screening trial
Authors: Cook Darrel A. , Krajden Mel , Brentnall Adam R. , Gondara Lovedeep , Chan Tracy , Law Jennifer H. , Smith Laurie W. , van Niekerk Dirk J. , Ogilvie Gina S. , Coldman Andrew J. , Warman Rhian , Reuter Caroline , Cuzick Jack , Lorincz Attila T.
Published: November 2018

Human papillomavirus (HPV)‐based cervical cancer screening requires triage of HPV positive women to identify those at risk of cervical intraepithelial neoplasia grade 2 (CIN2) or worse. We conducted a blinded case–control study within the HPV FOCAL randomized cervical cancer screening trial of women aged 25–65 to examine whether baseline methylation testing using the S5 classifier provided triage performance similar to an algorithm relying on cytology and HPV genotyping. Groups were randomly selected from women with known HPV/cytology results and pathology outcomes. Group 1: 104 HPV positive (HPV+), abnormal cytology (54 CIN2/3; 50 <CIN2); Group 2: 103 HPV+, normal cytology with HPV persistence at 12 mo. (53 CIN2/3; 50 <CIN2); Group 3: 50 HPV+, normal cytology with HPV clearance at 12 mo. (assumed <CIN2), total n=257. For the combined groups, S5 risk score CIN2/3 relative sensitivity, specificity and positive predictive value (PPV) were compared with other triage approaches. Methylation showed a highly significant increasing trend with disease severity. For CIN3, S5 relative sensitivity and specificity were: 93.2% (95%CI: 81.4–98.0) and 41.8% (35.2–48.8), compared to 86.4% (75.0–95.7) and 49.8% (43.1–56.6) respectively for combined abnormal cytology/HPV16/18 positivity (differences not statistically significant at 5% level); adjusted PPVs were 18.2% (16.2–20.4) and 19.3% (16.6–22.2) respectively. S5 was also positive in baseline specimens from eight cancers detected during or after trial participation. The S5 methylation score had high sensitivity and PPV for CIN3, compatible with US and European thresholds for colposcopy referral. Methylation signatures can identify most HPV positive women at increased risk of cervical cancer from their baseline screening specimens.
Retracted: Exosomal circRNA derived from gastric tumor promotes white adipose browning by targeting the miR‐133/PRDM16 pathway
Authors: Zhang Haiyang , Zhu Lei , Bai Ming , Liu Ying , Zhan Yang , Deng Ting , Yang Haiou , Sun Wu , Wang Xinyi , Zhu Kegan , Fan Qian , Li Jialu , Ying Guoguang , Ba Yi
Published: November 2018

Cancer‐related cachexia is a metabolic syndrome characterized by a wasting disorder of adipose and skeletal muscle and is accompanied by body weight loss and systemic inflammation. The treatment options for cancer cachexia are limited, and the molecular mechanism remains poorly understood. Circular RNAs (circRNAs) are a novel family of endogenous noncoding RNAs that have been proposed to regulate gene expression in mammals. Exosomes are small vesicles derived from cells, and recent studies have shown that circRNAs are stable in exosomes. However, little is known about the biological role of circRNAs in exosomes. In our study, we showed that circRNAs in plasma exosomes have specific expression features in gastric cancer (GC), and ciRS‐133 is linked with the browning of white adipose tissue (WAT) in GC patients. Exosomes derived from GC cells deliver ciRS‐133 into preadipocytes, promoting the differentiation of preadipocytes into brown‐like cells by activating PRDM16 and suppressing miR‐133. Moreover, knockdown of ciRS‐133 reduced cancer cachexia in tumor‐implanted mice, decreasing oxygen consumption and heat production. Thus, exosome‐delivered circRNAs are involved in WAT browning and play a key role in cancer‐associated cachexia.
Assisted reproductive outcomes in women with different polycystic ovary syndrome phenotypes
Authors: Eftekhar Maryam , Mirhashemi Elham S. , Tabibnejad Nasim
Published: November 2018

Objective

To explore assisted reproductive outcomes among women with different polycystic ovary syndrome (PCOS) phenotypes.

Methods

A retrospective cohort study included women with PCOS who were treated at Yazd Research and Clinical Center for Infertility, Yazd, Iran, using the GnRH antagonist protocol between April 1, 2015, and August 31, 2017. Clinical pregnancy was the primary outcome, and chemical pregnancy, implantation rate, fertilization rate, and spontaneous abortion rate, were the secondary outcomes that were evaluated among four defined phenotypes of women with PCOS.

Results

Significant differences were observed between the phenotypes for the levels of luteinizing hormone, anti‐Müllerian hormone, fasting blood sugar, and total testosterone concentration; similarly, the percentage of women with luteinizing hormone/follicle stimulating hormone ratio of at least 2.5 differed between PCOS phenotypes (all P<0.001). There were also significant differences in estradiol level (P<0.001) and the number of matured follicles (P=0.002) between different phenotypes. No significant differences were observed in the fertilization and implantation rates, as well as chemical and clinical pregnancy rates (all P>0.05).

Conclusion

No significant differences were observed in assisted reproductive technique outcome among women with different phenotypes of PCOS undergoing frozen‐thawed embryo transfer.
Effect of the Centers for Disease Control and Prevention opioid prescribing guidelines on postsurgical prescribing among veterans
Authors: Karst Allison C. , Hayes Brittany F. , Burka Abigail T. , Bean Jennifer R. , Wallace Jessica L.
Published: November 2018

Background

In 2016, the Centers for Disease Control and Prevention (CDC) published opioid prescribing guidelines. The literature review identified an association between opioids prescribed for acute pain and an increased risk for long‐term use. Guidelines recommend 3 days or less of therapy in most cases of acute pain. Prescriber education may be necessary.

Objective

To assess the impact of the CDC opioid prescribing guidelines and targeted prescriber education on postsurgical prescribing.

Methods

This study was a single‐center, retrospective, observational analysis of adult Veterans admitted for carotid endarterectomy or endovascular aneurysm repair during preguideline, postguideline, and posteducational intervention time frames. Exclusion criteria included chronic opioid use/abuse, hospitalization over 72 hours, and repeat operation. Pharmacists provided education on opioid prescribing during monthly surgery orientation. The primary end point was mean morphine equivalents (MMEs) prescribed at discharge. Secondary end points included distribution across morphine equivalents ranges, the days' supply of opioids prescribed, and percentage prescribed nonopioid therapy.

Results

MMEs decreased following guideline publication (295.82 MMEs preguidelines vs 160.68 MMEs postguidelines; P = 0.003). After prescriber education, a further absolute reduction in MMEs was seen, although not statistically significant (160.68 vs 139.29; P = 0.810). Days' supply prescribed decreased following guideline publication (8.17 days preguidelines vs 4.71 days postguidelines; P = 0.009); however, no statistical difference was observed posteducation (4.71 vs 3.29 days; P = 0.294). In addition, no difference was found in the percentage of nonopioid therapy prescribed postguidelines (70.83% vs 68.18%; P = 0.988) or posteducation (68.18% vs 64.29%; P = 1.00).

Conclusions

The 2016 CDC opioid prescribing guidelines likely had an impact on postsurgical opioid prescribing, evident by decreased MMEs and opioid days' supply following guideline publication. Although these end points did not reach statistical significance following prescriber education, the trends suggest clinical significance.
Pharmacist authorship on clinical practice guidelines
Authors: Thompkins April W. , Norman Brian F. , Hill Brandon K. , Antosz Kayla S. , Bookstaver P. Brandon
Published: November 2018

Introduction

The National Academy of Medicine (NAM; formerly the Institute of Medicine) recommends multidisciplinary authorship as a standard for developing trustworthy guideline panels. The purpose of this study is to describe pharmacist authorship on clinical practice guideline (CPG) expert panels.

Methods

Guidelines published between January 1, 2010 and December 31, 2016 and were available in the Agency for Healthcare Research and Quality National Guideline Clearinghouse database were eligible for study inclusion. Only guidelines with pharmacotherapeutic recommendations were included. The primary end point was the proportion of pharmacist authorship on national CPGs. Pharmacist authorship by specialty area and characteristics of pharmacist authors were described.

Results

Of the 143 guidelines included, 58 (40.6%) had at least one pharmacist author. Guidelines developed by the Veterans Affairs/Department of Defense (VA/DoD; n = 7) and the Clinical Pharmacogenetics Implementation Consortium (CPIC; n = 13) always included at least one pharmacist. Excluding VA/DoD and CPIC guidelines, the proportion of pharmacist authorship was 30.9% (38/123). A pharmacist served as the first, senior, and/or corresponding author on 19% (27/143) of CPGs. There were 1919 total authors with an average of 13.4 (+7.4) authors per guideline. Pharmacists represented 6.8% (130/1919) of all authors, and 83 were unique pharmacist authors. Critical care, emergency medicine, and adult internal medicine guidelines had the largest proportion of pharmacist authorship, while oncology and pediatric guidelines had the smallest. Pharmacy organizations sponsored or endorsed 5.2% (3/58) of CPGs with a pharmacist author.

Conclusion

The majority of CPGs in this cohort did not include a pharmacist in the authorship and when included, was often limited to a single pharmacist. It is imperative for pharmacy organizations to collaborate with sponsoring medical organizations and position clinical pharmacists to serve as expert members on CPGs consistent with NAM recommendations.
Serine hydroxymethyltransferase 1 promoter hypermethylation increases the risk of essential hypertension
Authors: Xu Guodong , Wang Changyi , Ying Xiuru , Kong Fanqian , Ji Huihui , Zhao Jinshun , Zhang Xiaohong , Duan Shiwei , Han Liyuan , Li Li
Published: November 2018

Background

Serine hydroxymethyltransferase 1 (SHMT1) is an enzyme involved in folic acid metabolism and is known to contribute to the development of hypertension. We evaluated the relationship between SHMT1 promoter methylation and essential hypertension (EH).

Methods

Quantitative methylation‐specific polymerase chain reaction was used to measure the SHMT1 promoter methylation level in 241 EH patients and 288 age‐ and gender‐matched healthy individuals. The diagnostic value of SHMT1 promoter hypermethylation was analyzed using a receiver operating characteristic (ROC) curve. The Gene Expression Omnibus (GEO) database and dual‐luciferase reporter assay were used to validate our findings.

Results

Compared with the control group, significant differences in SHMT1 promoter methylation were found in both EH and hyperhomocysteinemia groups (P < 0.001 and P = 0.029, respectively). The area under the curve of the diagnosis of SHMT1 promoter hypermethylation for EH was 0.808, with a sensitivity and specificity of 73.9% and 77.8%, respectively. The risk of SHMT1 promoter hypermethylation was significantly higher in the >65‐year group than in the ≤65‐year group (odds ratio = 3.925; 95% confidence interval = 2.141‐7.196). In addition, GEO database analysis showed that 5‐aza‐deoxycytidine increased gene expression in several carotid endothelial cell lines. A dual‐luciferase reporter assay revealed that the target sequence in the SHMT1 promoter upregulated gene expression.

Conclusion

Our findings indicate that SHMT1 promoter hypermethylation increases the risk of EH and may be a promising biomarker for EH.
Serum pentraxin‐3 levels and flow‐mediated dilation in dipper and non‐dipper hypertension
Authors: Alp Çağlar , Dogru Mehmet Tolga , Karadeniz Muhammed , Sarak Taner , Demir Vahit , Çelik Yunus , Kandemir Hüseyin , Kısa Üçler
Published: November 2018

Background

Endothelial dysfunction is one of the main pathological processes of hypertension. The association of serum pentraxin‐3 (PTX3) levels and endothelial dysfunction becomes a more interesting scientific research issue due to high potential of PTX3 as a diagnostic and prognostic biomarker. We aimed to investigate the relationship between serum PTX3 levels and flow‐mediated dilation results in patients with dipper and non‐dipper hypertension.

Methods

This study included 90 hypertensive patients were divided into two groups based on 24 hours ambulatory blood pressure monitoring (ABPM): 38 patients with a dipper pattern and 52 patients with non‐dipper pattern. Noninvasive evaluation of the endothelial functions was performed using flow‐mediated dilation (FMD) method.

Results

Serum pentraxin‐3 levels were higher in patients with non‐dipper HT compared to dipper hypertension (P = 0.028). In addition, we found negative correlation between serum PTX3 and FMD basal/FMD hyperemia ratio (r = −0.297, P = 0.05 for FMD basal/FMD hyperemia ratio, respectively).

Conclusions

Serum PTX3 levels are closely related with the measures of indirect noninvasive evaluation methods (FMD) in both DH and NDH patients.
Simulations of Valproate Doses Based on an External Evaluation of Pediatric Population Pharmacokinetic Models
Authors: Tauzin Manon , Tréluyer Jean‐Marc , Nabbout Rima , Billette de Villemeur Thierry , Desguerre Isabelle , Aboura Radia , Gana Ines , Zheng Yi , Benaboud Sihem , Bouazza Naim , Chenevier‐Gobeaux Camille , Freihuber Cécile , Hirt Déborah
Published: November 2018

Valproate is an old‐generation antiepileptic drug often used in children. The pharmacokinetics of valproate are noteworthy for a large and difficult to predict interindividual variability in measured serum concentrations and for saturable protein binding. A model‐based approach to personalize valproate treatment could be relevant in pediatric patients. The aims of this study were to review all published valproate population pharmacokinetic models in children and assess them by external validation to determine their predictive performance. Through simulations with the best model, we evaluated dosing regimen. A validation data set included valproate serum concentrations assayed during routine therapeutic drug monitoring of epileptic children. We applied to our population 11 published pediatric population pharmacokinetic models. For each model, predictive performance was assessed by external validation, using bias and precision calculations as well as goodness‐of‐fit plots. Dose simulations were conducted with the best predictive model to evaluate dosing regimen. The validation data set contained 178 valproate concentrations ranging from 13.4 to 128 mg/L from 114 patients. The best model exhibited a mean prediction error of 6.6 mg/L and a root mean squared error of 25.1 mg/L, with no model misspecification evidenced by visual predictive check. In our cohort, half the patients had a trough concentration <50 mg/L. Simulations suggested increasing doses, especially for children ≤40 kg. External evaluation of published valproate pharmacokinetic models enabled us to identify a suitable model for simulations and Bayesian forecasting. Dosing regimen should be adjusted to weight, with decreasing doses with increasing weight.
Complementary Pharmacokinetic Profiles of Netupitant and Palonosetron Support the Rationale for Their Oral Fixed Combination for the Prevention of Chemotherapy‐Induced Nausea and Vomiting
Authors: Gilmore James , Bernareggi Alberto
Published: November 2018

NEPA is the first fixed‐combination antiemetic composed of the neurokinin‐1 receptor antagonist netupitant (netupitant; 300 mg) and the 5‐hydroxytryptamine‐3 receptor antagonist palonosetron (palonosetron; 0.50 mg). This study evaluated the pharmacokinetic profiles of netupitant and palonosetron. The pharmacokinetic profiles of both drugs were summarized using data from phase 1‐3 clinical trials. netupitant and palonosetron have high absolute bioavailability (63%‐87% and 97%, respectively). Their overall systemic exposures and maximum plasma concentrations are similar under fed and fasting conditions. netupitant binds to plasma proteins in a high degree (>99%), whereas palonosetron binds to a low extent (62%). Both drugs have large volumes of distribution (cancer patients: 1656‐2257 L and 483‐679 L, respectively). netupitant is metabolized by cytochrome P450 3A4 to 3 major pharmacologically active metabolites (M1, M2, and M3). palonosetron is metabolized by cytochrome P450 2D6 to 2 major substantially inactive metabolites (M4 and M9). Both drugs have similar intermediate‐to‐low systemic clearances and long half‐lives (cancer patients: netupitant, 19.5‐20.8 L/h and 56.0‐93.8 hours; palonosetron: 7.0‐11.3 L/h and 43.8‐65.7 hours, respectively). netupitant and its metabolites are eliminated via the hepatic/biliary route (87% of the administered dose), whereas palonosetron and its metabolites are mainly eliminated via the kidneys (85%‐93%). Altogether, these data explain the lack of pharmacokinetic interactions between netupitant and palonosetron at absorption, binding, metabolic, or excretory level, thus highlighting their compatibility as the oral fixed combination NEPA, with administration convenience that may reduce dosing mistakes and increase treatment compliance.
Migration route of Fasciola into the liver
Authors: Lockart Ian , Das Amitabha , Merrett Neil D , Levy Miriam T
Published: November 2018

Humans usually acquire Fasciola infection by eating contaminated aquatic vegetation, such as watercress. After ingestion, Fasciola metacercariae excyst in the duodenum. In contrast to other liver flukes (Clonorchis and Opisthorchis) that migrate through the ampulla of Vater and ascend the biliary tree, Fasciola metacercariae penetrate the duodenal wall, migrate through the peritoneal cavity, and enter the liver. After a period of migrating randomly through the liver parenchyma, they eventually reach the larger biliary ducts and mature into adults. We present a case that illustrates this migration route of Fasciola.
Identification of dye content in colored BIC ballpoint pen inks by Raman spectroscopy and surface‐enhanced Raman scattering
Authors: Alyami Abeer , Barton Killian , Lewis Liam , Mirabile Antonio , Iacopino Daniela
Published: November 2018

Raman spectroscopy and surface‐enhanced Raman scattering (SERS) were used for the elucidation of dye content in commercial BIC ballpoint pens. In contrast to the majority of studies in this field on black and blue inks of forensic interest, this paper targeted characterization of colored (red, pink, purple, and green) pen inks, increasingly used for artistic purposes. Because of its not invasive nature, the capabilities of Raman spectroscopy were initially tested. However, overall SERS provided enhanced spectral features and quenching of fluorescence necessary for the unequivocal identification of dye mixtures in all analyzed pens. SERS analysis was carried out in situ, by deposition of Ag nanopastes directly on pen colored paper surfaces. Rhodamine B was identified as the main dye component in red, pink, and purple inks, whereas phthalocyanine dye Blue 38 was identified in all green inks; excitation at different wavelengths revealed that the darker hue of purple ink was achieved by addition of crystal violet to red Rhodamine B and that green hues were achieved by addition of yellow dyes to Blue 38. UV–vis spectroscopy and thin‐layer chromatography analyses complemented Raman/SERS measurements by revealing the presence of additional yellow/orange and blue components in red and green inks, respectively. The relevance of this analysis for art diagnostics was demonstrated through the real noninvasive analysis of BIC pens drawings, which led to successful identification of chemical ink composition and identification of production medium.
Effect of sequential twin screw extrusion and fungal pretreatment to release soluble nutrients from soybean residue for carotenoid production
Authors: Lee Jaslyn JL , Cooray Sachindra T , Mark Rita , Chen Wei N
Published: November 2018

BACKGROUND

Soybean residue (okara) is an agricultural by‐product, which is rich in protein and fiber. This study evaluated a novel sequential process which combined fungal pretreatment (F) and twin screw extruder (E), to hydrolyze okara. The sequence of the pretreatment steps, and extruder at screw speeds 200 rpm (200) or 600 rpm (600), were tested. Next, soluble nutrients were extracted to create Fokara, EFokara200, EFokara600, FEokara200 and FEokara600 okara media.

RESULTS

All the prepared okara media could support the growth and carotenoid production by the yeast Rhodosporidium toruloides. This suggested that okara proteins and polysaccharides were successfully hydrolyzed by extrusion and fungal pretreatment, into soluble nutrients. Rhodosporidium toruloides accumulated the highest biomass of 23.7 mg mL−1 dry cell weight (DCW), when grown on FEokara600 media. This was higher as compared to commercial YPG (yeast extract–peptone–glycerol) media (18.7 mg mL−1 DCW). However, R. toruloides accumulated the highest carotenoid production of 13.2 µg mL−1 when grown on EFokara200 media as the nutrient source. This was comparable to carotenoid production of 13.1 µg mL−1 when R. toruloides was grown on YPG media.

CONCLUSION

Extrusion in combination with fungal pretreatment, is a low cost process, to hydrolyze and re‐use okara, for carotenoid production. © 2018 Society of Chemical Industry
An agent‐based model of tourism destinations choice
Authors: Alvarez Emiliano , Brida Juan Gabriel
Published: November 2018

This study introduces a dynamic agent‐based model to represent the evolution of the choice of destinations by tourists. The model assumes that this choice depends on their personal tastes (characterized by their preferences for goods and services) and certain characteristics of other tourists (called crowding types), on the degree of inertia of the individuals and relevant information about the characteristics of visitors to other destinations. The model shows that the individual choices and the characterization of destinations are emergent properties of the system. The simulations show the formation of stable groups of individuals sharing destination, an endogenously increasing level of specialization of destinations, as well as an increasing market concentration, and that individuals of different characteristics can share destinations.
Diagnostic Performance and Accuracy of the 3 Interpreting Methods of Breast Strain Elastography: A Systematic Review and Meta‐analysis
Authors: Barr Richard G. , De Silvestri Annalisa , Scotti Valeria , Manzoni Federica , Rebuffi Chiara , Capittini Cristina , Tinelli Carmine
Published: November 2018

There are 3 methods of interpreting breast strain elastography: the elastographic–to–B‐mode length ratio (E/B), a 5‐point color scale (5P), and the strain ratio (SR). This meta‐analysis assessed which method is superior to the others. A systematic search of the medical literature was performed in July 2017. Studies were eligible for inclusion if they fulfilled the following criteria: (1) had biopsy‐proven or long‐term stability as the reference standard; (2) used either the E/B, 5P, or SR to interpret results; and (3) had at least 50 cases. A total of 220 records were retrieved; 60 full‐text articles were examined, and 46 were included in the meta‐analysis. Publication years ranged from 2007 and 2017. The quality of studies was generally high. The mean age of women was 48 years; 12,398 lesions (4242 malignant) were analyzed. For the 5P method, the sensitivity was 77%; specificity, 87%; positive likelihood ratio (LR), 5.3; and negative LR, 0.24. For the SR method, sensitivity was 87%; specificity, 81%; positive LR, 4.8; and negative LR, 0.16. For the E/B method, sensitivity was 96%; specificity, 88%; positive LR, 7.1; and negative LR, 0.03. Of the 3 methods, the E/B had the highest sensitivity, and the E/B and 5P had the highest specificity. With a negative LR of 0.03, the E/B method can downgrade lesions with a pretest probability of 50% to a 2% probability of malignancy.
Magnetic resonance imaging with cochlear implants and auditory brainstem implants: Are we truly practicing MRI safety?
Authors: Shew Matthew , Wichova Helena , Lin James , Ledbetter Luke N. , Staecker Hinrich
Published: November 2018

Objective

Our objective is to evaluate the safety in patients with cochlear implants (CIs) and auditory brainstem implants (ABI) undergoing 1.5 Tesla (T) magnetic resonance imaging (MRI). Secondly, we want to raise awareness on CI and MRI safety, and advocate for continued improvement and advancement to minimize morbidity for our CI patients.

Methods

Retrospective case series from 2006 to 2018 at a single tertiary academic center. Data was collected on patients with CI or auditory brainstem implants undergoing MRI. Outcomes collected include demographic data, age at time of MRI, MRI characteristics, complications, CI manufacturer, and image quality.

Results

Eighteen patients with CI or ABI collectively underwent a total of 62 MRI scans. Five of 15 (33%) CI patients with magnet had complications: five total of 24 MRI scans (21%). Two patients had magnet removal prior to 29 MRI scans without complications. Four of five MRI‐related complications were equipped with a U.S. Food and Drug Administration‐approved head wrap. Three of five required a trip to the operating room to explore and reposition the CI magnet; two could not complete MRI secondary to pain. Of the complications, two were Cochlear (Sydney, Australia), two Advanced Bionics (Valencia, CA), and one MED‐EL (Innsbruck, Austria). Synchrony model (MED‐EL) had 0 of seven complications, with a total of 19 MRI scans, which features a freely rotating and self‐aligning magnet.

Conclusion

Our series offers a diverse number of CI manufacturers and is in accordance with other literature that CI MRI‐related adverse events are occurring at an unacceptable frequency. We can promote CI MRI safety through our institutions' MRI CI patient protocols, raise awareness that diagnostic MRI benefits must outweigh CI‐related complications, and advocate for continued industry technological innovation.

Level of Evidence

4 Laryngoscope, 129:482–489, 2019
A Green and Highly Efficient Naphthalimide Visible Photoinitiator with an Ability Initiating Free Radical Polymerization under Air
Authors: Yang Jianjing , Xu Can , Xiong Ying , Wang Xiaoling , Xie Yujun , Li Zhen , Tang Hongding
Published: November 2018

A visible photoinitiator, 2‐(2‐(1,3‐dioxo‐6‐(piperidin‐1‐yl)‐1H‐benzo[de]‐isoquinolin‐2(3H)‐yl)ethoxy)ethyl acrylate (ND‐O‐EA), for attenuating the oxygen inhibition in the free radical polymerization, is designed and synthesized. The results show that it has an outstanding ability to overcome oxygen inhibition demonstrated by the fact that no induction period is observed during the free radical polymerization of the acrylate in the air. A possible preferred intramolecular hydrogen‐abstraction reaction in which a peroxyl radical regenerates a new carbon radical through a stable six‐member ring intermediate, should correspond to its anti‐oxygen capacity. After 1 min of irradiation under air atmosphere, the double‐bond conversion of 1,6‐hexanediol diacrylate in the ND‐O‐EA system can be up to 13.3%, while the camphorquinone‐N‐methyldiethanolamine (CQ‐MDEA) system is about 8.0%, and the phenylbis(2,4,6‐trimethylbenzoyl)phosphine oxide (BAPO) is only 0.13%. Furthermore, as a one‐component polymerizable photoinitiator, the mass fraction of the extracted ND‐O‐EA is about 6.2% with respect to the initial quality after photopolymerization.
Gallol‐Tethered Injectable AuNP Hydrogel with Desirable Self‐Healing and Catalytic Properties
Authors: Zhao Qiuxia , Mu Shengdong , Liu Xiong , Qiu Guirong , Astruc Didier , Gu Haibin
Published: November 2018

Injectable self‐healing hydrogels have drawn growing attention for their extensive applications in biomedical fields. Hydrogels containing nanoparticles also exhibit promising potentials in catalysis, wastewater treatment, and organic synthesis. Inspired by the multifunction of gallol presented herein, a simple one‐pot method to produce a gallol‐tethered gelatin hydrogel via Schiff base under oxidizing conditions using various oxidants is presented. The hydrogels prepared by NaIO4‐induced cross‐linking present a high self‐healing rate (up to 84.5%), injectable ability, tunable mechanical property, flexible viscoelasticity, and macroporous structure owing to the combination of covalent cross‐linking and supramolecular interactions. HAuCl4 contributes to the 3D structure formation of the gelatin hydrogel via oxidation cross‐linking. It is reduced by the gallol groups to produce nanogold (AuNP)‐decorated hydrogel (Au‐gel). This Au‐gel is fully characterized by UV–vis, XRD, TEM, SEM, EDX, and ICP‐MS and exhibits a high‐catalytic activity for the reduction of 4‐nitrophenol. The solid Au‐gel catalyst is robust, easily recyclable, and reused at least eight times.
Water Soluble Polymer Flocculants: Synthesis, Characterization, and Performance Assessment
Authors: Vajihinejad Vahid , Gumfekar Sarang P. , Bazoubandi Behnaz , Rostami Najafabadi Zahra , Soares João B. P.
Published: November 2018

Water soluble polymer flocculants are important constituents of solid–liquid separation units for the treatment of a variety of process‐affected effluents. The systematic development of a flocculant relies on a good understanding of flocculation process, polymer synthesis, polymer characterization, and, not the least, flocculation performance assessment as desired for a particular treatment process, all of which are essential to establish meaningful relationships between flocculant microstructure and flocculation efficiency. The aim of this article is to communicate the bigger picture of this research area to the readers. The recent advances in the application of bio/natural, synthetic, and stimuli‐responsive flocculants are reviewed. Then, the basic polymer reaction engineering tools to control the microstructure of flocculants are provided and the techniques for the quantification of flocculant microstructure are concisely discussed. This is followed by a review of the methods used for the characterization of particle‐polymer force measurement, and flocculation/dewatering assessment with attention to the characterization of aggregate structures.
Comparing Risperidone and Olanzapine to Tetrabenazine for the Management of Chorea in Huntington Disease: An Analysis from the Enroll‐HD Database
Authors: Schultz Jordan L. , Kamholz John A. , Nopoulos Peg C. , Killoran Annie
Published: November 2018

Introduction

Huntington's chorea (HC) is commonly managed with neuroleptic medications, though there is little evidence to support their use. This study aimed to perform a real‐world comparison of the efficacy of risperidone and olanzapine to tetrabenazine (TBZ) for HC.

Methods

The Enroll‐HD database was used to perform a propensity score‐matched comparison of risperidone and olanzapine to TBZ, regarding their efficacy in controlling chorea. Participants with motor manifest Huntington's disease (HD) were grouped according to their use of risperidone, olanzapine, or TBZ. For the three groups, independent propensity score matching was performed on participants’ baseline total functional score (TFC), baseline total motor score (TMS), disease burden score, CAG repeat length, baseline age, region, sex, and body mass index. Independent samples t test was used to calculate the differences between the groups in the annual rate of change of the TMS from the baseline to the second available visit.

Results

The risperidone (n = 72) and olanzapine groups (n = 77) had annualized increases (worsening) in the TMS of only 1.47 points and 3.20 points, respectively, compared to 5.70 points in the two matched TBZ groups (n = 72) (P = 0.019) and (n = 77) (P = 0.143), respectively.

Conclusions

In the absence of prospective data, this analysis of the Enroll‐HD database found that the neuroleptics risperidone and olanzapine seemed to at least be comparable to TBZ at controlling HC. These results demonstrate that neuroleptics may have comparable efficacy to TBZ for the treatment of HC. Further prospective studies are needed to confirm these findings.
Spectrum of Movement Disorders in 18p Deletion Syndrome
Authors: Crosiers David , Blaumeiser Bettina , Van Goethem Gert
Published: November 2018

Background

Deletion of the short arm of chromosome 18 leads to 18p deletion syndrome. Clinical features include short stature, facial dysmorphism, mental retardation, and several types of movement disorders.

Methods

The 18p deletion syndrome in our patient was diagnosed using karyotype analysis and confirmed by genome‐wide single‐nucleotide polymorphism array. We have performed a literature search and summarized all previously reported patients with 18p deletion syndrome and movement disorders.

Results

We present a 41‐year‐old male patient with childhood‐onset generalized dystonia. Dystonia is the most prevalent movement disorder in 18p deletion patients, with onset ranging from childhood to adulthood. Chorea, myoclonus, tremor, tics, and ataxia have been reported in a minority of these patients.

Conclusion

Dystonia is commonly observed in 18p deletion syndrome. The variable size of the deletion on 18p is probably responsible for the broad phenotypic variability of movement disorders in this syndrome.
Associations of genetic variants in endocytic trafficking of epidermal growth factor receptor super pathway with risk of nonsyndromic cleft lip with or without cleft palate
Authors: Li Bing , Ma Lan , Zhang Chi , Zhou Zhixuan , Yuan Hua , Jiang Hongbing , Pan Yongchu , Tan Qian
Published: November 2018

Background

The genetic etiology of nonsyndromic cleft lip with or without cleft palate (NSCL/P) has not been fully clarified to date. Epidermal growth factor receptor (EGFR) was reportedly involved in its biological establishment and regulation of cell migration during the embryonic stage.

Methods

We selected a super pathway of endocytic trafficking of EGFR and investigated the associations of single‐nucleotide polymorphisms (SNPs) in the super pathway with the risk of NSCL/P by analyzing our published genome‐wide association study (GWAS) data from 504 NSCL/P individuals and 455 controls. After the false discovery rate (FDR) control, we conducted linkage disequilibrium (LD) analyses and conditional regression analyses to obtain independent lead SNPs. We performed LD analyses between the lead SNPs and the reported SNPs to find novel ones from our study. We annotated the lead SNPs and investigated their mapped genes in silico.

Results

A total of 82 SNPs showed a statistical association with the risk of NSCL/P after FDR control. They contained three reported SNPs which were g.117068049G>A (rs7078160), g.117086783C>G (rs10886040), and g.117101266G>T (rs17095681). Four independent lead SNPs were obtained, including g.116979803 T>C (rs1905539) and g.117037960A>G (rs7902502) at 10q25.3, g.35720163G>C (rs75656820) at 17q12, and g.156864512G>A (rs1800877) at 1q23.1. Three of them were in low LD (r2 < 0.5) with the reported SNPs except g.117037960A>G (rs7902502), so these three were newly identified. Lead SNPs were mapped to three genes: SHTN1, AP2B1, and NTRK1. The three genes were relatively more highly expressed in the human craniofacial region and in the proximal maxillary location during the craniofacial development stage of the embryonic mouse.

Conclusion

Our results suggested that SHTN1, AP2B1, and NTRK1 might be associated with the development of NSCL/P.