bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of RAS and BRAF mutations in metastatic colorectal cancer patients by tumor sidedness: A systematic review and meta‐analysis
Authors: Bylsma Lauren C. , Gillezeau Christina , Garawin Tamer A. , Kelsh Michael A. , Fryzek Jon P. , Sangaré Laura , Lowe Kimberly A.
Published: December 2019

Studies have shown that the prevalence of RAS and BRAF mutations may differ by tumor sidedness among metastatic colorectal cancer (mCRC) patients. Both mutation status and tumor sidedness may impact survival and disease progression and RAS mutation status has been shown to predict response to anti‐epidermal growth factor receptor (EGFR) therapy. A systematic literature review and meta‐analysis were conducted to estimate the pooled prevalence of RAS and BRAF mutations by tumor sidedness in studies of mCRC patients. Forty‐four studies comprising 15 981 mCRC patients tested for RAS and/or BRAF mutations were included in the meta‐analyses. The prevalence of RAS mutations differed significantly by tumor side (32.4% among left‐sided tumors, 41.3% among right‐sided tumors; P = .017), as did the prevalence of KRAS mutations (35.8% among left‐sided tumors, 46.3% among right‐sided tumors; P < .0001) and BRAF mutations (4.3% among left‐sided tumors, 16.3% among right‐sided tumors; P < .0001). Among right‐sided tumors, the prevalence of RAS and KRAS mutations varied significantly by study design, with higher prevalence among observational studies than clinical trials, and there was significant variation by study location for the prevalence of KRAS mutations in left‐sided tumors and the prevalence of BRAF mutations in right‐sided tumors. These results help to better characterize the mCRC population to better inform clinicians and researchers. Few of the included studies reported overall or progression‐free survival (PFS) by both tumor sidedness and mutation status. As both of these factors may have prognostic impact, future studies should consider evaluating survival by these variables.
Methylation of CpG 5962 in L1 of the human papillomavirus 16 genome as a potential predictive marker for viral persistence: A prospective large cohort study using cervical swab samples
Authors: Fertey Jasmin , Hagmann Jörg , Ruscheweyh Hans‐Joachim , Munk Christian , Kjaer Susanne , Huson Daniel , Haedicke‐Jarboui Juliane , Stubenrauch Frank , Iftner Thomas
Published: December 2019

Several studies have demonstrated that the viral genome can be methylated by the host cell during progression from persistent infection to cervical cancer. The aim of this study was to investigate whether methylation at a specific site could predict the development of viral persistence and whether viral load shows a correlation with specific methylation patterns. HPV16‐positive samples from women aged 20–29 years (n = 99) with a follow‐up time of 13 years, were included from a Danish cohort comprising 11 088 women. Viral load was measured by real‐time PCR and methylation status was determined for 39 CpG sites in the upstream regulatory region (URR), E6/E7, and L1 region of HPV16 by next‐generation sequencing. Participants were divided into two groups according to whether they were persistently (≥ 24 months) or transiently HPV16 infected. The general methylation status was significantly different between women with a persistent and women with a transient infection outcome (P = .025). One site located in L1 (nt. 5962) was statistically significantly (P = .00048) different in the methylation status after correction using the Holm‐Sidak method (alpha = 0.05). Correlation analyses of samples from HPV16 persistently infected women suggest that methylation is higher although viral load is lower. This study indicates that methylation at position 5962 of the HPV16 genome within the L1 gene might be a predictive marker for the development of a persistent HPV16 infection.
Pinwheel Pedicle Flap Technique for Increasing Keratinized Tissue at Stage 2 Implant Surgery
Authors: Maldonado‐Alfandari Katherine , Chong Chol H.
Published: December 2019

Introduction

The goal of stage 2 implant surgery is to uncover implants while maintaining or augmenting the peri‐implant keratinized tissue. Although the absolute requirement for keratinized tissue around natural teeth can be debated, implants appear to have consistently improved postoperative clinical parameters and health when there is an adequate keratinized peri‐implant tissue.

Case Presentation

This article presents a new technique to optimize the keratinized tissue around implants during stage 2 surgery. Although there are many treatment options that can be considered at the time of surgery, the technique presented here has the advantage of increasing the keratinized tissue circumferentially around the implant without using a second donor site. The technique, called the “pinwheel,” is presented in two cases with the same clinical presentation. Two mandibular overdenture patients with ≤3 mm of keratinized tissue over implant sites, stage 2 surgery was performed using the “pinwheel technique” to increase the keratinized tissue on the facial and lingual surfaces.

Conclusion

The use of the pinwheel technique to augment keratinized tissue around implants is effective and is a viable treatment option during stage 2 implant surgery.
Changes in cellular processes occurring in mucopolysaccharidoses as underestimated pathomechanisms of these diseases
Authors: Gaffke Lidia , Pierzynowska Karolina , Podlacha Magdalena , Brokowska Joanna , Węgrzyn Grzegorz
Published: December 2019

Mucopolysaccharidoses (MPS) are a group of genetic disorders belonging to lysosomal storage diseases. They are caused by genetic defects leading to a lack or severe deficiency of activity of one of lysosomal hydrolases involved in degradation of glycosaminoglycans (GAGs). Partially degraded GAGs accumulate in lysosomes, which results in dysfunctions of cells, tissues, and organs. Until recently, it was assumed that GAG accumulation in cells is the major, if not the only, mechanism of pathogenesis in MPS, as GAGs may be a physical ballast for lysosomes causing inefficiency of cells due to a large amount of a stored material. However, recent reports suggest that in MPS cells there are changes in many different processes, which might be even more important for pathogenesis than lysosomal accumulation of GAGs per se. Moreover, there are many recently published results indicating that lysosomes not only are responsible for degradation of various macromolecules, but also play crucial roles in the regulation of cellular metabolism. Therefore, it appears plausible that previous failures in treatment of MPS (i.e., possibility to correct only some symptoms and slowing down of the disease rather than fully effective management of MPS) might be caused by underestimation of changes in cellular processes and concentration solely on decreasing GAG levels in cells.
Cutaneous horn: A rare subtype of juvenile xanthogranuloma
Authors: Iraji Fariba , Ganjei Zakiye , Kazemipour Samira
Published: December 2019

Because of variability in the JXG shape and the extensive range of a cutaneous horn differential diagnosis, dermatologists should keep this diagnosis in their mind in the time of encountering with infants or children cases of cutaneous horn.
High‐Pressure Jet Cleaning of Polymeric Microfiltration Membranes
Authors: Lam Zihim , Anlauf Harald , Nirschl Hermann
Published: December 2019

The cleaning effect of a high‐pressure jet of water on a polymeric microfiltration membrane was investigated at different pressures, durations, and angles. The angle of 70° at a pressure of 130 bar and a cleaning duration of 10 s were found to be promising parameters. Throughput measurements show that this cleaning method can restore about 80 % of the initial throughput of the membrane. Analyses by capillary flow porometer and UV‐vis spectrophotometer imply that an impact on the membrane was detectable after 1800 cleaning cycles at a pressure of 130 bar. Therefore, high‐pressure jet cleaning is a promising method for mechanical cleaning of track‐etched microfiltration membranes.
Location Planning for the Production of CO2‐Based Chemicals Using the Example of Olefin Production
Authors: Thonemann Nils , Stießel Sebastian , Maga Daniel , Dresen Boris , Hiebel Markus , Hunstock Björn , Deerberg Görge , Weidner Eckhard
Published: December 2019

A methodology for identifying suitable locations for the CO2‐based production of olefins in Germany is presented. Based on electricity and CO2 requirements, locations are identified that can provide sufficient CO2 and renewable energy for the conversion of CO2 to olefins. In addition, the use of existing infrastructures is taken into account. The regional, technical renewable energy potential in Germany is sufficient to produce ∼ 800 kt of olefins from CO2‐based methanol per year in one plant. But the currently available CO2 point sources with high CO2 concentrations of around 100 % are not sufficient to meet the CO2 requirement of an 800 kt a−1 methanol‐to‐olefins plant. If existing refineries are preferred due to existing infrastructure services, locations in the north of Cologne, in Lower Saxony, and in Brandenburg are particularly suitable. A full substitution of fossil olefins by CO2‐based olefins is possible in Germany. The challenge is to provide sufficient renewable electricity for the production of H2 with a low CO2 intensity.
Global environmental changes negatively impact temperate seagrass ecosystems
Authors: Perry Diana , Staveley Thomas , Deyanova Diana , Baden Susanne , Dupont Sam , Hernroth Bodil , Wood Hannah , Björk Mats , Gullström Martin
Published: December 2019

The oceans are increasingly affected by multiple aspects of global change, with substantial impacts on ecosystem functioning and food‐web dynamics. While the effects of single factors have been extensively studied, it has become increasingly evident that there is a need to unravel the complexities related to a multiple stressor environment. In a mesocosm experimental study, we exposed a simplified, multi‐trophic seagrass ecosystem (composed of seagrass, two shrimp species, and two intermediate predatory fish species) to three global change factors consisting of simulated storm events (Storms), heat shocks (Heat), and ocean acidification (OA), and the combination of all three factors (All). The most striking result indicated that when all factors were combined, there was a negative influence at all trophic levels, while the treatments with individual factors revealed species‐specific response patterns. It appeared, however, that single factors may drive the multi‐stressor response. All single factors (i.e., Storms, Heat, and OA) had either negative, neutral, or positive effects on fish and shrimp, whereas no effect was recorded for any single stressor on seagrass plants. The findings demonstrate that when several global change factors appear simultaneously, they can have deleterious impacts on seagrass ecosystems, and that the nature of factors and food‐web composition may determine the sensitivity level of the system. In a global change scenario, this may have serious and applicable implications for the future of temperate seagrass ecosystems.
Mixed‐Valent Compounds and their Properties – Recent Developments
Authors: Launay Jean‐Pierre
Published: December 2019

Recent evolutions, essentially in the last 15 years, are reviewed in the field of molecular mixed‐valent compounds and their properties. The considered systems are of the type Mn–BL–Mn where Mn is either a monometallic terminal site (n = 1) or a polymetallic cluster (n = 2, 3), and BL is a bridging ligand. A large variety of bridging ligands is considered: non‐innocent, long conjugated, ambidentate, cross‐conjugated, H‐bonded, switching. The theoretical descriptions are briefly reviewed and sorted according to their degree of complexity/accuracy: simple orbital models, modified Marcus–Hush diagrams, 3D diagrams with two nuclear degrees of freedom, and finally quantitative models (mainly from DFT) with geometrical optimization. With improved DFT functionals, the prediction of the class II or III nature of a symmetrical complex can now be addressed. Finally, applications in NIR electrochromism and molecular electronics are briefly reviewed.
Virgin Grape Seed Oil Alleviates Insulin Resistance and Energy Metabolism Disorder in Mice Fed a High‐Fat Diet
Authors: Li Xiaojing , Shen Yingbin , Zhu Jianhong , Xiao Junyong , Cong Renhuai , Zhang Hui , Wu Gangcheng , Qi Xiguang
Published: December 2019

This study aims to investigate the potential of virgin grape seed oil (VGSO) to improve insulin resistance and energy metabolism disorder in mice fed a high‐fat diet. The results show that respiratory exchange rate and energy consumption in mice can be increased by the administration of VGSO. Insulin resistance is significantly alleviated by VGSO, which can be attributed to its protective effect on hexokinase and α‐glucosidase activities and improvement in leptin resistance. The effect of refined grape seed oil (RGSO), RGSO reinforced with polyphenol, RGSO reinforced with unsaponifiables, and RGSO reinforced with polyphenol and unsaponifiables on oral glucose tolerance, homeostasis model assessment of insulin resistance and quantitative insulin sensitivity check index are determined and compared. The results suggest that polyphenol may be the most critical factor for regulating insulin resistance. Specific linear and polynomial equations are provided to explain the correlation between insulin resistance, energy metabolism, and hyperlipidemia.

Practical Applications: The effects of virgin grape seed oil (VGSO) on insulin resistance and energy metabolism disorder in mice fed a high‐fat diet were investigated. In addition, the key component in VGSO for regulating insulin resistance was preliminarily investigated. Furthermore, the correlations among fasting blood glucose, triglyceride/cholesterol concentration, and respiratory exchange rate/energy consumption/activity level were investigated. This research will provide a theoretical basis for the development of functional edible oil for high blood lipid, cholesterol, and diabetes patients.
Understand impact of antitrust law on agreements to limit enrollment solicitation
Authors: Gelpi Aileen
Published: December 2019

September was a tumultuous month in an already incendiary year for higher education enrollment. On the heels of the Varsity Blues scandal that rocked several colleges and universities around the country in the early part of the year came the news that in response to a U.S. Department of Justice antitrust investigation, the National Association for College Admission Counseling voted to eliminate four provisions of its Code of Ethics and Professional Practices.
First meeting with an administrator left an indelible impression
Authors: Enos Gary
Published: December 2019

A fortunate encounter during her first experience with a university office became a signature moment in Cathy Cole's life and future career.
Distribution, Cytology, Genetic Diversity and Molecular phylogeny of selected species of Zingiberaceae – A Review
Authors: Saha Kishan , Sinha Rabindra Kumar , Sinha Sangram
Published: December 2019

This review has been mainly focussed on distribution, cytology, genetic diversity and molecular phylogeny of selected species of Zingiberaceae belonging to four genera of high economic importance viz., Alpinia, Amomum, Curcuma and Hedychium. Zingiberaceae comprising ca.50 genera and more than 1600 species is mostly distributed in tropical and subtropical areas. Cytological and genetic diversity analyses so far carried out obviously, indicated the genetic relatedness or variation of the species both at intergeneric and intrageneric levels. The DNA barcode and molecular phylogeny also point towards the degree of phylogenetic relationships between the species and also supplement the details of preferred barcode candidates for precise identification of Zingiberean species.
Activation of alpha‐2 adrenergic receptors stimulates GABA release by astrocytes
Authors: Gaidin Sergei G. , Zinchenko Valery P. , Sergeev Alexander I. , Teplov Ilia Y. , Mal'tseva Valentina N. , Kosenkov Artem M.
Published: December 2019

Norepinephrine is one of the key neurotransmitters in the hippocampus, but its role in the functioning of the neuroglial networks remains unclear. Here we show that norepinephrine suppresses NH4Cl‐induced oscillations of the intracellular Ca2+ concentration ([Ca2+]i) in hippocampal neurons. We found that the inhibitory effect of norepinephrine against ammonium‐induced [Ca2+]i oscillations is mediated by activation of alpha‐2 adrenergic receptors. Furthermore, UK 14,304, an agonist of alpha‐2 adrenergic receptors, evokes a biphasic [Ca2+]i elevation in a minor population of astrocytes. This elevation consists of an initial fast, peak‐shaped [Ca2+]i rise, mediated by Giβγ subunit and subsequent PLC‐induced mobilization of Ca2+ from internal stores, and a plateau phase, mediated by a Ca2+ influx from the extracellular medium through store‐operated and TRPC3 channels. We show the correlation between the Ca2+ response in astrocytes and suppression of [Ca2+]i oscillations in neurons. The inhibitory effect of UK 14,304 is abolished in the presence of gallein, an inhibitor of Gβγ‐signaling. In turn, application of the agonist in the presence of the PLC inhibitor decreases the frequency and amplitude of [Ca2+]i oscillations in neurons but does not suppress them. The same effect is observed in the presence of bicuculline, a GABA(A) receptor antagonist. We demonstrate that UK 14,304 application increases the frequency and amplitude of slow outward chloride currents in neurons, indicating the release of GABA by astrocytes. Thus, our findings indicate that the activation of astrocytic alpha‐2 adrenergic receptors stimulates GABA release from astrocytes via Giβγ subunit‐associated signaling pathway, contributing to the suppression of neuronal activity.
Readmission treatment price and product quality in the hospital sector
Authors: Cellini Roberto , Lisi Domenico
Published: December 2019

In this paper, we study the effect of readmission treatment payment in a dynamic framework characterised by competition among hospitals and sluggish beliefs of patients concerning the service quality. We find that the effect of readmission treatment payment depends on the interplay between the effect of quality in lowering readmissions and its effect on future demand. When the readmission occurrence strongly depends on the service quality, the higher the readmission treatment payment for hospitals, the lower the incentive to provide quality. Instead, when readmission depends barely on quality, the readmission payment acts as the treatment price for first admissions, and thus it reinforces the incentive to provide quality. We also show that the detrimental effect of readmission payments on quality are fed by a high degree of demand sluggishness, that is, by situation where current quality has modest effect on future demand changes. Our findings are robust to different equilibrium concepts of the differential game (i.e., open‐loop and state‐feedback). The results suggest that a discounted regulated price for readmission can be an effective (and cost‐free) policy tool to improve health care quality, especially when the market is characterised by sluggish beliefs about quality.
Tumor cell viability in salvage neck dissections: Poor prognosis predicted by high postradiation nodal SUVmax, p16‐negativity, and low nodal shrinkage
Authors: Rüegg Pascal , Morand Grégoire B. , Kudura Ken , Rupp Niels J. , Hüllner Martin W. , Broglie Martina A.
Published: December 2019

Background

After primary chemoradiation in advanced oropharyngeal, laryngeal, and/or hypopharyngeal cancer, nodal disease may require a salvage neck dissection. However, salvage neck dissection is associated with increased morbidity and may only be necessary in case of persistence of viable tumor cells, which can be difficult to confirm and virtually impossible to exclude by fine needle aspiration cytology. We, therefore, aimed to identify predictive factors for the persistence of viable tumor cells in lymph node metastases from head and neck squamous cell cancer after chemoradiation.

Methods

We performed a retrospective review of neck dissection specimens performed after primary (chemo‐)radiation for oropharyngeal, laryngeal, or hypopharyngeal squamous cell carcinoma. All patients were treated at University Hospital Zurich from 2007 to 2016.

Results

A total of 78 patients were included. Thirty‐eight patients (48.7%) had viable tumor cells in their neck dissection sample. High postradiation nodal maximum standardized uptake value (SUVmax), p16 negativity, and low nodal shrinkage were predictors of viable tumor cells in salvage neck dissections (Mann‐Whitney U/chi‐squared test, P < .001, P = .025, and P = .042, respectively). Patients with viable tumor cells showed a significantly worse locoregional recurrence‐free survival, distant metastasis‐free survival, and disease‐specific survival (log‐rank test, P < .001).

Conclusions

Viable tumor cells can be predicted by high residual metabolic activity in the lymph nodes, negative p16 status, and low nodal shrinkage. Viable tumor cells in neck dissection specimens are associated with a poor survival and provide important prognostic information.
Comparing the effectiveness of different EGFR‐TKIs in patients with EGFR mutant non–small‐cell lung cancer: A retrospective cohort study in Taiwan
Authors: Hsieh Yao‐Yu , Fang Wei‐Tse , Lo Yu‐Wen , Chen Yi‐Han , Chien Li‐Nien
Published: December 2019

The study was to compare the effectiveness of different epidermal growth factor receptor—tyrosine kinase inhibitors (EGFR‐TKIs) in patients with advanced non‐small‐cell lung cancer (NSCLC) and received EGFR‐TKIs as first‐line therapy. This retrospective cohort study was conducted using data from real‐world settings. Patients with stage IIIB and IV NSCLC and first received gefitinib, erlotinib, or afatinib between 2011 and 2015 were included. The date of the first claim for EGFR‐TKIs was set as the index date. Study endpoints were all‐cause death and treatment failure that was defined when patients added on or switched to chemotherapy or terminal care. A total of 5,940 patients, including 3,982 (67.0%) receiving gefitinib, 1,207 (20.3%) receiving erlotinib, and 751 (12.7%) receiving afatinib, were eligible for this study. The 1‐year overall survival (OS) rates for gefitinib, erlotinib, and afatinib groups were 74% (95% confidence interval [CI]: 72–75%), 75% (95% CI: 73–77%), and 80% (95% CI: 77–83%), respectively. Compared to gefitinib, afatinib was associated with a lower risk of all‐cause death (adjusted hazard ratio [aHR] = 0.82, 95% CI: 0.72–0.93) but not erlotinib (aHR = 0.95, 95% CI: 0.86–1.05). Similar results were also found regarding the effectiveness of treatment. All the three EGFR‐TKIs showed no differences for both outcomes among patients with an Eastern Cooperative Oncology Group Performance Score of 2. The real‐world data exhibited afatinib was more likely to be used for younger patients in a better condition than other EGFR inhibitors, and observed prolonged OS and treatment effectiveness compared to gefitinib after performing a multivariate Cox regression analysis.
Age‐related changes in lymphocyte subpopulations in healthy Thai children
Authors: Lerkvaleekul Butsabong , Apiwattanakul Nopporn , Klinmalai Chompunuch , Hongeng Suradej , Vilaiyuk Soamarat
Published: December 2019

Background

Ethnicity and environmental factors can influence the percentages of lymphocyte subpopulations. This study aimed to assess the percentages of lymphocyte subpopulations according to age in Thai children.

Methods

This was a cross‐sectional study. The percentages of lymphocyte subpopulations were measured in umbilical cord blood and peripheral blood of healthy Thai children aged 1 month‐15 years. The participants were stratified into five age groups: (a) cord blood; (b) age < 2 years; (c) age 2‐5 years; (d) age 5‐10 years; and (e) age 10‐15 years.

Results

Of 182 total samples, 32, 39, 41, 28, and 42 were from cord blood, children aged <2 years, children aged 2‐5 years, children aged 5‐10 years, and children aged 10‐15 years, respectively. The percentages of most lymphocyte subpopulations including CD8 + T cells, CD19 + cells, γδ T cells, double‐negative T cells, NK cells, and NK T cells increased significantly with age. Only the CD4+ T‐cell percentage decreased in older children. Moderate correlations were observed between age and the percentages of CD4+ T cells, γδ T cells, NK cells, NK T cells, and double‐negative T cells. Weak correlations were observed between age and the percentages of CD8+ T cells and CD19+ cells.

Conclusion

Our study demonstrated age‐related changes in the percentages of lymphocyte subpopulations in Thai children, which differed from those described in other countries. Therefore, the establishment of age‐specific reference values for lymphocyte subsets in each country is recommended.
Nanoniosome‐encapsulated levoflaxicin as an antibacterial agent againstBrucella
Authors: Khan Sana , Akhtar Muhammad Usman , Khan Suhaib , Javed Farakh , Khan Abid Ali
Published: December 2019

A study was conducted to examine the prevalence of brucellosis (in animal farms) in the vicinity of Islamabad and Rawalpindi. A total of 170 milk samples were collected randomly from several farmhouses. The collected milk samples were initially screened by a Brucella selective medium. The bacterial isolates grown on the selective medium were subjected to biochemical identification for further confirmation of Brucella species. Among the tested samples, 28 (16.4%) were found positive for selective medium and 14 (8.2%) were found positive after biochemical confirmation. The antimicrobial susceptibility of several antibiotics performed by the disc‐diffusion method did not yield any significant findings. Encapsulating antimicrobial drugs in unilamellar niosomes is an effective approach to treat the endemic infection. In this study, the antimicrobial activity of niosome‐encapsulated levofloxacin is compared with free drug. The drug‐encapsulating and empty niosomes were synthesized by using two surfactants Tween 80 and Span 40. Niosomal characterization included electron microscopy, dynamic light scattering, and zeta potential. The encapsulation efficiency was found to be 78% and 74% for Span 40 and Tween 80 niosomes, respectively. The antibacterial activity of niosomal levofloxacin was evaluated against the identified Brucella species and the antimicrobial activity of the free drug was increased many folds after encapsulation. In this study, levofloxacin niosomes were successfully synthesized against Brucellosis.
Describing the process of creating an intellectual capital management framework: An interventionist case study
Authors: Costa Ricardo V. , Santos Ana
Published: December 2019

This article aims to address recent calls for a more practice‐based intellectual capital (IC) research by describing the process of creating an IC framework on a real firm. The ultimate goal is to understand how this process can improve IC identification, measurement, and management within the firm, eventually contributing to add an IC perspective to its management strategy. The article takes a Portuguese subsidiary of a multinational firm as a case study. A practice‐based, interventionist approach was adopted. By depicting the process of creating an IC framework, this research shows how IC can be gradually identified, recognized, and embraced by a company. The process also introduces a valuable, forward‐looking perspective of the company business and may induce change through the establishment of new organizational learning routines. The article contributes to IC literature by addressing recent calls for a more practice‐based, “performative” approach to IC research, thus strengthening its emerging “third stage.” It also bridges the gap between theory and practice by discussing how can the IC perspective be integrated in a company's day‐to‐day decisions and strategic challenges. The empirical insights provided can thus be useful to managers and IC researchers alike, particularly those interested in studying IC in practice.
Laryngeal adductor reflex hyperexcitability may predict permanent vocal fold paralysis
Authors: Sinclair Catherine F. , Téllez Maria J. , Sánchez Roldán M. Angeles , Ulkatan Sedat
Published: December 2019

Laryngeal adductor reflex–continuous intraoperative neuromonitoring (LAR‐CIONM) is a novel method of continuous intraoperative neuromonitoring. In contrast to other vagal nerve monitoring techniques, which elicit a laryngeal compound muscle action potential, LAR‐CIONM elicits a laryngeal reflex response (LAR). In 300 nerves at risk monitored with LAR‐CIONM, two patients have had postoperative permanent vocal fold immobility (VFI). Both patients exhibited a significant LAR amplitude increase prior to complete loss of signal. No other patients have exhibited LAR hyperexcitability. If confirmed in a larger sample, this represents the first time that a vagal intraoperative neuromonitoring technique can distinguish transient from permanent VFI, which could improve patient outcomes. Laryngoscope, 2019 Laryngoscope, 130:E625–E627, 2020
Integration of Atomistic Simulation with Experiment Using Time−Temperature Superposition for a Cross‐Linked Epoxy Network
Authors: Khare Ketan S. , Phelan Frederick R.
Published: December 2019

For glass‐forming polymers, direct quantitative comparison of atomistically detailed molecular dynamics simulations with thermomechanical experiments is hindered by the vast mismatch between the accessible timescales. Recently, the authors demonstrated the successful application of the time–temperature superposition (TTS) principle to perform such a comparison for the volumetric properties of an epoxy network. Here, the local translational dynamics of the same network is computationally followed‐up and studied. The mean squared displacement (MSD) and time‐scaling exponent trends of select atoms of the network are calculated over a temperature range that spans the glass transition. Using TTS, both trends collapse onto master curves that relate the reduced MSD and time‐scaling exponent to the reduced time at a reference temperature. Because the reduced time of these computational master curves extends to 109 s, they can be directly compared with experimental creep compliance for the same material from the literature. A quantitative comparison of the three master curves is performed to provide an integrated view that relates atomic‐level dynamics with macroscopic thermomechanics. The time‐shift factors needed for TTS in simulation show excellent agreement with experiment in the literature, further establishing the veracity of the approach.
Radionuclide spatial distribution and dose deposition for in vitro assessments of 212Pb‐αVCAM‐1 targeted alpha therapy
Authors: Frelin‐Labalme Anne‐Marie , Roger Thomas , Falzone Nadia , Quan Lee Boon , Sibson Nicola R. , Vallis Katherine A. , Bernaudin Myriam , Valable Samuel , Corroyer‐Dulmont Aurélien
Published: December 2019

Purpose

Targeted alpha therapy (TAT) takes advantage of the short‐range and high‐linear energy transfer of α‐particles and is increasingly used, especially for the treatment of metastatic lesions. Nevertheless, dosimetry of α‐emitters is challenging for the very same reasons, even for in vitro experiments. Assumptions, such as the uniformity of the distribution of radionuclides in the culture medium, are commonly made, which could have a profound impact on dose calculations. In this study we measured the spatial distribution of α‐emitting 212Pb coupled to an anti‐VCAM‐1 antibody (212Pb‐αVCAM‐1) and its evolution over time in the context of in vitro irradiations.

Methods

Two experimental setups were implemented without cells to measure α‐particle count rates and energy spectra in culture medium containing 15 kBq of 212Pb‐α‐VCAM‐1. Silicon detectors were placed above and below cell culture dishes for 20 h. One of the dishes had a 2.5‐µm‐thick mylar‐base allowing easy detection of the α‐particles. Monte Carlo simulations were performed to analyze experimental spectra. Experimental setups were modeled and α‐energy spectra were simulated in the silicon detectors for different decay positions in the culture medium. Simulated spectra were then used to deconvolute experimental spectra to determine the spatial distribution of 212Pb‐αVCAM‐1 in the medium. This distribution was finally used to calculate the dose deposition in cell culture experiments.

Results

Experimental count rates and energy spectra showed differences in measurements taken at the top and the bottom of dishes and temporal variations that did not follow 212Pb decay. The radionuclide spatial distribution was shown to be composed of a uniform distribution and concentration gradients at the top and the bottom, which were subjected to temporal variations that may be explained by gravity and electrostatic attraction. The absorbed dose in cells calculated from this distribution was compared with the dose expected for a uniform and static distribution and found to be 1.75 times higher, which is highly significant to interpret biological observations.

Conclusions

This study demonstrated that accurate dosimetry of α‐emitters requires the experimental determination of radionuclide spatial and temporal distribution and highlighted that in vitro assessment of dose for TAT cannot only rely on a uniform distribution of activity in the culture medium. The reliability and reproducibility of future experiments should benefit from specifically developed dosimetry tools and methods.
A 3D deep convolutional neural network approach for the automated measurement of cerebellum tracer uptake in FDG PET‐CT scans
Authors: Xiong Xiaofan , Linhardt Timothy J. , Liu Weiren , Smith Brian J. , Sun Wenqing , Bauer Christian , Sunderland John J. , Graham Michael M. , Buatti John M. , Beichel Reinhard R.
Published: December 2019

Purpose

The purpose of this work was to assess the potential of deep convolutional neural networks in automated measurement of cerebellum tracer uptake in F‐18 fluorodeoxyglucose (FDG) positron emission tomography (PET) scans.

Methods

Three different three‐dimensional (3D) convolutional neural network architectures (U‐Net, V‐Net, and modified U‐Net) were implemented and compared regarding their performance in 3D cerebellum segmentation in FDG PET scans. For network training and testing, 134 PET scans with corresponding manual volumetric segmentations were utilized. For segmentation performance assessment, a fivefold cross‐validation was used, and the Dice coefficient as well as signed and unsigned distance errors were calculated. In addition, standardized uptake value (SUV) uptake measurement performance was assessed by means of a statistical comparison to an independent reference standard. Furthermore, a comparison to a previously reported active‐shape‐model‐based approach was performed.

Results

Out of the three convolutional neural networks investigated, the modified U‐Net showed significantly better segmentation performance. It achieved a Dice coefficient of 0.911 ± 0.026, a signed distance error of 0.220 ± 0.103 mm, and an unsigned distance error of 1.048 ± 0.340 mm. When compared to the independent reference standard, SUV uptake measurements produced with the modified U‐Net showed no significant error in slope and intercept. The estimated reduction in total SUV measurement error was 95.1%.

Conclusions

The presented work demonstrates the potential of deep convolutional neural networks in automated SUV measurement of reference regions. While it focuses on the cerebellum, utilized methods can be generalized to other reference regions like the liver or aortic arch. Future work will focus on combining lesion and reference region analysis into one approach.
Characterization of and tissue density in the human lung: Application to neonatal imaging in the intensive care unit
Authors: Hahn Andrew D. , Malkus Annelise , Kammerman Jeffery , Higano Nara , Walkup Laura , Woods Jason , Fain Sean B.
Published: December 2019

Purpose

Novel demonstration of and tissue density estimation in infant lungs using 3D ultrashort echo time MRI. Differences between adult and neonates with no clinical indication of lung pathology is explored, as well as relationships between parameter estimates and gravitationally dependent position and lung inflation state. This provides a tool for probing physiologic processes that may be relevant to pulmonary disease and progression in newborns.

Methods

and tissue density were estimated in a phantom consisting of standards allowing for ground truth comparisons and in human subjects (N = 5 infants, N = 4 adults, no clinical indication of lung dysfunction) using a 3D radial multiecho ultrashort echo time MRI sequence. Whole lung averages were compared between infants and adults. Dependence of the metrics on anterior‐posterior position as well as between end‐tidal inspiration and expiration were explored, in addition to the general relationship between and tissue density.

Results

Estimates in the phantom did not differ significantly from ground truth. Neonates had significantly lower mean (P = .006) and higher mean tissue density (P = 1.5e‐5) than adults. Tissue density and were both significantly dependent on anterior‐posterior position and lung inflation state (P < .005). An overall inverse relationship was found between and tissue density, which was similar in both neonates and adults.

Conclusion

Estimation of tissue density and in free breathing, nonsedated, neonatal patients is feasible using multiecho ultrashort echo time MRI. was no different between infants and adults when matched for tissue density, although density of lung parenchyma was, on average, lower in adults than neonates.
Comparative‐fill urodynamics in individuals with and without detrusor overactivity supports a conceptual model for dynamic elasticity regulation
Authors: Cullingsworth Zachary E. , Klausner Adam P. , Li Rui , Nagle Anna S. , Carroll Ashley W. , Roseman John T. , Speich John E.
Published: December 2019

Aims

Dynamic elasticity was previously identified in individuals with overactive bladder (OAB) using comparative‐fill urodynamics (UD) and is a biomechanical mechanism for acutely regulating detrusor wall tension. On the basis of this data, a conceptual model of dynamic elasticity regulation mediated through a balance of passive mechanisms and active contractions was constructed. The present study tested this model by determining whether individuals with detrusor overactivity (DO) exhibit less dynamic elasticity than individuals without DO.

Methods

Individuals with and without urgency based on International Consultation on Incontinence Questionnaire‐OAB surveys were prospectively enrolled in a comparative‐fill UD study. An initial fill defined the presence or absence of DO and determined cystometric capacity. Three additional fills were employed with either passive emptying via a catheter or active voiding. To identify dynamic elasticity, average filling pressures (Pves) were compared for fill 1 (before strain softening), fill 2 (after strain softening), and fill 3 (after active void). A dynamic elasticity index was defined.

Results

From 28 participants, those without DO showed decreased Pves during filling after strain softening and restored Pves during filling following active voiding, revealing dynamic elasticity. Participants with DO did not show dynamic elasticity. A dynamic elasticity index less than 1.0 cmH2O/40% capacity was identified in 2 out of 13 participants without DO and 9 out of 15 with DO, revealing a significant association between DO and reduced/absent dynamic elasticity (P = .024).

Conclusions

This study supports a conceptual model for dynamic elasticity, a mechanism to acutely regulate detrusor wall tension through a balance of competing active contractile and passive strain mechanisms. Improved understanding of this mechanistic model may help us to identify novel treatment strategies for OAB.
Optimizing expiratory flows during mechanical cough in a pediatric neuromuscular lung model
Authors: Hov Brit , Andersen Tiina , Toussaint Michel , Fondenes Ove , Carlsen Karin C. L. , Hovland Vegard
Published: December 2019

Mechanical insufflation‐exsufflation (MI‐E) is recommended for subjects of all ages with neuromuscular disorders (NMDs) and weak cough. There is a lack of knowledge on the optimal treatment settings for young children. This study aims to determine the MI‐E settings providing high expiratory airflow while using safe inspiratory volumes, and to identify possible limits where the benefit of incrementing the MI‐E settings to achieve a higher expiratory airflow, decreased. Using an MI‐E device and a lung model imitating a 1‐year‐old child with NMD, we explored the impact of 120 combinations of MI‐E pressure and time settings on maximal expiratory airflow and inspiratory volume. High expiratory airflows were achieved with several pressure and time combinations where the exsufflation pressure, followed by insufflation pressure and time, had the greatest impact. The benefit of incrementing the settings to increase the expiratory airflow leveled off for the insufflation pressure and time, but not for the exsufflation pressure. Given exsufflation pressure of −40 or −50 cmH2O and insufflation time longer than 1 second, a plateau in the expiratory airflow curve was present at insufflation pressures from 25 cmH2O, whereas a plateau in the inspired volume curve occurred at insufflation pressures from 35 cmH2O. The present neuromuscular pediatric lung model study showed that expiratory pressure impacts expiratory airflow more than inspiratory pressure and time. An inspiratory and expiratory pressure set between 20 to 30 and −40 cmH2O, respectively, and an inspiratory time longer than 1 second may be considered as a basis when titrating MI‐E settings in young children with NMD. The findings must be confirmed in clinical trials.
A python script to design site‐directed mutagenesis primers
Authors: Bi Chuyun , Huang Xiaofang , Tang Dan , Shi Yuanyuan , Zhou Lixiang , Hu Yunzhuo , Chen Xuanyang , Qi Shiqian , Lin Shiqiang
Published: December 2019

Primer design is essential to conduct whole plasmid site‐directed mutagenesis for protein study. Traditionally, primers of mutagenesis are designed manually that is time‐consuming and fallible. Here, we present a Python script for searching primers by presetting parameters of nucleotide composition and percentage of guanine‐cytosine (GC content). The running results showed that the script is able to search primers with mutations of target residue automatically. This script may facilitate primer design for whole plasmid site‐directed mutagenesis and aid protein mutant construction.
Trade‐off between defense priming by herbivore‐induced plant volatiles and constitutive defense in tomato
Authors: Zhang Peng‐Jun , Zhao Chan , Ye Zi‐Hong , Yu Xiao‐Ping
Published: December 2019

BACKGROUND

Herbivore‐induced plant volatiles (HIPVs) can prime plant defenses and enhance herbivore resistance in neighboring plants. Although a trade‐off between constitutive defense and HIPV emission has been documented in many plant species, little is known about the effect of HIPV variation on defense priming, and whether there is a trade‐off between defense priming and constitutive defense in neighboring plants.

RESULTS

Using three tomato genotypes, including two wild types [Moneymaker (MM) and Castlemart (CM)] and one jasmonic acid (JA) overexpression 35S::prosys genotype, we investigated the effects of exposure to volatiles from plants infested by beet armyworm (Spodoptera exigua) caterpillars on the defenses and resistance of conspecific neighboring plants. We also analyzed the HIPV emissions from the three genotypes and their constitutive defense and resistance. Exposure to volatiles from S. exigua‐infested MM plants primed an array of defensive responses (including the accumulation of JA and PI‐II protein and the expression of the defense genes PI‐I and PI‐II), and enhanced plant resistance against the caterpillars. In contrast, exposure to volatiles from S. exigua‐infested CM or 35S::prosys did not result in defense priming or an increase in plant resistance. Analyses of HIPVs and gene expression indicated that defense priming in MM was due to enhanced emission of β‐ocimene and linalool. We further demonstrated that levels of constitutive defense and resistance are low in MM and high in CM and 35S::prosys, suggesting a negative correlation between defense priming and constitutive defense.

CONCLUSION

Our findings suggest that there is a trade‐off between defense priming by HIPVs and constitutive defense in tomato. This suggests that defense priming should be used with caution in agriculture. © 2020 Society of Chemical Industry
Spatial structures of student mobility: Social, economic and ethnic ‘geometries of power'
Authors: Donnelly Michael , Gamsu Sol
Published: December 2019

There now exists a growing literature on educational mobilities, and this paper contributes to understanding the way contemporary youth imagine the geography of the United Kingdom and how this translates to their mobility intentions. Using Giddens and Massey and drawing on a unique multi‐sited qualitative dataset, we examine how these flows can be understood as embedded within narratives of the self that are situated within a particular spatial structuring of social, economic, and ethnic difference. The multi‐sited dataset provides a unique opportunity to see the simultaneity of these social relations across space, mutually shaping, and reshaping each other over time. We illustrate how embedded within imagined mobility narratives are deeply unequal structures of economic power, (re)producing oppressed and dominant positions across social and geographic space. Geometries of race and ethnicity are also shown to structure the ways in which different ethnic groups look upon the geography of their university choices. The patterning of these imagined spatial flows around the United Kingdom at the point of university entry can be interpreted as one further manifestation of deep‐seated geometries of power that pervade social life.
Effectiveness of mepolizumab for eosinophilic pneumonia following bronchial thermoplasty
Authors: Otoshi Ryota , Baba Tomohisa , Komatsu Shigeru , Asaoka Masato , Hagiwara Eri , Ogura Takashi
Published: December 2019

A 57‐year‐old woman with poorly controlled diabetes was admitted to our hospital for additional treatment of severe asthma. Although bronchial thermoplasty was performed in the both upper lobes, cough and dyspnoea gradually appeared 2 weeks later. High‐resolution computed tomography revealed thickness of intralobular septa and a diffuse ground‐glass attenuation in the lung fields. Laboratory examination revealed elevated levels of serum eosinophils and total immunoglobulin E. Bronchoalveolar lavage fluid showed a remarkable increase of eosinophils as high as 48.5%, then eosinophilic pneumonia was diagnosed. Although treatment with steroids resulted in an improvement of eosinophilic pneumonia, the treatment was discontinued after 4 days because it worsened her diabetic condition. Since eosinophilic pneumonia recurred after discontinuing steroid, mepolizumab was administered, which subsequently improved her disease condition. Clinicians should be aware that bronchial thermoplasty can lead to eosinophilic pneumonia and mepolizumab might be an effective treatment in this setting.