bluuebunny/crossref_metadata_2025 huggingface dataset:
A General Proline‐Catalyzed Synthesis of 4,5‐Disubstituted N‐Sulfonyl‐1,2,3‐Triazoles from 1,3‐Dicarbonyl Compounds and Sulfonyl Azide
Authors: Rajasekar Shanmugam , Anbarasan Pazhamalai
Published: August 2019

An efficient proline‐catalyzed synthesis of 4,5‐disubstituted‐N‐sulfonyl‐1,2,3‐triazoles has been accomplished from 1,3‐dicarbonyl compounds and sulfonyl azides. The developed reaction is suitable for various symmetrical and unsymmetrical 1,3‐dicarbonyl compounds, tolerates various functional groups and affords 4,5‐disubstituted‐N‐sulfonyl‐1,2,3‐triazoles in good yield with excellent regioselectivity. Rhodium‐catalyzed denitrogenative functionalization of 4,5‐disubstituted‐N‐sulfonyl‐1,2,3‐triazoles further demonstrates their utility in organic synthesis.
Medication errors in a cohort of pediatric patients with acute lymphoblastic leukemia on remission induction therapy in a tertiary care hospital in Mexico
Authors: Vázquez‐Cornejo Edmundo , Morales‐Ríos Olga , Juárez‐Villegas Luis E. , Islas Ortega Erika J. , Vázquez‐Estupiñán Felipe , Garduño‐Espinosa Juan
Published: August 2019

Introduction

Medication errors (MEs) are the main type of preventable adverse events in medical care, as well as safety indicators in the medication processes. Advances in the quality of care in pediatric acute lymphoblastic leukemia (ALL) have enabled to improve clinical outcomes. However, ME epidemiology in pediatric oncology is still incipient in developing countries. In view of this, the objectives of this study were to estimate the incidence of MEs, determine their types and consequences, as well as their preventability in the induction treatment of children with ALL at Hospital Infantil de Mexico Federico Gómez.

Methods

We reviewed the remission‐induction chemotherapy records of children with ALL between January 2015 and December 2017. A two‐phase review was carried out for ME identification and verification. The consequences of errors were determined by agreement between reviewers.

Results

We reviewed 1762 chemotherapy orders involving 181 children. MEs were observed in 16.9% of orders and in 57.5% of patients. Prescription errors were the most common (93.3%), with wrong dose errors (90.2%) being predominant. Only 3.7% of wrong dose errors were intercepted, while 12.2% of the children experienced adverse drug events (ADEs) preceded by some wrong dose error.

Conclusions

MEs were common, since they occurred in 57.5% of children with ALL on induction treatment and involved 16.5% of chemotherapy orders. Only 3.7% of MEs were intercepted, while 12.2% of children had ADEs related to overdose. Measures are required to prevent calculation error in prescriptions, as well as training of the nursing staff to intercept MEs.
Pharmacology of mitochondrial permeability transition pore inhibitors
Authors: Naryzhnaya Natalia V. , Maslov Leonid N. , Oeltgen Peter R.
Published: August 2019

It is now firmly established that an important event in the formation of reperfusion injury of the heart is the opening of mitochondrial permeability transition pores (mPTPs), which changes the permeability of the mitochondria. mPTP opening results in the death of cardiomyocytes through activation of apoptosis and necroptosis. Experimental studies have shown that pharmacological inhibition of mPTP opening promotes the reduction in the infarct size and the suppression of apoptosis. Indeed, studies have shown the efficacy of mPTP inhibitors in animal models of myocardial reperfusion and isolated human myocardial trabeculae. However, clinical trials of cyclosporin A and TRO40303 have not provided a clear answer to the question of the effectiveness of mPTP inhibitors in patients with acute myocardial infarction. This article presents an analysis of possible approaches for the pharmacological regulation of mPTP during reperfusion injury of the heart.
Targeting age‐related differences in brain and cognition with multimodal imaging and connectome topography profiling
Authors: Lowe Alexander J. , Paquola Casey , Vos de Wael Reinder , Girn Manesh , Lariviere Sara , Tavakol Shahin , Caldairou Benoit , Royer Jessica , Schrader Dewi V. , Bernasconi Andrea , Bernasconi Neda , Spreng R. Nathan , Bernhardt Boris C.
Published: August 2019

Aging is characterized by accumulation of structural and metabolic changes in the brain. Recent studies suggest transmodal brain networks are especially sensitive to aging, which, we hypothesize, may be due to their apical position in the cortical hierarchy. Studying an open‐access healthy cohort (n= 102, age range = 30–89 years) with MRI and Aβ PET data, we estimated age‐related cortical thinning, hippocampal atrophy and Aβ deposition. In addition to carrying out surface‐based morphological and metabolic mapping experiments, we stratified effects along neocortical and hippocampal resting‐state functional connectome gradients derived from independent datasets. The cortical gradient depicts an axis of functional differentiation from sensory‐motor regions to transmodal regions, whereas the hippocampal gradient recapitulates its long‐axis. While age‐related thinning and increased Aβ deposition occurred across the entire cortical topography, increased Aβ deposition was especially pronounced toward higher‐order transmodal regions. Age‐related atrophy was greater toward the posterior end of the hippocampal long‐axis. No significant effect of age on Aβ deposition in the hippocampus was observed. Imaging markers correlated with behavioral measures of fluid intelligence and episodic memory in a topography‐specific manner, confirmed using both univariate as well as multivariate analyses. Our results strengthen existing evidence of structural and metabolic change in the aging brain and support the use of connectivity gradients as a compact framework to analyze and conceptualize brain‐based biomarkers of aging.
CLASTR: The Cellosaurus STR similarity search tool ‐ A precious help for cell line authentication
Authors: Robin Thibault , Capes‐Davis Amanda , Bairoch Amos
Published: August 2019

Despite an increased awareness of the problematic of cell line cross‐contamination and misidentification, it remains nowadays a major source of erroneous experimental results in biomedical research. To prevent it, researchers are expected to frequently test the authenticity of the cell lines they are working on. STR profiling was selected as the international reference method to perform cell line authentication. While the experimental protocols and manipulations for generating a STR profile are well described, the available tools and workflows to analyze such data are lacking. The Cellosaurus knowledge resource aimed to improve the situation by compiling all the publicly available STR profiles from the literature and other databases. As a result, it grew to become the largest database in terms of human STR profiles, with 6,474 distinct cell lines having an associated STR profile (release July 31, 2019). Here we present CLASTR, the Cellosaurus STR similarity search tool enabling users to compare one or more STR profiles with those available in the Cellosaurus cell line knowledge resource. It aims to help researchers in the process of cell line authentication by providing numerous functionalities. The tool is publicly accessible on the SIB ExPASy server (https://web.expasy.org/cellosaurus-str-search) and its source code is available on GitHub under the GPL‐3.0 license.
Quantitation of estradiol by competitive light‐initiated chemiluminescent assay using estriol as competitive antigen
Authors: Li Jiuzhi , Li Liuxu , Bian Ying , Yu Yang , Qiang Zhonghua , Zhang Yuexiang , Li Huiqiang
Published: August 2019

Background

Light‐initiated chemiluminescent assays (LICA) are homogeneous assays that are sensitive, specific, and free of separation and washing steps and have high throughput and high precision.

Methods

In this research, we developed a competitive method by LICA to achieve accurate quantification of estradiol (E2) in human serum. E2 competed with estriol (E3) for binding to anti‐human E2 antibodies. E3 was linked to biotin via bovine serum albumin as a linker. As this assay used competition between the labeled tracer and the analyte, an increase in E2 concentration will cause a signal decrease.

Results

The expected detection range of E2 was 20‐5000 pg/mL. The analytical and functional sensitivities were 7.16 and 13.7 pg/mL, respectively. The intra‐ and inter‐assay coefficients of variation were both below 15%, and the recovery rate ranged from 97.5% to 106.8%. The interference rates ranged from −3.6% to 5.4% and met detection requirements for E2 in hyperbilirubinemia, hemolysis, and lipemia in clinical samples. In addition, the cross‐reactivity rates between E2 and structural analogs and some reproductive hormones varied from 1.9% to 10.6% which showed that LICA is highly specific for E2. Moreover, our results showed high accordance with the IMMULITE 2000 (y = 0.6695x + 47.92, r2 = .843) and VIDAS systems (y = 1.099x − 821.5, r2 = .9392).

Conclusion

Our data show that the LICA, which is easy to automate, is a promising technique for quantification of E2 in human serum and could be used for clinical detection.
Effect of methyl methacrylate on the properties of transparent flame retardant unsaturated phosphate ester copolymer
Authors: Liu Hongli , Lin Nan , Huang Jie , Chang Guanjun , Wu Yilong , Li Xiuyun
Published: August 2019

The effect of methyl methacrylate (MMA) on the properties of transparent flame retardant unsaturated phosphate ester copolymer (poly[UPE‐co‐MMA]) prepared by bulk polymerization technique was investigated. Fourier transform infrared spectra, gel fraction (G) test, and dynamic mechanical analysis revealed the structure and crosslinking density of poly(UPE‐co‐MMA) copolymers. The thermal degradation and flame retardancy of copolymers were indicated by thermogravimetric analysis, limiting oxygen index (LOI), and microscale combustion calorimeter (MCC) test. Besides, the mechanical properties and transparency were tested with testing machines and solid ultraviolet absorption spectra. As the MMA content increased to 50%, the copolymer contained 50 wt% MMA showed the maximal G (88.93%) and transmittance was up to 91.72%. From the poly(UPE‐co‐MMA) copolymers, the tensile strength increased from 14.62 to 26.95 MPa, assigned to the increase of crosslinking density of copolymers. The char yield of poly(UPE‐co‐MMA) was up to 21.18 wt%, which was a result of decomposition of phosphate groups, producing a phosphorus‐rich layer that increased the thermal stability of the residues. LOI and MCC results confirm that the introduction of MMA can retain the flame retardancy of copolymer remarkably. POLYM. ENG. SCI., 59:2103–2109, 2019. © 2019 Society of Plastics Engineers
Spatial interpolation of two‐metre temperature over Norway based on the combination of numerical weather prediction ensembles and in situ observations
Authors: Lussana C. , Seierstad I. A. , Nipen T. N. , Cantarello L.
Published: August 2019

Accurate hourly two‐metre temperature gridded fields available in near real‐time are valuable products for numerous applications, such as civil protection and energy production planning. An analysis ensemble of temperature is obtained from the combination of a numerical weather prediction ensemble (background) and in situ observations. At the core of the flow‐dependent spatial interpolation method lies the analysis step of the local ensemble transform Kalman filter (LETKF). A scaling factor and a localization procedure have been added to correct for deficiencies of the background. Each observation is characterized by its own representativeness, which is allowed to vary in time. We call the method described here an Ensemble‐based Statistical Interpolation (EnSI) scheme for spatial analysis and it has been integrated into the operational post‐processing systems in use at the Norwegian Meteorological Institute (MET Norway). The benefits of the analysis are assessed over a 1‐year time period (July 2017–July 2018) and a case‐study is presented for a challenging situation over complex terrain. EnSI gives more accurate results than an interpolation method based exclusively on observations. The analysis ensemble provides a more informative representation of the uncertainty than a spatial analysis based on a single‐field background. EnSI reduces the number of large prediction errors in the analysis compared to the background by almost 50%, reduces the ensemble spread and increases its accuracy.
An Innovative Multidisciplinary Healthcare Model in Student Mental Health: Experience in Hong Kong
Authors: Lo Sze Mon , Wong Ho Cheong , Lam Ching Yee , Shek Daniel T. L.
Published: August 2019

Although studies showed that common mental disorders are prevalent amongst in the university students, non-stigmatizing mental health service tailor-made to university students is not often available within the health service setting in different parts of the world. In this paper, we review the current barriers for college students seeking help from student mental health service and discuss the pros and cons of different service models. It is argued that the traditional mode of addressing student mental health issues is grossly inadequate. Based on the review, the paper also shares the pilot experiences of the Mental Wellness Clinic operated under the University Health Service of one university in Hong Kong. We also explored the strengths and challenges of this multidisciplinary coordinated healthcare model in the promotion of well-being of university students.
Lighter, stiffer, faster – The case for carbon fiber composites in machinery
Authors: Carter Humphrey
Published: August 2019

The market for carbon fiber-reinforced plastics (CFRPs) has exploded since the turn of this century. For example, in the commercial aerospace sector, the substitution of aluminum with these strong, stiff and lightweight composites has become the norm. However, in the machine building industry, the adoption has been far slower. We are surely about to see a step change in this, as Humphrey Carter, Head of Business Development at CompoTech explains.
Intramolecular benzoallene–alkyne cycloaddition initiated by site-selective SN2′ reaction of epoxytetracene en route to π-extended pyracylene
Authors: Kitamura Kei , Asahina Kenta , Adachi Kazuhiko , Hamura Toshiyuki
Published: August 2019

A new synthetic route to π-extended pyracylene was developed by hydrogen halide promoted cascade reaction of epoxytetracene.
Chemical characterisation, antibacterial activity, and (nano)silver transformation of commercial personal care products exposed to household greywater
Authors: Khaksar Maryam , Vasileiadis Sotirios , Sekine Ryo , Brunetti Gianluca , Scheckel Kirk G. , Vasilev Krasimir , Lombi Enzo , Donner Erica
Published: August 2019

The objective of this study was to test the original speciation of silver (Ag) in eight different commercially available personal care products and investigate the chemical transformation of Ag during exposure to two types of synthetic greywater.
Fabrication and nonlinear optical characterization of fluorinated zinc phthalocyanine covalently modified black phosphorus/PMMA films using the nanosecond Z-scan technique
Authors: Liu Zhiwei , Gan Fan , Dong Ningning , Zhang Bin , Wang Jun , Chen Yu
Published: August 2019

Compared to the BP/PMMA and F12NH2PcZn/PMMA films, both the non-annealed and annealed F12PcZn–BP/PMMA films show more superior nonlinear optical (including optical limiting) properties.
Analysis of phased array antenna system via spherical harmonics decomposition
Authors: Famoriji Oluwole John , Akingbade Kayode , Ogunti Erastus , Apena Waliu , Fadamiro Akinwale , Lin Fujiang
Published: August 2019

Spherical phased‐array antenna has hemispherical scan coverage for transmission of satellite imagery data at high bit rates to the ground station. Different conditions have been assigned based on their effects on the overall performance of the communication link. Reliability analysis consequently becomes an important requirement of any system onboard a satellite. Although the phased array and some connected algorithms have been presented in the literatures; however, there is no extensive systematic and theoretical performance evaluation framework formulated. In this work, the authors present new method that efficiently and effectively analyses the statistical performance of phased‐array antenna systems using spherical harmonics expansion approach. Specifically, the errors caused by limited antenna element number, measurement noise of antenna, imprecision in phased‐array antenna elements positioning, and spatial aliasing are systematically and theoretically benchmarked via simulations. Spatial sampling mechanisms for the positioning of array antenna elements on a sphere are presented and evaluated. This study proposed design guide and analysis for spherical phased‐array antenna systems, and antenna arrays that do not employ spherical harmonics explicitly.
Fast algorithm for 3D wideband LFM source localisation based on time delay under a uniform circular array
Authors: Chen Xin , Liu Zhen , Liu Tianpeng , Peng Bo , Wei Xizhang , Li Xiang
Published: August 2019

Traditional localisation technologies for wideband linear frequency modulation (LFM) source are always confined to the far‐field situation and suffer from high computational cost for dealing with multiple sub‐narrowband components. In this study, by performing temporal delay‐and‐correlation to wideband LFM signals, a fast and closed‐form algorithm based on phase differences is proposed for three‐dimensional (3D) source localisation (azimuth angle, elevation angle, and range) under a uniform circular array. First, the cross‐correlation of the array outputs with their temporally delayed version is calculated to develop a new single‐frequency signal model. Then, the phase differences of adjacent sensors’ transformed outputs are exploited to construct indefinite equations. After that, the least‐square method is employed to estimate the source's 3D parameters simultaneously. Moreover, theoretical analysis and numerical examples show the aperture restriction in avoiding ambiguity can be relaxed under the new signal model. Finally, simulations demonstrate the effectiveness and advantages of the proposed algorithm.
Influence of surface roughness on the adhesion hysteresis of nano thin film
Authors: Lin Qijing , Zhang Fuzheng , Han Feng , Zhao Man , Jiang Zhuangde
Published: August 2019

The influence of surface roughness on adhesion hysteresis of Cu thin films with different thickness was studied. The Cu thin films were fabricated using dc magnetron sputtering technology and their surface adhesion forces were measured using force‐displacement curves of atomic force microscopy. The experiment results show that the unload curve exhibits obvious adhesion hysteresis and that the roughness and adhesion force have opposite change tendency. The theoretical analysis on the influence of thin film roughness to the adhesion hysteresis was carried out using the Johnson–Kendall–Roberts model. The results show that the load curve and unload curve constitute a closed curve and that the smoother the surface, the more obvious adhesion hysteresis, i.e. the rougher the surface, the less obvious adhesion hysteresis. The theoretical analysis results are in good agreement with the experimental results.
Elections and Capital Flight: A Response to Goldsmith
Authors: Frantz Erica
Published: August 2019

In a recent study, I show that capital flight follows an electoral cycle, such that it was higher in competitive election years than otherwise. This effect decreased as natural resource wealth increased. Goldsmith (forthcoming) reexamines the impact of competitive elections on capital flight using new data sources for both and finds little evidence of a relationship. In this response, I show that the primary reason that Goldsmith unearths mixed evidence is because his model specifications exclude an interaction term between elections and resource wealth that I use in my original study. Once this interaction term is included, the overall evidence suggests that elections—particularly those that are democratic—increase capital flight.
Merger signatures in low excitation radio galaxies
Authors: Garofalo David
Published: August 2019

While no consensus governs our understanding of the origin of low-redshift radio galaxies, the possibility that mergers may trigger accretion from hot cluster halo gas has spurred a recent search for such signatures. Evidence for mergers is at best tenuous, however, and even when found, generates more questions than answers. With scant evidence for minor mergers, some connection to major mergers is found in isolated environments but not where one would expect, i.e. in clusters. We provide an explanation for these recent results by Gordon et al. on the relevance of major mergers in low excitation radio galaxies (LERGs) at low redshift. While LERGs are not the direct result of a merger, we describe how they form in clusters in only a few million years while that time-scale is an order of magnitude longer in field environments. As a result of these different time-scales, the average lifetime of a cluster LERG is estimated at an order of magnitude greater value than for field LERGs. Observing an LERG in the cluster environment, therefore, will tend to occur when greater time has passed since the major merger event that produced its high excitation radio galaxy ancestor, such that fewer signatures of that event remain visible. We provide simple estimates for the fraction of LERGs as a function of environment that are directly related to these time-scales, obtaining a probability of about 7 per cent that field LERGs will show merger signatures and 3 per cent for clusters, showing that theory and observation match if major merger signatures remain visible for a few hundred million years.
Sparse Bayesian mass mapping with uncertainties: peak statistics and feature locations
Authors: Price M A , McEwen J D , Cai X , Kitching (for the LSST Dark Energy Science Collaboration) T D
Published: August 2019

Weak lensing convergence maps – upon which higher order statistics can be calculated – can be recovered from observations of the shear field by solving the lensing inverse problem. For typical surveys this inverse problem is ill-posed (often seriously) leading to substantial uncertainty on the recovered convergence maps. In this paper we propose novel methods for quantifying the Bayesian uncertainty in the location of recovered features and the uncertainty in the cumulative peak statistic – the peak count as a function of signal-to-noise ratio (SNR). We adopt the sparse hierarchical Bayesian mass-mapping framework developed in previous work, which provides robust reconstructions and principled statistical interpretation of reconstructed convergence maps without the need to assume or impose Gaussianity. We demonstrate our uncertainty quantification techniques on both Bolshoi N-body (cluster scale) and Buzzard V-1.6 (large-scale structure) N-body simulations. For the first time, this methodology allows one to recover approximate Bayesian upper and lower limits on the cumulative peak statistic at well-defined confidence levels.
The Relationship Between Tumor-Stroma Ratio, the Immune Microenvironment, and Survival in Patients With Spinal Chordoma
Authors: Zou Ming-Xiang , Zheng Bo-Wen , Liu Fu-Sheng , Wang Xiao-Bin , Hu Jia-Rui , Huang Wei , Dai Zhe-Hao , Zhang Qian-Shi , Liu Fu-Bing , Zhong Hua , Jiang Yi , She Xiao-Ling , Li Xiao-Bing , Lv Guo-Hua , Li Jing
Published: August 2019

BACKGROUND

Currently, little is known about the clinical relevance of tumor-stroma ratio (TSR) in chordoma and data discussing the relationship between TSR and immune status of chordoma are lacking.

OBJECTIVE

To characterize TSR distribution in spinal chordoma, and investigated its correlation with clinicopathologic or immunological features of patients and outcome.

METHODS

TSR was assessed visually on hematoxylin and eosin-stained sections from 54 tumor specimens by 2 independent pathologists. Multiplex immunofluorescence was used to quantify the expression levels of microvessel density, Ki-67, Brachyury, and tumor as well as stromal PD-L1. Tumor immunity status including the Immunoscore and densities of tumor-infiltrating lymphocytes (TILs) subtypes were obtained from our published data and reanalyzed.

RESULTS

Bland-Altman plot showed no difference between mean TSR derived from the two observers. TSR was positively associated with stromal PD-L1 expression, the Immunoscore and CD3+ as well as CD4+ TILs density, but negatively correlated with tumor microvessel density, Ki-67 index, surrounding muscle invasion by tumor and number of Foxp3+ and PD-1+ TILs. Low TSR independently predicted poor local recurrence-free survival and overall survival. Moreover, patients with low TSR and low Immunoscore chordoma phenotype were associated with the worst survival. More importantly, combined TSR and Immunoscore accurately reflected prognosis and enhanced the ability of TSR or Immunoscore alone for outcome prediction.

CONCLUSION

These data reveal the significant impact of TSR on tumor progression and immunological response of patients. Subsequent use of agents targeting the stroma compartment may be an effective strategy to treat chordoma especially in combination with immune-based drugs.
Use of Intraoperative CO2 Laser for the Resection of a Ventral Intradural Extramedullary Cervical Spinal Tumor: 2-Dimensional Operative Video
Authors: Osorio Joseph A , Liabres Guillermo Victorino T , Miller Catherine A , McDermott Michael W , Mummaneni Praveen V
Published: August 2019

Ventral spinal tumors are surgically challenging because the tumor resection should minimize spinal cord and nerve root manipulation to minimize morbidity, while providing access to a complete tumor resection. The CO2 laser has been useful in resection of central nervous system tumors, but little is described about the method used to resect spinal tumors.
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This video demonstrates the removal of a ventral cervical spinal meningioma using the CO2 laser. A 62-yr-old man presented with progressive paresthesias, gait instability, and urinary frequency. A 1-cm intradural extramedullary mass at C5 showed severe spinal cord compression. Patient consent was obtained prior to performing the procedure. A posterior lateral approach is shown, with a bone removal corridor created at C5 for accessing the tumor ventrally. A right-sided facetectomy and pediculectomy at C5 were performed being flush with the posterior vertebral body. A dural opening positioned laterally provided a working corridor between C5 and C6 nerve rootlets. Lateral portions of tumor were excised in wedge-shaped slices starting laterally and working medially. These slices created a successive and enlarging space to safely allow piecemeal tumor dissection and removal, while limiting retraction upon the spinal cord. The CO2 laser was used to cauterize the tumor capsule, create wedge resections of tumor, and coagulate the final dural attachment. The pathology was a meningioma WHO Grade I. The patient did well, with resolution of parasthesias and ataxia. The CO2 laser technique allowed for limited spinal cord retraction throughout the tumor resection and gross total resection of the tumor was achieved.
Techniques and Tips for Freehand Placement of C7 Pedicle Screws With Respect to Cervicothoracic Constructs: 2-Dimensional Operative Video
Authors: Clifton William , Edwards Steve , Louie Christopher , Dove Conrad , Damon Aaron , Nottmeier Eric , Pichelmann Mark
Published: August 2019

We present a surgical video highlighting the technical pearls for C7 pedicle screw placement with respect to cervicothoracic constructs. Pedicle screw placement into C7 has been shown to enhance the biomechanical stability of both cervical and cervicothoracic constructs and is safe for patient related outcomes.
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Rod placement across the cervicothoracic junction is known to be difficult because of the variable starting point of the C7 pedicle screw, which may cause misalignment of the polyaxial heads with respect to the C7 and C6 screw heads. Using our step-wise method of anatomic screw placement, this potential pitfall is minimized. The T1 pedicle screw is placed first. The C6 lateral mass screw starting point is displaced slightly superiorly from the midpoint of the lateral mass in order to make room for the polyaxial head of the C7 pedicle screw. A small laminotomy is performed in order to find the medial border of the C7 pedicle. Palpation of the medial border allows for an approximation of the pedicle limits. The cranial-caudal angle of drilling is perpendicular to the C7 superior facet, and the medial-lateral trajectory typically falls between 15 and 20 degrees medial. Once the pedicle is cannulated, a ball-tipped probe is used to confirm intraosseous position. A rod is cut and contoured to the appropriate length of the construct. The C7 pedicle screw should capture the rod easily with slight displacement of the polyaxial head. Postinstrumentation anteroposterior and lateral fluoroscopy are performed to confirm good position of the lateral mass and pedicle screws.

Patient consent was not required for this cadaveric surgical video.
Polypoid Atypical Spitz Tumor With a Fibrosclerotic Stroma, CLIP2-BRAF Fusion, and Homozygous Loss of 9p21
Authors: Donati Michele , Kastnerova Liubov , Ptakova Nikola , Michal Michal , Kazakov Dmitry V.
Published: August 2019

We report a case of a polypoid atypical Spitz tumor with a prominent fibrosclerotic stromal component, harboring a CLIP2-BRAF fusion, which has hitherto been not reported in melanocytic lesions. The neoplasm occurred in a 78-year-old male patient and appeared microscopically as a predominantly dermal, barely symmetrical, polypoid lesion composed mainly of epithelioid cells showing moderate degree of nuclear pleomorphism with ample amphophilic cytoplasm arranged in nests, fascicles, or single units. The mitotic rate was 2/mm2, and the mitoses were confined to the upper portion of the lesion. The Breslow thickness was 2.3 mm. The stroma contained conspicuous plumped fibroblasts and thickened collagen bundles associated with dilated medium-sized vessels. Focally, sclerotic areas were found. A moderately dense, lymphocyte-predominant inflammatory infiltrate scattered through the whole lesion was seen. Despite strong nuclear and cytoplasmic positivity of p16, FISH revealed homozygous loss in locus 9p21. A CLIP2-BRAF fusion was found by next-generation sequencing. No other genetic alterations including a TERT-promoter mutation was found. The patient is disease-free without recurrence or evidence of metastatic disease after 5 years and 2 months of follow-up.
Retention Rates Among Patients Undergoing Multimodal Facial Rejuvenation Treatment Versus a Single Monotherapy in Cosmetic Dermatology Practices
Authors: Gregory Allison , Humphrey Shannon , Chunharas Chatchadaporn , Ogilvie Patricia , Fabi Sabrina G.
Published: August 2019

BACKGROUND

Facial aging is a multifactorial process. Accordingly, expert opinion has largely been unanimous in that multimodal treatment targeting various aspects of the aging face provides superior results. However, there is a lack of studies exploring patient response.

OBJECTIVE

To compare patient retention between triple multimodal facial rejuvenation treatment (neuromodulator, filler, and energy-based therapy) and monotherapy (neuromodulator alone).

METHODS

A retrospective, multicenter (the United States, Canada, and Germany) study was performed. Cases were retrieved from July 2015 to June 2016. The study compared patients who had undergone monotherapy (neuromodulator), combined multimodal treatment (neuromodulator, filler, and energy-based therapy on the same day), and sequential multimodal treatment (neuromodulator, filler, and energy-based therapy over a 1-year period). Retention rates were calculated.

RESULTS

A total of 509 patients were included: monotherapy (300), sequential multimodal treatment (93), and combined multimodal treatment (116). Patient retention was significantly higher in the combined multimodal treatment group compared with the monotherapy and sequential multimodal treatment groups (p < .001). Subgroup analysis revealed similar trends at all sites.

CONCLUSION

Based on retention rates, patients are more likely to return to the clinic when multiple treatment modalities are used during 1 encounter. These data further solidify the importance of multimodal therapy for both the provider and the patient.
“The Constant by Our Side”—Mothers' Experiences of Early Intervention Therapy Services for Infants With Emerging Signs of Complex Neurodevelopmental Difficulties
Authors: Gibbs Deanna , Harniess Phillip , Crossley Siew-Lian
Published: August 2019

Infants who require admission to a neonatal unit and who ultimately present with complex neurodevelopmental difficulties often require more sustained engagement with early intervention services during admission and beyond. However, there is little research exploring families' experiences of early intervention (EI) therapy received throughout a neonatal unit admission and continuing through transition into the community setting. This study was designed to explore parents' perceptions of EI therapy for infants with complex emerging neurodevelopmental difficulties. Using a descriptive qualitative approach, interviews were conducted with 6 mothers whose infants had been admitted to a neonatal unit and were receiving EI therapy services for their child. Interviews were audio-recorded and transcribed and then thematically analyzed. Four key themes emerged articulating the parent experiences during their evolving relationship with therapy providers in the neonatal unit and following discharge: (a) a vulnerable start—adjusting to the unexpected; (b) becoming a mother—becoming a family; (c) the therapy journey; and (d) a new reality. Attributes that enhanced the developing parent–provider relationship were identified including the importance of developing collaborative communication styles, supporting families in developing their expectations of the parent–provider relationship, and ensuring clarity in the nature, scope, and contribution of EI therapy to their child and overall family development. Early introduction of EI therapists during an infant's admission to a neonatal unit can serve to strengthen the parent–provider relationship by offering a support continuum during a vulnerable time.
The Importance of Prioritizing Pre and Posttransplant Immunizations in an Era of Vaccine Refusal and Epidemic Outbreaks
Authors: Feldman Amy G. , Hsu Evelyn K. , Mack Cara L.
Published: August 2019

Vaccine-preventable infections are occurring at epidemic rates both nationally and internationally. At the same time, rates of vaccine hesitancy and refusal are increasing across the country leading to decreased herd immunity. For immunosuppressed transplant recipients, this situation poses great risk. Currently, 1 in 6 pediatric solid organ transplant recipients is hospitalized with a vaccine-preventable infection in the first 5 years posttransplant. For many recipients, these infections result in significant morbidity, mortality, and increased hospitalization costs. Surprisingly, despite this risk many transplant recipients are not up-to-date on age appropriate immunizations at the time of transplant and thereafter. As a transplant community, we must prioritize immunizations in both pre and posttransplant care. Research is needed to understand how to monitor immune response to vaccines in immunosuppressed patients and when to optimally immunize patients posttransplant. Finally, recommendations about administration of live vaccines posttransplant may need to be reevaluated in the setting of measles outbreaks and decreased herd immunity.
Cross-talks of glycosylphosphatidylinositol biosynthesis with glycosphingolipid biosynthesis and ER-associated degradation
Authors: Wang Yicheng , Maeda Yusuke , Liu Yishi , Takada Yoko , Ninomiya Akinori , Hirata Tetsuya , Fujita Morihisa , Murakami Yoshiko , Kinoshita Taroh
Published: August 2019

Glycosylphosphatidylinositol (GPI)-anchored proteins and glycosphingolipids interact with each other in the mammalian plasma membranes, forming dynamic microdomains. How their interaction starts in the cells has been unclear. Here, based on a genome-wide CRISPR-Cas9 genetic screen for genes required for GPI side-chain modification by galactose in the Golgi apparatus, we report that β1,3-galactosyltransferase 4 (B3GALT4), also called GM1 ganglioside synthase, additionally functions in transferring galactose to theN-acetylgalactosamine side-chain of GPI. Furthermore, B3GALT4 requires lactosylceramide for the efficient GPI side-chain galactosylation. Thus, our work demonstrates previously unexpected evolutionary and functional relationships between GPI-anchored proteins and glycosphingolipids in the Golgi. Through the same screening, we also show that GPI biosynthesis in the endoplasmic reticulum (ER) is severely suppressed by ER-associated degradation to prevent GPI accumulation when the transfer of synthesized GPI to proteins is defective. Our data demonstrates cross-talks of GPI biosynthesis with glycosphingolipid biosynthesis and the ER quality control system.
Crumbs2 mediates ventricular layer remodelling to form the adult spinal cord central canal
Authors: Tait Christine , Chinnaiya Kavitha , Murtaza Mariyam , Ashton John-Paul , Furley Nicholas , Hill Chris J. , Henrique Alves C , Wijnholds Jan , Erdmann Kai S. , Das Raman M. , Rashbass Penny , Storey Kate G. , Placzek Marysia
Published: August 2019

In the spinal cord, the adult central canal forms through a poorly-understood process termed dorsal collapse that involves attrition and remodelling of the pseudostratified dorsal ventricular layer. Here we show, in mouse, that dorsal ventricular layer cells adjacent to midline Nestin(+) radial glia downregulate the apical polarity proteins Crumbs2 (CRB2) and aPKC and delaminate in a step-wise manner; concomitantly, Nestin(+) radial glial end-feet ratchet down, to repeat this process. Nestin(+) radial glia secrete a factor that promotes cell delamination. This activity is mimicked by a secreted variant of CRB2 (CRB2S), which is specifically expressed by dorsal midline Nestin(+) radial glia. In cultured cells, CRB2S associated with apical membranes and decreased cell cohesion. Analysis of Crb2F/F/Nestin-Cre+/− mice further confirmed an essential role for CRB2 in dorsal collapse. We propose a model in which CRB2S promotes the progressive attrition of the ventricular layer without loss of overall integrity. This novel mechanism may operate more widely to promote orderly progenitor delamination.
Tagging enhances histochemical and biochemical detection of Ran Binding Protein 9 in vivo and reveals its interaction with Nucleolin
Authors: Soliman Shimaa , Stark Aaron E. , Gardner Miranda , Harshman Sean W. , Breece Chelssie C. , Amari Foued , Orlacchio Arturo , Chen Min , Tessari Anna , Martin Jennifer A. , Visone Rosa , Freitas Michael A. , La Perle Krista M.D. , Palmieri Dario , Coppola Vincenzo
Published: August 2019

The lack of tools to reliably detect RanBP9 in vivo has significantly hampered progress in understanding the biological functions of this scaffold protein. We report here the generation of a novel mouse strain, RanBP9-TT, in which the endogenous protein is fused with a double (V5-HA) epitope tag at the C-terminus. We show that the double tag does not interfere with the essential functions of RanBP9. In contrast to RanBP9 constitutive knock-out animals, RanBP9-TT mice are viable, fertile and do not show any obvious phenotype. The V5-HA tag allows unequivocal detection of RanBP9 both by IHC and WB. Importantly, immunoprecipitation and mass spectrometry analyses reveal that the tagged protein pulls down known interactors of wild type RanBP9. Thanks to the increased detection power, we are also unveiling a novel interaction with Nucleolin, a prominent nucleolar protein.

In summary, we report the generation of a new mouse line in which RanBP9 expression and interactions can be reliably studied by the use of commercially available αtag antibodies. The use of this line will help to overcome some of the existing limitations in the study of RanBP9 and potentially reveal novel functions of this protein in vivo such as those linked to Nucleolin.
Board interlocks and capital structure dynamics: evidence from China
Authors: Li Danmeng , Jiang Qiuju , Mai Yong
Published: August 2019

Using a sample of Chinese A‐share listed companies from the Shanghai and Shenzhen stock exchanges from 2007 to 2016, this paper investigates the effects of director network centrality on the speed of capital structure adjustment. The results indicate that firms in the central position of the director network have a higher speed of capital structure adjustment and a lower extent of deviation from the target capital structure. This effect is mainly significant for non‐state‐owned enterprises (non‐SOEs). Collectively, the evidence shows the network of interlocked directors creating mechanisms for information and resource exchanges, which enhance the efficiency of corporate financing polices.
“Home sweet home?” Struggles of intracultural “betweenness” of doctoral fieldwork in my home country of Jamaica
Authors: McFarlane‐Morris Shenika
Published: August 2019

The culture of silence surrounding the nuanced challenges of fieldwork is being broken but there is still a long way to go. In the last two decades or so, an interesting discourse has developed on experiences of “betweenness” in the field. However, a glaring issue is the underrepresentation of the experiences of Global South researchers and doctoral students returning to their homelands to conduct fieldwork. Much has been written about cross‐cultural fieldwork and its associated challenges, yet the “betweenness” experienced during intracultural research on the impacts of large‐scale tourism is scantly studied. This paper begins with an overview of producing knowledge through qualitative means, followed by an account of the insider/outsider debate that informs this paper. It sheds light on the intracultural dimensions of “betweenness,” which are framed within my experience of being an outsider and an insider during my return to my home country, Jamaica, for doctoral fieldwork. The nuanced challenges and negotiations that came with my “betweenness,” concerning phenomena such as “gazing back,” are at the centre of my discussion. My conclusion is that “betweenness” is not limited to those conducting cross‐cultural studies but also affects those conducting intracultural studies. Therefore, researchers returning home for fieldwork should be on their guard for the implications of “betweenness” for the success of the research process.
Glutaminolysis‐related genes determine sensitivity to xCT‐targeted therapy in head and neck squamous cell carcinoma
Authors: Okazaki Shogo , Umene Kiyoko , Yamasaki Juntaro , Suina Kentaro , Otsuki Yuji , Yoshikawa Momoko , Minami Yushi , Masuko Takashi , Kawaguchi Sho , Nakayama Hideki , Banno Kouji , Aoki Daisuke , Saya Hideyuki , Nagano Osamu
Published: August 2019

Targeting the function of membrane transporters in cancer stemlike cells is a potential new therapeutic approach. Cystine‐glutamate antiporter xCT expressed in CD44 variant (CD44v)‐expressing cancer cells contributes to the resistance to oxidative stress as well as cancer therapy through promoting glutathione (GSH)‐mediated antioxidant defense. Amino acid transport by xCT might, thus, be a promising target for cancer treatment, whereas the determination factors for cancer cell sensitivity to xCT‐targeted therapy remain unclear. Here, we demonstrate that high expression of xCT and glutamine transporter ASCT2 is correlated with undifferentiated status and diminished along with cell differentiation in head and neck squamous cell carcinoma (HNSCC). The cytotoxicity of the xCT inhibitor sulfasalazine relies on ASCT2‐dependent glutamine uptake and glutamate dehydrogenase (GLUD)‐mediated α‐ketoglutarate (α‐KG) production. Metabolome analysis revealed that sulfasalazine treatment triggers the increase of glutamate‐derived tricarboxylic acid cycle intermediate α‐KG, in addition to the decrease of cysteine and GSH content. Furthermore, ablation of GLUD markedly reduced the sulfasalazine cytotoxicity in CD44v‐expressing stemlike HNSCC cells. Thus, xCT inhibition by sulfasalazine leads to the impairment of GSH synthesis and enhancement of mitochondrial metabolism, leading to reactive oxygen species (ROS) generation and, thereby, triggers oxidative damage. Our findings establish a rationale for the use of glutamine metabolism (glutaminolysis)‐related genes, including ASCT2 and GLUD, as biomarkers to predict the efficacy of xCT‐targeted therapy for heterogeneous HNSCC tumors.
Association of urinary sodium/potassium ratio with structural and functional vascular changes in non‐diabetic hypertensive patients
Authors: Cunha Michelle R. , Cunha Ana R. , Marques Bianca C. A. A. , Mattos Samanta S. , D’El-Rei Jenifer , França Natalia M. , Oigman Wille , Neves Mario F.
Published: August 2019

Studies aiming to associate the sodium/potassium (Na/K) ratio with hypertension use 24‐hour urinary excretion as a daily marker of ingestion. The objective of this study was to evaluate the association between urinary Na/K ratio and structural and functional vascular alterations in non‐diabetic hypertensive patients. In hypertensive patients (n = 72), aged between 40 and 70 years, both sexes (61% women), in use of hydrochlorothiazide, we measured blood pressure, 24‐hour urine sample collection, assessment of carotid‐femoral pulse wave velocity (cf‐PWV, Complior), central hemodynamic parameters (SphygmoCor), and post‐occlusive reactive hyperemia (PORH). The participants were divided according to the tertile of 24‐hour urinary Na/K ratio. Each group contained 24 patients. Systolic blood pressure was higher in T2 (133 ± 9 vs 140 ± 9 mmHg, P = .029). C‐reactive protein (CRP) presented higher values in T3 as compared to T1 [0.20(0.10‐0.34) vs 1.19 (0.96‐1.42) mg/dL, P < .001]. Higher values in T3 were also observed for aortic systolic pressure (aoSP) [119(114‐130) vs 135(125‐147) mmHg, P = .002] and cf‐PWV (9.2 ± 1.6 vs 11.1 ± 1.5 m/s, P < .001). The urinary Na/K ratio presented significant correlations with proteinuria (r = .27, P = .023), CRP (r = .77, P < .001), cf‐PWV (r = .41, P < .001), and post‐occlusive reactive hyperemia on cutaneous vascular conductance (PORH CVC) (r = −.23, P = .047). By multivariate linear regression, it was detected an independent and significant association of cf‐PWV with urinary Na/K ratio (R2 = 0.17, P < .001) and PORH CVC with CRP (R2 = 0.30, P = .010). Our data indicated that increased urinary Na/K ratio in non‐diabetic hypertensive patients was associated with higher degree of inflammation, raised peripheral and central pressure levels, and changes suggestive of endothelial dysfunction and arterial stiffness.