bluuebunny/crossref_metadata_2025 huggingface dataset:
A dynamic wrapper‐based feature selection for improved precision in content‐based image retrieval
Authors: Sankar K. , Uma Maheswari P.
Published: June 2019

The content‐based image retrieval (CBIR) has been applied in the image processing as well as pattern recognition. A challenging task in the CBIR research has been through the feature extraction for decreasing any semantic gap that is an active research topic. Here, in this work, there is a texture feature that is extracted from an image, making use of a technique of curvelet transform. This curvelet is selected for a sparse representation that is quite critical for the estimation of images, which have been de‐noised with some inversed problems. The wrapping‐based curvelet transform will be even more robust as well as faster in the time of computation than the Ridge Transform. A technique of feature selection will be brought for selecting the optimal features. The correlation‐based feature selection (CFS) method has been adapted for improving the accuracy of the CBIR systems. The non‐deterministic polynomial (NP)–hard problems may be solved using the chemical reaction optimization (CRO) that has been motivated using the technique of chemical reaction. The benefits of proposed method is a necessity for marginal human intrusion for the purpose of retrieving the images needed from its database. The proposed mechanism has been again assessed depending on the Coral Database, and a performance study is ended using precision, f measure, and recall.
Image enhancement in embedded devices for internet of things
Authors: Jeon Gwanggil , Pasupa Kitsuchart , Anisetti Marco , Ahmad Awais
Published: June 2019

This paper proposes a new color interpolation method which can be used in embedded devices for IoT system. In this work, we use regression approach for generating and designing filters to restore color image. The filters are designed with four sizes, 5x5 training filter, 7x7 training filter, 9x9 training filter, and 11x11 training filter. The obtained filters are tested in 25 LC dataset to assess the performance. Experimental results inform that the proposed filters provide outstanding performance when they are compared with conventional methods. As compared with the other methods, the proposed filters produce the best average interpolation performance both objectively and visually.
Innovation strategies of energy firms
Authors: Costa‐Campi María Teresa , Duch‐Brown Néstor , García‐Quevedo José
Published: June 2019

Investment by energy firms in innovation can have substantial economic and environmental impacts and benefits. Firms engage in innovation for different reasons. The main objective of this paper is to analyse the role that the different innovation objectives have on firms' decisions to invest in each of three types of innovation activity: namely, internal R&D, external R&D, and the acquisition of advanced machinery, equipment, or software. We consider four objectives: process innovation, product innovation, reducing environmental impact, and meeting regulatory requirements. With this approach, we examine how energy firms innovate to reduce their environmental impact in comparison with other innovation objectives. In carrying out the empirical analysis, we draw on data for private energy firms included in the Spanish Technological Innovation Panel for the period 2004–2016. In the empirical analysis, we take the potential persistence of innovation activities into account and we use multivariate probit models to control for possible complementarities between the different R&D and innovation investments. Our results show that internal and external R&D are undertaken to address environmental objectives and to meet regulatory requirements whereas the acquisition of advanced machinery has the purpose of developing process innovations.
Utility of endoscopic ultrasound‐guided fine‐needle aspiration cytology in rapid on‐site evaluation for the diagnosis of gastric submucosal tumors: Retrospective analysis of a single‐center experience
Authors: Sandoh Kaori , Ishida Mitsuaki , Okano Kimiaki , Miyasaka Chika , Mori Shigeo , Tokuhara Mitsuo , Suzuki Ryou , Okazaki Takashi , Nakamura Naohiro , Tsuta Koji
Published: June 2019

Background

Recently, there have been reports of endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) cytology being used for the diagnosis of various kinds of tumors. This method has also been adopted in the diagnosis of gastric submucosal tumors (SMTs). The aim of this study was to analyze the utility of EUS‐FNA cytological examination in rapid on‐site evaluation (ROSE) for gastric SMTs.

Methods

Retrospective analyses of the cytological specimens of EUS‐FNA in ROSE for gastric SMTs and determination of the diagnostic accuracy of EUS‐FNA combined with immunohistochemical analysis of cell blocks and surgically resected specimens were performed.

Results

A total of 110 patients were enrolled in this study. The most common cytodiagnosis was spindle cell tumor (62 patients, 55.5%), followed by negative for tumor (34 patients), and malignant lymphoma and adenocarcinoma (five patients each). Cell blocks were prepared for 60 of the patients (96.8%), cytologically diagnosed with spindle cell tumor. Immunohistochemical analyses using cell block revealed gastrointestinal stromal tumor (GIST, c‐kit+/desmin−, 49 patients) and leiomyoma (desmin+/c‐kit−, five patients). Thus, using EUS‐FNA specimens, 83.1% of GIST patients were pre‐operatively diagnosed.

Conclusions

EUS‐FNA cytological examination in ROSE for gastric SMTs aided in the collection of sufficient amounts of tumor tissues for preparing cell blocks. This method led to a high rate of accurate pre‐operative diagnosis in patients with gastric SMTs.
Phylogeography and paleodistribution models of a widespread birch (Betula platyphylla Suk.) across East Asia: Multiple refugia, multidirectional expansion, and heterogeneous genetic pattern
Authors: Chen Tian‐Yi , Lou An‐Ru
Published: June 2019

Widespread tree species cover large geographical areas and play important roles in various vegetation types. Understanding how these species responded to historical climatic changes is important for understanding community assembly mechanisms with evolutionary and conservation implications. However, the location of refugial areas and postglacial history of widespread trees in East Asia remain poorly known. We combined microsatellite data (63 populations, 1756 individuals) and ecological niche modeling to examine the range‐wide population diversity, genetic structure, and historical demography of a pioneer tree species, Asian white birch (Betula platyphylla Suk.) across East Asia. We found a north‐to‐south trend of declining genetic diversity and five clusters, corresponding to geographical regions. Different clusters were inferred to have diverged through Pleistocene climatic oscillations and have different expansion routes, leading to genetic admixture in some populations. Ecological niche models indicated that the distribution of B. platyphylla during the last glacial maximum still had a large latitude span with slight shifts toward southeast, and northern populations had more variable distribution ranges than those in the south during later climatic oscillations. Our results reflect the relatively stable distribution through the last glacial–interglacial cycles and recent multidirectional expansion of B. platyphylla, providing new hypotheses for the response pattern of widespread tree species to climate change. The gradual genetic pattern from northeast to southwest and alternative distribution dynamics possibly resulted from environmental differences caused by latitude and topographic heterogeneity.
Origin and evolution of the major histocompatibility complex class I region in eutherian mammals
Authors: Abduriyim Shamshidin , Zou Da‐Hu , Zhao Huabin
Published: June 2019

Major histocompatibility complex (MHC) genes in vertebrates are vital in defending against pathogenic infections. To gain new insights into the evolution of MHC Class I (MHCI) genes and test competing hypotheses on the origin of the MHCI region in eutherian mammals, we studied available genome assemblies of nine species in Afrotheria, Xenarthra, and Laurasiatheria, and successfully characterized the MHCI region in six species. The following numbers of putatively functional genes were detected: in the elephant, four, one, and eight in the extended class I region, and κ and β duplication blocks, respectively; in the tenrec, one in the κ duplication block; and in the four bat species, one or two in the β duplication block. Our results indicate that MHCI genes in the κ and β duplication blocks may have originated in the common ancestor of eutherian mammals. In the elephant, tenrec, and all four bats, some MHCI genes occurred outside the MHCI region, suggesting that eutherians may have a more complex MHCI genomic organization than previously thought. Bat‐specific three‐ or five‐amino‐acid insertions were detected in the MHCI α1 domain in all four bats studied, suggesting that pathogen defense in bats relies on MHCIs having a wider peptide‐binding groove, as previously assayed by a bat MHCI gene with a three‐amino‐acid insertion showing a larger peptide repertoire than in other mammals. Our study adds to knowledge on the diversity of eutherian MHCI genes, which may have been shaped in a taxon‐specific manner.
New Cubic Phases for T2M[CN]6·xH2O with T = Ni, Cu and M = Ru, Os: Improving the Robustness and Modulating the Electron Density at the Cavity Surfaces
Authors: López Noeldris L. , Rodríquez‐Hernández Joelis , Reguera Leslie , Reguera Edilso
Published: June 2019

The four Prussian blue analogs (PBAs) under study in this contribution, T2[M(CN)6]·xH2O, have an open framework structure with 50 % of vacancies for the hexacyanometallate building block. In this series, the metal T is always found at the surface of the formed system of cavities and has a partially naked coordination environment. In the as‐synthesised materials, such available coordination sites are occupied by water molecules, which, in turn, stabilize additional water molecules inside the cavity through hydrogen bonding interactions. Herein, we report the synthesis, crystal structure, and related properties for the new title members of this family of coordination polymers, particularly for T = Ni, Cu and M = Ru, Os. To improve the material's crystallinity, the powders formed from the precipitation reaction were submitted to solvothermal recrystallization. Their crystal structure was solved and refined from the corresponding X‐ray diffraction (XRD) patterns. Unlike their FeII analogs, which crystallize in a Pm3m cubic structure, two types of cubic structures (depending on the external metal) were obtained: Fm3m for Ni2[M(CN)6]·xH2O and Pm3m for Cu2[M(CN)6]·xH2O. Such structural differences are properly supported by a detailed analysis of their IR and UV/Vis spectra. The stability of their porous network after water removal was evaluated by combining XRD, H2 adsorption isotherms, and thermogravimetric curves. Hydrogen adsorption was also used to explore the adsorption potential at the cavity surface. Except Cu2[Ru(CN)6]·xH2O, the other three materials appear to be stable after water removal under soft heating, which was ascribed to the role of the inner metal (RuII and OsII) on the framework robustness. These two metals have extended t2g orbitals, which favor the occurrence of a strong coupling between the inner and outer metals in the –T–N≡C‐M–C≡N‐T– chain. Apparently, such overlapping for charge density contributes to the material's stability.
Enhancing Specific Capacitance and Cyclic Stability through Incorporation of MnO2 into Bacterial Nanocellulose/PPy·CuCl2 Flexible Electrodes
Authors: Dias Gabriella M. V. , Müller Daliana , Wesling Bruno N. , Bernardes Joseane C. , Hotza Dachamir , Rambo Carlos R.
Published: June 2019

This study reports the polymerization of polypyrrole (PPy) in bacterial nanocellulose (BNC) membranes impregnated with manganese oxide (MnO2). Prior to polymerization, nanosized MnO2 is synthesized in situ using H2SO4 and KMnO4. PPy is then polymerized in situ in the MnO2 impregnated BNC membranes via chemical oxidation using copper chloride dihydrate (CuCl2·2H2O) as the oxidizing agent using two different concentrations of pyrrole (Py): 0.04 and 0.08 mol L−1 with a 1:4 molar ratio of Py/CuCl2·2H2O. Assembled symmetric supercapacitor devices exhibit specific capacitances as high as 1073 mF cm−2 (259 F cm−3) and a capacitance retention of 99.5% after 1000 cycles, which show that the combination of BNC membranes with a conductive polymer and a metallic oxide can be promising as an electrode for energy storage devices.
Spatiotemporal traffic matrix prediction: A deep learning approach with wavelet multiscale analysis
Authors: Zhao Jianlong , Qu Hua , Zhao Jihong , Jiang Dingchao
Published: June 2019

Network traffic analysis has always been a key technique for operating and managing a network. However, due to some (non) technical issues, it is not trivial to directly obtain network‐wide traffic data. Although a large number of traffic matrix (TM) prediction methods have been used to obtain future network‐wide traffic, they achieve somewhat limited accuracy due to neglecting spatiotemporal evolution features of TM series at different time scales. In order to improve the performance of TM prediction, we propose a novel end‐to‐end deep neural network based on wavelet multiscale analysis, called WSTNet. In this network, the original TM series is first decomposed into multilevel time‐frequency TM subseries at different time scales by using discrete wavelet decomposition, and then the convolutional neural network without pooling is used to extract the spatial patterns among traffic flows, and finally, the long short‐term memory neural network with a self‐attention mechanism by relating different positions of input sequences across entire time steps is employed to explore the temporal evolution features within TM series. To investigate the performance of our proposed model, extensive experiments are conducted on two real network traffic data sets from the Abilene and GÉANT backbone networks. The results show that WSTNet is significantly better than the other four state‐of‐the‐art deep learning methods.
Trusting forecasts
Authors: Önkal Dilek , Gönül M. Sinan , De Baets Shari
Published: June 2019

Accurate forecasting is necessary to remain competitive in today's business environment. Forecast support systems are designed to aid forecasters in achieving high accuracy. However, studies have shown that people are distrustful of automated forecasters. This has recently been dubbed “algorithm aversion.” In this study, we explore the relationship between trust and forecasts, and if trust can be boosted in order to achieve a higher acceptance rate of system forecasts and lessen the occurrence of damaging adjustments. In a survey with 134 executives, we ask them to rate the determinants of trust in forecasts, what trust in forecasting means to them, and how trust in forecasts can be increased. The findings point to four main factors that play a role in trusting forecasts: (a) the forecast bundle, (b) forecaster competence, (c) combination of forecasts, and (d) knowledge. Implications of these factors for designing effective forecast support and future‐focused management processes are discussed.
Modified Energy Efficiencies of Proton‐conducting SOFCs with Partial Conductions of Oxide‐ions and Holes
Authors: Matsuzaki Y. , Tachikawa Y. , Iinuma H. , Sato K. , Baba Y. , Otomo J. , Matsumoto H. , Taniguchi S. , Sasaki K.
Published: June 2019

An analytical method to determine the electrochemical energy efficiencies of electrolytes with partial electronic conduction has been developed previously and reported in the literature. However, this analytical method does not address the effects of differing ionic species in electrolytes, i.e., the oxide‐ions or protons. Therefore, we aimed to modify this analytical method to account for the effects of differing ionic species, and applied it to compare the energy efficiencies of oxide‐ion conducting solid electrolytes such as yttria‐stabilized zirconia (YSZ) and gadolinia‐doped ceria (GDC) to proton‐conducting solid electrolytes, such as yttria‐doped barium zirconate (BZY). With the modification, difference in the influence of the fuel consumption between the oxide‐ion conducting electrolyte and the proton‐conducting electrolyte has been successfully taken into account. The energy efficiency of the BZY electrolyte relatively increased against those of YSZ or GDC electrolytes by the modification. Additionally, partial oxide‐ion conduction in the proton‐conducting electrolyte was successfully estimated using the modified analytical method.
Fractionated stereotactic body radiotherapy for up to five prostate cancer oligometastases: Interim outcomes of a prospective clinical trial
Authors: Bowden Patrick , See Andrew W. , Frydenberg Mark , Haxhimolla Hodo , Costello Anthony J. , Moon Daniel , Ruljancich Paul , Grummet Jeremy , Crosthwaite Alan , Pranavan Ganes , Peters Justin S. , So Kevin , Gwini Stella M. , McKenzie Dean P. , Nolan Skye , Smyth Lloyd M.L. , Everitt Craig
Published: June 2019

Stereotactic body radiotherapy (SBRT) can delay escalation to systemic treatment in men with oligometastatic prostate cancer (PCa). However, large, prospective studies are still required to evaluate the efficacy of this approach in different patient groups. This is the interim analysis of a prospective, single institution study of men relapsing with up to five synchronous lesions following definitive local treatment for primary PCa. Our aim was to determine the proportion of patients not requiring treatment escalation following SBRT. In total, 199 patients were enrolled to receive fractionated SBRT (50 Gray in 10 fractions) to each visible lesion. Fourteen patients were castration resistant at enrolment. The proportion of patients not requiring treatment escalation 2 years following SBRT was 51.7% (95% CI: 44.1–59.3%). The median length of treatment escalation‐free survival over the entire follow‐up period was 27.1 months (95% CI; 21.8–29.4 months). Prior androgen deprivation therapy (ADT) predicted a significantly lower rate of freedom from treatment escalation at 2 years compared to no prior ADT (odds ratio = 0.21, 95% CI: 0.08–0.54, p = 0.001). There was no difference in the efficacy of SBRT when treating 4–5 vs. 1–3 initial lesions. A prostate‐specific antigen (PSA) decline was induced in 75% of patients, with PSA readings falling to an undetectable level in six patients. No late grade three toxicities were observed. These interim results suggest that SBRT can be used to treat up to five synchronous PCa oligometastases to delay treatment escalation.
Familial aggregation of early‐onset cancers
Authors: Heikkinen Sanna M. M. , Madanat‐Harjuoja Laura‐Maria , Seppä Karri J. M. , Rantanen Matti E. , Hirvonen Elli M. , Malila Nea K. , Pitkäniemi Janne M.
Published: June 2019

This registry‐linkage study evaluates familial aggregation of cancer among relatives of a population‐based series of early‐onset (≤40 years) cancer patients in Finland. A cohort of 376,762 relatives of early‐onset cancer patients diagnosed between 1970 and 2012 in 40,538 families was identified. Familial aggregation of early‐onset breast, colorectal, brain and other central nervous system (CNS) cancer and melanoma was explored by standardized incidence ratios (SIR), stratified by relatedness. Gender‐, age‐ and period‐specific population cancer incidences were used as reference. Cumulative risks for siblings and offspring of the proband up to age ≤40 years were also estimated. Almost all early‐onset cancers were sporadic (98% or more). Among first‐degree relatives, SIR was largest in colorectal cancer (14, 95% confidence interval 9.72–18), and lowest in melanoma (1.93, 1.05–3.23). Highest relative‐specific SIRs were observed for siblings in families, where also parent had concordant cancer, 90 (43–165) for colorectal cancer and 29 (11–64) for CNS cancer. In spouses, all SIRs were at population level. Cumulative risk of colorectal cancer by age 41 was 0.98% in siblings and 0.10% in population, while in breast cancer the corresponding risks were 2.05% and 0.56%. In conclusion, early‐onset cancers are mainly sporadic. Findings support high familial aggregation in early‐onset colorectal and CNS cancers. Familial aggregation in multiplex families with CNS cancers was mainly attributed to neurofibromatosis and in colorectal cancer to FAP‐ and HNPCC‐syndromes. The pattern of familial aggregation of early‐onset breast cancer could be seen to support very early exposure to environmental factors and/or rare genetic factors.
New perspectives on screening and early detection of endometrial cancer
Authors: Costas Laura , Frias‐Gomez Jon , Guardiola Magdalena , Benavente Yolanda , Pineda Marta , Pavón Miquel Á. , Martínez José M. , Climent Maite , Barahona Marc , Canet Júlia , Paytubi Sonia , Salinas Mónica , Palomero Luis , Bianchi Ilaria , Reventós Jaume , Capellà Gabriel , Diaz Mireia , Vidal August , Piulats Josep M. , Aytés Álvaro , Ponce Jordi , Brunet Joan , Bosch Francesc X. , Matias‐Guiu Xavier , Alemany Laia , de Sanjosé Silvia ,   on behalf of the Screenwide Team
Published: June 2019

Due to the anatomical continuity of the uterine cavity with the cervix, genomic exploitation of material from routine Pap smears and other noninvasive sampling methods represent a unique opportunity to detect signs of disease using biological material shed from the upper genital tract. Recent research findings offer a promising perspective in the detection of endometrial cancer, but certain questions need to be addressed in order to accelerate the implementation of novel technologies in a routine screening or clinical setting. We discuss here new perspectives on detection of endometrial cancer using genomic and other biomarkers in minimally invasive sampling methods with a special focus on public health classic screening criteria, highlighting current gaps in knowledge.
Bromodomain and extraterminal domain inhibition synergizes with WEE1‐inhibitor AZD1775 effect by impairing nonhomologous end joining and enhancing DNA damage in nonsmall cell lung cancer
Authors: Takashima Yuta , Kikuchi Eiki , Kikuchi Junko , Suzuki Motofumi , Kikuchi Hajime , Maeda Makie , Shoji Tetsuaki , Furuta Megumi , Kinoshita Ichiro , Dosaka‐Akita Hirotoshi , Sakakibara‐Konishi Jun , Konno Satoshi
Published: June 2019

Bromodomain and extraterminal domain (BET) inhibitors are broadly active against distinct types of cancer, including nonsmall cell lung cancer (NSCLC). Previous studies have addressed the effect of BET‐inhibiting drugs on the expression of oncogenes such as c‐Myc, but DNA damage repair pathways have also been reported to be involved in the efficacy of these drugs. AZD1775, an inhibitor of the G2‐M cell cycle checkpoint kinase WEE1, induces DNA damage by promoting premature mitotic entry. Thus, we hypothesized that BET inhibition would increase AZD1775‐induced cytotoxicity by impairing DNA damage repair. Here, we demonstrate that combined inhibition of BET and WEE1 synergistically suppresses NSCLC growth both in vitro and in vivo. Two BET inhibitors, JQ1 and AZD5153, increased and prolonged AZD1775‐induced DNA double‐strand breaks (DSBs) and concomitantly repressed genes related to nonhomologous end joining (NHEJ), including XRCC4 and SHLD1. Furthermore, pharmaceutical inhibition of BET or knockdown of the BET protein BRD4 markedly diminished NHEJ activity, and the BET‐inhibitor treatment also repressed myelin transcription factor 1 (MYT1) expression and promoted mitotic entry with subsequent mitotic catastrophe when combined with WEE1 inhibition. Our findings reveal that BET proteins, predominantly BRD4, play an essential role in DSB repair through the NHEJ pathway, and further suggest that combined inhibition of BET and WEE1 could serve as a novel therapeutic strategy for NSCLC.
Robot‐assisted radical cystectomy in a patient with muscle‐invasive bladder cancer following radiotherapy for prostate cancer
Authors: Kubota Yuka , Hatakeyama Shingo , Hashimoto Takuya , Fujita Naoki , Okamoto Teppei , Suzuki Yuichiro , Yamamoto Hayato , Imai Atsushi , Yoneyama Takahiro , Hashimoto Yasuhiro , Koie Takuya , Ohyama Chikara
Published: June 2019

Introduction

Muscle‐invasive bladder cancer following radiotherapy for prostate cancer is rare. We reported a case of muscle‐invasive bladder cancer who underwent robot‐assisted radical cystectomy following radiotherapy for prostate cancer.

Case presentation

A 72‐year‐old man was referred to our division with a muscle‐invasive bladder cancer. He had a history of intensity‐modulated radiation therapy for localized prostate cancer. After three courses of platinum‐based neoadjuvant chemotherapy, he obtained a radiologic complete response. He elected for robot‐assisted radical cystectomy, standard lymph node dissection, and intracorporeal ileal conduit urinary diversion. Pathological findings revealed no residual tumor within the bladder and residual tumor in the prostate. He had discharged without any complications; and quality of life had improved.

Conclusion

A robot‐assisted approach might be a potential option for well‐selected patients with muscle‐invasive bladder cancer who have previously received radiotherapy for localized prostate cancer.
Frontline Science: Late CD27 stimulation promotes IL-7Rα transcriptional re-expression and memory T cell qualities in effector CD8+ T cells
Authors: Dong Han , Buckner Andrew , Prince Jessica , Bullock Timothy
Published: June 2019

We previously demonstrated that CD27 co-stimulation during a primary CD8+ T-cell response was critical for the expression of IL-7Rα on acute effector CD8+ T cells, providing an essential element in the generation of CD8+ T-cell memory to infectious pathogens. IL-7 plays a critical role in the generation and maintenance of memory CD8+ T cells, and IL-7Rα has been regarded as a functional marker of long-lived memory precursor effector cells. While IL-7Rα is downregulated acutely upon TCR stimulation, the regulation of the emergence of IL-7Rα expressing cells around the peak of primary CD8+ responses is less clear. Re-expression could be a default outcome after withdrawal of TCR stimulation. Alternatively, specific stimuli could actively antagonize the downregulation or promote the recovery of IL-7Rα in Ag-activated CD8+ T cells. By utilizing agonistic mAb and transgenic models, here we show: (1) CD27 stimulation acts directly on CD8+ T cells to enhance IL-7Rα-expressing effectors; (2) CD27 stimulation neither alleviates the downregulation of IL-7Rα upon TCR signaling nor promotes the expansion/survival of IL-7Rα-expressing effectors, but facilitates IL-7Rα re-expression; (3) CD27 stimulation regulates Il7ra mRNA abundance but not protein distribution. Importantly, CD27 stimulation promotes not only IL-7Rα, but also the common γ chain of the receptor and the downstream signaling mediated by pSTAT5. Our results demonstrate a previously unappreciated role of CD27 stimulation as a positive regulator of IL-7Rα during CD8 T-cell responses, provide insights into the mechanistic basis by which CD27 stimulation influences CD8+ T-cell memory differentiation, and highlight the potential of targeting CD27-CD70 axis to enhance IL-7 signaling for antiviral/antitumor immunotherapy.
Quantitative Assessment of Trace‐Element Contamination in Parenteral Nutrition Components
Authors: Olson Logan M. , Wieruszewski Patrick M. , Jannetto Paul J. , Abbott Jillian C. , McMahon M. Molly , Nystrom Erin M.
Published: June 2019

Background

Trace‐element contamination of contemporary parenteral nutrition (PN) components exists in unknown quantities and, in combination with excessive amounts of certain trace elements provided in commercially available adult, pediatric, and neonatal multitrace‐element (MTE) products, could result in eventual accumulation and toxicity. This study aims to quantify trace‐element contamination in components used for PN compounding to further inform recommendations for MTE product reformulation and individualized trace‐element prescribing in PN.

Methods

A total of 32 unique components (65 products) available for PN compounding were tested for manganese, chromium, selenium, zinc, and copper contamination, utilizing inductively coupled plasma mass spectrometry. Theoretical adult, pediatric, and neonatal PNs were formulated to assess the impact of macronutrient and micronutrient component doses on PN trace‐element contamination.

Results

Trace‐element contamination was detected in 24 (75%) components tested. Chromium and manganese were common, present in 65.6% and 51.5% of all components, respectively. Eight components did not contain detectable trace‐element contamination, most notably sterile water, concentrated dextrose, and lipid emulsion. Manganese contamination in theoretical adult, pediatric, and neonatal PN was 25.18, 9.92, and 1.37 µg, respectively. Chromium contamination was 4.85, 1.5, and 0.28 µg, respectively.

Conclusion

Trace‐element contamination was prevalent in components used to compound PN. Our findings support reformulation of adult, pediatric, and neonatal manufactured MTE products to eliminate chromium, decrease manganese, and supply full daily physiologic requirements of selenium, zinc, and copper. Future study is needed to assess the additional contamination that could occur through the compounding and storage processes.
Exploration of the problems and solutions related to reference introduction prior to calibration of thermal desorber–gas chromatography
Authors: Asfaw Adissu Alemayehu , Van der Veken Matthias , Wolfs Kris , Van Schepdael Ann , Adams Erwin
Published: June 2019

Reference introduction in thermal desorption with gas chromatography is a critical aspect. It is mostly performed by offline liquid calibration using a micro syringe to inject a liquid standard solution on the sorbent in the thermal desorption tube. This is based on the assumptions that the adsorption‐desorption process is quantitative and that no sample is lost in manipulating the tube. However, for analytical procedures involving thermal extraction of solid matrices, the adsorption‐desorption processes for sample and reference differ and the assumptions are not always fulfilled. This is explored in this work. First, issues related to the online liquid calibration were investigated. With tubes containing only quartz filters, a relative loss of over 80% was noticed for some solvents due to tube manipulation processes. Enclosing a bed of mesoporous silica as sorbent limited the losses to about 25% when samples were immediately analysed, and even better results were obtained when tubes were stored for several hours so that proper adsorption could take place. An additional sweep gas during loading boosted the transfer of analytes with recoveries above 95%. Next, an inline injection system was installed on the thermal desorber instrument. This sorbent free, independent calibration tool avoids the drawbacks of other approaches.
Separation and identification of process‐related substances and degradation products in mycophenolate mofetil by liquid chromatography coupled with quadrupole‐time of flight mass spectrometry
Authors: Lu Yu‐ting , Qi Wen‐zhu , Chen Yan‐fei , Song Min , Hang Tai‐jun
Published: June 2019

Mycophenolate mofetil is an antiproliferative immunosuppressive agent. Since its clinical efficacy and safety highly depend on the quality, the stability, and impurity profiles of mycophenolate mofetil are paid ever‐increasing attention. However, there are few published studies reporting the complete characterization of both the process‐related substances and degradation products in mycophenolate mofetil. In the present study, a highly specific and efficient liquid chromatography coupled with quadrupole‐time of flight mass spectrometry method was developed for the separation and identification of all the potential impurities in mycophenolate mofetil. According to the ICH Q1A (R2) guideline, the forced degradation studies were conducted to elucidate the stability and degradation pathways of mycophenolate mofetil. A total of 15 related substances, including the process‐related substances and stress degradation products were characterized by the established hyphenated method, 11 of them have not been reported before. In view of the synthetic route and degradation pathways of mycophenolate mofetil, the origins and formation mechanisms of these related substances were discussed. Based on the obtained stability and impurity profiles, key points of the manufacturing process were proposed to deliver mycophenolate mofetil with high purity.
Initial experience of fecal microbiota transplantation in gastrointestinal disease: A case series
Authors: Wang Jiunn‐Wei , Wang Yao‐Kuang , Zhang Faming , Su Yu‐Chung , Wang Jaw‐Yuan , Wu Deng‐Chyang , Hsu Wen‐Hung
Published: June 2019

Current studies have proven the strong association between gut microbiota dysbiosis and the pathogenesis of gastrointestinal diseases. Fecal microbiota transplantation (FMT) from a healthy donor is a promising therapeutic strategy to change and restore composition of the recipient's gut microbiota. Rapidly increasing clinical literatures confirmed the truth of the benefits of FMT on recurrent Clostridium difficile infection (rCDI) and inflammatory bowel disease. This article retrospectively reviewed nine cases (four cases had ulcerative colitis [UC], five cases had rCDI) who received FMT in Kaohsiung Medical University Hospital from April 2016 to November 2018. We summarized the procedure including donor selection, fecal materials preparation, transplantation delivery methods, and clinical outcomes. All of the four UC cases got clinical improvement and four rCDI cases achieved clinical remission after FMT. The other one rCDI case remained positive stool Toxin A+B result after FMT, and got remission after salvage treatment with fidaxomicin. FMT is considered to be a well‐tolerated adjuvant treatment for UC and effective salvage treatment for rCDI in our initial experience. Multiple infusions of FMT in UC and rCDI might have exceptional clinical efficiency, and enteral tube insertion could be a useful method to reach this goal and make multiple sessions of FMT easier.
Ubiquitin‐specific protease 44 inhibits cell growth by suppressing AKT signaling in non‐small cell lung cancer
Authors: Zhang Yun‐Kui , Tian Wen‐Ze , Zhang Rong‐Sheng , Zhang Yu‐Jie , Ma Hai‐Tao
Published: June 2019

Ubiquitin‐specific protease 44 (USP44) has been reported as a tumor suppressor or promoter in some tumors, but its function in non‐small cell lung cancer (NSCLC) is still unclear. In this study, USP44 was found significantly downregulated in both of NSCLC tissues and cell lines, and low expression of USP44 predicted a poor prognosis for NSCLC patients. Overexpression of USP44 markedly downregulated the expression levels of Cyclin D1 and CDK4, but upregulated p53 expression, as a result of which, suppressing the cell growth of NSCLC cells. Further studies indicated that overexpression of USP44 significantly inhibited the phosphorylation of AKT, and its down‐stream signals, including mTOR and P70S6K. Moreover, overexpression of USP44 increased PTEN protein but not its mRNA levels, which suggested that USP44 inhibited AKT signaling by stabilizing PTEN in NSCLC cells. In conclusion, we demonstrated that USP44 showed prior evidence of a tumor suppressive function in NSCLC cells, and inhibited NSCLC cell growth by suppressing AKT signaling, suggesting that USP44 could be as a novel target for NSCLC therapy.
A layer potential analysis for transmission problems for Brinkman‐type systems in Lipschitz domains in
Authors: Albişoru Andrei‐Florin
Published: June 2019

The aim of this paper is to establish a well‐posedness result for a boundary value problem of transmission‐type for the standard and generalized Brinkman systems in two Lipschitz domains in , the former being bounded, and the latter, its complement in . As a first step, we establish a well‐posedness result for a transmission problem for the standard Brinkman systems on complementary Lipschitz domains in by making use of the Potential theory developed for such a system. As a second step, we prove our desired result (in L2‐based Sobolev spaces) by using a method based on Fredholm operator theory and the well‐posedness result from the previous step.
Persistent symbiont colonization leads to a maturation of hemocyte response in the Euprymna scolopes/Vibrio fischeri symbiosis
Authors: Rader Bethany , McAnulty Sarah J. , Nyholm Spencer V.
Published: June 2019

The binary association between the squid, Euprymna scolopes, and its symbiont, Vibrio fischeri, serves as a model system to study interactions between beneficial bacteria and the innate immune system. Previous research demonstrated that binding of the squid's immune cells, hemocytes, to V. fischeri is altered if the symbiont is removed from the light organ, suggesting that host colonization alters hemocyte recognition of V. fischeri. To investigate the influence of symbiosis on immune maturation during development, we characterized hemocyte binding and phagocytosis of V. fischeri and nonsymbiotic Vibrio harveyi from symbiotic (sym) and aposymbiotic (apo) juveniles, and wild‐caught and laboratory‐raised sym and apo adults. Our results demonstrate that while light organ colonization by V. fischeri did not alter juvenile hemocyte response, these cells bound a similar number of V. fischeri and V. harveyi yet phagocytosed only V. harveyi. Our results also indicate that long‐term colonization altered the adult hemocyte response to V. fischeri but not V. harveyi. All hemocytes from adult squid, regardless of apo or sym state, both bound and phagocytosed a similar number of V. harveyi while hemocytes from both wild‐caught and sym‐raised adults bound significantly fewer V. fischeri, although more V. fischeri were phagocytosed by hemocytes from wild‐caught animals. In contrast, hemocytes from apo‐raised squid bound similar numbers of both V. fischeri and V. harveyi, although more V. harveyi cells were engulfed, suggesting that blood cells from apo‐raised adults behaved similarly to juvenile hosts. Taken together, these data suggest that persistent colonization by the light organ symbiont is required for hemocytes to differentially bind and phagocytose V. fischeri. The cellular immune system of E. scolopes likely possesses multiple mechanisms at different developmental stages to promote a specific and life‐long interaction with the symbiont.
Mutational Analysis of TYR, OCA2, and SLC45A2 Genes in Chinese Families with Oculocutaneous Albinism
Authors: Lin Ye , Chen Xihui , Yang Ying , Che Fengyu , Zhang Sijia , Yuan Lijuan , Wu Yuanming
Published: June 2019

Background

Oculocutaneous albinism (OCA) is a group of heterogeneous autosomal recessive genetic disorder of melanin synthesis results in hypopigmented hair, skin, and eyes. OCA type 1, OCA type 2, and OCA type 4, which are respectively caused by mutations in TYR, OCA2, and SLC45A2 have high morbidity rates in Asia.

Methods

TYR, OCA2, and SLC45A2 mutation analysis was carried out on 18 nonconsanguineous OCA patients and four fetuses were included for prenatal diagnose. Three genes of all individuals were amplified by polymerase chain reaction and examined by Sanger sequencing. The pathogenicity of the detected mutations were analyzed by Mutation Taster, PolyPhen 2, and SIFT software, and the conservation of the substituted amino acids were analyzed by MEGA software.

Results

Eleven TYR mutations, three OCA2 mutations, and two SLC45A2 mutations were identified in 14 OCA type 1 patients, two OCA type 2 patients, and two OCA type 4 patients. c.1021A>G, p.R341G in TYR, c.1096_1104del, p.V366*, and c.1079C>T, p.S360F in OCA2 were novel. One of the four fetuses carried compound heterozygous mutation of TYR and became spontaneous abortion, the other three carried no mutations and appeared normal at birth.

Conclusion

In this study, specific clinical characteristics of OCA patients were described. Three novel pathogenic mutations were identified which will enrich the mutation spectrum of OCA, and the prenatal genetic screening in fetus at risk of OCA can provide vital information for genetic counseling.
Association of a homozygous GCK missense mutation with mild diabetes
Authors: Marucci Antonella , Biagini Tommaso , Di Paola Rosa , Menzaghi Claudia , Fini Grazia , Castellana Stefano , Cardinale Giuliana Marcella , Mazza Tommaso , Trischitta Vincenzo
Published: June 2019

Background

Homozygous inactivating GCK mutations have been repeatedly reported to cause severe hyperglycemia, presenting as permanent neonatal diabetes mellitus (PNDM). Conversely, only two cases of GCK homozygous mutations causing mild hyperglycemia have been so far described. We here report a novel GCK mutation (c.1116G>C, p.E372D), in a family with one homozygous member showing mild hyperglycemia.

Methods

GCK mutational screening was carried out by Sanger sequencing. Computational analyses to investigate pathogenicity and molecular dynamics (MD) were performed for GCK‐E372D and for previously described homozygous mutations associated with mild (n = 2) or severe (n = 1) hyperglycemia, used as references.

Results

Of four mildly hyperglycemic family‐members, three were heterozygous and one, diagnosed in the adulthood, was homozygous for GCK‐E372D. Two nondiabetic family members carried no mutations. Fasting glucose (p = 0.016) and HbA1c (p = 0.035) correlated with the number of mutated alleles (0–2).

In‐silico predicted pathogenicity was not correlated with the four mutations’ severity. At MD, GCK‐E372D conferred protein structure flexibility intermediate between mild and severe GCK mutations.

Conclusions

We present the third case of homozygous GCK mutations associated with mild hyperglycemia, rather than PNDM. Our in‐silico analyses support previous evidences suggesting that protein stability plays a role in determining clinical severity of GCK mutations.
Pathogenic missense mutation pattern of forkhead box genes in neurodevelopmental disorders
Authors: Han Lin , Chen Meilin , Wang Yazhe , Wu Huidan , Quan Yingting , Bai Ting , Li Kuokuo , Duan Guiqin , Gao Yan , Hu Zhengmao , Xia Kun , Guo Hui
Published: June 2019

Background

Forkhead box (FOX) proteins are a family of transcription factors. Mutations of three FOX genes, including FOXP1, FOXP2, and FOXG1, have been reported in neurodevelopmental disorders (NDDs). However, due to the lack of site‐specific statistical significance, the pathogenicity of missense mutations of these genes is difficult to determine.

Methods

DNA and RNA were extracted from peripheral blood lymphocytes. The mutation was detected by single‐molecule molecular inversion probe‐based targeted sequencing, and the variant was validated by Sanger sequencing. Real‐time quantitative PCR and western blot were performed to assay the expression of the mRNA and protein. To assess the pattern of disorder‐related missense mutations of NDD‐related FOX genes, we manually curated de novo and inherited missense or inframeshift variants within FOXP1, FOXP2, and FOXG1 that co‐segregated with phenotypes in NDDs. All variants were annotated by ANNOVAR.

Results

We detected a novel de novo missense mutation (NM_001244815: c.G1444A, p.E482K) of FOXP1 in a patient with intellectual disability and severe speech delay. Real‐time PCR and western blot revealed a dramatic reduction of mRNA and protein expression in patient‐derived lymphocytes, indicating a loss‐of‐function mechanism. We observed that the majority of the de novo or transmitted missense variants were located in the FOX domains, and 95% were classified as pathogenic mutations. However, 10 variants were located outside of the FOX domain and were classified as likely pathogenic or variants of uncertain significance.

Conclusion

Our study shows the pathogenicity of missense and inframeshift variants of NDD‐related FOX genes, which is important for clinical diagnosis and genetic counseling. Functional analysis is needed to determine the pathogenicity of the variants with uncertain clinical significance.
Efficient decoupling technique applied to the numerical time integration of advanced interaction models for railway dynamics
Authors: Giner‐Navarro Juan , Martínez‐Casas José , Denia Francisco D. , Baeza Luis
Published: June 2019

Railway interaction is characterised by the coupling between the train and the track introduced through the wheel/rail contact. The introduction of the flexibility in the wheelset and the track through the finite element (FE) method in the last four decades has permitted to study high‐frequency phenomena such as rolling noise and squeal, whose origin lies in the strongly non‐steady state and non‐linear behaviour of the contact forces that arise from the small contact area. In order to address models with a large number of degrees of freedom, innovative Eulerian‐modal models for wheelsets with rotation and cyclic tracks have been developed in recent years. The aim of this paper is to extend the resulting formulation to an uncoupled linear matrix equation of motion that allows solving each equation independently for each time step, considerably reducing the associated computational cost. The decoupling integration method proposed is compared in terms of computational performance with Newmark and Runge‐Kutta schemes, commonly used in vehicle dynamics, for simulations with the leading wheelset negotiating a tangent track and accounting the rail roughness.
High‐efficiency cross and linear‐to‐circular polarization converters based on novel frequency selective surfaces
Authors: Wang Zhenglong , Ge Yuehe , Lin Chengxiu , Liu Kaiting , Pu Jixiong
Published: June 2019

Most high‐efficiency polarization converters in literatures are based on reflective structures. Here we report the designs and experiments of high‐efficiency transmissive polarization converters using novel compact frequency‐selective surfaces (FSSs). By combining the common dipole and square ring based band‐pass FSSs, a novel FSS can be generated, whose high‐efficiency pass bands and transmissive phases for two orthogonal polarizations can be tuned by changing the dimensions of the FSS structure. As demonstrations of the concept, a transmissive cross polarization converter (a half‐wave plate) and a transmissive linear‐to‐circular polarization (LP‐CP) converter (a quarter‐wave plate) are designed and tested, respectively. Simulated results show that the polarization conversion ratio over 90% for the transmissive cross‐polarization converter is from 18.5 to 23.5 GHz, about 23.8%, and the 3‐dB LP‐CP conversion bandwidth is 19.6%. Experiments are carried out to validate both designs.