bluuebunny/crossref_metadata_2025 huggingface dataset:
Ductal obstruction promotes formation of preneoplastic lesions from the pancreatic ductal compartment
Authors: Cheng Tao , Zhang Zhiheng , Jian Ziying , Raulefs Susanne , Schlitter Anna Melissa , Steiger Katja , Maeritz Nadja , Zhao Yamin , Shen Shanshan , Zou Xiaoping , Ceyhan Güralp O. , Friess Helmut , Kleeff Jörg , Michalski Christoph W. , Kong Bo
Published: November 2018

Pancreatitis is a significant risk factor for pancreatic ductal adenocarcinoma (PDAC). Previous studies in mice have demonstrated that pancreatitis contributes to oncogenic Kras‐driven carcinogenesis, probably initiated in acinar cells; however, oncogenic Kras alone or in combination with caerulein‐induced pancreatitis is not sufficient in initiating PDAC from the ductal compartment. We thus introduced ductal obstruction – which induces a more severe form of pancreatitis – by pancreatic ductal ligation in mice harbouring oncogenic Kras. This induced a particular phenotype with highly proliferative nonmucinous cells with nuclear atypia. Around these lesions, there was a significant proliferation of activated fibroblasts and infiltration of immune cells, corroborating the pathological features of preneoplastic lesions. Lineage‐tracing experiments revealed that these preneoplastic cells derived from two distinctive cellular sources: acinar and ductal cells. Phenotypic characterisation revealed that the duct‐derived preneoplastic lesions show a high proliferative potential with persistent activation of tumour‐promoting inflammatory pathways while the acinar‐derived ones were less proliferative with persistent p53 activation. Furthermore, the duct‐derived preneoplastic cells have a particularly high nuclear‐to‐cytoplasmic ratio. These data demonstrate that ductal obstruction promotes preneoplastic lesion formation from the pancreatic ductal compartment.
Usefulness of repeat pelvic ultrasonography before surgery for benign ovarian mass
Authors: Lee Dong‐Yun , Kim Hyo‐Jeong , Lee Jee‐Yeon , Choi DooSeok
Published: November 2018

Objective

To evaluate the results of repeat pelvic ultrasonography before surgery in patients with suspicion of benign ovarian tumor.

Methods

A retrospective study included premenopausal women who were scheduled to undergo surgery for a benign‐appearing ovarian mass and who had repeat ultrasonography on the day before surgery at Samsung Medical Center, Seoul, South Korea, between January 1, 2007, and December 31, 2011, to check for any change in the mass. Ultrasonography findings and final histology were evaluated by medical record review.

Results

Of 1854 women studied, regression of mass was detected before surgery for 27 patients, and 105 patients had histologically proven functional cysts; considered together, 132 patients had functional cysts, and the remaining 1722 women had benign ovarian tumors. Evaluation of the findings of initial ultrasonography revealed that mean size (P=0.008) and proportion of bilateral cysts (P<0.001) were lower in the presence of functional cysts than benign tumors. Additionally, an anechoic pattern was more common among regressed functional cysts than among histologically proven functional cysts (P<0.001). In total, 105 (5.7%) patients required surgery for a functional cyst despite repeat ultrasonography.

Conclusion

Repeating ultrasonography prior to surgery may have only a limited ability to prevent unnecessary surgeries for functional cysts.
Big Data: An incoming challenge for vehicular ad‐hoc networking
Authors: Bourdy Emilien , Piamrat Kandaraj , Herbin Michel
Published: November 2018

Big Data is gaining lots of attentions from various research communities as massive data are becoming real issues, and processing such data is now possible thanks to available high‐computation capacity of today's equipment. This paper focuses especially on the network community where currently huge amount of data have to be processed in real time. In the meanwhile, it is also the beginning of vehicular ad‐hoc networking (VANET) era. Connected vehicles are being manufactured and will become an important part of vehicle market. Topology in this type of network is in constant evolution, accompanied by massive data coming from increasing volume of connected vehicles in the network. Therefore, we will handle this interesting topic by providing backgrounds on Big Data concerning vehicular networks. Key aspects of Big Data related to VANET (eg, data generation, preprocessing, and communication) are discussed. Finally, we will also illustrate how to analyze data in VANET by presenting a real experimentation and some representatives results.
The Synthesis of 2‐Amino‐4‐(4‐imidazolyl)pyridines
Authors: LaMattina John L.
Published: November 2018

A general synthetic scheme for the preparation of 2‐amino‐4,(4‐imidazolyl)pyridines, potential histamine H2 antagonists, is described. The synthesis is based on the Neber rearrangement of l,(4‐pyridyl)l‐alkanone oxime 0‐tosylates to the appropriate α‐aminoketones or α‐aminoketals, which are then converted to the corresponding imidazoles. The reaction of Grignard reagents with 2‐chloroisonicotinonitrile, as well as nucleophilic displacement of chloride by amines on 2‐chloroisonicotinonitrile and derivatives, are discussed in relation to the preparation of the ketone intermediates.
Regioselective Synthesis of 1,6‐Dihydropyrrolo[2,3‐g]indazole Derivatives via Three‐Component Domino Reaction
Authors: Chen Dong‐Sheng , Li Li , Liu Jia‐Yan , Wei Ming , Chu Ruo‐Han , An Qiong , Zhang Ming
Published: November 2018

A series of 1,6‐dihydropyrrolo[2,3‐g]indazole derivatives have been obtained by a three‐component domino reaction of 1H‐indazol‐6‐amine, arylglyoxal monohydrates, and cyclic 1,3‐dicarbonyl compounds in ethanol medium at 60°C catalyzed by acetic acid. The notable features of this synthesis are excellent regioselectivity, operational simplicity, relative mild reaction conditions, and good yields.
Quality characteristics of pomegranate juice concentrates produced by ohmic heating assisted vacuum evaporation
Authors: Sabanci Serdal , Cevik Mutlu , Cokgezme Omer F , Yildiz Hasan , Icier Filiz
Published: November 2018

BACKGROUND

Vacuum evaporation (VE) process is widely utilized in fruit juice evaporation to preserve quality attributes of final product. However, it has some disadvantages such as possible degradation of aroma components or volatile fatty acids due to long process time, and low energy efficiency of process. Pomegranate juice having 17.5% total soluble solid (TSS) content was evaporated to 40% TSS by ohmic heating assisted vacuum evaporation (OVE; 7.5, 10 and 12.5 V cm−1) and VE in the present study. The effects of the evaporation methods on pH, titratable acidity and colour values, antioxidant activity (AA), total monomeric anthocyanin (TMA), total phenolic content (TPC), hydroxymethylfurfural (HMF) and invert sugar content of pomegranate juice concentrates were compared.

RESULTS

The colour properties, TMA, TPC and AA values of pomegranate juice concentrates evaporated by OVE were more influenced than those evaporated by VE. The degradation of sugars was minimized for OVE processes at high voltage gradients (10 and 12.5 V cm−1), and HMF content of pomegranate juice concentrated by OVE was lower than VE.

CONCLUSION

It is thought that electrochemical reactions occurred because of the use of titanium electrodes during the OVE process caused these quality changes in pomegranate juice concentrates having high acidity. Hence, it was concluded that the utilization of relatively more electrochemically inert electrodes should be investigated in further studies to better evaluate the of influence of OVE method on quality attributes of different fruit juices. © 2018 Society of Chemical Industry
Simultaneous determination of levofloxacin and ciprofloxacin in human urine by ionic‐liquid‐based, dual‐template molecularly imprinted coated graphene oxide monolithic solid‐phase extraction
Authors: Ma Wanwan , Row Kyung Ho
Published: November 2018

A novel method was developed to simultaneously determine the ciprofloxacin and levofloxacin levels in human urine using an ionic‐liquid‐based, dual‐molecularly imprinted polymer‐coated graphene oxide solid‐phase extraction monolithic column coupled with high‐performance liquid chromatography. The molecularly imprinted monolithic column was prepared using ciprofloxacin and levofloxacin as templates, 1‐vinyl‐3‐ethylimidazolium bromide as the functional monomer, and graphene oxide as the core material. The resulting imprinted monoliths were characterized by scanning electron microscopy and fourier transform‐infrared spectroscopy. The efficiency and capacity of the ionic‐liquid‐based imprinted monolithic column were investigated by varying the synthesis conditions (ciprofloxacin/levofloxacin ratio and template/functional monomer/cross‐linker ratio). The solid‐phase extraction process was optimized by changing the washing and eluting conditions. The results suggested that the proposed ionic‐liquid‐based molecularly imprinted solid‐phase extraction monolithic‐high‐performance liquid chromatography method could separate ciprofloxacin and levofloxacin efficiently and simultaneously from human urine. The mean recoveries of ciprofloxacin and levofloxacin ranged from 89.2 to 93.8 and 86.7 to 94.6%, respectively. The intra‐ and interday relative standard deviation ranged from 0.9 to 3.2 and 0.8 to 2.9%, respectively. Under the optimized conditions, the recoveries of ciprofloxacin and levofloxacin were more than 93.8%.
Advances in the development of molecularly imprinted polymers for the separation and analysis of proteins with liquid chromatography
Authors: Boysen Reinhard I.
Published: November 2018

This review documents recent advances in the design, synthesis, characterization, and application of molecularly imprinted polymers in the form of monoliths and particles/beads for the use in the separation and analysis of proteins with solid‐phase extraction or liquid chromatography. The merits of three‐dimensional molecular imprinting, whereby the molecular template is randomly embedded in the polymer, and two‐dimensional imprinting, in which the template is confined to the surface, are described. Target protein binding can be achieved by either using the entire protein as a template or by using a protein substructure as template, that is, a peptide, as in the "epitope" approach. The intended approach and strategy then determine the choice of polymerization method. A synopsis has been provided on methods used for the physical, chemical, and functional characterizations and associated performance evaluations of molecularly imprinted and nonimprinted control polymers, involving a diverse range of analytical techniques commonly used for low and high molecular mass analytes. Examples of recent applications demonstrate that, due to the versatility of imprinting methods, molecularly imprinted monoliths or particles/beads can be adapted to protein extraction/depletion and separation procedures relevant to, for example, protein biomarker detection and quantification in biomedical diagnostics and targeted proteomics.
Postoperative respiratory complications and racial disparities following inpatient pediatric tonsillectomy: A cross‐sectional study
Authors: Kou Yann‐Fuu , Sakai Mark , Shah Gopi B. , Mitchell Ron B. , Johnson Romaine F.
Published: November 2018

Objectives/Hypothesis

To study rates of respiratory complications/interventions among inpatient tonsillectomy patients in the United States and identify risk factors for these events.

Study Design

Retrospective database review.

Methods

Children (age < 18 years) undergoing tonsillectomy with or without adenoidectomy in 2006, 2009, and 2012 were studied using the Kids Inpatient Database, Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality. Outcomes were analyzed for respiratory events (complications/interventions) and racial disparities. Pearson χ test was used to analyze categorical data and regression analysis was used for continuous variables. Respiratory events were analyzed by racial identity using logistic regression analysis. A P < .05 was considered significant.

Results

The study included 30,617 patients (41% female, 51% white, 24% African American, 23% Hispanic, 3.0% Asian). The mean age was 5.2 years, and mean length of stay 2.3 days. The overall complication rate was 6.0%, and overall intervention rate was 3.6%. Respiratory events were more common among African American children (odds ratio [OR]: 1.5, 95% confidence interval [CI]: 1.3‐1.6) and less common among white children (OR: 0.8, 95% CI: 0.8‐0.9). These differences were significant after controlling for age, gender, obesity, obstructive sleep apnea, and asthma. The mortality rate was 0.05% with no ethnic predilection.

Conclusions

Respiratory events after inpatient tonsillectomy included laryngo/bronchospasm, pneumonia, pulmonary edema, intubation, prolonged intubation, and ventilation. Although uncommon, these were more common among African American children. Further research is needed to understand the etiology of this disparity.

Level of Evidence

NA Laryngoscope, 129:995–1000, 2019
Recent Progress in Polymeric Carbonyl‐Based Electrode Materials for Lithium and Sodium Ion Batteries
Authors: Amin Kamran , Mao Lijuan , Wei Zhixiang
Published: November 2018

Advancement in mobile electronics is driving progress in lithium ion batteries. Recently, organic electrode materials have emerged as promising candidates for lithium ion batteries due to their high theoretical capacity, ease of synthesis, versatility of structure, and abundance. Polymerization is a strategy used to overcome the issues associated with small organic molecules for charge storage application. The focus of this review is on the most recent progress in the field of polymeric carbonyl materials for lithium ion batteries (LIBs) and sodium ion batteries (SIBs). Advantages of organic electrode materials, device architecture, and charge storage mechanism are discussed. Challenges associated with carbonyl‐based electrodes and some recent solutions are outlined. Later, a comparison of theoretical capacity, practical capacity, and cyclic life are presented for different carbonyl systems. Capacity‐fading phenomena and structural degradation during charging are discussed where necessary. Some key parameters for the design of flexible batteries are highlighted and an overview of some recent contributions of our group in this field are reported. Finally, some future prospects for researchers in this field are outlined.
MicroRNA‐590‐3p inhibits trophoblast‐dependent maternal spiral artery remodeling by repressing low‐density lipoprotein receptor‐related protein 6
Authors: Zhang Yinghong , Pan Xianzhen , Yu Xiaoyan , Li Lei , Qu Hongmei , Li Shuhong
Published: November 2018

Background

The remodeling of maternal spiral artery following embryo implantation, which relies on well‐regulated trophoblast functions, is a pivotal process to ensure a successful pregnancy. Low‐density lipoprotein receptor‐related protein 6 (LRP6) and microRNAs (miRNAs, miRs) are suggested to be involved in angiogenesis and several vascular diseases; however, their functions in the control of trophoblast remain elusive. We therefore aimed to examine the roles of LRP6 and miR‐590‐3p in the regulation of trophoblast during the remodeling of maternal spiral artery.

Methods

HTR‐8/SVneo cell, a trophoblast cell line, was utilized to study the effects of LRP6 and miR‐590‐3p on apoptosis, cell proliferation, migration, invasion, as well as tube formation. Expression of angiogenic factors placental growth factor (PlGF), matrix metalloproteinases (MMPs), vascular endothelial growth factor (VEGF), and activities of canonical Wnt/β‐catenin signaling pathway, which were implicated in the process of artery remodeling, were also examined.

Results

MiR‐590‐3p directly targeted 3′ untranslated region (3′‐UTR) of LRP6 mRNA and repressed LRP6 expression, which in turn inhibited proliferation, migration, invasion, as well as tube formation, and resulted in apoptosis in HTR‐8/SVneo cells. Further, inhibition of LRP6 through miR‐590‐3p significantly suppressed the expression of PlGF, MMPs, and VEGF and reduced the activation of Wnt/β‐catenin signaling pathway.

Conclusion

MicroRNAs‐590‐3p may inhibit trophoblast‐dependent maternal spiral artery remodeling, via both trophoblast invasion and endovascular formation, by repressing LRP6.
Higher Chain Length Distribution in Debranched Type‐3 Resistant Starches (RS3) Increases TLR Signaling and Supports Dendritic Cell Cytokine Production
Authors: Lépine Alexia F.P. , de Hilster Roderick H. J. , Leemhuis Hans , Oudhuis Lizette , Buwalda Piet L. , de Vos Paul
Published: November 2018

Scope

Resistant starches (RSs) are classically considered to elicit health benefits through fermentation. However, it is recently shown that RSs can also support health by direct immune interactions. Therefore, it has been hypothesized that the structural traits of RSs might impact the health benefits associated with their consumption.

Methods and results

Effects of crystallinity, molecular weight, and chain length distribution of RSs are determined on immune Toll‐like receptors (TLRs), dendritic cells (DCs), and T‐cell cytokines production. To this end, four type‐3 RSs (RS3) are compared, namely Paselli WFR, JD150, debranched Etenia, and Amylose fraction V, which are extracted from potatoes and enzymatically modified. Dextrose equivalent seems to be the most important feature influencing immune signaling via activation of TLRs. TLR2 and TLR4 are most strongly stimulated. Especially Paselli WFR is a potent activator of multiple receptors. Moreover, the presence of amylose, even to residual levels, enhances DC and T‐cell cytokine responses. Paselli WFR and Amylose fraction V influence T‐cell polarization.

Conclusions

It has been shown here that chain length and particularly dextrose equivalent are critical features for immune activation. This knowledge might lead to tailoring and design of immune‐active RS formulations.
Effective attenuation of glyphosate‐induced oxidative stress and granulosa cell apoptosis by vitamins C and E in caprines
Authors: Bhardwaj Jitender Kumar , Mittal Meenu , Saraf Priyanka
Published: November 2018

Pesticides are known to cause a wide range of reproductive problems that possess degenerative effects on mammalian fertility. Glyphosate (GLP), a broad‐spectrum organophosphate herbicide, is known to be a potent mammalian toxicant. The present study aims at assessing the GLP‐induced (0.1, 2.0, and 4.0 mg/ml) granulosa cells toxicity and evaluating the mitigating effects of vitamins C and E (0.5 mM and 1.0 mM) in healthy caprine antral follicles, cultured in vitro in a dose‐ and time‐dependent manner (24, 48, and 72 hr) and subjected to various cytotoxic and geno‐toxic analysis, namely, classic histology, EB/AO differential staining, oxidative stress parameters, and antioxidant enzymatic activity. The histomorphological analysis and EB/AO staining elucidated increase in the incidence of apoptotic attributes within granulosa cells with increasing dose and duration of the GLP treatment. The highest apoptotic frequency was observed at 4.0 mg/ml GLP after 72‐hr exposure duration in comparison with the control. GLP exposure also led to a significant decline in the antioxidant enzymes’ activity, namely, SOD, catalase, and GST along with enhanced lipid peroxidation and reduced FRAP activity in a dose‐ and time‐dependent manner. Vitamins C and E supplementation decreased oxidative stress‐mediated granulosa cells apoptosis, suggesting its efficiency to diminish GLP‐mediated GCs cytotoxicity and thereby, preventing associated fertility disorders.
Novel SPEG mutations in congenital myopathies: Genotype–phenotype correlations
Authors: Qualls Anita E. , Donkervoort Sandra , Herkert Johanna C. , D'gama Alissa M. , Bharucha‐Goebel Diana , Collins James , Chao Katherine R. , Foley A. Reghan , Schoots Mirthe H. , Jongbloed Jan D.H. , Bönnemann Carsten G. , Agrawal Pankaj B.
Published: November 2018

Introduction: Centronuclear myopathies (CNMs) are a subtype of congenital myopathies (CMs) characterized by muscle weakness, predominant type 1 fibers, and increased central nuclei. SPEG (striated preferentially expressed protein kinase) mutations have recently been identified in 7 CM patients (6 with CNMs). We report 2 additional patients with SPEG mutations expanding the phenotype and evaluate genotype–phenotype correlations associated with SPEG mutations.

Methods: Using whole exome/genome sequencing in CM families, we identified novel recessive SPEG mutations in 2 patients.

Results: Patient 1, with severe muscle weakness requiring respiratory support, dilated cardiomyopathy, ophthalmoplegia, and findings of nonspecific CM on muscle biopsy carried a homozygous SPEG mutation (p.Val3062del). Patient 2, with milder muscle weakness, ophthalmoplegia, and CNM carried compound heterozygous mutations (p.Leu728Argfs*82) and (p.Val2997Glyfs*52).

Conclusions: The 2 patients add insight into genotype–phenotype correlations of SPEG‐associated CMs. Clinicians should consider evaluating a CM patient for SPEG mutations even in the absence of CNM features. Muscle Nerve 59:357–362, 2019
Caffeine improves bladder function in streptozotocin‐induced diabetic rats
Authors: Liu Ya‐Dong , Zhang Si‐Cong , Xue Jun , Wei Zhong‐Qing , Shen Bai‐Xin , Ding Liu‐Cheng
Published: November 2018

Aims

To examine the protective effects of caffeine in rats with diabetes mellitus (DM) by using urodynamics.

Methods

Female Sprague‐Dawley rats (n = 24) were divided into four groups: control group, DM group, DM + caffeine (5 mg/kg/day), and DM + caffeine (10 mg/kg/day). DM was induced by streptozotocin (STZ). Cystometric studies were conducted on all rats. After 8 weeks of treatment with caffeine, the urodynamic parameters, including bladder capacity, residual urine volume, voiding time, and peak voiding pressure, were measured.

Results

DM rats had a higher bladder capacity and post‐void residual urine volume (PVR), an increased voiding time and peak voiding pressure, and a markedly lower voiding efficiency than the control group rats. After treatment with caffeine, bladder capacity, post‐void residual urine volume, and peak voiding pressure were significant lower than those in the DM group, but voiding efficiency was markedly higher.

Conclusion

The results suggested that caffeine (5 or 10 mg/kg/day) may improve the bladder function at 8 weeks after STZ induction. Thus, this may represent a potential strategy to increase voiding efficiency in diabetes.
Multimaterial topology design for optimal elastic and thermal response with material‐specific temperature constraints
Authors: Kang Ziliang , James Kai A.
Published: November 2018

We present an original method for multimaterial topology optimization with elastic and thermal response considerations. The material distribution is represented parametrically using a formulation in which finite element–style shape functions are used to determine the local material properties within each finite element. We optimize a multifunctional structure that is designed for a combination of structural stiffness and thermal insulation. We conduct parallel uncoupled finite element analyses to simulate the elastic and thermal response of the structure by solving the two‐dimensional Poisson problem. We explore multiple optimization problem formulations, including structural design for minimum compliance subject to local temperature constraints so that the optimized design serves as both a support structure and a thermal insulator. We also derive and implement an original multimaterial aggregation function that allows the designer to simultaneously enforce separate maximum temperature thresholds based upon the melting point of the various design materials. The nonlinear programming problem is solved using gradient‐based optimization with adjoint sensitivity analysis. We present results for a series of two‐dimensional example problems. The results demonstrate that the proposed algorithm consistently converges to feasible multimaterial designs with the desired elastic and thermal performance.
Understanding multi‐pill ingestion of prescription opioids: Prevalence, characteristics, and motivation
Authors: Ellis Matthew S. , Cicero Theodore J. , Dart Richard C. , Green Jody L.
Published: November 2018

Purpose

Oral use is the primary route of administration among non‐medical prescription opioid users. While progression to non‐oral routes and shifts to stronger opioids have been previously studied as ways to cope with tolerance, the prevalence and patterns of those who cope by increasing the number of pills/tablets ingested at one time (ie, multi‐pill use) has not been assessed.

Methods

A subset (N = 231) of treatment‐seeking opioid users from a national opioid surveillance system, participating in the Researchers and Participants Interacting Directly (RAPID) Program, completed an online survey centered on multi‐pill use.

Results

Over two‐thirds of non‐medical prescription opioid users had a history of multi‐pill use (67.7%), defined as ingesting four or more of the same pill, intact and at the same time. Among these (n = 154), the median maximum number of pills taken at one time was eight, with over 20% ingesting 11 or more pills in a single instance. Nearly half engaged in multi‐pill ingestion more than once a day in the past month (43.8%), with accessibility to lower dose pills being the primary motivator (85.4%). Hydrocodone immediate‐release (IR) compounds were by far the most frequently endorsed (90.3%), followed by oxycodone IR tablets with acetaminophen (76.0%) and oxycodone IR tablets containing no acetaminophen/ibuprofen (56.5%).

Conclusions

These results indicate that the ingestion of multiple opioid pills/tablets is extremely common among treatment‐seeking opioid users. This, and other forms of non‐medical oral use of prescription opioids, should be taken under consideration when developing prevention and intervention efforts targeting the opioid epidemic.
UFLC‐Derived CSF Extracellular Vesicle Origin and Proteome
Authors: Thompson Alexander G. , Gray Elizabeth , Mager Imre , Fischer Roman , Thézénas Marie‐Laëtitia , Charles Philip D , Talbot Kevin , El Andaloussi Samir , Kessler Benedikt M. , Wood Matthew , Turner Martin R.
Published: November 2018

Cerebrospinal fluid (CSF) extracellular vesicles (EVs) show promise as a source of neurological disease biomarkers, although their precise origin is poorly understood. Current extraction techniques produce disappointing yield and purity. This study describes the application of ultrafiltration LC (UFLC) to CSF‐EVs, compared with ultracentrifugation (UC), and explores CSF‐EV origin. EVs are extracted from human CSF by UC and UFLC and characterized using nanoparticle tracking analysis, electron microscopy, and immunoblotting. EV and CSF proteomes are analyzed by LC–MS/MS. UFLC‐isolated particles have size, morphology, and marker expression characteristic of EVs. UFLC provides greater EV yield (UFLC 7.90 × 108 ± SD 1.31 × 108 EVs mL–1 CSF, UC 1.06 × 108 ± 0.57 × 108 p < 0.001). UFLC enhances purity, proteomic depth (UFLC 622 ± 49, UC 298 ± 50, p = 0.001), and consistency of quantification (CV 17% vs 23%). EVs contain more intracellular proteins (Odds ratio [OR] 2.63 p < 0.001) and fewer plasma proteins than CSF (OR 0.60, p < 0.001). CSF and EV‐enriched proteomes show overrepresentation of brain‐specific proteins (EV OR 3.18, p < 0.001; CSF OR 3.37, p < 0.001). Overrepresentation of cerebral white matter (OR 1.99, p = 0.015) and choroid plexus proteins (OR 1.87, p<0.001) is observed in EVs. UFLC improves yield and purity of CSF‐EVs. The EV‐enriched proteome better reflects the intracellular and white matter proteome than whole CSF.
A conjugation polyimine vitrimer: Fabrication and performance
Authors: Zheng Hua , Liu Qi , Lei Xingfeng , Chen Yanhui , Zhang Baoliang , Zhang Qiuyu
Published: November 2018

Although polyimine vitrimers are a promising and invaluable class of self‐healing materials owing to their great maneuverability and fast exchange of crosslinks without catalysts, it remains a challenge to improve the mechanical properties and thermal stability of the material by simply designing their internal structures. Herein, we report a conjugation polyimine vitrimer, which was prepared by polycondensation of terephthaldehyde, m‐xylylene diamine and tris (2‐aminoethyl) amine as crosslinker. The incorporation of m‐xylylene diamine endows the materials with an expanded conjugation structure, which greatly improves its mechanical properties and thermal stabilities. On the other hand, m‐xylylene diamine is less toxic and irritant than the linear aliphatic ones usually used, which makes the reactions more environment‐friendly. Results show that these materials have excellent mechanical properties and thermal stability, perform good flexibilities after immersed in water and show very short relaxation times at elevated temperatures. In addition, especially, they exhibit good self‐healing efficiency under the condition of heat, water and amine solvents without the need for any catalyst. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 2531–2538
Feasibility Study for the MALDI‐MSI Analysis of Thyroid Fine Needle Aspiration Biopsies: Evaluating the Morphological and Proteomic Stability Over Time
Authors: Piga Isabella , Capitoli Giulia , Tettamanti Silvia , Denti Vanna , Smith Andrew , Chinello Clizia , Stella Martina , Leni Davide , Garancini Mattia , Galimberti Stefania , Magni Fulvio , Pagni Fabio
Published: November 2018

Purpose

MALDI–MS imaging (MALDI–MSI) is an emerging technology that enables the spatial distribution of biomolecules within tissue to be combined with the traditional morphological information familiar to clinicians. Thus, for diagnostic or prognostic purposes, along with predicting response to therapeutic treatment, it is important to properly collect and handle biological specimens in order to avoid degradation or the formation of artifacts in the morphological structure and proteomic profile.

Experimental design

In this work, the morphological and proteomic stability of thyroid fine needle aspiration biopsies in PreservCyt (up to 14 days) and CytoLyt (up to 7 days) solutions at 4 °C has been verified, by MALDI–MSI analysis. Moreover, a new measure has been introduced in order to assess the similarity of the obtained MALDI–MSI spectra, by equally taking into account the number of signals (fit and retrofit), and their intensities (Spearman's correlation and spectra overlap).

Results

Results show no degradation of the cellular morphology and a good stability of the samples up to 14 days in PreservCyt solution.

Conclusions and clinical relevance

Moreover, this protocol can be easily implemented in pathological units, allowing simple sample collection and shipment to be used not only for the proteomic MALDI–MSI analysis of thyroid FNABs but also for other biological liquid based specimens.
Identification of Proteomic Markers in Head and Neck Cancer Using MALDI–MS Imaging, LC–MS/MS, and Immunohistochemistry
Authors: Hoffmann Franziska , Umbreit Claudia , Krüger Thomas , Pelzel Daniela , Ernst Günther , Kniemeyer Olaf , Guntinas‐Lichius Orlando , Berndt Alexander , von Eggeling Ferdinand
Published: November 2018

Purpose

The heterogeneity of squamous cell carcinoma tissue greatly complicates diagnosis and individualized therapy. Therefore, characterizing the heterogeneity of tissue spatially and identifying appropriate biomarkers is crucial. MALDI–MS imaging (MSI) is capable of analyzing spatially resolved tissue biopsies on a molecular level.

Experimental design

MALDI–MSI is used on snap frozen and formalin‐fixed and paraffin‐embedded (FFPE) tissue samples from patients with head and neck cancer (HNC) to analyze m/z values localized in tumor and nontumor regions. Peptide identification is performed using LC–MS/MS and immunohistochemistry (IHC).

Results

In both FFPE and frozen tissue specimens, eight characteristic masses of the tumor's epithelial region are found. Using LC–MS/MS, the peaks are identified as vimentin, keratin type II, nucleolin, heat shock protein 90, prelamin‐A/C, junction plakoglobin, and PGAM1. Lastly, vimentin, nucleolin, and PGAM1 are verified with IHC.

Conclusions and Clinical Relevance

The combination of MALDI–MSI, LC‐MS/MS, and subsequent IHC furnishes a tool suitable for characterizing the molecular heterogeneity of tissue. It is also suited for use in identifying new representative biomarkers to enable a more individualized therapy.
Urotensin II receptor expression in prostate cancer patients: A new possible marker
Authors: Giulianelli Roberto , Nardoni Stefano , Falavolti Cristina , Mirabile Gabriella , Bellangino Mariangela , Tema Giorgia , Gentile Barbara Cristina , Albanesi Luca , Buscarini Maurizio , Tariciotti Paola , Lombardo Riccardo
Published: November 2018

Background

Urotensin II receptor has been poorly studied in prostate cancer. To evaluate the expression of urotensin II receptor (UII‐R) in patients undergoing radical prostatectomy.

Methods

Overall, we identified 140 patients treated with retropubic radical prostatectomy (RP) in one center. UII‐R was evaluated in prostate biopsies with immunohistochemical staining, resulting in a granular cytoplasmic positivity, through automated system using the kit Urotensin II Receptor Detection System provided by Pharmabullet srl. Immunostained slides were independently and blindly evaluated by ten uro‐pathologists. To evaluate UTII‐R expression three different parameters were considered: localization, granules dimensions and intensity of expression. A score from 0 to 3 was applied to each parameter to obtain a score from 0 to 9. Each parameter and the total score were evaluated as predictors of high grade disease on surgical pathology and of advanced stage disease. Accuracy of total score for the prediction of upgrading and upstaging was analyzed using receiver operator characteristics curve and decision curve analysis (DCA).

Results

On radical prostatectomy 92/140 (66%) presented high grade disease on surgical pathology. Patients with high grade disease presented an apical distribution of the receptor, larger granules and a more intense expression when compared to patients with low grade disease. A well they presented a higher total score. Subscores and total scores were found to be predictors of upgrading and upstaging. On ROC analysis total score presented an AUC of 0.72 and 0.70, respectively, for the prediction of upgrading and upstaging. On DCA total score showed a clinical benefit in the prediction of adverse pathological outcomes.

Conclusion

Urotensin II receptor is a potential marker of adverse pathological outcomes. Further studies should confirm our data and evaluate its role as a prognostic marker.
An emerging novel virus: Atypical porcine pestivirus (APPV)
Authors: Pan Shuonan , Mou Chunxiao , Chen Zhenhai
Published: November 2018

Emerging porcine pestivirus diseases frequently challenge prevention and control strategies in the swine industry. Over the past decade, a few novel pestiviruses have been identified in pigs. This article focuses on the recently emerging atypical porcine pestivirus (APPV) that potentially threatens global swine herd health security. The virus was first identified in 2016, in the United States and thereafter, accumulated evidence shows that it is currently distributed in three continents. The clinical presentation of APPV‐infected pigs is characterized by congenital tremor (CT) type A‐II in piglets, while adult pigs may become persistent carriers and shedders. Here, a literature review is conducted to summarize the published findings in the virus genomic biology, transmission, epidemiology, pathogenesis, and diagnosis, which would shed light on acceleration of development of anti‐APPV strategies.
Penalized variable selection for accelerated failure time models with random effects
Authors: Park Eunyoung , Ha Il Do
Published: November 2018

Accelerated failure time (AFT) models allowing for random effects are linear mixed models under the log‐transformation of survival time with censoring and describe dependence in correlated survival data. It is well known that the AFT models are useful alternatives to frailty models. To the best of our knowledge, however, there is no literature on variable selection methods for such AFT models. In this paper, we propose a simple but unified variable‐selection procedure of fixed effects in the AFT random‐effect models using penalized h‐likelihood (HL). We consider four penalty functions (ie, least absolute shrinkage and selection operator (LASSO), adaptive LASSO, smoothly clipped absolute deviation (SCAD), and HL). We show that the proposed method can be easily implemented via a slight modification to existing h‐likelihood estimation procedures. We thus demonstrate that the proposed method can also be easily extended to AFT models with multilevel (or nested) structures. Simulation studies also show that the procedure using the adaptive LASSO, SCAD, or HL penalty performs well. In particular, we find via the simulation results that the variable selection method with HL penalty provides a higher probability of choosing the true model than other three methods. The usefulness of the new method is illustrated using two actual datasets from multicenter clinical trials.
Statistical modeling and prediction of clinical trial recruitment
Authors: Lan Yu , Tang Gong , Heitjan Daniel F.
Published: November 2018

Real‐time prediction of clinical trial accrual can support logistical planning, ensuring that studies meet but do not exceed sample size targets. We describe a novel, simulation‐based prediction method that is founded on a realistic model for the underlying processes of recruitment. The model reflects key features of enrollment such as the staggered initiation of new centers, heterogeneity in enrollment capacity, and declining accrual within centers. The model's first stage assumes that centers join the trial (ie, initiate accrual) according to an inhomogeneous Poisson process in discrete time. The second part assumes that each center's enrollment pattern reflects an early plateau followed by a slow decline, with a burst at the end of the trial following the announcement of an imminent closing date. By summing up achieved and projected enrollment, one can predict accrual as a function of time and, thereby, the time when the trial will achieve a planned enrollment target. We applied our method retrospectively to two real‐world trials: NSABP B‐38 and REMATCH (Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure). In both studies, the proposed method produced prediction intervals for time to completion that were more accurate than those from conventional predictions that assume a constant rate of enrollment, estimated either from the entire trial to date or over a recent time window. The advantage is substantial in the early stages of NSABP B‐38. We conclude that a method based on a realistic accrual model offers improved accuracy in the prediction of enrollment landmarks, especially at the early stages of large trials that involve many centers.
Low‐Temperature and Large‐Scale Synthesis of Carbon Nanofiber Web via Electrospinning and Their Efficient Removal of Cr(VI) Ions
Authors: Pan Xinying , Nan Hui , Yang Pan , Yang Lijun , Wang Gang , Chen Huiyuan , Lin Hong , Zhao Xiaochong
Published: November 2018

The carbon nanofiber web (CNW) has been synthesized by electrospinning of polyacrylonitrile (PAN) and polyvinylpyrrolidone (PVP) co‐polymer precursor solution and a following rather low‐temperature (450 oC) thermal treatment. The effect of PAN to PVP ratios on morphology and structure of nanofibers were investigated. Furthermore, the CNW with the fixed composition (PAN:PVP=5:5) were hydroxylated by NaOH solution (obtained CNW‐03‐OH). The CNW‐03‐OH were evaluated for their adsorption performance with Cr(VI) ions. Effects of the initial pH, contact time and temperature for Cr(VI) adsorption were investigated. Results show that the CNW‐03‐OH has an efficient adsorption capacity of 56.9 mg/g for Cr(VI) ions. Moreover, the adsorption capacity remained up to 55% after five cycles, indicating that the CNW‐03‐OH has a promising in practice for application in Cr(VI) ions adsorption.
Single-Cell Transcriptomics of Human Mesenchymal Stem Cells Reveal Age-Related Cellular Subpopulation Depletion and Impaired Regenerative Function
Authors: Khong Sacha M. L. , Lee Ming , Kosaric Nina , Khong Danika M. , Dong Yixiao , Hopfner Ursula , Aitzetmüller Matthias M. , Duscher Dominik , Schäfer Richard , Gurtner Geoffrey C.
Published: November 2018

Although bone marrow-derived mesenchymal stem cells (BM-MSCs) are widely recognized as promising therapeutic agents, the age-related impacts on cellular function remain largely uncharacterized. In this study, we found that BM-MSCs from young donors healed wounds in a xenograft model faster compared with their aged counterparts (p < .001). Given this significant healing advantage, we then used single-cell transcriptomic analysis to provide potential molecular insights into these observations. We found that the young cells contained a higher proportion of cells characterized by a higher expression of genes involved in tissue regeneration. In addition, we identified a unique, quiescent subpopulation that was exclusively present in young donor cells. Together, these findings may explain a novel mechanism for the enhanced healing capacity of young stem cells and may have implications for autologous cell therapy in the extremes of age. Stem Cells  2019;37:240–246
The O‐Directed Free Radical Hydrostannation of Propargyloxy Dialkyl Acetylenes with Ph3SnH/cat. Et3B. A Refutal of the Stannylvinyl Cation Mechanism
Authors: Hale Karl J. , Manaviazar Soraya , Watson Hamish A.
Published: November 2018

In this Personal Account, we will give an overview of the room temperature O‐directed free radical hydrostannation reaction of propargylically‐oxygenated dialkyl acetylenes with Ph3SnH and catalytic Et3B/O2in PhMe. We will show how this excellent reaction evolved, and how it has since been used to stereoselectively construct the complex trisubstituted olefin regions of three synthetically challenging natural product targets: (+)‐pumiliotoxin B, (−)‐(3R)‐inthomycin C, and (+)‐acutiphycin. Throughout this Account, we will pay special attention to highlighting important facets of the I−SnPh3exchange processes that have so far been used in the various different steric settings that we have addressed, and we will document the range of cross coupling protocols that have critically underpinned the first successful applications of this method in complex natural product total synthesis. Last, but not least, we will comment on various aspects of the O‐directed free radical hydrostannation mechanism that have been published by ourselves, and others, and we will discuss all of the factors that can contribute to the observed stereo‐and regio‐chemical outcomes. We will also challenge and refute the recent non‐directed stannylvinyl cation mechanism put forward by Organ, Oderinde and Froese for our reaction, and we will show how it cannot be operating in these exclusively free radical hydrostannations.
Declawing the dinosaurs in the science classroom: Reducing Christian teachers’ anxiety and increasing their efficacy for teaching evolution
Authors: Hawley Patricia H. , Sinatra Gale M.
Published: November 2018

America's rank among the lowest of developed countries in evolution acceptance rates is due, at least in part, to religious and political opposition. The negative correlations among religiosity, political ideology, and evolution acceptance in the United States have been documented repeatedly, and comfort with evolution varies by region with reception being especially cool in the south and southwest. Teachers are on the frontlines of the tensions between science and faith and often avoid the topic even if such avoidance violates state laws. Even non‐creationist teachers in regions with creationist norms are pressured to conform to regional curricula preferences. The present study describes the outcomes of a professional development workshop that explicitly considerers motivational and identity features of largely conservative, religious science teachers residing in West Texas. Our goal was to reduce the perceived conflict between faith and science such that Christian teachers would feel less negative and more positive about the theory and teaching it, and thus more efficacious in the classroom such that they would be more willing to teach according to the standards. In a retrospective pretest‐posttest design, teachers reported reductions in misconceptions and negative emotions in response to the workshop, and gains in positive emotions and self‐efficacy. Change scores were particularly marked for female teachers. Moreover, the relationships between community support for teaching evolution and teacher emotions and self‐efficacy were reduced post‐workshop indicating that teachers became independent from the norms of their schools. Though not the first intervention to support teacher instruction of evolution, the present workshop is the first to our knowledge that seeks to integrate biological content, cognitive change, and motivational/identity models.
Internet of Things and data mining: From applications to techniques and systems
Authors: Gaber Mohamed Medhat , Aneiba Adel , Basurra Shadi , Batty Oliver , Elmisery Ahmed M. , Kovalchuk Yevgeniya , Rehman Muhammad Habib Ur
Published: November 2018

The Internet of Things (IoT) is the result of the convergence of sensing, computing, and networking technologies, allowing devices of varying sizes and computational capabilities (things) to intercommunicate. This communication can be achieved locally enabling what is known as edge and fog computing, or through the well‐established Internet infrastructure, exploiting the computational resources in the cloud. The IoT paradigm enables a new breed of applications in various areas including health care, energy management and smart cities. This paper starts off with reviewing these applications and their potential benefits. Challenges facing the realization of such applications are then discussed. The sheer amount of data stemmed from devices forming the IoT requires new data mining systems and techniques that are discussed and categorized later in this paper. Finally, the paper is concluded with future research directions.

This article is categorized under:

Fundamental Concepts of Data and Knowledge > Big Data Mining

Application Areas > Health Care

Application Areas > Industry Specific Applications
Physical, chemical, and synthetic virology: Reprogramming viruses as controllable nanodevices
Authors: Chen Maria Yanqing , Butler Susan S. , Chen Weitong , Suh Junghae
Published: November 2018

The fields of physical, chemical, and synthetic virology work in partnership to reprogram viruses as controllable nanodevices. Physical virology provides the fundamental biophysical understanding of how virus capsids assemble, disassemble, display metastability, and assume various configurations. Chemical virology considers the virus capsid as a chemically addressable structure, providing chemical pathways to modify the capsid exterior, interior, and subunit interfaces. Synthetic virology takes an engineering approach, modifying the virus capsid through rational, combinatorial, and bioinformatics‐driven design strategies. Advances in these three subfields of virology aim to develop virus‐based materials and tools that can be applied to solve critical problems in biomedicine and biotechnology, including applications in gene therapy and drug delivery, diagnostics, and immunotherapy. Examples discussed include mammalian viruses, such as adeno‐associated virus (AAV), plant viruses, such as cowpea mosaic virus (CPMV), and bacterial viruses, such as Qβ bacteriophage. Importantly, research efforts in physical, chemical, and synthetic virology have further unraveled the design principles foundational to the form and function of viruses.

This article is categorized under:

Diagnostic Tools > Diagnostic Nanodevices

Biology‐Inspired Nanomaterials > Protein and Virus‐Based Structures