bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of 6‐Trifluoromethylphenanthridines through Radical Trifluoromethylation of Isocyanides with Sodium Triflinate under Visible Light
Authors: Li Jianbin , Caiuby Clarice A. D. , Paixão Márcio W. , Li Chao‐Jun
Published: December 2017

Trifluoromethylation enabled by photochemistry enriched the toolbox of synthetic chemists, to allow the simple and efficient installation of CF3 groups in organic molecules. Herein, we report a cascade addition/annulation reaction of 2‐isocyanobiphenyls towards the synthesis of 6‐trifluoromethylphenanthridines. It is proposed that this reaction is triggered by the CF3 radical generated from photoexcited 2,3‐butanedione (diacetyl) and sodium triflinate. In contrast to classical aromatic trifluoromethylations, this work does not require any additives and features formation of a C–CF3 bond with concomitant construction of an aromatic scaffold.
Multifunctional Antioxidants with High Activity at Elevated Temperatures Based on Intramolecular Synergism
Authors: Yu Shasha , Liu Shenggao
Published: December 2017

Multifunctional antioxidants with three active fragments were prepared through a simple two‐step synthesis process. These novel compounds exhibited higher efficiency when inhibiting the oxidation of hydrocarbons compared to commercial products at 180 °C. The rational framework gives rise to the unique intramolecular synergism between arylamine moiety and sulfide moiety that can scavenge radicals and decompose peroxides simultaneously.
Ion Transfer Voltammetry at Thin Films Based on Functionalized Cationic [6]Helicenes
Authors: Jarolímová Zdeňka , Bosson Johann , Labrador Geraldine M. , Lacour Jérôme , Bakker Eric
Published: December 2017

We describe a new family of molecular ion‐to‐electron redox probes based on cationic diaza, azaoxa, and dioxa [6]helicenes and their derivatives. Their unique structure combines, in a single framework, two privileged families of molecules – helicenes and triaryl methyl carbenium moieties. These cationic [6]helicenes exhibit reversible and reproducible oxidation/reduction behavior and facilitate the ion transfer into thin layer sensing films composed of bis(2‐ethylhexyl)sebacate (DOS), polyurethane (PU), sodium tetrakis 3.5‐bis(trifluoromethyl)phenyl borate, sodium ionophore X and diaza+(C8)2Br2 for cation transfer. Cyclic voltammetry is used to interrogate the thin films. The cationic response can be tuned by adjusting the membrane loading. Addition of lipophilic cation exchanger into the membrane film results in transfer waves of Gaussian shape for cations. A peak separation of 60 mV and peak width of 110 mV are near the theoretical values for a surface confined process. While Nernstian shifts of the peak potentials with analyte concentration is obtained for membranes based on cationic [6]helicenes and doped with sodium‐selective ionophore X, this ionophore was found to promote a gradual loss of redox active species from the ionophore‐based membranes into the sample solution.
Accounting for uncertainty in source‐specific exposures in the evaluation of health effects of pollution sources on daily cause‐specific mortality
Authors: Park Eun Sug , Oh Man‐Suk
Published: December 2017

Assessment of source‐specific health effects has received growing attention in air pollution epidemiology over the past decade. Regardless of inherent uncertainty in the assessment of source‐specific exposures, only a handful of previous studies coped with model uncertainty in source apportionment and/or accounted for exposure measurement error in the estimation of health effects, all under normal health outcome models. We present a source‐specific health effects evaluation approach within a Bayesian framework that can handle both parameter uncertainty and model uncertainty in source apportionment under Poisson health outcome models for low daily mortality count data. While the use of a Poisson health outcome model is apparently more appropriate for low daily mortality count data for which normal approximation is not justified, it introduces additional complexity in estimating model uncertainty. We handle this complexity by introducing appropriate latent variables. The proposed method is illustrated with simulated data and daily ambient concentrations of the chemical composition of fine particulate matter (PM2.5), weather data, and counts of deaths from pneumonia in older adults (≥65 years of age) in Houston, Texas, from January 2002 to August 2005.
Investing in Student Success: Examining the Return on Investment for Minority‐Serving Institutions
Authors: Gasman Marybeth , Samayoa Andrés Castro , Nettles Michael
Published: December 2017

Although minority‐serving institutions (MSIs) educate nearly one fifth of the nation's college students, there is to date little research on MSI's return on investment (ROI). To address this, the University of Pennsylvania and Educational Testing Service commissioned four papers focusing on the ROI for MSIs, which were presented originally in December 2015 at the National Convening on Return on Investment for Minority Serving Institutions. This report contains the four papers presented at the seminar, as well as an introduction.
Network Analysis of Conversation Data for Engineering Professional Skills Assessment
Authors: Zhu Mengxiao , Zhang Mo
Published: December 2017

In this paper, we examine the student group discussion processes in a scenario‐based assessment of engineering professional skills called Engineering Professional Skills Assessment (EPSA). In the assessment, the students were evaluated through a discussion on a scenario related to an engineering problem with no clear‐cut solution. We applied various social network analysis (SNA) techniques and constructed 2 types of networks to model the patterns of the communication process in the student discussion and the connections among engineering professional skills (EPS) during the discussion process. We found that some network statistics were statistically related to team scores (or performance), such as the density of the EPS networks. We also investigated the temporal pattern of the discussion process by comparing the network statistics across 3 different time points. Results showed that the middle and end of the discussion processes differed significantly on 2 network measures: communication density and EPS connectedness. Results of the study have implications for instruction and scoring of such performance tasks. Limitations and next steps are also discussed.
Microfoundations of firm internationalization: The owner CEO effect
Authors: Chittoor Raveendra , Aulakh Preet S. , Ray Sougata
Published: December 2017

Research Summary

In this article, we examine the influence of owner CEOs’ motivations and authority on strategic risk‐taking behavior of firms as reflected by their investments in foreign markets. We theorize that owner CEOs, aided by their strategic leadership, long‐term orientation, and less‐restricted decision‐making powers, will facilitate their firms’ strategic decisions that are exploratory in nature and, thus, are more risky. We further propose that the owner CEO effect is likely to differentially interact with performance aspirations and governance structures of firms in influencing internationalization. We test our predictions on a longitudinal panel dataset of 226 Indian manufacturing firms over the 10‐year period from 2002 to 2011 and find support for our hypotheses. We contribute to the emerging literature on microfoundations and behavioral strategy.

Managerial Summary

Given that a large number of firms around the world are characterized by concentrated ownership and owners who also assume CEO roles, we explore the influence of owner CEOs on firms’ strategic risk‐taking behavior. We propose that firms with owner CEOs, particularly founder owner CEOs, are likely to exhibit a higher degree of internationalization as compared to firms with professional CEOs. Further, we propose that the positive owner CEO effect is stronger when the firm performance is above its aspirations and also in stand‐alone firms when compared to firms affiliated to business groups. We test our predictions using a sample of 226 Indian manufacturing firms over the 10‐year period from 2002 to 2011 and find support for our predictions.
Dendritic cell targeted HIV‐1 gag protein vaccine provides help to a recombinant Newcastle disease virus vectored vaccine including mobilization of protective CD8+ T cells
Authors: Ngu Loveline N. , Nji Nadesh N. , Ambada Georgia , Ngoh Apeh A. , Njambe Priso Ghislain D. , Tchadji Jules C. , Lissom Abel , Magagoum Suzanne H. , Sake Carol N. , Tchouangueu Thibau F. , Chukwuma George O. , Okoli Arinze S. , Sagnia Bertrand , Chukwuanukwu Rebecca , Tebit Denis M. , Esimone Charles O. , Waffo Alain B. , Park Chae G. , Überla Klaus , Nchinda Godwin W.
Published: December 2017

Introduction

Recombinant Newcastle Disease virus (rNDV) vectored vaccines are safe mucosal applicable vaccines with intrinsic immune‐modulatory properties for the induction of efficient immunity. Like all viral vectored vaccines repeated inoculation via mucosal routes invariably results to immunity against viral vaccine vectors. To obviate immunity against viral vaccine vectors and improve the ability of rNDV vectored vaccines in inducing T cell immunity in murine air way we have directed dendritic cell targeted HIV‐1 gag protein (DEC‐Gag) vaccine; for the induction of helper CD4+ T cells to a Recombinant Newcastle disease virus expressing codon optimized HIV‐1 Gag P55 (rNDV‐L‐Gag) vaccine.

Methods

We do so through successive administration of anti‐DEC205‐gagP24 protein plus polyICLC (DEC‐Gag) vaccine and rNDV‐L‐Gag. First strong gag specific helper CD4+ T cells are induced in mice by selected targeting of anti‐DEC205‐gagP24 protein vaccine to dendritic cells (DC) in situ together with polyICLC as adjuvant. This targeting helped T cell immunity develop to a subsequent rNDV‐L‐Gag vaccine and improved both systemic and mucosal gag specific immunity.

Results

This sequential DEC‐Gag vaccine prime followed by an rNDV‐L‐gag boost results to improved viral vectored immunization in murine airway, including mobilization of protective CD8+ T cells to a pathogenic virus infection site.

Conclusion

Thus, complementary prime boost vaccination, in which prime and boost favor distinct types of T cell immunity, improves viral vectored immunization, including mobilization of protective CD8+T cells to a pathogenic virus infection site such as the murine airway.
Prevention of the development of problem behavior: A laboratory model
Authors: Fahmie Tara A. , Macaskill Anne C. , Kazemi Ellie , Elmer Uilani C.
Published: December 2017

Few studies have isolated the preventive efficacy of common behavioral strategies like noncontingent reinforcement (NCR) and differential reinforcement of alternative behavior (DRA). The purpose of the current study was to develop and evaluate a laboratory model of these two problem behavior prevention strategies. Undergraduate students participated in a computer simulation, in which clicks to a designated area of the computer screen were analogous to the emergence of problem behavior. The responding of participants in a control group, who experienced a percentile schedule used to mimic the shaping of problem behavior, was compared to that of participants in two experimental groups, each with a history of either DRA or NCR. Between‐subjects group comparisons showed that both intervention strategies were equally effective in the prevention of our analog to problem behavior when compared to the control group. The strengths and limitations of a laboratory model for prevention are discussed in light of recent applied work in this area.
LncRNA NEAT1 promotes dexamethasone resistance in multiple myeloma by targeting miR‐193a/MCL1 pathway
Authors: Wu Yilan , Wang Han
Published: December 2017

Although dexamethasone (DEX) remains a first‐line agent for multiple myeloma (MM) therapy, the development of DEX resistance has become an indicator of poor prognosis in MM patients. It is thus urgent to develop strategies to restore the vulnerability of MM to DEX. This study demonstrated long non‐coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) was highly expressed in DEX‐resistant myeloma cell lines, and upregulation of NEAT1 was tightly linked to poor prognosis. The in‐depth study revealed that during the development of DEX resistance in these cells, the miR‐193a levels were decreased, which resulted in the increased expression of the target gene myeloid cell leukemia‐1 (MCL1). We also found knockdown of NEAT1, the DEX‐induced sensitivity was enhanced in the resistant cells. Meanwhile, overexpression of NEAT1 increased the DEX‐induced resistance in the sensitive cells. In conclusion, the NEAT1/miR‐193a/MCL1 pathway is closely associated with the development of DEX resistance in myeloma cells, and knockdown of NEAT1 can significantly improve DEX sensitivity in MM.
Retracted: microRNA‐137 promotes endothelial progenitor cell proliferation and angiogenesis in cerebral ischemic stroke mice by targeting NR4A2 through the Notch pathway
Authors: Liu Xing‐Li , Wang Gang , Song Wei , Yang Wei‐Xin , Hua Jian , Lyu Liang
Published: December 2017

Cerebral ischemic stroke (CIS) is one of the common causes of death and disability worldwide. This study aims to investigate effect of miR‐137 on endothelial progenitor cells and angiogenesis in CIS by targeting NR4A2 via the Notch pathway. Brain tissues were extracted from CIS and normal mice. Immunohistochemistry was used to determine positive rate of NR4A2 expression. Serum VEGF, Ang, HGF, and IκBα levels were determined by ELISA. RT‐qPCR and Western blotting were used to determine expression of related factors. Endothelial progenitor cells in CIS mice were treated and grouped into blank, NC, miR‐137 mimic, miR‐137 inhibitor, siRNA‐NR4A2, and miR‐137 inhibitor + siRNA‐NR4A2 groups, and cells in normal mice into normal group. Proliferation and apoptosis were determined by MTT and flow cytometry, respectively. NR4A2 protein expression was strongly positive in CIS mice, which showed higher serum levels of VEGF, Ang, and HGF but lower IκBα than normal mice. Compared with normal group, the rest groups (endothelial progenitor cells from CIS mice) showed decreased expressions of miR‐137, Hes1, Hes5, and IκBα but elevated NR4A2, Notch, Jagged1, Hey‐2, VEGF, Ang, and HGF, inhibited proliferation and enhanced apoptosis. Compared with blank and NC groups, the miR‐137 mimic and siRNA‐NR4A2 groups exhibited increased expression of miR‐137, Hes1, Hes5, and IκBα, but decreased NR4A2, Notch, Jagged1, and Hey‐2, with enhanced proliferation and attenuated apoptosis. The miR‐137 inhibitor group reversed the conditions. miR‐137 enhances the endothelial progenitor cell proliferation and angiogenesis in CIS mice by targeting NR4A2 through the Notch signaling pathway.
Hormone regulates endometrial function via cooperation of endoplasmic reticulum stress and mTOR‐autophagy
Authors: Yang Diqi , Jiang Tingting , Liu Jianguo , Hong Jin , Lin Pengfei , Chen Huatao , Zhou Dong , Tang Keqiong , Wang Aihua , Jin Yaping
Published: December 2017

In ruminant, the receptive endometrium and the elongation of the hatched blastocyst are required to complete the process of implantation. However, the mechanisms regulating goat endometrial function during the peri‐implantation period of pregnancy are still unclear. In this study, EECs were treated with progesterone, estradiol, and interferon‐tau (IFNT). We have found that endoplasmic reticulum (ER) stress was activated under hormones treatment. To identify the cellular mechanism of regulation of endometrial function, we investigated the effect of ER stress activator thapsigargin (TG) and inhibitor 4 phenyl butyric acid (4‐PBA) on EECs. We found that TG, which activated the three branches of UPR, increased the expression of genes associated with promoting conceptus elongation and cellular attachment, significantly up‐regulated the spheroid attachment rate and PGE2/PGF2α ratio. 4‐PBA pre‐treatment inhibited UPR and inhibited promoting conceptus elongation and cellular attachment related genes, but the spheroid attachment rate and PGE2/PGF2α ratio were not changed significantly. Moreover, knockdown of ATF6 via shATF6 promoted the conceptus elongation related genes, but increased the dissolution of the corpus luteum. Besides, blocking ATF6 attenuated autophagy by activating mammalian target of rapamycin (mTOR) pathway. Moreover, rapamycin (mTOR inhibitor) pre‐treatment inhibited the expression of promoting conceptus elongation and increased PGE2/PGF2α ratio. Taken together, our study indicated that physiological level of ER stress may contribute to early pregnancy success, and ATF6 signaling pathway cooperated with autophagy to regulate endometrial function by modulating mTOR pathway.
Evaluation of RNA from human trabecular bone and identification of stable reference genes
Authors: Cepollaro Simona , Della Bella Elena , de Biase Dario , Visani Michela , Fini Milena
Published: December 2017

The isolation of good quality RNA from tissues is an essential prerequisite for gene expression analysis to study pathophysiological processes. This study evaluated the RNA isolated from human trabecular bone and defined a set of stable reference genes. After pulverization, RNA was extracted with a phenol/chloroform method and then purified using silica columns. The A260/280 ratio, A260/230 ratio, RIN, and ribosomal ratio were measured to evaluate RNA quality and integrity. Moreover, the expression of six candidates was analyzed by qPCR and different algorithms were applied to assess reference gene stability. A good purity and quality of RNA was achieved according to A260/280 and A260/230 ratios, and RIN values. TBP, YWHAZ, and PGK1 were the most stable reference genes that should be used for gene expression analysis. In summary, the method proposed is suitable for gene expression evaluation in human bone and a set of reliable reference genes has been identified.
Evaluation of 17% EDTA and 10% citric acid in smear layer removal and tubular dentin sealer penetration
Authors: Machado Ricardo , Garcia Lucas da Fonseca Roberti , da Silva Neto Ulisses Xavier , Cruz Filho Antônio de Miranda da , Silva Ricardo Gariba , Vansan Luiz Pascoal
Published: December 2017

The purpose of this study was to compare the efficacy of different chelating solutions (17% EDTA and 10% citric acid) on the smear layer removal, and their effect on tubular dentin sealer penetration. Sixty root canals were prepared and distributed into four groups (n = 15) according to the final irrigation protocol: G1, final irrigation with 2.5 mL of distilled water; G2, final irrigation with 2.5 mL of 2.5% sodium hypochlorite solution; G3, final irrigation with 2.5 mL of 17% EDTA; and G4, final irrigation with 2.5 mL of 10% citric acid. Five specimens from each group were not filled to assess smear layer removal by scanning electron microscopy. Ten specimens from each group were filled for analysis of sealer penetration into dentinal tubules by confocal laser scanning microscopy. Smear layer removal (Kruskal–Wallis and Dunn's tests) and sealer penetration (F and Tukey's tests) were statistically analyzed with 95% of significance level. G3 and G4 had greater smear layer removal rates in the cervical and middle thirds, in comparison with G1 and G2 (p < .05). G3 and G4 had the highest percentages of sealer penetration in all thirds, in comparison with G1 and G2 (p < .05). Smear layer removal was effective only at the cervical and middle thirds when the chelating solutions were used. Sealer penetration into the dentinal tubules significantly increased in all root thirds when the specimens were treated with both chelating solutions.
4‐Formyl‐Pyrazole‐3‐Carboxylate: A Useful Aldo‐X Bifunctional Precursor for the Syntheses of Pyrazole‐fused/Substituted Frameworks
Authors: Devi Nisha , Shankar Ravi , Singh Virender
Published: December 2017

Pyrazole, a privileged class of heterocyclic compounds, constitute an interesting template for medicinal chemistry and is represented by several commercial drugs like Sildenafil, Zometapin, Celebrex, and Rimonabant. The presence of two functionalities with different reactivity in pyrazole moiety may open new avenues for insertion of diversity in pyrazole frameworks which may be of high medicinal significance. Ethyl 4‐formyl‐1H‐pyrazole‐3‐carboxylate is a potential Aldo‐X bifunctional building block (AXB3) which may be explored for generating complex pyrazole based molecular frameworks by using various organic transformations. The present manuscript is assimilation of literature pertaining to the synthesis and application of ethyl 4‐formyl‐1H‐pyrazole‐3‐carboxylates and similar AXB3 for the development of pyrazole substituted and fused derivatives.
An Efficient Approach for the Synthesis of 1,1‐bis(2‐phenyl‐3‐indolyl)ethylene Using ZnO Nanocatalyst
Authors: Madan Yogita , Gupta Ragini
Published: December 2017

A combination of nanocatalyst and green chemical route (mechanochemistry) was used to generate a series of substituted 1,1‐bis(2‐phenyl‐3‐indolyl)ethylene derivatives (4a–e) that were synthesized by reacting various 2‐arylindoles (1a–e) and acetyl chloride in absolute alcohol with or without ZnO nano as catalyst via two approaches, that is, classical and green solvent‐free route. The use of ZnO nano particles is preferred to absence of catalyst in terms of short reaction time and mild reaction conditions with reusability of the catalyst. All the synthesized compounds were characterized on the basis of their elemental and spectral data (IR, proton magnetic resonance, 13C NMR, and Mass).
Synthesis of New Fused Thienopyrimidines Derivatives as Anti‐inflammatory Agents
Authors: Tolba Mahmoud S. , Ahmed Mostafa , Kamal El‐Dean Adel M. , Hassanien Reda , Farouk Mahmoud
Published: December 2017

5‐Amino‐2‐(p‐tolylamino)‐4‐phenylthieno[2,3‐d]pyrimidine‐6‐carbonitrile 9, which was synthesized by an innovative method, was used as a versatile precursor for synthesizing pyrimido‐thienopyrimidine, triazolopyrimidothienopyrimidine, and pyrimidothienotriazine compounds. Thus, reaction of aminothienopyrimidinecarbonitrile 9 with chloroacetylchloride in dioxane afforded the chloroacetylaminocarbonitrile derivative 10, which underwent nucleophilic substitution reactions with various primary and secondary amines gave the corresponding N‐alkyl‐(aryl)amino acetamides 11a,b. On the other hand, the reaction of aminocarbonitrile 9 with triethyl orthoformate followed by cyclization with hydrazine yielded an aminoiminopyrimidine derivative 13. The latter was used as versatile precursor for synthesis of new heterocyclic compounds. The structures of all the new compounds have been established on the basis of their analytical and spectral data (IR, 1H NMR, 13C NMR, and MS). Some of the synthesized compounds were evaluated in vitro for their anti‐inflammatory activity. All the tested compounds exhibited remarkable anti‐inflammatory activity.
4D flow MRI, cardiac function, and T1‐mapping: Association of valve‐mediated changes in aortic hemodynamics with left ventricular remodeling
Authors: Geiger Julia , Rahsepar Amir A. , Suwa Kenichiro , Powell Alex , Ghasemiesfe Ahmadreza , Barker Alex J. , Collins Jeremy D. , Carr James C. , Markl Michael
Published: December 2017

Background

Patients with bicuspid aortic valve (BAV) show altered hemodynamics in the ascending aorta that can be assessed by 4D flow MRI.

Purpose

Comprehensive cardiac MRI was applied to test the hypothesis that BAV‐mediated changes in aortic hemodynamics (wall shear stress [WSS] and velocity) are associated with parameters of left ventricular (LV) remodeling.

Study Type

Retrospective data analysis.

Population

Forty‐nine BAV patients (mean age = 50.2 ± 13.5, 62% male).

Field Strength/Sequence

Balanced steady‐state free precession (bSSFP)‐CINE, pre‐ and postcontrast T1 mapping with modified Look–Locker inversion recovery (MOLLI), time‐resolved 3D phase‐contrast (PC) MRI with three‐directional velocity encoding (4D flow MRI) at 1.5 and 3T.

Assessment

Quantification of LV volumetric data and myocardial mass, extracellular volume fraction (ECV), aortic valve stenosis (AS), and regurgitation (AR). 3D aortic segmentation, quantification of peak systolic velocities, and 3D WSS in the ascending aorta (AAo), arch, and descending aorta (DAo).

Statistical Tests

Two‐sided nonpaired t‐test to compare subgroups. Pearson correlation coefficient for correlations between aortic hemodynamics and LV parameters.

Results

Of the 49 BAV patients, 35 had aortic valve dysfunction (AS [n = 7], AR [n = 16], both AS and AR [n = 12]). Mean systolic WSS in the AAo, peak systolic velocities in the AAo and arch, and LV mass were significantly higher (P < 0.001) in the AS/AR group compared to the patients without AS/AR. In the complete group, we observed significant relationships between increased LV mass and elevated peak systolic velocity (r = 0.57, r = 0.58; P < 0.001) and WSS in the AAo and arch, respectively (r = 0.54, r = 0.46; P < 0.001). We detected an association between ECV and WSS in the AAo (r = 0.38, P = 0.02). These relations did not hold true for patients without AV dysfunction.

Data Conclusion

AS and AR in BAV patients have a major impact on elevated aortic peak velocities and WSS that were associated with parameters of LV remodeling.

Level of Evidence: 3

Technical Efficacy: Stage 3

J. Magn. Reson. Imaging 2017.
Climate‐related trends of actual evapotranspiration over the Tibetan Plateau (1961–2010)
Authors: Zhang Tangtang , Gebremichael Mekonnen , Meng Xianhong , Wen Jun , Iqbal Mudassar , Jia Dongyu , Yu Ye , Li Zhenchao
Published: December 2017

Actual evapotranspiration (ETa) is an important component of the hydrologic cycle. In this study, ETa on the Tibetan Plateau (TP) is calculated using the advection‐aridity model (AA model) with data from 86 meteorological stations during the period from 1961 to 2010. Results show that the mean annual ETa over the TP was 543 mm and range from 147 to 687 mm, with higher values in the southern part and lower values in the northern part of the TP. During 1961–2010, annual and seasonal mean ETa show statistically increasing trend at most all stations. Annual ETa in area‐averaged over the TP changed +1.01 mm year−1. Among the four seasons, the changes were most pronounced in March, April, May (MAM) and June, July, August (JJA). ETa variation is significantly and positively correlated with a drought index, defined as the difference between precipitation (P) and potential evapotranspiration (ETp), i.e. P − ETp, showing that the ETa increases over the TP tend to be affected by an increasing soil water supply associated with global warming, such as the retreat of permafrost, increase in P, and decline of ETp.
Preclinical models for orthopedic research and bone tissue engineering
Authors: Schindeler Aaron , Mills Rebecca J. , Bobyn Justin D. , Little David G.
Published: December 2017

In this review, we broadly define and discuss the preclinical rodent models that are used for orthopedics and bone tissue engineering. These range from implantation models typically used for biocompatibility testing and high‐throughput drug screening, through to fracture and critical defect models used to model bone healing and severe orthopedic injuries. As well as highlighting the key methods papers describing these techniques, we provide additional commentary based on our substantive practical experience with animal surgery and in vivo experimental design. This review also briefly touches upon the descriptive and functional outcome measures and power calculations that are necessary for an informative study. Obtaining informative and relevant research outcomes can be very dependent on the model used, and we hope this evaluation of common models will serve as a primer for new researchers looking to undertake preclinical bone studies. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:832–840, 2018.
Risk of peritoneal metastases in patients who had negative peritoneal staging and received therapy for localized gastric adenocarcinoma
Authors: Mizrak Kaya Dilsa , Nogueras‐González Graciela M. , Harada Kazuto , Amlashi Fatemeh G. , Roy‐Chowdhuri Sinchita , Estrella Jeannelyn S. , Das Prajnan , Lee Jeffrey H. , Weston Brian , Bhutani Manoop S. , Matamoros Aurelio , Thomas Irene , Lin Quan , Badgwell Brian D. , Ajani Jaffer A.
Published: December 2017

Background

Positive peritoneal cytology (+PCyt) or gross carcinomatosis (GPC) carries a poor prognosis. Laparoscopic staging to detect +PCyt/GPC is recommended for all ≥T1b gastric adenocarcinoma (GAC). The natural history of patients with GAC who have baseline −PCyt and then undergo multimodality therapy is not well documented, particularly for the risk of subsequent GPC.

Methods

We identified 238 GAC patients with baseline −PCyt who were followed for the development of peritoneal carcinomatosis (PC). Standard statistical methods were employed.

Results

Of 238 patients, 192 had attempted surgery after preoperative therapy. Of these, 13 patients (6.8%) had GPC and one had liver metastases, thus surgery was aborted. We followed 164 patients who had an R0 resection. The median follow‐up duration was 3.4 (range, 0.6‐18) years. The rate of PC was 13.4%, (22/164 patients) and the median time to PC was 15.6 months. Female gender was associated with PC on multivariate analysis. The 5‐year OS rate for patients without subsequent PC was 75%.

Conclusion Even with baseline −Cyt, ∼25% of patients develop PC following multimodality therapy. Patients who do not develop PC have an excellent OS rate. Further research is warranted to detect PC at baseline by the use of biomarkers.
Integrated population models facilitate ecological understanding and improved management decisions
Authors: Arnold Todd W. , Clark Robert G. , Koons David N. , Schaub Michael
Published: December 2017

Integrated population models (IPMs) represent a formal statistical methodology for combining multiple data sets such as population counts, band recoveries, and fecundity estimates into a single unified analysis with dual objectives: better estimating population size, trajectory, and vital rates; and formally describing the ecological processes that generated these patterns. Although IPMs have been used in population ecology and fisheries management, their use in wildlife management has been limited. Data sets available for North American waterfowl are unprecedented in terms of time span (>60 years) and geographic coverage, and are especially well‐suited for development of IPMs that could improve the understanding of population ecology and help guide future harvest and habitat management decisions. In this overview, we illustrate 3 potential benefits of IPMs: integration of multiple data sources (i.e., population counts, mark‐recapture data, and fecundity estimates), increased precision of parameter estimates, and ability to estimate missing demographic parameters by reanalyzing results from a historical study of canvasbacks (Aythya valisineria). Drawing from our own published and unpublished work, we demonstrate how IPMs could be used to identify the critical vital rates that have had the greatest influence on population change in lesser scaup (Aythya affinis), evaluate potential mechanisms of harvest compensation for American black ducks (Anas rubripes), or prioritize the most appropriate places to conduct habitat management to benefit northern pintails (Anas acuta). Integrated population models provide a powerful platform for evaluating alternative hypotheses about population regulation and they have potential to advance the understanding of wildlife ecology and help managers make ecologically based decisions. © 2017 The Wildlife Society.
Association of palatine tonsil size and obstructive sleep apnea in adults
Authors: Jara Sebastian M. , Weaver Edward M.
Published: December 2017

Objective

The relationship between palatine tonsil (PT) size and obstructive sleep apnea (OSA) has not been well established in adults. The purpose of this study was to test the association between PT grade, PT volume, and OSA severity in U.S. adult patients.

Study Design

Cross‐sectional study of all patients (age ≥ 18 years) who underwent pharyngeal surgery for OSA that included palatine tonsillectomy with tonsil volume measurement from January 2011 to June 2016.

Methods

Medical records were reviewed for PT grade (measured on clinical exam by the Brodsky tonsil grading scale), PT volume (measured intraoperatively by water displacement), and apnea–hypopnea index (AHI). Associations were evaluated with multivariate linear regression adjusting for age, sex, body mass index (BMI), smoking status, lingual tonsil volume (AHI models only), and multilevel surgery aside from lingual tonsillectomy (PT volume vs. AHI model only).

Results

The cohort (N = 83) was middle‐aged (mean age 43 ± 12 years), predominantly male (61%), obese (mean BMI 33 ± 7 kg/m2), and had severe OSA (mean AHI 32 ± 28). After adjustment for confounders, PT grade was strongly associated with PT volume (beta = 1.8, 95% confidence interval [CI]: [1.0, 2.6], P < 0.001) and with AHI (beta = 13.5, 95% CI: [3.5, 23.6], P = 0.01); PT volume was not associated with AHI (beta = −0.2, 95% CI: [−2.2, 1.9], P = 0.89).

Conclusion

In contrast to past studies, subjective PT grade (vs. objective PT volume) was more strongly associated with AHI. These data suggest the space that the tonsils occupy within the oropharyngeal airway, instead of their actual measured volume, may be more predictive of OSA severity in a cohort of U.S. adult patients.

Level of Evidence

2c. Laryngoscope, 128:1002–1006, 2018
Biogeochemical characteristics and fluxes of suspended particulate organic matter in response to low‐tide rainfall
Authors: Chen Si , Torres Raymond
Published: December 2017

We evaluated the effects of low‐tide rainfall on salt marsh particulate organic carbon (POC) cycling. Suspended sediment samples from intertidal creeks were collected during rain and no‐rain conditions. Bulk (carbon, nitrogen) and molecular (e.g., lignin) compositions of organic constituents in particulates were analyzed. Temporal patterns of suspended sediment concentration mimic fluctuations in rainfall intensity, but all POC constituents do not necessarily follow these patterns. For example, particulate organic matter concentrations in water column covaried with rain intensity yet organic matter (OM) contents in the particles showed trivial correlations with rain. In general, rainfall effects raised the suspended sediment and organic constituent concentrations in the water column by up to three orders of magnitude. Multivariate statistical analysis revealed that the rainfall‐entrained particulates were compositionally distinct from calm weather suspended particulates, from salt marsh surface sediment, and from creek bank surface sediment. Rainfall‐entrained particulates are depleted in bulk organic carbon and phytoplankton‐derived OM but enriched in lignin phenols. These observations indicate that rainfall‐runoff processes preferentially mobilize POC derived from Spartina alterniflora from marsh platforms and effectively transport these materials to intertidal creeks following low‐tide rainfall events. Moreover, average net transport rates by rainfall are 0.020 ± 0.002 gPOC m−2 mmRain−1, and this POC turnover rate amounts to ∼ 19% of the annual POC export from estuary to ocean. Therefore, estuarine outwelling estimates typically made under calm weather conditions represent minimum levels of POC export. Hence, low‐tide rainfall can be expected to substantially enhance the delivery of marsh‐derived POC to the coastal ocean.
An evaluation of the WRF Mei‐yu rainfall forecasts in Taiwan, 2008–2010: differences in elevation and sub‐regions
Authors: Paul Sahana , Wang Chung‐Chieh , Chien Fang‐Ching , Lee Dong‐In
Published: December 2017

This study explores differences in the performance of the Mei‐yu quantitative precipitation forecast (QPF) in Taiwan by use of the Weather Research and Forecasting (WRF) model in continuation of an earlier study, with particular detailed focus on those among three elevation ranges and four sub‐regions at different stages of the season and within the diurnal cycle. Against data from about 400 rain gauges, both subjective and objective verifications are performed to complement each other. The Mei‐yu QPF's skill is shown to vary with evaluation periods (every half‐month) within the season, with elevation (categorized as plain (0–250 m), slope (0.25–1 km) and mountain (>1 km) areas), and also with sub‐region (northern, central, southern and eastern Taiwan). The diurnal cycle of rainfall produced by the model is strong over the mountains, but too weak over the plains. Overall, the model exhibits the highest skill in southern and central Taiwan, where more rain occurs due to forced uplift of the prevailing southwesterly flow over the windward slopes (mainly during the first half of June). In general, the more rainfall there is, the better the model performs (with higher skill) during the Mei‐yu season.
(‐)‐Epicatechin and the Colonic 2,3‐Dihydroxybenzoic Acid Metabolite Regulate Glucose Uptake, Glucose Production, and Improve Insulin Signaling in Renal NRK‐52E Cells
Authors: Álvarez‐Cilleros David , Martín María Ángeles , Ramos Sonia
Published: December 2017

Scope

(‐)‐Epicatechin (EC) and main colonic phenolic acids derived from flavonoid intake, such as 2,3‐dihydroxybenzoic acid (DHBA), 3,4‐dihydroxyphenylacetic acid (DHPAA), 3‐hydroxyphenylpropionic acid (HPPA), and vanillic acid (VA), have been suggested to exert beneficial effects in diabetes, although the mechanism for their actions remains unknown. In this study, the modulation of glucose homeostasis and insulin signaling by the mentioned compounds on renal proximal tubular NRK‐52E cells is investigated.

Methods and results

Levels of the glucose transporters SGLT‐2 and GLUT‐2, as well as glucose uptake, glucose production, and key proteins of the insulin pathways, namely insulin receptor (IR), insulin receptor substrate‐1 (IRS‐1), and PI3K/AKT pathway are analyzed. EC (5‐20 μm) and DHBA (20 μm) reduced both renal glucose uptake and production. Interestingly, EC and DHBA did not modify the levels of SGLT‐2 and GLUT‐2, and modulated the expression of phosphoenolpyruvate carboxykinase via AKT leading to a diminished glucose production. EC and DHBA also enhanced the tyrosine phosphorylation and total IR and IRS‐1 levels, and activated the PI3K/AKT pathway in NRK‐52E cells.

Conclusion

EC and DHBA regulate the renal glucose homeostasis by modulating both glucose uptake and production, and strengthen the insulin signaling by activating key proteins of that pathway in NRK‐52E cells.
Vitamin D Does Not Play a Functional Role in Adipose Tissue Development in Rodent Models
Authors: Schutkowski Alexandra , Max Daniela , Bönn Markus , Brandsch Corinna , Grundmann Sarah M. , Hirche Frank , Staege Martin S. , Stangl Gabriele I.
Published: December 2017

Scope

Several studies have proposed a role of vitamin D in adipogenesis. Here, we sought to study the impact of the vitamin D receptor (Vdr) on adipocyte size in young and old mice and the effect of maternal vitamin D deficiency on fetal adipogenesis.

Methods and results

Histological analysis of adipose tissues shows that Vdr knockout (KO) mice have smaller adipocytes than wild‐type (WT) mice. Next, we compare young and old Vdr‐KO and WT mice and find no differences in adipocyte sizes between weaned Vdr‐KO and WT mice. However, 1‐year‐old Vdr‐KO mice, suffering from alopecia, have smaller‐sized adipocytes than WT mice, although they consume more food. To elucidate whether vitamin D can directly impact adipocyte development at a critical stage of adipogenesis, we feed rat dams a vitamin D deficient (0 IU kg−1) or vitamin D adequate (1000 IU kg−1) diet. Neither DNA microarray analysis of the adipose tissues of the newborn rats nor the adipocyte sizes of 21‐day‐old offspring show significant differences between the two groups.

Conclusion

Data indicate that vitamin D does not play a fundamental role in adipogenesis because vitamin D does not affect fetal adipogenesis. Moreover, the smaller adipocytes observed in adult Vdr‐KO mice are presumably caused by an increased energy expenditure due to alopecia.
Directional scatter imaging for the stereoscopic tracking of fiducial markers in a single kV exposure
Authors: Garnica‐Garza Héctor Mauricio
Published: December 2017

Purpose

To demonstrate, via Monte Carlo simulation, that an image obtained from the patient‐generated scattered radiation forced to impinge on the detector from a known direction by means of parallel‐focused grids, can be used to complement the information conveyed by the primary image, such that accurate stereoscopic three‐dimensional localization of fiducial markers can be achieved in a single kV x‐ray exposure.

Methods

A voxelized Zubal phantom was used to model the process of fiducial marker localization. The markers were represented as made of gold and cylindrical in shape with dimensions of 5 mm in length and 1 mm in diameter. Three such markers were placed in the Zubal phantom at the prostate level. Two gantry‐mounted image acquisition geometries were modeled: a single kV imaging system and a dual kV–MV imaging system. The detector was modeled as a 30 cm × 40 cm Gd2O2S screen with a thickness of 0.2 cm and a resolution of 768 × 1024 pixels. The PENELOPE Monte Carlo code was used to calculate the absorbed dose in this detector imparted by the transmitted primary and directional scatter radiation. A grayscale conversion was then applied to obtain an image from which the positions of the markers were determined. Two parallel‐focused grid geometries were modeled, one based on the standard lead‐carbon fiber grids and a proposed modification using tungsten as the shielding material. Absorbed dose in the patient model was also calculated.

Results

It is shown that the combination of primary and directional scatter images provides the means for an accurate stereoscopic fiducial marker 3D localization in a single x‐ray exposure, provided the antiscatter grids are made thick enough to allow radiation traveling only in a particular direction to reach the detector. For the proposed tungsten grid and the x‐ray spectrum used in this work, grid ratios of 20 and thickness of 0.2 cm, provide the necessary shielding while for the standard lead grids, a ratio of at least 166 and a thickness of 2 cm are needed to obtain discernible directional scatter images.

Conclusions

We have shown that it is in principle possible to determine the 3D position of fiducial markers in a single exposure by making use of the radiation scattered by the patient to form an image that complements the information obtained with the primary beam. The method here proposed requires minimal modification of existing clinical hardware.
High dose‐per‐pulse electron beam dosimetry: Commissioning of the Oriatron eRT6 prototype linear accelerator for preclinical use
Authors: Jaccard Maud , Durán Maria Teresa , Petersson Kristoffer , Germond Jean‐François , Liger Philippe , Vozenin Marie‐Catherine , Bourhis Jean , Bochud François , Bailat Claude
Published: December 2017

Purpose

The Oriatron eRT6 is an experimental high dose‐per‐pulse linear accelerator (linac) which was designed to deliver an electron beam with variable dose‐rates, ranging from a few Gy/min up to hundreds of Gy/s. It was built to study the radiobiological effects of high dose‐per‐pulse/dose‐rate electron beam irradiation, in the context of preclinical and cognitive studies. In this work, we report on the commissioning and beam monitoring of the Oriatron eRT6 prototype linac.

Materials and Methods

The beam was characterized in different steps. The output stability was studied by performing repeated measurements over a period of 20 months. The relative output variations caused by changing beam parameters, such as the temporal electron pulse width, the pulse repetition frequency and the pulse amplitude were also analyzed. Finally, depth dose curves and field sizes were measured for two different beam settings, resulting in one beam with a conventional radiotherapy dose‐rate and one with a much higher dose‐rate. Measurements were performed with Gafchromic EBT3 films and with a PTW Advanced Markus ionization chamber. In addition, we developed a beam current monitoring system based on the signals from an induction torus positioned at the beam exit of the waveguide and from a graphite beam collimator.

Results

The stability of the output over repeated measurements was found to be good, with a standard deviation smaller than 1%. However, non‐negligible day‐to‐day variations of the beam output were observed. Those output variations showed different trends depending on the dose‐rate. The analysis of the relative output variation as a function of various beam parameters showed that in a given configuration, the dose‐rate could be reliably varied over three orders of magnitude. Interdependence effects on the output variation between the parameters were also observed. The beam energy and field size were found to be slightly dose‐rate‐dependent and suitable mainly for small animal irradiation. The beam monitoring system was able to measure in a reproducible way the total charge of electrons that exit the machine, as long as the electron pulse amplitude remains above a given threshold. Furthermore, we were able to relate the charge measured with the monitoring system to the absorbed dose in a solid water phantom.

Conclusion

The Oriatron eRT6 was successfully commissioned for preclinical use and is currently in full operation, with studies being performed on the radiobiological effects of high dose‐per‐pulse irradiation.
A cross‐sectional study of stress and its sources among health professional students at Makerere University, Uganda
Authors: Amanya Sharon Bright , Nakitende Joyce , Ngabirano Tom Denis
Published: December 2017

Aim

To assess prevalence of stress and its sources among undergraduate health professional students at Makerere University.

Design

This was a descriptive cross‐sectional study using quantitative methods of data collection.

Methods

The study was conducted among 258 undergraduate health professional students (Medical, Dental and, Nursing students) at Makerere University. From each programme, students were recruited proportionately, while being selected conveniently from each year of study. Stress was measured using the General Health Questionnaire 12 and stressors assessed using a questionnaire developed from literature. After obtaining ethics approval, data were collected from consenting students. Data collected were analysed using SPSS statistical program.

Results

The prevalence of stress was found to be 57.4% and stressors of academic and psychosocial origin were most frequently reported. The top stressors included; academic curriculum (38%), dissatisfaction with class lectures (30.9%), long distance walk (29.5%), lack of time for recreation (28.9%), performance in examination (28.3%), lack of special guidance from faculty (26.7%) and high parental expectations (26.7%).