bluuebunny/crossref_metadata_2025 huggingface dataset:
A multiple comparison procedure for dose‐finding trials with subpopulations
Authors: Thomas Marius , Bornkamp Björn , Posch Martin , König Franz
Published: September 2019

Identifying subgroups of patients with an enhanced response to a new treatment has become an area of increased interest in the last few years. When there is knowledge about possible subpopulations with an enhanced treatment effect before the start of a trial it might be beneficial to set up a testing strategy, which tests for a significant treatment effect not only in the full population, but also in these prespecified subpopulations. In this paper, we present a parametric multiple testing approach for tests in multiple populations for dose‐finding trials. Our approach is based on the MCP‐Mod methodology, which uses multiple comparison procedures (MCPs) to test for a dose–response signal, while considering multiple possible candidate dose–response shapes. Our proposed methods allow for heteroscedastic error variances between populations and control the family‐wise error rate over tests in multiple populations and for multiple candidate models. We show in simulations that the proposed multipopulation testing approaches can increase the power to detect a significant dose–response signal over the standard single‐population MCP‐Mod, when the specified subpopulation has an enhanced treatment effect.
Joint model for recurrent event data with a cured fraction and a terminal event
Authors: Kim Yang‐Jin
Published: September 2019

In a longitudinal study where the recurrence of an event and a terminal event such as death are observed, a certain portion of the subjects may experience no event during a long follow‐up period; this often denoted as the cure group which is assumed to be the risk‐free from both recurrent events and death. However, this assumption ignores the possibility of death, which subjects in the cure group may experience. In the present study, such misspecification is investigated with the addition of a death hazard model to the cure group. We propose a joint model using a frailty effect, which reflects the association between a recurrent event and death. For the estimation, an expectation‐maximization (EM) algorithm was developed and PROC NLMIXED in SAS was incorporated under a piecewise constant baseline. Simulation studies were performed to check the performance of the suggested method. The proposed method was applied to leukemia patients experiencing both infection and death after bone marrow transplant.
Integrated evaluation of targeted and non‐targeted therapies in a network meta‐analysis
Authors: Proctor Tanja , Jensen Katrin , Kieser Meinhard
Published: September 2019

Individualized therapies for patients with biomarkers are moving more and more into the focus of research interest when developing new treatments. Hereby, the term individualized (or targeted) therapy denotes a treatment specifically developed for biomarker‐positive patients. A network meta‐analysis model for a binary endpoint combining the evidence for a targeted therapy from individual patient data with the evidence for a non‐targeted therapy from aggregate data is presented and investigated. The biomarker status of the patients is either available at patient‐level in individual patient data or at study‐level in aggregate data. Both types of biomarker information have to be included. The evidence synthesis model follows a Bayesian approach and applies a meta‐regression to the studies with aggregate data. In a simulation study, we address three treatment arms, one of them investigating a targeted therapy. The bias and the root‐mean‐square error of the treatment effect estimate for the subgroup of biomarker‐positive patients based on studies with aggregate data are investigated. Thereby, the meta‐regression approach is compared to approaches applying alternative solutions. The regression approach has a surprisingly small bias even in the presence of few studies. By contrast, the root‐mean‐square error is relatively greater. An illustrative example is provided demonstrating implementation of the presented network meta‐analysis model in a clinical setting.
UTCPredictor: An uncertainty‐aware novel teaching cases predictor
Authors: Wu Xiaoxue , Zheng Wei , Mu Dejun , Li Ning
Published: September 2019

Teaching cases are crucial for computer science (e.g., software testing) teaching. With the fast development of computer science, old and outdated teaching cases cannot meet the requirements of teaching. Therefore, teachers need to update teaching case repository continually and timely. However, teaching case development is an extremely time‐consuming work. Given today's complex and fast‐moving environment of computer science, teachers often feel blind about about what types of cases should be added for teaching. This paper presents UTCPredictor—an automated approach of predicting novel teaching cases from real production by identifying the most uncertain data, which are always with new features that reflect the latest developments and trends in the field. The implementation of UTCPredictor is based on the idea of interactive machine learning as well as several text mining techniques. To evaluate the effectiveness of UTCPredictor, we take bug report case building in software testing teaching as an example, using UTCPredictor to perform 10‐fold cross‐validation on an existing teaching case set. The performance in terms of indicators; Recall, Precision, and F1‐score, achieved three very competitive values—0.91, 0.94, and 0.85, respectively. We further evaluate the effectiveness of UTCPredictor through a user study and a questionnaire. The results are very positive; the user study indicates that educators can build a teaching case set from latest bug report repository by spending only 8.16%–18.11% time costs compared with traditional manual approach; the responses from 2,000 students for the questionnaire show that the teaching cases built with UTCPredictor are very popular among students.
Antibiotic‐Potentiating Activity of Phanostenine Isolated from Cissampelos sympodialisEichler
Authors: Cunha Walmir E. M. , Camilo Cicera J. , de F. A. Nonato Carla , Mendes Johnatan W. S. , de Carvalho Natália K. G. , Coutinho Henrique D. M. , Menezes Irwin R. A. , de Lemos Telma L. G. , Braz‐Filho Raimundo , Rodrigues Fabiola F. G. , Matias Edinardo F. F. , Zengin Gokhan , Costa José G. M.
Published: September 2019

Cissampelos sympodialis Eichler is well studied and investigated for its antiasthmatic properties, but there are no data in the literature describing antibacterial properties of alkaloids isolated from this botanical species. This work reports the isolation and characterization of phanostenine obtained from roots of C. sympodialis and describes for the first time its antimicrobial and antibiotic modulatory properties. Phanostenine was first isolated from Cissampelos sympodialis and its antibacterial activities were determined. Chemical structures of the alkaloid isolate were determined using spectroscopic and chemical analyses. Phanostenine was also tested for its antibacterial activity against standard strains and clinical isolates of Escherichia coli and Staphylococcus aureus. Minimal inhibitory concentration (MIC) was determined in a microdilution assay and for the evaluation of antibiotic resistance‐modifying activity. MIC of the antibiotics was determined in the presence or absence of phanostenine at sub‐inhibitory concentrations. The evaluation of antibacterial activity by microdilution assay showed activity for all strains with better values against S. aureus ATCC 12692 and E. coli 27 (787.69 mm). The evaluation of aminoglycoside antibiotic resistance‐modifying activity showed reduction in the MIC of the aminoglycosides (amikacin, gentamicin and neomycin) when associated with phanostenine, MIC reduction of antibiotics ranging from 21 % to 80 %. The data demonstrated that phanostenine possesses a relevant ability to modify the antibiotic activity in vitro. We can suggest that phanostenine presents itself as a promising tool as an adjuvant for novel antibiotics formulations against bacterial resistance.
In Vitro Trypanocidal and Antibacterial Activities of Essential Oils from Four Species of the Family Annonaceae
Authors: Bay Marcia , Souza de Oliveira João Vitor , Sales Junior Policarpo Ademar , Fonseca Murta Silvane Maria , Rogério dos Santos Anderson , dos Santos Bastos Ivanildes , Puccinelli Orlandi Patrícia , Teixeira de Sousa Junior Paulo
Published: September 2019

The objective of this study was to evaluate the chemical composition, and the trypanocidal and antibacterial activities of the essential oils from four species of Annonaceae: Bocageopsis multiflora (Mart.) R.E.Fr., Duguetia quitarensis Benth., Fusaea longifolia (Aubl.) Saff., and Guatteria punctata (Aubl.) R.A.Howard. The chemical composition of the essential oils from the aerial parts yielded 23, 20, 21 and 23 constituents, respectively, which were identified by GC/MS. The trypanocidal activity was evaluated against the amastigote and trypomastigote forms of T. cruzi. The antibacterial activity was evaluated by the microdilution method against enterohemorrhagic Escherichia coli, Pseudomonas aeruginosa, Streptococcus mutans, Streptococcus pyogenes, and methicillin‐resistant Staphylococcus aureus. The results of trypanocidal activity showed that the essential oils of the four species were active at the tested concentrations, with G. punctata essential oil being the most active, with IC50=0.029 μg/mL, and selectivity index (SI)=32, being 34 times more active than the reference drug benznidazole. All EOs showed strong antibacterial activity (minimum inhibitory concentrations of 4.68–37.5 μg/mL) against strains of S. mutans.
Thermodynamic and Structural Behavior of α‐Galactosylceramide and C6‐Functionalized α‐GalCer in 2D Layers at the Air–Liquid Interface
Authors: Brezesinski Gerald , Calow Adam D. J. , Pereira Claney L. , Seeberger Peter H.
Published: September 2019

α‐Galactosylceramide (α‐GalCer; KRN7000) is a ligand for the glycoprotein CD1d that presents lipid antigens to natural killer T cells. Therefore, KRN7000 as well as some modified versions thereof have been widely investigated as part of novel immunotherapies. To examine the impact of structural modification, we investigated KRN7000 and C6‐modified KRN7000 at the air–liquid interface using monolayer isotherms, BAM, IRRAS, GIXD, and TRXF. The amino group has no influence on the highly ordered sub‐gel structures found at lateral pressures relevant for biological membranes. Neither lateral compression nor the protonation state of the amino group has a measurable effect on the lattice structure, which is defined by strong and rigid intermolecular hydrogen bonds. However, the first‐order phase transition found for the C6‐functionalized α‐GalCer is connected with an extraordinary surface‐inhibited nucleation. Our study demonstrates that KRN7000 can be functionalized at C6 without significantly changing the structural properties.
Sulfate Surfactant Assisted Approach to Fabricate Sulphur‐Doped Supported Nanodiamond Catalyst on Carbon Nanotube with Unprecedented Catalysis for Ethylbenzene Dehydrogenation
Authors: Zhou Qin , Zhao Zhongkui
Published: September 2019

Direct dehydrogenation (DDH) of ethylbenzene is an efficient chemical process for styrene production. Nanocarbon materials, as clean and low‐cost catalysts, have drawn more and more attention in this field. In this work, inspired by the promoting effect of support modulation on the catalytic performance of the general supported‐type catalyst, we present a facile sulfate surfactant assisted dispersion with subsequent annealing (SADA) approach for preparing sulphur‐doped supported nanodiamond catalyst on carbon nanotube (ND/CNT‐SDS) with abundant active sites by using sodium dodecyl sulfate (SDS) as both the dispersing agent for promoting the dispersion of catalytically active ND motif and the CNT support and the sulphur source for sulphur doping, yielding an outstanding supported ND catalyst for DDH of ethylbenzene to styrene with 7.7 mmol g−1cat. h−1 of styrene rate and 98.2 % of styrene selectivity. ND/CNT‐SDS catalyst demonstrates 3.0 times higher styrene rate of the pristine ND. Moreover, ND/CNT‐SDS catalyst shows 1.5 times higher styrene rate of the previously reported defect‐enriched N,O‐codoped ND/CNT (N,O‐ND/CNT‐d) with up to 98 % of similar styrene selectivity, ascribed to its more exposed C=O active sites and higher specific surface area originating from the promoted dispersion of both ND and CNT by SDS, as well as the sulphur‐doping. Moreover, this work also presents a novel and efficient method for the designing the other supported nanocarbon catalysts from dispersion‐required catalytically active nanocarbon motif and the nanocarbon carrier.
Binary Lead Fluoride Pb3F8
Authors: Deubner H. Lars , Sachs Malte , Bandemehr Jascha , Ivlev Sergei I. , Karttunen Antti J. , Kachel Stefan R. , Klein Benedikt P. , Ruppenthal Lukas , Schöniger Maik , Krug Claudio K. , Herritsch Jan , Gottfried J. Michael , Aman Jamal N. M. , Schmedt auf der Günne Jörn , Kraus Florian
Published: September 2019

The binary lead fluoride Pb3F8 was synthesized by the reaction of anhydrous HF with Pb3O4 or by the reaction of BrF3 with PbF2. The compound was characterized by single‐crystal and powder X‐ray diffraction, IR, Raman, and solid‐state MAS 19F NMR spectroscopy, as well as thermogravimetric analysis, XP and near‐edge X‐ray absorption fine structure (NEXAFS) spectroscopy. Solid‐state quantum‐chemical calculations are provided for the vibrational analyses and band assignments. The electronic band structure offers an inside view of the mixed valence compound.
One‐Pot Synthesis of Xanthate‐Functionalized Cellulose for the Detection of Micromolar Copper(II) and Nickel(II) Ions
Authors: Greis Kim , Bethke Kevin , Stückrath Julius B. , Ingber Tjark T. K. , Valiyaveettil Suresh , Rademann Klaus
Published: September 2019

A one‐pot synthesis and application of cellulose‐based sensors to efficiently detect various toxic metal ions in aqueous solutions in micromolar quantities is reported. Cellulose microfibers have been functionalized with carbon disulfide in alkaline solution to form cellulose xanthate. The material detects several toxic metal ions such as copper, nickel, or cobalt ions through color change detectable by the naked eye. The optical sensor can be used as an ideal flash test for assessing the quality of drinking water.
Health‐related quality of life in oncology drug reimbursement submissions in Canada: A review of submissions to the pan‐Canadian Oncology Drug Review
Authors: Raymakers Adam J. N. , Regier Dean A. , Peacock Stuart J.
Published: September 2019

Background

In Canada, the Canadian Agency for Drugs and Technologies in Health (CADTH) evaluates and makes recommendations for the reimbursement of cancer drugs. One component of its recommendation is based on an economic evaluation, which typically takes the form of a cost‐utility analysis. A cost‐utility analysis measures the effects of competing therapies with quality‐adjusted life‐years (QALYs). The data for this calculation typically come from generic, preference‐based measures of health‐related quality of life (HRQOL). The objective of this review is to determine the frequency at which HRQOL data are collected alongside cancer drug trials and used in the cost‐utility analysis submitted to the CADTH pan‐Canadian Oncology Drug Review (pCODR).

Methods

Submissions between 2015 and 2018 to pCODR, the group charged with evaluating cancer drug submissions at CADTH, were reviewed. All pCODR submissions, either in progress or completed, were publicly available online. The search was restricted to completed evaluations.

Results

Forty‐three submissions met the inclusion criteria. The incremental gain in QALYs in most submissions from the new technology was small (median incremental gain, 0.86; interquartile range, 0.6‐1.39). More than half of the submissions (56%) did not include original data on HRQOL, with most relying on previous studies of variable relevance and quality. Re‐analyses by pCODR based on concerns over HRQOL data used in the submitted model were common (52%).

Conclusions

Drug manufacturers do not consistently collect data on HRQOL alongside clinical trials and instead rely on evidence generated in previous studies to inform cost‐utility analyses. These findings should induce manufacturers to collect original HRQOL data that are simultaneously relevant to patients and decision makers.
Induction of Planar Chirality Using Asymmetric Click Chemistry by a Novel Desymmetrisation of 1,3‐Bisalkynyl Ferrocenes
Authors: Wright Adam J. , Hughes David L. , Bulman Page Phillip C. , Stephenson G. Richard
Published: September 2019

The new asymmetric click CuAAC reaction is used for the first time to induce asymmetry in planar chiral compounds. There are only three classes of stereogenicity (atom‐centred, axial and planar), and these results are therefore of fundamental importance as well as practical significance, providing access to chiral ferrocenes at near enantiopurity. Here, we report asymmetric induction (AI) and kinetic resolution (KR) studies on a novel library of prochiral 1,2,3‐trisubstituted bis‐alkynylferrocenes, obtained by diiodination, derivatisation (including reduction and etherification), double Sonogashira coupling and finally transesterification, azidation or silylation. Desymmetrisation using chiral ligands to modify the CuAAC reaction proceeds in up to 60 % yield and >99.5 % ee, yielding planar chiral ferrocenes. The absolute configuration of two of the preferred products was proved by chemical correlation and related to the entire series by circular dichroism spectroscopy (CD).
Evaluation of CO2 attack in wellbore class G cement: influence of epoxy resins, composites and minerals as additives
Authors: Schütz Marta K. , dos Santos Leonardo M. , Coteskvisk Patrícia M. , Menezes Sonia C. , Einloft Sandra , Dalla Vecchia Felipe
Published: September 2019

Carbon dioxide (CO2) injection into geological formations is pointed out as one of the most effective alternatives to reduce anthropogenic CO2 emissions to the atmosphere. To promote long‐term CO2 storage, wellbore integrity is a critical issue to be considered. Portland cement is commonly used for cementing wells, and considered chemically unstable in CO2‐rich media. In this context, this study investigated the CO2 chemical resistance of class G Portland cement modified with novel additives (epoxy resins, epoxy–clay composites, and clay minerals) at 1 and 2.5 wt% contents. Reaction times of 7 and 30 days of exposure to CO2 in supercritical conditions were evaluated. Samples were characterized by mechanical compression tests and phenolphthalein indicator as well as field emission scanning electron microscopy in order to determine the depth of carbonation in cement. Our results indicate that although there is slight reduction in the initial compressive strength, the addition of tested additives to cement paste offers improvements in terms of chemical resistance. The optimum content of different additives was 1 wt% in order to maintain compressive strength properties and improve chemical resistance to CO2. The best result was achieved with an epoxy resin blend as an additive, decreasing carbonation by up to 60% (7 days of exposure to CO2) and 52% (30 days of exposure to CO2). Addition of montmorillonite to the epoxy blend tends to improve chemical resistance of cement paste when compared to the neat epoxy blend. © 2019 Society of Chemical Industry and John Wiley & Sons, Ltd.
LRP6 regulates Rab7‐mediated autophagy through the Wnt/β‐catenin pathway to modulate trophoblast cell migration and invasion
Authors: Li Lei , Peng Wei , Zhou Qian , Wan Ji‐Peng , Wang Xie‐Tong , Qi Hong‐Bo
Published: September 2019

Pre‐eclampsia is a common complication during pregnancy; however, the underlying mechanisms of the crosstalk between low‐density lipoprotein receptor‐related protein 6 (LRP6) and autophagy in trophoblast cells are still not fully explored. Messenger RNA (mRNA) and protein levels of LRP6, beclin 1, Unc‐51‐like autophagy activating kinase 1 (ULK1), p62, vimentin, matrix metallopeptidase‐9 (MMP‐9), β‐catenin, c‐Myc, and Rab7, as well as the ratio of LC3‐II/LC3‐I, were analysed by quantitative real‐time polymerase chain reaction or Western blot analysis, respectively. An MTT assay was used to measure cell growth, and transwell and wound healing assays were carried out to evaluate the invasion and migration abilities of the trophoblasts used. An immunofluorescence assay was used to measure LC3. The mRFP‐GFP‐LC3 tandem fluorescence assay was applied to detect autophagic flow. LRP6 overexpression was achieved by constructing pcDNA3.1‐LRP6 vectors. LRP6 was expressed at low levels in HTR‐8/SVneo cells under hypoxia/reoxygenation (H/R) conditions. H/R inhibited the activation of autophagy. LRP6 overexpression promoted cell proliferation and activated autophagy, which led to the upregulation of beclin 1 and ULK1, as well as the ratio of LC3‐II/LC3‐I and the downregulation of p62. Furthermore, LRP6 overexpression elevated the migration and invasion abilities of the indicated cells and increased vimentin and MMP‐9 expression levels. Furthermore, LRP6 upregulated Rab7 and activated autophagy through the Wnt/β‐catenin pathway. The late autophagy inhibitor bafilomycin A1 (Baf‐A1) and the Wnt/β‐catenin pathway inhibitor PKF115‐584 reversed the effects of LRP6 on trophoblast autophagy, migration and invasion. LRP6 promotes Rab7‐mediated autophagy by activating the Wnt/β‐catenin pathway, which leads to increasing migration and invasion of trophoblast cells. Our study paves a new avenue for clinical treatment, and LRP6 may serve as an essential target in pre‐eclampsia.
Developmental transitions during adulthood and neighborliness: A multilevel cluster analysis
Authors: Aiyer Sophie M. , Zahnow Renee , Mazerolle Lorraine A.
Published: September 2019

Neighborliness plays a critical role in promoting social integration, and is known to positively influence health and psychosocial adjustment. We examined variation in neighborliness based on developmental transitions as well as on the neighborhood context. We examined the direct and moderating role of neighborhood factors, to determine whether the neighborhood context modified the influence of developmental transitions on neighborliness. We analyzed data from a longitudinal study of Australian communities, in addition to census data. First, we analyzed developmental transition clusters. Next, we employed multilevel modeling to assess the impact of clusters and other key factors on neighborliness. We tested interactions to determine whether the influence of cluster membership on neighborliness was modified by the neighborhood. We found evidence for direct effects of cluster membership and structural factors on neighborliness. In addition, the neighborhood context modified the influence of cluster membership on neighborliness. Our findings underscore the importance of promoting neighborhood social engagement throughout the life course.
The BioLuminescent‐OptoGenetic in vivo response to coelenterazine is proportional, sensitive, and specific in neocortex
Authors: Gomez‐Ramirez Manuel , More Alexander I. , Friedman Nina G. , Hochgeschwender Ute , Moore Christopher I.
Published: September 2019

BioLuminescent (BL) light production can modulate neural activity and behavior through co‐expressed OptoGenetic (OG) elements, an approach termed “BL‐OG.” Yet, the relationship between BL‐OG effects and bioluminescent photon emission has not been characterized in vivo. Further, the degree to which BL‐OG effects strictly depend on optogenetic mechanisms driven by bioluminescent photons is unknown. Crucial to every neuromodulation method is whether the activator shows a dynamic concentration range driving robust, selective, and nontoxic effects. We systematically tested the effects of four key components of the BL‐OG mechanism (luciferin, oxidized luciferin, luciferin vehicle, and bioluminescence), and compared these against effects induced by the Luminopsin‐3 (LMO3) BL‐OG molecule, a fusion of slow burn Gaussia luciferase (sbGLuc) and Volvox ChannelRhodopsin‐1 (VChR1). We performed combined bioluminescence imaging and electrophysiological recordings while injecting specific doses of Coelenterazine (substrate for sbGluc), Coelenteramide (CTM, the oxidized product of CTZ), or CTZ vehicle. CTZ robustly drove activity in mice expressing LMO3, with photon production proportional to firing rate. In contrast, low and moderate doses of CTZ, CTM, or vehicle did not modulate activity in mice that did not express LMO3. We also failed to find bioluminescence effects on neural activity in mice expressing an optogenetically nonsensitive LMO3 variant. We observed weak responses to the highest dose of CTZ in control mice, but these effects were significantly smaller than those observed in the LMO3 group. These results show that in neocortex in vivo, there is a large CTZ range wherein BL‐OG effects are specific to its active chemogenetic mechanism.
Characterization of chemical constituents and absorbed components, screening the active components of gelanxinning capsule and an evaluation of therapeutic effects by ultra‐high performance liquid chromatography with quadrupole time of flight mass spectrometry
Authors: Gao Xin , Hu Xiaohu , Zhang Qiong , Wang Xijing , Wen Xiuhong , Wang Yuan , Zhang Yanxia , Sun Wenjun
Published: September 2019

We revealed the potential biomarker and pathway of gelanxinning capsule on rat model with coronary heart disease, which aims to clarify holistic therapeutic effect and predict quality‐markers of gelanxinning capsule. Ultra‐high performance liquid chromatography coupled with mass spectrometry based on metabolomics technique was used to find the biomarkers and related metabolic pathways of coronary heart disease model, which evaluates the intervention effect of gelanxinning capsule. Using serum pharmacochemistry of traditional Chinese medicine and Pearson correlation analysis, effective ingredients in serum is analyzed to characterize the activity of gelanxinning capsule on coronary heart disease under valid state. A total of 20 biomarkers from coronary heart disease were identified and 12 of them were regulated by gelanxinning capsule treatment, which is mainly involved in sphingolipid metabolism and glycerophospholipid metabolism. With the high sensitivity liquid chromatography coupled with mass spectrometry technology, a total of 46 compounds from gelanxinning capsule were identified in vitro and 25 of them were absorbed in blood. The correlation analysis of serum biomarkers and absorbed components was used to find 11 compounds as quality‐markers to be responsible for the efficacy of gelanxinning capsule. This strategy was successfully applied to screening of potential mechanism and quality‐markers from herbal medicine.
Regio‐ and Stereospecific Cyclopolymerization of α,ω‐Diynes by Cationic Molybdenum Imido Alkylidene N‐Heterocyclic Carbene Complexes
Authors: Probst Patrick , Elser Iris , Schowner Roman , Benedikter Mathis J. , Buchmeiser Michael R.
Published: September 2019

Both solvent‐free and acetonitrile‐containing cationic molybdenum imido alkylidene N‐heterocyclic carbene (NHC) complexes of the general formula [Mo(NR′)(CHCMe2R)(NHC)(X)+ A−] (R′ = 2,6‐Cl2‐C6H3, tBu, 2‐CF3‐C6H4, 2‐tBu‐C6H4, 2,6‐iPr2‐C6H3, 2,6‐Me2‐C6H3; R = Me, Ph; NHC = 1,3‐dimesitylimidazol‐2‐ylidene (IMes), 1,3‐di‐iPr‐imidazol‐2‐ylidene (IPr), 1,3,5‐triphenyl‐1,3,4‐triazol‐2‐ylidene); X = CF3SO3, C6F5O, OCH(CF3)2, OC(CF3)3, pyrrolide, C6F5COO, 2,6‐(CF3)2‐C6H3COO; A− = B(ArF)4−, Al(OC(CF3)3)4−), have been investigated for their propensity to cyclopolymerize 4,4‐disubstituted 1,6‐heptadiynes. All metal complexes contain a stereogenic (chiral) metal center, which accounts for the high reactivity and high regioselectivity of insertion (>99%) that are observed for all metal complexes, leading to highly conjugated, α‐insertion‐derived polyenes that are based on a highly regular polymer backbone and that show absorption maxima close to 600 nm. With the chiral monomer 4‐(ethoxycarbonyl)‐4‐(1S,2R,5S)‐(‐)‐menthoxycarbonyl‐1,6‐heptadiyne, high syndiospecifity (>99% syndiotactic) is observed. A mechanism explaining the high regio‐ and stereoselectivity is presented. Thus, α‐addition of the monomers proceeds chain‐end‐controlled trans to the NHC and is preferred over β‐addition through intramolecular Mo‐O chelation. Insertion of the monomers entails double inversion at the stereogenic metal center in the course of one complete monomer insertion.
Heat‐induced shift in coral microbiome reveals several members of the Rhodobacteraceae family as indicator species for thermal stress in Porites lutea
Authors: Pootakham Wirulda , Mhuantong Wuttichai , Yoocha Thippawan , Putchim Lalita , Jomchai Nukoon , Sonthirod Chutima , Naktang Chaiwat , Kongkachana Wasitthee , Tangphatsornruang Sithichoke
Published: September 2019

The coral holobiont is a complex ecosystem consisting of coral animals and a highly diverse consortium of associated microorganisms including algae, fungi, and bacteria. Several studies have highlighted the importance of coral‐associated bacteria and their potential roles in promoting the host fitness and survival. Recently, dynamics of coral‐associated microbiomes have been demonstrated to be linked to patterns of coral heat tolerance. Here, we examined the effect of elevated seawater temperature on the structure and diversity of bacterial populations associated with Porites lutea, using full‐length 16S rRNA sequences obtained from Pacific Biosciences circular consensus sequencing. We observed a significant increase in alpha diversity indices and a distinct shift in microbiome composition during thermal stress. There was a marked decline in the apparent relative abundance of Gammaproteobacteria family Endozoicomonadaceae after P. lutea had been exposed to elevated seawater temperature. Concomitantly, the bacterial community structure shifted toward the predominance of Alphaproteobacteria family Rhodobacteraceae. Interestingly, we did not observe an increase in relative abundance of Vibrio‐related sequences in our heat‐stressed samples even though the appearance of Vibrio spp. has often been detected in parallel with the increase in the relative abundance of Rhodobacteraceae during thermal bleaching in other coral species. The ability of full‐length 16S rRNA sequences in resolving taxonomic uncertainty of associated bacteria at a species level enabled us to identify 24 robust indicator bacterial species for thermally stressed corals. It is worth noting that the majority of those indicator species were members of the family Rhodobacteraceae. The comparison of bacterial community structure and diversity between corals in ambient water temperature and thermally stressed corals may provide a better understanding on how bacteria symbionts contribute to the resilience of their coral hosts to ocean warming.
A shift from membranous and stromal syndecan‐1 (CD138) expression to cytoplasmic CD138 expression is associated with poor prognosis in breast cancer
Authors: Kind Simon , Jaretzke Annika , Büscheck Franziska , Möller Katharina , Dum David , Höflmayer Doris , Hinsch Andrea , Weidemann Sören , Fraune Christoph , Möller‐Koop Christina , Hube‐Magg Claudia , Simon Ronald , Wilczak Waldemar , Lebok Patrick , Witzel Isabell , Müller Volkmar , Schmalfeldt Barbara , Paluchowski Peter , Wilke Christian , Heilenkötter Uwe , von Leffern Ingo , Krech Till , Krech Rainer H. , von der Assen Albert , Bawahab Ahmed Abdulwahab , Burandt Eike
Published: September 2019

Syndecan‐1 (CD138) is a transmembrane proteoglycan expressed in normal and malignant tissues. It is of interest because of a possible prognostic effect in tumors and as a target for Indatuximab, a monoclonal antibody coupled to a cytotoxic agent. To assess the prognostic role of CD138 expression in breast cancer (BCa), a tissue microarray containing 1535 BCa specimens was analyzed by immunohistochemistry. Cytoplasmic, membranous, and stromal CD138 staining was separately analyzed. In normal breast tissue, CD138 staining was limited to epithelial cell membranes. In cancers, membranous staining tended to become weaker or even disappeared (38.3% of cancers with absence of membranous staining) but cytoplasmic and stromal staining newly appeared in 29.7% and 58.1% of cancers. Loss of membranous epithelial CD138 staining as well as presence of cytoplasmic and stromal CD138 positivity were—to a variable degree—associated with high pT, high grade, nodal metastasis, estrogen receptor‐negative, progesterone receptor‐negative, human epidermal growth factor receptor 2+, and poor overall patient survival. A combined analysis of epithelial and stromal CD138 expression revealed a link to overall patient survival (P < .0001) with best prognosis for patients with stromal positivity and absence of cytoplasmic staining, the worst prognosis for cancers with cytoplasmic staining and stromal negativity and intermediate prognosis for patients having either cytoplasmic staining or stromal negativity. In multivariate analyses, CD138 was not independent of established prognostic features. In summary, these data reveal a compartment depending prognostic effect of CD138 expression in BCa with cytoplasmic positivity being linked to aggressive cancer and stromal CD138 being linked to a more favorable prognosis.
OIG criticizes HHS on services for detained children
Authors: Knopf Alison
Published: September 2019

Children crossing the southern border are traumatized and in need of mental health services under conditions that were only exacerbated by Department of Homeland Security (DHS) policy last year, according to an Office of Inspector General (OIG) report evaluating the performance of the Department of Health and Human Services (HHS) in caring for these children.
Enrichment of transplantable germ cells in salmonids using a novel monoclonal antibody by magnetic‐activated cell sorting
Authors: Ichida Kensuke , Hayashi Makoto , Miwa Misako , Kitada Ryota , Takahashi Momo , Fujihara Ryo , Boonanuntanasarn Surintorn , Yoshizaki Goro
Published: September 2019

In the fish germ cell transplantation system, only type A spermatogonia (ASGs) and oogonia are known to be incorporated into the recipient genital ridges, where they undergo gametogenesis. Therefore, high colonization efficiency can be achieved by enriching undifferentiated germ cells out of whole testicular cells. In this study, we used magnetic‐activated cell sorting (MACS) for enriching undifferentiated germ cells of rainbow trout using a monoclonal antibody that recognizes a specific antigen located on the germ cell membrane. We screened the antibodies to be used for MACS by performing immunohistochemistry on rainbow trout gonads. Two antibodies, nos. 172 and 189, showed strong signals for ASGs and oogonia. Next, we performed MACS with antibody no. 172 using gonadal cells isolated from vasa‐gfp rainbow trout showing GFP in undifferentiated germ cells. We found that GFP‐positive cells are highly enriched in antibody no. 172‐positive fractions. Finally, to examine the transplantability of MACS‐enriched cells, we intraperitoneally transplanted sorted or unsorted cells into recipient larvae. We observed that transplantability of sorted cells, particularly ovarian cells, were significantly higher than that of unsorted cells. Therefore, MACS with antibody no. 172 could enrich ASGs and oogonia and become a powerful tool to improve transplantation efficiency in salmonids.
Field drift correction of proton resonance frequency shift temperature mapping with multichannel fast alternating nonselective free induction decay readouts
Authors: Ferrer Cyril J. , Bartels Lambertus W. , van der Velden Tijl A. , Grüll Holger , Heijman Edwin , Moonen Chrit T. W. , Bos Clemens
Published: September 2019

Purpose

To demonstrate that proton resonance frequency shift MR thermometry (PRFS‐MRT) acquisition with nonselective free induction decay (FID), combined with coil sensitivity profiles, allows spatially resolved B0 drift‐corrected thermometry.

Methods

Phantom experiments were performed at 1.5T and 3T. Acquisition of PRFS‐MRT and FID were performed during MR‐guided high‐intensity focused ultrasound heating. The phase of the FIDs was used to estimate the change in angular frequency δωdrift per coil element. Two correction methods were investigated: (1) using the average δωdrift over all coil elements (0th‐order) and (2) using coil sensitivity profiles for spatially resolved correction. Optical probes were used for independent temperature verification. In‐vivo feasibility of the methods was evaluated in the leg of 1 healthy volunteer at 1.5T.

Results

In 30 minutes, B0 drift led to an apparent temperature change of up to –18°C and –98°C at 1.5T and 3T, respectively. In the sonicated area, both corrections had a median error of 0.19°C at 1.5T and –0.54°C at 3T. At 1.5T, the measured median error with respect to the optical probe was –1.28°C with the 0th‐order correction and improved to 0.43°C with the spatially resolved correction. In vivo, without correction the spatiotemporal median of the apparent temperature was at –4.3°C and interquartile range (IQR) of 9.31°C. The 0th‐order correction had a median of 0.75°C and IQR of 0.96°C. The spatially resolved method had the lowest median at 0.33°C and IQR of 0.80°C.

Conclusion

FID phase information from individual receive coil elements allows spatially resolved B0 drift correction in PRFS‐based MRT.
Effects of Transport Duration and Water Quality on Age-0 Walleye Stress and Survival
Authors: Ball Emily Elise , Goode Katherine Jean , Weber Michael John
Published: September 2019

Age-0 Walleye Sander vitreus are stocked to achieve several management objectives. However, stocked Walleye are exposed to numerous handling- and transport-related stressors that can negatively influence disease resistance, survival, year-class strength, and fisheries management objectives. The objective of this study was to evaluate relationships between Walleye transport duration with changes in water chemistry, whole-blood glucose and plasma cortisol concentrations, and short-term (48-h) mortality. Walleye were transported between 3.5 and 6.0 h and stocked into holding cages located at one of seven sites. Water quality and stress (via whole-blood glucose and plasma cortisol) and mortality were evaluated prior to, during, and at 0, 2, 24, and 48 h posttransportation. During transport, water temperatures generally decreased, while carbon dioxide concentrations fluctuated between 2.7 and 22.5 mg/L. Walleye whole-blood glucose and plasma cortisol concentrations varied by site and time since transport. Changes in carbon dioxide concentrations were associated with changes in whole-blood glucose concentrations. However, cumulative survival rates and plasma cortisol concentrations were not associated with water quality or transportation duration. Understanding Walleye tolerance to transportation-induced stress has the potential to enhance stocking programs by providing the opportunity for managers to make informed transport decisions.
Clinical and Economic Value of Nutrition in Healthcare: A Nurse's Perspective
Authors: Meehan Anita , Partridge Jamie , Jonnalagadda Satya S.
Published: September 2019

In the US healthcare system, malnutrition is a common condition, yet it remains underreported and underdiagnosed. The financial costs of disease‐associated malnutrition are substantial; hospital‐acquired conditions, readmissions, and prolonged lengths of stay are reported to cost as much as $150 billion per year. By contrast, nutrition‐focused quality improvement programs for inpatients can help reduce the negative impact of disease‐associated malnutrition. Such programs include systematic screening for malnutrition risk on admission, timely malnutrition diagnoses, and prompt nutrition interventions, which have been shown to lower rates of hospital‐acquired infections, shorten lengths of stay, reduce readmissions, and lessen costs of care. Nurses are ideally positioned to play critical roles in nutrition‐related care—screening for malnutrition on admission, monitoring for and addressing conditions that impede nutrition intake, and ensuring that prescribed nutrition interventions are delivered and administered or consumed. Such nursing support of multidisciplinary nutrition care contributes to better patient outcomes at lower costs.
Mechanisms of Weight Loss After Sleeve Gastrectomy and Adjustable Gastric Banding: Far More Than Just Restriction
Authors: Wang Yanmin , Guo Xiaomei , Lu Xiao , Mattar Samer , Kassab Ghassan
Published: September 2019

Obesity has reached global epidemic proportions in recent decades. Bariatric surgery is currently accepted as most effective in alleviating morbid obesity and related disorders. Sleeve gastrectomy (SG) and adjustable gastric banding (AGB) have gained popularity since the beginning of this century because of their efficacy, safety, and simplicity. SG, in particular, has emerged as the most popular bariatric procedure because of its simpler concept and shorter operative time compared with gastric bypass. Caloric restriction, however, cannot account for the sustained weight loss and improved glucose metabolism seen following SG and AGB. Other mechanisms, including changes in gastrointestinal hormone secretion, rearrangement of hypothalamic and vagal control, alteration in energy expenditure, and re‐regulation of bile acid metabolism and the intestinal flora environment, are thought to contribute to the postoperative benefits. This review focuses on clinical and experimental literature addressing the potential mechanisms for SG and AGB procedures in human and animal models. Understanding such mechanisms can provide important insight into how current gastric restrictive procedures work and how future treatments of obesity, both surgical and nonsurgical, can be developed.
An alternative to fortified schools: Using crime prevention through environmental design (CPTED) to balance student safety and psychological well‐being
Authors: Lamoreaux Daniel , Sulkowski Michael L.
Published: September 2019

In response to tragic school shootings, heightened attention has been devoted to making schools safer through the implementation of security features. However, excessive security measures have a negative impact on school climate, student functioning, and academic achievement. Therefore, there is a critical need to design schools that are safe and secure, yet also welcoming and comfortable. As a promising approach in this regard, crime prevention through environmental design (CPTED) is an architectural philosophy that aims to deter criminal or antisocial behavior through environmental design, and it includes a focus on natural surveillance, access control, and territorial reinforcement. This review discusses pertinent effects of the school environment on student outcomes, extant research on the impact of visible security measures, the relationship between students’ perceptions of safety and academic functioning, and how using CPTED could concomitantly address the physical safety and psychological comfort of students at school.
Examining the relationship between grit and academic achievement within K‐12 and higher education: A systematic review
Authors: Lam Kelly Ka Lai , Zhou Mingming
Published: September 2019

In recent years, grit has drawn increasing attention from both researchers and practitioners. As an important noncognitive indicator, grit has been used to understand individual success and performance in various fields. However, past empirical research has shown inconsistent findings on the relationship between grit and academic achievement. This study aims to review and synthesize past empirical findings on the relationship between grit and academic achievement. Forty‐four relevant articles involving a total of 60,133 participants met the inclusion criteria and were synthesized in this meta‐analysis. Our findings suggest that (a) overall grit level and its two facets (consistency of interest and perseverance of effort) are positively associated with academic achievement; (b) the association between grit and academic achievement is moderated by grade level; and (c) perseverance of effort shows the largest effect size on students’ academic achievement when compared with overall grit level and consistency of interest.
Benzene transformation in two dielectric barrier discharge reactors having special arrangement
Authors: Dey Ghasiram
Published: September 2019

Argon–benzene (Ar–Bz) gas phase plasma chemistry work is explored for benzene transformation employing the dielectric barrier discharge (DBD) cold plasma technique. To do so, experiments are carried out with two identical coaxial DBD reactors in serial‐type arrangements. The first carries moist Ar having 100% relative humidity (90% of total Ar flowing over water) and its outlet is mixed with Bz, which is saturated in the remaining 10% Ar at the inlet of the second reactor before plasma generation. This type of arrangement perhaps favors Bz transformation significantly for explicit products because the H2 generated in the first reactor as one of the major in situ products in the Ar‐moisture DBD system might facilitate chemical reduction of Bz to biphenyl in the second reactor during DBD. Conversely, H2O2, another product in Ar‐moisture discharge, enhances the yields of phenol. DBD outlet products, such as methane and leftover Bz, are analyzed and estimated with online gas chromatograph–flame ionization detector analysis, whereas H2 is analyzed with gas chromatograph–thermal conductivity detector. Additionally, the offline gas chromatograph–mass spectrometer analysis of acetone solutions of surface deposits obtained after discharge reveals the formation of phenol and biphenyl along with other products. The periodically analyzed data reveal that the generation of phenol, biphenyl, and CH4 relate directly to discharge duration and input moisture concentration.
Synthesis and Biological Evaluation of Novel Tetrahydro‐1,2,4‐triazines Incorporating Triazene and Tetraazene Moieties
Authors: Afsah Elsayed M. , Arab Anas M. , Abdel‐Galil Ebrahim
Published: September 2019

Diazotization of the hydrazone (2), derived from 6‐Acetyl‐2,4‐diphenyl‐tetrahydro‐1,2,4‐triazine (1), gave the corresponding 1‐chlorotriaz‐2‐enylidene derivative 3. Coupling of 3 with resorcinol and 2‐naphthol afforded the triazenes 4 and 5. The synthesis of tetrahydro‐1,2,4‐triazine incorporating triazene and piperidine or piperazine moieties has been achieved by coupling of 3 with the respective amine. Coupling of 3 with aromatic amines and polyhydroxy amines gave the corresponding tetraazenes. Whereas, coupling with the hydrazone 2 afforded pentaazene. In addition, the coupling of aryl diazonium salts with the hydrazone 2 was investigated.
Aqueous Synthesis of 3,4‐Dihydropyridinones from Acryloyl Chloride and Enaminones by Domino Amidation and Intramolecular Michael Addition
Authors: Luo Tian , Xu Haishun , Liu Yunyun
Published: September 2019

A facile method for the synthesis of 3,4‐dihydropyridin‐2(1H)‐ones (3,4‐dihydropyridinones) has been developed via the reactions of acryloyl chloride and enaminones. With the promotion of simple AlCl3 Lewis acid, the reactions proceed well in aqueous THF to provide diverse 3,4‐dihydropyridinones via the formation of new C−N and C−C bonds resulting from domino amidation and intramolecular Michael addition transformation.