bluuebunny/crossref_metadata_2025 huggingface dataset:
Zur Biegung von Infraleichtbetonbauteilen – Werkstoff‐, Verbund‐, Trag‐ und Verformungsverhalten
Authors: Hückler Alex , Schlaich Mike
Published: May 2017

Infraleichtbeton (ILC) ist mit einer Trockenrohdichte von weniger als 800 kg/m3 ein Hochleistungsleichtbeton (HPLWAC). Seine guten Dämmeigenschaften erlauben ohne zusätzliche Wärmedämmung Sichtbetonkonstruktionen, die wegen eines monolithischen Wandaufbaus einfach zu recyceln sind und ILC zu einem potenziellen Kandidaten für nachhaltiges Bauen machen. Leichtbeton mit derart niedrigen Dichten neigt dazu, sich linear elastisch zu verhalten und ist vergleichbar spröde wie ein Ultrahochleistungsbeton (UHPC). In diesem Aufsatz werden neben dem Biegetragverhalten auch der Verbund zur Bewehrung und die Zugversteifung von ILC unter Berücksichtigung dieser besonderen Materialeigenschaften beschrieben. Die hier vorgestellte theoretische und experimentelle Forschung gibt auch Einblick in das Verformungs‐ und Rissverhalten sowie die Duktilität von ILC‐Bauteilen und liefert als Ergebnis eine Berechnungshilfe für biegebeanspruchte ILC‐Balken.
Group 4 Metal Complexes of Phenylene–Salalen Ligands in rac‐Lactide Polymerization Giving High Molecular Weight Stereoblock Poly(lactic acid)
Authors: Stopper Ayellet , Rosen Tomer , Venditto Vincenzo , Goldberg Israel , Kol Moshe
Published: May 2017

Phenylene–salalens—sequential tetradentate dianionic {ONNO}‐type ligands that include an ortho‐phenylene group bridging between an imine and amine internal donors bound to phenol arms with a broad variety of substitution patterns are described. Zirconium and hafnium complexes of the type [{ONNO}M(O‐tBu)2] were formed as single diastereomers, which, according to crystallographic structures, featured the fac(around the amine)‐mer(around the imine) wrapping mode. The reactivity and stereoselectivity in rac‐lactide (rac‐LA) polymerizations were found to depend on the substitution pattern: complexes featuring small groups on the imine‐side phenol and bulky groups on the amine‐side phenol exhibited the favorable combination of high activity and high isoselectivity (Pm≤0.91). Isotactic stereoblock copolymers of high molecular weights were prepared. The polymers crystallized in the stereocomplex phase according to thermal (differential scanning calorimetry) and crystallographic analysis.
Exceptionally Long‐Lived Photodriven Multi‐Electron Storage without Sacrificial Reagents
Authors: Kuss‐Petermann Martin , Wenger Oliver S.
Published: May 2017

Photoexcitation of a molecular pentad in the presence of Sc3+ in de‐aerated CH3CN leads to a quinone dianion that is stable on the millisecond timescale. Light‐driven electron accumulation on the quinone unit is sensitized by two Ru(bpy)32+ complexes in an intramolecular process, which relies on covalently attached triarylamine donors rather than on sacrificial reagents. Lewis acid–Lewis base interactions between Sc3+ and quinone dianion are responsible for the exceptionally long lifetime of this photoproduct. Our study of photoinduced multi‐electron transfer is relevant in the greater context of solar energy conversion.
Tandem Oxidative Derivatization of Nitrene Insertion Products for the Highly Diastereoselective Synthesis of 1,3‐aminoalcohols
Authors: Alderson Juliet M. , Schomaker Jennifer M.
Published: May 2017

Transition‐metal‐catalyzed nitrene insertion into tertiary C−H bonds located at stereogenic carbons often results in mixtures of diastereomeric products, especially if the reaction proceeds through a concerted pathway. In this communication, we report a solution to this problem that invokes a one‐pot, silver‐catalyzed C−H nitrene transfer reaction. Nitrene insertion is followed by facile oxidation of the amine to an imine and nucleophilic addition to furnish α‐tertiary amine 1,3‐aminoalcohol products in high diastereoselectivities. The silver catalyst, PhIO oxidant, and TEMPO additive are crucial to success in this unusual oxidation, which is proposed to occur via hydrogen‐atom abstraction from pre‐activation of the initial nitrene insertion product by additional oxidant.
Somatic mutation profiles of clear cell endometrial tumors revealed by whole exome and targeted gene sequencing
Authors: Le Gallo Matthieu , Rudd Meghan L. , Urick Mary Ellen , Hansen Nancy F. , Zhang Suiyuan ,   NISC Comparative Sequencing Program, Lozy Fred , Sgroi Dennis C. , Vidal Bel August , Matias‐Guiu Xavier , Broaddus Russell R. , Lu Karen H. , Levine Douglas A. , Mutch David G. , Goodfellow Paul J. , Salvesen Helga B. , Mullikin James C. , Bell Daphne W.
Published: May 2017

BACKGROUND

The molecular pathogenesis of clear cell endometrial cancer (CCEC), a tumor type with a relatively unfavorable prognosis, is not well defined. We searched exome‐wide for novel somatically mutated genes in CCEC and assessed the mutational spectrum of known and candidate driver genes in a large cohort of cases.

METHODS

We conducted whole exome sequencing of paired tumor‐normal DNAs from 16 cases of CCEC (12 CCECs and the CCEC components of 4 mixed histology tumors). Twenty‐two genes‐of‐interest were Sanger‐sequenced from another 47 cases of CCEC. Microsatellite instability (MSI) and microsatellite stability (MSS) were determined by genotyping 5 mononucleotide repeats.

Results

Two tumor exomes had relatively high mutational loads and MSI. The other 14 tumor exomes were MSS and had 236 validated nonsynonymous or splice junction somatic mutations among 222 protein‐encoding genes. Among the 63 cases of CCEC in this study, we identified frequent somatic mutations in TP53 (39.7%), PIK3CA (23.8%), PIK3R1 (15.9%), ARID1A (15.9%), PPP2R1A (15.9%), SPOP (14.3%), and TAF1 (9.5%), as well as MSI (11.3%). Five of 8 mutations in TAF1, a gene with no known role in CCEC, localized to the putative histone acetyltransferase domain and included 2 recurrently mutated residues. Based on patterns of MSI and mutations in 7 genes, CCEC subsets molecularly resembled serous endometrial cancer (SEC) or endometrioid endometrial cancer (EEC).

CONCLUSION

Our findings demonstrate molecular similarities between CCEC and SEC and EEC and implicate TAF1 as a novel candidate CCEC driver gene. Cancer 2017;123:3261‐8. © 2017 American Cancer Society.
Murine thymic NK cells: A case of identity
Authors: Male Victoria , Brady Hugh J. M.
Published: May 2017

Just over a decade ago, it was established that NK cells in the thymus do not follow precisely the same developmental pathway as conventional NK cells that develop in the bone marrow. Subsequently, it has emerged that NK cells are one branch of a family of innate lymphoid cells (ILCs). ILC1s and thymic NK cells have, however, sufficient similarities such that questions have been raised about how distinctive each cell type is from the other. In this issue of European Journal of Immunology, Gabrielli et al. [Eur. J. Immunol. 2017. 47: 800–805] make a detailed study of the transcription factor requirements of murine thymic NK cells. They provide a valuable insight into the distinctive identity of thymic NK cells with regard to Tbet, Nfil3, Id2, and Ets1. In addition, they clarify the nature of DX5 expression on NK cells and ILC‐like cells in the murine thymus.
Chemometric techniques to protect the traditional Austrian pumpkin seed oil
Authors: Zettl Daniela , Bandoniene Donata , Meisel Thomas , Wegscheider Wolfhard , Rantitsch Gerd
Published: May 2017

The aim of this work was to establish suitable chemometric techniques for establishing provenance of pumpkin seed and pumpkin seed oil from the regions of Austria, China and Russia, in order to protect the authentic Austrian products from fraud and mislabelling. To achieve this goal, three different chemometric approaches, projection to latent structures (PLS), soft independent modelling of class analogy (SIMCA) and support vector machines (SVM) were applied on two different trace element data sets. To evaluate the reliability of the classification achieved, the results were validated on an independent test set. PLS and SVM performed similarly in many situations. Also the prediction of the discriminating techniques was in accordance with the modelling technique SIMCA. But PLS alone can be used to separate Austrian from non‐Austrian pumpkin seed and pumpkin seed oil samples based on trace element data.

Practical applications: For various reasons, more and more consumers prefer local products with a defined geographical origin. Producers also advertise the geographical origin and are trying to increase the value of their products by praising the quality of their products through a geographical designation. Unfortunately, there is an increases of abuse in these products which also comprise the ‘Styrian pumpkin seed oil PGI’ with falsely declared geographical origin. The demand for an analytical approach how to counteract the falsification of origin of Styrian pumpkin seed oil has increased considerably. The aim of this work is to establish an analytical method with suitable chemometric techniques for establishing the provenance of pumpkin seed oil from the regions of Austria, China and Russia, in order to protect the authentic Austrian products from fraud and mislabelling.

PLS, SIMCA and SVM chemometric techniques are applied for establishing the provenance of pumpkin seed and pumpkin seed oil. PLS and SVM perform similarly in most situations and are in accordance with SIMCA models. However, the classification task can be solved by PLS only.
Use of genetic toxicity data in GHS mutagenicity classification and labeling of substances
Authors: Ball Nicholas S. , Hollnagel Heli M.
Published: May 2017

One of the key outcomes of testing the potential genotoxicity or mutagenicity of a substance is the conclusion on whether the substance should be classified as a germ cell mutagen and the significance of this for other endpoints such as carcinogenicity. The basis for this conclusion are the criteria presented in classification and labelling systems such as the Globally Harmonized System for classification and labeling (GHS). This article reviews the classification criteria for germ cell mutagenicity and carcinogenicity and how they are applied to substances with evidence of mutagenicity. The implications and suitability of such a classification for hazard communication, risk assessment, and risk management are discussed. It is proposed that genotoxicity assessments should not focus on specifically identifying germ cell mutagens, particularly given the challenges associated with communicating this information in a meaningful way. Rather the focus should be on deriving data to characterize the mode of action and for use in the risk assessment of mutagens, which could then feed into a more robust, risk based management of mutagenic substances versus the current more hazard based approaches. Environ. Mol. Mutagen. 58:354–360, 2017. © 2017 Wiley Periodicals, Inc.
Mechanisms of DNA damage, repair, and mutagenesis
Authors: Chatterjee Nimrat , Walker Graham C.
Published: May 2017

Living organisms are continuously exposed to a myriad of DNA damaging agents that can impact health and modulate disease‐states. However, robust DNA repair and damage‐bypass mechanisms faithfully protect the DNA by either removing or tolerating the damage to ensure an overall survival. Deviations in this fine‐tuning are known to destabilize cellular metabolic homeostasis, as exemplified in diverse cancers where disruption or deregulation of DNA repair pathways results in genome instability. Because routinely used biological, physical and chemical agents impact human health, testing their genotoxicity and regulating their use have become important. In this introductory review, we will delineate mechanisms of DNA damage and the counteracting repair/tolerance pathways to provide insights into the molecular basis of genotoxicity in cells that lays the foundation for subsequent articles in this issue. Environ. Mol. Mutagen. 58:235–263, 2017. © 2017 Wiley Periodicals, Inc.
Unconscious selection drove seed enlargement in vegetable crops
Authors: Kluyver Thomas A. , Jones Glynis , Pujol Benoît , Bennett Christopher , Mockford Emily J. , Charles Michael , Rees Mark , Osborne Colin P.
Published: May 2017

Domesticated grain crops evolved from wild plants under human cultivation, losing natural dispersal mechanisms to become dependent upon humans, and showing changes in a suite of other traits, including increasing seed size. There is tendency for seed enlargement during domestication to be viewed as the result of deliberate selection for large seeds by early farmers. However, like some other domestication traits, large seeds may have evolved through natural selection from the activities of people as they gathered plants from the wild, or brought them into cultivation in anthropogenic settings. Alternatively, larger seeds could have arisen via pleiotropic effects or genetic linkage, without foresight from early farmers, and driven by selection that acted on other organs or favored larger plants. We have separated these unconscious selection effects on seed enlargement from those of deliberate selection, by comparing the wild and domesticated forms of vegetable crops. Vegetables are propagated by planting seeds, cuttings, or tubers, but harvested for their edible leaves, stems, or roots, so that seed size is not a direct determinant of yield. We find that landrace varieties of seven vegetable crops have seeds that are 20% to 2.5-times larger than those of their closest wild relatives. These domestication effect sizes fall completely within the equivalent range of 14% to 15.2-times for grain crops, although domestication had a significantly larger overall effect in grain than vegetable crops. Seed enlargement in vegetable crops that are propagated vegetatively must arise from natural selection for larger seeds on the occasions when plants recruit from seed and are integrated into the crop gene pool, or via a genetic link to selection for larger plants or organs. If similar mechanisms operate across all species, then unconscious selection during domestication could have exerted stronger effects on the seed size of our staple crops than previously realized.
A genomic footprint of hybrid zone movement in crested newts
Authors: Wielstra Ben , Burke Terry , Butlin Roger K. , Avcı Aziz , Üzüm Nazan , Bozkurt Emin , Olgun Kurtuluş , Arntzen Jan W.
Published: May 2017

Speciation typically involves a stage in which species can still exchange genetic material. Interspecific gene flow is facilitated by the hybrid zones that such species establish upon secondary contact. If one member of a hybridizing species pair displaces the other, their hybrid zone would move across the landscape. Although theory predicts that moving hybrid zones quickly stagnate, hybrid zones tracked over one or a few decades do not always follow such a limitation. This suggests that hybrid zones have the potential to traverse considerable distances over extended periods of time. When hybrid zones move, introgression is predicted to result in biased gene flow of selectively neutral alleles, from the receding species into the advancing species. We test for such a genomic footprint of hybrid zone movement in a pair of crested newt species (genus Triturus) for which we have a priori support for westward hybrid zone movement. We perform a multilocus phylogeographical survey and conduct Bayesian clustering analysis, estimation of ancestry and heterozygosity, and geographical cline analysis. In a 600 km wide area east of the present day hybrid zone a genomic footprint constitutes empirical evidence consistent with westward hybrid zone movement. The crested newt case suggests that hybrid zone movement can occur over an extensive span of time and space. Inferring hybrid zone movement provides fundamental insight into historical biogeography and the speciation process, and we anticipate that hybrid zones will prove to be far more mobile than currently appreciated.
A high‐order element based adaptive mesh refinement strategy for three‐dimensional unstructured grid
Authors: Gou Jinlan , Yuan Xin , Su Xinrong
Published: May 2017

Adaptive mesh refinement (AMR) shows attractive properties in automatically refining the flow region of interest, and with AMR, better prediction can be obtained with much less labor work and cost compared to manually remeshing or the global mesh refinement. Cartesian AMR is well established; however, AMR on hybrid unstructured mesh, which is heavily used in the high‐Reynolds number flow simulation, is less matured and existing methods may result in degraded mesh quality, which mostly happens in the boundary layer or near the sharp geometric features. User intervention or additional constraints, such as freezing all boundary layer elements or refining the whole boundary layer, are required to assist the refinement process. In this work, a novel AMR strategy is developed to handle existing difficulties. In the new method, high‐order unstructured elements are first generated based on the baseline mesh; then the refinement is conducted in the parametric space; at last, the mesh suitable for the solver is output. Generating refined elements in the parametric space with high‐order elements is the key of this method and this helps to guarantee both the accuracy and robustness. With the current method, 3‐dimensional hybrid unstructured mesh of huge size and complex geometry can be automatically refined, without user intervention nor additional constraints. With test cases including the 2‐dimensional airfoil and 3‐dimensional full aircraft, the current AMR method proves to be accurate, simple, and robust.
The effect of health care expenditure on patient outcomes: Evidence from English neonatal care
Authors: Watson Samuel , Arulampalam Wiji , Petrou Stavros ,   on behalf of NESCOP
Published: May 2017

The relationship between health care expenditure and health outcomes has been the subject of recent academic inquiry in order to inform cost‐effectiveness thresholds for health technology assessment agencies. Previous studies in public health systems have relied upon data aggregated at the national or regional level; however, there remains debate about whether the supply side effect of changes to expenditure are identifiable using data at this level of aggregation. We use detailed patient data derived from electronic neonatal records across England along with routinely available cost data to estimate the effect of changes to patient expenditure on clinical health outcomes in a well‐defined patient population. A panel of 32 neonatal intensive care units for the period 2009–2013 was constructed. Accounting for the potential endogeneity of expenditure a £100 increase in the cost per intensive care cot day (sample average cost: £1,127) is estimated to reduce the risk of mortality of 0.38 percentage points (sample average mortality: 11.0%) in neonatal intensive care. This translates into a cost per life saved in neonatal intensive care of approximately £420,000.
Human hepatocellular carcinomas with a periportal phenotype have the lowest potential for early recurrence after curative resection
Authors: Désert Romain , Rohart Florian , Canal Frédéric , Sicard Marie , Desille Mireille , Renaud Stéphanie , Turlin Bruno , Bellaud Pascale , Perret Christine , Clément Bruno , Lê Cao Kim‐Anh , Musso Orlando
Published: May 2017

Hepatocellular carcinomas (HCCs) exhibit a diversity of molecular phenotypes, raising major challenges in clinical management. HCCs detected by surveillance programs at an early stage are candidates for potentially curative therapies (local ablation, resection, or transplantation). In the long term, transplantation provides the lowest recurrence rates. Treatment allocation is based on tumor number, size, vascular invasion, performance status, functional liver reserve, and the prediction of early (<2 years) recurrence, which reflects the intrinsic aggressiveness of the tumor. Well‐differentiated, potentially low‐aggressiveness tumors form the heterogeneous molecular class of nonproliferative HCCs, characterized by an approximate 50% β‐catenin mutation rate. To define the clinical, pathological, and molecular features and the outcome of nonproliferative HCCs, we constructed a 1,133‐HCC transcriptomic metadata set and validated findings in a publically available 210‐HCC RNA sequencing set. We show that nonproliferative HCCs preserve the zonation program that distributes metabolic functions along the portocentral axis in normal liver. More precisely, we identified two well‐differentiated, nonproliferation subclasses, namely periportal‐type (wild‐type β‐catenin) and perivenous‐type (mutant β‐catenin), which expressed negatively correlated gene networks. The new periportal‐type subclass represented 29% of all HCCs; expressed a hepatocyte nuclear factor 4A–driven gene network, which was down‐regulated in mouse hepatocyte nuclear factor 4A knockout mice; were early‐stage tumors by Barcelona Clinic Liver Cancer, Cancer of the Liver Italian Program, and tumor–node–metastasis staging systems; had no macrovascular invasion; and showed the lowest metastasis‐specific gene expression levels and TP53 mutation rates. Also, we identified an eight‐gene periportal‐type HCC signature, which was independently associated with the highest 2‐year recurrence‐free survival by multivariate analyses in two independent cohorts of 247 and 210 patients. Conclusion: Well‐differentiated HCCs display mutually exclusive periportal or perivenous zonation programs. Among all HCCs, periportal‐type tumors have the lowest intrinsic potential for early recurrence after curative resection. (Hepatology 2017;66:1502–1518).
Use of moist oral snuff (snus) and pancreatic cancer: Pooled analysis of nine prospective observational studies
Authors: Araghi Marzieh , Rosaria Galanti Maria , Lundberg Michael , Lager Anton , Engström Gunnar , Alfredsson Lars , Knutsson Anders , Norberg Margareta , Sund Malin , Wennberg Patrik , Trolle Lagerros Ylva , Bellocco Rino , Pedersen Nancy L. , Östergren Per‐Olof , Magnusson Cecilia
Published: May 2017

While smoking is a well‐established risk factor for pancreatic cancer, the effect of smokeless tobacco is less well understood. We used pooled individual data from the Swedish Collaboration on Health Effects of Snus Use to assess the association between Swedish snus use and the risk of pancreatic cancer. A total of 424,152 male participants from nine cohort studies were followed up for risk of pancreatic cancer through linkage to health registers. We used shared frailty models with random effects at the study level, to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for confounding factors. During 9,276,054 person‐years of observation, 1,447 men developed pancreatic cancer. Compared to never‐snus use, current snus use was not associated with risk of pancreatic cancer (HR 0.96, 95% CI 0.83–1.11) after adjustment for smoking. Swedish snus use does not appear to be implicated in the development of pancreatic cancer in men. Tobacco smoke constituents other than nicotine or its metabolites may account for the relationship between smoking and pancreatic cancer.
In‐vitro analysis of early calcification in aortic valvular interstitial cells using Laser‐Induced Breakdown Spectroscopy (LIBS)
Authors: Davari Seyyed Ali , Masjedi Shirin , Ferdous Zannatul , Mukherjee Dibyendu
Published: May 2017

Calcific aortic valve disease (CAVD) is a major cardiovascular disorder caused by osteogenic differentiation of valvular interstitial cells (VICs) within aortic valves. Conventional methods like colorimetric assays and histology fail to detect small calcium depositions during in‐vitro VIC cultures. Laser‐induced breakdown spectroscopy (LIBS) is a robust analytical tool used for inorganic materials characterizations, but relatively new to biomedical applications. We employ LIBS, for the first time, for quantitative in‐vitro detection of calcium depositions in VICs at various osteogenic differentiation stages. VICs isolated from porcine aortic valves were cultured in osteogenic media over various days. Colorimetric calcium assays based on arsenazo dye and Von Kossa staining measured the calcium depositions within VICs. Simultaneously, LIBS signatures for Ca I (422.67 nm) atomic emission lines were collected for estimating calcium depositions in lyophilized VIC samples. Our results indicate excellent linear correlation between the calcium assay and our LIBS measurements. Furthermore, unlike the assay results, the LIBS results could resolve calcium signals from cell samples with as early as 2 days of osteogenic culture. Quantitatively, the LIBS measurements establish the limit of detection for calcium content in VICs to be ∼0.17±0.04 μg which indicates a 5‐fold improvement over calcium assay. Picture: Quantitative LIBS enables in‐vitro analysis for early stage detection of calcium deposition within aortic valvular interstitial cells (VICs).

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Double‐hydrophobic elastin‐like polypeptides with added functional motifs: Self‐assembly and cytocompatibility
Authors: Le Duc H. T. , Tsutsui Yoko , Sugawara‐Narutaki Ayae , Yukawa Hiroshi , Baba Yoshinobu , Ohtsuki Chikara
Published: May 2017

We have recently developed a novel double‐hydrophobic elastin‐like triblock polypeptide called GPG, designed after the uneven distribution of two different hydrophobic domains found in elastin, an extracellular matrix protein providing elasticity and resilience to tissues. Upon temperature trigger, GPG undergoes a sequential self‐assembling process to form flexible beaded nanofibers with high homogeneity and excellent dispersibility in water. Given that GPG might be a potential elastin‐mimetic material, we sought to explore the biological activities of this block polypeptide. Besides GPG, several functionalized derivatives were also constructed by fusing functional motifs such as KAAK or KAAKGRGDS at the C‐terminal of GPG. Although the added motifs affected the kinetics of fiber formation and β‐sheet contents, all three GPGs assembled into beaded nanofibers at the physiological temperature. The resulting GPG nanofibers preserved their beaded structures in cell culture medium; therefore, they were coated on polystyrene substrates to study their cytocompatibility toward mouse embryonic fibroblasts, NIH‐3T3. Among the three polypeptides, GPG having the cell‐binding motif GRGDS derived from fibronectin showed excellent cell adhesion and cell proliferation properties compared to other conventional materials, suggesting its promising applications as extracellular matrices for mammalian cells. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2475–2484, 2017.
Regulation of RAW264.7 macrophage polarization on smooth and rough surface topographies by galectin‐3
Authors: Kianoush F. , Nematollahi M. , Waterfield J. D. , Brunette D. M.
Published: May 2017

Recognition of topographical features induces phenotypic changes in macrophages although the receptors and signaling pathways are not completely characterized. As integrin molecules in focal adhesions/podosomes are in intimate contact with topography and topography modulates the NFkB pathway through cholesterol enriched raft‐associated adhesive signaling structures we hypothesized that a cell‐surface signaling complex comprised of galectin‐3 together with its ligand CD98 and integrinβ1 is important for topography‐directed lineage determination. This study used polished, sand blasted and acid etched (SLA) surfaces and two novel grooved topographies (G1 and G2) produced by anisotropic etching of Si <1 1 0> to evaluate the role of galectin‐3 in macrophage polarization in RAW 264.7 macrophages, as determined by gene expression and morphology. In the presence of the galectin‐3 inhibitor, lactose, the M2 marker (mannose receptor) was down‐regulated while the M1 marker (iNOS) was up‐regulated on smooth and rough surfaces. This skewing of phenotype suggests a role for galectin‐3 in macrophage polarization towards the M2 phenotype. Additionally, we evaluated the role of PI3K on polarization using PI3K inhibitor LY294002. We found that the M2 marker was down‐regulated on both PO (surface polished) and G1 surfaces implicating PI3K in lineage determination. We also found that surface topography altered cell morphology; macrophages had a larger area on G2 surfaces. Lactose treatment significantly reduced the cell area on all topographies suggesting that the galectin‐3 is also involved in signaling complexes triggering the rearrangement of the actin cytoskeleton. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2499–2509, 2017.
Wear resistance of poly(2‐methacryloyloxyethyl phosphorylcholine)‐grafted carbon fiber reinforced poly(ether ether ketone) liners against metal and ceramic femoral heads
Authors: Yamane Shihori , Kyomoto Masayuki , Moro Toru , Hashimoto Masami , Takatori Yoshio , Tanaka Sakae , Ishihara Kazuhiko
Published: May 2017

Younger, active patients who undergo total hip arthroplasty (THA) have increasing needs for wider range of motion and improved stability of the joint. Therefore, bearing materials having not only higher wear resistance but also mechanical strength are required. Carbon fiber‐reinforced poly(ether ether ketone) (CFR‐PEEK) is known as a super engineering plastic that has great mechanical strength. In this study, we focused on poly(2‐methacryloyloxyethyl phosphorylcholine) (PMPC)‐grafted CFR‐PEEK and investigated the effects of PMPC grafting and the femoral heads materials on the wear properties of CFR‐PEEK liners. Compared with untreated CFR‐PEEK, the PMPC‐grafted CFR‐PEEK surface revealed higher wettability and lower friction properties under aqueous circumstances. In the hip simulator wear test, wear particles generated from the PMPC‐grafted CFR‐PEEK liners were fewer than those of the untreated CFR‐PEEK liners. There were no significant differences in the size and the morphology of the wear particles between the differences of PMPC‐grafting and the counter femoral heads. Zirconia‐toughened alumina (ZTA) femoral heads had significantly smoother surfaces compared to cobalt–chromium–molybdenum alloy femoral heads after the hip simulator test. Thus, we conclude that the bearing combination of the PMPC‐grafted CFR‐PEEK liner and ZTA head is expected to be a lifelong bearing interface in THA. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1028–1037, 2018.
Insulin‐Stimulated Bone Blood Flow and Bone Biomechanical Properties Are Compromised in Obese, Type 2 Diabetic OLETF Rats
Authors: Dirkes Rebecca K , Ortinau Laura C , Rector R Scott , Olver T Dylan , Hinton Pamela S
Published: May 2017

Type 2 diabetes (T2D) increases skeletal fragility and fracture risk; however, the underlying mechanisms remain to be identified. Impaired bone vascular function, in particular insulin‐stimulated vasodilation and blood flow is a potential, yet unexplored mechanism. The purpose of this study was to determine the effects of T2D on femoral biomechanical properties, trabecular microarchitecture, and insulin‐stimulated bone vasodilation by comparison of hyperphagic Otsuka Long‐Evans Tokushima Fatty (OLETF) rats with normoglycemic control OLETF rats. Four‐week old, male OLETF rats were randomized to two groups: type 2 diabetes (O‐T2D) or normoglycemic control (O‐CON). O‐T2D were allowed ad libitum access to a rodent chow diet and O‐CON underwent moderate caloric restriction (30% restriction relative to intake of O‐T2D) to maintain normal body weight (BW) and glycemia until 40 weeks of age. Hyperphagic O‐T2D rats had significantly greater BW, body fat, and blood glucose than O‐CON. Total cross‐sectional area (Tt.Ar), cortical area (Ct.Ar), Ct.Ar/Tt.Ar, and polar moment of inertia of the mid‐diaphyseal femur adjusted for BW were greater in O‐T2D rats versus O‐CON. Whole‐bone biomechanical properties of the femur assessed by torsional loading to failure did not differ between O‐T2D and O‐CON, but tissue‐level strength and stiffness adjusted for BW were reduced in O‐T2D relative to O‐CON. Micro–computed tomography (μCT) of the distal epiphysis showed that O‐T2D rats had reduced percent bone volume, trabecular number, and connectivity density, and greater trabecular spacing compared with O‐CON. Basal tibial blood flow assessed by microsphere infusion was similar in O‐T2D and O‐CON, but the blood flow response to insulin stimulation in both the proximal epiphysis and diaphyseal marrow was lesser in O‐T2D compared to O‐CON. In summary, impaired insulin‐stimulated bone blood flow is associated with deleterious changes in bone trabecular microarchitecture and cortical biomechanical properties in T2D, suggesting that vascular dysfunction might play a causal role in diabetic bone fragility. © 2017 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.
Adsorptive granulocyte/monocyte apheresis use in severe ulcerative colitis and determination of changes in plasma cytokines
Authors: Beltrán Belén , Sáez‐González Esteban , Moret Inés , Díaz‐Jaime Francia C. , Alvarez‐Sotomayor Diego , Cerrillo Elena , Iborra Marisa , Bastida Guillermo , Aguas Mariam , Nos Pilar
Published: May 2017

Despite controversy regarding the use of granulocyte/monocyte adsorption (GMA) in inflammatory bowel disease, some studies have shown favorable outcomes when it is used in steroid‐dependent patients with ulcerative colitis (UC). The mechanisms responsible for such outcomes are not well characterized, but changes in immune cell populations and cytokine levels have been suggested to play an important role. We report the cases of 3 patients with chronically active severe UC who underwent GMA due to an inadequate response to standard and rescue therapy, as well as changes to their plasma cytokine profile. All the patients presented severe UC that was only partially responsive to various immunosuppressive drugs, and they were, therefore, referred for colectomy; however, all 3 refused this option, which led to the compassionate use of GMA as a last therapeutic resort. Following GMA treatment, rapid normalization of the clinical, endoscopic and laboratory parameters was observed in all the patients. Despite having achieved a good response, most cytokines remained at high concentrations after GMA, and only two, IL‐6 and IL‐8, showed a clear decrease throughout the GMA sessions. In view of this outcome, we hypothesize that GMA can help to lower the inflammatory load, thereby enhancing the effect of biologic drugs. To confirm this hypothesis and explore further indications for GMA, we propose the need for research directed toward the characterization of immune cell populations and their specific cytokine production rather than global cytokine assessment.
Curcumin: A Naturally Occurring Modulator of Adipokines in Diabetes
Authors: Hajavi Jafar , Momtazi Amir Abbas , Johnston Thomas P. , Banach Maciej , Majeed Muhammed , Sahebkar Amirhossein
Published: May 2017

Curcumin, the bioactive component of turmeric, has been used for the treatment of several diseases including diabetes and its complications. Curcumin has been shown to exert pleiotropic effects by modulating different signaling molecules, including transcription factors, chemokines, cytokines, and adipokines. Disturbed regulation of adipokines, which include adiponectin, leptin, resistin, and visfatin, are implicated in the development of insulin resistance and Type 2 diabetes. Here, we review the findings of in vitro, in vivo, and clinical studies on the modulating effects that curcumin treatment exerts on adipokines. Additionally, we examine the potential beneficial effects of the activity of curcumin in the prevention and treatment of diabetes and its comorbidities. J. Cell. Biochem. 118: 4170–4182, 2017. © 2017 Wiley Periodicals, Inc.
A comparative study of the influence of salt concentration on the performance of an osmotic membrane bioreactor and a sequencing batch reactor
Authors: Soler‐Cabezas José L , Luján‐Facundo Maria J , Mendoza‐Roca José A , Vincent‐Vela Maria C , Pastor‐Alcañiz Laura
Published: May 2017

BACKGROUND

An osmotic membrane bioreactor (OMBR) is a wastewater treatment technique that presents low energy requirements, low membrane fouling and high removal of nutrients and organic matter. However, reverse salt flux is the main disadvantage because it causes conductivity increase in the bioreactor. This study compares the performance of a sequencing batch reactor (SBR) and an OMBR in terms of chemical oxygen demand (COD) removal, soluble microbial products (SMP) and extracellular polymeric substances (EPS) production. For that, the influent conductivity in the SBR was increased as this increases conductivity in the osmotic membrane bioreactor.

RESULTS

Comparing the results obtained at two mixed liquor suspended solids (MLSS) concentrations in terms of membrane fouling, a concentration of 5 g L−1 of MLSS was chosen for the comparison with the SBR. The SBR achieved slightly higher COD removal efficiencies than the OMBR is spite of the accumulation of cellular debris in the membrane bioreactor. The accumulation of SMP and EPS in the OMBR was also higher than in the SBR due to the cellular debris and organic matter accumulation. In both reactors the microbial activity measured in terms of standard oxygen uptake rate decreased due to the increase of salt concentration in the bioreactor.

CONCLUSIONS

As a conclusion, OMBR will be especially feasible when the draw solution is a residual stream of the same industry, like tannery wastewater or table olive processing. © 2017 Society of Chemical Industry
Serotonin axons in the neocortex of the adult female mouse regrow after traumatic brain injury
Authors: Kajstura Tymoteusz J. , Dougherty Sarah E. , Linden David J.
Published: May 2017

It is widely held that injured neurons in the central nervous system do not undergo axonal regrowth. However, there is mounting evidence that serotonin axons are a notable exception. Serotonin axons undergo long‐distance regrowth in the neocortex after amphetamine lesion, and, following a penetrating stab injury, they can regrow from cut ends to traverse the stab rift. Traumatic brain injury (TBI) is clinically prevalent and can lead to pathologies, such as depression, that are related to serotonergic dysfunction. Thus, whether serotonin axons can regrow after TBI is an important question. We used two models for TBI—a persistent open skull condition and controlled cortical impact—to evoke injury in adult female mouse neocortex, and assessed serotonin axon density 1 week, 1 month, and 3 months after injury by serotonin transporter immunohistochemistry. We found that after both forms of TBI, serotonin axon density is decreased posterior but not anterior to the injury site when measured in layer 1 at 1 week post surgery, and that serotonin axons are capable of regrowing into the distal zone to increase density by 1 month post surgery. This pattern is consistent with the anterior‐to‐posterior course of serotonin axons in the neocortex. TBI in these models is associated with significant reactive astrogliosis both anterior and posterior to the impact, but the degree of reactive astrogliosis is not correlated with serotonin axon density when measured 1 week after TBI. Microglial density remains constant following both types of injuries, but microglial condensation was detected 1 week after controlled cortical impact.
Non‐contrast‐enhanced T1‐weighted MRI of myocardial radiofrequency ablation lesions
Authors: Guttman Michael A. , Tao Susumu , Fink Sarah , Kolandaivelu Aravindan , Halperin Henry R. , Herzka Daniel A.
Published: May 2017

Purpose

To demonstrate imaging of radiofrequency ablation lesions with non‐contrast‐enhanced T1‐weighted (T1w) MRI.

Methods

Fifteen swine underwent left ventricular ablation followed by MRI using different preparations: endocardial or epicardial ablation of naïve animal, or endocardial ablation of animal with myocardial infarction. Lesion imaging was performed using free‐breathing, non‐contrast‐enhanced, T1w sequence with long inversion time (TI). Also acquired were T1 maps and delayed contrast‐enhanced (DCE) imaging. Hearts were excised for ex vivo imaging, and sliced for gross pathology and histology.

Results

All ablations were visibly enhanced in non‐contrast‐enhanced T1w imaging using TI = 700 ms. T1w enhancement agreed with regions of necrosis in gross pathology and histology. Enhanced lesion cores were surrounded by dark bands containing contraction band necrosis, hematoma, and edema. In animals with myocardial infarction, chronic scar was hypointense in T1w, whereas acute ablations were enhanced, allowing discrimination between chronic scar and acute lesions, unlike DCE. Contrast was sufficient to create 3D volume renderings of lesions after minor postprocessing.

Conclusions

Non‐contrast‐enhanced T1w imaging with long TI promises to be an effective method for visualizing necrosis within radiofrequency ablation lesions. Enhancement is more specific and stationary than that from DCE. The imaging can be repeated as needed, unlike DCE, and may be especially useful for assessing ablations during or after a procedure. Magn Reson Med 79:879–889, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
Renal medullary carcinoma: A national analysis of 159 patients
Authors: Ezekian Brian , Englum Brian , Gilmore Brian F. , Nag Uttara P. , Kim Jina , Leraas Harold J. , Routh Jonathan C. , Rice Henry E. , Tracy Elisabeth T.
Published: May 2017

Background

Renal medullary carcinoma (RMC) is an aggressive malignancy seen predominantly in young males with sickle cell trait. RMC is poorly understood, with fewer than 220 cases described in the medical literature to date. We used a large national registry to define the typical presentation, treatments, and outcomes of this rare tumor.

Methods

The National Cancer Database was queried for patients under 40 years of age diagnosed with RMC from 1998 to 2011. An analysis of patient and tumor characteristics, treatment details, and overall survival (OS) was undertaken, and factors associated with mortality were identified using multivariable regression analysis.

Results

In total, 159 patients with RMC were identified, of whom a majority were male (71%), African American (87%), and had metastatic disease (71%). Median tumor size was 6 cm and median survival was 7.7 months. Most patients underwent surgery (60%) and chemotherapy (65%). Few patients received radiation (12%). Patients with metastatic disease had a significantly worse median survival (4.7 vs. 17.8 months, P < 0.001) and were less likely to receive surgery (42% vs. 91%, P < 0.001). Age and tumor size did not appear to impact OS.

Conclusion

In the largest cohort to date of patients with RMC, we found a dismal median survival of less than 8 months. Age and tumor size were not associated with OS. Metastatic disease at presentation was the main negative prognostic indicator in RMC and was present in a majority of patients at the time of diagnosis.
Evaluation of algorithms to identify incident cancer cases by using French health administrative databases
Authors: Ajrouche Aya , Estellat Candice , De Rycke Yann , Tubach Florence
Published: May 2017

Purpose

Administrative databases are increasingly being used in cancer observational studies. Identifying incident cancer in these databases is crucial. This study aimed to develop algorithms to estimate cancer incidence by using health administrative databases and to examine the accuracy of the algorithms in terms of national cancer incidence rates estimated from registries.

Methods

We identified a cohort of 463 033 participants on 1 January 2012 in the Echantillon Généraliste des Bénéficiaires (EGB; a representative sample of the French healthcare insurance system). The EGB contains data on long‐term chronic disease (LTD) status, reimbursed outpatient treatments and procedures, and hospitalizations (including discharge diagnoses, and costly medical procedures and drugs). After excluding cases of prevalent cancer, we applied 15 algorithms to estimate the cancer incidence rates separately for men and women in 2012 and compared them to the national cancer incidence rates estimated from French registries by indirect age and sex standardization.

Results

The most accurate algorithm for men combined information from LTD status, outpatient anticancer drugs, radiotherapy sessions and primary or related discharge diagnosis of cancer, although it underestimated the cancer incidence (standardized incidence ratio (SIR) 0.85 [0.80–0.90]). For women, the best algorithm used the same definition of the algorithm for men but restricted hospital discharge to only primary or related diagnosis with an additional inpatient procedure or drug reimbursement related to cancer and gave comparable estimates to those from registries (SIR 1.00 [0.94–1.06]).

Conclusion

The algorithms proposed could be used for cancer incidence monitoring and for future etiological cancer studies involving French healthcare databases. Copyright © 2017 John Wiley & Sons, Ltd.
Exosomes contribute to endothelial integrity and acute chest syndrome risk: Preliminary findings
Authors: Lapping‐Carr Gabrielle , Khalyfa Abdelnaby , Rangel Stephanie , Darlington Wendy , Beyer Eric C. , Peddinti Radhika , Cunningham John M. , Gozal David
Published: May 2017

Background

Acute Chest Syndrome (ACS) is one of the leading causes of death among children with Sickle Cell Disease (SCD). Disruption of microvascular integrity is critical to the pathophysiology of ACS, but the factors governing its phenotypic variability are incompletely understood. Because circulating exosomes have been implicated in vascular dysfunction in various diseases, we hypothesized that exosomes induce endothelial dysfunction in patients who experience ACS.

Procedure

Cross‐sectional cohort study including 33 outpatients with SCD (without new health‐related complaints or recent transfusions) and a cohort of control patients. Exosomes were isolated from platelet‐free plasma.

Results

ImageStream showed that exosome counts were greatly increased in patients with SCD compared with controls, but there were few differences in the concentrations of exosomes between patients who had experienced ACS (ACS(+)) and those who had not (ACS(−)). Exosomes were added to human microvascular endothelial cells, and the exosomal effects on monolayer integrity was determined using Electric Cell‐substrate Impedance Sensing (ECIS). Exosomes from SCD patients without ACS differed minimally from control patients; however, exosomes from ACS(+) decreased endothelial cell resistance compared to ACS(−), (Relative resistance: ACS(+): 0.981 ± 0.055 vs ACS(−): 1.124 ± 0.042; P = 0.006). Treatment of endothelial cultures with exosomes from ACS(−) patients increased endothelial Nitric Oxide Synthase (eNOS) mRNA expression, while ACS(+)‐derived exosomes were not able to increase eNOS expression above that of controls.

Conclusions

These findings demonstrate that patients with SCD have circulating exosomes that produce differential effects that may contribute to the pathophysiology of ACS and may serve as risk‐related biomarkers.
Complete heart block complicating the acute phase of respiratory syncytial virus bronchiolitis
Authors: Karatza Ageliki A. , Kiaffas Maria , Rammos Spyros
Published: May 2017

Respiratory syncytial virus is the most common pathogen causing lower respiratory tract infection in infants. In recent years, the importance of extrapulmonary complications and longterm sequelae including those involving the cardiovascular system has become apparent. We report on a 10 month old infant with respiratory syncytial virus bronchiolitis, the acute phase of which was complicated by irreversible complete heart block, which was managed conservatively.