bluuebunny/crossref_metadata_2025 huggingface dataset:
Time-dependent trends in cardiovascular adverse events during follow-up after carotid or iliofemoral endarterectomy
Authors: van Koeverden I D , van Haelst S T W , Haitjema S , de Vries J-P P M , Moll F L , den Ruijter H M , Hoefer I E , Dalmeijer G W , de Borst G J , Pasterkamp G
Published: June 2017

Background

Recent observations have suggested a decline in vulnerable carotid artery and iliofemoral atherosclerotic plaque characteristics over the past decade. The aim of this study was to determine whether, in the presence of clinically manifest carotid or peripheral artery disease, secondary adverse cardiovascular events decreased over this period.

Methods

Patients included in the Athero-Express biobank between 2003 and 2012 were analysed. During 3-year follow-up, composite cardiovascular endpoints were documented yearly, including: myocardial infarction, coronary interventions, stroke, peripheral interventions and cardiovascular death. The major cardiovascular endpoint consisted of myocardial infarction, stroke and cardiovascular death.

Results

Some 1684 patients who underwent carotid endarterectomy (CEA) and another 530 who had iliofemoral endarterectomy (IFE) were analysed. In total, 405 (25·2 per cent) and 236 (45·9 per cent) patients had a composite cardiovascular endpoint within 3 years after CEA and IFE respectively. Corrected for possible confounders, the percentage of patients with a secondary cardiovascular event after CEA did not change over time (hazard ratio (HR) 0·91, 95 per cent c.i. 0·65 to 1·28; P = 0·590, for 2011–2012 versus 2003–2004). In patients who had IFE, the incidence of secondary cardiovascular events significantly decreased only in the last 2 years (HR 0·62, 0·41 to 0·94; P = 0·024), owing to a decrease in peripheral (re)interventions in 2011–2012 (HR 0·59, 0·37 to 0·94; P = 0·028). No decrease in major cardiovascular events was observed in either group.

Conclusion

In patients who had undergone either CEA or IFE there was no evidence of a decrease in all secondary cardiovascular events. There were no differences in major cardiovascular events.
Improving the baculovirus expression vector system with vankyrin‐enhanced technology
Authors: Steele Kendra H. , Stone Barbara J. , Franklin Kathleen M. , Fath‐Goodin Angelika , Zhang Xiufeng , Jiang Haobo , Webb Bruce A. , Geisler Christoph
Published: June 2017

The baculovirus expression vector system (BEVS) is a widely used platform for the production of recombinant eukaryotic proteins. However, the BEVS has limitations in comparison to other higher eukaryotic expression systems. First, the insect cell lines used in the BEVS cannot produce glycoproteins with complex‐type N‐glycosylation patterns. Second, protein production is limited as cells die and lyse in response to baculovirus infection. To delay cell death and lysis, we transformed several insect cell lines with an expression plasmid harboring a vankyrin gene (P‐vank‐1), which encodes an anti‐apoptotic protein. Specifically, we transformed Sf9 cells, Trichoplusia ni High FiveTM cells, and SfSWT‐4 cells, which can produce glycoproteins with complex‐type N‐glycosylation patterns. The latter was included with the aim to increase production of glycoproteins with complex N‐glycans, thereby overcoming the two aforementioned limitations of the BEVS. To further increase vankyrin expression levels and further delay cell death, we also modified baculovirus vectors with the P‐vank‐1 gene. We found that cell lysis was delayed and recombinant glycoprotein yield increased when SfSWT‐4 cells were infected with a vankyrin‐encoding baculovirus. A synergistic effect in elevated levels of recombinant protein production was observed when vankyrin‐expressing cells were combined with a vankyrin‐encoding baculovirus. These effects were observed with various model proteins including medically relevant therapeutic proteins. In summary, we found that cell lysis could be delayed and recombinant protein yields could be increased by using cell lines constitutively expressing vankyrin or vankyrin‐encoding baculovirus vectors. © 2017 The Authors Biotechnology Progress published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers Biotechnol. Prog., 33:1496–1507, 2017
High throughput screening identifies novel, cell cycle‐arresting small molecule enhancers of transient protein expression
Authors: Meyer Hermann‐Josef , Turincio Rebecca , Ng Shirley , Li Juan , Wilson Blair , Chan Pamela , Zak Mark , Reilly Dorothea , Beresini Maureen H. , Wong Athena W.
Published: June 2017

Transient gene expression in mammalian cells is an efficient process for producing recombinant proteins for various research applications to support large molecule therapeutics development. For the first time, we report a high throughput small molecule (SM) screen to identify novel compounds that increase antibody titers after polyethylenimine (PEI) transient transfection of a HEK293 cell line. After screening 31,413 SMs in a 50 μL scaled‐down process, we validated 164 SMs to improve yields by up to twofold. The titer increase mediated by the SMs varied for different antibodies. SM dose optimizations resulted in almost threefold higher titers. The top 2, structurally distinct SM hits, increased antibody titers more than twofold in a 1 mL production process. Averaged across three antibodies of different expression levels, the compounds enhanced transient productivity by ∼80%. Intriguingly, both compounds arrested cells in the G2/M cell cycle phase leading to a decrease in growth and nutrient consumption, while elevating titer, nuclear plasmid DNA (pDNA) copy numbers, and mRNA levels. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 3:1579–1588, 2017
Rapid “Mix‐and‐Stir” Preparation of Well‐Defined Palladium on Carbon Catalysts for Efficient Practical Use
Authors: Yakukhnov Sergey A. , Pentsak Evgeniy O. , Galkin Konstantin I. , Mironenko Roman M. , Drozdov Vladimir A. , Likholobov Vladimir A. , Ananikov Valentine P.
Published: June 2017

A facile direct deposition approach for the preparation of recyclable Pd/C catalysts simply by stirring a solution of tris(dibenzylideneacetone)dipalladium(0) with a suitable carbon material was evaluated. An extraordinarily rapid catalyst preparation procedure (<5 min) under mild conditions and its excellent performance in cross‐coupling and hydrogenation reactions were demonstrated. The key point for catalyst design is the direct deposition of Pd0 centers onto the highly accessible surface area and the avoidance of ill‐defined PdII/Pd0 states.
Thermal Synthesis of Perchlorinated Oligosilanes: A Fresh Look at an Old Reaction
Authors: Neumeyer Felix , Schweizer Julia I. , Meyer Lioba , Sturm Alexander G. , Nadj Andor , Holthausen Max C. , Auner Norbert
Published: June 2017

A combined experimental and theoretical study of the high‐temperature reaction of SiCl4 and elemental silicon is presented. The nature and reactivity of the product formed upon rapid cooling of the gaseous reaction mixture is investigated by comparison with the defined model compounds cyclo‐Si5Cl10, n‐Si5Cl12 and n‐Si4Cl10. A DFT assessment provides mechanistic insight into the oligosilane formation. Experimental 29Si NMR investigations, supported by quantum‐chemical 29Si NMR calculations, consistently show that the reaction product is composed of discrete molecular perchlorinated oligosilanes. Low‐temperature chlorination is an unexpectedly selective means for the transformation of cyclosilanes to acyclic species by endocyclic Si−Si bond cleavage, and we provide a mechanistic rationalization for this observation. In contrast to the raw material, the product obtained after low‐temperature chlorination represents an efficient source of neo‐Si5Cl12 or the amine‐stabilized disilene EtMe2N⋅SiCl2Si(SiCl3)2 through reaction with aliphatic amines.
Metal‐Ion‐Activated DNAzymes Used for Regulation of Telomerase Activity in Living Cells
Authors: Wang Jiasi , Qin Hongshuang , Wang Faming , Ren Jinsong , Qu Xiaogang
Published: June 2017

Telomerase is a key regulator in cell metabolism, tissue renewal, and organismal lifespan. Here we develop a simple strategy to modulate cellular telomerase activity, and further control cell fate based on Mg2+‐ and Zn2+‐activated DNAzymes in living cells. Through modulation of telomerase activity, we can regulate cell behavior, including cell migration, cell differentiation, cell senescence, and cell cycle. Our work provides a new way to modulate telomerase activity in living cells by using DNAzymes.
Two Structurally Characterized Conformational Isomers with Different C−P Bonds
Authors: Roy Sudipta , Mondal Kartik Chandra , Kundu Subrata , Li Bin , Schürmann Christian J. , Dutta Sayan , Koley Debasis , Herbst‐Irmer Regine , Stalke Dietmar , Roesky Herbert W.
Published: June 2017

The cyclic alkyl(amino) carbene (cAAC) bonded chlorophosphinidene (cAAC)P−Cl (2/2') was isolated from the direct reaction between cAAC and phosphorus trichloride (PCl3). Compound 2/2' has been characterized by NMR spectroscopy and mass spectrometry. 31P NMR investigations [δ≈160 ppm (major) and δ≈130 ppm (minor)] reveal that there are two different P environments of the P−Cl unit. X‐ray single‐crystal determination suggests a co‐crystallization of two conformational isomers of (cAAC)P−Cl (2/2'); the major compound possessing a cAAC−PCl unit with CcAAC−P 1.75 Å. This C−P bond length is very close to that of (NHC)2P2 [NHC=N‐heterocyclic carbene]. The residual density can be interpreted as a conformational isomer with a shorter CcAAC−P bond similar to a non‐conjugated phosphaalkene [R−P=CR2]. Our study shows an unprecedented example of two conformational isomers with different Ccarbene−element bonds. Additionally, Br (3c/3c'), I (4c/4c'), and H (5c/5c') analogues [(Me2‐cAAC)P−X; X=Br (3), I (4), H (5)] of 2c/2c'[(Me2‐cAAC)P−Cl] were also synthesized and characterized by NMR spectroscopy suggesting similar equilibrium in solution. The unique property of cAAC and the required electronegativity of the X (X=Cl, Br, I, and H) atom play a crucial role for the existence of the two isomers which were further studied by theoretical calculations.
Synthesis and pKa determination of new enantiopure dimethyl‐substituted acridino‐crown ethers containing a carboxyl group: Useful candidates for enantiomeric recognition studies
Authors: Németh Tamás , Dargó Gergő , Petró József Levente , Petrik Zsófia , Lévai Sándor , Krámos Balázs , Béni Zoltán , Nagy József , Balogh György Tibor , Huszthy Péter , Tóth Tünde
Published: June 2017

New enantiopure dimethyl‐substituted acridino‐18‐crown‐6 and acridino‐21‐crown‐7 ethers containing a carboxyl group at position 9 of the acridine ring [(S,S)‐8, (S,S)‐9, (R,R)‐10] were synthesized. The pKa values of the new crown ethers [(S,S)‐8, (S,S)‐9, (R,R)‐10] and of an earlier reported macrocycle [(R,R)‐2] were determined by UV‐pH titrations. Crown ether (S,S)‐8 was attached to silica gel by covalent bonds and the enantiomeric separation ability of the newly prepared chiral stationary phase [(S,S)‐CSP‐12] was studied by high‐performance liquid chromatography (HPLC). Homochiral preference was observed and the best separation was achieved for the enantiomers of 1‐NEA. Ligands (S,S)‐9 and (R,R)‐10 are precursors of enantioselective sensor and selector molecules for the enantiomers of protonated primary amines, amino acids, and their derivatives.
Organization of the catecholaminergic systems in the brain of lungfishes, the closest living relatives of terrestrial vertebrates
Authors: López Jesús M. , González Agustín
Published: June 2017

Lungfishes are a group of sarcopterygian fishes currently considered the closest living relatives of tetrapods, and represent an interesting group for the study of evolutionary traits in the transition from fishes to tetrapods. Catecholaminergic systems in the brain are among the most carefully analyzed neurotransmitter systems in the brain of most vertebrate groups. Their organization shows major shared characteristics, although traits particular to each vertebrate class have also been found, primarily between anamniotes and amniotes. Given the relevance of lungfishes in evolutionary terms, the present study provides the first comprehensive and detailed map of the catecholaminergic structures in the brain of two representative species of lungfishes, an African lungfish (Protopterus dolloi) and the Australian lungfish (Neoceratodus forsteri), as revealed by immunohistochemistry. Distinct groups of catecholaminergic cells were observed in the olfactory bulb, pallium, and preoptic area of the telencephalon, and the subpallium is devoid of these cells. Hypothalamic and diencephalic groups were detected and, in particular, the dopaminergic nucleus of the periventricular organ was evidenced with dopamine antibodies but not with anti‐tyrosine hydroxylase. A well developed mesostriatal system was revealed formed by conspicuous groups of dopamine cells in the midbrain tegmentum and profuse innervation of the subpallium. Comparison of these results with those from other classes of vertebrates shows numerous common traits shared by most groups and also highlights particular features in lungfishes different from actinopterygian fishes that resemble those of amphibians and amniotes.
Role of Dynamic Heterogeneities in Ionic Liquids: Insights from All‐Atom and Coarse‐Grained Molecular Dynamics Simulation Studies
Authors: Pal Tamisra , Vogel Michael
Published: June 2017

We performed molecular dynamics simulations for the room‐temperature ionic liquid 1‐butyl‐3‐methylimidazolium hexafluorophosphate ([Bmim][PF6]). By employing all‐atom (AA) and coarse‐grained (CG) models, we compared the characteristic times of various dynamical modes, from vibration to diffusion, and the importance of dynamical heterogeneities at different levels of chemical resolution and over broad temperature ranges. It was shown that coarse graining leads to a substantial speedup in molecular dynamics, whereas it weakly affects the strength of dynamical heterogeneities. Despite the general speedup, several relationships between dynamical modes on different timescales were preserved. In particular, the heterogeneity timescales of the AA and CG models collapse onto the same curve as a function of the structural (α) relaxation time τα. Moreover, vibrational amplitudes and relaxation times τα are related at both levels of chemical resolution. We argue that the robustness of these relationships assists the development of dynamically consistent coarse‐graining strategies and justifies the use of simplified models for a theoretical understanding of viscous liquids.
Low‐Cost Perovskite Solar Cells Employing Dimethoxydiphenylamine‐Substituted Bistricyclic Aromatic Enes as Hole Transport Materials
Authors: Rakstys Kasparas , Paek Sanghyun , Grancini Giulia , Gao Peng , Jankauskas Vygintas , Asiri Abdullah M. , Nazeeruddin Mohammad Khaja
Published: June 2017

The synthesis, characterization and photovoltaic performance of series of novel molecular hole transport materials (HTMs) based on bistricyclic aromatic enes (BAEs) are presented. The new derivatives were obtained following a simple and straightforward procedure from inexpensive starting reagents mimicking the synthetically challenging 9,9′‐spirobifluorene moiety of the well‐studied spiro‐OMeTAD. The novel HTMs were tested in mixed cations and anions perovskite solar cells (PSCs) yielding a power conversion efficiency (PCE) of 19.2 % under standard global 100 mW cm−2 AM1.5G illumination using 9‐{2,7‐bis[bis(4‐methoxyphenyl)amino]‐9H‐fluoren‐9‐ylidene}‐N2,N2,N7,N7‐tetrakis(4‐methoxyphenyl)‐9H‐thioxanthene‐2,7‐diamine (coded as KR374). The power conversion efficiency data confirms the easily attainable heteromerous fluorenylidenethioxanthene structure as valuable core for low‐cost and highly efficient HTM design and paves the way towards cost‐effective PSC technology.
Microvascular dysfunction and cardiac fibrosis in heart failure with preserved ejection fraction: a case report
Authors: Narang Nikhil , Medvedofsky Diego , Dryer Kathryn , Shah Sanjiv J. , Davidson Charles J. , Patel Amit R. , Blair John E.A.
Published: June 2017

We report the case of a 55‐year‐old woman with heart failure with preserved ejection fraction (HFpEF), who presented with hypertensive urgency and pulmonary oedema. The patient was medically optimized and underwent cardiac catheterization revealing pulmonary hypertension, elevated pulmonary capillary wedge pressure, normal cardiac index, and non‐obstructive coronary disease. Invasive evaluation of coronary flow revealed blunted coronary flow reserve and increased index of microvascular resistance. Cardiac magnetic resonance imaging demonstrated reduced global myocardial perfusion and diffuse interstitial fibrosis. This case exhibits a potential HFpEF phenotype associated with microvascular dysfunction, fibrosis, and elevated filling pressures.
Homogeneous Catalysis by Manganese‐Based Pincer Complexes
Authors: Garbe Marcel , Junge Kathrin , Beller Matthias
Published: June 2017

Base‐metal catalysis, especially with non‐noble‐metal pincer‐type catalysts, is increasingly used in organic synthesis and thus becoming more and more important for organometallic chemistry. After ruthenium‐, iridium‐ and iron‐based pincer‐type complexes became established as state‐of‐the‐art catalysts for (de)hydrogenation reactions in the past decade, manganese complexes have most recently been successfully applied in related transformations. Specifically, this microreview covers their recent progress in (de)hydrogenation and transfer (de)hydrogenation as well as in C–C and C–X bond‐forming reactions.
Ugi Reaction Followed by Intramolecular Diels–Alder Reaction and Elimination of HCl: One‐Pot Approach to Arene‐Fused Isoindolinones
Authors: Huang Jianjun , Du Xiaochen , Van Hecke Kristof , Van der Eycken Erik V. , Pereshivko Olga P. , Peshkov Vsevolod A.
Published: June 2017

A one‐pot procedure involving a four‐component Ugi reaction followed by an intramolecular Diels–Alder reaction/HCl elimination cascade has been developed to provide rapid access to the isoindolinone framework in a diversity‐oriented fashion. The scope of the process has been investigated with respect to all four components, and a comparison between the one‐pot and sequential approaches is given. The possibility of a late‐stage one‐pot functionalization through Suzuki coupling has been explored.
Synthesis of N‐Nitroso CHF2‐Pyrazolines and Their Transformation into CHF2‐Isoxazolines and ‐Pyrazoles
Authors: Lebed Pavlo S. , Fenneteau Johan , Wu Yong , Cossy Janine , Mykhailiuk Pavel K.
Published: June 2017

N‐Nitroso CHF2‐pyrazolines were synthesized from in situ generated difluoromethyldiazomethane (CF2HCHN2), tert‐butyl isonitrite (tBuONO), and alkenes. The synthesis of representative CHF2‐pyrazoles and CHF2‐oxazolines was also performed.
Can integrating wildlife and livestock enhance ecosystem services in central Kenya?
Authors: Allan Brian F , Tallis Heather , Chaplin‐Kramer Rebecca , Huckett Steven , Kowal Virginia A , Musengezi Jessica , Okanga Sharon , Ostfeld Richard S , Schieltz Jennifer , Warui Charles M , Wood Spencer A , Keesing Felicia
Published: June 2017

Because wildlife and livestock compete for grazing resources, biodiversity conservation and livestock ranching typically have been portrayed as conflicting uses of African savannas. Here, we offer an alternative perspective by describing a savanna ecosystem in central Kenya where wildlife and livestock exhibit a suite of potential positive interactions. For example, treating livestock with an acaricide offers the unintended benefit of removing ticks from the landscape, a result that has now been shown to occur at both large and small scales. When humans derive financial benefits both from wildlife (through tourism) and from livestock (through food production), they may achieve greater economic stability than when income is derived solely from one source. The integrated management of wildlife and livestock can simultaneously improve human health and wildlife conservation. Optimization of human and wildlife benefits will require the management of ecological and socioeconomic trade‐offs when conflicts occur between stakeholders.
Volcanic rocks distribution and basement structure in western–central Junggar Basin revealed by gravitational and magnetic data
Authors: Zhou Yaoming , Zhu Wenbin , Chen Zhengle , Zheng Bihai , Shao Xinglai , Xue Feng
Published: June 2017

The Junggar Basin is a large superimposed basin with multistage evolution. The Carboniferous volcanic rock in the middle‐lower part of the basin has been an important target of oil and gas exploration. Therefore, it is crucial to establish a set of efficient methods and techniques to find out the distribution of the Carboniferous volcanic rock and the tectonic factors related to the reservoir forming of the volcanic rock. Our research reveals that the density and magnetism of the Carboniferous volcanic rock are obviously higher than those of the Mesozoic and Cenozoic sedimentary rocks. With a series of frequency domain filters and boundary enhancement techniques, we determine the residual gravitational and magnetic anomalies caused by the Carboniferous volcanic rock. Combined with borehole and seismic data from the studied areas, the horizontal and vertical distributions of the Carboniferous volcanic rock are defined, and the lithologies of different types of volcanic rocks are predicted. Furthermore, the gravitational and magnetic anomalies are used to estimate the basement faults and topography. The regional deep faults and their secondary faults of the basement are outlined, and the model of basement relief is constructed. Finally, the effects of the fracture structure and the basement topography in the process of volcanic activity and hydrocarbon accumulation are fully discussed. These results provide fundamental information for optimal selection of the favorable area of volcanic reservoir.
Geochronology, geochemistry, and tectonic significance of Permian intrusive rocks from the Shaolanghe region, northern margin of the North China Craton
Authors: Guo Yunpeng , Zeng Qingdong , Liu Jian‐ming , Chu Shao‐xiong , Wang Yongbin , Gao Shuai
Published: June 2017

In situ zircon U–Pb ages and Hf isotopic data, whole‐rock major and trace element contents, and Sr–Nd isotopic compositions are reported for Permian intrusive rocks at Shaolanghe in Eastern Inner Mongolia in order to explore the magmatic origin and tectonic significance of these rocks for the evolution of the northern margin of the North China Craton. Three intrusive rocks, quartz diorite, Xishuiquan granite, and Xinglong granite, yield zircon U–Pb ages of 285.9 ± 3.1, 274.2 ± 2.9, and 260.0 ± 8.4 Ma, respectively. The quartz diorite and Xishuiquan granite belong to the high‐K calc‐alkaline series, enriched in large ion lithophile elements (e.g., Rb) and depleted in high field strength elements (e.g., Nb and Ti). They are defined as I‐type granites. The quartz diorite has initial 87Sr/86Sr ratios of 0.7049–0.7051, εNd(t) values of −10.0 to −11.4, and εHf(t) values of −15.2 to −9.9. The εHf(t) values of the Xishuiquan granite (−4.8 to 4.0) vary in discrete segments, whereas the εNd(t) values (−12.9 to −13.3) are consistent with those of the quartz diorites (−10.0 to −11.4). A magma mixing model is proposed for the formation of the quartz diorites of the Shaolanghe region, and the Xishuiquan granite was likely derived from partial melting of the Paleoproterozoic crust with involvement of mantle components. Geochemical analyses show that the tectonic setting of the northern margin of the North China Craton during the late Palaeozoic was an Andes‐type active continental margin associated with subduction of the Paleo‐Asian Ocean plate.
Polymeric drug delivery systems for intraoral site‐specific chemoprevention of oral cancer
Authors: Desai Kashappa Goud H.
Published: June 2017

Oral cancer is among the most prevalent cancers in the world. Moreover, it is one of the major health problems and causes of death in many regions of the world. The traditional treatment modalities include surgical removal, radiation therapy, systemic chemotherapy, or a combination of these methods. In recent decades, there has been significant interest in intraoral site‐specific chemoprevention via local drug delivery using polymeric systems. Because of its easy accessibility and clear visibility, the oral mucosa is amenable for local drug delivery. A variety of polymeric systems—such as gels, tablets, films, patches, injectable systems (e.g., millicylindrical implants, microparticles, and in situ‐forming depots), and nanosized carriers (e.g., polymeric nanoparticles, nanofibers, polymer–drug conjugates, polymeric micelles, nanoliposomes, nanoemulsions, and polymersomes)—have been developed and evaluated for the local delivery of natural and synthetic chemopreventive agents. The findings of in vitro, ex vivo, and in vivo studies and the positive outcome of clinical trials demonstrate that intraoral site‐specific drug delivery is an attractive, highly effective and patient‐friendly strategy for the management of oral cancer. Intraoral site‐specific drug delivery provides unique therapeutic advantages when compared to systemic chemotherapy. Moreover, intraoral drug delivery systems are self‐administrable and can be removed when needed, increasing patient compliance. This article covers important aspects and advances related to the design, development, and efficacy of polymeric systems for intraoral site‐specific drug delivery. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1383–1413, 2018.
Hydroxyapatite–polymer biocomposites for bone regeneration: A review of current trends
Authors: Ramesh Niranjan , Moratti Stephen C. , Dias George J.
Published: June 2017

Bone tissue engineering has emerged as one of the most indispensable approaches to address bone trauma in the past few decades. This approach offers an efficient and a risk‐free alternative to autografts and allografts by employing a combination of biomaterials and cells to promote bone regeneration. Hydroxyapatite (HA) is a ceramic biomaterial that mimics the mineral composition of bones and teeth in vertebrates. HA, commonly produced via several synthetic routes over the years has been found to exhibit good bioactivity, biocompatibility, and osteoconductivity under both in vitro and in vivo conditions. However, the brittle nature of HA restricts its usage for load bearing applications. To address this problem, HA has been used in combination with several polymers in the form of biocomposite implants to primarily improve its mechanical properties and also enhance the implants' overall performance by simultaneously exploiting the positive effects of both HA and the polymer involved in making the biocomposite. This review article summarizes the past and recent developments in the evolution of HA–polymer biocomposite implants as an “ideal” biomaterial scaffold for bone regeneration. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2046–2057, 2018.
DOK3 Modulates Bone Remodeling by Negatively Regulating Osteoclastogenesis and Positively Regulating Osteoblastogenesis
Authors: Cai Xiaofeng , Xing Junjie , Long Courtney L , Peng Qisheng , Humphrey Mary Beth
Published: June 2017

Osteoclastogenesis is essential for bone remodeling and normal skeletal maintenance. Receptor activator of NF-κB ligand (RANKL) promotes osteoclast differentiation and function but requires costimulation of immunoreceptor tyrosine-based activation motif (ITAM)-coupled immunoreceptors. Triggering receptor expressed on myeloid cells-2 (TREM2) coupled to ITAM-adaptor protein DNAX activation protein 12kDA (DAP12) provides costimulation of intracellular calcium signaling during osteoclastogenesis. Previously, we found that downstream of kinase-3 (DOK3) physically associates with DAP12 to inhibit toll-like receptor (TLR)-induced inflammatory signaling in macrophages. However, whether and how DOK3 modulates DAP12-dependent osteoclastogenesis is unknown and the focus of this study. Bone microarchitecture and histology of sex- and age-matched wild-type (WT) and DOK3-deficient (DOK3-/-) mice were evaluated. Male and female DOK3-/- mice have significantly reduced trabecular bone mass compared with WT mice with increased TRAP+ osteoclasts in vivo. In vitro, DOK3-/- bone marrow-derived macrophages (BMMs) have increased macrophage colony-stimulating factor (M-CSF)-induced proliferation and increased sensitivity to RANKL-induced osteoclastogenesis. Compared with WT, DOK3-/- osteoclasts are significantly larger with more nuclei and have increased resorptive capacity. Mechanistically, DOK3 limits osteoclastogenesis by inhibiting activation of Syk and ERK in response to RANKL and M-CSF. DOK3 is phosphorylated in a DAP12-dependent manner and associates with Grb2 and Cbl. Compared with DAP12-/- mice with high bone mass, DOK3- and DAP12- doubly deficient mice (DKO) have normalized bone mass, indicating that DOK3 also limits DAP12-independent osteoclastogenesis in vivo. In vitro osteoclasts derived from DKO mice are mononuclear with poor resorptive capacity similar to DAP12-/- osteoclasts. Histomorphometry reveals that DOK3-/-mice also have reduced osteoblast parameters. DOK3-/- osteoblasts have reduced in vitro osteoblastogenesis and increased osteoprotegerin (OPG) to RANKL expression ratio compared with WT osteoblasts. Co-culture of WT and DOK3-/- osteoblasts with pre-osteoclasts reveals a reduced capacity of DOK3-/- osteoblasts to support osteoclastogenesis. These data indicate that DOK3 regulates bone remodeling by negatively regulating M-CSF- and RANKL-mediated osteoclastogenesis and positively regulating osteoblastogenesis. © 2017 American Society for Bone and Mineral Research.
NaOH–HCl neutralized urine preparation for direct testing of uropathogens by Bruker MS
Authors: Choi Ji Seon , Kim Jayoung , Kim Han‐Soo , Kwon Chang‐wan , Kim Min‐sung , Choi Seong‐hyeok
Published: June 2017

Background

We evaluated the analytical performance of a NaOH–HCl neutralization protocol for identifying uropathogens directly from urine samples by a Bruker MS system (Bruker Daltonics, German) and sought to establish a protocol for integrating the method with conventional screening.

Methods

Among all urine samples requested for Gram staining, UF‐1000i, and urine cultures by physicians, we selected samples that were positive by both Gram staining and UF‐1000i testing. Urine was prepared by neutralization using 0.01M NaOH–HCl, and the samples were processed by Bruker MS. For the low detection limit, one strain each of Escherichia coli and Enterococcus faecium was inoculated in sterile deionized water and sterile urine specimens at sequential dilutions.

Results

In a total of 1270 urine samples, 125 samples (9.8%) were positive by both Gram staining and UF‐1000i. Of 94 samples showing a single morphotype on agar plates, 82 samples had colony counts ≥105 CFU/mL and most uropathogens (95.1%, 78 of 82) had UF‐1000i counts ≥106 bacteria/mL. Among them, Bruker MS correctly identified 86.6% (71/82) of all isolates, 89.2% (66/74) of Gram‐negative bacteria (GNB), and 62.5% (5/8) of Gram‐positive cocci (GPC) with higher average scores for GPC (mean score 2.013) and GNB (mean score 2.110).

Conclusions

Bruker MS with urine preparation by NaOH–HCl neutralization provides a simple, cost‐effective, and accurate method for identifying uropathogens directly from urine. Using Bruker MS when single morphotype Gram staining and the UF‐1000i count as ≥106 bacteria/mL may improve the efficiency of bacterial identification in routine practice.
Anti‐D reagents should be chosen accordingly to the prevalence of D variants in the obstetric population
Authors: Lukacevic Krstic Jelena , Dajak Slavica , Bingulac‐Popovic Jasna , Dogic Vesna , Mratinovic‐Mikulandra Jela
Published: June 2017

Background

Resolving ambiguous results of D antigen typing is crucial for appropriate and rational administration of anti‐D immunoprophylaxis and transfusion practice in obstetric population. The aim of the study was to establish selection criteria of anti‐D reagents for our population.

Methods

A total of 12 689 samples from primiparous women in Split‐Dalmatia County, Croatia, were typed for RhD antigen during the period of 5 years. Ambiguous results were submitted to additional serologic investigation and genotyping. RHD genotyping was performed by commercial genotyping kits (Ready Gene weak D ®and Ready gene CDE, Inno‐Train, Kronberg, Germany). Relative frequencies and accompanying 95% confidence intervals were used to estimate the prevalence of variants.

Results

The prevalence of D variants was 0.42% (95% CI 0.31; 0.53). The most common partial D variant was D Va (RHD*05.05), with the prevalence of 0.08% (95% CI 0.03; 0.13). All weak D variants were weak D types 1, 2 and 3 (RHD*weak D type 1, RHD*weak D type 2, RHD*weak D type 3). Weak D samples were distinguishable from partial D in routine typing due to the difference in reactivity of partial D samples with clones D7B8 and RUM‐1. Cell line RUM‐1 gives weak or negative reactions with partial DVa category.

Conclusion

The most common partial D variant in our population is DVa. It is recommended to use cell lines which do not strongly agglutinate DVa variant in routine RhD typing. The appropriate choice of reagents will enable the serology methods to recognize the cases in which RHD genotyping is required.
A retrospective analysis of the application of the Elecsys®HIV combi PT assay in southern China
Authors: Liang Shaocong , Deng Guihua , Zhou Shaosong , Zeng Jing , Tan Weiqing , Yuan Xiaopeng
Published: June 2017

Background

Fourth‐generation HIV assays have been implemented worldwide as a screening test for many years. Understanding the performance of fourth‐generation assay in low HIV prevalence region is pivotal to interpret the test result correctly. In this study, retrospective analysis was used to evaluate application of the Elecsys® HIV combi PT assay.

Methods

A total of 85 043 specimens from a low prevalence setting were detected between June 2013 and October 2015. We evaluated the false‐positive rate (FPR), specificity, and positive predictive value (PPV).

Results

The specificity between male and female were 99.85% and 99.82%, respectively. The PPV on male (50.75%) was higher than female (17.05%) significantly, while the FPR was 0.15% and 0.18%. The gap between false‐positive (median: 1.83, [IQR]: 1.30, 3.38) and confirmed‐positive (median: 407.5, [IQR]: 184.2, 871.7) is enormous. The highest s/co ratio for false‐positive cases was 85.45, while the lowest s/co ratio for confirmed‐positive cases was 59.68. Various reasons were attributed to false‐positive cases.

Conclusion

Optimal cutoff value is needed to be set to reduce the false‐positive cases and predict the final status of HIV infection reliably. Retrospective analysis will help us to understand more about diagnosis of HIV.
Composition of the root mycorrhizal community associated with Coffea arabica in Fifa Mountains (Jazan region, Saudi Arabia)
Authors: Mahdhi Mosbah , Tounekti Taieb , Al‐Turki Turki Ali , Khemira Habib
Published: June 2017

Arbuscular mycorrhizal fungi (AMF) constitute a key functional group of soil biota that can greatly contribute to crop productivity and ecosystem sustainability. They improve nutrient uptake and enhance the ability of plants to cope with abiotic stresses. The presence of AMF in coffee (Coffea arabica L.) plant roots have been reported in several locations but not in Saudi Arabia despite the fact that coffee has been in cultivation here since ancient times. The objective of the present study was to investigate the diversity of AMF communities colonizing the roots of coffee trees growing in two sites of Fifa Mountains (south‐west Saudi Arabia): site 1 at 700 m altitude and site 2 at 1400 m. The AMF large subunit rDNA regions (LSU) were subjected to nested PCR, cloning, sequencing, and phylogenetic analysis. Microscopic observations indicated higher mycorrhizal intensity (24.3%) and spore density (256 spores/100 g of soil) in site 2 (higher altitude). Phylogenetic analysis revealed 10 phylotypes, six belonging to the family Glomeraceae, two to Claroideoglomercea, one to Acaulosporaceae and one to Gigasporaceae family. Glomus was the dominant genus at both sites and the genus Gigaspora was detected only at site 2. This is the first study reporting the presence of AMF in coffee roots and the composition of this particular mycorrhizal community in Saudi Arabia.
Surveillance for lung metastasis from giant cell tumor of bone
Authors: Rosario Mamer , Kim Han‐Soo , Yun Ji Yeon , Han Ilkyu
Published: June 2017

Background and Objectives

Literature on surveillance for lung metastasis from giant cell tumor of bone (GCTB) is scarce. We aimed to develop one by determining: (1) the optimal surveillance schedule by analyzing time‐to‐event data, taking into account the predictive factors, and (2) the effective diagnostic modality.

Methods

A total of 333 patients who underwent surgery for GCTB were followed for at least 2 years. All had chest radiography, and 169 had additional CT for surveillance. Time to lung metastasis and cumulative incidence were calculated, and diagnostic performance between chest radiography and CT was compared.

Results

Twenty‐five (7.5%) of 333 patients developed lung metastasis, and local recurrence (LR) was the only predictive factor (RR = 6.54). Median interval from LR to metastasis was 15 months, and 17 (85%) of the 20 metastases with LR occurred within 3 years of LR. Cumulative post‐LR incidences at 1, 3, and 5 years were 15.4%, 21.5%, and 21.5%, respectively. CT was more sensitive (100% vs 32%), and had higher positive predictive value (81% vs 57%) and accuracy (96% vs 93%).

Conclusions

Intensified lung surveillance is warranted for GCTB patients with LR, especially for 3 years from diagnosis of LR. CT is effective for detecting lung metastasis from GCTB.
Perioperative BRAF inhibitors in locally advanced stage III melanoma
Authors: Zippel Douglas , Markel Gal , Shapira‐Frommer Roni , Ben‐Betzalel Guy , Goitein David , Ben‐Ami Eytan , Nissan Aviram , Schachter Jacob , Schneebaum Schlomo
Published: June 2017

Background and Objectives

Stage III malignant melanoma is a heterogeneous disease where those cases deemed marginally resectable or irresecatble are frequently incurable by surgery alone. Targeted therapy takes advantage of the high incidence of BRAF mutations in melanomas, most notably the V600E mutation. These agents have rarely been used in a neoadjuvant setting prior to surgery.

Methods

Thirteen consecutive patients with confirmed BRAFV600E regionally advanced melanoma deemed marginally resectable or irrresectable, were treated with BRAF inhibiting agents, prior to undergoing surgery. The primary outcome measures were a successful resection and pathological response. Disease‐free survival was a secondary outcome measure.

Results

Overall, 12/13 patients showed a marked clinical responsiveness to medical treatment, enabling a macroscopically successful resection in all cases. Four patients had a complete pathological response with no viable tumor evident in the resected specimens and eight patients showed evidence of minimally residual tumor with extensive tumoral necrosis and fibrosis. One patient progressed and died before surgery. At a median follow up of 20 months, 10 patients remain free of disease.

Conclusions

Perioperative treatment with BRAF inhibiting agents in BRAFV600E mutated Stage III melanoma patients facilitates surgical resection and affords satisfactory disease free survival.
Coupled simulation of high‐frequency dynamics of dissolved oxygen and chlorophyll widens the scope of lake metabolism studies
Authors: Istvánovics Vera , Honti Márk
Published: June 2017

High frequency time series of dissolved oxygen (DO), delayed chlorophyll fluorescence (Chl) and relevant background variables were recorded on nearly 900 d during 7 yr in large, shallow, meso‐eutrophic Lake Balaton (Hungary). Novel models were developed for coupled simulation of diel dynamics of DO and Chl using sequential learning and uncertainty assessment in a Bayesian framework. Despite the generally good model fit for both variables, the uncertainty of the metabolic estimates was high, due primarily to the identification problem of individual metabolic processes. Deviations between observed and simulated DO concentrations suggested that neglect of transient stratification might be responsible for the bulk of the systematic model errors. Net ecosystem production (NEP) was uncertain. Unless air‐water oxygen exchange can be estimated from direct measurements, the free‐water DO method cannot reliably estimate NEP. Gross primary production (GPP) could satisfactorily be hindcasted assuming non‐linear multiplicative dependence on Chl, water temperature and light. Hindcast of community respiration (CR) was less successful, possibly due to the impact of local benthic respiration. Results suggested a major shift in lake metabolism at about 16°C. Below and above this temperature, 70% and 90% of net primary production could be utilized by heterotrophs within a day, respectively. Indirect evidence suggested that biomass‐specific net primary production was determined by phosphorus. The large difference between reproductive rates and net growth rates estimated from GPP and Chl and from daily change in Chl, respectively indicated that loss rates of phytoplankton were as important determinants of algal dynamics as reproductive rates.
Developing a framework for integrating health equity into the learning health system
Authors: Brooks Danielle , Douglas Megan , Aggarwal Neelum , Prabhakaran Shyam , Holden Kisha , Mack Dominic
Published: June 2017

While there have been gains in the overall quality of health care, racial and ethnic disparities in health outcomes continue to persist in the United States. The Learning Health System (LHS) has the potential to significantly improve health care quality using patient‐centered design, data analytics, and continuous improvement. To ensure that health disparities are also being addressed, targeted approaches must be used. This document sets forth a practical framework to incorporate health equity into a developing LHS. Using a case study approach, the framework is applied to 2 projects focused on the reduction of health disparities to highlight its application.
Extreme Toughness Exhibited in Electrospun Polystyrene Fibers
Authors: Zhang Fengfeng , Barber Asa H.
Published: June 2017

Polystyrene (PS) commonly exhibits brittle behavior and poor mechanical properties due to the presence of structural heterogeneities promoting localized failure. The removal of this localized failure is shown here by processing PS into fibers with a range of diameters using electrospinning. Mechanical properties of individual electrospun fibers were quantified with atomic force microscopy based nanomechanical tensile testing. The resultant stress–strain behavior of PS fibers highlights considerable enhancement of mechanical properties when fiber diameter decreases below 600 nm such that polystyrene toughness increases significantly by over two orders of magnitude compared to the bulk. Consideration of the network properties of polystyrene is used to demonstrate the increase of draw ratio toward a theoretical limit and is potentially applicable to a range of glassy polymeric materials.

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Automatic segmentation of the spine by means of a probabilistic atlas with a special focus on ribs suppression
Authors: Ruiz‐España Silvia , Domingo Juan , Díaz‐Parra Antonio , Dura Esther , D'Ocón‐Alcañiz Víctor , Arana Estanislao , Moratal David
Published: June 2017

Purpose

The development of automatic and reliable algorithms for the detection and segmentation of the vertebrae are of great importance prior to any diagnostic task. However, an important problem found to accurately segment the vertebrae is the presence of the ribs in the thoracic region. To overcome this problem, a probabilistic atlas of the spine has been developed dealing with the proximity of other structures, with a special focus on ribs suppression.

Methods

The data sets used consist of Computed Tomography images corresponding to 21 patients suffering from spinal metastases. Two methods have been combined to obtain the final result: firstly, an initial segmentation is performed using a fully automatic level‐set method; secondly, to refine the initial segmentation, a 3D volume indicating the probability of each voxel of belonging to the spine has been developed. In this way, a probability map is generated and deformed to be adapted to each testing case.

Results

To validate the improvement obtained after applying the atlas, the Dice coefficient (DSC), the Hausdorff distance (HD), and the mean surface‐to‐surface distance (MSD) were used. The results showed up an average of 10 mm of improvement accuracy in terms of HD, obtaining an overall final average of 15.51 ± 2.74 mm. Also, a global value of 91.01 ± 3.18% in terms of DSC and a MSD of 0.66 ± 0.25 mm were obtained. The major improvement using the atlas was achieved in the thoracic region, as ribs were almost perfectly suppressed.

Conclusion

The study demonstrated that the atlas is able to detect and appropriately eliminate the ribs while improving the segmentation accuracy.
Intake of Energy and Protein is Associated with Overweight Risk at Age 5.5 Years: Results from the Prospective TEDDY Study
Authors: Beyerlein Andreas , Uusitalo Ulla M. , Virtanen Suvi M. , Vehik Kendra , Yang Jimin , Winkler Christiane , Kersting Mathilde , Koletzko Sibylle , Schatz Desmond , Aronsson Carin Andrén , Elding Larsson Helena , Krischer Jeffrey P. , Ziegler Anette‐G. , Norris Jill M. , Hummel Sandra ,   for the TEDDY Study Group
Published: June 2017

Objective

The associations of energy, protein, carbohydrate, and fat intake with weight status up to the age of 5.5 years were prospectively assessed in The Environmental Determinants of Diabetes in the Young (TEDDY) study.

Methods

Food record data (over 3 days) and BMI measurements between 0.25 and 5.5 years were available from 5,563 children with an increased genetic risk for type 1 diabetes followed from shortly after birth. Odds ratios (ORs) were calculated for overweight and obesity by previous intake of energy, protein, carbohydrate, and fat with adjustment for potential confounders.

Results

Having overweight or obesity at the age of 5.5 years was positively associated with mean energy intake in previous age intervals (e.g., adjusted OR [95% CI] for overweight: 1.06 [1.04‐1.09] per 100 kcal intake at the age of 4.5‐5.0 years) and with protein intake after the age of 3.5 and 4.5 years, respectively (e.g., adjusted OR for overweight: 1.06 [1.03‐1.09] per 1% of energy intake at the age of 4.5‐5.0 years). The respective associations with carbohydrate and fat intake were less consistent.

Conclusions

These findings indicate that energy and protein intake are positively associated with increased risk for overweight in childhood but yield no evidence for potential programming effects of protein intake in infancy.
N‐alkoxypyridinium salts as coinitiators in radical polymerization: Synthesis and Photochemical Properties
Authors: Kabatc Janina , Kostrzewska Katarzyna , Dobosz Robert , Orzeł Łukasz , Jurek Katarzyna
Published: June 2017

A few N‐alkoxypyridinium salts are developed as photoinitiators for efficient polymerization reactions. They are characterized by absorption properties below 300 nm, and generate alkoxy radicals on UV‐Vis light exposure. The squarylium dye was used as a blue‐light photosensitizer. Polymerization results are correlated with the photochemistry of N‐alkoxypyridinium salts. The quenching of the excited singlet state of squarylium dye by pyridinium salt and the formation of the semioxidized species of squaraine suggests an electron transfer from an excited dye to a coinitiator, and that the resulting oxygen‐centered radical initiates the polymerization process. The chemical mechanism was investigated by steady state photolysis and nanosecond laser flash photolysis experiments. Photoinitiating activity of new photoinitiators for initiation of polymerization of trimethylolpropane triacrylate in the UV‐blue light region was compared with photoinitiating ability of selected commercially available initiators. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017, 55, 2840–2850