bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of the Lupus Foundation of America–Rapid Evaluation of Activity in Lupus to More Complex Disease Activity Instruments As Evaluated by Clinical Investigators or Real‐World Clinicians
Authors: Askanase Anca D. , Nguyen Samantha C. , Costenbader Karen , Lim S. Sam , Kamen Diane , Aranow Cynthia , Grossman Jennifer , Kapoor Teja M. , Baker‐Frost DeAnna , Aberle Teresa , Thanou‐Stavraki Aikaterini , Hanrahan Leslie M. , Kim Mimi , Merrill Joan T.
Published: October 2017

Objective

Lupus disease measures such as the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the British Isles Lupus Assessment Group (BILAG) index are challenging to interpret. The Lupus Foundation of America–Rapid Evaluation of Activity in Lupus (LFA‐REAL) is intended to provide an efficient application of anchored visual analog scores, each representing the individual severity of active symptoms, with the sum of individual scores deriving an overall disease activity assessment. Our objective was to compare the performance of LFA‐REAL to systemic lupus erythematosus disease activity assessments and compare scores between trained lupus clinical investigators and clinicians.

Methods

Investigators scored the SLEDAI, BILAG, physician's global assessment (PGA), and LFA‐REAL, while the clinicians scored the LFA‐REAL. The level of agreement between physicians and instruments was determined.

Results

The study included 99 patients (93% women, 31% white, mean ± SD ages 43.4 ± 13.2 years). At the first visit, the mean ± SD SLEDAI score was 5.5 ± 4.5, BILAG score 6.7 ± 7.8, and PGA score 33.6 ± 24.5. The mean ± SD investigator LFA‐REAL score was 46.2 ± 42.9, and clinician LFA‐REAL score 56.1 ± 53.6. At the second visit, the mean ± SD investigator LFA‐REAL score was 41.3 ± 36.7, and clinician LFA‐REAL score 48.3 ± 42.6. Total LFA‐REAL scores correlated positively with PGA, SLEDAI, and BILAG (ρ = 0.58–0.88, P < 0.001). LFA‐REAL scores produced correlation coefficients of ρ > 0.7 for musculoskeletal, mucocutaneous, and renal BILAG domains. The intraclass correlation coefficient between the LFA‐REAL scores of investigators and clinicians was 0.79 for visit 1 (P < 0.001) and 0.86 for visit 2 (P < 0.001).

Conclusion

The LFA‐REAL provides a reliable surrogate for more complicated disease activity measures when used by lupus clinical investigators or clinicians.
Highly Conductive Transition Metal Carbide/Carbonitride(MXene)@polystyrene Nanocomposites Fabricated by Electrostatic Assembly for Highly Efficient Electromagnetic Interference Shielding
Authors: Sun Renhui , Zhang Hao‐Bin , Liu Ji , Xie Xi , Yang Rui , Li Yue , Hong Song , Yu Zhong‐Zhen
Published: October 2017

Highly conductive polymer nanocomposites are greatly desired for electromagnetic interference (EMI) shielding applications. Although transition metal carbide/carbonitride (MXene) has shown its huge potential for producing highly conductive films and bulk materials, it still remains a great challenge to fabricate extremely conductive polymer nanocomposites with outstanding EMI shielding performance at minimal amounts of MXenes. Herein, an electrostatic assembly approach for fabricating highly conductive MXene@polystyrene nanocomposites by electrostatic assembling of negative MXene nanosheets on positive polystyrene microspheres is demonstrated, followed by compression molding. Thanks to the high conductivity of MXenes and their highly efficient conducting network within polystyrene matrix, the resultant nanocomposites exhibit not only a low percolation threshold of 0.26 vol% but also a superb conductivity of 1081 S m−1 and an outstanding EMI shielding performance of >54 dB over the whole X‐band with a maximum of 62 dB at the low MXene loading of 1.90 vol%, which are among the best performances for electrically conductive polymer nanocomposites by far. Moreover, the same nanocomposite has a highly enhanced storage modulus, 54% and 56% higher than those of neat polystyrene and conventional MXene@polystyrene nanocomposite, respectively. This work provides a novel methodology to produce highly conductive polymer nanocomposites for highly efficient EMI shielding applications.
Microfabricated Drug Delivery Devices: Design, Fabrication, and Applications
Authors: Zhang Hongbin , Jackson John K. , Chiao Mu
Published: October 2017

Microfabrication technology has enabled the development of novel controlled‐release devices that possess an integration of structural, mechanical, and perhaps electronic features, which may address challenges associated with conventional delivery systems. In this feature article, microfabricated devices are described in terms of materials, mechanical design, working principles, and fabrication methods, all of which are key features for production of multifunctional, highly effective drug delivery systems. In addition, the current status and future prospects of different types of microfabricated devices for controlled drug delivery are summarized and analyzed with an emphasis on various routes of administration including ocular, oral, transdermal, and implantable systems. It is likely that microfabrication technology will continue to offer new, alternative solutions to design advanced and sophisticated drug delivery devices that promise to significantly improve medical care.
Structure Confined Porous Mo2C for Efficient Hydrogen Evolution
Authors: Wan Jun , Wu Jiabin , Gao Xiang , Li Tianqi , Hu Zhimi , Yu Huimin , Huang Liang
Published: October 2017

Molybdenum carbide (Mo2C) has been widely applied in energy conversion, electrocatalysis, and other electronic devices, but its nanostructure with certain morphology and porous structure is tough to control. In this work, 1D or 2D porous Mo2C nanostructures can be synthesized by carburizing cobalt‐based zeolitic imidazolate framework (ZIF‐67) cladding MoO3 nanowires or nanosheets hybrid structure under high temperature. The obtained 2D porous Mo2C shows a low onset overpotential (η = 25 and 36 mV) and a small Tafel slope (40 and 47 mV dec−1) in 0.1 m HClO4 and 0.1 m KOH as well as great stability. This work highlights a new strategy for the design and synthesis of porous nanostructure Mo2C electrocatalysts.
Facile Two‐Step Synthesis of All‐Inorganic Perovskite CsPbX3 (X = Cl, Br, and I) Zeolite‐Y Composite Phosphors for Potential Backlight Display Application
Authors: Sun Jia‐Yi , Rabouw Freddy T. , Yang Xian‐Feng , Huang Xie‐Yi , Jing Xi‐Ping , Ye Shi , Zhang Qin‐Yuan
Published: October 2017

Recently developed CsPbX3 (X = Cl, Br, and I) perovskite quantum dots (QDs) hold great potential for various applications owing to their superior optical properties, such as tunable emissions, high quantum efficiency, and narrow linewidths. However, poor stability under ambient conditions and spontaneous ion exchange among QDs hinder their application, for example, as phosphors in white‐light‐emitting diodes (WLEDs). Here, a facile two‐step synthesis procedure is reported for luminescent and color‐tunable CsPbX3–zeolite‐Y composite phosphors, where perovskite QDs are encapsulated in the porous zeolite matrix. First zeolite‐Y is infused with Cs+ ions by ion exchange from an aqueous solution and then forms CsPbX3 QDs by diffusion and reaction with an organic solution of PbX2. The zeolite encapsulation reduces degradation and improves the stability of the QDs under strong illumination. A WLED is fabricated using the resulting microscale composites, with Commission Internationale de I'Eclairage (CIE) color coordinates (0.38, 0.37) and achieving 114% of National Television Standards Committee (NTSC) and 85% of the ITU‐R Recommendation BT.2020 (Rec.2020) coverage.
Synthesis, Functionalization, and Design of Magnetic Nanoparticles for Theranostic Applications
Authors: Mosayebi Jalal , Kiyasatfar Mehdi , Laurent Sophie
Published: October 2017

In order to translate nanotechnology into medical practice, magnetic nanoparticles (MNPs) have been presented as a class of non‐invasive nanomaterials for numerous biomedical applications. In particular, MNPs have opened a door for simultaneous diagnosis and brisk treatment of diseases in the form of theranostic agents. This review highlights the recent advances in preparation and utilization of MNPs from the synthesis and functionalization steps to the final design consideration in evading the body immune system for therapeutic and diagnostic applications with addressing the most recent examples of the literature in each section. This study provides a conceptual framework of a wide range of synthetic routes classified mainly as wet chemistry, state‐of‐the‐art microfluidic reactors, and biogenic routes, along with the most popular coating materials to stabilize resultant MNPs. Additionally, key aspects of prolonging the half‐life of MNPs via overcoming the sequential biological barriers are covered through unraveling the biophysical interactions at the bio–nano interface and giving a set of criteria to efficiently modulate MNPs' physicochemical properties. Furthermore, concepts of passive and active targeting for successful cell internalization, by respectively exploiting the unique properties of cancers and novel targeting ligands are described in detail. Finally, this study extensively covers the recent developments in magnetic drug targeting and hyperthermia as therapeutic applications of MNPs. In addition, multi‐modal imaging via fusion of magnetic resonance imaging, and also innovative magnetic particle imaging with other imaging techniques for early diagnosis of diseases are extensively provided.
Realization of Large Electric Polarization and Strong Magnetoelectric Coupling in BiMn3Cr4O12
Authors: Zhou Long , Dai Jianhong , Chai Yisheng , Zhang Huimin , Dong Shuai , Cao Huibo , Calder Stuart , Yin Yunyu , Wang Xiao , Shen Xudong , Liu Zhehong , Saito Takashi , Shimakawa Yuichi , Hojo Hajime , Ikuhara Yuichi , Azuma Masaki , Hu Zhiwei , Sun Young , Jin Changqing , Long Youwen
Published: October 2017

Magnetoelectric multiferroics have received much attention in the past decade due to their interesting physics and promising multifunctional performance. For practical applications, simultaneous large ferroelectric polarization and strong magnetoelectric coupling are preferred. However, these two properties have not been found to be compatible in the single‐phase multiferroic materials discovered as yet. Here, it is shown that superior multiferroic properties exist in the A‐site ordered perovskite BiMn3Cr4O12 synthesized under high‐pressure and high‐temperature conditions. The compound experiences a ferroelectric phase transition ascribed to the 6s2 lone‐pair effects of Bi3+ at around 135 K, and a long‐range antiferromagnetic order related to the Cr3+ spins around 125 K, leading to the presence of a type‐I multiferroic phase with huge electric polarization. On further cooling to 48 K, a type‐II multiferroic phase induced by the special spin structure composed of both Mn‐ and Cr‐sublattices emerges, accompanied by considerable magnetoelectric coupling. BiMn3Cr4O12 thus provides a rare example of joint multiferroicity, where two different types of multiferroic phases develop subsequently so that both large polarization and significant magnetoelectric effect are achieved in a single‐phase multiferroic material.
Enhanced Open‐Circuit Voltage in Colloidal Quantum Dot Photovoltaics via Reactivity‐Controlled Solution‐Phase Ligand Exchange
Authors: Jo Jea Woong , Kim Younghoon , Choi Jongmin , de Arquer F. Pelayo García , Walters Grant , Sun Bin , Ouellette Olivier , Kim Junghwan , Proppe Andrew H. , Quintero‐Bermudez Rafael , Fan James , Xu Jixian , Tan Chih Shan , Voznyy Oleksandr , Sargent Edward H.
Published: October 2017

The energy disorder that arises from colloidal quantum dot (CQD) polydispersity limits the open‐circuit voltage (VOC) and efficiency of CQD photovoltaics. This energy broadening is significantly deteriorated today during CQD ligand exchange and film assembly. Here, a new solution‐phase ligand exchange that, via judicious incorporation of reactivity‐engineered additives, provides improved monodispersity in final CQD films is reported. It has been found that increasing the concentration of the less reactive species prevents CQD fusion and etching. As a result, CQD solar cells with a VOC of 0.7 V (vs 0.61 V for the control) for CQD films with exciton peak at 1.28 eV and a power conversion efficiency of 10.9% (vs 10.1% for the control) is achieved.
Re Doping in 2D Transition Metal Dichalcogenides as a New Route to Tailor Structural Phases and Induced Magnetism
Authors: Kochat Vidya , Apte Amey , Hachtel Jordan A. , Kumazoe Hiroyuki , Krishnamoorthy Aravind , Susarla Sandhya , Idrobo Juan Carlos , Shimojo Fuyuki , Vashishta Priya , Kalia Rajiv , Nakano Aiichiro , Tiwary Chandra Sekhar , Ajayan Pulickel M.
Published: October 2017

Alloying in 2D results in the development of new, diverse, and versatile systems with prospects in bandgap engineering, catalysis, and energy storage. Tailoring structural phase transitions using alloying is a novel idea with implications in designing all 2D device architecture as the structural phases in 2D materials such as transition metal dichalcogenides are correlated with electronic phases. Here, this study develops a new growth strategy employing chemical vapor deposition to grow monolayer 2D alloys of Re‐doped MoSe2 with show composition tunable structural phase variations. The compositions where the phase transition is observed agree well with the theoretical predictions for these 2D systems. It is also shown that in addition to the predicted new electronic phases, these systems also provide opportunities to study novel phenomena such as magnetism which broadens the range of their applications.
Magnetically Controlled Growth‐Factor‐Immobilized Multilayer Cell Sheets for Complex Tissue Regeneration
Authors: Zhang Wenjie , Yang Guangzheng , Wang Xiansong , Jiang Liting , Jiang Fei , Li Guanglong , Zhang Zhiyuan , Jiang Xinquan
Published: October 2017

The scaffold‐free cell‐sheet technique plays a significant role in stem‐cell‐based regeneration. Furthermore, growth factors are known to direct stem cell differentiation and enhance tissue regeneration. However, the absence of an effective means to incorporate growth factors into the cell sheets hinders further optimization of the regeneration efficiency. Here, a novel design of magnetically controlled “growth‐factor‐immobilized cell sheets” is reported. A new Fe3O4 magnetic nanoparticle (MNP) coated with nanoscale graphene oxide (nGO@Fe3O4) is developed to label stem cells and deliver growth factors. First, the nGO@Fe3O4 MNPs can be easily swallowed by dental‐pulp stem cells (DPSCs) and have no influence on cell viability. Thus, the MNP‐labeled cells can be organized via magnetic force to form multilayered cell sheets in different patterns. Second, compared to traditional Fe3O4 nanoparticles, the graphene oxide coating provides plenty of carboxyl groups to bind and deliver growth factors. Therefore, with these nGO@Fe3O4 MNPs, bone‐morphogenetic‐protein‐2 (BMP2) is successfully incorporated into the DPSCs sheets to induce more bone formation. Furthermore, an integrated osteochondral complex is also constructed using a combination of DPSCs/TGFβ3 and DPSCs/BMP2. All these results demonstrate that the new cell‐sheet tissue‐engineering approach exhibits promising potential for future use in regenerative medicine.
Pinhole‐Free Inkjet Printing Strategies for Organic Electronics
Authors: Heinrichsdobler Armin , Roigk Julia Christina , Schirmeier Frank , Brabec Christoph Josef , Wehlus Thomas
Published: October 2017

Inkjet printing is a widely used technique in the field of printed electronics. Yet its reliability is limited because absent droplets induced by defective, e.g., clogged, nozzles can lead to pinholes in the printed layers causing a reduction of the quality of printed films or a breakdown of the functionality in microelectronic devices. Therefore, pinholes in inkjet‐printed layers need to be avoided. In this study the origins for pinholes in inkjet‐printed films are examined. It is found that single missing droplets cannot lead to pinholes but certain formations can. This paper presents the corresponding responsible combinations of defective nozzles necessary to create a pinhole. To enable a statistical approach the pinhole occurrence probabilities are computed depending on the number of broken nozzles as well as quality factors and step sizes with a Monte Carlo simulation. The model shows that by choosing the right print strategy the pinhole probability can be reduced by three orders of magnitude. Finally, a novel print strategy is suggested, which is not yet supported by default printer settings but can reduce the pinhole probability even further by a factor of over 2000 in total. This represents the smallest pinhole occurrence probability ever achieved.
Exome sequencing reveals NAA15 and PUF60 as candidate genes associated with intellectual disability
Authors: Zhao Jin J. , Halvardson Jonatan , Zander Cecilia S. , Zaghlool Ammar , Georgii‐Hemming Patrik , Månsson Else , Brandberg Göran , Sävmarker Helena E. , Frykholm Carina , Kuchinskaya Ekaterina , Thuresson Ann‐Charlotte , Feuk Lars
Published: October 2017

Intellectual Disability (ID) is a clinically heterogeneous condition that affects 2–3% of population worldwide. In recent years, exome sequencing has been a successful strategy for studies of genetic causes of ID, providing a growing list of both candidate and validated ID genes. In this study, exome sequencing was performed on 28 ID patients in 27 patient‐parent trios with the aim to identify de novo variants (DNVs) in known and novel ID associated genes. We report the identification of 25 DNVs out of which five were classified as pathogenic or likely pathogenic. Among these, a two base pair deletion was identified in the PUF60 gene, which is one of three genes in the critical region of the 8q24.3 microdeletion syndrome (Verheij syndrome). Our result adds to the growing evidence that PUF60 is responsible for the majority of the symptoms reported for carriers of a microdeletion across this region. We also report variants in several genes previously not associated with ID, including a de novo missense variant in NAA15. We highlight NAA15 as a novel candidate ID gene based on the vital role of NAA15 in the generation and differentiation of neurons in neonatal brain, the fact that the gene is highly intolerant to loss of function and coding variation, and previously reported DNVs in neurodevelopmental disorders.
Is Teleparallel Gravity Really Equivalent to General Relativity?
Authors: Combi Luciano , Romero Gustavo E.
Published: October 2017

An axiomatization of the so‐called Teleparallel Equivalent to General Relativity is presented. A set of formal and semantic postulates are elaborated from where the physical meaning of various key concepts of the theory are clarified. These concepts include those of inertia, Lorentz and diffeomorphism invariance, and reference frame. It is shown that Teleparallel Gravity admits a wider representation of space‐time than General Relativity, allowing to define properties of the gravitational field such as energy and momentum that are usually considered problematic. In this sense, although the dynamical equations of both theories are equivalent, their inequivalence from a physical point of view is demonstrated. Finally, the axiomatic formulation is used to compare Teleparallel Gravity with other theories of gravity based on absolute parallelism such as non‐local and f(T) gravity.
Freeform Metagratings Based on Complex Light Scattering Dynamics for Extreme, High Efficiency Beam Steering
Authors: Yang Jianji , Sell David , Fan Jonathan A.
Published: October 2017

Conventional phased‐array metasurfaces utilize subwavelength‐scale nanoparticles or nanowaveguides to specify spatially‐dependent amplitude and phase responses to light. An alternative design strategy is based on freeform inverse optimization, in which wavelength‐scale elements are designed to produce devices that possess exceptionally high efficiencies. In this report, we theoretically analyze the physical mechanisms enabling high efficiency in freeform‐based periodic metasurfaces, i.e., metagratings. An in‐depth coupled mode analysis of ultra‐wide‐angle beam deflectors and wavelength splitters shows that the extraordinary performance of these designs originates from the large number of propagating modes supported by the metagrating, in combination with complex multiple scattering dynamics exhibited by these modes. We also apply our coupled mode analysis to conventional nanowaveguide‐based metagratings to understand and quantify the factors limiting the efficiencies of these devices. We envision that freeform metasurface design methods will open new avenues towards high‐performance, multi‐functional optics by utilizing strongly coupled nanophotonic modes and elements.
Identification of three prophenoloxidase‐activating factors (PPAFs) from an invasive beetle Octodonta nipae Maulik (Coleoptera: Chrysomelidae) and their roles in the prophenoloxidase activation
Authors: Zhang HuaJian , Tang BaoZhen , Lin YaPing , Chen ZhiMing , Zhang XiaFang , Ji TianLiang , Zhang XiaoMei , Hou YouMing
Published: October 2017

A typical characteristic of the insect innate immune system is the activation of the serine protease cascade in the hemolymph. As being the terminal component of the extracellular serine protease cascade in the prophenoloxidase (proPO) activating system, proPO‐activating factors (PPAFs) activated by the upstream cascade may generate active phenoloxidase, which then induces downstream melanization. In the present study, we reported three PPAFs from the nipa palm hispid beetle Octodonta nipae (Maulik) (designated as OnPPAF1, OnPPAF2, OnPPAF3). All three OnPPAFs contained a single clip domain at the amino‐terminus followed by a trypsin‐like serine protease domain at the carboxyl‐terminus, except the Ser in the active sites of OnPPAF2 and OnPPAF3 was substituted with Gly. Transcript expression analysis revealed that all OnPPAFs were highly expressed in hemolymph, whereas OnPPAF2 showed an extremely low mRNA abundance compared with that of OnPPAF1 and OnPPAF3, and that the abundance of all three OnPPAFs was dramatically increased upon bacterial challenge. Knockdown of OnPPAF1 or OnPPAF3 resulted in a reduction of hemolymph phenoloxidase activity and an inhibition of hemolymph melanization, whereas the knockdown of OnPPAF2 did not affect the proPO cascade. Our work thus implies that the three OnPPAFs may have different functions and regulation during immune responses in O. nipae.
Visualization of Peripheral Neuron Sensitization in a Surgical Mouse Model of Osteoarthritis by In Vivo Calcium Imaging
Authors: Miller Rachel E. , Kim Yu Shin , Tran Phuong B. , Ishihara Shingo , Dong Xinzhong , Miller Richard J. , Malfait Anne‐Marie
Published: October 2017

Objective

To develop a method for analyzing sensory neuron responses to mechanical stimuli in vivo, and to evaluate whether these neuronal responses change after destabilization of the medial meniscus (DMM).

Methods

DMM or sham surgery was performed in 10‐week‐old male C57BL/6 wild‐type or Pirt‐GCaMP3+/‐ mice. All experiments were performed 8 weeks after surgery. Knee and hind paw hyperalgesia were assessed in wild‐type mice. The retrograde label DiI was injected into the ipsilateral knee to quantify the number of knee‐innervating neurons in the L4 dorsal root ganglion (DRG) in wild‐type mice. In vivo calcium imaging was performed on the ipsilateral L4 DRG of Pirt‐GCaMP3+/‐ mice as mechanical stimuli (paw pinch, knee pinch, or knee twist) were applied to the ipsilateral hind limb.

Results

Eight weeks after surgery, mice subjected to DMM had more hyperalgesia in the knee and hind paw compared to mice subjected to sham surgery. Intraarticular injection of DiI labeled similar numbers of neurons in the L4 DRG of mice subjected to sham surgery and mice subjected to DMM. Increased numbers of sensory neurons responded to all 3 mechanical stimuli in mice subjected to DMM, as assessed by in vivo calcium imaging. The majority of responses in mice subjected to sham surgery and mice subjected to DMM were in small to medium‐sized neurons, consistent with the size of nociceptors. The magnitude of responses was similar between mice subjected to sham surgery and mice subjected to DMM.

Conclusion

Our findings indicate that increased numbers of small to medium‐sized DRG neurons respond to mechanical stimuli 8 weeks after DMM surgery, suggesting that nociceptors have become sensitized by lowering the response threshold.
Brief Report: Loss of Muscle Strength Prior to Knee Replacement: A Question of Anatomic Cross‐Sectional Area or Specific Strength?
Authors: Culvenor Adam G. , Hamler Felix C. , Kemnitz Jana , Wirth Wolfgang , Eckstein Felix
Published: October 2017

Objective

To determine whether loss in thigh muscle strength prior to knee replacement is caused by reductions of muscle strength in the anatomic cross‐sectional area or by reductions of specific strength.

Methods

All 100 of the participants in the Osteoarthritis Initiative who underwent knee replacement and whose medical records included data on thigh isometric muscle strength and magnetic resonance imaging (MRI) (58 women, and 42 men, mean ± SD age 65 ± 8 years, mean ± SD body mass index [BMI] 29 ± 5 kg/m2) were matched with a control (no knee replacement) for age, sex, height, BMI, and radiographic severity. Thigh muscle anatomic cross‐sectional area was determined by MRI at the research visit before knee replacement (time 0) and 2 years before time 0 (time −2). Specific strength (strength/anatomic cross‐sectional area) was calculated, and the measures were compared by conditional logistic regression (i.e., odds ratio [OR] per standard deviation). ORs adjusted for pain (ORadj) and 95% confidence intervals (95% CIs) were also calculated.

Results

Knee replacement cases had significantly smaller extensor (but not flexor) anatomic cross‐sectional areas than controls at time 0 (women, ORadj 1.89 [95% CI 1.05–3.90]; men, ORadj 2.22 [95% CI 1.04–4.76]), whereas no significant differences were found at time −2. Women who had knee replacement showed lower levels of extensor specific strength than controls at time 0 (OR 1.59 [95% CI 1.02–2.50]), although this difference was not observed in men and did not maintain significance after adjustment for pain (ORadj 1.22 [95% CI 0.71–2.08]). Female cases lost significantly more extensor specific strength between time −2 and time 0 than controls (ORadj 3.76 [95% CI 1.04–13.60]), whereas no significant differences were noted at time −2, or in men.

Conclusion

Prior to knee replacement, a significant reduction in knee extensor strength appears to occur in women through 2 mechanisms: one driven by pain (loss of specific strength) and one independent of pain (loss of muscle anatomic cross‐sectional area). Men who underwent knee replacement showed significantly reduced levels of extensor anatomic cross‐sectional area, but not significantly lower strength or specific strength.
Preparation and Thermal Properties of Polycarbonates/esters Catalyzed by Using Dinuclear Salph‐Al from Ring‐Opening Polymerization of Epoxide Monomers
Authors: Zhou Yanchuan , Duan Ranlong , Li Xiang , Pang Xuan , Wang Xianhong , Chen Xuesi
Published: October 2017

A dinuclear Salph‐Al complex/bis(triphenylphosphine)iminium chloride catalyst system was synthesized and employed for cyclohexene oxide (CHO) and CO2 copolymerization. The catalyst system had an excellent selectivity of 99 % for carbonate linkages and the resultant poly(cyclohexene carbonate) (PCHC) had a high glass transition temperature (Tg) of 123.8 °C and a thermal decomposition temperature (5 % weight loss; Td 5 %) of 265 °C. Furthermore, this catalyst system was active in the polymerization of phthalic anhydride (PA) and epoxides. Poly(CHO‐alt‐PA) was completely alternating, and had improved thermal properties (Tg=142.7 and Td 5 %=295 °C) compared with PCHC. The Tg values of the polyesters could be adjusted by addition of PO to the CHO/PA reaction system. For the CHO/PO/PA terpolymerization, CHO and PO participated concurrently and proportionally in the chain growth and the obtained terpolyesters had tunable Tg values from 62.8 to 142.7 °C depending on the CHO/PO feed ratio.
Rational strain engineering interventions to enhance cellulase secretion by Saccharomyces cerevisiae
Authors: Kroukamp Heinrich , den Haan Riaan , van Zyl John‐Henry , van Zyl Willem Heber
Published: October 2017

Lignocellulosic biomass remains an attractive feedstock for the production of fuels if a technology can be developed to overcome its recalcitrance. Consolidated bioprocessing (CBP) is one technology under development that aims to make this conversion process economically feasible. While no ideal CBP organism has been developed, several options have been pursued including engineering of the ethanologenic yeast Saccharomyces cerevisiae. Considering the genetic malleability of this model organism, a variety of chemicals and chemical precursors could also be produced directly from cellulosic feedstocks, assuming an enzymatic system for the hydrolysis of the feedstock sugar polymers can be established. While there have been several accounts of the secretion of cellulases by strains of S. cerevisiae and the successful conversion of limited amounts of amorphous and model crystalline cellulose feedstocks to ethanol, substantial conversion of crystalline cellulose by these strains in the absence of exogenous cellulases has not been reported. The most cited reasons for this were the low secretion titer of cellulases in general and of cellobiohydrolases in particular. This review will compare the efforts that have been made to enhance heterologous protein secretion in the yeast S. cerevisiae through rational strain engineering with a focus on cellulases and will investigate important factors in developing successful CBP‐yeast strains. © 2017 Society of Chemical Industry and John Wiley & Sons, Ltd
ATP Binding Cassette Sub‐family Member 2 (ABCG2) and Xenobiotic Exposure During Early Mouse Embryonic Stem Cell Differentiation
Authors: Rosen Mitchell B. , Jeffay Susan C. , Nichols Harriette P. , Hoopes Maria R. , Hunter E. Sidney
Published: October 2017

Background

ATP binding cassette sub‐family member 2 (ABCG2) is a well‐defined efflux transporter found in a variety of tissues. The role of ABCG2 during early embryonic development, however, is not established. Previous work which compared data from the ToxCast screening program with that from in‐house studies suggested an association exists between exposure to xenobiotics that regulate Abcg2 transcription and differentiation of mouse embryonic stem cells (mESC), a relationship potentially related to redox homeostasis.

Methods

mESC were grown for up to 9 days. Pharmacological inhibitors were used to assess transporter function with and without xenobiotic exposure. Proliferation and differentiation were evaluated using RedDot1 and quantiative reverse transcriptase‐polymerase chain reaction, respectively. ABCG2 activity was assessed using a Pheophorbide a‐based fluorescent assay. Protein expression was measured by capillary‐based immunoassay.

Results

ABCG2 activity increased in differentiating mESC. Treatment with K0143, an inhibitor of ABCG2, had no effect on proliferation or differentiation. As expected, mitoxantrone and topotecan, two chemotherapeutics, displayed increased toxicity in the presence of K0143. Exposure to K0143 in combination with chemicals predicted by ToxCast to regulate ABCG2 expression did not alter xenobiotic‐induced toxicity. Moreover, inhibition of ABCG2 did not shift the toxicity of either tert‐Butyl hydroperoxide or paraquat, two oxidative stressors.

Conclusion

As previously reported, ABCG2 serves a protective role in mESC. The role of ABCG2 in regulating redox status, however, was unclear. The hypothesis that ABCG2 plays a fundamental role during mESC differentiation or that regulation of the receptor by xenobiotics may be associated with altered mESC differentiation could not be supported. Birth Defects Research, 110:35–47, 2018. Published 2017. This article is a U.S. Government work and is in the public domain in the USA
Thalidomide Embryopathy as Possible Cause of Anterior Sacral Meningocele: A Case Report
Authors: Croci Davide Marco , Dalolio Martina , Schaeren Stefan , Wasner Morten G. , Mariani Luigi , Jost Gregory F.
Published: October 2017

A 54‐year‐old male presented with a sudden burning sensation during urination and left flank pain. Apart from having congenital facial palsy and malformation of the inner right ear that was linked to thalidomide embryopathy, the patient has always been in good health. Urine examination showed the presence of a urinary tract infection. An abdominal ultrasound revealed a large cyst in the lower abdomen, which on MRI corresponded to a large anterior sacral meningocele (ASM) with sacral agenesis at S1/S2. After antibiotic treatment and the spontaneous passage of a kidney stone, the symptoms resolved. This suggests that the patient's acute symptoms were caused by the urolithiasis and not the ASM. Thalidomide is teratogenic between days 17 and 30 after conception. The neural tube closes between days 20 and 36, therefore, thalidomide embryopathy was the possible cause of ASM in this patient. Birth Defects Research 109:1390–1392, 2017.© 2017 Wiley Periodicals, Inc.
Sickness Status and Neural Tube Defects: A Case–Control Study in a North Indian Population
Authors: Deb Roumi , Arora Gupta Jyoti , Saraswathy Kallur N. , Kalla Aloke K.
Published: October 2017

Background

The prevalence of neural tube defects (NTDs) in India is high in comparison to other regions in the world, with the Northern part reporting the highest prevalence.

Methods

To explore the risk factors for NTDs, a case–control study was carried out in Delhi from January 2008 to June 2011. Using multivariate logistic regression model analysis, 308 cases were compared with 580 controls and adjusted odds ratio (AOR) was calculated using SPSS version 17.

Results

Maternal factors that were significantly associated with increased risk of NTDs were inter‐pregnancy interval (AOR = 3.175; 95% confidence interval [CI], 2.007–5.024), hyperthermia during the first trimester (AOR = 2.07; 95% CI, 1.131–3.788), maturation ill pregnancy (AOR = 1.956; 95% CI, 1.385–2.763), chronic illness (AOR = 1.648; 95% CI, 1.103–2.462), and use of antibiotics (AOR = 5.589; 95% CI, 1.789–17.455). Differences in the risk were also found between upper and lower NTD. It was observed that all of the former five variables, except for chronic illness, were associated with risk for upper NTDs (AOR = 1.532; 95% CI, 0.916–2.563). In contrast, hyperthermia before conception (and not during the first trimester) was found to be additionally associated with risk for lower NTDs (AOR = 2.782; 95% CI, 1.302–5.944).

Conclusion

These findings highlight heterogeneity in the etiology of upper and lower NTDs. The study also highlights the risk factors that should be considered in combating the risk of NTDs. Birth Defects Research 109:1393–1399, 2017.© 2017 Wiley Periodicals, Inc.
Axillary tumour burden in women with a fine-needle aspiration/core biopsy-proven positive node on ultrasonography compared to women with a positive sentinel node
Authors: Lloyd P , Theophilidou E , Newcombe R G , Pugh L , Goyal A
Published: October 2017

Background

The sensitivity of axillary ultrasonography (AUS) has increased in recent years, enabling detection of even low-volume axillary nodal metastases. The aim here was to evaluate the axillary tumour burden in women with a fine-needle aspiration/core biopsy-proven positive node on AUS and in those with a positive sentinel node biopsy (SNB).

Methods

This retrospective cohort study included all patients with early breast cancer who had AUS and axillary lymph node dissection (ALND) between 2011 and 2014.

Results

A total of 332 patients who had ALND were eligible for the study, 191 (57·5 per cent) in the AUS-positive group and 141 (42·5 per cent) in the SNB-positive group. Patients in the AUS-positive group were older at diagnosis (P = 0·018), more likely to have larger tumours (P = 0·002), higher tumour grade (P = 0·005), positive human epidermal growth factor 2 status (P = 0·015), and negative oestrogen receptor status (P < 0·001). The AUS-positive group also had a larger number of lymph nodes with macrometastases (P < 0·001) and were more likely to have extranodal invasion (P < 0·001). In the AUS-positive group, 40·3 per cent of patients (77 of 191) had only one or two nodes with macrometastases identified at histology after ALND. Tumour size no larger than 20 mm, invasive ductal or lobular histology and breast-conserving surgery were associated with the presence of two or fewer macrometastases at ALND. Only tumour size and tumour histology remained significant in multiple logistic regression analysis.

Conclusion

Patients with AUS-detected metastases had a higher axillary tumour burden than those with SNB-detected metastases. Around 40 per cent of patients with AUS-detected nodal disease had one or two nodes with macrometastases and were thus overtreated by ALND.
Receptor‐guided 3D‐Quantitative Structure–Activity Relationship and Docking Studies of 6‐Substituted 2‐Arylaminopurines as CDK2 Kinase Inhibitors
Authors: Keretsu Seketoulie , Balasubramanian Pavithra Kuruchi , Bhujbal Swapnil Pandurang , Cho Seung Joo
Published: October 2017

Cyclin‐dependent kinase 2 (CDK2) plays important roles in cell cycle regulation. Owing to its multiple roles in many cancer types, it is considered as a significant target for cancer drug design. In this study, we used docking techniques and 3D‐quantitative structure–activity relationship (3D‐QSAR) studies on a series of 6‐substituted 2‐arylaminopurine derivatives as CDK2 kinase inhibitors. Receptor‐guided comparative molecular field analysis (CoMFA) (q2 = 0.653, optimal number of component [ONC] = 6, r2 = 0.965) and comparative molecular similarity indices analysis (CoMSIA) (q2 = 0.718, ONC = 6, r2 = 0.872) models were developed. Validation by progressive scrambling, bootstrapping (BS), and leave‐five‐out method suggests that the developed 3D‐QSAR models (CoMFA and CoMSIA) have reasonable predictive ability and reliability. Docking analysis revealed five hydrogen bond interactions between the compound 13 (most active compound) and CDK2 active site residues namely Glu81, Leu83, and Asp86. Contour map analysis gave comprehensive information regarding favorable and unfavorable substitution groups. Bulky, electropositive, and hydrophobic substitution groups at the R2 region can enhance the inhibitory activity of compounds whereas electronegative, hydrogen bond donor, and nonhydrophobic substitution groups at the position R1 will increase the inhibitory activity. Our contour map results can be used as a guideline in designing new potent compounds for CDK2 inhibition.
A review of bioanalytical quantitative methods for selected sphingosine 1‐phosphate receptor modulators
Authors: Dash Ranjeet Prasad , Srinivas Nuggehally R. , Rais Rana
Published: October 2017

Sphingosine 1‐phosphate (S1P1) modulators provide an emerging therapeutic approach for various autoimmune disorders such as multiple sclerosis and psoriasis. Fingolimod is the first approved orally active, selective and potent drug of this class. Other drugs belonging to this class include siponimod, ponesimod, ceralifimod, amiselimod, CS‐0777 and GSK2018682. However, owing to the high protein binding, polarity and zwitter‐ionic nature of the phosphate metabolite of parent drugs, it becomes challenging to optimize the extraction method for this class of compounds. Although, there are individual published bioanalytical methods for the analysis of selected S1P1 modulators to support preclinical and clinical drug development, no extensive review compiling all the bioanalytical methods for the important drugs in the class is available. Thus, we attempted to prepare a comprehensive review on various bioanalytical methods for selected S1P1 modulators which will provide all the relevant bioanalytical information as required by bioanalytical researchers. This review focuses on the various liquid chromatography with tandem mass spectrometry methods that have been used to quantify S1P1 modulators in various biological matrices. Extraction methods included liquid–liquid extraction, solid‐phase extraction and one‐step protein precipitation for extracting the analytes. This review captures key information regarding sample processing options and chromatographic/detection conditions.
Antimalarial and Antileishmanial Activities of Phytophenolics and Their Synthetic Analogues
Authors: Morimoto Masanori , Cantrell Charles L. , Khan Shabana , Tekwani Babu L. , Duke Stephen O.
Published: October 2017

Thirty‐seven phytophenolics and their synthetic analogues were evaluated for activity against two protozoal pathogens, Leishmania donovani and Plasmodium falciparum (D6 and W2 clones), respectively. 4,6‐Dimethoxyaurone demonstrated the highest activity with IC50 values of 13.2 and 16.9 μm against L. donovani and P. falciparum (W2 clone), respectively, without undesired cytotoxicity against VERO cells. The moiety having two benzene rings was critical to maintain the antiprotozoal activities based on the observation that both coumaranones and chromones were inactive while other test compounds, including coumarans and aurones, remained active. There was no correlation between antiprotozoal activities and previously evaluated insect antifeedant activity against common cutworms (Spodoptera litura). Flavonoids, including aurones, pterocarpans, and lignan like dihydrobenzofurans, structural analogues of coumarans, are abundant in fruits and vegetables, so these phytophenolics may act as natural antiprotozoal agents in humans.
Synthesis, Characterization, Antimicrobial Activity, and Docking Studies of New Triazolic Tripodal Ligands
Authors: Harit Tarik , Bellaouchi Reda , Rokni Yahya , Riahi Abdelkhalek , Malek Fouad , Asehraou Abdeslam
Published: October 2017

The synthesis and characterization of new N‐donor bitriazolic tripods were reported. The in vitro antibacterial and antifungal activities of these products were screened against fungal strain (Candida pelliculosa) and against four bacterial strains (Micrococcus luteus, Bacillus subtilis, Listeria innocua, and Escherichia coli). Biological data revealed the effect of the chemical structure on antimicrobial activity. Molecular docking studies of some compounds showed that they could act as inhibitors for the biotin carboxylase enzyme.
Hospital outcomes of transcatheter versus surgical aortic valve replacement in female in the United States
Authors: Ando Tomo , Akintoye Emmanuel , Telila Tesfaye , Briasoulis Alexandros , Takagi Hisato , Schreiber Theodore , Afonso Luis , Grines Cindy L.
Published: October 2017

Objectives

To assess the in‐hospital mortality and complications in female between transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR).

Background

Female is one of the risk factors for increased adverse events in cardiac surgery.

Methods and results

Nationwide Inpatient Sample database was queried from 2011 to 2014 for patients who underwent TAVR or SAVR in female patients. The primary endpoint was in‐hospital all‐cause mortality and second endpoints were perioperative complications. We performed a propensity score analysis to calculate the adjusted odds ratio (OR) for each outcome. Patients who had concomitant cardiac surgery and those who had TAVR or SAVR mainly for aortic regurgitation were excluded. Our query from 2011 to 2014 resulted in a total of 3,067 TAVR and 18,594 SAVR in female patients. TAVR patients were in general elder and had a higher burden of comorbidities. The primary endpoint was similar between TAVR and SAVR (4.2% vs. 3.9%, OR 1.0, P = 0.89). Compared to SAVR, female TAVR patients had less hemorrhage requiring transfusion (12% vs. 21%, OR 0.41, P < 0.001), perioperative cardiac arrest and nonfatal myocardial infarction (9.8% vs. 17%, OR 0.38, P < 0.001), respiratory complication (1.6% vs. 4.4%, OR 0.28, P < 0.001), post‐op sepsis (1.7% vs. 2.9%, OR 0.65, P = 0.03), acute myocardial infarction (3.0% vs. 4.9%, OR 0.60, P < 0.001), and acute kidney injury (15% vs. 18%, OR 0.62, P < 0.001). Conversely, female TAVR patients had significantly increased risk of new pacemaker implantation (11% vs. 5.9%, OR 1.7, P < 0.001) and use of extracorporeal membrane oxygenation (0.66% vs. 0.24%, OR 2.8, P < 0.001). TAVR patients had less nonroutine discharge. The median hospital cost was significantly higher in TAVR than SAVR (median $51,274 vs. $43,677, P < 0.001) but the length of stay was shorter (mean 7.8 days vs. 10.5 days).

Conclusions

TAVR may be a better option for those patients with underlying comorbidities that predispose them at higher risk for complications that was less observed in TAVR group. However, higher cost and increased risk of need for extracorporeal membrane oxygenation, although rare, should be taken into consideration upon deciding the optimal mode for aortic valve replacement.
Treatment goals and discharge criteria for hospitalized patients with acute heart failure
Authors: Bakosis G. , Christofilis I. , Karavidas A.
Published: October 2017

Acute heart failure (AHF) represents a potentially fatal disease that needs immediate hospital care. In‐hospital management can be divided into three consecutive phases: an early phase of intensive management of symptoms, an intermediate phase of stabilization and transition from intravenous to oral medication, and a late phase of discharge and outpatient management. However, despite its life‐threatening features (increased mortality and readmission rates), many treatment decisions are opinion based and only few are evidence based. The present paper describes in‐hospital treating modalities and attempts to provide clinical and laboratory criteria for patient evaluation that will help doctors determine readiness and safety of discharge. In addition, it highlights some unresolved issues that need to be addressed by future research.

Answer questions and earn CME: https://wileyhealthlearning.com/Activity2/5608938/Activity.aspx
Inotropes in acute heart failure
Authors: Bistola V. , Chioncel O.
Published: October 2017

Acute heart failure (AHF) encompasses a wide range of clinical presentations, from acute hypertensive heart failure (HF) to low cardiac output hypoperfusion syndromes with cardiogenic shock at the extreme end of this side. Inotropes are pharmacologic agents that enhance cardiac contractility, thereby augmenting cardiac output. Currently, there are three classes of inotropes available in clinical practice with distinct mechanisms of action: beta‐adrenergic agonists, phosphodiesterase III inhibitors, and the calcium‐sensitizer levosimendan. Inotropes are indicated as short‐term therapy in low cardiac output AHF and cardiogenic shock (usually with coadministration of a vasoconstrictor) to increase cardiac output, restore peripheral perfusion, and prevent end‐organ dysfunction. Inotropes can cause serious cardiovascular adverse effects, most commonly tachyarrhythmias and myocardial ischemia and are associated with increased medium‐ and long‐term mortality in HF. Therefore, intense monitoring is necessary during their administration, while long‐term infusion is contraindicated with the exception of advanced HF patients in whom inotropes may be used as a bridge to a definitive therapy (transplantation or ventricular assist device implantation) or as palliative treatment. Emerging inotropes acting through novel pathways independent of those targeted by conventional agents may overcome safety limitations of currently available agents.

Answer questions and earn CME: https://wileyhealthlearning.com/Activity2/5608943/Activity.aspx