bluuebunny/crossref_metadata_2025 huggingface dataset:
Different Impact Of Antiretroviral Drugs On Bone Differentiation In An In Vitro Model
Authors: Esposito Vincenzo , Perna Angelica , Lucariello Angela , Carleo Maria Aurora , Viglietti Rosaria , Sangiovanni Vincenzo , Coppola Nicola , Guerra Germano , De Luca Antonio , Chirianni Antonio
Published: March 2015

Recently increasing emphasis is placed on preventive health and management of chronic comorbidities avoiding long‐term toxicities of antiretroviral therapy (ART).

Drawing from this background we decided to use the Saos‐2, osteosarcoma cell line, as a cellular model, to evaluate the effects of some antiretroviral drugs such as abacavir (ABC), tenofovir (TDF), efavirenz (EFV), etravirine (ETR), and darunavir (DRV), on bone differentiation related pathways.

According to our observation, treatment with TDF and ABC affects the ability of the cells to produce calcium deposits with a reduced expression of type I collagen gene and p21 mRNA, also increasing the activity of Wnt3a related pathway. On the other hand treatment with EFV and DRV was not related to any significant reduction of calcium deposits but displayed a decrease in the expression of Wnt3a at day 14 and Type I Collagen at day 7 compared with untreated cells, even if this last down regulation was not confirmed at day 14. Instead ETR administration to Saos‐2 cells increases the calcium deposits collagen type I production, as a result of Wnt3a mRNA overexpression, and of an upregulation of collagen type I expression, being also the only drug able to increase the expression of p21 cdk inhibitor as further marker of terminal differentiation.

In summary these data suggest the potential negative interference of TDF and ABC on bone differentiation. DRV and EFV partially affect collagen type I production, instead ETR facilitates a positive bone balance as a result of an increased osteoblasts terminal differentiation. J. Cell. Biochem. 116: 2188–2194, 2015. © 2015 Wiley Periodicals, Inc.
Integrating Between‐Session Interventions (Homework) in Therapy: The Importance of the Therapeutic Relationship and Cognitive Case Conceptualization
Authors: Cronin Timothy J. , Lawrence Katherine A. , Taylor Kate , Norton Peter J. , Kazantzis Nikolaos
Published: March 2015

Between‐session interventions, or homework, are crucial to a range of psychological therapies, including cognitive behavior therapy (CBT). Therapeutic interventions often involve experiencing emotions and situations, or examining strongly held views about their problems, that clients can find distressing. Hence, the clinician faces a particular challenge in collaborating with the client to carry out these interventions between sessions. In this article, we convey how this process in CBT requires not only a consideration of the theoretically meaningful determinants of adherence behavior but also a sophisticated cognitive case conceptualization. Using case material, we illustrate the interplay between in‐session design, planning, and review of between‐session interventions and the conceptualization. We also include a distinction between generic elements of the therapeutic relationship and CBT‐specific elements. The case material also attends to the person of the therapist, and his or her own cognitive and emotional reactions occurring throughout the process of discussing between‐session interventions.
The prediction and recovery of the flux of PVDF membrane during dead‐end microfiltration
Authors: Zhou Yuenan , Zhu Zhongya , Wang Zhan , Zhang Ximing , Gao Kui , Liu Liping , Cheng Lina
Published: March 2015

BACKGROUND

This research focused on the fouling behavior of 0.1 µm PVDF membrane caused by activated sludge suspension in dead‐end filtration mode and the chemical cleaning of the fouled PVDF membrane by alkaline solutions. A combined intermediate pore blockage and cake filtration model was established to describe flux decline behavior. A series of experiments were performed to validate the proposed model and to explore the impacts of operating conditions on flux decline and recovery.

RESULTS

Flux decline was much faster with increasing transmembrane pressure (TMP) and concentration of mixed liquor suspended solids (MLSS). The proposed model predictions in this paper showed good agreement with the experimental data. The cleaning effect of sodium hypochlorite solution was superior to that of sodium hydroxide solution. Temperature was the dominant factor affecting flux recovery in the cleaning operation and the optimum chemical cleaning operating conditions were as follows: CNaOCl= 1%, r = 300 rpm, t = 30 min, T = 318 K.

CONCLUSIONS

The combined model was valid in predicting the flux decline process and more accurate than classical fouling models under the same operating conditions. Flux recovery was significantly improved under optimized cleaning conditions. © 2015 Society of Chemical Industry
Directed evolution of a β‐1,3‐1,4‐glucanase from Bacillus subtilis MA139 for improving thermal stability and other characteristics
Authors: Pei Honglei , Guo Xiaojing , Yang Wenhan , Lv Junnan , Chen Yiqun , Cao Yunhe
Published: March 2015

In order to improve some characteristics of a β‐1,3‐1,4‐glucanase from Bacillus subtilis MA139, directed evolution was conducted in this study. After error‐prone PCR, the β‐1,3‐1,4‐glucanase gene, glu‐opt, was cloned into the vector pBGP1 and transformed into Pichia pastoris X‐33 to construct a mutant library. Three variants named as 7‐32, 7‐87, and 7‐115 were screened from 8000 colonies. Amino‐acid sequence analysis showed that these mutants had one or two amino‐acid substitutions (7‐32: T113S, 7‐87: M44V/N53H, and 7‐115: N157D). The variants were over‐expressed in P. pastoris by methanol induction. After purification of the enzyme proteins, the characteristics of the variants were analyzed in detail. It indicated that these mutant enzymes had broader ranges of pH value and better pH stability than the wild‐type enzyme. The mutant enzyme 7‐87 had the best ability to tolerate an acid environment (pH 2.0), while the wild‐type enzyme had no activity under this condition. Moreover, all these mutants demonstrated improved thermal stability. In particular, the mutant enzyme 7‐32 had residual enzymatic activity of 60% and 40% after being incubated at 80 °C and 90 °C for 10 min. While, the wild‐type enzyme had no residual enzymatic activity after being incubated at 80 °C for 4 min. In addition, the mutant enzymes had better tolerance to some chemicals than the wild‐type enzyme. The improved stability could enhance the prospects for this enzyme to have use in the feed industry to reduce the effects of the anti‐nutritional factor β‐glucan.
Ag nanoparticles obtained by pulsed laser ablation in water: surface properties and SERS activity
Authors: Giorgetti Emilia , Marsili Paolo , Giammanco Francesco , Trigari Silvana , Gellini Cristina , Muniz‐Miranda Maurizio
Published: March 2015

We studied the surface properties and reactivity of silver nanoparticles obtained by picosecond or nanosecond pulsed laser ablation in water and with 1064‐nm wavelength. Ultraviolet–visible spectroscopy results and subsequent modelling by Mie theory indicated the presence of an oxide layer on the nanoparticle surface, which favours the colloidal stability, but reduces the interaction with the environment. The oxide layer is also responsible for the reduced surface enhanced Raman spectroscopy (SERS) activity of these colloids with respect to those obtained by chemical reduction. However, SERS activation can be efficiently obtained by addition of chloride ions to the colloids, leading to SERS enhancement factors that are comparable with those of the chemically prepared counterparts. Copyright © 2015 John Wiley & Sons, Ltd.
Supramolecular Polyelectrolyte Complexes of Bone Morphogenetic Protein‐2 with Sulfonated Polyrotaxanes to Induce Enhanced Osteogenic Differentiation
Authors: Terauchi Masahiko , Ikeda Go , Nishida Kei , Tamura Atsushi , Yamaguchi Satoshi , Harada Kiyoshi , Yui Nobuhiko
Published: March 2015

Although bone morphogenetic protein‐2 (BMP‐2) has received considerable attention because of its strong osteoinductivity, the clinical application of BMP‐2 is limited due to its degradation and deactivation under physiological conditions. Negatively charged heparin is known to form polyelectrolyte complexes with BMP‐2 to prevent deactivation and enhance the osteoinduction capability of BMP‐2. Herein, we report the sulfonated polyrotaxanes (S‐PRX) composed of α‐cyclodextrin threaded onto a linear polymer for the protection of BMP‐2 through the polyelectrolyte complex formation. When MC3T3‐E1 osteoprogenitor cells were treated with the S‐PRX/BMP‐2 complexes, significantly high alkaline phosphatase production and mineralized matrix deposition were observed compared with that of free BMP‐2 and heparin/BMP‐2 complexes. Note that the S‐PRXs showed negligible anticoagulant activity and cytotoxicity, whereas heparin showed strong anticoagulant activity. Accordingly, the S‐PRXs are promising candidates for enhanced osteoinduction ability of BMP‐2 without toxicity and anticoagulant activity and could contribute to clinical bone regeneration.
Synthesis and Application of Nanohybrids Based on Upconverting Nanoparticles and Polymers
Authors: Cheng Ziyong , Lin Jun
Published: March 2015

Lanthanide‐doped upconversion nanoparticles (UCNPs) have been an emerging and exciting research field in recent years due to their unique luminescent properties of converting near‐infrared light to shorter wavelength radiation. UCNPs offer excellent prospects in luminescent labeling, displays, bioimaging, bioassays, drug delivery, sensors, and anticounterfeiting applications. Along with the abundant studies and rapid progress in this area, UCNPs are promising to be a new class of luminescent probe owing to their special advantages over the conventional organic dyes and quantum dots. Among them, polymers play an important role to improve properties or endow new function of UCNPs such as for matrix materials, water solubility, linking active targeting molecules, biocompatibility, and stimuli‐responsive behavior. This article briefly reviews the compositions, optical mechanisms, architectures of upconversion nanocrystals and highlights the works on various functional UCNPs/polymer nanohybrids as well as many new interesting fruits in applications.

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International validation of a behavioral scale in Parkinson's disease without dementia
Authors: Rieu Isabelle , Martinez‐Martin Pablo , Pereira Bruno , De Chazeron Ingrid , Verhagen Metman Leo , Jahanshahi Marjan , Ardouin Claire , Chéreau Isabelle , Brefel‐Courbon Christine , Ory‐Magne Fabienne , Klinger Helene , Peyrol Fleur , Schupbach Michael , Dujardin Kathy , Tison François , Houeto Jean Luc , Krack Paul , Durif Franck
Published: March 2015

The “Ardouin Scale of Behavior in Parkinson's Disease” is a new instrument specifically designed for assessing mood and behavior with a view to quantifying changes related to Parkinson's disease, to dopaminergic medication, and to non‐motor fluctuations. This study was aimed at analyzing the psychometric attributes of this scale in patients with Parkinson's disease without dementia. In addition to this scale, the following measures were applied: the Unified Parkinson's Disease Rating Scale, the Montgomery and Asberg Depression Rating Scale, the Lille Apathy Rating Scale, the Bech and Rafaelsen Mania Scale, the Positive and Negative Syndrome Scale, the MacElroy Criteria, the Patrick Carnes criteria, the Hospital Anxiety and Depression Scale, and the Mini‐International Neuropsychiatric Interview. Patients (n = 260) were recruited at 13 centers across four countries (France, Spain, United Kingdom, and United States). Cronbach's alpha coefficient for domains ranged from 0.69 to 0.78. Regarding test–retest reliability, the kappa coefficient for items was higher than 0.4. For inter‐rater reliability, the kappa values were 0.29 to 0.81. Furthermore, most of the items from the Ardouin Scale of Behavior in Parkinson's Disease correlated with the corresponding items of the other scales, depressed mood with the Montgomery and Asberg Depression Rating Scale (ρ = 0.82); anxiety with the Hospital Anxiety and Depression Scale—anxiety (ρ = 0.56); apathy with the Lille Apathy Rating Scale (ρ = 0.60). The Ardouin Scale of Behavior in Parkinson's disease is an acceptable, reproducible, valid, and precise assessment for evaluating changes in behavior in patients with Parkinson's disease without dementia. © 2015 International Parkinson and Movement Disorder Society
SMN1 and SMN2 copy numbers in cell lines derived from patients with spinal muscular atrophy as measured by array digital PCR
Authors: Stabley Deborah L. , Harris Ashlee W. , Holbrook Jennifer , Chubbs Nicholas J. , Lozo Kevin W. , Crawford Thomas O. , Swoboda Kathryn J. , Funanage Vicky L. , Wang Wenlan , Mackenzie William , Scavina Mena , Sol‐Church Katia , Butchbach Matthew E. R.
Published: March 2015

Proximal spinal muscular atrophy (SMA) is an early‐onset motor neuron disease characterized by loss of α‐motor neurons and associated muscle atrophy. SMA is caused by deletion or other disabling mutation of survival motor neuron 1 (SMN1). In the human genome, a large duplication of the SMN‐containing region gives rise to a second copy of this gene (SMN2) that is distinguishable by a single nucleotide change in exon 7. Within the SMA population, there is substantial variation in SMN2 copy number; in general, those individuals with SMA who have a high SMN2 copy number have a milder disease. Because SMN2 functions as a disease modifier, its accurate copy number determination may have clinical relevance. In this study, we describe the development of an assay to assess SMN1 and SMN2 copy numbers in DNA samples using an array‐based digital PCR (dPCR) system. This dPCR assay can accurately and reliably measure the number of SMN1 and SMN2 copies in DNA samples. In a cohort of SMA patient‐derived cell lines, the assay confirmed a strong inverse correlation between SMN2 copy number and disease severity. Array dPCR is a practical technique to determine, accurately and reliably, SMN1 and SMN2 copy numbers from SMA samples.
Polytrimethylene Terephthalate: An Example of an Industrial Polymer Platform Development in China
Authors: Xie Qiongdan , Hu Xilong , Hu Tengjiao , Xiao Pan , Xu Youyong , Leffew Kenneth W.
Published: March 2015

Poly(trimethylene terephthalate) (PTT) which combines properties of polyethylene terephthalate (PET) and polybutylene terephthalate (PBT), is used in everyday products such as apparel and carpet. DuPont has successfully developed a renewably sourced building block, bio‐based 1,3‐propanediol (PDO), through industrial bio‐technology using glucose as the raw material. This green technology has significantly promoted the commercialization of PTT and its development activities. In DuPont's China R&D center, an industrial polymer technology platform has been established to serve the local China market with PTT manufacturing and application support. This platform explores new industrial applications for and modifications to PTT, such as expansion of the application space into engineering polymers (EP), development of fire retardancy, melt viscosity regulation for PTT fiber spinning and the use of PTT in nanocomposite preparations.
Reducing sensitivity losses due to respiration and motion in accelerated echo planar imaging by reordering the autocalibration data acquisition
Authors: Polimeni Jonathan R. , Bhat Himanshu , Witzel Thomas , Benner Thomas , Feiweier Thorsten , Inati Souheil J. , Renvall Ville , Heberlein Keith , Wald Lawrence L.
Published: March 2015

Purpose

To reduce the sensitivity of echo‐planar imaging (EPI) auto‐calibration signal (ACS) data to patient respiration and motion to improve the image quality and temporal signal‐to‐noise ratio (tSNR) of accelerated EPI time‐series data.

Methods

ACS data for accelerated EPI are generally acquired using segmented, multishot EPI to distortion‐match the ACS and time‐series data. The ACS data are, therefore, typically collected over multiple TR periods, leading to increased vulnerability to motion and dynamic B0 changes. The fast low‐angle excitation echo‐planar technique (FLEET) is adopted to reorder the ACS segments so that segments within any given slice are acquired consecutively in time, thereby acquiring ACS data for each slice as rapidly as possible.

Results

Subject breathhold and motion phantom experiments demonstrate that artifacts in the ACS data reduce tSNR and produce tSNR discontinuities across slices in the accelerated EPI time‐series data. Accelerated EPI data reconstructed using FLEET‐ACS exhibit improved tSNR and increased tSNR continuity across slices. Additionally, image quality is improved dramatically when bulk motion occurs during the ACS acquisition.

Conclusion

FLEET‐ACS provides reduced respiration and motion sensitivity in accelerated EPI, which yields higher tSNR and image quality. Benefits are demonstrated in both conventional‐resolution 3T and high‐resolution 7T EPI time‐series data. Magn Reson Med 75:665–679, 2016. © 2015 Wiley Periodicals, Inc.
Autoimmune spontaneous chronic urticaria and generalized myasthenia gravis in a patient with polyglandular autoimmune syndrome type 3
Authors: De Marchi Sergio Umberto , Cecchin Emanuela , De Marchi Sergio
Published: March 2015

Introduction: Autoimmune polyglandular syndromes (APS) are a group of disorders characterized by the presence of autoimmune processes in several endocrine and non‐endocrine organs that are classified into 4 types. Methods: We describe the case of a woman affected with APS type 3 who presented initially with Hashimoto thyroiditis and pernicious anemia and subsequently developed autoimmune chronic urticaria, myasthenia gravis, and type 1 diabetes mellitus. Results: This patient had a combination of components of APS types 3b, 3a, and 3c. She was referred for evaluation of chronic spontaneous urticaria and subsequently developed severe generalized myasthenia gravis, which was apparently unmasked by antihistamines used to control urticaria. Conclusions: Patients with APS should have a more thorough evaluation to better clarify their autoimmune background. Early detection of autoantibodies and latent organ‐specific dysfunction may help physicians take appropriate action to prevent full‐blown disease. Muscle Nerve 52:440–444, 2015
Three dimensional numerical simulation of residential building on shrink–swell soils in response to climatic conditions
Authors: Zhang Xiong , Briaud Jean‐Louis
Published: March 2015

Shrink–swell soils can cause distresses in buildings, and every year, the economic loss associated with this problem is huge. This paper presents a comprehensive system for simulating the soil–foundation–building system and its response to daily weather conditions. Weather data include rainfall, solar radiation, air temperature, relative humidity, and wind speed, all of which are readily available from a local weather station or the Internet. These data are used to determine simulation flux boundary conditions. Different methods are proposed to simulate different boundary conditions: bare soil, trees, and vegetation. A coupled hydro‐mechanical stress analysis is used to simulate the volume change of shrink–swell soils due to both mechanical stress and water content variations. Coupled hydro‐mechanical stress‐jointed elements are used to simulate the interaction between the soil and the slab, and general shell elements are used to simulate structural behavior. All the models are combined into one finite element program to predict the entire system's behavior. This paper first described the theory for the simulations. A site in Arlington, Texas, is then selected to demonstrate the application of the proposed system. Simulation results are shown, and a comparison between measured and predicted movements for four footings in Arlington, Texas, over a 2‐year period is presented. Finally, a three‐dimensional simulation is made for a virtual residential building on shrink–swell soils to identify the influence of various factors. Copyright © 2015 John Wiley & Sons, Ltd.
Quantitative description of radiofrequency (RF) power‐based ratiometric chemical exchange saturation transfer (CEST) pH imaging
Authors: Wu Renhua , Longo Dario Livio , Aime Silvio , Sun Phillip Zhe
Published: March 2015

Chemical exchange saturation transfer (CEST) MRI holds great promise for the imaging of pH. However, routine CEST measurement varies not only with the pH‐dependent chemical exchange rate, but also with CEST agent concentration, providing pH‐weighted information. Conventional ratiometric CEST imaging normalizes the confounding concentration factor by analyzing the relative CEST effect from different exchangeable groups, requiring CEST agents with multiple chemically distinguishable labile proton sites. Recently, a radiofrequency (RF) power‐based ratiometric CEST MRI approach has been developed for concentration‐independent pH MRI using CEST agents with a single exchangeable group. To facilitate quantification and optimization of the new ratiometric analysis, we quantified the RF power‐based ratiometric CEST ratio (rCESTR) and derived its signal‐to‐noise and contrast‐to‐noise ratios. Using creatine as a representative CEST agent containing a single exchangeable site, our study demonstrated that optimized RF power‐based ratiometric analysis provides good pH sensitivity. We showed that rCESTR follows a base‐catalyzed exchange relationship with pH independent of creatine concentration. The pH accuracy of RF power‐based ratiometric MRI was within 0.15–0.20 pH units. Furthermore, the absolute exchange rate can be obtained from the proposed ratiometric analysis. To summarize, RF power‐based ratiometric CEST analysis provides concentration‐independent pH‐sensitive imaging and complements conventional multiple labile proton group‐based ratiometric CEST analysis. Copyright © 2015 John Wiley & Sons, Ltd.
Imaging chemical exchange saturation transfer (CEST) effects following tumor‐selective acidification using lonidamine
Authors: McVicar Nevin , Li Alex X. , Meakin Susan O. , Bartha Robert
Published: March 2015

Increased lactate production through glycolysis in aerobic conditions is a hallmark of cancer. Some anticancer drugs have been designed to exploit elevated glycolysis in cancer cells. For example, lonidamine (LND) inhibits lactate transport, leading to intracellular acidification in cancer cells. Chemical exchange saturation transfer (CEST) is a novel MRI contrast mechanism that is dependent on intracellular pH. Amine and amide concentration‐independent detection (AACID) and apparent amide proton transfer (APT*) represent two recently developed CEST contrast parameters that are sensitive to pH. The goal of this study was to compare the sensitivity of AACID and APT* for the detection of tumor‐selective acidification after LND injection. Using a 9.4‐T MRI scanner, CEST data were acquired in mice approximately 14 days after the implantation of 105 U87 human glioblastoma multiforme (GBM) cells in the brain, before and after the administration of LND (dose, 50 or 100 mg/kg). Significant dose‐dependent LND‐induced changes in the measured CEST parameters were detected in brain regions spatially correlated with implanted tumors. Importantly, no changes were observed in T1‐ and T2‐weighted images acquired before and after LND treatment. The AACID and APT* contrast measured before and after LND injection exhibited similar pH sensitivity. Interestingly, LND‐induced contrast maps showed increased heterogeneity compared with pre‐injection CEST maps. These results demonstrate that CEST contrast changes after the administration of LND could help to localize brain cancer and monitor tumor response to chemotherapy within 1 h of treatment. The LND CEST experiment uses an anticancer drug to induce a metabolic change detectable by endogenous MRI contrast, and therefore represents a unique cancer detection paradigm which differs from other current molecular imaging techniques that require the injection of an imaging contrast agent or tracer. Copyright © 2015 John Wiley & Sons, Ltd.
Fighting to the Death: Weapon Injuries in a Mass Grave (16th–17th Century) from Bucharest, Romania
Authors: Constantinescu M. , Gavrilă E. , Greer S. , Soficaru A. , Ungureanu D.
Published: March 2015

Archaeological excavations carried out in 1972 and 2010–2011 in the University Square, Bucharest, Romania, brought to light 688 graves belonging to the Saint Sava Church Cemetery, dating between the middle of the 16th century and middle of the 19th century. At 35 metres from the western boundary of the cemetery, a mass grave containing three adult male skeletons was unearthed. The unusual position of the skeletons and the high incidence of traumatic injuries on the bones posed several questions concerning the historical and archaeological context of this grave. Osteological analysis of the skeletons revealed that all three individuals exhibited a series of occupational stress markers, indicating similar activities and associated with moderate physical activity during life. A total number of 24 perimortem lesions (caused mainly by sabres but also by blunt objects and projectiles) were recorded on the skeletal remains. The high percentage of cranial injuries may indicate that the head was the main target, demonstrating the intention to incapacitate the victims quickly and being different from those connected to executions in the period. Eight of these lesions were produced by sharp objects similar to sabres used by professional soldiers during the 16th–17th century in southeastern Europe.

The osteological profile of the individuals and the injuries they sustained suggest that the victims had a military background and were probably killed at the end of the 16th century during a violent dispute. Copyright © 2015 John Wiley & Sons, Ltd.
The Retromolar Space: A Morphological Curiosity Observed Amongst the Protohistoric Arikara and Mandan
Authors: De la Cova C.
Published: March 2015

The retromolar space (RMS), defined in palaeoanthropology as a space posterior to the third molar, between the distal edge of the tooth and the anterior margin of the ascending ramus when the mandible is held in lateral view, has been described as an autapomorphic trait unique to Neanderthals despite its presence in anatomically modern humans. This study examined RMS prevalence in a sample of protohistoric Arikara and Mandan Amerindians to determine what craniofacial morphology is correlated with the RMS. It was hypothesised that the feature would be present in the Amerindians studied and associated with a long cranial length, a large nasal height, midfacial prognathism, a broad mandible, and dental wear. The results indicated that RMSs were present in the Arikara and Mandan and significantly correlated with cranial length, cranial breadth, nasal height, bizygomatic breadth, basion‐nasion length, basion‐nasiospinale, mandible length, gonial angle, bigonial breadth, and dental wear. Thus, RMSs are associated with a dolichocephalic skull, wide cranial and facial breadth, a prognathic face, large nose and a corresponding wide and long mandible with a reduced gonial angle. This suggests that the RMS is the result of these features merging together in the craniofacial complex and should not be considered a Neanderthal autapomorphy. Copyright © 2015 John Wiley & Sons, Ltd.
A Note on the Demographic and Health Pattern of a Historical Sleeping Sickness Cemetery at Letsholathebe Memorial Hospital, Maun, Botswana
Authors: Mosothwane M. N.
Published: March 2015

A part of a historical cemetery used to bury victims of sleeping sickness in Maun, Botswana, was recently uncovered by a water supply improvement construction project. The cemetery had become obliterated from the surface and from the memories of the people resulting in the use of the land for residential purposes. Twelve skeletons were excavated along the water supply trench and have since been buried at one of the new village cemeteries. There were eight males, two females and two individuals of unknown sex. They were young adults ranging in age from 18 to 35 years at the time of death. Dental modifications were used to estimate the cultural identities of two individuals. Some of the remains had been buried with body clothing such as belts and necklaces. Poor dental health was most probably associated with poor nutrition and poor oral hygiene among the population. Copyright © 2015 John Wiley & Sons, Ltd.
Tetra‐ versus Pentavalent Inhibitors of Cholera Toxin
Authors: Fu Ou , Pukin Aliaksei V. , van Ufford H. C. Quarles , Branson Thomas R. , Thies‐Weesie Dominique M. E. , Turnbull W. Bruce , Visser Gerben M. , Pieters Roland J.
Published: March 2015

The five B‐subunits (CTB5) of the Vibrio cholerae (cholera) toxin can bind to the intestinal cell surface so the entire AB5 toxin can enter the cell. Simultaneous binding can occur on more than one of the monosialotetrahexosylganglioside (GM1) units present on the cell surface. Such simultaneous binding arising from the toxins multivalency is believed to enhance its affinity. Thus, blocking the initial attachment of the toxin to the cell surface using inhibitors with GM1 subunits has the potential to stop the disease. Previously we showed that tetravalent GM1 molecules were sub‐nanomolar inhibitors of CTB5. In this study, we synthesized a pentavalent version and compared the binding and potency of penta‐ and tetravalent cholera toxin inhibitors, based on the same scaffold, for the first time. The pentavalent geometry did not yield major benefits over the tetravalent species, but it was still a strong inhibitor, and no major steric clashes occurred when binding the toxin. Thus, systems which can adopt more geometries, such as those described here, can be equally potent, and this may possibly be due to their ability to form higher‐order structures or simply due to more statistical options for binding.
Dioxomolybdenum(VI) and dioxotungsten(VI) complexes: efficient catalytic activity for crosslinking reaction in ethylene‐vinyl acetate copolymer/alkoxysilane composites
Authors: Adachi Kenta , Toyomura Shoko , Miyakuni Yuko , Yamazaki Suzuko , Honda Kensuke , Hirano Tomoyuki
Published: March 2015

The catalytic performances of several bis(acetylacetonato)metal complexes [Cu(acac)2, Zn(acac)2, TiO(acac)2, VO(acac)2, MoO2(acac)2, and WO2(acac)2] were investigated for the crosslinking reaction via transesterifications in the ethylene‐vinyl acetate copolymer/tetraethoxysilane (EVA/TEOS) composite system by means of dynamic attenuated total reflectance Fourier transform infrared, solvent swelling, and solid‐state 29Si cross polarization/magic angle spinning nuclear magnetic resonance techniques. Results of the kinetic examination revealed that MoO2(acac)2 and WO2(acac)2 exhibited a higher catalytic activity than di‐n‐butyltin(IV) oxide, which is a catalyst most commonly used for the transesterification process in polymer system, but has a toxic effect on the environmental health. And furthermore, the crosslink density and final siloxane network structure of crosslinked EVA/TEOS composites are found to be greatly correlated with the catalyst used. On the basis of the SN2‐Si pathway, a plausible catalytic mechanism of MoO2(acac)2 and WO2(acac)2 was proposed for the crosslinking reaction via transesterifications of the vinyl acetate moieties in EVA backbone with the ethoxysilane groups in one TEOS molecule. The findings in this study may fill the blank in the high performance and environmentally friendly catalyst in the field of the crosslinking reactions in polymer system and provide useful clue for other transesterifications. Copyright © 2015 John Wiley & Sons, Ltd.
Efficient molecular subtype classification of high‐grade serous ovarian cancer
Authors: Leong Huei San , Galletta Laura , Etemadmoghadam Dariush , George Joshy ,   The Australian Ovarian Cancer Study, Köbel Martin , Ramus Susan J , Bowtell David
Published: March 2015

High‐grade serous carcinomas (HGSCs) account for approximately 70% of all epithelial ovarian cancers diagnosed. Using microarray gene expression profiling, we previously identified four molecular subtypes of HGSC: C1 (mesenchymal), C2 (immunoreactive), C4 (differentiated), and C5 (proliferative), which correlate with patient survival and have distinct biological features. Here, we describe molecular classification of HGSC based on a limited number of genes to allow cost‐effective and high‐throughput subtype analysis. We determined a minimal signature for accurate classification, including 39 differentially expressed and nine control genes from microarray experiments. Taqman‐based (low‐density arrays and Fluidigm), fluorescent oligonucleotides (Nanostring), and targeted RNA sequencing (Illumina) assays were then compared for their ability to correctly classify fresh and formalin‐fixed, paraffin‐embedded samples. All platforms achieved > 90% classification accuracy with RNA from fresh frozen samples. The Illumina and Nanostring assays were superior with fixed material. We found that the C1, C2, and C4 molecular subtypes were largely consistent across multiple surgical deposits from individual chemo‐naive patients. In contrast, we observed substantial subtype heterogeneity in patients whose primary ovarian sample was classified as C5. The development of an efficient molecular classifier of HGSC should enable further biological characterization of molecular subtypes and the development of targeted clinical trials. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Gremlin regulates renal inflammation via the vascular endothelial growth factor receptor 2 pathway
Authors: Lavoz Carolina , Alique Matilde , Rodrigues‐Diez Raquel , Pato Janos , Keri Gyorgy , Mezzano Sergio , Egido Jesús , Ruiz‐Ortega Marta
Published: March 2015

Inflammation is a main feature of progressive kidney disease. Gremlin binds to bone morphogenetic proteins (BMPs), acting as an antagonist and regulating nephrogenesis and fibrosis among other processes. Gremlin also binds to vascular endothelial growth factor receptor‐2 (VEGFR2) in endothelial cells to induce angiogenesis. In renal cells, gremlin regulates proliferation and fibrosis, but there are no data about inflammatory‐related events. We have investigated the direct effects of gremlin in the kidney, evaluating whether VEGFR2 is a functional gremlin receptor. Administration of recombinant gremlin to murine kidneys induced rapid and sustained activation of VEGFR2 signalling, located in proximal tubular epithelial cells. Gremlin bound to VEGFR2 in these cells in vitro, activating this signalling pathway independently of its action as an antagonist of BMPs. In vivo, gremlin caused early renal damage, characterized by activation of the nuclear factor (NF)‐κB pathway linked to up‐regulation of pro‐inflammatory factors and infiltration of immune inflammatory cells. VEGFR2 blockade diminished gremlin‐induced renal inflammatory responses. The link between gremlin/VEGFR2 and NF‐κB/inflammation was confirmed in vitro. Gremlin overexpression was associated with VEGFR2 activation in human renal disease and in the unilateral ureteral obstruction experimental model, where VEGFR2 kinase inhibition diminished renal inflammation. Our data show that a gremlin/VEGFR2 axis participates in renal inflammation and could be a novel target for kidney disease. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Cerebrospinal fluid proteomics in children during induction for acute lymphoblastic leukemia: A pilot study
Authors: Priola Ginna M. , Foster Matthew W. , Deal Allison M. , Richardson Brenna M. , Thompson J. Will , Blatt Julie
Published: March 2015

Background

Thrombosis in patients with acute lymphocytic leukemia (ALL) can develop after treatment with L‐asparaginase (asp) and is often localized to the central nervous system (CNS). We hypothesize that changes in the cerebrospinal fluid (CSF) proteome will occur after asp therapy and will anticipate CNS clots.

Methods

Five newly diagnosed patients, ages 1–11 years, with ALL (n = 4) or lymphoblastic lymphoma (LL) (n = 1) underwent serial lumbar punctures during induction. CSF was depleted of abundant plasma proteins and analyzed by gel‐free, label‐free quantitative proteomics.

Results

More than 600 proteins were quantified across all CSF samples. In four subjects, the expression of proteins involved in coagulation such as protein C Inhibitor (SERPINA5) and heparin cofactor II (SERPIND1) changed over the course of asp therapy. Antithrombin III (ATIII) and plasminogen (PLMN) levels were shown to have decreased expression over time in one child who developed a CNS thrombosis, compared to other subjects.

Conclusions

CSF proteomics is feasible and reproducible in ALL and LL. CSF ATIII and PLMN should be further investigated as predictive markers of CNS thrombosis. Pediatr Blood Cancer 2015;62:1190–1194. © 2015 Wiley Periodicals, Inc.
13‐valent pneumococcal conjugate vaccine (PCV13) is immunogenic and safe in children 6‐17 years of age with sickle cell disease previously vaccinated with 23‐valent pneumococcal polysaccharide vaccine (PPSV23): Results of a phase 3 study
Authors: De Montalembert Mariane , Abboud Miguel R. , Fiquet Anne , Inati Adlette , Lebensburger Jeffrey D. , Kaddah Normeen , Mokhtar Galila , Piga Antonio , Halasa Natasha , Inusa Baba , Rees David C. , Heath Paul T. , Telfer Paul , Driscoll Catherine , Al Hajjar Sami , Tozzi Alberto , Jiang Qin , Emini Emilio A. , Gruber William C. , Gurtman Alejandra , Scott Daniel A.
Published: March 2015

Background

A large population of older children with sickle cell disease (SCD) is currently vaccinated with only 23‐valent pneumococcal polysaccharide vaccine (PPSV23). In immunocompetent adults, PPSV23 vaccination reduces immune responses to subsequent vaccination with a pneumococcal vaccine. The 13‐valent pneumococcal conjugate vaccine (PCV13), which addresses this limitation, may offer an advantage to this population at high risk of pneumococcal disease. [This article was corrected after initial online publication with an erratum. The National Clinical Trial (NCT) number was omitted from the article abstract. That number is NCT00918580.]

Procedure

Children with SCD 6–17 years of age previously vaccinated with PPSV23 at least 6 months before study enrollment received two doses of PCV13 6 months apart. Anti‐pneumococcal polysaccharide immunoglobulin G (IgG) geometric mean concentrations (GMCs) and opsonophagocytic activity (OPA) geometric mean titers (GMTs) were measured before, 1 month after each administration, and 1 year after the second administration.

Results

Following each PCV13 administration, IgG GMCs and OPA GMTs significantly increased, and antibody levels after doses 1 and 2 were generally comparable. Antibody levels declined over the year following dose 2. At 1 year after the second administration, OPA GMTs for all and IgG GMCs for most serotypes remained above pre‐vaccination levels. Most adverse events were due to vaso‐occlusive crises, a characteristic of the underlying condition of SCD.

Conclusions

Children with SCD who were previously vaccinated with PPSV23 responded well to 1 PCV13 dose, and a second dose did not increase antibody response. PCV13 antibodies persisted above pre‐vaccination levels for all serotypes 1 year after dose 2. Children with SCD may benefit from at least one dose of PCV13. Pediatr Blood Cancer 2015;62:1427–1436. © 2015 Wiley Periodicals, Inc.
A strategy to improve treatment‐related mortality and abandonment of therapy for childhood ALL in a developing country reveals the impact of treatment delays
Authors: Suarez Amaranto , Piña Martha , Nichols‐Vinueza Diana X. , Lopera John , Rengifo Lyda , Mesa Mauricio , Cardenas Marcela , Morrissey Lisa , Veintemilla Galo , Vizcaino Martha , Del Toro Ligia , Vicuna Victor , Fernandez Jorge , Neuberg Donna , Stevenson Kristen , Gutierrez Alejandro
Published: March 2015

Background

Treatment‐related mortality and abandonment of therapy are major barriers to successful treatment of childhood acute lymphoblastic leukemia (ALL) in the developing world.

Procedure

A collaboration was undertaken between Instituto Nacional de Cancerologia (Bogota, Colombia), which serves a poor patient population in an upper‐middle income country, and Dana‐Farber/Boston Children's Cancer and Blood Disorders Center (Boston, USA). Several interventions aimed at reducing toxic deaths and abandonment were implemented, including a reduced‐intensity treatment regimen and a psychosocial effort targeting abandonment. We performed a cohort study to assess impact.

Results

The Study Population comprised 99 children with ALL diagnosed between 2007 and 2010, and the Historic Cohort comprised 181 children treated prior to the study interventions (1995–2004). Significant improvements were achieved in the rate of deaths in complete remission (13% to 3%; P = 0.005), abandonment (32% to 9%; P < 0.001), and event‐free survival with abandonment considered an event (47% to 65% at 2 years; P = 0.016). However, relapse rate did not improve. Medically unnecessary treatment delays were common, and landmark analysis revealed that initiating the PIII phase of therapy ≥4 weeks delayed predicted markedly inferior disease‐free survival (P = 0.016). Conversely, patients who received therapy without excessive delays had outcomes approaching those achieved in high‐income countries.

Conclusions

Implementation of a twinning program was followed by reductions in abandonment and toxic deaths, but relapse rate did not improve. Inappropriate treatment delays were common and strongly predicted treatment failure. These findings highlight the importance of adherence to treatment schedule for effective therapy of ALL. Pediatr Blood Cancer 2015;62:1395–1402. © 2015 Wiley Periodicals, Inc.
Comparison of childhood cancer survivors' nutritional intake with US dietary guidelines
Authors: Zhang Fang Fang , Saltzman Edward , Kelly Michael J. , Liu Shanshan , Must Aviva , Parsons Susan K. , Roberts Susan B.
Published: March 2015

Background

Despite improved survival, childhood cancer survivors experience significantly elevated risk of premature mortality and serious morbidity due to chronic health conditions. Poor diet quality can exacerbate chronic health conditions in the survivors but their nutritional intake has not been adequately studied.

Procedure

We assessed the Healthy Eating Index 2010 (HEI‐2010) in 22 survivors of pediatric acute lymphoblastic leukemia and lymphoma (median age = 11.7 years) and compared survivors' dietary intake to the 2010 Dietary Guidelines for Americans. Dietary data were collected using repeated 24 hr dietary recalls over a 1‐year period, which were averaged to estimate habitual intake.

Results

The mean HEI‐2010 in childhood cancer survivors was 52.7, about 50 percent of the maximum score. Long‐term survivors (time from diagnosis ≥10 years) had a significantly lower HEI‐2010 than recent survivors (time from diagnosis <5 years) (β = −11.5, 95% CI: −22.1, −0.9,P = 0.047). For individual food groups and nutrients, survivors had a particularly poor adherence to green vegetables and beans, total vegetables, and whole fruits. None of the survivors met the guidelines for dietary fiber and potassium intake. Only 4%, 19%, 24%, and 29% met the guidelines for vitamin D, sodium, calcium, and saturated fat intake. The average intake in relative to the recommended intake was 32% for vitamin D, 50% for potassium, 63% for fiber, and 85% for calcium, but was 115% for saturated fat and 143% for sodium.

Conclusions

Childhood cancer survivors, in particular long‐term survivors, have a poor adherence to the US dietary guidelines. Pediatr Blood Cancer 2015;62:1461–1467. © 2015 Wiley Periodicals, Inc.
Graphene nanoplatelets and fullerene in polypropylene matrix as nanosized dielectric probe
Authors: Shevchenko Vitaliy G. , Polschikov Sergey V. , Nedorezova Polina M. , Klyamkina Alla N. , Aladyshev Alexander M. , Chvalun Sergei N.
Published: March 2015

Composite materials of polypropylene, graphene nanoplatelets (GNP) or fullerene C60 were synthesized by in situ polymerization. GNP particles consist of 3–5 graphene layers and have aspect ratio 40. In composites with pristine GNP particles their aspect ratio is 110, whereas ultrasonic processing reduces it to 40–50. This change of aspect ratio of filler particles and their aggregates results in different properties of composites with pristine and sonicated GNP. Percolation threshold for composites with pristine GNP is 0.25% vol. In composites with sonicated GNP it is 2–3% vol. This is due to reduction in the size of filler particles aggregates and more uniform distribution of particles in polymer matrix after ultrasonic treatment. The presence of nanocarbon filler (GNP or fullerene) makes α‐transition, associated with the glass transition of the amorphous phase of polypropylene, clearly resolved. Its intensity increases with the concentration of nanofiller, which acts as a dielectric probe. POLYM. COMPOS., 36:1006–1011, 2015. © 2015 Society of Plastics Engineers
SPECIFIC COGNITIVE PREDICTORS OF EARLY MATH PROBLEM SOLVING
Authors: Decker Scott L. , Roberts Alycia M.
Published: March 2015

Development of early math skill depends on a prerequisite level of cognitive development. Identification of specific cognitive skills that are important for math development may not only inform instructional approaches but also inform assessment approaches to identifying children with specific learning problems in math. This study investigated the specific cognitive correlates of math problem solving across early grade levels (1–4) while controlling for basic calculation skills. As expected, basic calculation skill was a significant predictor of math problem solving across the entire sample. However, the addition of cognitive measures almost doubled the variance explained (R2 = .61). Additionally, only select cognitive variables contributed to the prediction of math problem solving, and these variables change in importance as children develop higher‐level math skills. Results are discussed within a developmental model, which emphasizes the increasing importance of abstract code representations required in higher levels of math performance.
Proteomic analysis of the herpes simplex virus 1 virion protein 16 transactivator protein in infected cells
Authors: Oh Hyung Suk , Knipe David M.
Published: March 2015

The herpes simplex virus 1 virion protein 16 (VP16) tegument protein forms a transactivation complex with the cellular proteins host cell factor 1 (HCF‐1) and octamer‐binding transcription factor 1 (Oct‐1) upon entry into the host cell. VP16 has also been shown to interact with a number of virion tegument proteins and viral glycoprotein H to promote viral assembly, but no comprehensive study of the VP16 proteome has been performed at early times postinfection. We therefore performed a proteomic analysis of VP16‐interacting proteins at 3 h postinfection. We confirmed the interaction of VP16 with HCF‐1 and a large number of cellular Mediator complex proteins, but most surprisingly, we found that the major viral protein associating with VP16 is the infected cell protein 4 (ICP4) immediate‐early (IE) transactivator protein. These results raise the potential for a new function for VP16 in associating with the IE ICP4 and playing a role in transactivation of early and late gene expression, in addition to its well‐documented function in transactivation of IE gene expression.