bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic malicious node detection with semi‐supervised multivariate classification in cognitive wireless sensor networks
Authors: Dai Hongjun , Liu Huabo , Jia Zhiping
Published: July 2014

Usually, wireless sensor networks are distributed massively with a number of nodes in an open large‐scale environment, and they are vulnerable to malicious attacks because the communications change dynamically and unpredictably. In this paper, we present a detection method based on multivariate classification to find out the malicious sensor nodes. It learns the features of a few type‐known node, classifies them with dynamical multivariate classification, and then establishes the sample space of all sensor nodes in the network activities to deduce the malicious nodes. The experiment results show that as long as the value of sensor node preferences and the number of active sensor nodes is stable, the false detection rate is stabilized below 0.5%. This proves that the algorithm can be used to the cognitive wireless sensor networks widely. Copyright © 2014 John Wiley & Sons, Ltd.
A game‐based incentive model for service cooperation in VANETs
Authors: Mao Yuxin , Zhu Ping , Wei Guiyi , Hassan Mohammad Mehedi , Hossain M. Anwar
Published: July 2014

Because of the highly dynamic topology and the unstable service status of nodes, services in vehicular ad hoc networks (VANETs) are not always reliable enough for users. Nodes in such a VANET incline to be selfish, which will even enhance this situation. In this work, we present an incentive model for VANETs to support more reliable services in network. We model the situation of service request and response in VANETs by using game theory. We consider the competitive and cooperative relationship between the nodes to formulate the game for VANETs. A contribution measurement is given in order to encourage cooperation during the game. Nodes are encouraged to provide more services to their neighbors in order to acquire more services from other nodes in our model. We also conduct a simulation for the proposed model and give detailed analysis in this work. From the results of the simulation, we argue that we could enable a VANET to support more reliable service by configuring suitable parameters for it. Copyright © 2014 John Wiley & Sons, Ltd.
A Pulse Radiolysis Study of the Dynamics of Ascorbic Acid Free Radicals within a Liposomal Environment
Authors: Kobayashi Kazuo , Seike Yumiko , Saeki Akinori , Kozawa Takahiro , Takeuchi Fusako , Tsubaki Motonari
Published: July 2014

The dynamics of free‐radical species in a model cellular system are examined by measuring the formation and decay of ascorbate radicals within a liposome with pulse radiolysis techniques. Upon pulse radiolysis of an N2O‐saturated aqueous solution containing ascorbate‐loaded liposome vesicles, ascorbate radicals are formed by the reaction of OH. radicals with ascorbate in unilamellar vesicles exclusively, irrespective of the presence of vesicle lipids. The radicals are found to decay rapidly compared with the decay kinetics in an aqueous solution. The distinct radical reaction kinetics in the vesicles and in bulk solution are characterized, and the kinetic data are analyzed.
High‐Yielding Synthesis of a Hetero‐Pacman Compound and the Characterization of Intermediates and Side‐Products
Authors: Schwalbe Matthias , Wrzolek Pierre , Lal Garima , Braun Beatrice
Published: July 2014

Through an optimized synthetic procedure, metalloligand 5, which features a hetero‐Pacman scaffold comprising a porphyrin and a terpyridine moiety, has been assembled by a double Suzuki reaction. In a subsequent step, a ruthenium‐bipyridine fragment was introduced at the terpyridine coordination site of metalloligand 5 to form complex 6, which was fully characterized and its potential application in water oxidation catalysis tested. A number of side‐products were isolated and characterized during the two‐step synthesis procedure, including a hydroxylated version of the boronic acid substituted precursor molecule derived by a base‐assisted rearrangement. The compounds described herein extend the Pacman concept to the assembly of different metal combinations with different coordination spheres and their interactions in the activation of small molecules.
Inclusion of an Iodine Molecule in a Tiara‐Like Octanuclear Palladium Thiolate Complex
Authors: Yamashina Yukari , Kataoka Yasutaka , Ura Yasuyuki
Published: July 2014

An iodine molecule was successfully inserted into the inner cavity of a tiara‐like octanuclear palladium thiolate complex, [Pd(μ‐SCH2CO2Me)2]8. The included iodine molecule coordinated weakly to six palladium atoms in both linear and bent modes, as confirmed by X‐ray crystallography and DFT calculations. The inclusion complex reacted with an excess amount of I2 to produce a disulfide, which was accompanied by decomposition of the tiara ring.
2,5‐Diamide‐Substituted Five‐Membered Heterocycles: Challenging Molecular Synthons
Authors: Fabbro Chiara , Armani Simone , Carloni Laure‐Elie , De Leo Federica , Wouters Johan , Bonifazi Davide
Published: July 2014

We describe synthetic routes for preparing previously unknown 2,5‐diamide‐substituted five‐membered heterocycles based on the thiophene, pyrrole, and furan ring systems by exploiting Curtius‐like rearrangement reactions. Conformation analysis of the 2,5‐diamidothiophene derivatives identified a “closed” conformation, in which the two carbonyl O atoms are in close contact with the thiophene S atom.
Highly Enantioselective Construction of Spirocyclopentaneoxindoles Containing Four Consecutive Stereocenters through an Organocatalytic Iminium–Enamine Cascade Reaction
Authors: Ding Liang‐Zhong , Zhong Tong‐Sheng , Wu Hao , Wang Yong‐Mei
Published: July 2014

Spirocyclopentaneoxindole derivatives containing four consecutive stereocenters, including a spiro quaternary center, were constructed by an organocatalytic iminium–enamine cascade sequence in good yields (up to 86 %) with excellent enantiomeric (up to >99 % ee) and diastereomeric purities (up to >99:1 dr). This highly efficient procedure will allow diversity‐oriented syntheses of this intriguing class of compounds with potential biological activities.
Synthesis of 1,2,4‐Thiadiazoles by Oxidative Dimerization of Carbothioamides by Using Oxone
Authors: Yoshimura Akira , Todora Anthony D. , Kastern Brent J. , Koski Steven R. , Zhdankin Viktor V.
Published: July 2014

1,2,4‐Thiadiazoles were efficiently synthesized in good yields through the oxidative dimerization of carbothioamides by using Oxone as a readily available, inexpensive, and environmentally safe oxidant. A similar reaction of phenylselenoamide led to the corresponding 1,2,4‐phenylselenadiazole in high yield.
Could surface roughness be a poor proxy for landslide age? Results from the Swabian Alb, Germany
Authors: Goetz Jason N. , Bell Rainer , Brenning Alexander
Published: July 2014

The potential of surface roughness to quantify geomorphological landforms and processes has been enhanced with the availability of high‐resolution digital terrain models (DTM). Recent studies that attempt to identify landslide features with surface roughness have suggested that this measure of topographic heterogeneity may also be applied to estimate the relative age of landslides. This is a provisional study that explores the potential of this relationship by assessing the ability of surface roughness to act as a proxy for relative landslide age. The surface roughness for a set of 12 dated landslides in the Swabian Alb that occurred between 1789 and 1985 was calculated from a 1 m2 spatial resolution LiDAR DTM with three algorithms: root‐mean‐square‐height (RMSH), standard deviation of slope (SDS), and direction cosine eigenvalue ratios (DCE). Scale‐dependence was analysed by calculating surface roughness for a range of moving window sizes (3 × 3, 5 × 5, 9 × 9 and 15 × 15), and surface roughness for each landslide was summarized by the median and upper quartile. Only weak correlations (best Spearman's rho 0.58) were present between landslide age and surface roughness. This correlation becomes weaker with increasing moving window size. Given weak observed associations and discussed challenges pertaining to the complexities of landslide morphology change over time, we currently find that surface roughness alone may not be justifiable to act as a proxy for landslide age for our study region. Furthermore, we recommend future studies should focus on addressing possible natural and anthropogenic factors such as land use change that may alter surface roughness. These studies may focus on one of the three roughness measures used here as they are strongly correlated. Copyright © 2014 John Wiley & Sons, Ltd.
Rehydration characteristics of dehydrated West African pepper (Piper guineense) leaves
Authors: Okpala Laura C. , Ekechi Constance A.
Published: July 2014

The rehydration characteristics of dehydrated West African pepper leaves were investigated at hydration temperatures of 28, 60, 70, and 80°C. Four treatments were given to the leaves: blanched and sun dried, unblanched and sun dried, blanched and shade dried, and unblanched and shade dried. The hydration process of the dehydrated leaves was adequately described by the Peleg's equation. As the hydration temperature increased from 28 to 70°C, there was a significant decrease in the Peleg's constant K1, while for most of the leaves the Peleg's constant K2 varied with temperature. Rehydration ratio values ranged from 3.75 in blanched shade dried leaves to 4.26 in unblanched sun dried leaves with the unblanched leaves generally exhibiting higher ratios than the blanched leaves.
Lysyl oxidase-like 2 is critical to tumor microenvironment and metastatic niche formation in hepatocellular carcinoma
Authors: Wong Carmen Chak-Lui , Tse Aki Pui-Wah , Huang Yan-Ping , Zhu Yan-Ting , Chiu David Kung-Chun , Lai Robin Kit-Ho , Au Sandy Leung-Kuen , Kai Alan Ka-Lun , Lee Joyce Man-Fong , Wei Larry Lai , Tsang Felice Ho-Ching , Lo Regina Cheuk-Lam , Shi Jue , Zheng Yong-Ping , Wong Chun-Ming , Ng Irene Oi-Lin
Published: July 2014

Poor prognosis of cancers, including hepatocellular carcinoma (HCC), is mainly associated with metastasis; however, the underlying mechanisms remain poorly understood. This article investigates the role of lysyl oxidase-like 2 (LOXL-2) in the biology of HCC metastasis. First, we showed that HCC metastasis relies on a collagen-modifying enzyme, LOXL2, which was significantly overexpressed in tumorous tissues and sera of HCC patients, indicating that LOXL2 may be a good diagnostic marker for HCC patients. Second, we delineated a complex, interlinked signaling network that involves multiple regulators, including hypoxia, transforming growth factor beta (TGF-β), and microRNAs (miRNAs), converging to control the expression of LOXL2. We found not only that LOXL2 was regulated by hypoxia/hypoxia-inducible factor 1 alpha (HIF-1α), but also that TGF-β activated LOXL2 transcription through mothers against decapentaplegic homolog 4 (Smad4), whereas two frequently underexpressed miRNA families, miR-26 and miR-29, cooperatively suppressed LOXL2 transcription through interacting with the 3' untranslated region of LOXL2. Third, we demonstrated the imperative roles of LOXL2 in modifying the extracellular matrix components in the tumor microenvironment and metastatic niche of HCC. LOXL2 promoted intrahepatic metastasis by increasing tissue stiffness, thereby enhancing the cytoskeletal reorganization of HCC cells. Furthermore, LOXL2 facilitated extrahepatic metastasis by enhancing recruitment of bone-marrow–derived cells to the metastatic site.

Conclusion

: These findings integrate the clinical relevance, molecular regulation, and functional implications of LOXL2 in HCC metastasis. (Hepatology 2014;60:1645–1658)
Evaluation of clinical trial eligibility and prognostic indices in a population‐based cohort of systemic peripheral T‐cell lymphomas from the Danish Lymphoma Registry
Authors: Pedersen Martin Bjerregaard , Hamilton‐Dutoit Stephen Jacques , Bendix Knud , Møller Michael Boe , Nørgaard Peter , Johansen Preben , Ralfkiaer Elisabeth , Brown Peter De Nully , Hansen Per Boye , Jensen Bo Amdi , Madsen Jakob , Schöllkopf Claudia , d'Amore Francesco
Published: July 2014

Clinical trials (CTs) are needed to improve the outcome for peripheral T‐cell lymphomas (PTCL), and accrual into CTs is one of the main recommendations in international treatment guidelines. The use of risk‐adapted strategies has been suggested as a way to optimize treatment outcome in PTCL. The aim of the present study was to evaluate CT eligibility and selected prognostic indices in a population‐based PTCL cohort of 481 PTCL patients identified from the Danish Lymphoma Registry in the period 2000–2010. According to five predefined parameters (age, performance status, P‐creatinine, P‐ALAT and measurable tumour lesion), patients were subdivided into four groups: ‘younger fit’, ‘elderly fit’, ‘frail’ and ‘not CT eligible’. International prognostic index (IPI), prognostic index for T‐cell lymphoma (PIT) and anaplastic lymphoma kinase (ALK) protein expression were tested at subtype‐specific level. Overall, 41% of the patients were considered eligible for interventional CTs implicating curatively intended multiagent chemotherapy, including, if considered appropriate, consolidating stem cell transplantation (SCT), as part of the upfront management strategy. Moreover, 28% was elderly fit and eligible for interventional CT, including those with SCT as part of the trial design. Approximately 7% were defined as ‘too frail’ for aggressive treatment schedules, whereas 24% were deemed not to be eligible for any CT. Both overall and progression‐free survivals were effectively predicted by IPI and PIT (p < 0.001). ALK‐positive anaplastic large cell lymphoma patients were significantly younger (median age 40 vs. 62, p < 0.001) and had a better outcome than their ALK‐negative counterparts (p < 0.001). However, ALK expression lost its prognostic significance when adjusting for age. In a population‐based cohort of adult Caucasian PTCL patients, approximately half were eligible for multiagent chemotherapy with or without consolidating SCT. Both IPI and PIT are useful prognostic indices in all ‘primary nodal’ PTCL entities. The prognostic value of ALK protein expression in anaplastic large cell lymphoma is significantly downsized when adjusting for age. Copyright © 2014 John Wiley & Sons, Ltd.
Fluorescence‐based endoscopic imaging of Thomsen–Friedenreich antigen to improve early detection of colorectal cancer
Authors: Sakuma Shinji , Yu James Y. H. , Quang Timothy , Hiwatari Ken‐Ichiro , Kumagai Hironori , Kao Stephanie , Holt Alex , Erskind Jalysa , McClure Richard , Siuta Michael , Kitamura Tokio , Tobita Etsuo , Koike Seiji , Wilson Kevin , Richards‐Kortum Rebecca , Liu Eric , Washington Kay , Omary Reed , Gore John C. , Pham Wellington
Published: July 2014

Thomsen–Friedenreich (TF) antigen belongs to the mucin‐type tumor‐associated carbohydrate antigen. Notably, TF antigen is overexpressed in colorectal cancer (CRC) but is rarely expressed in normal colonic tissue. Increased TF antigen expression is associated with tumor invasion and metastasis. In this study, we sought to validate a novel nanobeacon for imaging TF‐associated CRC in a preclinical animal model. We developed and characterized the nanobeacon for use with fluorescence colonoscopy. In vivo imaging was performed on an orthotopic rat model of CRC. Both white light and fluorescence colonoscopy methods were utilized to establish the ratio‐imaging index for the probe. The nanobeacon exhibited specificity for TF‐associated cancer. Fluorescence colonoscopy using the probe can detect lesions at the stage which is not readily confirmed by conventional visualization methods. Further, the probe can report the dynamic change of TF expression as tumor regresses during chemotherapy. Data from this study suggests that fluorescence colonoscopy can improve early CRC detection. Supplemented by the established ratio‐imaging index, the probe can be used not only for early detection, but also for reporting tumor response during chemotherapy. Furthermore, since the data obtained through in vivo imaging confirmed that the probe was not absorbed by the colonic mucosa, no registered toxicity is associated with this nanobeacon. Taken together, these data demonstrate the potential of this novel probe for imaging TF antigen as a biomarker for the early detection and prediction of the progression of CRC at the molecular level.
Fatty liver creates a pro‐metastatic microenvironment for hepatocellular carcinoma through activation of hepatic stellate cells
Authors: Mikuriya Yoshihiro , Tashiro Hirotaka , Kuroda Shintaro , Nambu Junko , Kobayashi Tsuyoshi , Amano Hironobu , Tanaka Yuka , Ohdan Hideki
Published: July 2014

Fatty liver (FL) is associated with development of hepatocellular carcinoma (HCC). However, whether FL itself promotes the progression of HCC is unclear. We recently found that hepatic stellate cells (HSCs) were prominently activated in the steatotic liver. Here, we investigated whether steatotic livers promote HCC progression and whether HSCs of steatotic liver are associated with HCC progression. We implanted rat HCC cells into diet‐induced steatotic livers in rats via portal vein injection. Thereafter, HSCs and HCC cells were co‐implanted subcutaneously into nude rats. Migration and proliferation of HCC cells were measured, and activation of ERK and Akt in these cells was determined by western blotting. Chemokines secreted from HSCs and HCC cells were also evaluated by ELISA. Steatotic livers significantly promoted HCC metastasis compared with non‐steatotic livers. Additionally, co‐implantation of HCC cells with HSCs from steatotic livers produced significantly larger tumors in recipient rats as compared to those induced by HCC cells co‐implanted with HSCs from normal livers (NLs). HSCs isolated from steatotic livers, compared with HSCs isolated from NLs, secreted greater amounts of interleukin‐1α, vascular endothelial growth factor, and transforming growth factor‐β. These cytokines may enhance the proliferation and migration of HCC cells by increasing the phosphorylation of ERK and Akt in HCC cells. Moreover, we noted that the Rho‐kinase inhibitor deactivated activated HSCs and attenuated HCC progression. In conclusion, the rat steatotic liver microenvironment favors HCC metastasis, and this effect appears to be promoted by activated HSCs in the steatotic liver.
Wear particles and ions from cemented and uncemented titanium‐based hip prostheses—A histological and chemical analysis of retrieval material
Authors: Grosse Susann , Haugland Hans Kristian , Lilleng Peer , Ellison Peter , Hallan Geir , Høl Paul Johan
Published: July 2014

Wear debris‐induced inflammation is considered to be the main cause for periprosthetic osteolysis in total hip replacements (THR). The objective of this retrieval study was to examine the tissue reactions and exposure to metal ions and wear particles in periprosthetic tissues and blood samples from patients with titanium (Ti)‐based hip prostheses that were revised due to wear, osteolysis, and/or aseptic loosening. Semiquantitative, histological tissue evaluations in 30 THR‐patients revealed numerous wear debris‐loaded macrophages, inflammatory cells, and necrosis in both groups. Particle load was highest in tissues adjacent to loosened cemented Ti stems that contained mainly submicron zirconium (Zr) dioxide particles. Particles containing pure Ti and Ti alloy elements were most abundant in tissues near retrieved uncemented cups. Polyethylene particles were also detected, but accounted only for a small portion of the total particle number. The blood concentrations of Ti and Zr were highly elevated in cases with high abrasive wear and osteolysis. Our findings indicate that wear particles of different chemical composition induced similar inflammatory responses, which suggests that particle size and load might be more important than the wear particle composition in periprosthetic inflammation and osteolysis. © 2014 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials Published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 103B:709–717, 2015.
Creep loading during degradation attenuates mechanical property loss in PLGA
Authors: Dreher Maureen L. , Nagaraja Srinidhi , Li Jian
Published: July 2014

While absorbable materials and medical devices primarily degrade through hydrolysis, their degradation kinetics are sensitive to environmental conditions, including temperature, pH, and mechanical loading. While there is some consistent information in the literature suggesting that strain controlled loading accelerates strength loss, there is much more limited information on the interaction between degradation and mechanical load applied under force control. Force control conditions impose a different stress state on the material and therefore, may exhibit different effects on degradation. In this study, the interaction between loading and degradation rate for an exemplary absorbable polymer, poly(l‐lactide‐co‐glycolide), was investigated. The results indicated that load during degradation results in significant polymer creep, which is associated with increased force loss, but decreased strength loss (i.e., stress based parameters such as ultimate stress). This study further identified that changes to the degradation kinetics from exposure to loading were not associated with alterations to polymer crystallinity but were associated with delayed loss of molecular weight. Overall, these results demonstrate the importance of investigating the interaction between loading and degradation and that physical changes, such as those induced by creep, rather than chemical changes offer the strongest explanation for alteration of degradation kinetics. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 103B: 700–708, 2015.
Studying the antiemetic effect of vitamin B6 for morning sickness: Pyridoxine and pyridoxal are prodrugs
Authors: Matok Ilan , Clark Shannon , Caritis Steve , Miodovnik Menachem , Umans Jason G. , Hankins Gary , Mattison Donald R. , Koren Gideon
Published: July 2014

Vitamin B6 has been known to possess antiemetic effects since 1942. This water soluble compound has several forms in the circulation including pyridoxine, pyridoxal, and pyridoxal phosphate. The active antiemetic form of vitamin B6 is unknown. This was a pre‐specified substudy of a randomized, placebo‐controlled trial comparing the antiemetic effect of the doxylamine–vitamin B6 combination (Diclectin®) (n = 131) to placebo (n = 126) in women with nausea and vomiting of pregnancy. Serum concentrations of pyridoxine, pyridoxal, and pyridoxal 5′ phosphate (PLP) and doxylamine were measured on Days 4, 8, and 15. With Diclectin® exhibiting a significant antiemetic effect in pregnancy, serum concentrations of pyridoxine were unmeasurable in almost all patients and those of pyridoxal were undetectable in half of patients. In contrast, PLP was measurable at sustained, stable steady‐state levels in all patients. Our data suggest that there is a correlation between PLP levels and PUQE score of morning sickness symptoms when pyridoxine and pyridoxal levels are undetectable, and hence they might be prodrugs of PLP, which may be the active antiemetic form of vitamin B6.
Bioremediation by alkaline protease (AkP) from edible mushroom Termitomyces clypeatus: optimization approach based on statistical design and characterization for diverse applications
Authors: Majumder Rajib , Banik Samudra Prosad , Ramrakhiani Lata , Khowala Suman
Published: July 2014

BACKGROUND

Bioremediation using enzymes has become an attractive approach for removing hazardous chemicals from the environment. The present study investigated the production, optimization and applications of an extracellular alkaline protease (AkP) from the edible mushroom Termitomyces clypeatus focusing on bioremediation.

RESULTS

For optimized enzyme production, the variables significantly influencing the protease activity were screened through the 11 factorial Plackett–Burman design. The optimum values of the selected variables and their mutual interactions were determined through response surface methodology using the Box–Behnken experimental design. Overall a 10‐fold increase in enzyme activity (1830 U mL‐1) was obtained which closely matched the yield predicted by the statistical model (1778.63 U mL‐1) with R2 = 0.9819. AkP could efficiently dehair the goat skin, detached bird feather vanes from its shaft and reduce BOD, COD and pH of tannery waste effluent. The AkP also demonstrated bactericidal property against Staphylococcus aureus as detected by MIC and flow cytometry analyses.

CONCLUSION

As an ecofriendly alternative, the enzyme showed significant promise for bioremediation and industrial applications through time‐saving bioprocesses. This is first report of alkaline protease from T. clypeatus or from a fungal source with wide‐ranging application potential. © 2014 Society of Chemical Industry
Differences in Word Usage by Truth Tellers and Liars in Written Statements and an Investigative Interview After a Mock Crime
Authors: Matsumoto David , Hwang Hyisung C.
Published: July 2014

Although much is known about word usage differences between truths and lies, most of the research to date involves an examination of truths and lies in low stakes situations, written statements or interviews but not both, and native speakers of a single language. We examined differences in word usage between truth tellers and liars in a moderately high stakes, real‐life scenario (mock crime) involving participants from four cultural/ethnic groups—European‐Americans, Chinese, Hispanics and Middle Easterners. Each participant produced a written statement and participated in an investigative interview; word usage in both was analyzed. Word usage differentiated truths from lies in both the written statement and the investigative interview, and the effect sizes associated with these findings were substantial. For the written statement, word usage predicted truths from lies at 68.90% classification accuracy; for the investigative interview, word usage predicted truths from lies at 71.10% accuracy. Ethnicity did not moderate these effects. These findings are discussed in terms of their implications to cross‐cultural applicability of the psychological demands placed on liars and in terms of their practical field utility. Copyright © 2014 John Wiley & Sons, Ltd.
MR system operator: Recommended minimum requirements for performing MRI in human subjects in a research setting
Authors: Calamante Fernando , Faulkner William H. , Ittermann Bernd , Kanal Emanuel , Kimbrell Vera , Owman Titti , Reeder Scott B. , Sawyer Anne M. , Shellock Frank G. , van den Brink Johan S. ,   on behalf of the ISMRM Safety Committee
Published: July 2014

This article is intended to provide guidelines for the minimum level of safety and operational knowledge that an MR system operator should exhibit in order to safely perform an MR procedure in a human subject in a research setting. This article represents the position of the International Society for Magnetic Resonance in Medicine (ISMRM) regarding this important topic and was developed by members of this society's MR Safety Committee. J. Magn. Reson. Imaging 2015;41:899–902. © 2014 Wiley Periodicals, Inc.
Hepatitis C virus NS3 protease genotyping and drug concentration determination during triple therapy with telaprevir or boceprevir for chronic infection with genotype 1 viruses, southeastern France
Authors: Aherfi Sarah , Solas Caroline , Motte Anne , Moreau Jacques , Borentain Patrick , Mokhtari Saadia , Botta‐Fridlund Danielle , Dhiver Catherine , Portal Isabelle , Ruiz Jean‐Marie , Ravaux Isabelle , Bregigeon Sylvie , Poizot‐Martin Isabelle , Stein Andreas , Gérolami René , Brouqui Philippe , Tamalet Catherine , Colson Philippe
Published: July 2014

Telaprevir and boceprevir, the two first hepatitis C virus (HCV) NS3 protease inhibitors (PIs), considerably increase rates of sustained virologic response in association with pegylated interferon and ribavirin in chronic HCV genotype 1 infections. The 30 first patients treated by telaprevir or boceprevir including anti‐HCV therapies since 2011 in Marseille University hospitals, France, were monitored. HCV loads and plasmatic concentrations of telaprevir and boceprevir were determined on sequential blood samples. HCV NS3 protease gene population sequencing was performed at baseline of treatment and in case of treatment failure. Fifteen patients (including 7 co‐infected with HIV) received telaprevir and the other 15 patients (including 4 co‐infected with HIV) received boceprevir. At baseline, HCV NS3 protease from six patients harbored amino acid substitutions associated with PI‐resistance. Treatment failure occurred at week 12 for 7 patients. Amino acid substitutions associated with PI‐resistance were observed in six of these cases. HCV NS3 R155K and T54A/S mutants, all of genotype 1a, were found from four patients. Median (interquartile range) plasma concentrations were 3,092 ng/ml (2,320–3,525) for telaprevir and 486 ng/ml (265–619) for boceprevir. For HIV–HCV co‐infected patients, median concentrations were 3,162 ng/ml (2,270–4,232) for telaprevir and 374 ng/ml (229–519) for boceprevir. Plasma drug concentration monitoring revealed undetectable concentrations for two patients at week 4, and probable non‐adherence to therapy for another patient. These findings indicate that routine HCV NS3 protease sequencing and plasma PI concentration monitoring might be helpful to characterize cases of therapy failure, at a cost dramatically low compared to that of anti‐HCV therapy. J. Med. Virol. 86:1868–1876, 2014. © 2014 Wiley Periodicals, Inc.
Crocoite PbCrO4 and mimetite Pb5(AsO4)3Cl: rare minerals in highly degraded mediaeval murals in Northern Bohemia
Authors: Hradil David , Hradilová Janka , Bezdička Petr , Švarcová Silvie , Čermáková Zdeňka , Košařová Veronika , Němec Ivan
Published: July 2014

Mural paintings of exceptional quality, which can be discerned in spite of their extensive mechanical damage and colour fading, have been uncovered in the church of St. Gallus in Kuřívody, Northern Bohemia, dated to the second half of the 13th century. Materials research with particular use of portable X‐ray fluorescence, Raman micro‐spectroscopy and powder X‐ray micro‐diffraction revealed the presence of rare pigments. In Kuřívody, it is only a second identification of intentionally used yellow mineral crocoite (PbCrO4) in European art. Its identification is facilitated by providing a very good Raman scattering, even when present in small amounts in fragmentarily preserved colour layers. Light yellow mimetite (Pb5(AsO4)3Cl) was never before mentioned as intentionally used pigment in Europe. Its finding in Kuřívody, however, corresponds more likely with undesirable physical–chemical conditions causing its formation by alteration of orpiment (As2S3) and minium (Pb3O4). Obtained results highlight the importance of Raman spectroscopy for direct identification of mineral pigments in low concentrations, which may be crucial for interpreting cultural heritage objects in historical context. By materials, the almost forgotten paintings in Kuřívody can be seen as outstanding and rare example of ancient artistic tradition that has spread to Europe from Mediterranean in early Middle Ages. After all, mineral crocoite was already used by ancient Egyptians to paint sarcophagi and degraded orpiment decorates the walls of the Nefertari's tomb in Thebes. Copyright © 2014 John Wiley & Sons, Ltd.
Postcricoid carcinoma: Is organ preservation justified in T3?
Authors: Kadapa Nagendra , Mangale Kunal , Watve Parag , Rao S L. M. Chandrasekhara , Raju A. K. , Subramanyeshwar Rao T.
Published: July 2014

Introduction

Postcricoid carcinoma in India, is seen especially in middle‐aged females. Surgical treatment for postcricoid carcinoma has reduced because of increased organ‐preserving nonsurgical strategies. Surgical intervention leads to morbidity in the form of laryngectomy.

Objectives/Hypothesis

To study the outcomes of nonsurgical management and to assess whether organ preservation is justified or if radical surgery should be the first line of management for T3 postcricoid carcinoma.

Study Design/Methods

This retrospective study analyzed 59 patients with T3 postcricoid carcinoma who were treated with nonsurgical modality in the form of radiotherapy (RT) or concurrent chemoradiotherapy (CCRT). End points studied were locoregional control, disease‐free survival (DFS), and overall survival. We also observed feeding tube and tracheostomy tube dependency.

Results

Locoregional control rate, DFS rate, and overall survival at the end of 2 years were 8.98%, 8.59%, and 15.71% respectively. Seventeen and 12 patients of the study population were dependent on nasogastric tube and tracheostomy tube, respectively, until their last follow‐up.

Conclusion

Results of organ preservation with radical RT or CCRT do not show promising outcomes in the locally advanced T3 carcinoma of postcricoid. Radical surgery with appropriate reconstruction and postoperative radiotherapy is probably better in terms of local control as well as overall survival. Proper preoperative counseling and postoperative rehabilitation of speech and stoma can improve the quality of life of T3 postcricoid carcinoma patients

Level of Evidence

4. Laryngoscope, 125:356–359, 2015
Genome sequence of the model sulfate reducer Desulfovibrio gigas: a comparative analysis within the Desulfovibrio genus
Authors: Morais‐Silva Fabio O. , Rezende Antonio Mauro , Pimentel Catarina , Santos Catia I. , Clemente Carla , Varela–Raposo Ana , Resende Daniela M. , da Silva Sofia M. , de Oliveira Luciana Márcia , Matos Marcia , Costa Daniela A. , Flores Orfeu , Ruiz Jerónimo C. , Rodrigues‐Pousada Claudina
Published: July 2014

Desulfovibrio gigas is a model organism of sulfate‐reducing bacteria of which energy metabolism and stress response have been extensively studied. The complete genomic context of this organism was however, not yet available. The sequencing of the D. gigas genome provides insights into the integrated network of energy conserving complexes and structures present in this bacterium. Comparison with genomes of other Desulfovibrio spp. reveals the presence of two different CRISPR/Cas systems in D. gigas. Phylogenetic analysis using conserved protein sequences (encoded by rpoB and gyrB) indicates two main groups of Desulfovibrio spp, being D. gigas more closely related to D. vulgaris and D. desulfuricans strains. Gene duplications were found such as those encoding fumarate reductase, formate dehydrogenase, and superoxide dismutase. Complexes not yet described within Desulfovibrio genus were identified: Mnh complex, a v‐type ATP‐synthase as well as genes encoding the MinCDE system that could be responsible for the larger size of D. gigas when compared to other members of the genus. A low number of hydrogenases and the absence of the codh/acs and pfl genes, both present in D. vulgaris strains, indicate that intermediate cycling mechanisms may contribute substantially less to the energy gain in D. gigas compared to other Desulfovibrio spp. This might be compensated by the presence of other unique genomic arrangements of complexes such as the Rnf and the Hdr/Flox, or by the presence of NAD(P)H related complexes, like the Nuo, NfnAB or Mnh.
Refined modeling and movement characteristics analyses of irregularly shaped particles
Authors: Zeng Y. W. , Jin L. , Du X. , Gao R.
Published: July 2014

Irregularly shaped (IRS) particles widely exist in many engineering and industrial fields. The macro physical and mechanical properties of the particle system are governed by the interaction between the particles in the system. The interaction between IRS particles is more complicated because of their complex geometric shape with extremely irregular and co‐existed concave and convex surfaces. These particles may interlock each other, making the sliding and friction of IRS particles more complex than that of particles with regular shape. In order to study the interaction of IRS particles more efficiently, a refined method of constructing discrete element model based on computed tomography scanning of IRS particles is proposed. Three parameters were introduced to control the accuracy and the number of packing spheres. Subsequently, the inertia tensor of the IRS particle model was optimized. Finally, laboratory and numerical open bottom cylinder tests were carried out to verify the refined modeling method. The influence of particle shape, particle position, and mesoscopic friction coefficient on the interaction of particles was also simulated. It is noteworthy that with the increase of mesoscopic friction coefficient, the fluidity of IRS particle assembly decreases, and intermittent limit equilibrium state may appear. Copyright © 2014 John Wiley & Sons, Ltd.
Circulating Stories: East Timorese in Australia and Questions of Post‐Independence Identity
Authors: Askland Hedda Haugen
Published: July 2014

During the Indonesian occupation of East Timor, diasporic groups played a central role in the campaign for self‐determination. Throughout the occupation, East Timorese in Australia maintained a strong sense of long‐distance nationalism, which drove, directly or indirectly, communal and social activities. The fight to free East Timor was at the core of the exiles' collective imagination, defining them as a largely homeland‐focused community. However, in the aftermath of the independence, the role and position of the diaspora have been less clear and the exiles have struggled to redefine their relationship with their home country. Personal experiences upon return and perceptions of political, cultural, economic, and social development (or lack thereof) have led to renewed questioning of identity and belonging. This article explores the renewed questioning of identity and belonging embedded in people's ‘circulating stories’ of change, sacrifice and return.
Development and evaluation of an algorithm to identify users of Prolia® during the early postmarketing period using health insurance claims data
Authors: Hoffman Veena , Xue Fei , Gardstein Betsey , Skerry Kathleen , Critchlow Cathy W. , Enger Cheryl
Published: July 2014

Purpose

The goal of this study is to develop and validate an algorithm to identify Prolia® users within a health insurance claims database.

Methods

Patients with a denosumab‐specific or nonspecific administration claim during the early period of Prolia availability in the USA (June 1, 2010 to March 31, 2012) were classified as definite, probable, possible, and nonusers of Prolia using an algorithm consisting of nine different components based on claims patterns consistent with Prolia use. Medical record review confirmed a sample of definite, probable, and possible users and the positive predictive value (PPV) was estimated.

Results

The PPV of the claims‐based algorithm components varied (17.8–95.8%). Requiring claims for a bone or cartilage disorder or osteoporotic fracture after excluding claims for cancer prior to a denosumab‐specific administration code gave the highest PPV (95.8%), followed by requiring a Prolia National Drug Code on the same claim as a denosumab‐specific or nonspecific administration code (88.2%). Among the 87 confirmed Prolia users, osteoporosis diagnoses were seen more frequently in the medical record than in claims (83% vs 62%).

Conclusions

Prolia users are most accurately identified with administration code claims in conjunction with claims for Prolia National Drug Code and bone disorder treatment and diagnosis codes. Osteoporosis diagnoses may be under‐recorded in claims data. The algorithm may require reassessment as uptake for more recently approved indications increases. Copyright © 2014 John Wiley & Sons, Ltd.
The Questionnaire Big Six in 26 Nations: Developing Cross–Culturally Applicable Big Six, Big Five and Big Two Inventories
Authors: Thalmayer Amber Gayle , Saucier Gerard
Published: July 2014

The Big Five is a useful model of attributes now commonly used in cross–cultural research, but without the support of strong measurement invariance (MI) evidence. The Big Six has been proposed as a cross–culturally informed update, and the broader Big Two (Social Self–Regulation and Dynamism) draws on even more cross–cultural evidence. However, neither has been rigorously tested for cross–cultural MI. Here a Big Six inventory (36QB6) and measures of the Big Five and Big Two derived from it were tested and refined for cross–cultural usability in samples from 26 nations, divided into three subsets. Confirmatory factor analysis of the models in the first subset of nations demonstrated fit as strong in translation as typical personality measures achieve in their nation of origin (although poor per standard benchmarks). Items that performed inconsistently across cultures were removed, and alternates considered in a second subset of nations. Fit and invariance were improved for refined 30–item QB6, 25–item Big Five and 14–item Big Two measures in the third subset of nations. For all models, decrease in comparative fit index between MI levels was larger than .01, indicating lack of support for higher levels. Configural and factorial invariance were relatively stronger, compared to scalar and full. Copyright © 2014 European Association of Personality Psychology
Provider perspectives on presenting risk information and managing worry about recurrence among breast cancer survivors
Authors: Janz Nancy K. , Leinberger Rebecca L. , Zikmund‐Fisher Brian J. , Hawley Sarah T. , Griffith Kent , Jagsi Reshma
Published: July 2014

Background

Although worry about recurrence is a persistent concern among breast cancer survivors, little is known about physicians' confidence about presenting recurrence risk information, identifying women with considerable worry, and helping women manage worry.

Methods

Between January and June 2012, we surveyed 750 surgeons and 750 medical oncologists randomly sampled from the American Medical Association Physician Masterfile. We tested differences between surgeons and medical oncologists on confidence of presenting risk, identifying and managing worry using chi‐square statistic and Student's t‐tests and developed multiple variable logistic regression models to explain odds regarding confidence and use of different strategies for managing worry.

Results

The analytic sample included 403 surgeons and 363 medical oncologists (n = 766; response rate = 60%). Compared with surgeons, medical oncologists were significantly more likely to report confidence in: presenting risk information (87.5% vs 73.2%), identifying women who are worried (74.1% vs 63.9%), and managing worry (66.9% vs 52.4%). Confidence in managing worry was associated with more regular inquiry about worry (p = 0.009). Models of the likelihood of using different management strategies varied by provider type (e.g., surgeons more likely than medical oncologists to recommend support group or online resources, oncologists more likely to refer to psychologist or use medications, all p < 0.05).

Conclusion

Cancer providers, particularly surgeons, may benefit from educational training to raise confidence in identifying women with high levels of worry and managing women with considerable worry. Communication between specialties and primary care physicians on efforts to manage worry is necessary for coordinated, quality care for women with breast cancer. Copyright © 2014 John Wiley & Sons, Ltd.
Feasibility of automated slope III and Scond analysis in children
Authors: Bigler Anja , Yammine Sophie , Singer Florian , Riedel Thomas , Latzin Philipp
Published: July 2014

Background

Multiple breath washout (MBW) derived Scond is an established index of ventilation inhomogeneity. Time‐consuming post hoc calculations of the expirogram's slope of alveolar phase III (SIII) and the lack of available software hampered widespread application of Scond.

Methods

Seventy‐two school‐aged children (45 with cystic fibrosis; CF) performed 3 nitrogen MBW. We tested a new automated algorithm for Scond analysis (Scondauto) which comprised breath selection for SIII detection, calculation and reporting of test quality. We compared Scondauto to (i) standard Scond analysis (Scondmanual) with manual breath selection and to (ii) pragmatic Scond analysis including all breaths (Scondall). Primary outcomes were success rate and agreement between different Scond protocols, and Scond fitting quality (linear regression R2).

Results

Average Scondauto (0.06 for CF and 0.01 for controls) was not different from Scondmanual (0.06 for CF and 0.01 for controls) and showed comparable fitting quality (R2 0.53 for CF and 0.13 for controls vs. R2 0.54 for CF and 0.13 for controls). Scondall was similar in CF and controls but with inferior fitting quality compared to Scondauto and Scondmanual.

Conclusions

Automated Scond calculation is feasible and produces robust results comparable to the standard manual way of Scond calculation. This algorithm provides a valid, fast and objective tool for regular use, even in children. Pediatr Pulmonol. 2015; 50:805–813. © 2014 Wiley Periodicals, Inc.
Protein charge ladders reveal that the net charge of ALS‐linked superoxide dismutase can be different in sign and magnitude from predicted values
Authors: Shi Yunhua , Abdolvahabi Alireza , Shaw Bryan F.
Published: July 2014

This article utilized “protein charge ladders”—chemical derivatives of proteins with similar structure, but systematically altered net charge—to quantify how missense mutations that cause amyotrophic lateral sclerosis (ALS) affect the net negative charge (Z) of superoxide dismutase‐1 (SOD1) as a function of subcellular pH and Zn2+ stoichiometry. Capillary electrophoresis revealed that the net charge of ALS‐variant SOD1 can be different in sign and in magnitude—by up to 7.4 units per dimer at lysosomal pH—than values predicted from standard pKa values of amino acids and formal oxidation states of metal ions. At pH 7.4, the G85R, D90A, and G93R substitutions diminished the net negative charge of dimeric SOD1 by up to +2.29 units more than predicted; E100K lowered net charge by less than predicted. The binding of a single Zn2+ to mutant SOD1 lowered its net charge by an additional +2.33 ± 0.01 to +3.18 ± 0.02 units, however, each protein regulated net charge when binding a second, third, or fourth Zn2+ (ΔZ < 0.44 ± 0.07 per additional Zn2+). Both metalated and apo‐SOD1 regulated net charge across subcellular pH, without inverting from negative to positive at the theoretical pI. Differential scanning calorimetry, hydrogen‐deuterium exchange, and inductively coupled plasma mass spectrometry confirmed that the structure, stability, and metal content of mutant proteins were not significantly affected by lysine acetylation. Measured values of net charge should be used when correlating the biophysical properties of a specific ALS‐variant SOD1 protein with its observed aggregation propensity or clinical phenotype.