bluuebunny/crossref_metadata_2025 huggingface dataset:
The NIK of time for B cells
Authors: Myles Arpita , Cancro Michael P.
Published: February 2016

NF‐κB‐inducing kinase (NIK) is a key mediator of the noncanonical NF‐κB signaling pathway, which is critical for B‐cell development and function. Although complete deletion of NIK in mice has been shown to result in defective B cells and impaired secondary lymphoid organogenesis, the consequences of deleting NIK exclusively in B cells have not been determined. In this issue of the European Journal of Immunology, Hahn et al. [Eur. J. Immunol. 2016. 46: 732–741] describe mice in which the NF‐κB2 pathway mediator, NIK, is deleted at different points in B‐cell lineage differentiation and activation. The results show that the survival of mature peripheral B cells, as well as appropriate kinetics of germinal center reactions, rely on noncanonical NF‐κB signaling. These findings confirm and extend prior observations implicating a nonredundant role for NF‐κB2 downstream of BAFF signaling via BAFF‐R, and prompt assessment of the growing literature regarding the relative roles of BCR and BAFF signals in B‐cell homeostasis, as well as the downstream pathways responsible.
Chip‐based electrochromatography coupled to ESI‐MS detection
Authors: Dietze Claudia , Hackl Claudia , Gerhardt Renata , Seim Stephan , Belder Detlev
Published: February 2016

In this study, we present the coupling of chip‐based electrochromatography to MS using a glass chip with a monolithically integrated nanoelectrospray emitter. As separation column, an acrylate‐based porous polymer monolith is implemented into the glass chip by photopolymerization. For the establishment and development of this method, we used a test mixture detectable with both fluorescence and ESI‐MS. After successful evaluation of the approach with the test solutes, it was applied exemplarily for drug analysis such as high‐speed separations of benzodiazepines in pharmaceuticals.
Modeling of wind gap formation and development of sedimentary basins during fold growth: application to the Zagros Fold Belt, Iran
Authors: Collignon Marine , Yamato Philippe , Castelltort Sébastien , Kaus Boris J. P.
Published: February 2016

Mountain building and landscape evolution are controlled by interactions between river dynamics and tectonic forces. Such interactions have been extensively studied, however a quantitative evaluation of tectonic/geomorphic feedbacks, which is imperative for understanding sediments routing within orogens and fold‐and‐thrust belts, remains to be undertaken. Here, we employ numerical simulations to assess the conditions of uplift and river incision necessary to deflect an antecedent drainage network during the growth of one, or several, folds. We propose that a partitioning of the river network into internal (endorheic) and longitudinal drainage arises as a result of lithological differences within the deforming crustal sedimentary cover. Using examples from the Zagros Fold Belt (ZFB), we show that drainage patterns can be linked to the non‐dimensional incision ratio R between successive lithological layers, corresponding to the ratio between their relative erodibilities or incision coefficients. Transverse drainage networks develop for uplift rates smaller than 0.8 mm yr−1 and low incision ratios (−10 < R < 10). Intermediate drainage networks are obtained for uplift rates up to 2 mm yr−1 and large incision ratios (R > 20). Parallel drainage networks and the formation of sedimentary basins occur for large values of incision ratio (R > 20) and uplift rates between 1 and 2 mm yr−1. These results have implications for predicting the distribution of sediment depocenters in fold‐and‐thrust belts, which can be of direct economic interest for hydrocarbon exploration. They also put better constraints on the fluvial and geomorphic responses to fold growth induced by crustal‐scale tectonics. Copyright © 2016 John Wiley & Sons, Ltd.
Impact of neck failure on survival in older patients with differentiated thyroid cancer
Authors: Marcus David M. , Jiang Renjian , Ward Kevin C. , Higgins Kristin A. , Saba Nabil F. , Wadsworth J. Trad , Beitler Jonathan J.
Published: February 2016

Background

Regional recurrence of differentiated thyroid cancer (DTC) is often salvaged with neck dissection without survival penalty. It is unknown whether recurrence may be associated with inferior survival in older patients.

Methods

Surveillance, Epidemiology, and End Results (SEER) and Medicare data were linked to identify patients age ≥65 with nonmetastatic DTC. Patients undergoing neck dissection >6 months after their initial diagnosis were considered to have regional recurrent disease. We compared overall survival (OS) and cause‐specific survival (CSS) for patients with recurrent disease versus a matched cohort of patients with non‐recurrent DTC.

Results

Of 6235 patients, 143 had treatment‐defined recurrent disease. Patients with recurrent disease had inferior OS (p < .01) and CSS (p < .01). Multivariate analysis demonstrated that recurrent disease was independently associated with inferior 10‐year OS (hazard ratio [HR] = 1.75; p < .01) and CSS (HR = 3.05; p < .01).

Conclusion

Regional recurrence of DTC may negatively impact OS and CSS in patients ≥65 years old. © 2016 Wiley Periodicals, Inc. Head Neck 38: 919–924, 2016
Functional benefits of implants placed during ablative surgery: A 5‐year prospective study on the prosthodontic rehabilitation of 56 edentulous oral cancer patients
Authors: Wetzels Jan Willem , Koole Ron , Meijer Gert J. , de Haan Anton F. J. , Merkx Matthias A. W. , Speksnijder Caroline M.
Published: February 2016

Background

The timing of placement as well as the functional benefit of interforaminal implants in edentulous patients treated for oral cancer is unclear.

Methods

Fifty‐six patients were recruited at 2 institutions. In 1 institution, interforaminal implants were placed during ablative surgery, the other institution used conventional prosthodontics with optional placement of implants postsurgery (postponed‐placement). Masticatory performance, bite force, and subjective masticatory function were assessed before and 6 months, 1 year, and 5 years after surgery.

Results

Implant‐retained overdentures (IODs) demonstrated the highest bite force and the least problems with solid food and food choice. Masticatory performance was equal for IODs and conventional dentures. After 5 years, IODs from patients in the during‐ablative‐surgery cohort tend to have higher bite force and masticatory performance than those from patients in the postponed‐placement cohort.

Conclusion

IODs produce the highest overall masticatory function. Implant placement during ablative surgery seems to be functionally beneficial. © 2016 Wiley Periodicals, Inc. Head Neck 38: E2103–E2111, 2016
Thermal Interaction between Two Forced‐Convection Boundary Layers across a Conductive Solid Wall
Authors: Mosaad Mohamed El‐sayed
Published: February 2016

This paper presents an analytical model to the problem of thermal interaction between two forced convection layers of parallel flow on opposite wall sides. The problem is formulated in dimensionless terms to generalize the solution. The two convection layers are analyzed separately by employing the integral technique. The two analyses are then coupled by applying the solid–fluid interfacial conditions. The study indicates that the thermal interaction process is governed mainly by two dimensionless parameters relating the heat transfer effectiveness of two interactive convection modes and wall conduction. The effects of governing parameters on the flow and heat transfer characteristics of two coupled convection layers are documented. Results regarding mean conjugate Nusselt number are obtained for wide ranges of governing parameters.
TERT promoter mutations in melanoma survival
Authors: Nagore Eduardo , Heidenreich Barbara , Rachakonda Sívaramakrishna , Garcia‐Casado Zaida , Requena Celia , Soriano Virtudes , Frank Christoph , Traves Victor , Quecedo Esther , Sanjuan‐Gimenez Josefa , Hemminki Kari , Landi Maria Teresa , Kumar Rajiv
Published: February 2016

Despite advances in targeted therapies, the treatment of advanced melanoma remains an exercise in disease management, hence a need for biomarkers for identification of at‐risk primary melanoma patients. In this study, we aimed to assess the prognostic value of TERT promoter mutations in primary melanomas. Tumors from 300 patients with stage I/II melanoma were sequenced for TERT promoter and BRAF/NRAS mutations. Cumulative curves were drawn for patients with and without mutations with progression‐free and melanoma‐specific survival as outcomes. Cox proportional hazard regression models were used to determine the effect of the mutations on survivals. Individually, presence of TERT promoter and BRAF/NRAS mutations associated with poor disease‐free and melanoma‐specific survival with modification of the effect by the rs2853669 polymorphism within the TERT promoter. Hazard ratio (HR) for simultaneous occurrence of TERT promoter and BRAF/NRAS mutations for disease‐free survival was 2.3 (95% CI 1.2–4.4) and for melanoma‐specific survival 5.8 (95% CI 1.9–18.3). The effect of the mutations on melanoma‐specific survival in noncarriers of variant allele of the polymorphism was significant (HR 4.5, 95% CI 1.4–15.2) but could not be calculated for the carriers due to low number of events. The variant allele per se showed association with increased survival (HR 0.3, 95% CI 0.1–0.9). The data in this study provide preliminary evidence that TERT promoter mutations in combination with BRAF/NRAS mutations can be used to identify patients at risk of aggressive disease and the possibility of refinement of the classification with inclusion of the rs2853669 polymorphism within TERT promoter.
Multimodal optical analysis of meningioma and comparison with histopathology
Authors: Zanello Marc , Poulon Fanny , Varlet Pascale , Chretien Fabrice , Andreiuolo Felipe , Pages Mélanie , Ibrahim Ali , Pallud Johan , Dezamis Edouard , Abi‐Lahoud Georges , Nataf François , Turak Baris , Devaux Bertrand , Abi Haidar Darine
Published: February 2016

Meningioma is the most frequent primary central nervous system tumor. The risk of recurrence and the prognosis are correlated with the extent of the resection that ideally encompasses the infiltrated dura mater and, if required, the infiltrated bone. No device can deliver real‐time intraoperative histopathological information on the tumor environment to help the neurosurgeon to achieve a gross total removal. This study assessed the abilities of nonlinear microscopy to provide relevant and real‐time data to help resection of meningiomas. Nine human meningioma samples (four World Health Organization Grade I, five Grade II) were analyzed using different optical modalities: spectral analysis and imaging, lifetime measurements, fluorescence lifetime imaging microscopy, fluorescence emitted under one‐ and two‐photon excitation and the second‐harmonic generation signal imaging using a multimodal setup. Nonlinear microscopy produced images close to histopathology as a gold standard. The second‐harmonic generation signal delineated the collagen background and two‐photon fluorescence underlined cell cytoplasm. The matching between fluorescence images and Hematoxylin and Eosin staining was possible in all cases. Grade I meningioma emitted less autofluorescence than Grade II meningioma and Grade II meningioma exhibited a distinct lifetime value. Autofluorescence was correlated with the proliferation rates and seemed to explain the observed differences between Grade I and II meningiomas. This preliminary multimodal study focused on human meningioma samples confirms the potential of tissue autofluorescence analysis and nonlinear microscopy in helping intraoperatively neurosurgeons to reach the actual boundaries of the tumor infiltration.

Correspondence between H&E staining (top pictures) and the two‐photon fluorescence imaging (bottom pictures)

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Correspondence between H&E staining (top pictures) and the two‐photon fluorescence imaging (bottom pictures)
Kinetic analysis of nanoparticle‐protein interactions using a plasmon waveguide resonance
Authors: Bahrami Farshid , Maisonneuve Mathieu , Meunier Michel , Montazeri Arthur O. , Kim Yujin , Kherani Nazir P. , Aitchison J. Stewart , Mojahedi Mo
Published: February 2016

A plasmon waveguide resonance (PWR) sensor is proposed for studying the interaction between gold nanoparticles and proteins. The ability of the PWR sensor to operate in both TM and TE Polarizations, i.e. its polarization diversity, facilitates the simultaneous spectroscopy of the nanoparticles surface reactions using both polarizations. The response of each polarization to streptavidin‐biotin binding at the surface of gold nanoparticles is investigated in real time. Finally, using the principles of multimode spectroscopy, the nanoparticle's surface reactions are decoupled from the bulk solution refractive index variations.

Schematic diagram of the NP‐modified PWR sensor

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Schematic diagram of the NP‐modified PWR sensor
Multicolor multiphoton microscopy based on a nanosecond supercontinuum laser source
Authors: Lefort Claire , O'Connor Rodney P. , Blanquet Véronique , Magnol Laetitia , Kano Hideaki , Tombelaine Vincent , Lévêque Philippe , Couderc Vincent , Leproux Philippe
Published: February 2016

Multicolor multiphoton microscopy is experimentally demonstrated for the first time on a spectral bandwidth of excitation of 300 nm (full width half maximum) thanks to the implementation a nanosecond supercontinuum (SC) source compact and simple with a low repetition rate. The interest of such a wide spectral bandwidth, never demonstrated until now, is highlighted in vivo: images of glioma tumor cells stably expressing eGFP grafted on the brain of a mouse and its blood vessels network labelled with Texas Red® are obtained. These two fluorophores have a spectral bandwidth covering the whole 300 nm available. In parallel, a similar image quality is obtained on a sample of mouse muscle in vitro when excited with this nanosecond SC source or with a classical high rate, femtosecond and quasi monochromatic laser. This opens the way for (i) a simple and very complete biological characterization never performed to date with multiphoton processes, (ii) multiple means of contrast in nonlinear imaging allowed by the use of numerous fluorophores and (iii) other multiphoton processes like three‐photon ones.

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Fully unsupervised inter‐individual IR spectral histology of paraffinized tissue sections of normal colon
Authors: Nguyen Thi Nguyet Que , Jeannesson Pierre , Groh Audrey , Piot Olivier , Guenot Dominique , Gobinet Cyril
Published: February 2016

In label‐free Fourier‐transform infrared histology, spectral images are individually recorded from tissue sections, pre‐processed and clustered. Each single resulting color‐coded image is annotated by a pathologist to obtain the best possible match with tissue structures revealed after Hematoxylin‐Eosin staining. However, the main limitations of this approach are the empirical choice of the number of clusters in unsupervised classification, and the marked color heterogeneity between the clustered spectral images. Here, using normal murine and human colon tissues, we developed an automatic multi‐image spectral histology to simultaneously analyze a set of spectral images (8 images mice samples and 72 images human ones). This procedure consisted of a joint Extended Multiplicative Signal Correction (EMSC) to numerically deparaffinize the tissue sections, followed by an automated joint K‐Means (KM) clustering using the hierarchical double application of Pakhira‐Bandyopadhyay‐Maulik (PBM) validity index. Using this procedure, the main murine and human colon histological structures were correctly identified at both the intra‐ and the inter‐individual levels, especially the crypts, secreted mucus, lamina propria and submucosa. Here, we show that batched multi‐image spectral histology procedure is insensitive to the reference spectrum but highly sensitive to the paraffin model of joint EMSC. In conclusion, combining joint EMSC and joint KM clustering by double PBM application allows to achieve objective and automated batched multi‐image spectral histology.

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Sequential culture on biomimetic nanoclay scaffolds forms three‐dimensional tumoroids
Authors: Katti Kalpana S. , Molla MD Shahjahan , Karandish Fataneh , Haldar Manas K. , Mallik Sanku , Katti Dinesh R.
Published: February 2016

In recent times, the limitation of two‐dimensional cultures and complexity ofin vivomodels has paved the way for the development of three‐dimensional models for studying cancer. Here we report the development of a new tumor model using PCL/HAPClay scaffolds seeded with a sequential culture of human mesenchymal stem cells (hMSCs) followed by human prostate cancer cells (HPCCs). This nanocomposite system is used as a test‐bed for studying cancer metastasis and efficacy of anti‐cancer drugs using a polymersome delivery method. A novel sequential cell culture system in three‐dimensionalin vitrobone model provides a unique bone mimetic environment. The hMSCs seeded scaffolds are seeded with prostate cancer cells after the hMSCs have differentiated into osteoblasts. Sequential culture on the scaffolds has shown formation of tumoroids or microtissue consisting of organized, densely packed round cells with hypoxic core regions similar toin vivotumors. Such tumoroids are not observed on HPCC seeded scaffolds or when HPCCs sequentially cultured with human osteoblast cells. Clearly, the newly differentiated hMSCs play a vital role in the ability of cancer cells to grow into tumoroids and cause disease. The PCL/HAPclay scaffold system seeded with the sequential culture of hMSCs, and HPCCs presents a good model system for study of the interactions between prostate cancer cells and bone microenvironment. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1591–1602, 2016.
Distinct Patterns of Colocalization of the CCND1 and CMYC Genes With Their Potential Translocation Partner IGH at Successive Stages of B‐Cell Differentiation
Authors: Sklyar Ilya , Iarovaia Olga V. , Gavrilov Alexey A. , Pichugin Andrey , Germini Diego , Tsfasman Tatiana , Caron Gersende , Fest Thierry , Lipinski Marc , Razin Sergey V. , Vassetzky Yegor S.
Published: February 2016

The immunoglobulin heavy chain (IGH) locus is submitted to intra‐chromosomal DNA breakages and rearrangements during normal B cell differentiation that create a risk for illegitimate inter‐chromosomal translocations leading to a variety of B‐cell malignancies. In most Burkitt's and Mantle Cell lymphomas, specific chromosomal translocations juxtapose the IGH locus with a CMYC or Cyclin D1 (CCND1) gene, respectively. 3D‐fluorescence in situ hybridization was performed on normal peripheral B lymphocytes induced to mature in vitro from a naive state to the stage where they undergo somatic hypermutation (SHM) and class switch recombination (CSR). The CCND1 genes were found very close to the IGH locus in naive B cells and further away after maturation. In contrast, the CMYC alleles became localized closer to an IGH locus at the stage of SHM/CSR. The colocalization observed between the two oncogenes and the IGH locus at successive stages of B‐cell differentiation occurred in the immediate vicinity of the nucleolus, consistent with the known localization of the RAGs and AID enzymes whose function has been demonstrated in IGH physiological rearrangements. We propose that the chromosomal events leading to Mantle Cell lymphoma and Burkitt's lymphoma are favored by the colocalization of CCND1 and CMYC with IGH at the time the concerned B cells undergo VDJ recombination or SHM/CSR, respectively. J. Cell. Biochem. 117: 1506–1510, 2016. © 2016 Wiley Periodicals, Inc.
Absence of K‐Ras Reduces Proliferation and Migration But Increases Extracellular Matrix Synthesis in Fibroblasts
Authors: Muñoz‐Félix José M. , Fuentes‐Calvo Isabel , Cuesta Cristina , Eleno Nélida , Crespo Piero , López‐Novoa José M. , Martínez‐Salgado Carlos
Published: February 2016

The involvement of Ras‐GTPases in the development of renal fibrosis has been addressed in the last decade. We have previously shown that H‐ and N‐Ras isoforms participate in the regulation of fibrosis. Herein, we assessed the role of K‐Ras in cellular processes involved in the development of fibrosis: proliferation, migration, and extracellular matrix (ECM) proteins synthesis. K‐Ras knockout (KO) mouse embryonic fibroblasts (K‐ras−/−) stimulated with transforming growth factor‐β1 (TGF‐β1) exhibited reduced proliferation and impaired mobility than wild‐type fibroblasts. Moreover, an increase on ECM production was observed in K‐Ras KO fibroblasts in basal conditions. The absence of K‐Ras was accompanied by reduced Ras activation and ERK phosphorylation, and increased AKT phosphorylation, but no differences were observed in TGF‐β1‐induced Smad signaling. The MEK inhibitor U0126 decreased cell proliferation independently of the presence of K‐ras but reduced migration and ECM proteins expression only in wild‐type fibroblasts, while the PI3K‐AKT inhibitor LY294002 decreased cell proliferation, migration, and ECM synthesis in both types of fibroblasts. Thus, our data unveil that K‐Ras and its downstream effector pathways distinctively regulate key biological processes in the development of fibrosis. Moreover, we show that K‐Ras may be a crucial mediator in TGF‐β1‐mediated effects in this cell type. J. Cell. Physiol. 231: 2224–2235, 2016. © 2016 Wiley Periodicals, Inc.
A New In Vitro Co‐Culture Model Using Magnetic Force‐Based Nanotechnology
Authors: Takanari Hiroki , Miwa Keiko , Fu XianMing , Nakai Junichi , Ito Akira , Ino Kousuke , Honda Hiroyuki , Tonomura Wataru , Konishi Satoshi , Opthof Tobias , van der Heyden Marcel AG , Kodama Itsuo , Lee Jong‐Kook
Published: February 2016

Skeletal myoblast (SkMB) transplantation has been conducted as a therapeutic strategy for severe heart failure. However, arrhythmogenicity following transplantation remains unsolved. We developed an in vitro model of myoblast transplantation with “patterned” or “randomly‐mixed” co‐culture of SkMBs and cardiomyocytes enabling subsequent electrophysiological, and arrhythmogenic evaluation. SkMBs were magnetically labeled with magnetite nanoparticles and co‐cultured with neonatal rat ventricular myocytes (NRVMs) on multi‐electrode arrays. SkMBs were patterned by a magnet beneath the arrays. Excitation synchronicity was evaluated by Ca2+ imaging using a gene‐encoded Ca2+ indicator, G‐CaMP2. In the monoculture of NRVMs (control), conduction was well‐organized. In the randomly‐mixed co‐culture of NRVMs and SkMBs (random group), there was inhomogeneous conduction from multiple origins. In the “patterned” co‐culture where an en bloc SKMB‐layer was inserted into the NRVM‐layer, excitation homogenously propagated although conduction was distorted by the SkMB‐area. The 4‐mm distance conduction time (CT) in the random group was significantly longer (197 ± 126 ms) than in control (17 ± 3 ms). In the patterned group, CT through NRVM‐area did not change (25 ± 3 ms), although CT through the SkMB‐area was significantly longer (132 ± 77 ms). The intervals between spontaneous excitation varied beat‐to‐beat in the random group, while regular beating was recorded in the control and patterned groups. Synchronized Ca2+ transients of NRVMs were observed in the patterned group, whereas those in the random group were asynchronous. Patterned alignment of SkMBs is feasible with magnetic nanoparticles. Using the novel in vitro model mimicking cell transplantation, it may become possible to predict arrhythmogenicity due to heterogenous cell transplantation. J. Cell. Physiol. 231: 2249–2256, 2016. © 2016 Wiley Periodicals, Inc.
The Effect of a High‐Fat Meal on the Pharmacokinetics of Ixazomib, an Oral Proteasome Inhibitor, in Patients With Advanced Solid Tumors or Lymphoma
Authors: Gupta Neeraj , Hanley Michael J. , Venkatakrishnan Karthik , Wang Bingxia , Sharma Sunil , Bessudo Alberto , Hui Ai‐Min , Nemunaitis John
Published: February 2016

Ixazomib is the first oral proteasome inhibitor to be investigated in the clinic. This clinical study assessed whether the pharmacokinetics of ixazomib would be altered if administered after a high‐calorie, high‐fat meal. In a 2‐period, 2‐sequence, crossover study design, adult patients with advanced solid tumors or lymphoma received a 4‐mg oral dose of ixazomib as immediate‐release capsules on day 1 without food (fasted, administered following an overnight fast) or with food (fed, following consumption of a high‐calorie, high‐fat meal), followed by another dose on day 15 in the alternate food intake condition (fasted to fed or fed to fasted). Twenty‐four patients were enrolled; of these, 15 were included in the pharmacokinetic‐evaluable population. Administration of ixazomib after a high‐fat meal reduced both the rate and extent of absorption of ixazomib. Under fed conditions, the median time to peak plasma concentration (Tmax) of ixazomib was delayed by approximately 3 hours compared with administration in the fasted state (1.02 hours vs 4.0 hours), and there was a 28% reduction in total systemic exposure (area under the curve, AUC) and a 69% reduction in peak plasma concentration (Cmax). Together, the results support the administration of ixazomib on an empty stomach, at least 1 hour before or at least 2 hours after food. These recommendations are reflected in the United States Prescribing Information for ixazomib (clinicaltrials.gov identifier NCT01454076).
A Critical Evaluation of Pharmacogenetic Information in Package Inserts for Selected Drugs Marketed in India and Its Comparison With US FDA‐Approved Package Inserts
Authors: Pai Sarayu Arvind , Kshirsagar Nilima
Published: February 2016

Our objective was to compare the pharmacogenetic information provided in the package inserts (PIs) of 7 drugs marketed in the United States and India, namely, abacavir, capecitabine, carbamazepine, clopidogrel, irinotecan, valproic acid, and warfarin. We evaluated the pharmacogenetic information provided in Indian PIs for the highest level where it was included, robustness and completeness, clinical validity, and clinical utility and compared it with corresponding data of US PIs. Pharmacogenetic studies carried out in India were identified using PubMed. Pharmacogenetic information was provided in Indian PIs of all the drugs except irinotecan. It appeared in the same section as in US PIs for abacavir, capecitabine, carbamazepine (HLA‐*3101), valproic acid (urea cycle disorders), and warfarin (protein C and protein S), whereas it appeared at lower levels for other drug‐gene combinations. The robustness of pharmacogenetic testing was graded convincing for abacavir, adequate for carbamazepine and clopidogrel, and incomplete for the remaining drugs, and only abacavir and clopidogrel PIs provided full details of supporting studies. These details, when provided in the Indian PIs were identical to those in the US PIs. The Indian PIs did not provide data on Indian patients, although published studies are available. Both US and Indian PIs lacked critical information on the clinical validity and utility of pharmacogenetic testing. The pharmacogenetic information should provide country/ethnicity‐specific data so that they are useful to clinicians. Where data are not available, the prevalence of genetic variation in the population of a country needs to be determined and should then be translated to the PIs.
Microtensile strength of resin cement bond to indirect composite treated by different output powers of Er:YAG laser
Authors: Garshasbzadeh Nazanin Zeinab , Mirzaie Mansoreh , Yassini Esmaeil , Shahabi Sima , Benedicenti Stefano , Angiero Francesca , Chiniforush Nasim
Published: February 2016

The study aimed to evaluate the effect of different output powers of Er:YAG laser on microtensile bonding strength of indirect composite to resin cements.36 indirect composite blocks (GC Gradia DA2, Japan) size 15 × 10 × 10 mm3 were constructed, and divided into 12 groups, as follows:G1: control group (no treatment); Groups G2 to G6: treated with Er:YAG laser (2,940 nm) in noncontact mode, frequency 20 Hz, pulse duration 470 µs, with output power ranging from 2W to 6W; Groups G7 sandblasting, Groups 8 to G12: as Groups G2 to G 6 with preparatory sandblasting. One specimen from each group was analyzed by SEM; each specimen was fixed to a specialized metal jig using cyanoacrylate (Mitreapel, Beta Kimya San. Ve TIC, Iran) and debonded under tension with a universal testing machine (Zwick, Germany) at a crosshead speed of 0.5 mm min−1. Sandblasting and laser can improve bond strength above an energy level of 150 mJ. SEM evaluation of laser‐treated specimens showed irregularities and deep undercuts. T test analysis showed no significant difference between sandblasted and non‐sandblasted group, with laser output power of 0, 100, or 150 mJ (P = 0.666, P = 0.875, and P = 0.069); in the specimens irradiated with energy output of 200, 250, or 300 mJ, sandblasted specimens showed higher bond strength than non‐sandblasted ones. The results demonstrate that, in composite resin irradiated with laser at energy output of 200–300 mJ, sandblasting might be a suitable procedure to enhance bond strength of resin cement. Microsc. Res. Tech. 79:328–333, 2016. © 2016 Wiley Periodicals, Inc.
From lizard body form to serpentiform morphology: The atlas–axis complex in African cordyliformes and their relatives
Authors: Čerňanský Andrej
Published: February 2016

The comparative vertebral morphology of the atlas–axis complex in cordyliforms, xantusiid and several skinks is studied here. These lizards are particularly interesting because of their different ecological adaptations and anti‐predation strategies, where conformation ranges from the lizard‐like body to a snake‐like body. This transition to serpentiform morphology shows several evolutionary patterns in the atlas–axis complex: 1) the zygapophyseal articulations are lost in the early stage of the transition. In contrast to mammals, the atlas is more or less locked to the axis in lepidosaurs, but the absence of zygapophyseal articulation releases this locking for rotation. However despite its serpentiform morphology, Chamaesaura is different, in possessing this articulation; 2) the first intercentrum of Chamaesaura and Tetradactylus africanus (serpentiform grass‐swimmers) is fully curved anteriorly, underlying the occipital condyle. While this limits ventral skull rotation beyond a certain angle, it locks the skull, which is a crucial adaptation for a sit‐and‐wait position in grassland habitats that needs to keep the head stabilized; and 3) in Acontias, most of the atlas articular surface with the occipital condyle is formed by the lateral aspect of the articulation area relative to the area located in the dorsal region of the slightly reduced intercentrum. A similar state occurs in amphisbaenians, most likely reflecting a fossorial lifestyle of the limbless lizards.

Although Chamaesaura and Tetradactylus live sympatrically in grasslands, Chamaesaura differs in several ways in atlas–axis complex: for example, aforementioned presence of the atlas–axis zygapophyseal articulation, and long posterodorsal processes. Its occipital condyle protrudes further posteriorly, placing the atlas–axis complex further from the endocranium than in Tetradactylus. Hence, adaptation in the same niche, even among sister clades, can lead to different atlas–axis morphology due to different lifestyle strategies, for example, different foraging mode, while similar atlas–axis morphology can evolve in two lineages occupying different niches, as in Ablepharus and Scelotes. J. Morphol. 277:512–536, 2016. © 2016 Wiley Periodicals, Inc.
and T1 assessment of abdominal tissue response to graded hypoxia and hypercapnia using a controlled gas mixing circuit for small animals
Authors: Ganesh Tameshwar , Estrada Marvin , Duffin James , Cheng Hai Ling
Published: February 2016

Purpose

To characterize
and T1 relaxation time response to a wide spectrum of gas challenges in extracranial tissues of healthy rats.

Materials and Methods

A range of graded gas mixtures (hyperoxia, hypercapnia, hypoxia, and hypercapnic hypoxia) were delivered through a controlled gas‐mixing circuit to mechanically ventilated and intubated rats. Quantitative magnetic resonance imaging (MRI) was performed on a 3T clinical scanner;
and T1 maps were computed to determine tissue response in the liver, kidney cortex, and paraspinal muscles. Heart rate and blood oxygen saturation (SaO2) were measured through a rodent oximeter and physiological monitor.

Results

decreases consistent with lowered SaO2 measurements were observed for hypercapnia and hypoxia, but decreases were significant only in liver and kidney cortex (P < 0.05) for >10% CO2 and <15% O2, with the new gas stimulus, hypercapnic hypoxia, producing the greatest
decrease. Hyperoxia‐related
increases were accompanied by negligible increases in SaO2. T1 generally increased, if at all, in the liver and decreased in the kidney. Significance was observed (P < 0.05) only in kidney for >90% O2 and >5% CO2.

Conclusion

and T1 provide complementary roles for evaluating extracranial tissue response to a broad range of gas challenges. Based on both measured and known physiological responses, our results are consistent with
as a sensitive marker of blood oxygen saturation and T1 as a weak marker of blood volume changes. J. Magn. Reson. Imaging 2016;44:305–316.
Value of preoperative 3T multiparametric MRI for surgical margin status in patients with prostate cancer
Authors: Tamada Tsutomu , Sone Teruki , Kanomata Naoki , Miyaji Yoshiyuki , Kido Ayumu , Jo Yoshimasa , Yamamoto Akira , Ito Katsuyoshi
Published: February 2016

Purpose

To examine the value of preoperative multiparametric magnetic resonance imaging (MRI) as a predictor of surgical margin (SM) status in patients with prostate cancer (PC).

Materials and Methods

The Institutional Review Board approved this retrospective study; the requirement for informed consent was waived. Fifty‐six male patients with histologically proven PC underwent preoperative 3T multiparametric MRI including high b value (0, 2000 s/mm2) diffusion‐weighted imaging. In each patient, clinical data, such as biopsy Gleason score and D'Amico clinical risk score, and multiparametric MRI findings, such as tumor location, tumor size, tumor extension in the apical or proximal region, tumor apparent diffusion coefficient (ADC), and the presence or absence of MRI findings of extracapsular extension (ECE) were evaluated. Statistical evaluations included the Fisher's exact test, χ2 test, Mann–Whitney U‐test, and logistic regression analysis.

Results

On histopathological evaluation, 15 patients (27%) were SM‐positive (SMP group), and 41 (73%) were SM‐negative (SMN group). The tumor ADC was significantly lower in the SMP group than in the SMN group (P = 0.001). The frequency of tumor extension in the apex or base and suspected ECE on MRI were significantly higher in the SMP group than in the SMN group (P = 0.037 and 0.011, respectively). On multivariate analysis, tumor ADC was the only predictor of SM status in PC (P = 0.003).

Conclusion

PC with positive SM was characterized by tumor extension in the apical and proximal regions, lower tumor ADC, and tumors with positive MRI findings of ECE, compared to tumors with negative SM. J. Magn. Reson. Imaging 2016;44:584–593.
Age‐related optimization of screw placement for reduced loosening risk in locked plating
Authors: MacLeod Alisdair R. , Simpson A. Hamish R. W. , Pankaj Pankaj
Published: February 2016

When using locked plating for bone fracture fixation, screw loosening is reported as one of the most frequent complications and is commonly attributed to an incorrect choice of screw configuration. Choosing a patient‐optimized screw configuration is not straightforward as there are many interdependent variables that affect device performance. The aim of the study was to evaluate the influence that locking screw configuration has on loosening risk and how this is influenced by bone quality. This study uses finite element models that incorporate cortical bone heterogeneity, orthotropy, and geometrical nonlinearity to examine the effect of screw configuration on variables associated with loosening and interfragmentary motion. Strain levels within the bone were used as indicators of regions that may undergo loosening. The study found that, in healthy bone under axial loading, the most important variables influencing strain levels within the bone were the size of the bridging span (working length) and the plate rigidity. Unlike healthy bone, osteoporotic bone was found to be particularly sensitive to the spacing of the screws within the plate. Using two empty screw holes between the screws closest to the fracture was found to reduce the strain levels at the first screw by 49% in osteoporotic bone (compared to only 2.4% in healthy bone). The study also found that under torsional loading the total number of screws used was the most important variable with a 59% reduction in the strain around the screws closest to the fracture when using six rather than four screws in osteoporotic bone. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1856–1864, 2016.
Stereo‐imaging AUV detects trends in sea urchin abundance on deep overgrazed reefs
Authors: Ling S. D. , Mahon I. , Marzloff M. P. , Pizarro O. , Johnson C. R. , Williams S. B.
Published: February 2016

Remote underwater vehicles are cutting‐edge tools for mapping benthic habitats, yet their reliability for detecting patterns in abundance of benthic species remains largely unexplored. Here, we use a stereo‐imaging AUV to investigate changes in abundance of the overgrazing sea urchin, Centrostephanus rodgersii, which has undergone climate driven range‐extension to Tasmania. As part of ongoing bi‐yearly monitoring of urchin impacts (June 2009–2013), the benthic stereo‐imaging AUV (Sirius) surveyed fixed geo‐referenced 25 × 25 m plots (625 m2) on deep “urchin barrens” (25–30 m depth) and shallow barren/kelp transition zones (8–16 m) at two sites at St. Helens, northeast Tasmania (−41.25; 148.34). Coincident with initial AUV deployments, urchin abundance was also estimated in the same reef plots using conventional SCUBA diver belt‐transects; with comparison of AUV and diver sampling showing AUV‐derived estimates to be ∼ 40% lower; while additional AUV sampling at night (high risk for divers in deep water) detected abundances only ∼16% lower than that measured by daytime divers, demonstrating strong nocturnal emergence of C. rodgersii. Importantly, patterns in C. rodgersii abundance across reefs and depths were similar between methods; and long‐term population trends were concordant between diver and AUV methods. At finer‐scales, AUV detections were compromised where remnant kelp canopies obscured urchins, indicating divers to be superior for detecting early‐warning of population increases within intact kelp beds. Comparison of C. rodgersii with two other macro‐invertebrates (sea cucumber Australostichopus mollis and sea urchin Heliocidaris erythrogramma) revealed that while stereo‐imaging AUVs can detect space/time variability in macro‐invertebrate abundance, detectability is highly dependent on local ecologies and species‐specific behaviours.
On strong forms of reflection in set theory
Authors: Friedman Sy‐David , Honzik Radek
Published: February 2016

In this paper we review the most common forms of reflection and introduce a new form which we call sharp‐generated reflection. We argue that sharp‐generated reflection is the strongest form of reflection which can be regarded as a natural generalization of the Lévy reflection theorem. As an application we formulate the principle sharp‐maximality with the corresponding hypothesis . The statement is an analogue of the (Inner Model Hypothesis, introduced in ) which is compatible with the existence of large cardinals.
Towards a Ryll‐Nardzewski‐type theorem for weakly oligomorphic structures
Authors: Pech Christian , Pech Maja
Published: February 2016

A structure is called weakly oligomorphic if its endomorphism monoid has only finitely many invariant relations of every arity. The goal of this paper is to show that the notions of homomorphism‐homogeneity, and weak oligomorphy are not only completely analogous to the classical notions of homogeneity and oligomorphy, but are actually closely related. We first prove a Fraïssé‐type theorem for homomorphism‐homogeneous relational structures. We then show that the countable models of the theories of countable weakly oligomorphic structures are mutually homomorphism‐equivalent (we call first order theories with this property weakly ω‐categorical). Furthermore we show that every weakly oligomorphic homomorphism‐homogeneous structure contains (up to isomorphism) a unique homogeneous, homomorphism‐homogeneous core, to which it is homomorphism‐equivalent. As a consequence we obtain that every countable weakly oligomorphic structure is homomorphism‐equivalent to a finite or ω‐categorical structure. As a corollary we obtain a characterization of positive existential theories of weakly oligomorphic structures as the positive existential parts of ω‐categorical theories.
Single‐molecule mass spectrometry
Authors: Keifer David Z. , Jarrold Martin F.
Published: February 2016

In single‐molecule mass spectrometry, the mass of each ion is measured individually; making it suitable for the analysis of very large, heterogeneous objects that cannot be analyzed by conventional means. A range of single‐molecule mass spectrometry techniques has been developed, including time‐of‐flight with cryogenic detectors, a quadrupole ion trap with optical detection, single‐molecule Fourier transform ion cyclotron resonance, charge detection mass spectrometry, quadrupole ion traps coupled to charge detector plates, and nanomechanical oscillators. In addition to providing information on mass and heterogeneity, these techniques have been used to study impact craters from cosmic dust, monitor the assembly of viruses, elucidate the fluorescence dynamics of quantum dots, and much more. This review focuses on the merits of each of these technologies, their limitations, and their applications. © 2016 Wiley Periodicals, Inc. Mass Spec Rev 36:715–733, 2017
Study of levodopa response in Parkinson's disease: Observations on rates of motor progression
Authors: Ding Catherine , Ganesvaran Ganga , Alty Jane E. , Clissold Benjamin G. , McColl Craig D. , Reardon Katrina A. , Schiff Mark , Srikanth Velandai , Kempster Peter A.
Published: February 2016

Introduction

It is important to understand how the rate of motor progression in PD relates to dopaminergic treatment.

Methods

The methods for this study comprised prospective defined off state measurements of the levodopa response at 3‐year intervals over a mean 13.3‐year period in 34 patients enrolled before treatment initiation.

Results

Despite worsening of on and off scores, the magnitude of the l‐dopa short‐duration response is maintained as the disease progresses. A linear mixed‐effects regression analysis of off phase motor scores showed a yearly deterioration of 2.3% of the maximum disability score. Greater motor disability at the commencement of treatment was an independent predictor of faster progression. Demented patients had worse motor function than those without dementia (P = 0.02), and motor deficit appeared to accelerate toward the end of the disease course in patients who had died.

Conclusions

These observations should inform clinical trial design for drugs with possible neuroprotective properties. © 2016 International Parkinson and Movement Disorder Society
Detection of novel metabolites of flaxseed lignans in vitro and in vivo
Authors: Quartieri Andrea , García‐Villalba Rocío , Amaretti Alberto , Raimondi Stefano , Leonardi Alan , Rossi Maddalena , Tomàs‐Barberàn Francisco
Published: February 2016

Scope

This study aimed to improve the knowledge of secoisolariciresinol diglucoside (SDG) transformation by human gut microbiota.

Methods and results

SDG‐supplemented microbiota cultures were inoculated with the feces of five subjects. The same volunteers received a flaxseed supplement for 7 days. SDG metabolites in cultures, feces, and urine were monitored by LC‐ESI‐QTOF and LC‐DAD. In all cultures, SDG was deglycosylated to secoisolariciresinol (SECO) within 12 h. SECO underwent successive dehydroxylations and demethylations yielding enterodiol (4–18% conversion) and enterolactone (0.2–6%) after 24 h. Novel intermediates related to SECO, matairesinol (MATA), and anhydrosecoisolariciresinol (AHS) were identified in fecal cultures. These metabolites were also found after flaxseed consumption in feces and urine (in approximate amounts between 0.01–47.03 μg/g and 0.01–13.49 μg/mL, respectively) in their native form and/or modified by phase II human enzymes (glucuronide, sulfate and sulfoglucuronide conjugates).

Conclusions

Derivatives of MATA and AHS are described for the first time as intermediates of SDG biotransformation by intestinal bacteria, providing a more comprehensive knowledge of lignan intestinal metabolism. The transformations observed in vitro seem to occur in vivo as well. The detection in urine of SDG intermediates indicates their gut absorption, opening new perspectives on the study of their systemic biological effects.
Urolithin A, C, and D, but not iso‐urolithin A and urolithin B, attenuate triglyceride accumulation in human cultures of adipocytes and hepatocytes
Authors: Kang Inhae , Kim YongEun , Tomás‐Barberán Francisco A. , Espín Juan Carlos , Chung Soonkyu
Published: February 2016

Scope

Urolithins (Uro) are ellagic acid (EA)‐derived metabolites produced by gut microbes. There is a growing interest in the biological activities of Uro. Our aim was to evaluate the impacts of Uro on regulating triglyceride (TG) accumulation using cultures of primary human adipocytes and hepatoma Huh7 cells.

Methods and results

UroA, UroB, UroC, UroD, and iso‐UroA were used to determine the effect of Uro on adipogenesis and lipogenesis. Individual Uro (30 μM) were added to human adipogenic stem cells during differentiation. UroA, UroC, and UroD, but not iso‐UroA and UroB, significantly inhibited new fat cell formation by decreasing TG accumulation and adipogenic protein and gene expressions. The regulation of TG synthesis by Uro was investigated via metabolic chasing with radiolabeled precursors. UroA, UroC, and UroD attenuated TG accumulation, while increasing the fatty acid (FA) oxidation in adipocytes and h/epatoma Huh7 cells. Furthermore, UroC, UroD, and UroA promoted the phosphorylation of AMP‐activated protein kinase, suggesting that Uro may alter energy‐sensing metabolic pathways in primary human adipocytes.

Conclusions

Taken together, our results demonstrated that UroA, UroC, and UroD, but not isoUroA and UroB, reduce TG accumulation and increase FA oxidation in adipocytes as well as hepatocytes.
Immediate effect of vibratory stimuli on quadriceps function in healthy adults
Authors: Pamukoff Derek N. , Pietrosimone Brian , Lewek Michael D. , Ryan Eric D. , Weinhold Paul S. , Lee Dustin R. , Blackburn J. Troy
Published: February 2016

Introduction: The purpose of this study was to compare the effect of whole body vibration (WBV) and local muscle vibration (LMV) on quadriceps function. Methods: Sixty adults were randomized to WBV, LMV, or control groups. Quadriceps function [Hoffmann (H)‐reflex, active motor threshold (AMT), motor evoked potential (MEP) and electromyographic amplitude, peak torque (PT), rate of torque development (RTD), and central activation ratio (CAR)] was assessed before and immediately after and 10 and 20 minutes after interventions. Results: WBV improved PT, CAR, AMT, EMG, and MEP amplitude, and EMG amplitude and CAR were greater than control after application. LMV improved EMG amplitude and AMT, and EMG amplitude was greater than control after application. AMT remained lower 10 and 20 minutes after WBV and LMV. No differences were noted between LMV and WBV. Vibration did not influence H‐reflex or RTD. Conclusions: WBV and LMV increased quadriceps function and may be used to enhance the efficacy of strengthening protocols. Muscle Nerve 54: 469–478, 2016