bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toward the integration of Omics data in epidemiological studies: still a “long and winding road”
Authors: López de Maturana Evangelina , Pineda Sílvia , Brand Angela , Van Steen Kristel , Malats Núria 
Published: July 2016

ABSTRACTPrimary and secondary prevention can highly benefit a personalized medicine approach through the accurate discrimination of individuals at high risk of developing a specific disease from those at moderate and low risk. To this end precise risk prediction models need to be built. This endeavor requires a precise characterization of the individual exposome, genome, and phenome. Massive molecular omics data representing the different layers of the biological processes of the host and the nonhost will enable to build more accurate risk prediction models. Epidemiologists aim to integrate omics data along with important information coming from other sources (questionnaires, candidate markers) that has been proved to be relevant in the discrimination risk assessment of complex diseases. However, the integrative models in large‐scale epidemiologic research are still in their infancy and they face numerous challenges, some of them at the analytical stage. So far, there are a small number of studies that have integrated more than two omics data sets, and the inclusion of non‐omics data in the same models is still missing in most of studies. In this contribution, we aim at approaching the omics and non‐omics data integration from the epidemiology scope by considering the “massive” inclusion of variables in the risk assessment and predictive models. We also provide already available examples of integrative contributions in the field, propose analytical strategies that allow considering both omics and non‐omics data in the models, and finally review the challenges imbedding this type of research.
Preparation of Compound I in P450cam: The Prototypical P450
Authors: Yosca Timothy H. , Green Michael T. 
Published: July 2016

AbstractCytochrome P450cam occupies a central position in the heme monooxygenase landscape. For many years, P450cam has served as a prototype for understanding structure and function in bacterial, fungal, microsomal, and plant P450s. The enzyme is believed to function through a highly reactive iron(IV)oxo radical species called compound I. While the first glimpses of compound I were observed in P450cam over thirty years ago, subsequent attempts to prepare the intermediate for further characterizations have proven unsuccessful. Given that the initial reports provided great promise, the nature of the subsequent failures has been extremely puzzling. Here we detail the preparation of compound I in P450cam. Using insights gained from previous investigations, we have obtained the intermediate in ∼ 45 % yield, allowing characterizations by UV/Visible, Mössbauer, and EPR spectroscopies. This report provides a missing piece of the monooxygenase landscape, verifying the existence of compound I in the most studied P450.
Inverse SORS for detecting a low Raman‐active turbid sample placed inside a highly Raman‐active diffusely scattering matrix – A feasibility study
Authors: Khan Khan Mohd. , Dutta Surjendu B. , Krishna Hemant , Majumder Shovan K. 
Published: July 2016

The broad range of applications of spatially‐offset Raman spectroscopy (SORS) were found to involve samples having only marginal differences in Raman cross‐sections between the surface and subsurface targets. We report the results of a feasibility study to evaluate the potential of the approach to identify the presence of a very low Raman‐active turbid sample placed inside a highly Raman‐active diffusely scattering matrix. Paraffin sandwiched tissue blocks prepared by embedding slices of chicken muscle tissue into solid paraffin blocks were employed as representative samples for the study. It was found that in contrast to the several millimetres of probing depth reported in the earlier applications, the Raman signatures of tissue were best recovered when it was located beneath the surface of the paraffin block at a depth of around a millimetre, beyond which the quality of recovery was increasingly poorer. However, the probing depth could be further increased by increasing the thickness of the embedded tissue sections. The results clearly suggest that though the probing depth achievable under the current condition is less than that found in previous applications, nevertheless it is sufficient for various other applications that would not require probing as deep as was required earlier.
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Genipin crosslinker releasing sutures for improving the mechanical/repair strength of damaged connective tissue
Authors: Sundararaj Sharath , Slusarewicz Paul , Brown Matt , Hedman Thomas 
Published: July 2016

AbstractThe most common mode of surgical repair of ruptured tendons and ligaments involves the use of sutures for reattachment. However, there is a high incidence of rerupture and repair failure due to pulling out of the suture material from the damaged connective tissue. The main goal of this research was to achieve a localized delivery of crosslinking agent genipin (GP) from rapid‐release biodegradable coatings on sutures, for strengthening the repair of ruptured connective tissue. Our hypothesis is that GP released from the suture coating will lead to exogenous crosslinking of native connective tissue resulting in beneficial effects on clinically relevant mechanical parameters such as tear resistance, tissue strength, and energy required to rupture the tissue (toughness). Sutures were successfully coated with a biodegradable polymer layer loaded with the crosslinking agent genipin, without compromising the mechanical properties of the suture. The rapid‐release of genipin was achieved under both in vitro and ex vivo conditions. Exogenous crosslinking using these genipin releasing sutures was demonstrated using equine tendons. The tendons treated with genipin releasing sutures showed significant improvement in failure load, energy required for pull‐out failure, and stiffness. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2199–2205, 2017.
1H MR spectroscopy in cervical carcinoma using external phase array body coil at 3.0 Tesla: Prediction of poor prognostic human papillomavirus genotypes
Authors: Lin Gigin , Lai Chyong‐Huey , Tsai Shang‐Yueh , Lin Yu‐Chun , Huang Yu‐Ting , Wu Ren‐Chin , Yang Lan‐Yan , Lu Hsin‐Ying , Chao Angel , Wang Chiun‐Chieh , Ng Koon‐Kwan , Ng Shu‐Hang , Chou Hung‐Hsueh , Yen Tzu‐Chen , Hung Ji‐Hong 
Published: July 2016

PurposeTo assess the clinical value of proton (1H) MR spectroscopy in cervical carcinomas, in the prediction of poor prognostic human papillomavirus (HPV) genotypes as well as persistent disease following concurrent chemoradiotherapy (CCRT).Materials and Methods1H MR spectroscopy using external phase array coil was performed in 52 consecutive cervical cancer patients at 3 Tesla (T). Poor prognostic HPV genotypes (alpha‐7 species or absence of HPV infection) and persistent cervical carcinoma after CCRT were recorded. Statistical significance was calculated with the Mann‐Whitney two‐sided nonparametric test and areas under the receiver operating characteristics curve (AUC) analysis.ResultsA 4.3‐fold (P = 0.032) increased level of methyl resonance at 0.9 ppm was found in the poor prognostic HPV genotypes, mainly attributed to the presence of HPV18, with a sensitivity of 75%, a specificity of 81%, and an AUC of 0.76. Poor prognostic HPV genotypes were more frequently observed in patients with adeno‐/adenosquamous carcinoma (Chi‐square, P < 0.0001). In prediction of the four patients with persistent disease after CCRT, elevated methyl resonance demonstrated a sensitivity of 100%, a specificity of 74%, and an AUC of 0.82.Conclusion1H MR spectroscopy at 3T can be used to depict the elevated lipid resonance levels in cervical carcinomas, as well as help to predict the poor prognostic HPV genotypes and persistent disease following CCRT. Further large studies with longer follow up times are warranted to validate our initial findings.Level of Evidence: 1J. Magn. Reson. Imaging 2017;45:899–907.
Early global radiation measurements: a review
Authors: Stanhill Gerald , Achiman Ori 
Published: July 2016

ABSTRACTMeasurements of global radiation Eg↓ made in the first half of the 20th century are reviewed. The thermoelectric pyranometers used to measure Eg↓ in the United States, Western Europe and Russia are described and the published sources of data available up to and including the 1957 International Geophysical Year are documented together with the few analyses of this data which have been reported. Two 100‐year‐long series measured at Potsdam, Germany and Washington, DC in the United States are presented to illustrate the potential value of the early measurements in understanding the changes in Eg↓ which have occurred in the last 60 years.
How many RCM ensemble members provide confidence in the impact of land‐use land cover change?
Authors: Laux Patrick , Nguyen Phuong N. B. , Cullmann Johannes , Van Tan Phan , Kunstmann Harald 
Published: July 2016

ABSTRACTRegional climate models (RCMs) include both terrestrial and atmospheric compartments and thereby allow studying land–atmosphere feedback, in particular, the impact of land‐use land cover driven by biogeophysical processes on regional climate. In this study, a method is developed to separate the signals from the noise in RCM simulations of the effects of changes in land use, using perturbed initial boundary conditions (PICs). We want to know how many ensemble members are required to identify robust and statistically significant land‐use land cover change (LULCC) effects from RCM LULCC studies. The method is applied to a case study of urbanization and deforestation, for which LULCC scenarios are implemented in the RCM Weather Research and Forecasting (WRF). Based on WRF ensemble simulations with PICs for 2010, the signal‐to‐noise ratio (SNR) is used to identify areas with pronounced effect of an LULCC or, rather, the parametrization of the land‐use classes. While in the urbanization scenarios clear and statistically significant signals are found for air temperature and for both latent‐ and sensible heat (SNR values up to 24), the effects are less pronounced for precipitation, and for deforestation in general (SNR values < 1). For the case study of urbanization and precipitation, the impact of the ensemble size is studied in order to derive robust conclusions about the effects of LULCC on precipitation. We conclude that single RCM realizations of different land‐use representations are not sufficient to derive LULCC‐induced signals, particularly not for precipitation. Small ensemble sizes led to concluding there were significant LULCC‐induced precipitation signals, but these disappeared when the ensemble size was increased. Our regional analysis suggests the need for ensemble sizes well above 10 for precipitation.
Carotenoids in fresh and processed tomato (Solanum lycopersicum) fruits protect cells from oxidative stress injury
Authors: Del Giudice Rita , Petruk Ganna , Raiola Assunta , Barone Amalia , Monti Daria Maria , Rigano Maria Manuela 
Published: July 2016

AbstractBACKGROUNDLipophilic antioxidants in tomato (Solanum lycopersicum) fruits exert important functions in reducing the risk of human diseases. Here the effect of thermal processing on the antioxidant activity of lipophilic extracts from the commercial tomato hybrid ‘Zebrino’ was analysed. Carotenoid content and lipophilic antioxidant activity were determined and the ability of tomato extracts in rescuing cells from oxidative stress was assessed.RESULTSLipophilic antioxidant activity was completely retained after heat treatment and extracts were able to mitigate the detrimental effect induced by oxidative stress on different cell lines. Lycopene alone was able to rescue cells from oxidative stress, even if to a lower extent compared with tomato extracts. These results were probably due to the synergistic effect of tomato compounds in protecting cells from oxidative stress injury.CONCLUSIONThe current study provides valuable insights into the health effect of the dietary carotenoids present in fresh and processed tomato fruits. © 2016 Society of Chemical Industry
Kinetics of Ge(IV) Extraction Using a Microstructured Membrane Contactor
Authors: Willersinn Stefan , Bart Hans‐Jörg 
Published: July 2016

ABSTRACTFor hydrometallurgical metal extraction, the mass transfer by diffusion is additionally coupled with a chemical reaction of the metal ion with the extractant molecule, usually at the interface. Consequently, the kinetics is either limited by diffusion or chemical reaction (or both, respectively, in a mixed regime). Conventional methods for determining the extraction kinetics often lead to a misinterpretation, especially for fast reactions, and an isolated view of the interfacial reaction is restricted. With a new microcontactor setup, it is possible to perform a comprehensive kinetic analysis with very low sample volumes compared to established methods. Additionally, it is possible to quantify all individual mass transfer resistances and identify the extraction regime with the developed mass transfer model. The chemical reaction part is investigated isolated, to derive rate laws and kinetic constants. The methodology is discussed for the extraction of Ge(IV) from aqueous solutions with the two extractants 5,8‐diethyl‐7‐hydroxydodecan‐6‐oxime (LIX 63) and 7‐(4‐ethyl‐1‐methyloctyl)‐8‐hydroxyquinoline (Kelex 100). It was found that the extraction with LIX 63 is reaction limited and with Kelex 100 the reaction resistance is in the same order of magnitude as the diffusion resistances. The obtained results provide fundamental kinetic data for the design of solvent extraction equipment.
Synthesis of pH‐Cleavable dPG‐Amines for Gene Delivery Application
Authors: Dimde Mathias , Steinhilber Dirk , Neumann Falko , Li Yan , Paulus Florian , Ma Nan , Haag Rainer 
Published: July 2016

The development of effective nonviral vectors for gene therapy is still a challenge in research, due to the high toxicity of many existing polycationic nanocarriers. In this paper, the development of two pH‐cleavable polyglycerol‐amine‐based nanocarriers is described. The benz­acetal bond represents the pH‐sensitive cleavage site between dendritic polyglycerol (dPG) and glycerol‐based 1,2‐diamines that can complex genetic material. Due to the acid lability of the acetal moiety, the cleavable dPG‐amines are less toxic in vitro. Cell‐mediated degradation results in non‐toxic dPG with low amine functionalization and low molecular weight cleavage products (cp). The genetic material is released because of the loss of multivalent amine groups. Interestingly, the release kinetics at the endosomal pH could be controlled by simple chemical modification of the acetals. In vitro experiments demonstrate the ability of the cleavable dPG‐amine to transfect HeLa cells with GFP‐DNA, which resulted in cell‐compatible cleavage products.image
Photopolymerization of an Epoxy Resin: Conversion and Temperature Dependence of its Refractive Index
Authors: Aloui Faten , Lecamp Laurence , Lebaudy Philippe , Burel Fabrice 
Published: July 2016

Obtaining photocomposite materials with predefined optical properties requires a good knowledge of the refractive index evolution of the photopolymerizable media. In this aim, relationships between refractive index and conversion in the course of an epoxy resin photopolymerization are first established due to real time refractometric and infrared spectroscopic techniques. Refractive index value increases with conversion as long as the photocured material is not in glassy state. A shift of the relationship toward lowest refractive index values is observed when the reaction temperature increases. Second, the final photocured materials previously obtained are characterized. It is highlighted that the higher the photocuring temperature, the higher the epoxy conversion but the lower the material density at room temperature. This unusual result can be explained by the evolution of the material thermo‐optic coefficient, dn/dT. Indeed, the higher the conversion, the lower this coefficient.image
The “Grafting‐to” of Well‐Defined Polystyrene on Graphene Oxide via Nitroxide‐Mediated Polymerization
Authors: García‐Valdez Omar , Ledezma‐Rodríguez Raquel , Torres‐Lubian Román , Yate Luis , Saldívar‐Guerra Enrique , Ziolo Ronald F. 
Published: July 2016

The grafting of well‐defined polystyrene to graphene oxide (GO) using nitroxide‐mediated polymerization (NMP) is demonstrated by a two‐step reaction. In the first step, GO is functionalized with glycidyl methacrylate (GMA) to yield GO‐GMA. Polystyrene (PS), previously synthesized via SG1‐based NMP, is then grafted to GO‐GMA by a simple reaction between the SG1 end group and the GMA double bond to yield GO‐GMA‐g‐PS. 1H, heteronuclear single‐quantum correlation (HSQC), nuclear magnetic resonance (NMR), X‐ray photoelectron spectroscopy (XPS), Raman, Fourier transform infrared spectroscopy (FTIR), gel permeation chromatography (GPC), and thermogravimetric analysis (TGA) are consistent with attachment of the GMA group to the GO surface and with polystyrene being grafted to the GO surface to form the GO‐GMA‐g‐PS nanocomposite (NC). GPC analysis shows a number‐average molecular weight of 3330 g mol−1 for the PS with molecular weight dispersity (Ð) of 1.13. Up to 28 mass% of PS has been introduced into the GO NC. The present “grafting‐to” methodology holds promise for the facile and clean synthesis of graphene oxide polymer NCs.
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Unmasking levodopa resistance in Parkinson's disease
Authors: Nonnekes Jorik , Timmer Monique H.M. , de Vries Nienke M. , Rascol Olivier , Helmich Rick C. , Bloem Bastiaan R. 
Published: July 2016

ABSTRACTSome motor and nonmotor features associated with Parkinson's disease (PD) do not seem to respond well to levodopa (or other forms of dopaminergic medication) or appear to become resistant to levodopa treatment with disease progression and longer disease duration. In this narrative review, we elaborate on this issue of levodopa resistance in PD. First, we discuss the possibility of pseudoresistance, which refers to dopamine‐sensitive symptoms or signs that falsely appear to be (or have become) resistant to levodopa, when in fact other mechanisms are at play, resulting in suboptimal dopaminergic efficacy. Examples include interindividual differences in pharmacodynamics and pharmacokinetics and underdosing because of dose‐limiting side effects or because of levodopa phobia. Moreover, pseudoresistance can emerge as not all features of PD respond adequately to the same dosage of levodopa. Second, we address that for several motor features (eg, freezing of gait or tremor) and several nonmotor features (eg, specific cognitive functions), the response to levodopa is fairly complex, with a combination of levodopa‐responsive, levodopa‐resistant, and even levodopa‐induced characteristics. A possible explanation relates to the mixed presence of underlying dopaminergic and nondopaminergic brain lesions. We suggest that clinicians take these possibilities into account before concluding that symptoms or signs of PD are totally levodopa resistant. © 2016 International Parkinson and Movement Disorder Society
Arm swing as a potential new prodromal marker of Parkinson's disease
Authors: Mirelman Anat , Bernad‐Elazari Hagar , Thaler Avner , Giladi‐Yacobi Eytan , Gurevich Tanya , Gana‐Weisz Mali , Saunders‐Pullman Rachel , Raymond Deborah , Doan Nancy , Bressman Susan B. , Marder Karen S. , Alcalay Roy N. , Rao Ashwini K. , Berg Daniela , Brockmann Kathrin , Aasly Jan , Waro Bjørg Johanne , Tolosa Eduardo , Vilas Dolores , Pont‐Sunyer Claustre , Orr‐Urtreger Avi , Hausdorff Jeffrey M. , Giladi Nir 
Published: July 2016

ABSTRACTBackgroundReduced arm swing is a well‐known clinical feature of Parkinson's disease (PD), often observed early in the course of the disease. We hypothesized that subtle changes in arm swing and axial rotation may also be detectable in the prodromal phase.ObjectiveThe purpose of this study was to evaluate the relationship between the LRRK2‐G2019S mutation, arm swing, and axial rotation in healthy nonmanifesting carriers and noncarriers of the G2019S mutation and in patients with PD.MethodsA total of 380 participants (186 healthy nonmanifesting controls and 194 PD patients) from 6 clinical sites underwent gait analysis while wearing synchronized 3‐axis body‐fixed sensors on the lower back and bilateral wrists. Participants walked for 1 minute under the following 2 conditions: (1) usual walking and (2) dual‐task walking. Arm swing amplitudes, asymmetry, variability, and smoothness were calculated for both arms along with measures of axial rotation.ResultsA total of 122 nonmanifesting participants and 67 PD patients were carriers of the G2019S mutation. Nonmanifesting mutation carriers walked with greater arm swing asymmetry and variability and lower axial rotation smoothness under the dual task condition when compared with noncarriers (P < .04). In the nonmanifesting mutation carriers, arm swing asymmetry was associated with gait variability under dual task (P = .003). PD carriers showed greater asymmetry and variability of movement than PD noncarriers, even after controlling for disease severity (P < .009).ConclusionsThe G2019S mutation is associated with increased asymmetry and variability among nonmanifesting participants and patients with PD. Prospective studies should determine if arm swing asymmetry and axial rotation smoothness may be used as motor markers of prodromal PD. © 2016 International Parkinson and Movement Disorder Society
Temporal summation to thermal stimuli is elevated in women with overactive bladder syndrome
Authors: Reynolds William Stuart , Brown Elizabeth Timbrook , Danford Jill , Kaufman Melissa , Wein Alan , Dmochowski Roger , Bruehl Stephen 
Published: July 2016

IntroductionThis study sought to provide a preliminary assessment of whether spinally mediated afferent hyperactivity (i.e., central sensitization) might contribute to manifestations of overactive bladder syndrome (OAB) in women as indexed by elevated temporal summation of evoked heat pain stimuli.MethodsWe recruited 20 adult women with OAB who were planning to undergo interventional therapy for OAB with either onabotulinumtoxinA injection or sacral neuromodulation and 23 healthy controls without OAB symptoms to undergo quantitative sensory testing with cutaneous thermal pain temporal summation. The primary study outcome was the degree of temporal summation, as reflected in the magnitude of positive slope of the line fitted to the series of 10 stimuli at the 49°C target temperatures. Linear regression and analysis of covariance were utilized to compare the degree of temporal summation between study groups.ResultsThe standardized slope of temporal summation trials for women with OAB was significantly higher than for controls (β = 3.43, 95% confidence interval = 0.6–6.2, P = 0.017). The adjusted means ±SE of the standardized temporal summation slopes for the full OAB and control groups were 3.0 ± 0.5 (95% confidence interval = 2.0, 4.1) and 1.7 ± 0.5 (95% confidence interval = 0.7, 2.7), respectively.ConclusionIn this preliminary study, we demonstrated that women with OAB refractory to primary and secondary therapies exhibited greater thermal cutaneous temporal summation than women without OAB symptoms. This suggests that central sensitization, indexed by temporal summation, may be an underlying factor contributing to OAB in some women. Neurourol. Urodynam. 36:1108–1112, 2017. © 2016 Wiley Periodicals, Inc.