bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prostate cancer molecular profiling: the Achilles heel for the implementation of precision medicine
Authors: Oliveira‐Barros Eliane Gouvêa , Nicolau‐Neto Pedro , Da Costa Nathalia Meireles , Pinto Luís Felipe Ribeiro , Palumbo Antonio , Nasciutti Luiz Eurico 
Published: May 2017

AbstractCancer has been mainly treated by traditional therapeutic approaches which do not consider the human genetic diversity and present limitations, probably as a consequence of a poor knowledge of both patient's genetic background and tumor biology. Due to genome project conclusion and large‐scale gene analyses emergence, the therapeutic management of several prevalent and aggressive tumors has dramatically improved and represents the closest examples of a precision medicine intervention in this field. Nonetheless, prostate cancer (PCa) remains as a challenge to personalized medicine implementation, probably due to its notorious heterogeneous molecular profile. Cancer treatment personalized approaches rely on the premise that a well‐defined panorama of tumor molecular alterations can help selecting new and specific therapeutic targets for its treatment and potentially discriminate tumors which behave differentially. Lately, molecular and genetic studies have been investigating PCa basis, revealing multiple recurrent genomic alterations that include mutations, DNA copy‐number variations, rearrangements, and gene fusions, among others. In addition to the increment on PCa molecular biology knowledge, mapping the molecular alterations pattern of this neoplasia, especially the differences existent between tumors displaying distinct behaviors, could represent a great improvement concerning the identification of new targets, personalized medicine, and patients’ management and prognosis.
Acromelia‐oligodontia syndrome
Authors: Talasila Jyothirmai , Pachigolla Ramaswamy , Yarlagadda Kiranmai V. S. N. , Vuppala Ramu , Grzeschik Karl‐Heinz , Kiran K.V.S Sai , Rose Catherine M. , Gottesman Gary S. , Urban Zsolt 
Published: May 2017

Key Clinical MessageThis case report describes a patient with ankyloglossia, oligodontia, unilateral hypoplasia of the zygoma and mandible, along with bilateral distal reduction anomalies of his limbs without long bone abnormalities. This may represent a mild variant of oromandibular limb hypogenesis syndrome, expanding the phenotypic spectrum, or a previously unrecognized malformation syndrome.
Direct Insight into Ethane Oxidative Dehydrogenation over Boron Nitrides
Authors: Huang Rui , Zhang Bingsen , Wang Jia , Wu Kuang‐Hsu , Shi Wen , Zhang Yajie , Liu Yuefeng , Zheng Anmin , Schlögl Robert , Su Dang Sheng 
Published: May 2017

AbstractThe ultimate objective of chemical conversion is to achieve 100 % selectivity from catalysis, and this is also a prodigious challenge for the conversion of light paraffins into olefins, because it involves controlled activation of highly stable aliphatic C−H bonds. Herein, we show that metal‐free boron nitride (BN) nanosheets not only enable the oxidative dehydrogenation of ethane to ethylene exclusively at near 10 % conversion, but they also deliver a remarkable 60 % selectivity at an ethane conversion of 78 % and remain stable over 400 h at 575 °C. Our operando infrared spectroscopy and 18O isotope tracer study explicitly demonstrates that B−O(H) active sites are formed at the edges of BN through the aid of ethane, and the dehydrogenation circle is completed over these B−O sites by the assistance of O2.
2′β‐Fluoro‐Tricyclo Nucleic Acids (2′F‐tc‐ANA): Thermal Duplex Stability, Structural Studies, and RNase H Activation
Authors: Istrate Alena , Katolik Adam , Istrate Andrei , Leumann Christian J. 
Published: May 2017

AbstractWe describe the synthesis, thermal stability, structural and RNase H activation properties of 2′β‐fluoro‐tricyclo nucleic acids (2′F‐tc‐ANA). Three 2′F‐tc‐ANA nucleosides (T, 5MeC and A) were synthesized starting from a previously described fluorinated tricyclo sugar intermediate. NMR analysis and quantum mechanical calculations indicate that 2′F‐tc‐ANA nucleosides prefer sugar conformations in the East and South regions of the pseudorotational cycle. UV‐melting experiments revealed that non‐consecutive insertions of 2′F‐tc‐ANA units in DNA reduce the affinity to DNA and RNA complements. However, an oligonucleotide with five contiguous 2′F‐tc‐ANA‐T insertions exhibits increased affinity to complementary RNA. Moreover, a fully modified 10‐mer 2′F‐tc‐ANA oligonucleotide paired to both DNA (+1.6 °C/mod) and RNA (+2.5 °C/mod) with significantly higher affinity compared to corresponding unmodified DNA, and similar affinity compared to corresponding tc‐DNA. In addition, CD spectroscopy and molecular dynamics simulations indicate that the conformation of the 2′F‐tc‐ANA/RNA duplex is similar to that of a DNA/RNA duplex. Moreover, in some sequence contexts, 2′F‐tc‐ANA promotes RNase H‐mediated cleavage of a complementary RNA strand. Taken together, 2′F‐tc‐ANA represents a nucleic acid analogue that offers the advantage of high RNA affinity while maintaining the ability to activate RNase H, and can be considered a prospective candidate for gene silencing applications.
A Spontaneous Structural Transition of {U24Pp12} Clusters Triggered by Alkali Counterion Replacement in Dilute Solution
Authors: Gao Yunyi , Dembowski Mateusz , Szymanowski Jennifer E. S. , Yin Wenbin , Chuang Steven S. C. , Burns Peter C. , Liu Tianbo 
Published: May 2017

AbstractA transition between two isomeric clusters involving the change of the main skeleton structure of a well‐defined, rigid molecular cluster [(UO2)24(O2)24(P2O7)12]48−, {U24Pp12}, is achieved by simply introducing proper alkali cations into its dilute aqueous solution. While the unique structural transition can be triggered by introducing any of the Na+/K+/Rb+/Cs+ alkali ions, the two isomers, Li/Na‐{U24Pp12} and Na/K‐{U24Pp12}, as typical macroions, can accurately choose among different alkali counter‐cations based on their hydrated sizes, and the ion selectivity process clearly showed endothermic features. The preferred K+ and Rb+ ions have suitable sizes to be incorporated into the proper windows on {U24Pp12} nanocapsules, as supported by the transition points in both ITC studies and IR measurements.
The effect of statins on renal outcomes in patients with diabetic kidney disease: A systematic review and meta‐analysis
Authors: Qin Xin , Dong Hui , Fang Ke , Lu Fuer 
Published: May 2017

SummaryThe effects of statins on renal outcomes in patients with diabetic kidney disease were conflicting. The aim of the study was to investigate whether statins treatment could affect renal outcomes (albuminuria or proteinuria, estimated glomerular filtration rate [eGFR]) for diabetic kidney disease patients. We searched the PubMed, OVID (including MEDLINE and EMBASE), Web of Science and the Cochrane Central Register of Controlled Trials. Randomized controlled trials evaluating the efficacy of statins in diabetic kidney disease patients were selected. The main outcomes were albuminuria (or proteinuria). Secondary outcomes were levels of eGFR. Two authors independently assessed study quality and extracted the information from enrolled trials. Eleven randomized controlled trials with a total number of 543 diabetic kidney disease participants were included in our study. The overall estimates showed that statins statistically reduced albuminuria (standardized mean differences −0.71, 95% CI −1.20 to −0.23, P = .004), though marked heterogeneity was found within studies. However, the analysis results indicated that statins could not reduce overt proteinuria (standardized mean differences −0.14, 95% CI −0.53 to 0.26, P = .49) or slow the rate of reduction in eGFR (standardized mean differences 0.06, 95% CI −0.14 to 0.26, P = .53). In general, our study demonstrated that statins might have beneficial effects on reducing albuminuria in diabetic kidney disease patients. However, there was no strong evidence that the same intervention had an effect on overt proteinuria or eGFR outcomes in these patients.
Chronic effects of an invasive species on an animal community
Authors: Doody J. Sean , Rhind David , Green Brian , Castellano Christina , McHenry Colin , Clulow Simon 
Published: May 2017

AbstractInvasive species can trigger trophic cascades in animal communities, but published cases involving their removal of top predators are extremely rare. An exception is the invasive cane toad (Rhinella marina) in Australia, which has caused severe population declines in monitor lizards, triggering trophic cascades that facilitated dramatic and sometimes unexpected increases in several prey of the predators, including smaller lizards, snakes, turtles, crocodiles, and birds. Persistence of isolated populations of these predators with a decades‐long sympatry with toads suggests the possibility of recovery, but alternative explanations are possible. Confirming predator recovery requires longer‐term study of populations with both baseline and immediate post‐invasion densities. Previously, we quantified short‐term impacts of invasive cane toads on animal communities over seven years at two sites in tropical Australia. Herein, we test the hypothesis that predators have begun to recover by repeating the study 12 yr after the initial toad invasion. The three predatory lizards that experienced 71–97% declines in the short‐term study showed no sign of recovery, and indeed a worse fate: two of the three species were no longer detectable in 630 km of river surveys, suggesting local extirpation. Two mesopredators that had increased markedly in the short term due to these predator losses showed diverse responses in the medium term; a small lizard species increased by ~500%, while populations of a snake species showed little change. Our results indicate a system still in ecological turmoil, having not yet reached a “new equilibrium” more than a decade after the initial invasion; predator losses due to this toxic invasive species, and thus downstream effects, were not transient. Given that cane toads have proven too prolific to eradicate or control, we suggest that recovery of impacted predators must occur unassisted by evolutionary means: dispersal into extinction sites from surviving populations with alleles for toxin resistance or toad avoidance. Evolution and subsequent dispersal may be the only solution for a number of species or communities affected by invasive species for which control is either prohibitively expensive, or not possible.
Length scales and statistical characteristics of outer bank roughness for large elongate meander bends: The influence of bank material properties, floodplain vegetation and flow inundation
Authors: Konsoer Kory , Rhoads Bruce , Best James , Langendoen Eddy , Ursic Mick , Abad Jorge , Garcia Marcelo 
Published: May 2017

AbstractThis article explores the length scales and statistical characteristics of form roughness along the outer banks of two elongate bends on a large meandering river through investigation of topographic variability of the bank face. The analysis also examines how roughness varies over the vertical height of the banks and when the banks are exposed subaerially and inundated during flood stage. Detailed data on the topography of the outer banks were obtained subaerially using terrestrial LiDAR during low flow conditions and subaqueously using multibeam echo sounding (MBES) during near‐bankfull conditions. The contributions of various length scales of topographic irregularity to roughness for subaerial conditions were evaluated for different elevation contours on the bank faces using Hilbert–Huang Transform (HHT) spectral analysis. Statistical characteristics for discrete areas on the bank faces were determined by calculating the root‐mean‐square of normal distances from a triangulated irregular network (TIN) surface. Results of the HHT analysis show that the characteristics of roughness along bank faces composed primarily of non‐cohesive sediment, and eroding into cropland, vary with bank elevation and exhibit a dominant range of roughness length scales (~15–50 m). However, bank faces composed predominantly of cohesive material and carved into a forested floodplain have relatively uniform topographic roughness characteristics over the vertical extent of the bank face and do not exhibit a dominant roughness length scale or range of length scales. Additionally, comparison between local surface roughness for subaerial versus subaqueous conditions shows that roughness decreases considerably when the banks are submerged, most likely because of the removal of vegetation and eradication of small‐scale erosional features in non‐cohesive bank materials by flow along the bank face. Thus, roughness appears to be linked to the hydraulic conditions affecting the bank, at least relative to conditions that develop when banks are exposed subaerially. Copyright © 2017 John Wiley & Sons, Ltd.
Changes in carbon and nutrient fluxes from headwaters to ocean in a mountainous temperate to subtropical basin
Authors: Mutema Macdex , Chivenge Pauline , Nivet Fantine , Rabouille Christophe , Thieu Vincent , Chaplot Vincent 
Published: May 2017

AbstractWater erosion provides major links in global cycles of carbon (C), nitrogen (N) and phosphorus (P). Although significant research on erosion mechanisms has been done, there is still little knowledge on C, N and P fluxes across landscapes to the ocean and their controlling factors in subtropical climates. A four‐year study quantifying and comparing particulate and dissolved C, N and P from multiple scales (microplot, plot, microcatchment, subcatchment, catchment, sub‐basin and basin) was performed in Thukela basin (≈30 000 km2), South Africa. The basin climate was largely subtropical‐humid [mean annual precipitation (MAP) > 980 mm yr‐1], but temperate (MAP >2000 mm yr‐1) on the highlands. Open grassland, cropland and bushland were the major land uses. On average, 65, 24 and 4 g m‐2 yr‐1 C, N and P were displaced from original topsoil positions, but only 0.33, 0.005 and 0.002 mg m‐2 yr‐1 were, respectively, exported to the ocean. The fluxes decreased by 95, 97 and 84%, respectively, from plot to microcatchment outlet; and decreased further in downstream direction by >99% from microcatchment to basin outlet. The hillslope (microplot to microcatchment) fluxes correlated strongly with rainfall parameters. Particulate contributions dominated hillslope fluxes at 73, 81 and 76% of total annual C, N and P, respectively. Although particulate C dominated in the microcatchment‐catchment reach (55%), N (54%) and P (69%) were dominated by dissolved forms. The lower basin zone was dominated by dissolved flux contributions at 93, 81 and 78% for C, N and P for the sub‐basin outlet. These results suggested spatially varying drivers of C, N and P losses from the landscape to the ocean, via the river network. Deposition was envisaged the dominant hillslope level loss process, which gradually gave way to mineralization and biotic uptake in the river network as flux contributions shifted from being predominantly particulate to dissolved forms. Copyright © 2017 John Wiley & Sons, Ltd.
Forest water use in the initial stages of reclamation in the Athabasca Oil Sands Region
Authors: Strilesky Stacey L. , Humphreys Elyn R. , Carey Sean K. 
Published: May 2017

AbstractFollowing large‐scale surface oil sands mining, large tracts of the boreal forest in the Athabasca Oil Sands Region of Western Canada are legally required to be reclaimed. A greater understanding of how these novel ecosystems function and develop with regard to water use is crucial to aid in the development of regulatory practices and protocols based on information from ecosystem recovery. In this paper, a 12‐year (2003–2014) eddy covariance measurement record of latent and sensible heat fluxes and gross ecosystem productivity of carbon dioxide is analysed to evaluate how a reclaimed boreal forest has developed during its initial growth period. The study site is a reclaimed oil sands saline‐sodic clay shale overburden deposit that was topped with 100 cm of glacial till and 20 cm of peat mineral mix. The site was seeded with barley (Hordeum spp.) in 2001 to reduce erosion of the soil cover whereas aspen (Populus tremuloides Michx.) and spruce (Picea glauca [Moench] Voss) boreal tree species were planted in 2004. Changes in structure and function corresponded to the transition of dominant vegetation cover from early successional species to forest. Leaf area index increased from a growing season peak of 0.9 in 2003 to 4.0 in 2014 and was associated with an increased growing season gross ecosystem productivity (4.9 to 8.9 g C m−2 day−1), an increased evapotranspiration (1.6 to 3.4 mm day−1), and a decreased partitioning of energy to sensible heat (Bowen's ratio decreased from 1.1 to 0.4). Although canopy conductance increased throughout the 12 years, the shift from early successional species to trees with more conservative water use resulted in a decrease in conductance normalized by leaf area. Water use efficiency has increased slightly since 2008 with an average of 10.0 g CO2 kg−1 H2O for the last 6 years. No prolonged dry periods were observed during the study period. The functioning of this novel ecosystem is evolving as expected on the basis of the trends observed for other natural and disturbed boreal forests.
The Lrp4R1170Q Homozygous Knock-In Mouse Recapitulates the Bone Phenotype of Sclerosteosis in Humans
Authors: Boudin Eveline , Yorgan Timur , Fijalkowski Igor , Sonntag Stephan , Steenackers Ellen , Hendrickx Gretl , Peeters Silke , De Maré Annelies , Vervaet Benjamin , Verhulst Anja , Mortier Geert , D'Haese Patrick , Schinke Thorsten , Van Hul Wim 
Published: May 2017

ABSTRACT

Sclerosteosis is a rare autosomal recessive bone disorder marked by hyperostosis of the skull and tubular bones. Initially, we and others reported that sclerosteosis was caused by loss-of-function mutations in SOST, encoding sclerostin. More recently, we identified disease-causing mutations in LRP4, a binding partner of sclerostin, in three sclerosteosis patients. Upon binding to sclerostin, LRP4 can inhibit the canonical WNT signaling that is known to be an important pathway in the regulation of bone formation. To further investigate the role of LRP4 in the bone formation process, we generated an Lrp4 mutated sclerosteosis mouse model by introducing the p.Arg1170Gln mutation in the mouse genome. Extensive analysis of the bone phenotype of the Lrp4R1170Q/R1170Q knock-in (KI) mouse showed the presence of increased trabecular and cortical bone mass as a consequence of increased bone formation by the osteoblasts. In addition, three-point bending analysis also showed that the increased bone mass results in increased bone strength. In contrast to the human sclerosteosis phenotype, we could not observe syndactyly in the forelimbs or hindlimbs of the Lrp4 KI animals. Finally, we could not detect any significant changes in the bone formation and resorption markers in the serum of the mutant mice. However, the serum sclerostin levels were strongly increased and the level of sclerostin in the tibia was decreased in Lrp4R1170Q/R1170Q mice, confirming the role of LRP4 as an anchor for sclerostin in bone. In conclusion, the Lrp4R1170Q/R1170Q mouse is a good model for the human sclerosteosis phenotype caused by mutations in LRP4 and can be used in the future for further investigation of the mechanism whereby LRP4 regulates bone formation. © 2017 American Society for Bone and Mineral Research.
A “mix‐and‐use” approach for formulation of human clinical doses of 177Lu‐DOTMP at hospital radiopharmacy for management of pain arising from skeletal metastases
Authors: Chakraborty Sudipta , Vimalnath K.V. , Rajeswari A. , Chakravarty Rubel , Sarma H.D. , Radhakrishnan E. , Kamaleshwaran K. , Shinto Ajit S. , Dash Ashutosh 
Published: May 2017

Use of bone‐seeking radiopharmaceuticals is an established modality in the palliative care of pain due to skeletal metastases. 177Lu‐DOTMP is a promising radiopharmaceutical for this application owing to the ideally suited decay properties of 177Lu and excellent thermodynamic stability and kinetic rigidity of the macrocyclic complex. The aim of the present study is to develop a robust and easily adaptable protocol for formulation of clinical doses of 177Lu‐DOTMP at hospital radiopharmacy. After extensive radiochemical studies, an optimized strategy for formulation of clinical doses of 177Lu‐DOTMP was developed, which involves simple mixing of approximately 3.7 GBq of 177Lu activity as 177LuCl3 solution to an aqueous solution containing 5 mg of DOTMP and 8 mg of NaHCO3. The proposed protocol yielded 177Lu‐DOTMP with >98% radiochemical purity, and the resultant formulation showed excellent in vitro stability and desired pharmacokinetic properties in animal model. Preliminary clinical investigations in 5 patients showed specific skeletal accumulation with preferential localization in the osteoblastic lesion sites and almost no uptake in soft tissue or any other major nontarget organ. The developed “mix‐and‐use” strategy would be useful for large number of nuclear medicine centers having access to 177Lu activity and would thereby accelerate the clinical translation of 177Lu‐DOTMP.
Evaluating the accuracy of 4D‐CT ventilation imaging: First comparison with Technegas SPECT ventilation
Authors: Hegi‐Johnson Fiona , Keall Paul , Barber Jeff , Bui Chuong , Kipritidis John 
Published: May 2017

PurposeComputed tomography ventilation imaging (CTVI) is a highly accessible functional lung imaging modality that can unlock the potential for functional avoidance in lung cancer radiation therapy. Previous attempts to validate CTVI against clinical ventilation single‐photon emission computed tomography (V‐SPECT) have been hindered by radioaerosol clumping artifacts. This work builds on those studies by performing the first comparison of CTVI with 99mTc‐carbon (‘Technegas’), a clinical V‐SPECT modality featuring smaller radioaerosol particles with less clumping.MethodsEleven lung cancer radiotherapy patients with early stage (T1/T2N0) disease received treatment planning four‐dimensional CT (4DCT) scans paired with Technegas V/Q‐SPECT/CT. For each patient, we applied three different CTVI methods. Two of these used deformable image registration (DIR) to quantify breathing‐induced lung density changes (CTVIDIR‐HU), or breathing‐induced lung volume changes (CTVIDIR‐Jac) between the 4DCT exhale/inhale phases. A third method calculated the regional product of air‐tissue densities (CTVIHU) and did not involve DIR. Corresponding CTVI and V‐SPECT scans were compared using the Dice similarity coefficient (DSC) for functional defect and nondefect regions, as well as the Spearman's correlation r computed over the whole lung. The DIR target registration error (TRE) was quantified using both manual and computer‐selected anatomic landmarks.ResultsInterestingly, the overall best performing method (CTVIHU) did not involve DIR. For nondefect regions, the CTVIHU, CTVIDIR‐HU, and CTVIDIR‐Jac methods achieved mean DSC values of 0.69, 0.68, and 0.54, respectively. For defect regions, the respective DSC values were moderate: 0.39, 0.33, and 0.44. The Spearman r‐values were generally weak: 0.26 for CTVIHU, 0.18 for CTVIDIR‐HU, and −0.02 for CTVIDIR‐Jac. The spatial accuracy of CTVI was not significantly correlated with TRE, however the DIR accuracy itself was poor with TRE > 3.6 mm on average, potentially indicative of poor quality 4DCT. Q‐SPECT scans achieved good correlations with V‐SPECT (mean r > 0.6), suggesting that the image quality of Technegas V‐SPECT was not a limiting factor in this study.ConclusionsWe performed a validation of CTVI using clinically available 4DCT and Technegas V/Q‐SPECT for 11 lung cancer patients. The results reinforce earlier findings that the spatial accuracy of CTVI exhibits significant interpatient and intermethod variability. We propose that the most likely factor affecting CTVI accuracy was poor image quality of clinical 4DCT.