bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of mortality following paclitaxel drug-coated balloon angioplasty of femoropopliteal lesions in patients with ulcerations and gangrene – a single center experience
Authors: Böhme Tanja , Noory Elias , Beschorner Ulrich , Jacques Börries , Bürgelin Karlheinz , Macharzina Roland , Kuhn Lisa-Marie , Nührenberg Thomas , Neumann Franz-Josef , Zeller Thomas 
Published: October 2020

Summary: Background: A recent meta-analysis of randomized controlled trials suggested an increased long-term mortality risk following femoropopliteal angioplasty using paclitaxel coated devices. To assess the long-term mortality after paclitaxel drug-coated (DCB) and uncoated balloon angioplasty (POBA) of femoropopliteal lesions in patients with ulcerations and gangrene in real world practice. Patients and methods: A retrospective mortality analysis of patients with at least 3-year follow-up who underwent balloon based endovascular therapy of femoropopliteal lesions was performed. Results: Overall 624 patients with femoropopliteal lesions were included in this study. Of those, 197 patients were treated with POBA without crossover to a paclitaxel coated device during follow-up and 427 patients with DCB angioplasty. Mean follow-up time was 33.3 ± 25.4 months. Mortality incidence was 81.7% (95% confidence interval [95% CI]: 76.1–86.8) after POBA and 59.0% (95% CI: 54.6–63.9) after DCB (p < 0.001). Multivariate logistic regression analysis revealed type of treatment (POBA vs. DCB, (hazard ratio [HR]: 0.332, 95% CI: 0.215–0.514, p < 0.001), age per year (HR: 1.065, 95% CI: 1.046–1.087, p < 0.001), coronary heart disease (HR: 1.969, 95% CI: 1.323–2.930, p = 0.001), renal insufficiency (HR: 1.583, 95% CI: 1.079–2.323, p = 0.019), stroke (HR: 2.505, 95% CI: 1.431–4.384, p = 0.001) as predictors for all-cause mortality. In the subgroup excluding octogenarians, mortality predictors were type of treatment (HR: 0.463, 95% CI: 0.269–0.796, p = 0.005), age per year (HR: 1.035, 95% CI: 1.002–1.069, p = 0.038), coronary heart disease (HR: 2.082, 95% CI: 1.274–3.400, p = 0.003), stroke (HR: 2.203, 95% CI: 1.156–4.197, p = 0.016) and renal insufficiency (HR: 2.201, 95% CI: 1.357–3.571, p < 0.001). Conclusions: This monocentric retrospective analysis showed no survival disadvantage for patients in Rutherford-Becker stage 5 after treatment with paclitaxel-coated balloons.
Field Evaluation of Column CO2 Retrievals From Intensity‐Modulated Continuous‐Wave Differential Absorption Lidar Measurements During the ACT‐America Campaign
Authors: Campbell Joel F. , Lin Bing , Dobler Jeremy , Pal Sandip , Davis Kenneth , Obland Michael D. , Erxleben Wayne , McGregor Doug , O'Dell Chris , Bell Emily , Weir Brad , Fan Tai‐Fang , Kooi Susan , Gordon Iouli , Corbett Abigail , Kochanov Roman 
Published: October 2020

AbstractWe present an evaluation of airborne intensity‐modulated continuous‐wave (IM‐CW) lidar measurements of atmospheric column CO2 mole fractions during the Atmospheric Carbon and Transport–America (ACT‐America) project. This lidar system transmits online and offline wavelengths simultaneously on the 1.57111‐μm CO2 absorption line, with each modulated wavelength using orthogonal swept frequency waveforms. After the spectral characteristics of this system were calibrated through short‐path measurements, we used the HITRAN spectroscopic database to calculate the average‐column CO2 mole fraction (XCO2) from the lidar‐measured optical depths. Using in situ measurements of meteorological parameters and CO2 concentrations for calibration data, we demonstrate that our lidar CO2 measurements were consistent from season to season and had an absolute calibration error (standard deviation) of 0.80 ppm when compared to XCO2 values calculated from in situ measurements. By using a 10‐s or longer moving average, a precision of 1 ppm or better was obtained. The estimated CO2 measurement precision for 0.1‐, 1‐, 10‐, and 60‐s averages was determined to be 3.4, 1.2, 0.43, and 0.26 ppm, respectively. These correspond to measurement signal‐to‐noise ratios of 120, 330, 950, and 1,600, respectively. The drift in XCO2 over 1‐hr of flight time was found to be below 0.1 ppm. These analyses demonstrate that the measurement stability, precision, and accuracy are all well below the thresholds needed to study synoptic‐scale variations in atmospheric XCO2.
Reply to Comment by Peterie Et Al. on “Accelerated Fill‐Up of the Arbuckle Group Aquifer and Links to U.S. Midcontinent Seismicity”
Authors: Ansari Esmail , Bidgoli Tandis S. 
Published: October 2020

AbstractPeterie et al. question one observation in our paper: associating pressure increases to injection volumes at distances of up to 25 km from an injection well. In this reply, we show that the comment misunderstands our analysis and the evidence that led to this conclusion. We also show that gauge‐depth‐corrected pressures, used by the authors to produce statewide pressure maps, are discrepant with the static fluid level data, provided in our original compilation and analysis. The discrepancies are a result of the pressure correction method employed, which naïvely substitutes formation pressure for bottomhole pressure to calculate wellbore fluid density. Their linearly interpolated pressure maps, based on sparse data, contain interpolation and extrapolation artifacts that contradict injection trends in the state, the Theis solution, and the superposition principle. We reiterate that pressure and static fluid level increases in Class I wells existed prior to 2013, most notably in central Kansas, where recent earthquakes are cited in the comment as evidence of a pressure plume emanating from the Kansas‐Oklahoma border, 90 km away. We show that the space‐time pattern of seismicity in this area is inconsistent with a northward propagating pressure plume and, instead, seismicity appears to be centered on and near a cluster of high‐rate injection wells, two of which are among the highest rate wells in the state. These observations, along with recent M4 + earthquakes during continued decreases in wastewater injection in southern Kansas and northern Oklahoma, question the usefulness of the comment for understanding and managing societally significant earthquakes.
Long‐Wavelength Gravity Field Constraint on the Lower Mantle Viscosity in North America
Authors: Reusen J. M. , Root B. C. , Szwillus W. , Fullea J. , van der Wal W. 
Published: October 2020

AbstractThe long‐wavelength negative gravity anomaly over Hudson Bay coincides with the area depressed by the Laurentide Ice Sheet during the Last Glacial Maximum, suggesting that it is, at least partly, caused by glacial isostatic adjustment (GIA). Additional contributions to the static gravity field stem from surface dynamic topography, core‐mantle boundary (CMB) topography, and density anomalies in the subsurface. Previous estimates of the contribution of GIA to the gravity anomaly range from 25% to more than 80%. However, these estimates did not include uncertainties in all components that contribute to the gravity field. In this study, we develop a forward model for the gravity anomaly based on density models and dynamic models, investigating uncertainty in all components. We derive lithospheric densities from equilibrium constraints but extend the concept of lithospheric isostasy to a force balance that includes the dynamic models. The largest uncertainty in the predicted gravity anomaly is due to the lower mantle viscosity, uncertainties in the ice history, the crustal model, the lithosphere‐asthenosphere boundary, and the conversion from seismic velocities to density have a smaller effect. A preference for lower mantle viscosities >1022 Pa s is found, in which case at least 60% of the observed long‐wavelength gravity anomaly can be attributed to GIA. This lower bound on the lower mantle viscosity has implications for inferences based on models for mantle convection and GIA.
Prolonged Lifetime of the Transient Ionized Layer in the Martian Atmosphere Caused by Comet Siding Spring
Authors: Luppen Z. A. , Girazian Z. , Morgan D. D. , Kopf A. J. , Chu F. , Halekas J. S. , Gurnett D. A. 
Published: October 2020

AbstractIn October 2014, the close encounter between Mars and comet Siding Spring produced a transient ionized layer in the upper atmosphere composed primarily of Mg+ and Fe+ ions. The layer was detected by instruments on three spacecraft, including the Mars Advanced Radar for Subsurface and Ionosphere Sounding (MARSIS) on Mars Express. Analyses of the MARSIS data indicated the transient layer persisted up to 19 h after the comet's closest approach. We report MARSIS observations that suggest the transient layer lasted at least 7 days—and potentially as long as 32 days—after closest approach. During this period, the transient layer was mostly confined to a narrow latitude range between 20°N and 60°N and a longitude range spanning 275°E to 95°E. Since this period coincided with a highly active Sun, we discuss how solar flares may have contributed to the layer's prolonged lifetime.
Exploring the Interactions Between Rift Propagation and Inherited Crustal Fabrics Through Experimental Modeling
Authors: Maestrelli Daniele , Montanari Domenico , Corti Giacomo , Del Ventisette Chiara , Moratti Giovanna , Bonini Marco 
Published: October 2020

AbstractContinental rifting is a geodynamic process that involves the breakup of the crust and may eventually evolve to seafloor spreading. Although it is often assumed to be a product of orthogonal divergence, continental rifting may result from oblique extension, and in several cases, it is related to the rotation of plates or crustal blocks about a vertical axis. This implies the occurrence of rifts with straight but not parallel margins and rift axis‐parallel gradients in extension velocity and amount of strain. The effects of rift propagation through the continental crust has only recently started to be addressed, and even less investigated is the interaction between rift propagation and inherited crustal fabrics. We have studied this issue by carrying out a series of analog laboratory experiments. Modeling results suggest that inherited linear discontinuities in the model brittle upper crust that are oriented above a threshold angle (≥45°) from the orthogonal to the rift axis have the ability to interact with rift‐related structures. Depending on their orientation, such inherited discontinuities are reactivated as either transfer zones or rift‐bounding faults. We compare our models with four natural prototypes in which rift propagation is likely to have occurred (the Trans Mexican Volcanic belt, the Gofa Province, the Gulf of Suez, and the Kenya Rift). For each case study, we show how the kinematics of propagating rifts is comparable to our model results, and we provide insights into how rift‐related deformation may interact with inherited crustal fabrics.
Why Is the Terrestrial Water Storage in Dryland Regions Declining? A Perspective Based on Gravity Recovery and Climate Experiment Satellite Observations and Noah Land Surface Model With Multiparameterization Schemes Model Simulations
Authors: Chang Li‐Ling , Yuan Ruiqiang , Gupta Hoshin V. , Winter C. Larrabee , Niu Guo‐Yue 
Published: October 2020

AbstractDrylands cover over 40% of the global land area and are home to more than 2 billion humans. Here, we use the terrestrial water storage (TWS) anomaly data derived from GRACE satellites to assess water storage changes globally and find that drylands lost ~15.9 ± 9.1 mm of water between April 2002 and January 2017. The TWS trends are more significant and apparent in dry regions than in humid regions. The decrease in TWS occurred mainly in hyperarid and arid regions. Exact causes to the observed declines in TWS remain elusive due to anthropogenic water withdrawals, atmospheric demand (potential evapotranspiration,PET) in contrast to supply (precipitation,P) caused by the warming, and terrestrial ecohydrological responses. Therefore, we use a process‐based model forced by climate data to interpret the causes over three selected dryland regions showing the strongest drying trends. We find that the modeled TWS without considering anthropogenic water withdrawals explains most of the declining GRACE TWS over the southwestern North America (NA) and Middle East but underestimates the drying trend over North China. This suggests that TWS declines in the southwestern NA and the Middle East were primarily driven by the contrast between atmospheric demand and supply, whereas anthropogenic water withdrawals may have played a relatively more dominant role in TWS declines over North China. Additional model experiments indicate that terrestrial ecohydrological processes that help extract deep substrate water are critical for providing water supply additional to precipitation to sustainETin the drying drylands at decadal scales.
Impact of Uncertainty in Precipitation Forcing Data Sets on the Hydrologic Budget of an Integrated Hydrologic Model in Mountainous Terrain
Authors: Schreiner‐McGraw Adam P. , Ajami Hoori 
Published: October 2020

AbstractPrecipitation is a key input variable in distributed surface water‐groundwater models, and its spatial variability is expected to impact watershed hydrologic response via changes in subsurface flow dynamics. Gridded precipitation data sets based on gauge observations, however, are plagued by uncertainty, especially in mountainous terrain where gauge networks are sparse. To examine the mechanisms via which uncertainty in precipitation data propagates through a watershed, we perform a series of numerical experiments using an integrated surface water‐groundwater hydrologic model, ParFlow.CLM. The Kaweah River watershed in California, USA, is used as our virtual catchment laboratory to characterize watershed response to variable precipitation forcing from headwaters to groundwaters. By applying the three‐cornered hat method, we quantify the spatially distributed uncertainty in four publically available precipitation forcing data sets and their simulated hydrology. Simulations demonstrate that uncertainty in the simulated groundwater storage is primarily a result of topographic redistribution of uncertainty in precipitation forcing. Soil water redistribution is the primary pathway that redistributes uncertainty downslope. We also find that topography exerts a larger impact than variable subsurface parameters on propagating uncertainty in simulated fluxes. Finally, we find that improvement in model performance metrics is higher for a single simulation forced with the mean precipitation from the available data sets than the averaged simulated results of separate simulations forced with each data set. Results from this study highlight the importance of topography‐moderated flow through the critical zone in shaping the groundwater response to climate variability.
Groundwater Flow and Moisture Dynamics in the Swash Zone: Effects of Heterogeneous Hydraulic Conductivity and Capillarity
Authors: Geng Xiaolong , Heiss James W. , Michael Holly A. , Boufadel Michel C. , Lee Kenneth 
Published: October 2020

AbstractA density‐dependent, variably saturated groundwater flow and solute transport model was used to investigate the influence of swash motions on subsurface flow and moisture dynamics in beach aquifers with heterogeneous distributions of hydraulic conductivity (K) and capillarity. The numerical simulations were performed within a Monte Carlo framework using field measurements conducted in the swash zone of a sandy beach. Our results show that heterogeneous capillarity causes spatially variable capillary rise above the groundwater table. In response to swash motions, heterogeneity creates capillary barriers that result in pockets of elevated moisture content beneath the swash zone. These moisture hotspots persist within the unsaturated zone even at ebb tide when the swash motions recede seaward. Heterogeneous capillarity also results in highly tortuous preferential flow paths and alters the flow rates from the sand surface to the water table. Heterogeneous K greatly enhances the seawater infiltration into the swash zone and modulates its spatial distribution along the beach surface. Due to heterogeneous K and capillarity, complex mixing patterns emerge. Both strain‐dominated and vorticity‐dominated flow regions develop and dissipate as tides and waves move across the beach surface. Complex mixing patterns of seawater percolating from the swash zone surface to the water table, with localized areas of high and low mixing intensities, are further demonstrated by analysis of dilution index. Our findings reveal the influence of geologic heterogeneity on swash zone moisture and flow dynamics, which may have important implications for sediment transport and chemical processing in beach aquifers.
Epigenetic silencing of LncRNA LINC00261 promotes c-myc-mediated aerobic glycolysis by regulating miR-222-3p/HIPK2/ERK axis and sequestering IGF2BP1
Authors: Zhai Shuyu , Xu Zhiwei , Xie Junjie , Zhang Jun , Wang Xinjing , Peng Chenghong , Li Hongwei , Chen Hao , Shen Baiyong , Deng Xiaxing 
Published: October 2020

AbstractLong noncoding RNAs have been identified as key regulators in the progression of various cancers. LINC00261 has been reported as a tumor suppressor in multiple cancers. However, its function and underlying mechanisms in pancreatic cancer remain largely unclear. Quantitative real-time PCR was performed to detect RNA expression. In situ hybridization was used to discover the subcellular location. The direct binding of LINC00261 to miR-222-3p was verified using a dual-luciferase reporter assay and RNA immunoprecipitation. LINC00261-binding proteins were detected using an RNA pulldown assay. LINC00261 was downregulated in pancreatic cancer tissues and cell lines. Its reduced expression was correlated with advanced pathological stage and poor prognosis. Forced expression of LINC00261 suppressed pancreatic cancer glycolysis and proliferation and induced cell cycle arrest and apoptosis. Mechanistically, downregulation of LINC00261 was caused by hypermethylation of the CpG island in the promoter region and EZH2-mediated histone H3 lysine 27 trimethylation. Moreover, LINC00261 exerted its biological function by binding to miR-222-3p to activate the HIPK2/ERK/c-myc pathway. In addition, LINC00261 could also reduce c-myc expression by sequestering IGF2BP1. Our study suggests that LINC00261 functions as a tumor suppressor in pancreatic cancer and identifies novel epigenetic and posttranscriptional regulatory mechanisms of LINC00261, which contribute to the targeted therapy of pancreatic cancer.
RALB GTPase: a critical regulator of DR5 expression and TRAIL sensitivity in KRAS mutant colorectal cancer
Authors: Khawaja Hajrah , Campbell Andrew , Roberts Jamie Z. , Javadi Arman , O’Reilly Paul , McArt Darragh , Allen Wendy L. , Majkut Joanna , Rehm Markus , Bardelli Alberto , Di Nicolantonio Federica , Scott Christopher J. , Kennedy Richard , Vitale Nicolas , Harrison Timothy , Sansom Owen J. , Longley Daniel B. , Evergren Emma , Van Schaeybroeck Sandra 
Published: October 2020

AbstractRAS mutant (MT) metastatic colorectal cancer (mCRC) is resistant to MEK1/2 inhibition and remains a difficult-to-treat group. Therefore, there is an unmet need for novel treatment options for RASMT mCRC. RALA and RALB GTPases function downstream of RAS and have been found to be key regulators of several cell functions implicated in KRAS-driven tumorigenesis. However, their role as regulators of the apoptotic machinery remains to be elucidated. Here, we found that inhibition of RALB expression, but not RALA, resulted in Caspase-8-dependent cell death in KRASMT CRC cells, which was not further increased following MEK1/2 inhibition. Proteomic analysis and mechanistic studies revealed that RALB depletion induced a marked upregulation of the pro-apoptotic cell surface TRAIL Death Receptor 5 (DR5) (also known as TRAIL-R2), primarily through modulating DR5 protein lysosomal degradation. Moreover, DR5 knockdown or knockout attenuated siRALB-induced apoptosis, confirming the role of the extrinsic apoptotic pathway as a regulator of siRALB-induced cell death. Importantly, TRAIL treatment resulted in the association of RALB with the death-inducing signalling complex (DISC) and targeting RALB using pharmacologic inhibition or RNAi approaches triggered a potent increase in TRAIL-induced cell death in KRASMT CRC cells. Significantly, high RALB mRNA levels were found in the poor prognostic Colorectal Cancer Intrinsic Subtypes (CRIS)-B CRC subgroup. Collectively, this study provides to our knowledge the first evidence for a role for RALB in apoptotic priming and suggests that RALB inhibition may be a promising strategy to improve response to TRAIL treatment in poor prognostic RASMT CRIS-B CRC.
MicroRNA-200b/c-3p regulate epithelial plasticity and inhibit cutaneous wound healing by modulating TGF-β-mediated RAC1 signaling
Authors: Tang Huiyi , Wang Xueer , Zhang Min , Yan Yuan , Huang Simin , Ji Jiahao , Xu Jinfu , Zhang Yijia , Cai Yongjie , Yang Bobo , Lan Wenqi , Huang Mianbo , Zhang Lin 
Published: October 2020

AbstractCutaneous wound healing is pivotal for human skin to regain barrier function against pathogens. MicroRNAs (miRNAs) have been found to play regulatory roles in wound healing. However, the mechanism of miRNA regulation remains largely unknown. In this study, we focused on microRNA-200b/c-3p (miR-200b/c-3p) whose expression was abundant in intact epidermis, but dramatically decreased in skin wounds. In silico prediction identified RAC1 as a potential miR-200b/c-3p target. Luciferase reporter assay confirmed that miR-200b/c-p repressed RAC1 by direct targeting to its mRNA 3′UTR. Consistently, miR-200b/c-3p expression was discordantly related to RAC1 protein level during wound healing. Forced miR-200b/c-3p expression repressed RAC1 and inhibited keratinocyte migration as well as re-epithelialization in a mouse back skin full-thickness wound healing model. Mechanistically, miR-200b/c-3p modulated RAC1 to inhibit cell migration by repressing lamellipodia formation and intercellular adhesion dissolution in keratinocytes. Furthermore, we found that TGF-β1, which was highly expressed in skin wounds, contributed to the downregulation of miR-200b/c-3p in wound edge keratinocytes. Taken together, miR-200b/c-3p-mediated RAC1 repression inhibited keratinocyte migration to delay re-epithelialization. TGF-β1 induction attenuated miR-200b/c-3p regulation of RAC1 signaling in cutaneous wounds and the repression of miR-200b/c-3p accelerated keratinocyte migration to promote wound healing. Our data provide new insight into how miR-200b/c-3p affects keratinocyte migration and highlight the potential of miR-200b/c-3p targeting for accelerating wound healing.
Combating acquired resistance to MAPK inhibitors in melanoma by targeting Abl1/2-mediated reactivation of MEK/ERK/MYC signaling
Authors: Tripathi Rakshamani , Liu Zulong , Jain Aditi , Lyon Anastasia , Meeks Christina , Richards Dana , Liu Jinpeng , He Daheng , Wang Chi , Nespi Marika , Rymar Andrey , Wang Peng , Wilson Melissa , Plattner Rina 
Published: October 2020

AbstractMetastatic melanoma remains an incurable disease for many patients due to the limited success of targeted and immunotherapies. BRAF and MEK inhibitors reduce metastatic burden for patients with melanomas harboring BRAF mutations; however, most eventually relapse due to acquired resistance. Here, we demonstrate that ABL1/2 kinase activities and/or expression are potentiated in cell lines and patient samples following resistance, and ABL1/2 drive BRAF and BRAF/MEK inhibitor resistance by inducing reactivation of MEK/ERK/MYC signaling. Silencing/inhibiting ABL1/2 blocks pathway reactivation, and resensitizes resistant cells to BRAF/MEK inhibitors, whereas expression of constitutively active ABL1/2 is sufficient to promote resistance. Significantly, nilotinib (2nd generation ABL1/2 inhibitor) reverses resistance, in vivo, causing prolonged regression of resistant tumors, and also, prevents BRAFi/MEKi resistance from developing in the first place. These data indicate that repurposing the FDA-approved leukemia drug, nilotinib, may be effective for prolonging survival for patients harboring BRAF-mutant melanomas.