bluuebunny/crossref_metadata_2025_split huggingface dataset:
Managing embryonic and calves losses after twin pregnancies induced by transfer of in vitro-produced Nellore embryos
Authors: Souza Juliano F. , Lubov Rotar , Paiva Clesio J. F. , Tavora Nilda F. C. , Santos Regiane R. , Figueiredo Jose R. 
Published: April 2020

SummaryTwo farms applying reproductive technology for the Nellore beef cattle were selected. Both farms had the same technology programme of oestrous synchronization and embryo transfer, but management was different, especially regarding twins pregnancies. In the present study, we followed the farms from the moment of oestrous synchronization, embryo transfer (two per cow), until delivery and first care of the calves. In farm A, cows presenting twin pregnancies (5 from 13) were submitted to delivery induction, as well as calves and cows were monitored after birth. In farm B, such management was not followed with the twin pregnant cows (31 from 49). In both farms, freemartinism was detected, but this was not a problem as none of the animals would be selected for breeding. No dystocia was observed in farm A, while 48% of the twin pregnancies in farm B ended up in dystocia. Furthermore, the mortality rate of new-born calves in farm A was 10%, while in farm B it reached 32%. Although twin pregnancies remain a concern, we showed here that proper management during and after delivery minimizes animal and economic losses.
Estimating 24-h urinary sodium excretion from casual spot urine specimen among hypertensive patients in Northwest China: the Salt Substitute and Stroke Study
Authors: Zhao Yi , Liu Wanlu , Liu Sha , Li Xiaoxia , Yin Ting , Liu Xiuying , Wang Faxuan , Chang Xiaoyu , Zhang Tianjing , Tian Maoyi , Zhang Yuhong 
Published: April 2020

AbstractObjective:To develop an equation that can estimate the 24-h urinary Na excretion by using casual spot urine specimen for older hypertensive participants in rural Ningxia and further to compare with the INTERSALT method, Kawasaki method and Tanaka method.Design:Older hypertensive participants in rural Ningxia provided their casual spot urine samples and 24-h urine samples between January 2015 and February 2017. Sex-specific equation was developed using linear forward stepwise regression analysis. Model fit was assessed using adjusted R2. Approximately half of all participants were randomly selected to validate the equation. Mean differences, intraclass correlation coefficients and Bland–Altman plots were used to evaluate the performance of all methods.Setting:Pingluo County and Qingtongxia County in Ningxia Hui Autonomous Region, China.Participants:Older hypertensive participants in rural Ningxia.Results:Totally, 807 of 1120 invited participants provided qualified 24-h urine samples and spot urine samples. There was no statistical difference comparing the laboratory-based method against the new method and the INTERSALT method, while Kawasaki method had the largest bias with a mean difference of 40·81 g/d (95 % CI 39·27, 42·35 g/d). Bland–Altman plots showed similar pattern of the results.Conclusion:The INTERSALT method and the new equation have the potential to estimate the 24-h urinary Na excretion in this study population. However, the extrapolation of the results to other population needs to be careful. Future research is required to establish a more reliable method to estimate 24-h urinary Na excretion.
Esketamine clinical trials: reply to Maju et al.
Authors: Gastaldon C. , Papola D. , Ostuzzi G. , Barbui C. 
Published: April 2020

Abstract
Maju et al. provided clarifications on important and controversial issues related to esketamine clinical trial data, in response to a vivid debate triggered by the marketing authorisation recently granted by this new medicine. In this commentary, we reply to their comments attempting to critically discuss the evidence base needed to obtain regulatory approval.
Volatile‐Rich Magmas Distributed Through the Upper Crust in the Main Ethiopian Rift
Authors: Iddon Fiona , Edmonds Marie 
Published: April 2020

AbstractUnderstanding magma storage and differentiation in the East African Rift underpins our understanding of volcanism in continental rift settings. Here, we present the geochemistry of melt inclusions erupted in Main Ethiopian Rift transitional basalts, trachytes, and peralkaline rhyolites, produced by fractional crystallization. Basalts stored on‐ and off‐axis are saturated in an exsolved volatile phase at up to 18 km in the upper crust. Much of the CO2 outgassed from the magmas is likely lost through diffuse degassing. Observed CO2 fluxes require the intrusion of up to 0.14 km3 of basalt beneath the rift each year. On‐axis peralkaline rhyolites are stored shallowly, at ~4–8 km depth. In the Daly Gap, magmas saturate in sulfide and an exsolved volatile phase, which promotes magma rise to shallower levels in the crust. Here, magmas undergo further protracted fractional crystallization and degassing, leading to the formation of a substantial exsolved volatile phase, which may accumulate in a gas‐rich cap. The exsolved volatile phase is rich in sulfur and halogens: their projected loadings into the atmosphere during explosive peralkaline eruptions in the MER are predicted to be substantially higher than their metaluminous counterparts in other settings. The high fraction of exsolved volatiles in the stored magmas enhances their compressibility and must be considered when interpreting ground displacements thought to be caused by magma intrusion at depth; otherwise, intruding volumes will be underestimated. Pockets of exsolved volatiles may be present at the roof zones of magma reservoirs, which may be resolvable using geophysical techniques.
Three‐Dimensional Pore Fluid Pressures in Source Region of 2017 Pohang Earthquake Inferred From Earthquake Focal Mechanisms
Authors: Terakawa Toshiko , Seo Wooseok , Kim Kwang‐Hee , Ree Jin‐Han 
Published: April 2020

AbstractWe analyzed 91 focal mechanism data with relocated hypocenters to estimate the 3‐D pore fluid pressure field in the source region of the 2017 Pohang earthquake in South Korea using the method of focal mechanism tomography. The upper limit of pore fluid pressure was 8 ± 3 MPa in a location northwest of the enhanced geothermal system. The overpressurized fluids were localized in the footwall of the causative fault. It was directly connected to the open hole section of PX2, and fluid injection into this hole could have triggered the mainshock.
A Comparison of the Polarimetric Radar Characteristics of Heavy Rainfall From Hurricanes Harvey (2017) and Florence (2018)
Authors: DeHart Jennifer C. , Bell Michael M. 
Published: April 2020

AbstractPolarimetric coastal radar data are used to compare the rainfall characteristics of Hurricanes Harvey (2017) and Florence (2018). Intense rainfall was an infrequent yet important contributor to the total rainfall in Harvey, but its relative contribution varied spatially. The total rainfall over land maximized near the coast over Beaumont, TX, due to intense convection resulting from prolonged onshore flow downshear from the circulation center. Overall, polarimetric radar observations in Harvey show a dominance of high concentrations of small‐to‐medium drops, consistent with prior tropical cyclone studies. The microphysical characteristics were spatially and temporally inhomogeneous however, with larger drops more frequent on 27 August and higher number concentrations more frequent on 28 and 30 August. The polarimetric variables and raindrop characteristics observed during Florence share broad similarities to Harvey, but had reduced variability, fewer observations of stronger reflectivity and differential reflectivity, and a lower frequency of high number concentrations and medium‐sized drops. The radar data indicate Florence had reduced coverage of stronger convection compared to Harvey. We hypothesize that differences in storm motion, intensity decay rates, and vertical wind shear produce the distinct precipitation structures and microphysical differences seen in Harvey and Florence.
Unraveling the Mysteries of Asymmetric Topography at Gabilan Mesa, California
Authors: Richardson P. W. , Perron J. T. , Miller S. R. , Kirchner J. W. 
Published: April 2020

AbstractWe investigated the potential causes of topographic asymmetry at Gabilan Mesa, CA, a site that exhibits large aspect‐dependent differences in hillslope gradients and microclimates. Competing hypotheses have been proposed to explain the asymmetry observed at Gabilan Mesa. One hypothesis states that different microclimates on opposing slopes are responsible for differences in runoff or soil strength, which generates asymmetric topography. A second hypothesis states that differences in sediment flux from opposing slopes causes southward lateral channel migration and oversteepening of north facing slopes. To test these hypotheses, we carried out numerical modeling experiments, terrain analysis, and field measurements. We also considered the role of initial tilting in causing the asymmetry. We found that saturated hydraulic conductivity is considerably lower on south facing slopes in one highly asymmetric basin. This is consistent with the hypothesis that aspect‐dependent runoff is responsible for the asymmetry. We also used cosmogenic radionuclide‐derived erosion rates and topographic characteristics at Gabilan Mesa to test predictions from numerical landscape evolution models that incorporate asymmetry‐forming mechanisms. The aspect‐dependent models reproduce the erosional and topographic characteristics of Gabilan Mesa better than the lateral channel migration model. We conclude that aspect‐dependent runoff is the most likely explanation for most of the topographic asymmetry at Gabilan Mesa. Our results do not rule out tilting as a possible influence on the initial development of asymmetry nor do they rule out the possibility that lateral channel migration has contributed to the asymmetry, but we suggest that tilting and lateral channel migration are not primarily responsible for it.
A Data Assimilation Framework for Generating Space‐Time Continuous Daily SWOT River Discharge Data Products
Authors: Li Dongyue , Andreadis Konstantinos M. , Margulis Steven A. , Lettenmaier Dennis P. 
Published: April 2020

AbstractThe Surface Water and Ocean Topography (SWOT) satellite will provide global observations of surface water storage and river discharge at an unprecedented high resolution and accuracy after its scheduled launch in 2021, but a limitation of SWOT observations is their spatial and temporal discontinuity associated with the SWOT orbital characteristics. Here, we describe a prototype data assimilation framework to assimilate synthetic SWOT water surface elevation observations into the LISFLOOD‐FP hydrodynamic model to generate a spatially and temporally continuous SWOT discharge data product. We develop the assimilation system with realistic errors in both the SWOT observations and model predictions. During a 3‐year period (consistent with the designed SWOT mission life), the assimilation effectively fills the observation gaps in both time and space across the 5,094‐km Upper Mississippi river network, where SWOT observations provide an average spatial sampling coverage of 55%. The assimilation results in a posterior discharge estimate agree well with the synthetic truth and better capture the peak flows in the significant 1993 flooding in this region; the daily posterior discharge estimates collectively increase the accuracy of the open‐loop (model‐only) discharge estimate by 41%. The posterior estimates show the largest improvement in areas where SWOT has higher sampling frequency and spatial sampling density and where the river has larger volumetric water storage. The accuracy improvement from the assimilation of SWOT data persists well between subsequent observations. Correcting the effects of bathymetric errors on hydrodynamic modeling prior to the assimilation is critical for the assimilation to improve discharge estimates.
Machine Learning Augmented Time‐Lapse Bathymetric Surveys: A Case Study From the Mississippi River Delta Front
Authors: Obelcz Jeffrey , Wood Warren T. , Phrampus Benjamin J. , Lee Taylor R. 
Published: April 2020

AbstractThe subaqueous Mississippi River Delta Front is prone to seabed instabilities >1 m of vertical bathymetric change per year, but the ability to predict the location and magnitude of instability‐driven depth change is limited. Here we demonstrate that data‐driven geospatial models can predict MRDF depth change from a small amount (1% of full coverage) of training data. We predict depth change at 100 m2 resolution between 2005 and 2017 over a ~100 km2 area. Models trained on ~1% of full‐coverage depth change data produce comparable and relatively low average predicted depth change errors (1–2 cm). K‐nearest neighbors best reproduce the spatial variability of depth change and can interpolate and extrapolate from training data. This approach has immediate applications for geohazard monitoring on the MRDF and other geologically similar settings and can be applied in other settings if the drivers of depth change variance are well known.
Stearoyl-CoA-desaturase-1 regulates gastric cancer stem-like properties and promotes tumour metastasis via Hippo/YAP pathway
Authors: Gao Yunhe , Li Jiyang , Xi Hongqing , Cui Jianxin , Zhang Kecheng , Zhang Jiabing , Zhang Yanmei , Xu Wei , Liang Wenquan , Zhuang Ziwei , Wang Pengpeng , Qiao Zhi , Wei Bo , Chen Lin 
Published: April 2020

Abstract
Background
Stearoyl-CoA desaturase-1 (SCD1) is reported to play essential roles in cancer stemness among several cancers. Our previous research revealed significant overexpression of SCD1 in primary gastric cancer stem cells (GCSCs), with its functional role still unknown.

Methods
We stably established three primary GCSCs by sphere-forming assays and flow cytometry. Protein quantification and bioinformatics analysis were performed to reveal the differential protein pattern. Lentivirus-based small-interfering RNA (siRNA) knockdown and pharmacological inhibition approaches were used to characterise the function and molecular mechanism role of SCD1 in the regulation of GC stemness and tumour metastasis capacity both in vitro and in vivo.

Results
SCD1 was found to increase the population of GCSCs, whereas its suppression by an SCD1 inhibitor or knockdown by siRNA attenuated the stemness of GCSCs, including chemotherapy resistance and sphere-forming ability. Furthermore, SCD1 suppression reversed epithelial-to-mesenchymal transition and reduced the GC metastasis probability both in vitro and in vivo. Downregulation of SCD1 in GCSCs was associated with the expression of Yes-associated protein (YAP), a key protein in the Hippo pathway, and nuclear YAP translocation was also blocked by the SCD1 decrease.

Conclusions
SCD1 promotes GCSC stemness through the Hippo/YAP pathway. Targeting SCD1 might be a novel therapeutic strategy, especially to suppress GC metastasis and sensitise chemotherapy.
Scheduling nab-paclitaxel combined with gemcitabine as first-line treatment for metastatic pancreatic adenocarcinoma
Authors: Corrie P. G. , Qian W. , Basu B. , Valle J. W. , Falk S. , lwuji C. , Wasan H. , Palmer D. , Scott-Brown M. , Wadsley J. , Arif S. , Bridgewater J. , Propper D. , Gillmore R. , Gopinathan A. , Skells R. , Bundi P. , Brais R. , Dalchau K. , Bax L. , Chhabra A. , Machin A. , Dayim A. , McAdam K. , Cummins S. , Wall L. , Ellis R. , Anthoney A. , Evans J. , Ma Y. T. , Isherwood C. , Neesse A. , Tuveson D. , Jodrell D. I. 
Published: April 2020

Abstract
Background
Nab-paclitaxel plus gemcitabine (nabP+gemcitabine) offers modest survival gains for patients with metastatic pancreatic ductal adenocarcinoma (PDAC). Sequential scheduling of nabP+gemcitabine in a PDAC mouse model improved efficacy; this hypothesis was tested in a clinical trial.

Methods
Patients with previously untreated metastatic PDAC were randomised to receive nabP+gemcitabine administered either concomitantly on the same day, or sequentially, with gemcitabine administered 24 h after nabP. The primary outcome measure was progression-free survival (PFS). Secondary outcome measures were objective response rate (ORR), overall survival (OS), safety, quality of life (QoL) and predictive biomarkers.

Results
In total, 71 patients received sequential (SEQ) and 75 concomitant (CON) treatment. Six-month PFS was 46% with SEQ and 32% with CON scheduling. Median PFS (5.6 versus 4.0 months, hazard ratio [HR] 0.67, 95% confidence interval [95% CI] 0.47–0.95, p = 0.022) and ORR (52% versus 31%, p = 0.023) favoured the SEQ arm; median OS was 10.2 versus 8.2 months (HR 0.93, 95% CI 0.65–1.33, p = 0.70). CTCAE Grade ≥3 neutropaenia incidence doubled with SEQ therapy but was not detrimental to QoL. Strongly positive tumour epithelial cytidine deaminase (CDA) expression favoured benefit from SEQ therapy (PFS HR 0.31, 95% CI 0.13–0.70).

Conclusions
SEQ delivery of nabP+gemcitabine improved PFS and ORR, with manageable toxicity, but did not significantly improve OS.

Clinical trial registration
ISRCTN71070888; ClinialTrials.gov (NCT03529175).
A live cell reporter of exosome secretion and uptake reveals pathfinding behavior of migrating cells
Authors: Sung Bong Hwan , von Lersner Ariana , Guerrero Jorge , Krystofiak Evan S. , Inman David , Pelletier Roxanne , Zijlstra Andries , Ponik Suzanne M. , Weaver Alissa M. 
Published: April 2020

AbstractSmall extracellular vesicles called exosomes affect multiple autocrine and paracrine cellular phenotypes. Understanding the function of exosomes requires a variety of tools, including live imaging. Our previous live-cell reporter, pHluorin-CD63, allows dynamic subcellular monitoring of exosome secretion in migrating and spreading cells. However, dim fluorescence and the inability to make stably-expressing cell lines limit its use. We incorporated a stabilizing mutation in the pHluorin moiety, M153R, which now exhibits higher, stable expression in cells and superior monitoring of exosome secretion. Using this improved construct, we visualize secreted exosomes in 3D culture and in vivo and identify a role for exosomes in promoting leader–follower behavior in 2D and 3D migration. Incorporating an additional non-pH-sensitive red fluorescent tag allows visualization of the exosome lifecycle, including multivesicular body (MVB) trafficking, MVB fusion, exosome uptake and endosome acidification. This reporter will be a useful tool for understanding both autocrine and paracrine roles of exosomes.
MALT-1 mediates IL-17 neural signaling to regulate C. elegans behavior, immunity and longevity
Authors: Flynn Sean M. , Chen Changchun , Artan Murat , Barratt Stephen , Crisp Alastair , Nelson Geoffrey M. , Peak-Chew Sew-Yeu , Begum Farida , Skehel Mark , de Bono Mario 
Published: April 2020

AbstractBesides pro-inflammatory roles, the ancient cytokine interleukin-17 (IL-17) modulates neural circuit function. We investigate IL-17 signaling in neurons, and the extent it can alter organismal phenotypes. We combine immunoprecipitation and mass spectrometry to biochemically characterize endogenous signaling complexes that function downstream of IL-17 receptors in C. elegans neurons. We identify the paracaspase MALT-1 as a critical output of the pathway. MALT1 mediates signaling from many immune receptors in mammals, but was not previously implicated in IL-17 signaling or nervous system function. C. elegans MALT-1 forms a complex with homologs of Act1 and IRAK and appears to function both as a scaffold and a protease. MALT-1 is expressed broadly in the C. elegans nervous system, and neuronal IL-17–MALT-1 signaling regulates multiple phenotypes, including escape behavior, associative learning, immunity and longevity. Our data suggest MALT1 has an ancient role modulating neural circuit function downstream of IL-17 to remodel physiology and behavior.
Multi-model functionalization of disease-associated PTEN missense mutations identifies multiple molecular mechanisms underlying protein dysfunction
Authors: Post Kathryn L. , Belmadani Manuel , Ganguly Payel , Meili Fabian , Dingwall Riki , McDiarmid Troy A. , Meyers Warren M. , Herrington Caitlin , Young Barry P. , Callaghan Daniel B. , Rogic Sanja , Edwards Matthew , Niciforovic Ana , Cau Alessandro , Rankin Catharine H. , O’Connor Timothy P. , Bamji Shernaz X. , Loewen Christopher J. R. , Allan Douglas W. , Pavlidis Paul , Haas Kurt 
Published: April 2020

AbstractFunctional variomics provides the foundation for personalized medicine by linking genetic variation to disease expression, outcome and treatment, yet its utility is dependent on appropriate assays to evaluate mutation impact on protein function. To fully assess the effects of 106 missense and nonsense variants of PTEN associated with autism spectrum disorder, somatic cancer and PTEN hamartoma syndrome (PHTS), we take a deep phenotypic profiling approach using 18 assays in 5 model systems spanning diverse cellular environments ranging from molecular function to neuronal morphogenesis and behavior. Variants inducing instability occur across the protein, resulting in partial-to-complete loss-of-function (LoF), which is well correlated across models. However, assays are selectively sensitive to variants located in substrate binding and catalytic domains, which exhibit complete LoF or dominant negativity independent of effects on stability. Our results indicate that full characterization of variant impact requires assays sensitive to instability and a range of protein functions.
Non-Invasive MRI of Blood–Cerebrospinal Fluid Barrier Function
Authors: Evans P. G. , Sokolska M. , Alves A. , Harrison I. F. , Ohene Y. , Nahavandi P. , Ismail O. , Miranda E. , Lythgoe M. F. , Thomas D. L. , Wells J. A. 
Published: April 2020

AbstractThe blood–cerebrospinal fluid barrier (BCSFB) is a highly dynamic transport interface that serves brain homeostasis. To date, however, understanding of its role in brain development and pathology has been hindered by the absence of a non-invasive technique for functional assessment. Here we describe a method for non-invasive measurement of BSCFB function by using tracer-free MRI to quantify rates of water delivery from arterial blood to ventricular cerebrospinal fluid. Using this method, we record a 36% decrease in BCSFB function in aged mice, compared to a 13% decrease in parenchymal blood flow, itself a leading candidate biomarker of early neurodegenerative processes. We then apply the method to explore the relationship between BCSFB function and ventricular morphology. Finally, we provide proof of application to the human brain. Our findings position the BCSFB as a promising new diagnostic and therapeutic target, the function of which can now be safely quantified using non-invasive MRI.