bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biomarkers for Hepatobiliary Cancers
Authors: Nault Jean‐Charles , Villanueva Augusto 
Published: February 2020

The clinical management of primary liver cancers such as hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) has significantly changed in the last 3 years. The introduction of systemic therapies, including immune‐based therapies and biomarker‐driven therapies, has significantly improved survival, particularly in patients at advanced stages of disease. Survival is still poor, and projections from the World Health Organization underscore the need to improve outcomes in these patients. Biomarkers have emerged as powerful tools for the diagnosis, prognosis, and prediction of treatment responses to improve patient stratification and maximize clinical benefits. Recent advances in understanding the molecular alterations of HCC have not yet translated into biomarkers. Some reasons for the lack of progress are the absence of druggable mutations in the majority of liver cancers and the significant heterogeneity of the disease. In contrast, several therapeutic targets have been identified in CCA, and biomarker‐driven therapies are currently under evaluation in phase 2/3 clinical trials. Here, we summarize the status on biomarker development for HCC and CCA.
Baclofen modulates cardiovascular responses to appetitive cues in treatment‐seeking alcohol use disorder individuals
Authors: Logge Warren B. , Baillie Andrew J. , Haber Paul S. , Morley Kirsten C. 
Published: February 2020

AbstractObjectiveTo assess whether baclofen‐treated alcohol dependent participants show different subjective and psychophysiological responses to appetitive cues during an alcohol cue reactivity task compared to placebo, and whether these responses are associated with prospective drinking outcomes.MethodsForty‐two alcohol dependent participants (placebo: n = 12, low‐dose baclofen [30 mg/day] n = 18, high‐dose baclofen [75 mg/day]: n = 12) completed an alcohol cue reactivity task, whereby water and alcohol beverage cues were presented, with subsequent recovery periods, and subjective alcohol craving and psychophysiological indices (skin conductance; cardiovascular measures: heart rate, high‐frequency heart rate variability) were recorded.ResultsHigh‐dose baclofen‐treated participants showed both overall cue reactivity to water and alcohol cues and greater recovery effects during recovery periods, revealed by high‐frequency heart rate variability, when compared to low‐dose‐ and placebo‐treated participants. There were no medication effects on subjective craving. In high‐dose baclofen participants only, there was a predictive effect of lower baseline heart rate variability and fewer post‐test percentage of heavy drinking days.ConclusionThere was a dose‐specific rescuing effect of high‐dose baclofen on the dynamic modulation of cardiovascular responses to eliciting cues. Investigation of treatment responses using psychophysiological techniques may elucidate baclofen's mechanisms of action, and identify subgroups amenable to treatment.
Amplification of hydrological model uncertainties in projected climate simulations of the Upper Indus Basin: Does it matter where the water is coming from?
Authors: Dolk Michaela , Penton David J. , Ahmad Mobin D. 
Published: February 2020

AbstractThere is a growing appreciation of the uncertainties in the estimation of snow‐melt and glacier‐melt as a result of climate change in high elevation catchments. Through a detailed examination of three hydrological models in two catchments, and interpretation of results from previous studies, we observed that many variations in estimated streamflow could be explained by the selection of a best parameter set from the possible good model parameters. The importance of understanding changing glacial dynamics is critically important for our study areas in the Upper Indus Basin where Pakistan's policymakers are planning infrastructure to meet the future energy and water needs of hundreds of millions of people downstream. Yet, the effect of climate on glacial runoff and climate on snowmelt runoff is poorly understood. With the HBV model, for example, we estimated glacial melt as between 56% and 89% for the Hunza catchment. When rainfall was a scaled parameter, the models estimated glacial melt as between 20% and 100% of streamflow. These parameter sets produced wildly different projections of future climate for RCP8.5 scenarios in 2046–2075 compared to 1976–2005. Assuming no glacial shrinkage, for one climate projection, we found that the choice among good parameter sets resulted in projected values of future streamflow across a range from +54% to +125%. Parameter selection was the most significant source of uncertainty in the glaciated catchment and amplified climate model uncertainty, whereas climate model choice was more important in the rainfall dominated catchment. Although the study focuses on Pakistan, the overall conclusions are instructive for other similar regions in the world. We suggest that modellers of glaciated catchments should present results from at least the book‐ends: models with low sensitivity to ice‐melt and models with high sensitivity to ice‐melt. This would reduce confusion among decision makers when they are faced with similar contrasting results.
Effects of forest cover change on catchment evapotranspiration variation in China
Authors: Ning Tingting , Li Zhi , Feng Qi , Chen Wen , Li Zongxing 
Published: February 2020

AbstractSeveral large‐scale revegetation programs in China have resulted in significant changes in forest cover (ΔF) during the past three decades. As forests have important effects on catchment hydrology, evaluating the effects of ΔF on hydrology is essential. Using data from 44 catchments across China, this study derived a rational analytical equation to link changes in actual evapotranspiration (ΔET) with those in F within the Budyko framework, and further quantified the effects of ΔF on ET variation during 1976–2015. The elasticity of ET to ΔF was found to be the greatest in the dry catchments in northwest China, followed by the humid catchments in south China, and was the smallest in the subhumid and semiarid catchments in north China. F averaged across all the catchments has increased, and has further led to the increase in ET. The F‐ET relationship has become more prominent in the recent decade (2006–2015), with 68.0% of the catchments showing an average increase in F of 4.5% and a resultant average increase in ET of 8.2% compared with the baseline period (1976–1985). These results are helpful for quantitative assessment of hydrological responses to afforestation, especially in water‐limited regions.
Assessing the impact of a family nurse‐led intervention on young mothers’ references to internal states
Authors: Paine Amy L. , Cannings‐John Rebecca , Channon Susan , Lugg‐Widger Fiona , Waters Cerith S. , Robling Michael 
Published: February 2020

ABSTRACTA mother's propensity to refer to internal states during mother–child interactions is important for her child's developing social understanding. However, adolescent mothers are less likely to reference internal states when interacting with their children. We investigated whether young mothers’ references to internal states are promoted by the Family Nurse Partnership (FNP) intervention, an intensive home‐visiting programme designed to support adolescent mothers in England. We also investigated family, maternal, and child factors associated with young mothers’ references to inner states during interactions with their children. Adolescent mothers (n = 483, aged ≤ 19 years when recruited in pregnancy) and their children participated in an observational substudy of a randomized controlled trial investigating the impact of FNP compared to usual care. Mother–child dyads were video‐recorded during free play, and mothers’ speech was coded for use of internal state language (references to cognitions, desires, emotions, intentions, preferences, physiology, and perception). We found no differences in mothers’ use of internal state language between the FNP and usual care groups. A sample‐wide investigation identified that other features of mothers’ language and relationship status with the child's father were associated with internal state language use. Findings are discussed with reference to targeted interventions and implications for future research.
Silver nanoparticles regulate autophagy through lysosome injury and cell hypoxia in prostate cancer cells
Authors: Chen Yue , Yang Tong , Chen Shiqun , Qi Shiyong , Zhang Zhihong , Xu Yong 
Published: February 2020

AbstractWith the rapid development of nanotechnology, nanomaterials are now being used for cancer treatment. Although studies on the application of silver nanoparticles in cancer treatment are burgeoning, few studies have investigated the toxicology mechanisms of autophagy in cancer cells under exposure to sublethal silver nanoparticles. Here, we clarified the distinct mechanisms of silver nanoparticles for the regulation of autophagy in prostate cancer PC‐3 cells under sublethal exposure. Silver nanoparticle treatment caused lysosome injury, including the decline of lysosomal membrane integrity, decrease of lysosomal quantity, and attenuation of lysosomal protease activity, which resulted in blockage of autophagic flux. In addition, sublethal silver nanoparticle exposure activated AMP‐activated protein kinase/mammalian target of rapamycin‐dependent signaling pathway to modulate autophagy, which resulted from silver nanoparticles‐induced cell hypoxia and energy deficiency. Taken together, the results show that silver nanoparticles could regulate autophagy via lysosome injury and cell hypoxia in PC‐3 cells under sublethal dose exposure. This study will provide an experimental basis for the cancer therapy of nanomaterials.
Handgrip weakness, low fat‐free mass, and overall survival in non‐small cell lung cancer treated with curative‐intent radiotherapy
Authors: Burtin Chris , Bezuidenhout Jacques , Sanders Karin J.C. , Dingemans Anne‐Marie C. , Schols Annemie M.W.J. , Peeters Stephanie T.H. , Spruit Martijn A. , De Ruysscher Dirk K.M. 
Published: February 2020

AbstractBackgroundAssessment of handgrip strength and fat‐free mass provides quick and objective information on muscle performance and mass that might complement subjective World Health Organization Performance Status (WHO PS). We investigated to what extent the presence of pre‐treatment handgrip weakness and low fat‐free mass index (FFMI) provides additional prognostic information on top of well‐established prognostic factors (including WHO PS) in non‐small cell lung cancer (NSCLC) patients selected for curative‐intent (chemo)radiation.MethodsProspectively, patients with early and locally advanced NSCLC (stages I‐III) treated with (chemo)radiation were enrolled. Handgrip weakness and low FFMI, derived from bioelectrical impedance analysis, were defined using normative values and were correlated with overall survival (OS).ResultsWe included 936 patients (age 68 ± 10 years; 64% male; 19% stage I, 9% stage II, and 72% stage III disease; 26% handgrip weakness; 27% low FFMI). In patients with good performance status (WHO PS 0 or 1), handgrip weakness and low FFMI were significant prognostic factors for OS, after adjustment for age, gender, disease stage, and co‐morbidities. The combined presence of handgrip weakness and low FFMI was a strong prognostic factor for OS when compared with patients with normal handgrip strength and FFMI (hazard ratio: 1.79, 95% confidence interval: 1.34–2.40, P < 0.0001). In patients with impaired performance status (WHO PS ≥ 2, 19% of sample), handgrip weakness and low FFMI were not related to OS.ConclusionsIn early and locally advanced NSCLC patients treated with curative‐intent (chemo)radiation who have good WHO PS, patients with combined handgrip weakness and low FFMI have the worst prognosis.
Robust adaptive least squares polynomial chaos expansions in high‐frequency applications
Authors: Loukrezis Dimitrios , Galetzka Armin , De Gersem Herbert 
Published: February 2020

AbstractWe present an algorithm for computing sparse, least squares‐based polynomial chaos expansions, incorporating both adaptive polynomial bases and sequential experimental designs. The algorithm is employed to approximate stochastic high‐frequency electromagnetic models in a black‐box way, in particular, given only a dataset of random parameter realizations and the corresponding observations regarding a quantity of interest, typically a scattering parameter. The construction of the polynomial basis is based on a greedy, adaptive, sensitivity‐related method. The sequential expansion of the experimental design employs different optimality criteria, with respect to the algebraic form of the least squares problem. We investigate how different conditions affect the robustness of the derived surrogate models, that is, how much the approximation accuracy varies given different experimental designs. It is found that relatively optimistic criteria perform on average better than stricter ones, yielding superior approximation accuracies for equal dataset sizes. However, the results of strict criteria are significantly more robust, as reduced variations regarding the approximation accuracy are obtained, over a range of experimental designs. Two criteria are proposed for a good accuracy‐robustness trade‐off.
A multi‐year assessment of sub‐hourly gridded precipitation for Switzerland based on a blended radar—Rain‐gauge dataset
Authors: Barton Yannick , Sideris Ioannis V. , Raupach Timothy H. , Gabella Marco , Germann Urs , Martius Olivia 
Published: February 2020

AbstractBlended high‐resolution sub‐hourly precipitation fields are increasingly needed for nowcasting and automatic warnings systems. Here we present a 7‐year (2012–2018) assessment of (5‐min) precipitation characteristics for the topographically complex region of Switzerland. We use CombiPrecip, a blended radar—rain‐gauge product that provides high resolution (1 km2) hourly precipitation fields. Five‐minute fields (CPCD), fine enough to disentangle even the shortest convective events from longer‐lasting precipitation, are obtained by temporally disaggregating these hourly fields. A rain‐gauge verification of the sub‐hourly precipitation fields shows that CPCD out‐performs the radar‐only estimates both in terms of quantitative error and in detecting wet/extreme periods, making CPCD sufficiently accurate to be used with confidence as input fields for hydrological modelling or for regional model validation. The quantitative error of CombiPrecip at the 60 (10)‐min time‐scale, as expressed by the scatter, is 40% (22%) lower than that of the radar‐only product. Radar‐gauge discrepancies are large and the quantitative error of CPCD increases by 30% when decreasing aggregation times from 60 to 10 min. Although summertime 5‐min precipitation extremes are strongest and more frequent on average south of the Alps, where they contribute to approximately 10% of the seasonal total precipitation, the most intense extremes are observed over the Jura Mountains in the afternoon and the highest wet 5‐min frequency in the Prealps around the same time. Intense precipitation is more evenly distributed throughout the day south of the Alps. Extreme intensity and frequency peaks 2 hr earlier in the Prealps, the Jura Mountains and the Alps (~1600 UTC) compared to the Swiss Plateau (~1800 UTC). Extremes are less intense and frequent at high elevations (>2,000 MASL) than over the Swiss Plateau (<800 MASL).
Short communication: On the use of the Benjamini–Hochberg procedure in wavelet analysis and its inferior performance to the cumulative arc‐wise and area‐wise tests
Authors: Schulte Justin 
Published: February 2020

AbstractThe Benjamini–Hochberg (BH) procedure is a well‐recognized and powerful tool for controlling the number of statistical artefacts arising from the simultaneous testing of multiple hypotheses. However, its performance as a statistical tool in wavelet analysis is unknown. A series of experiments suggests that the BH method is too conservative and too frequently rejects truly significant features such as periodicities as insignificant. In contrast, the recently developed cumulative area‐wise and arc‐wise tests strongly control the false positive rate yet liberally deem truly significant features as significant. Besides cone of influence impacts, statistical inferences made from the cumulative area‐wise and arc‐wise tests change very little when time series are lengthened, promoting the reproducibility of results in the face of continually lengthening climate time series. There is no such guarantee for BH method results, as they depend on the chosen family of tests, which will continually change as time series lengthen. The findings from the theoretical experiments and practical applications to Susquehanna streamflow suggest that the cumulative arc‐wise and area‐wise tests should be the preferred methods for statistical hypothesis testing in wavelet analysis.
The observed recent surface air temperature development across Svalbard and concurring footprints in local sea ice cover
Authors: Dahlke Sandro , Hughes Nicholas E. , Wagner Penelope M. , Gerland Sebastian , Wawrzyniak Tomasz , Ivanov Boris , Maturilli Marion 
Published: February 2020

AbstractThe Svalbard archipelago in the Arctic North Atlantic is experiencing rapid changes in the surface climate and sea ice distribution, with impacts for the coupled climate system and the local society. This study utilizes observational data of surface air temperature (SAT) from 1980–2016 across the whole Svalbard archipelago, and sea ice extent (SIE) from operational sea ice charts to conduct a systematic assessment of climatologies, long‐term changes and regional differences. The proximity to the warm water mass of the West Spitsbergen Current drives a markedly warmer climate in the western coastal regions compared to northern and eastern Svalbard. This imprints on the SIE climatology in southern and western Svalbard, where the annual maxima of 50–60% area ice coverage are substantially less than 80–90% in the northern and eastern fjords. Owing to winter‐amplified warming, the local climate is shifting towards more maritime conditions, and SIE reductions of between 5 and 20% per decade in particular regions are found, such that a number of fjords in the west have been virtually ice‐free in recent winters. The strongest decline comes along with SAT forcing and occurs over the most recent 1–2 decades in all regions; while in the 1980s and 1990s, enhanced northerly winds and sea ice drift can explain 30–50% of SIE variability around northern Svalbard, where they had correspondingly lead to a SIE increase. With an ongoing warming it is suggested that both the meteorological and cryospheric conditions in eastern Svalbard will become increasingly similar to what is already observed in the western fjords, namely suppressed typical Arctic climate conditions.
Ultra‐high performance separation of basic compounds on reversed‐phase columns packed with fully/superficially porous silica and hybrid particles by using ultraviolet transparent hydrophobic cationic additives
Authors: Manetto Simone , Mazzoccanti Giulia , Ciogli Alessia , Villani Claudio , Gasparrini Francesco 
Published: February 2020

AbstractThe use of the tetrabutylammonium additive was investigated in the ultra‐high performance reversed‐phase liquid chromatographic elution of basic molecules of pharmaceutical interest. When added to the mobile phase at low pH, the hydrophobic tetrabutylammonium cation interacts with the octadecyl chains and with the residual silanols, thus imparting a positive charge to the stationary phase, modulating retention and improving peak shape of protonated basic solutes. Two sources of additive were tested: a mixture of tetrabutylammonium hydroxide/trifluoroacetic acid and tetrabutylammonium hydrogen sulfate. Retention and peak shape of 11 basic pharmaceutical compounds were evaluated on commercially available ultra‐fast columns packed with octadecyl stationary phases (Ascentis Express C18 2.0 µm, Acquity BEH C18 1.7 µm, Titan C18 1.9 µm). All columns benefit from the use of additive, especially tetrabutylammonium hydrogen sulfate, providing very symmetric peaks with reasonable retention times. Focusing on the probe compounds amitriptyline and sertraline, efficiency and asymmetry values were investigated at increasing retention factor. The trend is very different to that obtained in reversed‐phase conditions and the effect lies in the complex molecular interaction mechanisms based on hydrophobic and ion exchange interactions as well as electrostatic repulsion.
“Pseudogestational Sac” and Other 1980s‐Era Concepts in Early First‐Trimester Ultrasound
Authors: Phillips Catherine H. , Benson Carol B. , Durfee Sara M. , Heller Howard T. , Doubilet Peter M. 
Published: February 2020

ObjectivesTo determine whether an intrauterine round or oval fluid collection (“saclike structure”) can prove to be either an intrauterine pregnancy or intrauterine fluid in conjunction with an ectopic pregnancy (sometimes termed “pseudogestational sac”) and whether ultrasound features, including the presence or absence of an echogenic rim, “double sac sign” (DSS), or “intradecidual sign” (IDS), are helpful for establishing the diagnosis or predicting the prognosis.MethodsWe identified all sonograms obtained from women with positive serum human chorionic gonadotropin results at our institution between January 1, 2012, and June 30, 2018, meeting the following criteria: presence of an intrauterine saclike structure without a yolk sac or embryo; no extraovarian adnexal mass; and follow‐up information identifying the location of the pregnancy as intrauterine or ectopic. Study authors reviewed sonograms in all cases and recorded the following information: presence or absence of each of an echogenic rim around the collection, a DSS, and an IDS, as well as the mean sac diameter. The indications for the initial ultrasound examinations were recorded.ResultsA total of 649 sonograms met the inclusion criteria. Of these, 598 fluid collections showed an echogenic rim, 182 a DSS, and 347 an IDS (findings not mutually exclusive). In all 649 cases, a subsequent sonogram or other clinical follow‐up confirmed that the patient had an intrauterine pregnancy. That is, none of the fluid collections proved to be a pseudogestational sac. In total, 41.2% were live at the end of the first trimester, and 58.8% miscarried. The prognosis was better in cases with, compared to without, an IDS (P = .01, χ2), but no ultrasound feature was clinically useful for ruling in or excluding a good prognosis.ConclusionsIn a woman with positive human chorionic gonadotropin results and no extraovarian adnexal mass, the ultrasound finding of an intrauterine saclike structure is virtually certain to be a gestational sac. Ultrasound features of the structure are of no diagnostic or clinically useful prognostic value. Concepts introduced 30 to 40 years ago when ultrasound equipment had far lower resolution than currently, including a DDS, an IDS, and a pseudogestational sac, have no role today in assessing early pregnancy.