bluuebunny/crossref_metadata_2025_split huggingface dataset:
Controlling Nutritional Status score does not predict patients' overall survival or hepatocellular carcinoma recurrence after deceased donor liver transplantation
Authors: Pravisani Riccardo , Mocchegiani Federico , Isola Miriam , Lorenzin Dario , Adani Gian Luigi , Cherchi Vittorio , Righi Elda , Terrosu Giovanni , Vivarelli Marco , Risaliti Andrea , Baccarani Umberto 
Published: January 2020

AbstractBackgroundThe Controlling Nutritional Status (CONUT) score is a newly developed laboratory‐derived immunonutritional score which has been validated as prognostic marker for survival and tumor recurrence in surgically treated patients with various tumor types, including hepatocellular carcinoma (HCC). The aim of the present study was to test the CONUT score performance in HCC patients treated with liver transplantation (LT).MethodsA retrospective study on a bi‐centers cohort of 280 HCC patients submitted to LT between 2006 and 2017 was performed. Indication to LT was limited to Milan criteria or UCSF criteria, defined by preoperative imaging.ResultsMedian pre‐LT CONUT score was 5 (interquartile range 3‐7). Overall patients' survival at 1, 3, and 5 years was 84%, 76.6%, and 68.3%, respectively. Multivariate analysis showed that HCC recurrence (hazard ratio [HR] = 1.987, P = .012] and pre‐LT neutrophil to lymphocyte ratio (NLR) (HR = 1.064, P = .003) were independent risk factors for reduced survival. Cumulative incidence of HCC recurrence at 1, 3, and 5 years was 5.1%, 11.5%, and 15.5%, respectively. Pre‐LT platelet‐to‐lymphocyte ratio (PLR) (subdistribution hazard ratio [SHR] = 1.086, P = .044], tumor max diameter (SHR = 1.695, P < .001), and bilobar tumor distribution (SHR = 6.892, P = .006) were independent risk factors for tumor recurrence. The CONUT score did not show any prognostic value.ConclusionsThe CONUT score did not predict poor survival or tumor recurrence in LT recipients.
Comparative effects of sulphonylureas, dipeptidyl peptidase‐4 inhibitors and sodium‐glucose co‐transporter‐2 inhibitors added to metformin monotherapy: a propensity‐score matched cohort study in UK primary care
Authors: Wilkinson Samantha , Williamson Elizabeth , Pokrajac Ana , Fogarty Damian , Stirnadel‐Farrant Heide , Smeeth Liam , Douglas Ian J. , Tomlinson Laurie A. 
Published: January 2020

AbstractAimTo assess the comparative effects of sodium‐glucose co‐transporter‐2 (SGLT2) inhibitors, sulphonylureas (SUs) and dipeptidyl peptidase‐4 (DPP‐4) inhibitors on cardiometabolic risk factors in routine care.Materials and methodsUsing primary care data on 10 631 new users of SUs, SGLT2 inhibitors or DPP‐4 inhibitors added to metformin, obtained from the UK Clinical Practice Research Datalink, we created propensity‐score matched cohorts and used linear mixed models to describe changes in glycated haemoglobin (HbA1c), estimated glomerular filtration rate (eGFR), systolic blood pressure (BP) and body mass index (BMI) over 96 weeks.ResultsHbA1c levels fell substantially after treatment intensification for all drugs: mean change at week 12: SGLT2 inhibitors: −15.2 mmol/mol (95% confidence interval [CI] –16.9, −13.5); SUs: −14.3 mmol/mol (95% CI –15.5, −13.2); and DPP‐4 inhibitors: −11.9 mmol/mol (95% CI –13.1, −10.6). Systolic BP fell for SGLT2 inhibitor users throughout follow‐up, but not for DPP‐4 inhibitor or SU users: mean change at week 12: SGLT2 inhibitors: −2.3 mmHg (95% CI –3.8, −0.8); SUs: −0.8 mmHg (95% CI –1.9, +0.4); and DPP‐4 inhibitors: −0.9 mmHg (95% CI –2.1,+0.2).BMI decreased for SGLT2 inhibitor and DPP‐4 inhibitor users, but not SU users: mean change at week 12: SGLT2 inhibitors: −0.7 kg/m2 (95% CI –0.9, −0.5); SUs: 0.0 kg/m2 (95% CI –0.3, +0.2); and DPP‐4 inhibitors: −0.3 kg/m2 (95% CI –0.5, −0.1). eGFR fell at 12 weeks for SGLT2 inhibitor and DPP‐4 inhibitor users. At 60 weeks, the fall in eGFR from baseline was similar for each drug class.ConclusionsIn routine care, SGLT2 inhibitors had greater effects on cardiometabolic risk factors than SUs. Routine care data closely replicated the effects of diabetes drugs on physiological variables measured in clinical trials.
Pharmacokinetic and pharmacodynamic analysis of (2S,3S)‐sec‐butylpropylacetamide (SPD) in rats and pigs—A CNS‐active stereoisomer of SPD
Authors: Bibi David , Bialer Meir 
Published: January 2020

AbstractObjectivesTo advance the development of (2S,3S)‐sec‐butylpropylacetamide (SPD) as a new treatment for acute repetitive seizures (ARS), by studying its pharmacokinetics (PK) in pigs and its PK‐pharmacodynamic (PK‐PD) correlation in rats.MethodsTwo (2S,3S)‐SPD intramuscular formulations (FA and FB) were administered to pigs and rats and blood samples were withdrawn at different times after dosing. Major PK parameters were estimated in both species. PD analysis was conducted in rats utilizing the maximal‐electroshock seizure threshold (MEST) test. Because ARS treatment requires a rapid action, the MEST test allows comparative evaluation of (2S,3S)‐SPD intramuscular injection on rat susceptibility to electroconvulsive shock at various times after dosing.ResultsIn rats, (2S,3S)‐SPD plasma exposure increased proportionally following intramuscular dosing (20, 25 and 40 mg/kg) of FA and FB. Peak plasma concentration (Cmax) was obtained at 1‐2 hours after dosing and ranged between 6.8 and 9.4 mg/L. (2S,3S)‐SPD plasma concentration at 10 minutes after dosing (C10) ranged between 2.1 and 3.5 mg/mL, and its half‐life ranged between 0.9 and 2.3 hours. The highest C10 value, which may indicate rapid activity onset, and the highest Cmax were observed following administration of FA (40 mg/kg): C10 = 3.5 mg/L and Cmax = 9.5 mg/L. In the MEST test, (2S,3S)‐SPD (20 and 60 mg/kg) significantly raised the tonic seizure threshold compared to vehicle at 4, 7, 10, and 20 minutes after dosing, with a 1.6‐fold increase at 20 minutes, which coincided with (2S,3S)‐SPD brain Cmax. Following intramuscular dosing of (2S,3S)‐SPD (12 mg/kg) to pigs of FA and FB, a Cmax value of 0.9 mg/L was obtained 0.42 and 0.75 hours after dosing, respectively. (2S,3S)‐SPD C10 was 0.27 mg/L (FA) and 0.49 mg/L (FB). (2S,3S)‐SPD clearance, volume of distribution, and half‐life were 2 L/h/kg, 18‐28 L/kg, and 6.1‐9.7 hours, respectively.Significance(2S,3S)‐SPD demonstrated a good PK‐PD correlation in the rat MEST test, with a rapid onset. (2S,3S)‐SPD first PK study in pigs showed that doses >12 mg/kg are required to achieve in pigs the plasma concentrations associated with activity at the rat MEST test.
Genotyping‐by‐sequencing illuminates high levels of divergence among sympatric forms of coregonines in the Laurentian Great Lakes
Authors: Ackiss Amanda S. , Larson Wesley A. , Stott Wendylee 
Published: January 2020

AbstractEffective resource management depends on our ability to partition diversity into biologically meaningful units. Recent evolutionary divergence, however, can often lead to ambiguity in morphological and genetic differentiation, complicating the delineation of valid conservation units. Such is the case with the “coregonine problem,” where recent postglacial radiations of coregonines into lacustrine habitats resulted in the evolution of numerous species flocks, often with ambiguous taxonomy. The application of genomics methods is beginning to shed light on this problem and the evolutionary mechanisms underlying divergence in these ecologically and economically important fishes. Here, we used restriction site‐associated DNA (RAD) sequencing to examine genetic diversity and differentiation among sympatric forms in the Coregonus artedi complex in the Apostle Islands of Lake Superior, the largest lake in the Laurentian Great Lakes. Using 29,068 SNPs, we were able to clearly distinguish among the three most common forms for the first time, as well as identify putative hybrids and potentially misidentified specimens. Population assignment rates for these forms using our RAD data were 93%–100% with the only mis‐assignments arising from putative hybrids, an improvement from 62% to 77% using microsatellites. Estimates of pairwise differentiation (FST: 0.045–0.056) were large given the detection of hybrids, suggesting that reduced fitness of hybrid individuals may be a potential mechanism for the maintenance of differentiation. We also used a newly built C. artedi linkage map to look for islands of genetic divergence among forms and found widespread differentiation across the genome, a pattern indicative of long‐term drift, suggesting that these forms have been reproductively isolated for a substantial amount of time. The results of this study provide valuable information that can be applied to develop well‐informed management strategies and stress the importance of re‐evaluating conservation units with genomic tools to ensure they accurately reflect species diversity.
Rare and unique adaptations to cancer in domesticated species: An untapped resource?
Authors: Thomas Frédéric , Giraudeau Mathieu , Dheilly Nolwenn M. , Gouzerh Flora , Boutry Justine , Beckmann Christa , Biro Peter A. , Hamede Rodrigo , Abadie Jerome , Labrut Sophie , Bieuville Margaux , Misse Dorothée , Bramwell Georgina , Schultz Aaron , Le Loc'h Guillaume , Vincze Orsolya , Roche Benjamin , Renaud François , Russell Tracey , Ujvari Beata 
Published: January 2020

AbstractStrong and ongoing artificial selection in domestic animals has resulted in amazing phenotypic responses that benefit humans, but often at a cost to an animal's health, and problems related to inbreeding depression, including a higher incidence of cancer. Despite high rates of cancer in domesticated species, little attention has been devoted to exploring the hypothesis that persistent artificial selection may also favour the evolution of compensatory anticancer defences. Indeed, there is evidence for effective anti‐cancer defences found in several domesticated species associated with different cancer types. We also suggest that artificial selection can favour the “domestication” of inherited oncogenic mutations in rare instances, retaining those associated to late and/or less aggressive cancers, and that by studying these seemingly rare anticancer adaptations, novel cancer treatments may be found.
Melanoma—Time to fast or time to feast? An interplay between PPARs, metabolism and immunity
Authors: Grabacka Maja , Plonka Przemyslaw M. , Reiss Krzysztof 
Published: January 2020

AbstractDevelopment and progression of melanoma can be accelerated by intensification of particular metabolic pathways, such as aerobic glycolysis and avid amino acid catabolism, and is accompanied by aberrant immune responses within the tumor microenvironment. Contrary to other cancer types, melanoma reveals some unique tissue‐specific features, such as melanogenesis, which is intertwined with metabolism. Nuclear peroxisome proliferator‐activated receptors (PPARs) take part in regulation of systemic and cellular metabolism, inflammation and melanogenesis. They appear as a focal regulatory point for these three distinct processes by occupying the intersection among AMP‐dependent protein kinase (AMPK), mammalian target of rapamycin (mTOR) and PPAR gamma coactivator 1‐alpha (PGC‐1α) signalling pathways. When deregulated, they may accelerate melanoma malignant growth. Presenting the contribution of PPARα and PPARγ in melanoma biology, we attempt to ask how two contrasting metabolic states: obesity and fasting, can change progression of the disease and possible outcome of the treatment. This short essay is aimed to provoke a discussion about some practical implications for melanoma prevention and treatment, especially: how metabolic manipulation may be exploited to overcome immunosuppression and support immune checkpoint blockade efficacy.
Disentangling the potential effects of land‐use and climate change on stream conditions
Authors: Maloney Kelly O. , Krause Kevin P. , Buchanan Claire , Hay Lauren E. , McCabe Gregory J. , Smith Zachary M. , Sohl Terry L. , Young John A. 
Published: January 2020

AbstractLand‐use and climate change are significantly affecting stream ecosystems, yet understanding of their long‐term impacts is hindered by the few studies that have simultaneously investigated their interaction and high variability among future projections. We modeled possible effects of a suite of 2030, 2060, and 2090 land‐use and climate scenarios on the condition of 70,772 small streams in the Chesapeake Bay watershed, United States. The Chesapeake Basin‐wide Index of Biotic Integrity, a benthic macroinvertebrate multimetric index, was used to represent stream condition. Land‐use scenarios included four Special Report on Emissions Scenarios (A1B, A2, B1, and B2) representing a range of potential landscape futures. Future climate scenarios included quartiles of future climate changes from downscaled Coupled Model Intercomparison Project ‐ Phase 5 (CMIP5) and a watershed‐wide uniform scenario (Lynch2016). We employed random forests analysis to model individual and combined effects of land‐use and climate change on stream conditions. Individual scenarios suggest that by 2090, watershed‐wide conditions may exhibit anywhere from large degradations (e.g., scenarios A1B, A2, and the CMIP5 25th percentile) to small degradations (e.g., scenarios B1, B2, and Lynch2016). Combined land‐use and climate change scenarios highlighted their interaction and predicted, by 2090, watershed‐wide degradation in 16.2% (A2 CMIP5 25th percentile) to 1.0% (B2 Lynch2016) of stream kilometers. A goal for the Chesapeake Bay watershed is to restore 10% of stream kilometers over a 2008 baseline; our results suggest meeting and sustaining this goal until 2090 may require improvement in 11.0%–26.2% of stream kilometers, dependent on land‐use and climate scenario. These results highlight inherent variability among scenarios and the resultant uncertainty of predicted conditions, which reinforces the need to incorporate multiple scenarios of both land‐use (e.g., development, agriculture, etc.) and climate change in future studies to encapsulate the range of potential future conditions.
Modeling and empirical validation of long‐term carbon sequestration in forests (France, 1850–2015)
Authors: Le Noë Julia , Matej Sarah , Magerl Andreas , Bhan Manan , Erb Karl‐Heinz , Gingrich Simone 
Published: January 2020

AbstractThe development of appropriate tools to quantify long‐term carbon (C) budgets following forest transitions, that is, shifts from deforestation to afforestation, and to identify their drivers are key issues for forging sustainable land‐based climate‐change mitigation strategies. Here, we develop a new modeling approach, CRAFT (CaRbon Accumulation in ForesTs) based on widely available input data to study the C dynamics in French forests at the regional scale from 1850 to 2015. The model is composed of two interconnected modules which integrate biomass stocks and flows (Module 1) with litter and soil organic C (Module 2) and build upon previously established coupled climate‐vegetation models. Our model allows to develop a comprehensive understanding of forest C dynamics by systematically depicting the integrated impact of environmental changes and land use. Model outputs were compared to empirical data of C stocks in forest biomass and soils, available for recent decades from inventories, and to a long‐term simulation using a bookkeeping model. The CRAFT model reliably simulates the C dynamics during France's forest transition and reproduces C‐fluxes and stocks reported in the forest and soil inventories, in contrast to a widely used bookkeeping model which strictly only depicts C‐fluxes due to wood extraction. Model results show that like in several other industrialized countries, a sharp increase in forest biomass and SOC stocks resulted from forest area expansion and, especially after 1960, from tree growth resulting in vegetation thickening (on average 7.8 Mt C/year over the whole period). The difference between the bookkeeping model, 0.3 Mt C/year in 1850 and 21 Mt C/year in 2015, can be attributed to environmental and land management changes. The CRAFT model opens new grounds for better quantifying long‐term forest C dynamics and investigating the relative effects of land use, land management, and environmental change.
Modeled spatial assessment of biomass productivity and technical potential ofMiscanthus × giganteus,Panicum virgatumL., andJatrophaon marginal land in China
Authors: Zhang Bingquan , Hastings Astley , Clifton‐Brown John C. , Jiang Dong , Faaij André P. C. 
Published: January 2020

AbstractThis article identifies marginal land technically available for the production of energy crops in China, compares three models of yield prediction forMiscanthus × giganteus,Panicum virgatumL.(switchgrass), andJatropha, and estimates their spatially specific yields and technical potential for 2017. Geographic Information System (GIS) analysis of land use maps estimated that 185 Mha of marginal land was technically available for energy crops in China without using areas currently used for food production. Modeled yields were projected forMiscanthus × giganteus, a GIS‐based Environmental Policy Integrated Climate model for switchgrass and Global Agro‐Ecological Zone model forJatropha. GIS analysis and MiscanFor estimated more than 120 Mha marginal land was technically available forMiscanthuswith a total potential of 1,761 dry weight metric million tonne (DW Mt)/year. A total of 284 DW Mt/year of switchgrass could be obtained from 30 Mha marginal land, with an average yield of 9.5 DW t ha−1 year−1. More than 35 Mha marginal land was technically available forJatropha, delivering 9.7 Mt/year ofJatrophaseed. The total technical potential from available marginal land was calculated as 31.7 EJ/year forMiscanthus, 5.1 EJ/year for switchgrass, and 0.13 EJ/year forJatropha. A total technical bioenergy potential of 34.4 EJ/year was calculated by identifying best suited crop for each 1 km2grid cell based on the highest energy value among the three crops. The results indicate that the technical potential per hectare ofJatrophais unable to compete with that of the other two crops in each grid cell. This modeling study provides planners with spatial overviews that demonstrate the potential of these crops and where biomass production could be potentially distributed in China which needs field trials to test model assumptions and build experience necessary to translate into practicality.
Coining the Pablo Picasso Syndrome
Authors: Suri Ritika , Ali Ashhar 
Published: January 2020

BackgroundThe Alice in Wonderland Syndrome has been well described in the literature. Along with sensory disturbances, patients notably experience metamorphopsias, or distortions in size (micropsia/macropsia) and distance (teleopsia), particularly of body parts. Some migraineurs, however, report dislocation and disorientation of body parts, which are common features found in paintings of Pablo Picasso.MethodsA 60‐year‐old female with a 20‐year history of chronic migraine presented for evaluation of frequent headaches and visual disturbances. In between her attacks of migraine, she would occasionally notice alterations which she describes as a “Picasso” painting. When looking at people, she would note their ear on top of their head, or their right arm would be short and attached to the face. This would occur 1‐2 times per week and would last 5 to 10 minutes. Inanimate objects, however, would not appear distorted.ResultsThe available literature, including published works and biographies, suggests Picasso did not suffer from migraine. Nonetheless, careful descriptions taken from migraineurs with visual disturbances may uncover features that resemble his paintings, be it dislocation of limbs with hints of cubism, as reported above, or illusory splitting as has been previously reported.ConclusionDislocation or disorientation of body parts as a migraine‐related visual phenomenon is rare and only sparsely reported in the medical literature. Coining of a “Pablo Picasso Syndrome” may better describe this occurrence.
SYSTEMATIC MONETARY POLICY AND THE MACROECONOMIC EFFECTS OF SHIFTS IN RESIDENTIAL LOAN‐TO‐VALUE RATIOS
Authors: Bachmann Rüdiger , Rüth Sebastian K. 
Published: January 2020

AbstractWhat are the macroeconomic consequences of changing aggregate lending standards in residential mortgage markets, as measured by loan‐to‐value (LTV) ratios? Using a structural vector autoregression (VAR), we find that GDP and business investment increase following an expansionary LTV shock. Residential investment, by contrast, falls after a small initial uptick, a result that depends on the systematic reaction of monetary policy. We show that, historically, the Fed tended to respond to expansionary LTV shocks by raising the monetary policy instrument, and, as a result, mortgage rates increased and residential investment declined. House prices are affected in a similar manner.
Clinical performance of automated chemiluminescent methods for anticardiolipin and anti‐β2‐glycoprotein I antibodies detection in a large cohort of Chinese patients with antiphospholipid syndrome
Authors: Wan Li‐yan , Gu Jie‐yu , Liu Ting‐ting , Hu Qiong‐yi , Jia Jin‐chao , Teng Jia‐lin , Sun Yue , Liu Hong‐lei , Cheng Xiao‐bing , Ye Jun‐na , Su Yu‐tong , Wu Xin‐yao , Chi Hui‐hui , Zhou Zhuo‐chao , Wang Zhi‐hong , Zhou Jin‐feng , Norman Gary L. , Dai Jing , Yang Cheng‐de , Shi Hui 
Published: January 2020

AbstractIntroductionTo assess the clinical performance and correlations of automated chemiluminescence assay (CIA) and enzyme‐linked immunosorbent assay (ELISA) for detecting antiphospholipid (aPL) antibodies in the diagnosis of antiphospholipid syndrome (APS).MethodsThe study recruited 505 subjects, including 192 with APS, 193 with connective tissue diseases other than APS, and 120 healthy donors. We measured anticardiolipin (aCL) and anti‐β2‐glycoprotein I (anti‐β2GPI) antibodies IgG, IgM, and IgA in all the samples using both CIA and ELISA.ResultsTotal agreement between the two methods ranged from 83.50% for anti‐β2GPI IgG antibodies to 92.76% for anti‐β2GPI IgM antibodies in all the groups. Anti‐β2GPI and aCL IgG assays showed the highest Spearman's rho coefficients (anti‐β2GPI IgG = 0.742, aCL IgG = 0.715). Anti‐β2GPI IgG CIA showed the highest sensitivity for diagnosis of APS at 80.21%, which was significantly higher than the sensitivity of anti‐β2GPI IgG ELISA (52.08%). For diagnosis of APS, anti‐β2GPI IgG CIA had the best discrimination power with the area under the curves (AUC) of 0.922, followed by aCL IgG CIA (AUC of 0.905). While the CIA AUC was slightly higher in all cases, the difference was not statistically significant.ConclusionCIA measurements had a good agreement and correlation with comparative ELISA assays. The CIA anti‐β2GPI IgG however was significantly more sensitive for APS diagnosis. The two assay methodologies showed comparable predictive powers and support the value of the CIA method for improved diagnosis and management of patients with APS.
Corporate irresponsibility and stock price crash risk
Authors: Zaman Rashid , Bahadar Stephen , Mahmood Haroon 
Published: January 2020

AbstractWe investigate the impact of corporate irresponsibility on future stock price crash by employing a unique dataset of 1,529 penalties imposed on 411 United States (U.S.) firms, from 2003 to 2015. We provide robust evidence that the total amount of penalties (in U.S. dollars) imposed on firms are negatively associated with firm‐specific future stock price crash risk. Our findings are consistent with the following view that imposition of penalties remove uncertainty about a particular firm's future, investors please that the case is closed, the firm successfully manages the aftermath of misconduct and the firm's financial gains are often larger compared to the total cost of the penalty imposed. Moreover, we find corporate social responsibility (CSR) to be a channel through which penalties impact stock price crash risk. Our findings demonstrate that the negative association between monetary penalties and stock price crash risk is more pronounced in the postfinancial crisis and in environmentally sensitive firms.