bluuebunny/crossref_metadata_2025_split huggingface dataset:
First-in-Human Phase I Study of ABBV-085, an Antibody–Drug Conjugate Targeting LRRC15, in Sarcomas and Other Advanced Solid Tumors
Authors: Demetri George D. , Luke Jason J. , Hollebecque Antoine , Powderly John D. , Spira Alexander I. , Subbiah Vivek , Naumovski Louie , Chen Chris , Fang Hua , Lai Dominic W. , Yue Huibin , Polepally Akshanth R. , Purcell James W. , Robinson Randy , Sharma Padmanee , Allison James P. , Tolcher Anthony , Villalobos Victor M. 
Published: April 2021

AbstractPurpose:Leucine-rich repeat containing 15 (LRRC15) is expressed on stromal fibroblasts in the tumor microenvironment of multiple solid tumor types and may represent an interesting target for therapy, particularly in patients with sarcomas where LRRC15 is also expressed by malignant cells. ABBV-085 is a monomethyl auristatin-E antibody–drug conjugate that targets LRRC15 and showed antineoplastic efficacy in preclinical experiments. Herein, we report findings of ABBV-085 monotherapy or combination therapy in adult patients with sarcomas and other advanced solid tumors.Patients and Methods:This first-in-human phase I study (NCT02565758) assessed ABBV-085 safety, pharmacokinetics/pharmacodynamics, and preliminary antitumor activity. The study consisted of two parts: dose escalation and dose expansion. ABBV-085 was administered by intravenous infusion at 0.3 to 6.0 mg/kg every 14 days.Results:In total, 85 patients were enrolled; 45 patients received the recommended expansion dose of 3.6 mg/kg ABBV-085 monotherapy, including 10 with osteosarcoma and 10 with undifferentiated pleomorphic sarcoma (UPS). Most common treatment-related adverse events were fatigue, nausea, and decreased appetite. The overall response rate for patients with osteosarcoma/UPS treated at 3.6 mg/kg was 20%, including four confirmed partial responses. No monotherapy responses were observed for other advanced cancers treated at 3.6 mg/kg. One patient treated with ABBV-085 plus gemcitabine achieved partial response.Conclusions:ABBV-085 appeared safe and tolerable at a dose of 3.6 mg/kg every 14 days, with preliminary antitumor activity noted in patients with osteosarcoma and UPS. Given the high unmet need in these orphan malignancies, further investigation into targeting LRRC15 in these sarcomas may be warranted.
Lipid Testing, Lipid-Modifying Therapy, and PCSK9 (Proprotein Convertase Subtilisin-Kexin Type 9) Inhibitor Eligibility in 27 979 Patients With Incident Acute Coronary Syndrome
Authors: Sarak Bradley , Savu Anamaria , Kaul Padma , McAlister Finlay A. , Welsh Robert C. , Yan Andrew T. , Goodman Shaun G. 
Published: April 2021

Background:
While registry-based studies have shown that as many as 1 in 2 patients with stable atherosclerotic cardiovascular disease would be eligible for PCSK9i (proprotein convertase subtilisin-kexin type 9 inhibitor) therapy, this has not been studied in a large population-based postacute coronary syndrome (ACS) cohort.

Methods:
We examined lipid testing performed in hospital or within 90 days of discharge and lipid-lowering therapies dispensed within 90 days of discharge in patients surviving for at least 1 year after their first ACS between 2012 and 2018 in the province of Alberta, Canada. We estimated the proportion of patients eligible for PCSK9i and the expected benefits of treatment.

Results:

Of the 27 979 patients (median age 64.0 years, 29.3% female, 28.0% diabetic), 3750 (13.4%) did not have lipid testing in-hospital or within 90 days postdischarge. Untested patients were more likely to be older, female, from rural areas, to have more comorbidities, to already be on cardioprotective therapies, to present with unstable angina, and were less likely to have invasive interventions (all
P
<0.0001). Of the 24 229 tested, 18 767 (77.5%) had at least one lipid value above guideline-recommended threshold (LDL [low-density lipoprotein] ≥1.8 mmol/L [70 mg/dL] and non-HDL [high-density lipoprotein] ≥2.6 mmol/L [100 mg/dL]), of which 7284 (38.8%) did not have repeat testing within the year after discharge. Lipid testing in hospital was associated with higher rates of initiation or escalation of statin therapy within 90 days of their ACS (adjusted odds ratio, 2.13 [95% CI, 1.97–2.30). In total, 9592 patients (39.6% of the tested cohort) would be eligible for PCSK9i use, which could result in 184 fewer cardiovascular events over 3.4 years, including cardiovascular death, nonfatal ACS (myocardial infarction or unstable angina requiring hospitalization), and ischemic stroke.

Conclusions:
Within 90 days of incident ACS, ≈80% of patients did not meet guideline-recommended lipid thresholds and more than one-third would potentially be eligible for PCSK9i.
Trends of Coronary Artery Bypass Grafting Performance in a Cohort of Hospitals in China Between 2013 and 2018
Authors: Li Xi , Gu Dachuan , Wang Xianqiang , Diao Xiaolin , Chen Sipeng , Ma Hanping , Zhang Heng , Zhao Yan , Zheng Zhe 
Published: April 2021

Background:
China has witnessed a rapid increase in the volume of coronary artery bypass grafting (CABG) but substantial gaps in the performance for CABG across the nation. The present study aimed to investigate the change in CABG performance after years of quality improvement measures in a national registry in China.

Methods:
The study included 66 971 patients who underwent isolated CABG in a cohort of 74 tertiary hospitals in China between January 2013 and December 2018. Data were collected from the Chinese Cardiac Surgery Registry. Outcomes were in-hospital mortality and postoperative length of stay. Five process measures for surgical technique and secondary prevention were also analyzed. We described the changes in the overall performance and interhospital heterogeneity across the years.

Results:

The in-hospital mortality declined from 0.9% in 2013 to 0.6 in 2018, with a risk-adjusted odds ratio of 0.66 (95% CI, 0.46–0.93;
P
<0.001). The standard mean difference for risk-standardized mortality rate between hospitals in the lowest and highest quartile narrowed from 1.63 in 2013 to 1.35 in 2018. The median (interquartile range) hospital-level rate of using arterial graft increased from 93.9% (86.0%–97.8%) to 94.6% (83.3%–99.2%), but the difference was not statistically significant. Meanwhile, the rate of free from blood transfusion increased from 17.0% (2.6%–32.0%) to 34.1% (8.8%–52.9%). The hospital-level rate of prescribing β-blockers at discharge significantly increased from 82.8% (66.7%–90.3%) to 91.1% (82.1%–97.1%), statin from 75.8% (55.7%–88.9%) to 88.9% (75.0%–96.0%), and aspirin from 90.3% (83.9%–95.2%) to 95.3% (88.9%–98.1%).

Conclusions:
In the Chinese Cardiac Surgery Registry, there were notable improvements in the treatment process related to CABG and decline of in-hospital mortality with reduced interhospital heterogeneity.
Multistability and Rare Spontaneous Transitions in Barotropic β-Plane Turbulence
Authors: Simonnet Eric , Rolland Joran , Bouchet Freddy 
Published: April 2021

AbstractWe demonstrate that turbulent zonal jets, analogous to Jovian ones, which are quasi stationary, are actually metastable. After extremely long times, they randomly switch to new configurations with a different number of jets. The genericity of this phenomenon suggests that most quasi-stationary turbulent planetary atmospheres might have many climates and attractors for fixed values of the external forcing parameters. A key message is that this situation will usually not be detected by simply running the numerical models, because of the extremely long mean transition time to change from one climate to another. To study such phenomena, we need to use specific tools: rare-event algorithms and large-deviation theory. With these tools, we make a full statistical mechanics study of a classical barotropic beta-plane quasigeostrophic model. It exhibits robust bimodality with abrupt transitions. We show that new jets spontaneously nucleate from westward jets. The numerically computed mean transition time is consistent with an Arrhenius law showing an exponential decrease of the probability as the Ekman dissipation decreases. This phenomenology is controlled by rare noise-driven paths called instantons. Moreover, we compute the saddles of the corresponding effective dynamics. For the dynamics of states with three alternating jets, we uncover an unexpectedly rich dynamics governed by the symmetric group of permutations, with two distinct families of instantons, which is a surprise for a system where everything seemed stationary in the hundreds of previous simulations of this model. We discuss the future generalization of our approach to more realistic models.
On the Momentum Flux of Vertically-Propagating Orographic Gravity Waves Excited in Nonhydrostatic Flow over Three-dimensional Orography
Authors: Xu Xin , Li Runqiu , Teixeira Miguel A. C. , Lu Yixiong 
Published: April 2021

AbstractThis work studies nonhydrostatic effects (NHE) on the momentum flux of orographic gravity waves (OGWs) forced by isolated three-dimensional orography. Based on linear wave theory, an asymptotic expression for low horizonal Froude number ( where (U, V) is the mean horizontal wind, γ and a are the orography anisotropy and half-width and N is the buoyancy frequency) is derived for the gravity wave momentum flux (GWMF) of vertically-propagating waves. According to this asymptotic solution, which is quite accurate for any value of Fr, NHE can be divided into two terms (NHE1 and NHE2). The first term contains the high-frequency parts of the wave spectrum that are often mistaken as hydrostatic waves, and only depends on Fr. The second term arises from the difference between the dispersion relationships of hydrostatic and nonhydrostatic OGWs. Having an additional dependency on the horizontal wind direction and orography anisotropy, this term can change the GWMF direction. Examination of NHE for OGWs forced by both circular and elliptical orography reveals that the GWMF is reduced as Fr increases, at a faster rate than for two-dimensional OGWs forced by a ridge. At low Fr, the GWMF reduction is mostly attributed to the NHE2 term, whereas the NHE1 term starts to dominate above about Fr = 0.4. The behavior of NHE is mainly determined by Fr, while horizontal wind direction and orography anisotropy play a minor role. Implications of the asymptotic GWMF expression for the parameterization of nonhydrostatic OGWs in high-resolution and/or variable-resolution models are discussed.
Relationship between Boreal Summer Circulation Trend and Destructive Stationary–Transient Wave Interference in the Western Hemisphere
Authors: Kim Dong Wan , Lee Sukyoung 
Published: April 2021

AbstractThis study examines the role of the latent heating in exciting the upper-level circulation anomaly, which destructively interferes with the climatological stationary wave in the Western Hemisphere during boreal summer. This destructive interference pattern closely resembles the circulation trend that is known to be responsible for surface heat extreme trends. To investigate the mechanism behind this circulation anomaly, daily stationary–transient wave interference and related meteorological variables are analyzed using reanalysis data for the period of 1979–2017. Numerical model simulations forced by reanalysis heating anomalies indicate that the destructive interference pattern is most effectively excited by latent heating anomalies over the North Pacific Ocean and eastern Canada. The North Pacific heating anomaly drives circulation anomalies that not only resemble the destructive interference pattern, but also transport moisture into eastern Canada. The resulting latent heating over eastern Canada drives circulation that further reinforces the destructive interference pattern, which includes a prominent high pressure system over Greenland. Tropical heating also plays a role in driving the destructive interference pattern. On intraseasonal time scales, the destructive interference pattern is preceded by suppressed Indo–western Pacific heating and enhanced North American monsoon heating. On decadal time scales, both heating centers have strengthened, but the trend of the North American monsoon heating was greater than that of the Indo–western Pacific heating. These uneven heating trends help to explain the resemblance between the destructive interference pattern and the circulation trend over the Western Hemisphere.
A single column simulation-based decomposition of the tropical upper tropospheric warming
Authors: Wang Yuwei , Huang Yi 
Published: April 2021

AbstractAn atmospheric global climate model (GCM) and its associated single-column model are used to study the tropical upper tropospheric warming and elucidate how different processes drive this warming. In this modeling framework, on average the direct radiative process accounts for 13% of the total warming. The radiation increases the atmospheric lapse rate and triggers more convection, which further produces 74% of the total warming. The rest 13% is attributable to the circulation adjustment. The relative importance of these processes differs in different regions. In the deep tropics, the radiative-convective adjustment produces the most significant warming and accounts for almost 100% of the total warming. In the subtropics, the radiative-convective adjustment accounts for 73% of the total warming and the circulation adjustment plays a more important role than in the deep tropics, especially at the levels above 200 hPa. When the lateral boundary conditions, i.e. the temperature and water vapor advections, are held fixed in single-column simulations, the tropospheric relative humidity significantly increases in the radiative-convective adjustment in response to the surface warming. This result, in contrast to the relative humidity conservation behavior in the GCM, highlights the importance of circulation adjustment in maintaining the constant relative humidity. The tropical upper tropospheric warming in both the full GCM and the single-column simulations is found to be less strong than the warming predicted by reference moist adiabats. This evidences that the sub-moist-adiabat warming occurs even without the dilution effect of the large-scale circulation adjustment.
Atlantic Multidecadal Oscillation Drives Interdecadal Pacific Variability via Tropical Atmospheric Bridge
Authors: An Xiaohe , Wu Bo , Zhou Tianjun , Liu Bo 
Published: April 2021

AbstractThe interdecadal Pacific oscillation (IPO) and Atlantic multidecadal oscillation (AMO), two leading modes of decadal climate variability, are not independent. It was proposed that ENSO-like sea surface temperature (SST) variations play a central role in the Pacific responses to the AMO forcing. However, observational analyses indicate that the AMO-related SST anomalies in the tropical Pacific are far weaker than those in the extratropical North Pacific. Here, we show that SST in the North Pacific is tied to the AMO forcing by convective heating associated with precipitation over the tropical Pacific, instead of by SST there, based on an ensemble of pacemaker experiments with North Atlantic SST restored to the observation in a coupled general circulation model. The AMO modulates precipitation over the equatorial and tropical southwestern Pacific through exciting an anomalous zonal circulation and an interhemispheric asymmetry of net moist static energy input into the atmosphere. The convective heating associated with the precipitation anomalies drives SST variations in the North Pacific through a teleconnection, but it remarkably weakens the ENSO-like SST anomalies through a thermocline damping effect. This study has implications that the IPO is a combined mode generated by both AMO forcing and local air–sea interactions, but the IPO-related global warming acceleration/slowdown is independent of the AMO.
A Statistical Method for Generating Temporally Downscaled Geochemical Tracers in Precipitation
Authors: Finkenbiner Catherine E. , Good Stephen P. , Allen Scott T. , Fiorella Richard P. , Bowen Gabriel J. 
Published: April 2021

AbstractSampling intervals of precipitation geochemistry measurements are often coarser than those required by fine-scale hydrometeorological models. This study presents a statistical method to temporally downscale geochemical tracer signals in precipitation so that they can be used in high-resolution, tracer-enabled applications. In this method, we separated the deterministic component of the time series and the remaining daily stochastic component, which was approximated by a conditional multivariate Gaussian distribution. Specifically, statistics of the stochastic component could be explained from coarser data using a newly identified power-law decay function, which relates data aggregation intervals to changes in tracer concentration variance and correlations with precipitation amounts. These statistics were used within a copula framework to generate synthetic tracer values from the deterministic and stochastic time series components based on daily precipitation amounts. The method was evaluated at 27 sites located worldwide using daily precipitation isotope ratios, which were aggregated in time to provide low resolution testing datasets with known daily values. At each site, the downscaling method was applied on weekly, biweekly and monthly aggregated series to yield an ensemble of daily tracer realizations. Daily tracer concentrations downscaled from a biweekly series had average (+/- standard deviation) absolute errors of 1.69‰ (1.61‰) for δ2H and 0.23‰ (0.24‰) for δ18O relative to observations. The results suggest coarsely sampled precipitation tracers can be accurately downscaled to daily values. This method may be extended to other geochemical tracers in order to generate downscaled datasets needed to drive complex, fine-scale models of hydrometeorological processes.
Validating the Land-Atmosphere Coupling Behavior in Weather and Climate Models Using Observationally-Based Global Products
Authors: Abdolghafoorian Abedeh , Dirmeyer Paul A. 
Published: April 2021

AbstractThe interactions between land and atmosphere (with terrestrial and atmospheric coupling segments) play a significant role in weather and climate. A predominant segment of land-atmosphere (L-A) feedbacks is the coupling between soil moisture (SM) and surface heat fluxes, the terrestrial coupling leg. The lack of high-quality long-term globally distributed observations, however, has hindered a robust, realistic identification of the terrestrial leg strength on a global scale. This exploratory study provides insight into how SM signals are translated into surface flux signals through the construction of a global depiction of the terrestrial leg from several recently developed global, gridded, observationally- and satellite-based data sets. The feasibility of producing global gridded estimates of L-A coupling metrics is explored. Five weather and climate models used for subseasonal to seasonal forecasting are confronted with the observational estimates to discern discrepancies that may affect their ability to predict phenomena related to L-A feedbacks, such as drought or heat waves. The terrestrial feedback leg from observations corroborates the “hot spots” of L-A coupling found in modeling studies, but the variances in daily time series of surface fluxes differ markedly. Better agreement and generally higher confidence are seen in metrics using latent heat flux than sensible heat flux. Observational metrics allow for clear stratification of model fidelity that is consistent across seasons, despite observational uncertainty. The results highlight the impact of SM on partitioning available surface energy and illustrate the potential of global observationally-based data sets for the assessment of such relationships in weather and climate models.
A Nearshore Oceanic Front Induced By Wave Streaming
Authors: Wang Peng , McWilliams James C. , Uchiyama Yusuke 
Published: April 2021

AbstractCoastal fronts impact cross-shelf exchange of materials, such as plankton and nutrients, which are important to the ecosystems in continental shelves. Here using numerical simulation we demonstrate a nearshore front induced by wave streaming. Wave streaming is a bottom Eulerian current along the surface wave direction, and it is caused by the wave bottom dissipation. Wave streaming drives a Lagrangian overturning circulation in the inner shelf and pumps up deep and cold water into the overturning circulation. The water inside the overturning circulation is quickly mixed and cooled because of the wave streaming-enhanced viscosity. However, the offshore water outside the overturning circulation remains stratified and warmer. Hence, a front develops between the water inside and outside the overturning circulation. The front is unstable and generates submesoscale shelf eddies, which lead the offshore transport across the front. This study presents a new mechanism for coastal frontogenesis.
Deep-learning-based precipitation observation quality control
Authors: Sha Yingkai , Gagne David John , West Gregory , Stull Roland 
Published: April 2021

AbstractWe present a novel approach for the automated quality control (QC) of precipitation for a sparse station observation network within the complex terrain of British Columbia, Canada. Our QC approach uses Convolutional Neural Networks (CNNs) to classify bad observation values, incorporating a multi-classifier ensemble to achieve better QC performance. We train CNNs using human QC’d labels from 2016 to 2017 with gridded precipitation and elevation analyses as inputs. Based on the classification evaluation metrics, our QC approach shows reliable and robust performance across different geographical environments (e.g., coastal and inland mountains), with 0.927 Area Under Curve (AUC) and type I/type II error lower than 15%. Based on the saliency-map-based interpretation studies, we explain the success of CNN-based QC by showing that it can capture the precipitation patterns around, and upstream of the station locations. This automated QC approach is an option for eliminating bad observations for various applications, including the pre-processing of training datasets for machine learning. It can be used in conjunction with human QC to improve upon what could be accomplished with either method alone.
A Progress Report on the Development of the High-Resolution Rapid Refresh Ensemble
Authors: Kalina Evan A. , Jankov Isidora , Alcott Trevor , Olson Joseph , Beck Jeffrey , Berner Judith , Dowell David , Alexander Curtis 
Published: April 2021

AbstractThe High-Resolution Rapid Refresh Ensemble (HRRRE) is a 36-member ensemble analysis system with 9 forecast members that utilizes the Advanced Research version of the Weather Research and Forecasting (ARW-WRF) dynamic core and the physics suite from the operational Rapid Refresh/High-Resolution Rapid Refresh deterministic modeling system. A goal of HRRRE development is a system with sufficient spread among members, comparable in magnitude to the random error in the ensemble mean, to represent the range of possible future atmospheric states. HRRRE member diversity has traditionally been obtained by perturbing the initial and lateral boundary conditions of each member, but recent development has focused on implementing stochastic approaches in HRRRE to generate additional spread. These techniques were tested in retrospective experiments and in the May 2019 Hazardous Weather Testbed Spring Experiment (HWT-SE). Results show a 6%–25% increase in the ensemble spread in 2-m temperature, 2-m mixing ratio, and 10-m wind speed when stochastic parameter perturbations are used in HRRRE (HRRRE-SPP). Case studies from HWT-SE demonstrate that HRRRE-SPP performed similar to or better than the operational High-Resolution Ensemble Forecast system, version 2 (HREFv2), and the nonstochastic HRRRE. However, subjective evaluations provided by HWT-SE forecasters indicated that overall, HRRRE-SPP predicted lower probabilities of severe weather (using updraft helicity as a proxy) compared to HREFv2. A statistical analysis of the performance of HRRRE-SPP and HREFv2 from the 2019 summer convective season supports this claim, but also demonstrates that the two systems have similar reliability for prediction of severe weather using updraft helicity.