bluuebunny/crossref_metadata_2025_split huggingface dataset:
VERONICA: Randomized Phase II Study of Fulvestrant and Venetoclax in ER-Positive Metastatic Breast Cancer Post-CDK4/6 Inhibitors – Efficacy, Safety, and Biomarker Results
Authors: Lindeman Geoffrey J. , Fernando Tharu M. , Bowen Rebecca , Jerzak Katarzyna J. , Song Xinni , Decker Thomas , Boyle Frances , McCune Steve , Armstrong Anne , Shannon Catherine , Bertelli Gianfilippo , Chang Ching-Wei , Desai Rupal , Gupta Kushagra , Wilson Timothy R. , Flechais Aulde , Bardia Aditya 
Published: May 2022

Abstract

Purpose:
Despite promising activity in hematopoietic malignancies, efficacy of the B-cell lymphoma 2 (BCL2) inhibitor venetoclax in solid tumors is unknown. We report the prespecified VERONICA primary results, a randomized phase II clinical trial evaluating venetoclax and fulvestrant in estrogen receptor (ER)-positive, HER2-negative metastatic breast cancer, post–cyclin-dependent kinase (CDK) 4/6 inhibitor progression.

Patients and Methods:
Pre-/postmenopausal females ≥18 years were randomized 1:1 to venetoclax (800 mg orally daily) plus fulvestrant (500 mg intramuscular; cycle 1: days 1 and 15; subsequent 28-day cycles: day 1) or fulvestrant alone. The primary endpoint was clinical benefit rate (CBR); secondary endpoints were progression-free survival (PFS), overall survival, and safety. Exploratory biomarker analyses included BCL2 and BCL extra-large (BCLXL) tumor expression, and PIK3CA circulating tumor DNA mutational status.

Results:
At primary analysis (cutoff: August 5, 2020; n = 103), venetoclax did not significantly improve CBR [venetoclax plus fulvestrant: 11.8% (n = 6/51; 95% confidence interval (CI), 4.44–23.87); fulvestrant: 13.7% (7/51; 5.70–26.26); risk difference –1.96% (95% CI, –16.86 to 12.94)]. Median PFS was 2.69 months (95% CI, 1.94–3.71) with venetoclax plus fulvestrant versus 1.94 months (1.84–3.55) with fulvestrant (stratified HR, 0.94; 95% CI, 0.61–1.45; P = 0.7853). Overall survival data were not mature. A nonsignificant improvement of CBR and PFS was observed in patients whose tumors had strong BCL2 expression (IHC 3+), a BCL2/BCLXL Histoscore ratio ≥1, or PIK3CA-wild-type status.

Conclusions:
Our findings do not indicate clinical utility for venetoclax plus fulvestrant in endocrine therapy–resistant, CDK4/6 inhibitor–refractory metastatic breast tumors, but suggest possible increased dependence on BCLXL in this setting.
Estimated Yield of Screening for Heterozygous Familial Hypercholesterolemia With and Without Genetic Testing in US Adults
Authors: Bellows Brandon K. , Khera Amit V. , Zhang Yiyi , Ruiz‐Negrón Natalia , Stoddard Henry M. , Wong John B. , Kazi Dhruv S. , de Ferranti Sarah D. , Moran Andrew E. 
Published: May 2022

Background
Heterozygous familial hypercholesterolemia (FH) is a common genetic disorder causing premature cardiovascular disease. Despite this, there is no national screening program in the United States to identify individuals with FH or likely pathogenic FH genetic variants.

Methods and Results
The clinical characteristics and FH variant status of 49 738 UK Biobank participants were used to develop a regression model to predict the probability of having any FH variants. The regression model and modified Dutch Lipid Clinic Network criteria were applied to 39 790 adult participants (aged ≥20 years) in the National Health and Nutrition Examination Survey to estimate the yield of FH screening programs using Dutch Lipid Clinic Network clinical criteria alone (excluding genetic variant status), genetic testing alone, or combining clinical criteria with genetic testing. The regression model accurately predicted FH variant status in UK Biobank participants (observed prevalence, 0.27%; predicted, 0.26%; area under the receiver‐operator characteristic curve, 0.88). In the National Health and Nutrition Examination Survey, the estimated yield per 1000 individuals screened (95% CI) was 3.7 (3.0–4.6) FH cases with the Dutch Lipid Clinic Network clinical criteria alone, 3.8 (2.7–5.1) cases with genetic testing alone, and 6.6 (5.3–8.0) cases by combining clinical criteria with genetic testing. In young adults aged 20 to 39 years, using clinical criteria alone was estimated to yield 1.3 (95% CI, 0.6–2.5) FH cases per 1000 individuals screened, which was estimated to increase to 4.2 (95% CI, 2.6–6.4) FH cases when combining clinical criteria with genetic testing.

Conclusions
Screening for FH using a combination of clinical criteria with genetic testing may increase identification and the opportunity for early treatment of individuals with FH.
From Dynamics to Novelty: An Agent-Based Model of the Economic System
Authors: Recio Gustavo , Banzhaf Wolfgang , White Roger 
Published: May 2022

Abstract
The modern economy is both a complex self-organizing system and an innovative, evolving one. Contemporary theory, however, treats it essentially as a static equilibrium system. Here we propose a formal framework to capture its complex, evolving nature. We develop an agent-based model of an economic system in which firms interact with each other and with consumers through market transactions. Production functions are represented by a pair of von Neumann technology matrices, and firms implement production plans taking into account current price levels for their inputs and output. Prices are determined by the relation between aggregate demand and supply. In the absence of exogenous perturbations the system fluctuates around its equilibrium state. New firms are introduced when profits are above normal, and are ultimately eliminated when losses persist. The varying number of firms represents a recurrent perturbation. The system thus exhibits dynamics at two levels: the dynamics of prices and output, and the dynamics of system size. The model aims to be realistic in its fundamental structure, but is kept simple in order to be computationally efficient. The ultimate aim is to use it as a platform for modeling the structural evolution of an economic system. Currently the model includes one form of structural evolution, the ability to generate new technologies and new products.
The Late-Eighteenth-Century Climate of Cape Town, South Africa, Based on the Dutch East India Company “Day Registers” (1773–91)
Authors: Grab Stefan , Williams Mark 
Published: May 2022

Abstract
We introduce the Dutch East India Company “day registers” as one of the world’s longest known pre-nineteenth-century corporate chronicles (1652–1791) containing near-continuous, systematic, noninstrumental daily weather information for Cape Town, South Africa. This transcript provides the longest-known continuous seventeenth- to eighteenth-century daily weather record for Africa and the Southern Hemisphere. An 18-yr (1773–91) climate chronology from this record is presented, thus providing unique insight to the late-eighteenth-century climate of Cape Town. Extraction of daily weather information for basic statistical analysis includes precipitation, wind, sky conditions, and accounts of storms, drought, and floods. From this, we provide monthly and annual number of rain days, a rain index (relative rainfall amount), hot and cold days, and occurrence of storm-strength winds. Results show extreme weather and climate variability in Cape Town during the mid- to late 1780s.
Intraseasonal Melting of Northern Barents Sea Ice Forced by Circumpolar Clockwise-Propagating Atmospheric Waves during Early Summer
Authors: Yang Jing , Li Siyu , Zhu Tao , Qi Xin , Liu Jiping , Kim Seong-Joong , Gong Daoyi 
Published: May 2022

Abstract
Arctic sea ice intraseasonal variation (ISV) is crucial for understanding and predicting atmospheric subseasonal variations over the middle and high latitudes but unclear. Sea ice concentration (SIC) over the northern Barents Sea (NBS) features large ISV during the melting season (April–July). Based on the observed SIC, this study finds that the NBS SIC ISV in the melting season is dominated by 30–60-day periodicity. The composite analysis, using 34 significant 30–60-day sea ice melting events during 1989–2017, demonstrates that 30–60-day circumpolar clockwise-propagating atmospheric waves (CCPW) are concurrent with the NBS SIC ISV, which features zonal wavenumber 1 along 65°N and a typical quasi-barotropic structure. Further analysis finds that the 30–60-day surface air temperature (SAT) evidently leads the SIC variations by nearly 6 days over the NBS, which is primarily caused by low-level meridional thermal advection linked with the 30–60-day CCPW. The positive anomalies of the downward sensible heat and longwave radiative fluxes, caused by the increased SAT and atmospheric moisture, play the dominant roles in melting the sea ice on the 30–60-day time scale over the NBS. The increased atmospheric moisture is mainly ascribed to the increased horizontal moisture advection influence by the 30–60-day CCPW. This study strongly suggests that the atmospheric ISV is a crucial precursor for NBS sea ice intraseasonal changes in boreal summer, and more accurate subseasonal predictions of atmospheric circulation, temperature, and moisture are indispensable for improving sea ice subseasonal prediction over the Arctic region.

Significance Statement
Northern Barents Sea (NBS) sea ice intraseasonal variation (ISV) is crucial for understanding mid- to high-latitude climate variations as well as new trans-Arctic shipping predictions but lacks solid knowledge. This study found that the 30–60-day variation is the dominant ISV periodicity of NBS sea ice change during summer, which is essentially modulated by circumpolar clockwise-propagating atmospheric waves. The atmospheric wave-induced meridional thermal advection modulates the surface temperature and atmospheric moisture, causes the changes of downward sensible heat and longwave radiative fluxes, and eventually dominantly regulates the 30–60-day sea ice variations. The mechanism of sea ice ISV strongly suggests that accurately predicting the atmospheric fields is indispensable for obtaining more accurate sea ice subseasonal prediction.
The British–Okhotsk Corridor Pattern and Its Linkage to the Silk Road Pattern
Authors: Xu Peiqiang , Wang Lin , Dong Zizhen , Li Yanjie , Shen Xiaocen , Chen Wen 
Published: May 2022

Abstract
Based on observation and reanalysis datasets, numerical experiments with a simple dynamical model, and climate model outputs, this study investigates the second leading waveguide teleconnection along the summer polar front jet (PFJ) over Eurasia on the interannual time scale, the British–Okhotsk Corridor (BOC) pattern. The BOC pattern explains 20.8% of the total variance over northern Eurasia, which is only slightly lower than the first leading teleconnection, the British–Baikal Corridor pattern. It consists of four zonally oriented action centers over the British Isles, western Russia, northern Siberia, and the Sea of Okhotsk. It is primarily confined to northern Eurasia and leads to wavelike temperature and precipitation anomalies along its routine. Besides, it is occasionally coupled to the dominant waveguide teleconnection along the subtropical jet (STJ), the Silk Road pattern (SRP). A bifurcated wavelike pattern appears over Eurasia when the coupling is strong, with two branches of waves over the PFJ and the STJ, respectively. The fluctuations of the BOC–SRP linkage play a profound role in shaping the dominant climate variability modes over Eurasia. Numerical experiments with a simple dynamical model suggest that the basic flow cannot directly influence the BOC–SRP linkage by affecting the propagation condition of Rossby waves. Nevertheless, the basic flow can indirectly influence the linkage by changing the exciting locations of the BOC pattern through modulating the wave–mean flow interaction at the exit of the Atlantic jet stream. The climate model INMCM4.0 can reproduce the observed BOC–SRP linkage and its time-varying characteristics, supporting the observation and the proposed mechanism.

Significance Statement
Over Eurasia, extreme summer weather events are often related to long-lasting stagnant atmospheric circulation anomalies in the upper troposphere, which can be well determined by a few recurring modes called atmospheric teleconnections. Atmospheric teleconnections over Eurasia usually propagate along the subtropical jet (STJ) and the polar front jet (PFJ). Although the teleconnections along the STJ have been well understood, the teleconnections along the PFJ are currently not fully understood. This paper investigates the British–Okhotsk Corridor (BOC) pattern, a newly defined major summer teleconnection along the PFJ. The BOC pattern can be occasionally coupled to a dominant teleconnection along the STJ. Fluctuations of this linkage play a profound role in shaping the dominant surface climate variability modes over Eurasia. Observation and reanalysis datasets, numerical experiments with a simple dynamical model, and climate model output are used to understand this linkage in the study.
Wind Drift in a Homogeneous Equilibrium Sea
Authors: Samelson R. M. 
Published: May 2022

Abstract
A simple dynamical model is proposed for the near-surface drift current in a homogeneous, equilibrium sea. The momentum balance is formulated for a mass-weighted mean in curvilinear surface-conforming coordinates. Stokes drifts computed analytically for small wave slopes by this approach for inviscid linear sinusoidal and Pollard–Gerstner waves agree with the corresponding Lagrangian means, consistent with a mean momentum balance that determines mean parcel motion. A wave-modified mixing length model is proposed, with a depth-dependent eddy viscosity that depends on an effective ocean surface roughness length z0o, distinct from the atmospheric bulk-flux roughness length z0a, and an additional wave-correction factor ϕw. Kinematic Stokes drift profiles are computed for two sets of quasi-equilibrium sea states and are interpreted as mean wind drift profiles to provide calibration references for the model. A third calibration reference, for surface drift only, is provided by the traditional 3%-of-wind rule. For 10-m neutral wind U10N ≤ 20 m s−1, the empirical z0o ranges from 10−4 to 10 m, while ϕw ranges from 1.0 to 0.1. The model profiles show a shallow log-layer structure at the smaller wind speeds and a nearly uniform near-surface shear at the larger wind speeds. Surface velocities are oriented 10°–20° from downwind for U10N ≤ 10 m s−1 and 20°–35° from downwind for 10 ≤ U10N ≤ 20 m s−1. A small correction to the drag coefficient is implied. The model predictions show a basic consistency with several sets of previously published near-surface current measurements, but the comparison is not definitive.
Development of New Observation Operators for Assimilating GOES-R Geostationary Lightning Mapper Flash Extent Density Data Using GSI EnKF: Tests with Two Convective Events over the United States
Authors: Kong Rong , Xue Ming , Liu Chengsi , Fierro Alexandre O. , Mansell Edward R. 
Published: May 2022

Abstract
In a prior study, GOES-R Geostationary Lightning Mapper (GLM) flash extent density (FED) data were assimilated using ensemble Kalman filter into a convection-allowing model for a mesoscale convective system (MCS) and a supercell storm. The FED observation operator based on a linear relation with column graupel mass was tuned by multiplying a factor to avoid large FED forecast bias. In this study, new observation operators are developed by fitting a third-order polynomial to GLM FED observations and the corresponding FED forecasts of graupel mass of the MCS and/or supercell cases. The new operators are used to assimilate the FED data for both cases, in three sets of experiments called MCSFit, SupercellFit, and CombinedFit, and their performances are compared with the prior results using the linear operator and with a reference simulation assimilating no FED data. The new nonlinear operators reduce the frequency biases (root-mean-square innovations) in the 0–4-h forecasts of the FED (radar reflectivity) relative to the results using the linear operator for both storm cases. The operator obtained by fitting data from the same case performs slightly better than fitting to data from the other case, while the operator obtained by fitting forecasts of both cases produce intermediate but still very similar results, and the latter is considered more general. In practice, a more general operator can be developed by fitting data from more cases.

Significance Statement
Prior studies found that assimilation of satellite lightning observation can benefit storm forecasts for up to 4 h. A linear lightning observation operator originally developed for assimilating pseudo-satellite lightning observations was tuned earlier through sensitivity experiments when assimilating real lightning data. However, the linear relation does not fit the model and observational data well and significant bias can exist. This study develops new lightning observation operators by fitting a high-order polynomial to satellite lightning observations and model-predicted quantities that directly relate to lightning. The new operator was found to reduce the frequency biases and root-mean-square innovations for lightning and radar reflectivity forecasts, respectively, up to several hours relative to the linear operator. The methodology can be applied to larger data samples to obtain a more general operator for use in operational data assimilation systems.
Adolescent Trauma During the COVID Pandemic: Just Like Adults, Children, or Someone Else?
Authors: Ruhi-Williams Perisa , Yeates Eric O. , Grigorian Areg , Schellenberg Morgan , Owattanapanich Natthida , Barmparas Galinos , Margulies Daniel , Juillard Catherine , Garber Kent , Cryer Henry , Tillou Areti , Burruss Sigrid , Penaloza-Villalobos Liz , Lin Ann , Figueras Ryan Arthur , Coimbra Raul , Brenner Megan , Costantini Todd , Santorelli Jarrett , Curry Terry , Wintz Diane , Biffl Walter L. , Schaffer Kathryn B. , Duncan Thomas K. , Barbaro Casey , Diaz Graal , Johnson Arianne , Chinn Justine , Naaseh Ariana , Leung Amanda , Grabar Christina , Nahmias Jeffry 
Published: May 2022

COVID-19 stay-at-home (SAH) orders were impactful on adolescence, when social interactions affect development. This has the potential to change adolescent trauma. A post-hoc multicenter retrospective analysis of adolescent (13-17 years-old) trauma patients (ATPs) at 11 trauma centers was performed. Patients were divided into 3 groups based on injury date: historical control (CONTROL:3/19/2019-6/30/2019, before SAH (PRE:1/1/2020-3/18/2020), and after SAH (POST:3/19/2020-6/30/2020). The POST group was compared to both PRE and CONTROL groups in separate analyses. 726 ATPs were identified across the 3 time periods. POST had a similar penetrating trauma rate compared to both PRE (15.8% vs 13.8%, P = .56) and CONTROL (15.8% vs 14.5%, P = .69). POST also had a similar rate of suicide attempts compared to both PRE (1.2% vs 1.5%, P = .83) and CONTROL (1.2% vs 2.1%, P = .43). However, POST had a higher rate of drug positivity compared to CONTROL (28.6% vs 20.6%, P = .032), but was similar in all other comparisons of alcohol and drugs to PRE and POST periods (all P > .05). Hence ATPs were affected differently than adults and children, as they had a similar rate of penetrating trauma, suicide attempts, and alcohol positivity after SAH orders. However, they had increased drug positivity compared to the CONTROL, but not PRE group.
Postoperative Outcomes in the Plain Community Population of Western Wisconsin
Authors: Seiler Rachel L. , Kallies Kara J. , Borgert Andrew J. , Reetz Scott R. , Jarman Benjamin T. 
Published: May 2022

Background Residents of plain communities constitute an underserved minority population that is not reliably captured in contemporary surgical outcomes research. We hypothesized that plain communities (PC) patients would have higher postoperative complication rates than a general surgical population. Methods A retrospective review of 30-day postoperative outcomes for PC patients compared to a majority (non-PC) matched patient population from September 2014 to March 2020 was performed. The primary outcome measure was any complication within 30 days of surgery. Results 270 PC patients were matched with 493 non-PC patients. The 30-day complication rate was higher for the PC group (6.3% vs 3.7%, P = .09), though not statistically significant. There was significantly lower utilization of preventive care services, and postoperative follow-up among PC patients. Discussion Although our regional PC surgical patient population utilized preventive and postoperative health care services less than the non-PC population, there was no statistically significant difference in overall 30-day postoperative morbidity or mortality.
Association of Postoperative Dieting, Exercise, Dietitian, and Surgeon Follow up With Bariatric Surgery Outcomes
Authors: Samaan Jamil S. , Srinivasan Nitin , Mirocha James , Premkumar Agnes , Toubat Omar , Qian Elaine , Subramanyam Chaitra , Malik Yousaf , Lee Nayun , Sandhu Kulmeet , Dobrowolsky Adrian , Samakar Kamran 
Published: May 2022

Although postoperative diet modification, exercise, and regular dietitian and surgeon follow-up are often recommended after bariatric surgery (BS), their impact on weight loss is unclear. A Retrospective chart review was conducted for patients who received sleeve gastrectomy or Roux-en-Y gastric bypass (RYGB) between August 2000 and November 2017 with telephone follow-up. Multivariable logistic regression models were used for analyses. There were 514 patients included in our study. Most were female (76.3%), mean age was 46.9 years (Standard Deviation [SD] = 11.8), and mean weight loss was 11.6 (SD = 6.5) BMI points at a mean follow-up of 7 years (SD = 4.3). Current surgeon follow-up OR = 2.08 (P < .01) was positively associated with postoperative weight loss, while current dietitian follow-up=OR .41 (P < .01) was negatively associated. Current weight loss supplement use OR = .45 (P = .03) was associated with reduced willingness to undergo surgery again. Increasing preoperative BMI OR = 1.06 (P = .04) and increasing age OR = 1.04 (P = .02) were associated with improved quality of life (QoL) due to BS. Lack of surgeon follow-up and regular dietician consultation was associated with suboptimal weight loss after BS. Older age was positively associated with improved QoL, while current weight loss supplement use was associated with lower likelihood of undergoing surgery again, both independent of weight loss.