bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations between socioeconomic deprivation and pharmaceutical prescribing in primary care in England
Authors: Mooney Jessica , Yau Roger , Moiz Haseeb , Kidy Farah , Evans Andrew , Hillman Sarah , Todkill Dan , Shantikumar Saran 
Published: December 2020

AbstractBackgroundSocioeconomic deprivation is associated with health inequality. Previous studies have described associations between primary care prescribing rates and deprivation for individual drugs or drug classes. We explore the correlation between socioeconomic deprivation and the rate of prescribing of individual pharmaceutical drugs, and drug classes, in primary care in England, to identify prescribing inequalities that would require further investigation.MethodsIn this cross-sectional study, national primary care prescribing data, by primary care practice, were retrieved for the calendar year 2019 in England. Socioeconomic deprivation was quantified using the Index of Multiple Deprivation (IMD) score. Correlations were calculated using Spearman's rank correlation coefficient (ρ), adjusting for practice list size and demographics, with a Bonferroni-corrected p value threshold of 5×10−5.ResultsWe included 1.05 billion prescription items dispensed from 6896 England practices. 142/206 (69%) drug classes and 505/774 (65%) drugs were significantly correlated with IMD score (p&lt;5×10−5). Of the 774 included drugs, 31 (4%) were moderately positively associated with IMD score (ρ&gt;0.4). Only one was moderately negatively correlated with IMD score (ρ&lt;−0.4), suggesting higher prescribing rates in more affluent areas. The drug classes most strongly associated with IMD score included opioid and non-opioid analgesics, antipsychotics and reflux medications. Drug classes most strongly associated with affluence included epinephrine, combined oral contraceptives and hormone replacement therapy.ConclusionWe identify novel associations of prescribing with deprivation. Further work is required to identify the underlying reasons for these associations so that appropriate interventions can be formulated to address drivers of inequality.
Predictors of renal damage in systemic lupus erythematous patients: data from a multiethnic, multinational Latin American lupus cohort (GLADEL)
Authors: Reátegui-Sokolova Cristina , Ugarte-Gil Manuel F , Harvey Guillermina B , Wojdyla Daniel , Pons-Estel Guillermo J , Quintana Rosana , Serrano-Morales Rosa M , Sacnun Mónica P , Catoggio Luis J , Soriano Enrique R , García Mercedes A , Saurit Verónica , Alvarellos Alejandro , Caeiro Francisco , Berbotto Guillermo A , Sato Emilia I , Borba Neto Eduardo Ferreira , Bonfa Eloisa , de Oliveira e Silva Montandon Ana Carolina , Da Silva Nilzio A , Cavalcanti Fernando , Vásquez Gloria , Guibert-Toledano Marlene , Reyes-Llerena Gil A , Massardo Loreto , Neira Oscar J , Cardiel Mario H , Barile-Fabris Leonor A , Amigo Mary-Carmen , Silveira Luis H , Portela-Hernández Margarita , Garcia de la Torre Ignacio , Segami María Inés , Chacón-Diaz Rosa , Esteva-Spinetti María H , Alarcón Graciela S , Pons-Estel Bernardo A 
Published: December 2020

AimA decrease in proteinuria has been considered protective from renal damage in lupus nephritis (LN), but a cut-off point has yet to be established. The aim of this study was to identify the predictors of renal damage in patients with LN and to determine the best cut-off point for a decrease in proteinuria.MethodsWe included patients with LN defined clinically or histologically. Possible predictors of renal damage at the time of LN diagnosis were examined: proteinuria, low complement, anti-double-stranded DNA antibodies, red cell casts, creatinine level, hypertension, renal activity (assessed by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)), prednisone dose, immunosuppressive drugs and antimalarial use. Sociodemographic variables were included at baseline. Proteinuria was assessed at baseline and at 12 months, to determine if early response (proteinuria <0.8 g/day within 12 months since LN diagnosis) is protective of renal damage occurrence. Renal damage was defined as an increase of one or more points in the renal domain of The Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index (SDI). Cox regression models using a backward selection method were performed.ResultsFive hundred and two patients with systemic lupus erythematosus patients were included; 120 patients (23.9%) accrued renal damage during their follow-up. Early response to treatment (HR=0.58), antimalarial use (HR=0.54) and a high SES (HR=0.25) were protective of renal damage occurrence, whereas male gender (HR=1.83), hypertension (HR=1.86) and the renal component of the SLEDAI (HR=2.02) were risk factors for its occurrence.ConclusionsEarly response, antimalarial use and high SES were protective of renal damage, while male gender, hypertension and higher renal activity were risk factors for its occurrence in patients with LN.
Quantum speed limit time in the presence of disturbance
Authors: Haseli S. , Salimi S. , Dolatkhah H. , Khorashad A. S. 
Published: December 2020

Quantum theory sets a bound on the minimal time it takes for a system to evolve from initial state to target state. This bound is called the quantum speed limit (QSL) time. The quantum speed limit time is used to quantify the maximal speed of the quantum evolution. The quantum evolution will be faster if the quantum speed limit time decreases. In this work, we study the quantum speed limit time for an open quantum system in the presence of disturbance in an environment. We use the model which is provided by Ban [Phys. Rev. A 99, 012116 (2019)]. In this model, two quantum systems [Formula: see text] and [Formula: see text] interact with environment sequentially. At first, quantum system [Formula: see text] interacts with the environment [Formula: see text] as an auxiliary system, then quantum system [Formula: see text] starts its interaction with disturbed environment immediately. In this work, we consider the dephasing coupling with two types of environment that has different spectral density: Ohmic and Lorentzian. We observe that, non-Markovian effects will appear in the dynamics of the second quantum system [Formula: see text] due to the interaction of the first quantum system [Formula: see text] with the environment. Given the fact that the quantum speed limit time reduces due to the non-Markovian feature of quantum evolution, we show that disturbance effects will reduce the quantum speed limit time for the dynamics of the second quantum system [Formula: see text].
Epidemiology and Outcomes of Young-Onset Esophageal Adenocarcinoma: An Analysis from a Population-Based Database
Authors: Codipilly Don C. , Sawas Tarek , Dhaliwal Lovekirat , Johnson Michele L. , Lansing Ramona , Wang Kenneth K. , Leggett Cadman L. , Katzka David A. , Iyer Prasad G. 
Published: December 2020

AbstractBackground:Esophageal adenocarcinoma is a lethal cancer with rising incidence. There are limited data in younger (&lt;50 years) patients with esophageal adenocarcinoma. We aimed to assess time trends in the incidence and outcomes of “young-onset” esophageal adenocarcinoma using a population-based database.Methods:We queried the Surveillance, Epidemiology, and End Results 9 database to identify patients with esophageal adenocarcinoma between 1975 and 2015. Patients were stratified into three age strata: &lt;50, 50 to 69, and ≥70 years. Staging was stratified as localized, regional, and distant. Trends in incidence, disease stage, and survival were assessed in three periods (1975–89, 1990–99, and 2000–2015). Univariate and multivariate models were created to identify predictors of mortality.Results:Esophageal adenocarcinoma incidence has increased in patients &lt;50 years of age, with an annual percentage change of 2.9% (95% confidence interval, 1.4%–4.4%) from 1975 to 2015. Young-onset esophageal adenocarcinoma presented at more advanced stages (regional + distant) compared with older patients (84.9% vs. 67.3%; P &lt; 0.01), with increasing proportion of advanced stages over the study period. These patients also experienced poorer 5-year esophageal adenocarcinoma–free survival compared with older patients (22.9%% vs. 29.6%; P &lt; 0.01), although this finding was attenuated on stage-stratified analysis.Conclusions:Young-onset esophageal adenocarcinoma, while uncommon, is rising in incidence. Concerningly, the proportion of advanced disease continues to increase. Young-onset esophageal adenocarcinoma also presents at more advanced stages, resulting in poorer esophageal adenocarcinoma–free survival.Impact:Patients with esophageal adenocarcinoma younger than 50 years present at more advanced stages with higher esophageal adenocarcinoma–specific mortality compared with older peers. Current diagnostic and management strategies for young-onset esophageal adenocarcinoma may need to be reevaluated.
Proteasome Inhibition Overcomes ALK-TKI Resistance in ALK-Rearranged/TP53-Mutant NSCLC via Noxa Expression
Authors: Tanimoto Azusa , Matsumoto Shingo , Takeuchi Shinji , Arai Sachiko , Fukuda Koji , Nishiyama Akihiro , Yoh Kiyotaka , Ikeda Takaya , Furuya Naoki , Nishino Kazumi , Ohe Yuichiro , Goto Koichi , Yano Seiji 
Published: December 2020

Abstract

Purpose:
In ALK-rearranged non–small cell lung cancer (NSCLC), impacts of concomitant genetic alterations on targeted therapies with ALK-tyrosine kinase inhibitors (ALK-TKI) are not yet well understood. Here, we investigated genetic alterations related to ALK-TKI resistance using clinico-genomic data and explored effective therapies to overcome the resistance in preclinical models through the identification of underlying molecular mechanisms.

Experimental Design:
We used integrated clinical and next-generation sequencing data generated in a nationwide lung cancer genome screening project (LC-SCRUM-Japan). ALK-rearranged NSCLC cell lines expressing wild-type or mutant TP53 were used to evaluate cellular apoptosis induced by ALK-TKIs.

Results:
In 90 patients with ALK-rearranged NSCLC who were treated with a selective ALK-TKI, alectinib, TP53 comutated patients showed significantly worse progression-free survival (PFS) than TP53 wild-type patients [median PFS, 11.7 months (95% confidence interval, CI, 6.3–not reached, NR) vs. NR (23.6–NR); P = 0.0008; HR, 0.33 (95% CI, 0.17–0.65)]. ALK-rearranged NSCLC cell lines that lost p53 function were resistant to alectinib-induced apoptosis, but a proteasome inhibitior, ixazomib, markedly induced apoptosis in the alectinib-treated cells by increasing the expression of a proapoptotic protein, Noxa, which bound to an antiapoptotic protein, Mcl-1. In subcutaneous tumor models, combination of ixazomib and alectinib prominently induced tumor regression and apoptosis even though the tumors were generated from ALK-rearranged NSCLC cells with nonfunctional p53.

Conclusions:
These clinical and preclinical results indicate concomitant TP53 mutations reduce the efficacy of alectinib for ALK-rearranged NSCLC and the combined use of a proteasome inhibitor with alectinib is a promising therapy for ALK-rearranged/TP53-mutated NSCLC.
Targeted Therapy of TERT-Rearranged Neuroblastoma with BET Bromodomain Inhibitor and Proteasome Inhibitor Combination Therapy
Authors: Chen Jingwei , Nelson Christopher , Wong Matthew , Tee Andrew E. , Liu Pei Y. , La Ting , Fletcher Jamie I. , Kamili Alvin , Mayoh Chelsea , Bartenhagen Christoph , Trahair Toby N. , Xu Ning , Jayatilleke Nisitha , Wong Marie , Peng Hui , Atmadibrata Bernard , Cheung Belamy B. , Lan Qing , Bryan Tracy M. , Mestdagh Pieter , Vandesompele Jo , Combaret Valerie , Boeva Valentina , Wang Jenny Y. , Janoueix-Lerosey Isabelle , Cowley Mark J. , MacKenzie Karen L. , Dolnikov Alla , Li Jinyan , Polly Patsie , Marshall Glenn M. , Reddel Roger R. , Norris Murray D. , Haber Michelle , Fischer Matthias , Zhang Xu D. , Pickett Hilda A. , Liu Tao 
Published: December 2020

Abstract

Purpose:
TERT gene rearrangement with transcriptional superenhancers leads to TERT overexpression and neuroblastoma. No targeted therapy is available for clinical trials in patients with TERT-rearranged neuroblastoma.

Experimental Design:
Anticancer agents exerting the best synergistic anticancer effects with BET bromodomain inhibitors were identified by screening an FDA-approved oncology drug library. The synergistic effects of the BET bromodomain inhibitor OTX015 and the proteasome inhibitor carfilzomib were examined by immunoblot and flow cytometry analysis. The anticancer efficacy of OTX015 and carfilzomib combination therapy was investigated in mice xenografted with TERT-rearranged neuroblastoma cell lines or patient-derived xenograft (PDX) tumor cells, and the role of TERT reduction in the anticancer efficacy was examined through rescue experiments in mice.

Results:
The BET bromodomain protein BRD4 promoted TERT-rearranged neuroblastoma cell proliferation through upregulating TERT expression. Screening of an approved oncology drug library identified the proteasome inhibitor carfilzomib as the agent exerting the best synergistic anticancer effects with BET bromodomain inhibitors including OTX015. OTX015 and carfilzomib synergistically reduced TERT protein expression, induced endoplasmic reticulum stress, and induced TERT-rearranged neuroblastoma cell apoptosis which was blocked by TERT overexpression and endoplasmic reticulum stress antagonists. In mice xenografted with TERT-rearranged neuroblastoma cell lines or PDX tumor cells, OTX015 and carfilzomib synergistically blocked TERT expression, induced tumor cell apoptosis, suppressed tumor progression, and improved mouse survival, which was largely reversed by forced TERT overexpression.

Conclusions:
OTX015 and carfilzomib combination therapy is likely to be translated into the first clinical trial of a targeted therapy in patients with TERT-rearranged neuroblastoma.
Cardiovascular Disease Events and Mortality After Myocardial Infarction Among Black and White Adults
Authors: Blackston J. Walker , Safford Monika M. , Mefford Matthew T. , Freeze Elizabeth , Howard George , Howard Virginia J. , Naftel David C. , Brown Todd M. , Levitan Emily B. 
Published: December 2020

Background:
Despite improvements in prognosis following myocardial infarction (MI), racial disparities persist. The objective of this study was to examine disparities between Black and White adults in cardiovascular disease (CVD), coronary heart disease, stroke, heart failure (HF), and mortality after MI and characteristics that may explain the disparities.

Methods:
This prospective cohort study included 1122 REGARDS (Reasons for Geographic and Racial Differences in Stroke) study participants with incident MI between 2003 and 2016. We followed participants for subsequent CVD events (MI, stroke, HF hospitalization, or death from CVD; n=431), coronary heart disease events (MI or death from coronary heart disease; (n=277), stroke (n=68), HF events (HF hospitalization or death from HF; n=191), and all-cause mortality (n=527; 3-year median follow-up after MI).

Results:
Among 1122 participants with incident MI, 37.5% were Black participants, 45.4% were women, and mean age was 73.2 (SD, 9.5) years. The unadjusted hazard ratio for CVD events comparing Black to White participants was 1.42 (95% CI, 1.17–1.71). Adjusting for sociodemographic characteristics did not attenuate the association (1.41 [95% CI, 1.14–1.73]), but further adjusting for pre-MI health status (1.25 [95% CI, 1.00–1.56]) and characteristics of the MI (1.01 [95% CI, 0.80–1.27]) resulted in substantial attenuation. Similar patterns were observed for the other outcomes, although the number of strokes was small.

Conclusions:
Black individuals had a higher risk of CVD events and mortality after MI than White individuals. The disparities were explained by health status before MI and characteristics of the MI. These findings suggest that both primordial prevention of risk factors and improved acute treatment strategies are needed to reduce disparities in post-MI outcomes.
Target: Stroke Was Associated With Faster Intravenous Thrombolysis and Improved One-Year Outcomes for Acute Ischemic Stroke in Medicare Beneficiaries
Authors: Man Shumei , Xian Ying , Holmes DaJuanicia N. , Matsouaka Roland A. , Saver Jeffrey L. , Smith Eric E. , Bhatt Deepak L. , Schwamm Lee H. , Fonarow Gregg C. 
Published: December 2020

Background:
The benefit of intravenous thrombolytic therapy for acute ischemic stroke is time dependent. To assist hospitals in providing faster thrombolytic treatment, the American Heart Association launched target: stroke quality initiative in January 2010 which disseminated feasible strategies to shorten door-to-needle times for thrombolytic therapy. This study aimed to examine whether target: stroke was associated with improved door-to-needle times and 1-year outcomes.

Methods:
We analyzed Medicare beneficiaries aged ≥65 years receiving intravenous thrombolytic treatment for acute ischemic stroke at 1490 Get With The Guidelines-Stroke hospitals during January 2006 and December 2009 (preintervention, n=10 804) and January 2010 and December 2014 (postintervention, n=31 249). The median age was 80 years and 42.7% were male.

Results:

The median door-to-needle times decreased from 80 minutes for the preintervention to 68 minutes for the postintervention (
P
<0.001). The proportion of patients receiving intravenous thrombolysis with door-to-needle times 45 minutes and 60 minutes increased from 9.6% and 24.8% for preintervention to 17.1% and 40.6% for postintervention, respectively (
P
<0.001). The annual rate of increase in the door-to-needle times of 60 minutes or less accelerated from 0.20% (95% CI, −0.43% to 0.83%) per each 4 quarters for preintervention to 5.68% (95% CI, 5.23%–6.13%) for postintervention (
P
<0.001) which was further confirmed in piecewise multivariable generalized estimating analysis (adjusted odds ratio, 1.27 [95% CI, 1.19–1.35]). Cox proportional hazards analysis, after adjusting for patient and hospital characteristics and within-hospital clustering, showed that target: stroke was associated with lower all-cause readmission (40.4% versus 44.1%; hazard ratio, 0.91 [95% CI, 0.88–0.95]), cardiovascular readmission (19.7% versus 22.9%; hazard ratio, 0.85 [95% CI, 0.80–0.89]), and composite of all-cause mortality or readmission (56.0% versus 58.4%; hazard ratio, 0.96 [95% CI, 0.93–1.00]). The risk decline in all-cause mortality dissipated after risk adjustment (adjusted hazard ratio, 0.98 [95% CI, 0.94–1.02]).

Conclusions:
Target: stroke quality initiative was associated with faster thrombolytic treatment times for acute ischemic stroke and modestly lower 1-year all-cause and cardiovascular readmissions.
Interaction–Transformation Evolutionary Algorithm for Symbolic Regression
Authors: de Franca F. O. , Aldeia G. S. I. 
Published: December 2020

AbstractInteraction–Transformation (IT) is a new representation for Symbolic Regression that reduces the space of solutions to a set of expressions that follow a specific structure. The potential of this representation was illustrated in prior work with the algorithm called SymTree. This algorithm starts with a simple linear model and incrementally introduces new transformed features until a stop criterion is met. While the results obtained by this algorithm were competitive with the literature, it had the drawback of not scaling well with the problem dimension. This article introduces a mutation-only Evolutionary Algorithm, called ITEA, capable of evolving a population of IT expressions. One advantage of this algorithm is that it enables the user to specify the maximum number of terms in an expression. In order to verify the competitiveness of this approach, ITEA is compared to linear, nonlinear, and Symbolic Regression models from the literature. The results indicate that ITEA is capable of finding equal or better approximations than other Symbolic Regression models while being competitive to state-of-the-art nonlinear models. Additionally, since this representation follows a specific structure, it is possible to extract the importance of each original feature of a data set as an analytical function, enabling us to automate the explanation of any prediction. In conclusion, ITEA is competitive when comparing to regression models with the additional benefit of automating the extraction of additional information of the generated models.
The Micro-Origins of Business Cycles: Evidence from German Metropolitan Areas
Authors: Daniele Federica , Stüber Heiko 
Published: December 2020

Abstract
How large is volatility due to large firms? We answer this question through both reduced-form analysis and a calibration exercise. First, we exploit time and spatial variation across German cities and show that higher concentration is associated with more persistent local business cycles, and local concentration Granger causes local employment volatility. From a business cycle perspective, we find evidence in favor of granularity-driven recessions only. Next, we calibrate a structural model along the lines of Carvalho and Grassi (2019) and find that the more fat-tailed productivity distribution in bigger cities crucially depends also on the higher probability that firms will grow.
The Effect of Labor Market Conditions at Entry on Workers' Long-Term Skills
Authors: Arellano-Bover Jaime 
Published: December 2020

Abstract
Using data on adults' cognitive skills from nineteen countries, this paper shows that labor market conditions during the education-to-work transition affected workers' long-term skill development. Workers who faced higher unemployment rates at ages 18 to 25 have lower skills at ages 36 to 59. Unemployment rates at ages 26 to 35 do not have such an effect. Skill inequality is affected: those with less educated parents experience most of the negative effects. Using German panel data on skills, I document a mechanism related to heterogeneous skill development across firms: young workers at large firms experience higher skill growth than those at small firms.
Exposure to the COVID-19 Stock Market Crash and Its Effect on Household Expectations
Authors: Hanspal Tobin , Weber Annika , Wohlfart Johannes 
Published: December 2020

Abstract
We survey a representative sample of U.S. households to study how exposure to the COVID-19 stock market crash affects expectations and planned behavior. Wealth shocks are associated with upward adjustments of expectations about retirement age, desired working hours, and household debt but have only small effects on expected spending. We provide correlational and experimental evidence that beliefs about the duration of the stock market recovery shape households' expectations about their own wealth and their planned investment decisions and labor market activity. Our findings shed light on the implications of household exposure to stock market crashes for expectation formation.
Cheeks, Jaws, Effort and Auletics
Authors: Akhunova Olga L. 
Published: December 2020

Abstract
This paper is an attempt to clarify a number of difficult places in Pindar’s description of the Gorgons’ lament in Pythian 12, which have given rise to inconsistent interpretations and remain insufficiently clear (δυσπενθέϊ σὺν καμάτῳ, 10; εὐπαράου Μεδοίσας, 16; τὸν … ἐκ καρπαλιμᾶν γενύων χριμφθέντα … γόον, 20-21). The central contention is that these details are directly relevant to the technical aspects of aulos-playing (the strain which is required to produce the sound, the position and movement of the mouth, the ‘good-quality’ cheeks) and provide clues to intriguing details of the myth that Pindar tells in Pythian 12.