bluuebunny/crossref_metadata_2025_split huggingface dataset:
Study protocol for a comparative effectiveness evaluation of abiraterone acetate against enzalutamide: a longitudinal study based on Swedish administrative registers
Authors: Johansson Per , Jonéus Paulina , Langenskiöld Sophie 
Published: October 2021

IntroductionThis paper presents a study protocol for a comparative effectiveness evaluation of abiraterone acetate against enzalutamide in clinical practice, two cancer drugs given to patients suffering from advanced prostate cancer.Method and analysisThe protocol designs a comparative-effectiveness analysis of abiraterone acetate against enzalutamide. With the substantial number of covariates a two-step procedure is suggested in choosing relevant covariates in the matching design. In the first step, an exploratory factor analysis reduces the dimension of a large set of continuous covariates to nine factors. In the second step, we reduce the dimension of the covariates, interactions and second order terms for the continuous covariates using propensity score estimation. The final design makes use of a genetic matching algorithm. The study protocol provides a detailed statistical analysis plan of the analysis sample derived from the matching design. The analysis will make use of linear regression and robust inference adjusted for multisignificance testing.DiscussionAs in a randomised experiment the focus is on the design of the assignment to treatment. This allows the publication of this preanalysis plan before having access to outcome data. This means that the p values will be correct if the maintained assumption of uncounfoundedness is valid. Given that is p-hacking is substantial problem in empirical research, this is a substantial strength of this study. However, while design yields, balance on the observed covariates one cannot discard the possibility that unobserved confounders are not balanced. For that reason, sensitivity tests for the maintained assumption of uncounfoundedness are presented.Ethics and disseminationThe study was approved by the Regional Ethical Review Board in Uppsala, Sweden (Dnr 2017/482). Results will be published in a peer-reviewed journal and distributed to relevant stakeholders in healthcare.
Fraction of acute work-related injuries attributable to hazardous occupational noise across the USA in 2019
Authors: Shkembi Abas , Smith Lauren , Roberts Benjamin , Neitzel Richard 
Published: October 2021

IntroductionThe contribution of hazardous noise—a ubiquitous exposure in workplaces—to occupational injury risk is often overlooked. In this ecological study, the fraction of US workplace acute injuries resulting in days away from work in 2019 attributable to hazardous occupational noise exposure was estimated.MethodsUsing the NoiseJEM, a job exposure matrix of occupational noise, and 2019 Occupational Employment and Wage Statistics data, the proportion of workers experiencing hazardous occupational noise (≥85 dBA) was estimated for every major US Standard Occupational Classification (SOC) group. Population attributable fractions (PAFs) were calculated for each major SOC group using the relative risk (RR) taken from a published 2017 meta-analysis on this relationship.ResultsAbout 20.3 million workers (13.8%) are exposed to hazardous levels of occupational noise. Nearly 3.4% of acute injuries resulting in days away from work in 2019 (95% CI 2.4% to 4.4%) were attributable to hazardous occupational noise, accounting for roughly 14 794 injuries (95% CI 10 367 to 18 994). The occupations with the highest and the lowest PAFs were production (11.9%) and office and administrative support (0.0%), respectively.DiscussionHazardous noise exposure at work is an important and modifiable factor associated with a substantial acute occupational injury burden.
Effect of a ‘tobacco-free nicotine’ claim on intentions and perceptions of Puff Bar e-cigarette use among non-tobacco-using young adults
Authors: Chen-Sankey Julia , Ganz Ollie , Seidenberg Andrew , Choi Kelvin 
Published: October 2021

IntroductionPuff Bar disposable e-cigarettes are now marketed with a ‘tobacco-free nicotine’ claim. We assessed the effect of this claim on non-tobacco-using young adults’ perceptions of and intentions of using Puff Bar.MethodsWe conducted an online randomised between-subjects experiment among non-tobacco-using young adults (ages 18–29 years; n=1822). Participants viewed depictions of Puff Bar e-cigarettes with the claim that the product contains ‘tobacco-free nicotine’ (experimental group; n=909) or simply ‘nicotine’ (control group; n=913). Multivariable regressions were used to assess the associations between experimental conditions and Puff Bar use intentions, harm perceptions, use expectancies and perceived relative use of Puff Bar versus other e-cigarettes, controlling for participant characteristics.ResultsCompared with the control group, the experimental group who saw the ‘tobacco-free nicotine’ claim reported higher intentions of using Puff Bar (coefficient=0.17, p<0.001). The experimental group had a lower likelihood of perceiving Puff Bar use as ‘extremely or very harmful’ (OR=0.63, p<0.001) and ‘strongly or somewhat’ agreeing with the negative expectancy of using Puff Bar (OR=0.67, p<0.001). Additionally, the experimental group reported being ‘much more or more likely’ to use Puff Bar over other e-cigarettes (OR=1.67, p<0.001).DiscussionPuff Bar’s tobacco-free nicotine claim may increase non-tobacco-using young adults’ intentions of using Puff Bar and reduce harm perceptions and negative expectancy towards using Puff Bar. The claim may also prompt the use of Puff Bar over other e-cigarette brands and types. These findings are concerning given the health effects and regulations for tobacco-free nicotine products are not immediately clear.
Quark and lepton flavor model with leptoquarks in a modular $$A_4$$ symmetry
Authors: Nomura Takaaki , Okada Hiroshi , Orikasa Yuta 
Published: October 2021

AbstractWe propose a quark-lepton model via leptoquarks and modular $$A_4$$

A
4

symmetry. Since the neutrino mass is induced at one-loop level mediated by down quarks as well as leptoquarks, we have to explain lepton and quark masses and mixings with a single modulus $$\tau $$
τ
. Here, we find predictions for lepton and quark sectors with unified modulus $$\tau $$
τ
, and show several constraints originating from leptoquarks.
Cosmological evolution with quadratic gravity and nonideal fluids
Authors: Chakraborty Saikat , Gregoris Daniele 
Published: October 2021

AbstractSome cosmological models based on the gravitational theory$$f(R)=R+\zeta R^2$$f(R)=R+ζR2, and on fluids obeying to the equations of state of Redlich–Kwong, Berthelot, and Dieterici are proposed for describing smooth transitions between different cosmic epochs. A dynamical system analysis reveals that these models contain fixed points which correspond to an inflationary, a radiation dominated and a late-time accelerating epoch, and a nonsingular bouncing solution, the latter being an asymptotic fixed point of the compactified phase space. The infinity of the compactified phase space is interpreted as a region in which the non-ideal behaviors of the previously mentioned cosmic fluids are suppressed. Physical constraints on the adopted dimensionless variables are derived by demanding the theory to be free from ghost and tachyonic instabilities, and a novel cosmological interpretation of such variables is proposed through a cosmographic analysis. The different effects of the equation of state parameters on the number of equilibrium solutions and on their stability nature are clarified. Some generic properties of these models, which are not sensitive to the particular fluid considered, are identified, while differences are critically examined by showing that the Redlich–Kwong scenario admits a second radiation-dominated epoch and a Big Rip Singularity.
Mapping class group representations from non-semisimple TQFTs
Authors: De Renzi Marco , Gainutdinov Azat M. , Geer Nathan , Patureau-Mirand Bertrand , Runkel Ingo 
Published: October 2021

In [M. De Renzi, A. Gainutdinov, N. Geer, B. Patureau-Mirand and I. Runkel, 3-dimensional TQFTs from non-semisimple modular categories, preprint (2019), arXiv:1912.02063[math.GT]], we constructed 3-dimensional topological quantum field theories (TQFTs) using not necessarily semisimple modular categories. Here, we study projective representations of mapping class groups of surfaces defined by these TQFTs, and we express the action of a set of generators through the algebraic data of the underlying modular category [Formula: see text]. This allows us to prove that the projective representations induced from the non-semisimple TQFTs of the above reference are equivalent to those obtained by Lyubashenko via generators and relations in [V. Lyubashenko, Invariants of 3-manifolds and projective representations of mapping class groups via quantum groups at roots of unity, Comm. Math. Phys. 172(3) (1995) 467–516, arXiv:hep-th/9405167]. Finally, we show that, when [Formula: see text] is the category of finite-dimensional representations of the small quantum group of [Formula: see text], the action of all Dehn twists for surfaces without marked points has infinite order.
Phenotype Discovery and Geographic Disparities of Late-Stage Breast Cancer Diagnosis across U.S. Counties: A Machine Learning Approach
Authors: Dong Weichuan , Bensken Wyatt P. , Kim Uriel , Rose Johnie , Berger Nathan A. , Koroukian Siran M. 
Published: October 2021

Abstract

Background:
Disparities in the stage at diagnosis for breast cancer have been independently associated with various contextual characteristics. Understanding which combinations of these characteristics indicate highest risk, and where they are located, is critical to targeting interventions and improving outcomes for patients with breast cancer.

Methods:
The study included women diagnosed with invasive breast cancer between 2009 and 2018 from 680 U.S. counties participating in the Surveillance, Epidemiology, and End Results program. We used a machine learning approach called Classification and Regression Tree (CART) to identify county “phenotypes,” combinations of characteristics that predict the percentage of patients with breast cancer presenting with late-stage disease. We then mapped the phenotypes and compared their geographic distributions. These findings were further validated using an alternate machine learning approach called random forest.

Results:
We discovered seven phenotypes of late-stage breast cancer. Common to most phenotypes associated with high risk of late-stage diagnosis were high uninsured rate, low mammography use, high area deprivation, rurality, and high poverty. Geographically, these phenotypes were most prevalent in southern and western states, while phenotypes associated with lower percentages of late-stage diagnosis were most prevalent in the northeastern states and select metropolitan areas.

Conclusions:
The use of machine learning methods of CART and random forest together with geographic methods offers a promising avenue for future disparities research.

Impact:
Local interventions to reduce late-stage breast cancer diagnosis, such as community education and outreach programs, can use machine learning and geographic modeling approaches to tailor strategies for early detection and resource allocation.
Brugada Syndrome: New Insights From Cardiac Magnetic Resonance and Electroanatomical Imaging
Authors: Pappone Carlo , Santinelli Vincenzo , Mecarocci Valerio , Tondi Lara , Ciconte Giuseppe , Manguso Francesco , Sturla Francesco , Vicedomini Gabriele , Micaglio Emanuele , Anastasia Luigi , Pica Silvia , Camporeale Antonia , Lombardi Massimo 
Published: October 2021

Background:
Brugada syndrome (BrS) is considered a purely electrical disease with variable electrical substrates. Variable rates of mechanical abnormalities have been also reported. Whether exists a link between electrical and mechanical abnormalities has never been previously explored. This investigational physiopathological study aimed to determine the relationship between the substrate size/location, as exposed by ajmaline provocation, and the severity of mechanical abnormalities, as assessed by cardiac magnetic resonance in patients with BrS.

Methods:
Twenty-four consecutive high-risk patients with BrS (mean age, 38±11 years, 17 males), presenting with malignant syncope and documented polymorphic ventricular tachycardia/ventricular fibrillation, and candidate to implantable cardioverter defibrillator implantation, underwent cardiac magnetic resonance and electroanatomic maps. During each examination, ajmaline test (1 mg/kg over 5 minutes) was performed. Cardiac magnetic resonance findings were compared with 24 age, sex, and body surface area-matched controls. In patients with BrS, the correlation between the electrical substrate extent and right ventricular regional mechanical abnormalities before/after ajmaline challenge was analyzed.

Results:

After ajmaline, patients with BrS showed a reduction of right ventricular (RV) ejection fraction (
P
<0.001), associated with decreased transversal displacement (U,
P
<0.001) and longitudinal strain (ε,
P
<0.001) localized at RV outflow tract. In patients with BrS significant preajmaline/postajmaline changes of transversal displacement (ΔU,
P
<0.001) and longitudinal strain (Δε,
P
<0.001) were found. In the control group, no mechanical changes were observed after ajmaline. The electrical substrate consistently increased after ajmaline from 1.7±2.8 cm
2
to 14.2±7.3 cm
2
(
P
<0.001), extending from the RV outflow tract to the neighboring segments of the RV anterior wall. Postajmaline RV ejection fraction inversely correlated with postajmaline substrate extent (
r
=−0.830,
P
<0.001). In patients with BrS and normal controls, cardiac magnetic resonance detected neither myocardial fibrosis nor RV outflow tract morphological abnormalities.

Conclusions:
BrS is a dynamic RV electromechanical disease, where functional abnormalities correlate with the maximal extent of the substrate size. These findings open new lights on the physiopathology of the disease.

Registration:

URL:
https://clinicaltrial.gov
; Unique identifier: NCT03524079.
Sequential Defects in Cardiac Lineage Commitment and Maturation Cause Hypoplastic Left Heart Syndrome
Authors: Krane Markus , Dreßen Martina , Santamaria Gianluca , My Ilaria , Schneider Christine M. , Dorn Tatjana , Laue Svenja , Mastantuono Elisa , Berutti Riccardo , Rawat Hilansi , Gilsbach Ralf , Schneider Pedro , Lahm Harald , Schwarz Sascha , Doppler Stefanie A. , Paige Sharon , Puluca Nazan , Doll Sophia , Neb Irina , Brade Thomas , Zhang Zhong , Abou-Ajram Claudia , Northoff Bernd , Holdt Lesca M. , Sudhop Stefanie , Sahara Makoto , Goedel Alexander , Dendorfer Andreas , Tjong Fleur V.Y. , Rijlaarsdam Maria E. , Cleuziou Julie , Lang Nora , Kupatt Christian , Bezzina Connie , Lange Rüdiger , Bowles Neil E. , Mann Matthias , Gelb Bruce D. , Crotti Lia , Hein Lutz , Meitinger Thomas , Wu Sean , Sinnecker Daniel , Gruber Peter J. , Laugwitz Karl-Ludwig , Moretti Alessandra 
Published: October 2021

Background:
Complex molecular programs in specific cell lineages govern human heart development. Hypoplastic left heart syndrome (HLHS) is the most common and severe manifestation within the spectrum of left ventricular outflow tract obstruction defects occurring in association with ventricular hypoplasia. The pathogenesis of HLHS is unknown, but hemodynamic disturbances are assumed to play a prominent role.

Methods:
To identify perturbations in gene programs controlling ventricular muscle lineage development in HLHS, we performed whole-exome sequencing of 87 HLHS parent–offspring trios, nuclear transcriptomics of cardiomyocytes from ventricles of 4 patients with HLHS and 15 controls at different stages of heart development, single cell RNA sequencing, and 3D modeling in induced pluripotent stem cells from 3 patients with HLHS and 3 controls.

Results:
Gene set enrichment and protein network analyses of damaging de novo mutations and dysregulated genes from ventricles of patients with HLHS suggested alterations in specific gene programs and cellular processes critical during fetal ventricular cardiogenesis, including cell cycle and cardiomyocyte maturation. Single-cell and 3D modeling with induced pluripotent stem cells demonstrated intrinsic defects in the cell cycle/unfolded protein response/autophagy hub resulting in disrupted differentiation of early cardiac progenitor lineages leading to defective cardiomyocyte subtype differentiation/maturation in HLHS. Premature cell cycle exit of ventricular cardiomyocytes from patients with HLHS prevented normal tissue responses to developmental signals for growth, leading to multinucleation/polyploidy, accumulation of DNA damage, and exacerbated apoptosis, all potential drivers of left ventricular hypoplasia in absence of hemodynamic cues.

Conclusions:
Our results highlight that despite genetic heterogeneity in HLHS, many mutations converge on sequential cellular processes primarily driving cardiac myogenesis, suggesting novel therapeutic approaches.
Arms Control as Wedge Strategy: How Arms Limitation Deals Divide
Alliances
Authors: Crawford Timothy W. , Vu Khang X. 
Published: October 2021

Abstract
Strategic arms control is in crisis. The United States and Russia have retreated from agreements that formed the framework for post–Cold War arms cuts and strategic stability, such as the Anti-Ballistic Missile Treaty, the Treaty on Conventional Armed Forces in Europe, and the Intermediate-Range Nuclear Forces Treaty. The only strategic arms control agreement between the United States and Russia (i.e., New START) expires in 2026. The political forcefield that sustained the old framework has been altered by major technological revolutions and China's rise. Motives for strategic arms control are conventionally framed in terms of their potential to enhance stability by limiting certain weapons, avoiding costly arms races, or preserving military advantage. But states can also use strategic arms control to divide adversaries. Wedge strategy theory explains how arms control can do so by affecting adversaries' threat perceptions, their beliefs about the costs and benefits of formal commitments, and their degree of trust in one another. Three landmark strategic arms control negotiations (the Five-Power Treaty and the Four-Power Treaty at the Washington Naval Conference, the Limited Nuclear Test Ban Treaty, and the Strategic Arms Limitation Talks) show how the wedge motive informed these negotiations and influenced great power relations. The wedge logic remains relevant today. For example, the United States may employ future arms control agreements to drive a wedge between China and Russia, and it must be cautious about arms control deals with North Korea that would negatively affect its relationship with South Korea.
Caught Red-Handed: How States Wield Proof to Coerce
Wrongdoers
Authors: Nutt Cullen G. , Pauly Reid B.C. 
Published: October 2021

Abstract
States frequently acquire proof of other states' norm violations, from nuclear proliferation to harboring terrorists to interfering in elections. Existing theories do not fully explain how states that catch others red-handed wield a form of coercive power over the wrongdoers. Discoverers may conceal proof of wrongdoing, share such proof with other actors privately, or reveal their proof to the world. States with more leverage over wrongdoers have two incentives to conceal proof of wrongdoing. They can blackmail wrongdoers by threatening to go public with proof of their guilt, and they can simultaneously allow wrongdoers to save face. States that possess proof of wrongdoing but have less leverage are more likely to share that proof with others. If a discoverer distrusts the intentions of states with more leverage, it will reveal evidence publicly, catalyzing others to act. Publicizing proof weaponizes the prospect that other states will pay reputation and hypocrisy costs if they do not follow through on punishing norm violations. Four case studies of nuclear proliferation (Taiwan, Libya, South Africa, and North Korea) probe this novel theory.
Classification and Evaluation of Stable and Unstable Cloud Forecasts
Authors: Nachamkin Jason E. , Bienkowski Adam , Bankert Rich , Pattipati Krishna , Sidoti David , Surratt Melinda , Gull Jacob , Nguyen Chuyen 
Published: October 2021

Abstract
A physics-based cloud identification scheme, originally developed for a machine-learning forecast system, was applied to verify cloud location and coverage bias errors from two years of 6-h forecasts. The routine identifies stable and unstable environments by assessing the potential for buoyant versus stable cloud formation. The efficacy of the scheme is documented by investigating its ability to identify cloud patterns and systematic forecast errors. Results showed that stable cloud forecasts contained widespread, persistent negative cloud cover biases most likely associated with turbulent, radiative, and microphysical feedback processes. In contrast, unstable clouds were better predicted despite being poorly resolved. This suggests that scale aliasing, while energetically problematic, results in less-severe short-term cloud cover errors. This study also evaluated Geostationary Operational Environmental Satellite (GOES) cloud-base retrievals for their effectiveness at identifying regions of lower-tropospheric cloud cover. Retrieved cloud-base heights were sometimes too high with respect to their actual values in regions of deep-layered clouds, resulting in underestimates of the extent of low cloud cover in these areas. Sensitivity experiments indicate that the most accurate cloud-base estimates existed in regions with cloud tops at or below 8 km.

Significance Statement
Cloud forecasts are difficult to verify because the height, depth, and type of the clouds are just as important as the spatial location. Satellite imagery and retrievals are good for verifying location, but these measurements are sometimes uncertain because of obscuration from above. Despite these uncertainties, we can learn a lot about specific forecast errors by tracking general areas of clouds based on their physical forcing mechanisms. We chose to sort by atmospheric stability because buoyant and stable processes are physically very distinct. Studies of this nature exist, but they typically assess mean cloud frequencies without considering spatial and temporal displacements. Here, we address displacement error by assessing the direct overlap between the observed and predicted clouds.