bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rolling Contact Fatigue Damage of High-Speed Railway Wheels With Upper Bainite
Authors: Zhang Guan-Zhen , Liu Chun-Peng , Wu Si , Zhao Sa , Zhang Bin 
Published: October 2021

Abstract
This work investigates the effect of abnormal microstructure on rolling contact fatigue (RCF) damage of high-speed railway wheels under service and the formation mechanism of abnormal microstructure by optical microscopy, scanning electron microscopy, transmission electron microscopy, nano indentation and laser-induced break down spectroscopy. Results show that there are large amounts of upper bainite in the wheel tread, which destroyed the uniformity of the microstructures of the wheel matrix. The bainite is composed of ferrite with high density of dislocations and short bar-shaped cementite. The bainite exhibited higher hardness and elasticity but lower plasticity than the matrix microstructure. The incongruity of plastic deformation between upper bainite and matrix microstructures will lead to stress concentration at boundary of the microstructures, thus accelerating the RCF crack initiation and propagation. The formation of upper bainite is caused by carbon segregation. Segregation of carbon element will make the continuous cooling transformation (CCT) curve shift to the right significantly, thus increasing the probability of bainite transformation in segregation zone at higher cooling rate. Therefore, large amounts of upper bainite were formed at wheel tread.
Selection of eligible participants for screening for lung cancer using primary care data
Authors: O'Dowd Emma L , ten Haaf Kevin , Kaur Jaspreet , Duffy Stephen W , Hamilton William , Hubbard Richard B , Field John K , Callister Matthew EJ , Janes Sam M , de Koning Harry J , Rawlinson Janette , Baldwin David R 
Published: October 2021

Lung cancer screening is effective if offered to people at increased risk of the disease. Currently, direct contact with potential participants is required for evaluating risk. A way to reduce the number of ineligible people contacted might be to apply risk-prediction models directly to digital primary care data, but model performance in this setting is unknown.MethodThe Clinical Practice Research Datalink, a computerised, longitudinal primary care database, was used to evaluate the Liverpool Lung Project V.2 (LLPv2) and Prostate Lung Colorectal and Ovarian (modified 2012) (PLCOm2012) models. Lung cancer occurrence over 5–6 years was measured in ever-smokers aged 50–80 years and compared with 5-year (LLPv2) and 6-year (PLCOm2012) predicted risk.ResultsOver 5 and 6 years, 7123 and 7876 lung cancers occurred, respectively, from a cohort of 842 109 ever-smokers. After recalibration, LLPV2produced a c-statistic of 0.700 (0.694–0.710), but mean predicted risk was over-estimated (predicted: 4.61%, actual: 0.9%). PLCOm2012showed similar performance (c-statistic: 0.679 (0.673–0.685), predicted risk: 3.76%. Applying risk-thresholds of 1% (LLPv2) and 0.15% (PLCOm2012), would avoid contacting 42.7% and 27.4% of ever-smokers who did not develop lung cancer for screening eligibility assessment, at the cost of missing 15.6% and 11.4% of lung cancers.ConclusionRisk-prediction models showed only moderate discrimination when applied to routinely collected primary care data, which may be explained by quality and completeness of data. However, they may substantially reduce the number of people for initial evaluation of screening eligibility, at the cost of missing some lung cancers. Further work is needed to establish whether newer models have improved performance in primary care data.
Probing the interaction of semi-hard quarks and gluons with the underlying event in light- and heavy-flavor triggered proton-proton collisions
Authors: Vértesi Róbert , Bencédi Gyula , Misák Anett , Ortiz Antonio 
Published: October 2021

AbstractWe study underlying-event observables in inelastic proton-proton (pp) collisions at a centre-of-mass energy of $$\sqrt{s} = 13$$

s

=
13

TeV with identified light and heavy-flavor triggers using the PYTHIA 8 event generator. The study is performed as a function of the transverse momentum of the leading particle ($$p_\mathrm {T}^\mathrm{trigger}$$

p

T

trigger

). While at high $$p_\mathrm {T}^\mathrm{trigger}$$

p

T

trigger

($$>10$$

>
10

GeV/c) the underlying-event activity is independent of the leading particle species, at intermediate $$p_\mathrm {T}^\mathrm{trigger}$$

p

T

trigger

($$2<p_\mathrm {T}^\mathrm{trigger} <8$$

2
<

p

T

trigger

<
8

GeV/c) it is larger in pion-triggered events than in events triggered with B mesons. Moreover, the underlying event in pion-triggered events, the majority of which are initiated by gluons, shows a stronger effect of color reconnection than events triggered with B-hadrons, that are mostly initiated by quark jets. The effect is observed at both hadronic and partonic level. Given that color reconnection affects the interaction among final partons before the hadronization, and that in the string model quarks (gluons) are connected to one (two) string piece(s), we conclude that the observed effect can be attributed to differences in the interactions of gluon and quark jets with the underlying event.
Inverse Seesaw, dark matter and the Hubble tension
Authors: Fernandez-Martinez E. , Pierre M. , Pinsard E. , Rosauro-Alcaraz S. 
Published: October 2021

AbstractWe consider the inverse Seesaw scenario for neutrino masses with the approximate Lepton number symmetry broken dynamically by a scalar with Lepton number two. We show that the Majoron associated to the spontaneous symmetry breaking can alleviate the Hubble tension through its contribution to $$\Delta N_\text {eff}$$

Δ

N
eff

and late decays to neutrinos. Among the additional fermionic states required for realizing the inverse Seesaw mechanism, sterile neutrinos at the keV-MeV scale can account for all the dark matter component of the Universe if produced via freeze-in from the decays of heavier degrees of freedom.
Répartition jointe dans les classes de résidus de la somme des chiffres pour deux représentations d’Ostrowski
Authors: Amri Myriam , Spiegelhofer Lukas , Thuswaldner Jörg 
Published: October 2021

Résumé. Pour deux entiers [Formula: see text], nous posons [Formula: see text] et [Formula: see text] (où [Formula: see text]) et nous notons respectivement [Formula: see text] et [Formula: see text] les fonctions sommes des chiffres dans les [Formula: see text] et [Formula: see text]-représentations d’Ostrowski de [Formula: see text]. Soient [Formula: see text] des entiers positifs tels que [Formula: see text] et [Formula: see text], nous obtenons une estimation en [Formula: see text] avec un terme d’erreur [Formula: see text] pour le cardinal de l’ensemble suivant [Formula: see text] pour tous les entiers [Formula: see text] et [Formula: see text] Notre résultat peut être comparé à celui de Bésineau et Kim qui ont traité le cas des [Formula: see text]-représentations dans différentes bases (qui sont premières entre elles).
Results from Phase I Extension Study Assessing Pexidartinib Treatment in Six Cohorts with Solid Tumors including TGCT, and Abnormal CSF1 Transcripts in TGCT
Authors: Tap William D. , Singh Arun S. , Anthony Stephen Patrick , Sterba Mike , Zhang Chao , Healey John H. , Chmielowski Bartosz , Cohn Allen Lee , Shapiro Geoffrey I. , Keedy Vicki L. , Wainberg Zev A. , Puzanov Igor , Cote Gregory M. , Wagner Andrew J. , Braiteh Fadi , Sherman Eric , Hsu Henry H. , Peterfy Charles , Gelhorn Heather L. , Ye Xin , Severson Paul , West Brian L. , Lin Paul S. , Tong-Starksen Sandra 
Published: October 2021

Abstract

Purpose:
To assess the response to pexidartinib treatment in six cohorts of adult patients with advanced, incurable solid tumors associated with colony-stimulating factor 1 receptor (CSF1R) and/or KIT proto-oncogene receptor tyrosine kinase activity.

Patients and Methods:
From this two-part phase I, multicenter study, pexidartinib, a small-molecule tyrosine kinase inhibitor that targets CSF1R, KIT, and FMS-like tyrosine kinase 3 (FLT3), was evaluated in six adult patient cohorts (part 2, extension) with advanced solid tumors associated with dysregulated CSF1R. Adverse events, pharmacokinetics, and tumor responses were assessed for all patients; patients with tenosynovial giant cell tumor (TGCT) were also evaluated for tumor volume score (TVS) and patient-reported outcomes (PRO). CSF1 transcripts and gene expression were explored in TGCT biopsies.

Results:
Ninety-one patients were treated: TGCT patients (n = 39) had a median treatment duration of 511 days, while other solid tumor patients (n = 52) had a median treatment duration of 56 days. TGCT patients had response rates of 62% (RECIST 1.1) and 56% (TVS) for the full analysis set. PRO assessments for pain showed improvement in patient symptoms, and 76% (19/25) of TGCT tissue biopsy specimens showed evidence of abnormal CSF1 transcripts. Pexidartinib treatment of TGCT resulted in tumor regression and symptomatic benefit in most patients. Pexidartinib toxicity was manageable over the entire study.

Conclusions:
These results offer insight into outcome patterns in cancers whose biology suggests use of a CSF1R inhibitor. Pexidartinib results in tumor regression in TGCT patients, providing prolonged control with an acceptable safety profile.
Clinical Activity of Single-Agent Cabozantinib (XL184), a Multi-receptor Tyrosine Kinase Inhibitor, in Patients with Refractory Soft-Tissue Sarcomas
Authors: O'Sullivan Coyne Geraldine , Kummar Shivaani , Hu James , Ganjoo Kristen , Chow Warren A. , Do Khanh T. , Zlott Jennifer , Bruns Ashley , Rubinstein Lawrence , Foster Jared C. , Juwara Lamin , Meehan Robert , Piekarz Richard , Streicher Howard , Sharon Elad , Takebe Naoko , Voth Andrea Regier , Bottaro Donald , Costello Rene , Wright John J. , Doroshow James H. , Chen Alice P. 
Published: October 2021

Abstract

Purpose:
Soft-tissue sarcomas (STS) are a rare, heterogeneous group of mesenchymal tumors. For decades the mainstay of treatment for advanced, unresectable STS has been palliative chemotherapy. High levels of activated MET receptor have been reported in various sarcoma cell lines, together with elevated vascular endothelial growth factor (VEGF) levels in patients with STS, suggesting that dual targeting of the VEGF and MET pathways with the multi-receptor tyrosine kinase inhibitor cabozantinib would result in clinical benefit in this population.

Patients and Methods:
We performed an open-label, multi-institution, single-arm phase II trial of single-agent cabozantinib in adult patients with advanced STS and progressive disease after at least 1 standard line of systemic therapy. Patients received 60 mg oral cabozantinib once daily in 28-day cycles, and dual primary endpoints of overall response rate and 6-month progression-free survival (PFS) were assessed. Changes in several circulating biomarkers were assessed as secondary endpoints.

Results:
Six (11.1%; 95% CI, 4.2%–22.6%) of the 54 evaluable patients enrolled experienced objective responses (all partial responses). Six-month PFS was 49.3% (95% CI, 36.2%–67.3%), with a median time on study of 4 cycles (range, 1–99). The most common grade 3/4 adverse events were hypertension (7.4%) and neutropenia (16.7%). Patients' levels of circulating hepatocyte growth factor (HGF), soluble MET, and VEGF-A generally increased after a cycle of therapy, while soluble VEGFR2 levels decreased, regardless of clinical outcome.

Conclusions:
Cabozantinib single-agent antitumor activity was observed in patients with selected STS histologic subtypes (alveolar soft-part sarcoma, undifferentiated pleomorphic sarcoma, extraskeletal myxoid chondrosarcoma, and leiomyosarcoma) highlighting the biomolecular diversity of STS.
Influence of
GAS5
/MicroRNA‐223‐3p/P2Y12 Axis on Clopidogrel Response in Coronary Artery Disease
Authors: Liu Yan‐Ling , Hu Xiao‐Lei , Song Pei‐Yuan , Li He , Li Mu‐Peng , Du Yin‐Xiao , Li Mo‐Yun , Ma Qi‐Lin , Peng Li‐Ming , Song Ming‐Yu , Chen Xiao‐Ping 
Published: October 2021

Background
Dual antiplatelet therapy based on aspirin and P2Y12 receptor antagonists such as clopidogrel is currently the primary treatment for coronary artery disease (CAD). However, a percentage of patients exhibit clopidogrel resistance, in which genetic factors play vital roles. This study aimed to investigate the roles of GAS5 (growth arrest‐specific 5) and its rs55829688 polymorphism in clopidogrel response in patients with CAD.

Methods and Results

A total of 444 patients with CAD receiving dual antiplatelet therapy from 2017 to 2018 were enrolled to evaluate the effect of
GAS5
single nucleotide polymorphism rs55829688 on platelet reactivity index. Platelets from 37 patients of these patients were purified with microbeads to detect GAS5 and microRNA‐223‐3p (miR‐223‐3p) expression. Platelet‐rich plasma was isolated from another 17 healthy volunteers and 46 newly diagnosed patients with CAD to detect GAS5 and miR‐223‐3p expression. A dual‐luciferase reporter assay was performed to explore the interaction between miR‐223‐3p and
GAS5
or
P2Y12
3′‐UTR in (human embryonic kidney 293 cell line that expresses a mutant version of the SV40 large T antigen) HEK 293T and (megakaryoblastic cell line derived in 1983 from the bone marrow of a chronic myeloid leukemia patient with megakaryoblastic crisis) MEG‐01 cells. Loss‐of‐function and gain‐of‐function experiments were performed to reveal the regulation of GAS5 toward P2Y12 via miR‐223‐3p in MEG‐01 cells. We observed that rs55829688 CC homozygotes showed significantly decreased platelet reactivity index than TT homozygotes in
CYP2C19
poor metabolizers. Platelet GAS5 expression correlated positively with both platelet reactivity index and
P2Y12
mRNA expressions, whereas platelet miR‐223‐3p expression negatively correlated with platelet reactivity index. Meanwhile, a negative correlation between GAS5 and miR‐223‐3p expressions was observed in platelets. MiR‐223‐3p mimic reduced while the miR‐223‐3p inhibitor increased the expression of GAS5 and P2Y12 in MEG‐01 cells. Knockdown of GAS5 by siRNA increased miR‐223‐3p expression and decreased P2Y12 expression, which could be reversed by the miR‐223‐3p inhibitor. Meanwhile, overexpression of GAS5 reduced miR‐223‐3p expression and increased P2Y12 expression, which could be reversed by miR‐223‐3p mimic.

Conclusions

GAS5
rs55829688 polymorphism might affect clopidogrel response in patients with CAD with the
CYP2C19
poor metabolizer genotypes, and GAS5 regulates P2Y12 expression and clopidogrel response by acting as a competitive endogenous RNA for miR‐223‐3p.
Long‐Term Medication Adherence Trajectories to Direct Oral Anticoagulants and Clinical Outcomes in Patients With Atrial Fibrillation
Authors: An Jaejin , Bider Zoe , Luong Tiffany Q. , Cheetham T. Craig , Lang Daniel T. , Fischer Heidi , Reynolds Kristi 
Published: October 2021

Background
Direct oral anticoagulants (DOACs) are widely used in patients with nonvalvular atrial fibrillation for stroke prevention. However, long‐term adherence to DOACs and clinical outcomes in real‐world clinical practice is not well understood. This study evaluated long‐term medication adherence patterns to DOAC therapy and clinical outcomes in a large US integrated health care system.

Methods and Results

We included adult patients with nonvalvular atrial fibrillation who newly initiated DOACs between 2012 and 2018 in Kaiser Permanente Southern California. Long‐term (3.5 years) adherence trajectories to DOAC were investigated using monthly proportion of days covered and group‐based trajectory models. Factors associated with long‐term adherence trajectories were investigated. Multivariable Poisson regression analyses were used to investigate thromboembolism and major bleeding events associated with long‐term adherence trajectories. Of 18 920 patients newly initiating DOACs, we identified 3 DOAC adherence trajectories: consistently adherent (85.2%), early discontinuation within 6 months (10.6%), and gradually declining adherence (4.2%). Predictors such as lower CHA
2
DS
2
‐VASc (0–1 versus ≥5) and previous injurious falls were associated with both early discontinuation and gradually declining adherence trajectories. Early discontinuation of DOAC therapy was associated with a higher risk of thromboembolism (rate ratio, 1.40; 95% CI, 1.05–1.86) especially after 12 months from DOAC initiation but a lower risk of major bleed compared with consistent adherence (rate ratio, 0.48; 95% CI, 0.30–0.75), specifically during the first 12 months following DOAC initiation. A gradual decline in adherence to DOACs was not statistically significantly associated with thromboembolism outcomes compared with consistent adherence.

Conclusions
Although a large proportion of patients with nonvalvular atrial fibrillation were adherent to DOAC therapy over 3.5 years, early discontinuation of DOAC was associated a higher risk of thromboembolic events. Future tailored interventions for early discontinuers may improve clinical outcomes.
The Protective Role of Yin‐Yang 1 in Cardiac Injury and Remodeling After Myocardial Infarction
Authors: Huang Yu , Li Liangpeng , Chen Hongmei , Liao Qiao , Yang Xiaoli , Yang Dezhong , Xia Xuewei , Wang Hongyong , Wang Wei Eric , Chen Lianglong , Zeng Chunyu 
Published: October 2021

Background
Exploring potential therapeutic target is of great significance for myocardial infarction (MI) and post‐MI heart failure. Transcription factor Yin‐Yang 1 (YY1) is an essential regulator of apoptosis and angiogenesis, but its role in MI is unclear.

Methods and Results
The expression of YY1 was assessed in the C57BL/6J mouse heart following MI. Overexpression or silencing of YY1 in the mouse heart was achieved by adeno‐associated virus 9 injection. The survival, cardiac function, and scar size, as well as the apoptosis, angiogenesis, cardiac fibrosis, T helper 2 lymphocyte cytokine production, and macrophage polarization were assessed. The effects of YY1 on Akt phosphorylation and vascular endothelial growth factor production were also investigated. The expression of YY1 in heart was significantly stimulated by MI. The survival rate, cardiac function, scar size, and left ventricular volume of mice were improved by YY1 overexpression but worsened by YY1 silencing. YY1 alleviated cardiac apoptosis and fibrosis, promoted angiogenesis, T helper 2 cytokine production, and M2 macrophage polarization in the post‐MI heart, it also enhanced the tube formation and migration ability of endothelial cells. Enhanced Akt phosphorylation, along with the increased vascular endothelial growth factor levels were observed in presence of YY1 overexpression.

Conclusions
YY1 ameliorates cardiac injury and remodeling after MI by repressing cardiomyocyte apoptosis and boosting angiogenesis, which might be ascribed to the enhancement of Akt phosphorylation and the subsequent vascular endothelial growth factor up‐regulation. Increased T helper 2 cytokine production and M2 macrophage polarization may also be involved in YY1’s cardioprotective effects. These findings supported YY1 as a potential target for therapeutic investigation of MI.
Derivation and Validation of Genome‐Wide Polygenic Score for Ischemic Heart Failure
Authors: Paranjpe Ishan , Tsao Noah L. , De Freitas Jessica K. , Judy Renae , Chaudhary Kumardeep , Forrest Iain S. , Jaladanki Suraj K. , Paranjpe Manish , Sharma Pranav ,   CBIPM Genomics Team,   Regeneron Genetics Center, Glicksberg Benjamin S. , Narula Jagat , Do Ron , Damrauer Scott M. , Nadkarni Girish N. 
Published: October 2021

Background
Despite advances in cardiovascular disease and risk factor management, mortality from ischemic heart failure (HF) in patients with coronary artery disease (CAD) remains high. Given the partial role of genetics in HF and lack of reliable risk stratification tools, we developed and validated a polygenic risk score for HF in patients with CAD, which we term HF‐PRS.

Methods and Results

Using summary statistics from a recent genome‐wide association study for HF, we developed candidate PRSs in the Mount Sinai Bio
Me
CAD patient cohort (N=6274) by using the pruning and thresholding method and LDPred. We validated the best score in the Penn Medicine BioBank (N=7250) and performed a subgroup analysis in a high‐risk cohort who had undergone coronary catheterization. We observed a significant association between HF‐PRS score and ischemic HF even after adjusting for evidence of obstructive CAD in patients of European ancestry in both Bio
Me
(odds ratio [OR], 1.14 per SD; 95% CI, 1.05–1.24;
P
=0.003) and Penn Medicine BioBank (OR, 1.07 per SD; 95% CI, 1.01–1.13;
P
=0.016). In European patients with CAD in Penn Medicine BioBank who had undergone coronary catheterization, individuals in the top 10th percentile of PRS had a 2‐fold increased odds of ischemic HF (OR, 2.0; 95% CI, 1.1–3.7;
P
=0.02) compared with the bottom 10th percentile.

Conclusions
A PRS for HF enables risk stratification in patients with CAD. Future prospective studies aimed at demonstrating clinical utility are warranted for adoption in the patient setting.
Genesis 1–3 and the Formation of Subjectivity in the Hodayot and the Two Spirits Teaching
Authors: Newsom Carol A. 
Published: October 2021

Abstract
Although the lived experience of subjectivity for persons in antiquity cannot be known directly, one can study certain texts as tools for the formation of subjects. Among the Dead Sea Scrolls two compositions are particularly instructive, the Hodayot found in 1QHa 2–9, 18–28 (the Hodayot of the Maskil, also known as Hodayot of the Community) and the Two Spirits Teaching (1QS 3:13–4:26). Each develops an understanding of subjectivity based on subtle interpretations of creation traditions, developed through sophisticated intertextual readings. The Hodayot privilege Gen 2–3; the Two Spirits Teaching emphasizes Gen 1. Although mutually contradictory on the surface, the two accounts actually develop subjectivities that share many similarities. By analyzing these converging patterns one may get some sense of the lived subjectivity that was created by the various texts and practices of the Yahad community.
The Eschatological Key
Authors: Douglass Rachel 
Published: October 2021

Abstract
In the first volume of his systemic series, German theologian Jürgen Moltmann begins his systematics with a musical metaphor; “The eschatological is not one element of Christianity, but it is the medium of Christian faith as such, the key in which everything is set …” Moltmann then goes on to propose that the eschaton is a temporal event, which breaks the logic of his initial metaphor of the key signature. This essay will explore the differences between understanding the eschaton explicated as the key that Christian hope is set as opposed to a temporal alternative, such as the time signature. Jeremy Begbie is brought into the conversation to explicate how “harmony” can guide our conversation of music theory, and Miguel De La Torre illuminates how Moltmann’s claim, which while revolutionary in many aspects, continues to rely on Eurocentric understanding of salvation history, just as music theory tends towards Eurocentrism. We also examine what we lose out on when we leave this uninterrogated. To conclude, we explore how Moltmann’s proposal about Christian hope becomes more coherent within the metaphor of key signature and right relationship instead of time signature and temporality.