bluuebunny/crossref_metadata_2025_split huggingface dataset:
The path to $$\hbox {N}^3\hbox {LO}$$ parton distributions
Authors: Ball Richard D. , Barontini Andrea , Candido Alessandro , Carrazza Stefano , Cruz-Martinez Juan , Del Debbio Luigi , Forte Stefano , Giani Tommaso , Hekhorn Felix , Kassabov Zahari , Laurenti Niccolò , Magni Giacomo , Nocera Emanuele R. , Rabemananjara Tanjona R. , Rojo Juan , Schwan Christopher , Stegeman Roy , Ubiali Maria ,   The NNPDF Collaboration
Published: July 2024

AbstractWe extend the existing leading (LO), next-to-leading (NLO), and next-to-next-to-leading order (NNLO) NNPDF4.0 sets of parton distribution functions (PDFs) to approximate next-to-next-to-next-to-leading order ($$\hbox {aN}^3\hbox {LO}$$aN3LO). We construct an approximation to the$$\hbox {N}^3\hbox {LO}$$N3LOsplitting functions that includes all available partial information from both fixed-order computations and from small and largexresummation, and estimate the uncertainty on this approximation by varying the set of basis functions used to construct the approximation. We include known$$\hbox {N}^3\hbox {LO}$$N3LOcorrections to deep-inelastic scattering structure functions and extend the FONLL general-mass scheme to$$\mathcal {O}\left( \alpha _s^3\right) $$Oαs3accuracy. We determine a set of$$\hbox {aN}^3\hbox {LO}$$aN3LOPDFs by accounting both for the uncertainty on splitting functions due to the incomplete knowledge of$$\hbox {N}^3\hbox {LO}$$N3LOterms, and to the uncertainty related to missing higher corrections (MHOU), estimated by scale variation, through a theory covariance matrix formalism. We assess the perturbative stability of the resulting PDFs, we study the impact of MHOUs on them, and we compare our results to the$$\hbox {aN}^3\hbox {LO}$$aN3LOPDFs from the MSHT group. We examine the phenomenological impact of$$\hbox {aN}^3\hbox {LO}$$aN3LOcorrections on parton luminosities at the LHC, and give a first assessment of the impact of$$\hbox {aN}^3\hbox {LO}$$aN3LOPDFs on the Higgs and Drell–Yan total production cross-sections. We find that the$$\hbox {aN}^3\hbox {LO}$$aN3LONNPDF4.0 PDFs are consistent within uncertainties with their NNLO counterparts, that they improve the description of the global dataset and the perturbative convergence of Higgs and Drell–Yan cross-sections, and that MHOUs on PDFs decrease substantially with the increase of perturbative order.
Observational constraints on the emergent universe with non-linear equation of state and interacting fluids
Authors: Chanda Anirban , Roy Bikash Chandra , Bamba Kazuharu , Paul Bikash Chandra 
Published: July 2024

AbstractWe investigate a flat emergent universe (EU) with a nonlinear equation of state equivalent to three different composition of fluids. In the EU initially, the evolution of the universe began with no interaction but as time evolves an interaction sets in among the three fluids leading to the observed universe. The characteristic of an EU is that it is a singularity free universe that evolves with all the basic features of the early evolution. For a given nonlinear equation of state parameter, it permits a universe with three different fluids, we get a universe with dark energy, cosmic string, and radiation domination to begin with which at a later epoch transits into a universe with three different fluids with matter domination (baryonic as well as dark matter) and dark energy for a given interaction strength among the cosmic fluids. The evolution of the universe is probed with exponential interactions to obtain a universe with late acceleration. The model parameters are constrained using the observed Hubble data and Type Ia Supernova (SnIa) data from the Pantheon data set. An interacting EU transforms to a matter dominated phase with DE accommodating the present universe satisfactorily. The stability of the cosmological model is also discussed.
A Pan-Cancer Patient-Derived Xenograft Histology Image Repository with Genomic and Pathologic Annotations Enables Deep Learning Analysis
Authors: White Brian S. , Woo Xing Yi , Koc Soner , Sheridan Todd , Neuhauser Steven B. , Wang Shidan , Evrard Yvonne A. , Chen Li , Foroughi pour Ali , Landua John D. , Mashl R. Jay , Davies Sherri R. , Fang Bingliang , Raso Maria Gabriela , Evans Kurt W. , Bailey Matthew H. , Chen Yeqing , Xiao Min , Rubinstein Jill C. , Sanderson Brian J. , Lloyd Michael W. , Domanskyi Sergii , Dobrolecki Lacey E. , Fujita Maihi , Fujimoto Junya , Xiao Guanghua , Fields Ryan C. , Mudd Jacqueline L. , Xu Xiaowei , Hollingshead Melinda G. , Jiwani Shahanawaz , Acevedo Saul ,   PDXNet Consortium, Davis-Dusenbery Brandi N. , Robinson Peter N. , Moscow Jeffrey A. , Doroshow James H. , Mitsiades Nicholas , Kaochar Salma , Pan Chong-xian , Carvajal-Carmona Luis G. , Welm Alana L. , Welm Bryan E. , Govindan Ramaswamy , Li Shunqiang , Davies Michael A. , Roth Jack A. , Meric-Bernstam Funda , Xie Yang , Herlyn Meenhard , Ding Li , Lewis Michael T. , Bult Carol J. , Dean Dennis A. , Chuang Jeffrey H. 
Published: July 2024

Abstract
Patient-derived xenografts (PDX) model human intra- and intertumoral heterogeneity in the context of the intact tissue of immunocompromised mice. Histologic imaging via hematoxylin and eosin (H&E) staining is routinely performed on PDX samples, which could be harnessed for computational analysis. Prior studies of large clinical H&E image repositories have shown that deep learning analysis can identify intercellular and morphologic signals correlated with disease phenotype and therapeutic response. In this study, we developed an extensive, pan-cancer repository of &gt;1,000 PDX and paired parental tumor H&E images. These images, curated from the PDX Development and Trial Centers Research Network Consortium, had a range of associated genomic and transcriptomic data, clinical metadata, pathologic assessments of cell composition, and, in several cases, detailed pathologic annotations of neoplastic, stromal, and necrotic regions. The amenability of these images to deep learning was highlighted through three applications: (i) development of a classifier for neoplastic, stromal, and necrotic regions; (ii) development of a predictor of xenograft-transplant lymphoproliferative disorder; and (iii) application of a published predictor of microsatellite instability. Together, this PDX Development and Trial Centers Research Network image repository provides a valuable resource for controlled digital pathology analysis, both for the evaluation of technical issues and for the development of computational image–based methods that make clinical predictions based on PDX treatment studies.
Significance: A pan-cancer repository of &gt;1,000 patient-derived xenograft hematoxylin and eosin–stained images will facilitate cancer biology investigations through histopathologic analysis and contributes important model system data that expand existing human histology repositories.
Contribution of Prediagnostic Host Factors to Shaping the Stromal Microenvironment of Breast Cancer among Sub-Saharan African Women
Authors: Abubakar Mustapha , Ahearn Thomas U. , Duggan Maire A. , Lawrence Scott , Adjei Ernest K. , Clegg-Lamptey Joe-Nat , Yarney Joel , Wiafe-Addai Beatrice , Awuah Baffour , Wiafe Seth , Nyarko Kofi , Aitpillah Francis S. , Ansong Daniel , Hewitt Stephen M. , Brinton Louise A. , Figueroa Jonine D. , Garcia-Closas Montserrat , Edusei Lawrence , Titiloye Nicolas ,   for the Ghana Breast Health Study Team
Published: July 2024

Abstract

Background:
The stromal microenvironment (SME) is integral to breast cancer biology, impacting metastatic proclivity and treatment response. Emerging data indicate that host factors may impact the SME, but the relationship between prediagnostic host factors and SME phenotype remains poorly characterized, particularly among women of African ancestry.

Methods:
We conducted a case-only analysis involving 792 patients with breast cancer (17–84 years) from the Ghana Breast Health Study. High-accuracy machine-learning algorithms were applied to standard H&E-stained images to characterize SME phenotypes [including percent tumor-associated connective tissue stroma, Ta-CTS (%); tumor-associated stromal cellular density, Ta-SCD (%)]. Associations between prediagnostic host factors and SME phenotypes were assessed in multivariable linear regression models.

Results:
Decreasing Ta-CTS and increasing Ta-SCD were associated with aggressive, mostly high-grade tumors (P-value &lt; 0.001). Several prediagnostic host factors were associated with Ta-SCD independently of tumor characteristics. Compared with nulliparous women, parous women had higher levels of Ta-SCD [mean (standard deviation, SD) = 31.3% (7.6%) vs. 28.9% (7.1%); P-value = 0.01]. Similarly, women with a positive family history of breast cancer had higher levels of Ta-SCD than those without family history [mean (SD) = 33.0% (7.5%)] vs. 30.9% (7.6%); P-value = 0.03]. Conversely, increasing body size was associated with decreasing Ta-SCD [mean (SD) = 31.6% (7.4%), 31.4% (7.3%), and 30.1% (8.0%) for slight, average, and large body sizes, respectively; P-value = 0.005].

Conclusions:
Epidemiological risk factors were associated with varying degrees of stromal cellularity in tumors, independently of clinicopathological characteristics.

Impact:
The findings raise the possibility that epidemiological risk factors may partly influence tumor biology via the stromal microenvironment.
Prognostic Significance of SASP-Related Gene Signature of Radiation Therapy in Head and Neck Squamous Cell Carcinoma
Authors: Lee Min Kyeong , Woo Seon Rang , Noh Joo Kyung , Min Soonki , Kong Moonkyoo , Lee Young Chan , Ko Seong-Gyu , Eun Young-Gyu 
Published: July 2024

Abstract
In this study, we developed and validated the clinical significance of senescence-associated secretory phenotype (SASP)-related gene signature and explored its association with radiation therapy (RT) in patients with head and neck squamous cell carcinoma (HNSCC). First, we searched the three published review literature associated with SASP and selected all 81 genes to develop SASP-related gene signature. Then, 81 SASP-related genes were adapted to gene expression dataset from The Cancer Genome Atlas (TCGA). Patients with HNSCC of TCGA were classified into clusters 1 and 2 via unsupervised clustering according to SASP-related gene signature. Kaplan–Meier plot survival analysis showed that cluster 1 had a poorer prognosis than cluster 2 in 5-year overall survival and recurrence-free survival. Similarly, cluster 1 showed a worse prognosis than cluster 2 in three validation cohorts (E-MTAB-8588, FHCRC, and KHU). Cox proportional hazards regression observed that the SASP-related signature was an independent prognostic factor for patients with HNSCC. We also established a nomogram using a relevant clinical parameter and a risk score. Time-dependent receiver operating characteristic analysis was carried out to assess the accuracy of the prognostic risk model and nomogram. Senescence SASP-related gene signature was associated with the response to RT. Therefore, subsequent, in vitro experiments further validated the association between SASP-related gene signature and RT in HNSCC. In conclusion, we developed a SASP-related gene signature, which could predict survival of patients with HNSCC, and this gene signature provides new clinical evidence for the accurate diagnosis and targeted RT of HNSCC.
METTL14-Mediated Bim mRNA m6A Modification Augments Osimertinib Sensitivity in EGFR-Mutant NSCLC Cells
Authors: Fan Siwen , Lv Xinwu , Zhang Chuantao , Zeng Bingbing , Liang Yanqing , Chen Danyang , Xu Zumin , Li Pan , Wu Shanshan , Liu Hao , Luo Kai , Liu Zongcai , Yi Yanmei 
Published: July 2024

Abstract
Resistance to osimertinib represents a significant challenge for the successful treatment of non–small cell lung cancer (NSCLC) harboring activating mutations in EGFR. N6-methyladenosine (m6A) on mRNAs is critical for various biological processes, yet whether m6A regulates osimertinib resistance of NSCLC remains unknown. In this study, we demonstrated that developing osimertinib-resistant phenotypes depends on m6A reduction resulting from downexpression of m6A methyltransferase METTL14 in EGFR-mutant NSCLCs. Both in vitro and in vivo assays showed that specific knockdown of METTL14 was sufficient to confer osimertinib resistance and that elevated expression of METTL14 rescued the efficacy of osimertinib in the resistant NSCLC cells. Mechanistically, METTL14 promoted m6A methylation of pro-apoptotic Bim mRNA and increased Bim mRNA stability and expression, resulting in activating the Bim-dependent pro-apoptotic signaling and thereby promoting osimertinib-induced cell apoptosis. Analysis of clinical samples revealed that decreased expression of METTL14 was observed in osimertinib-resistant NSCLC tissues and significantly associated with a poor prognosis. In conclusion, our study reveals a novel regulatory mechanism by which METTL14-mediated m6A methylation of Bim mRNA inhibited osimertinib resistance of NSCLC cells. It offers more evidences for the involvement of m6A modification in regulation of osimertinib resistance and provides potential therapeutic targets for novel approaches to overcome the tolerance of osimertinib and other EGFR tyrosine kinase inhibitors.
Implications: This study offers more evidences for the involvement of METTL14-mediated N6-methyladenosine modification in regulation of osimertinib resistance and provides potential therapeutic targets for novel approaches to overcome the tolerance of osimertinib and other EGFR tyrosine kinase inhibitors.
E2F1-Associated Purine Synthesis Pathway Is a Major Component of the MET-DNA Damage Response Network
Authors: Poliaková Turan Michaela , Riedo Rahel , Medo Matúš , Pozzato Chiara , Friese-Hamim Manja , Koch Jonas P. , Coggins Si’Ana A. , Li Qun , Kim Baek , Albers Joachim , Aebersold Daniel M. , Zamboni Nicola , Zimmer Yitzhak , Medová Michaela 
Published: July 2024

Abstract

Various lines of investigation support a signaling interphase shared by receptor tyrosine kinases and the DNA damage response. However, the underlying network nodes and their contribution to the maintenance of DNA integrity remain unknown. We explored MET-related metabolic pathways in which interruption compromises proper resolution of DNA damage. Discovery metabolomics combined with transcriptomics identified changes in pathways relevant to DNA repair following MET inhibition (METi). METi by tepotinib was associated with the formation of γH2AX foci and with significant alterations in major metabolic circuits such as glycolysis, gluconeogenesis, and purine, pyrimidine, amino acid, and lipid metabolism. 5′-Phosphoribosyl-N-formylglycinamide, a de novo purine synthesis pathway metabolite, was consistently decreased in in vitro and in vivo MET-dependent models, and METi-related depletion of dNTPs was observed. METi instigated the downregulation of critical purine synthesis enzymes including phosphoribosylglycinamide formyltransferase, which catalyzes 5′-phosphoribosyl-N-formylglycinamide synthesis. Genes encoding these enzymes are regulated through E2F1, whose levels decrease upon METi in MET-driven cells and xenografts. Transient E2F1 overexpression prevented dNTP depletion and the concomitant METi-associated DNA damage in MET-driven cells. We conclude that DNA damage following METi results from dNTP reduction via downregulation of E2F1 and a consequent decline of de novo purine synthesis.

Significance:
Maintenance of genome stability prevents disease and affiliates with growth factor receptor tyrosine kinases. We identified de novo purine synthesis as a pathway in which key enzymatic players are regulated through MET receptor and whose depletion via MET targeting explains MET inhibition-associated formation of DNA double-strand breaks. The mechanistic importance of MET inhibition-dependent E2F1 downregulation for interference with DNA integrity has translational implications for MET-targeting-based treatment of malignancies.
High‐Density Lipoprotein Particle Concentration and Size Predict Incident Coronary Artery Disease Events in a Cohort With Type 1 Diabetes
Authors: Costacou Tina , Vaisar Tomas , Miller Rachel G. , Davidson W. Sean , Heinecke Jay W. , Orchard Trevor J. , Bornfeldt Karin E. 
Published: July 2024

Background
The cholesterol efflux capacity of high density lipoprotein (HDL) is negatively associated with cardiovascular risk. Small HDL particles account almost quantitatively for cholesterol efflux capacity, perhaps mediated through efflux of cholesterol and outer leaflet plasma membrane phospholipids by ABCA1 (ATP binding cassette subfamily A member 1). People with type 1 diabetes are at increased coronary artery disease (CAD) risk despite normal HDL‐cholesterol concentrations. We therefore tested the hypothesis that small HDL particles (HDL‐P)—rather than HDL‐cholesterol—predict incident CAD in type 1 diabetes.

Methods and Results
Incident CAD (CAD death, myocardial infarction, or coronary revascularization) was determined in 550 individuals with childhood‐onset type 1 diabetes. HDL‐P was quantified by calibrated ion mobility analysis and cholesterol efflux capacity was quantified with validated assays. During a median follow‐up of 26 years, 36.5% of the participants developed incident CAD, for an incidence density of 181.3 per 10 000 person‐years. In multivariable Cox models, neither HDL‐cholesterol nor apolipoprotein A1 concentration was significantly associated with CAD risk. In contrast, higher extra‐small HDL‐P concentrations were significantly associated with decreased CAD risk (hazard ratio [HR], 0.26 [95% CI, 0.14–0.50]). Weaker associations were observed for total HDL‐P (HR, 0.88 [95% CI, 0.83–0.93]), small HDL (HR, 0.83 [95% CI, 0.68–1.02]), medium HDL (HR, 0.79 [95% CI, 0.71–0.89]), and large HDL (HR, 0.72 [95% CI, 0.59–0.89]). Although cholesterol efflux capacity was negatively associated with incident CAD, this association was no longer significant after adjustment for total HDL‐P.

Conclusions
Lower concentrations of total HDL‐P and HDL subpopulations were positively associated with incident CAD independently of HDL‐cholesterol, apolipoprotein A1, and other common CVD risk factors. Extra‐small HDL was a much stronger predictor of risk than the other HDLs. Our data are consistent with the proposal that extra‐small HDL plays a critical role in cardioprotection in type 1 diabetes, mediated by macrophage cholesterol efflux by the ABCA1 pathway.
Moral Engagement in Design: Five Considerations for Unpacking the Ethical Dimensions of Design Methods
Authors: Ozkaramanli Deger , Nagenborg Michael 
Published: July 2024

Abstract
What society experiences today as morally questionable design—from gendered toys for children to public benches that prevent sleeping—can be considered the aftermath of an underdeveloped foundation for systematic ethical reflection in design methodologies. Although designing is an inherently moral activity, research on how to recognize and handle ethical questions and moral dilemmas in early (conceptual) design activities is scarce. In this article, we use an interdisciplinary lens to analyze and respond to the challenges of bridging moral psychology, ethics of technology, and design methodologies. For this, we introduce the concept of moral engagement in design, which is inspired by Moral Disengagement Theory. Finally, we propose five preliminary considerations for enacting moral engagement in design practices. These considerations form an interdisciplinary bridge to help us reflect on the moral dimensions of methodological choices in conceptual design practices.
Interannual Variation of Summer Compound Hot and Drought Events in Xinjiang and Its Relationship with the North Atlantic Sea Surface Temperature
Authors: Zhang Xiaolu , Miao Jiapeng , Wang Xiaoxin , Zhou Botao 
Published: July 2024

Abstract
Xinjiang suffers compound hot and drought events under global warming. However, less attention has been paid to physical mechanisms of the variability of compound hot and drought events in this region. This article investigates the interannual variation of summer (June–August) compound hot and drought events in Xinjiang and its relationship with the sea surface temperature (SST) over the North Atlantic. The results show that its first empirical orthogonal function (EOF) mode features a spatially homogenous pattern. This mode is closely connected with the simultaneous meridional negative–positive–negative SST anomalies over the North Atlantic. The summer North Atlantic tripole SST anomalies can trigger a remarkable wave train extending from the North Atlantic to Eurasia, consequently inducing an anomalous high pressure system over the Iran–Pamir Plateau, which is conducive to the increase in air temperature from the surface to the upper troposphere over Xinjiang. The warmer troposphere further strengthens the western Asian subtropical meridional temperature gradient and thereby enhances the westerly wind to the north flank of the West Asian subtropical westerly jet (WASWJ). As a result, the WASWJ is displaced northward, which intensifies the sinking motion and prevents the water vapor transport to Xinjiang, leading to a decrease in precipitation in the target region. The higher temperature and less precipitation contribute to the occurrence of compound hot and drought events over Xinjiang. Numerical simulations based on the Community Atmosphere Model, version 4 (CAM4), further confirm the relationship between the North Atlantic tripole SST anomalies and compound hot and drought events in Xinjiang during summer on the interannual time scale.

Significance Statement
Xinjiang, located in northwest China, suffers from frequent and intense compound hot and drought events in recent decades. It is thus urgent to understand the physical mechanisms associated with its occurrence in order for disaster prevention and mitigation. In this study, we reveal that the leading mode of summer compound hot and drought events over Xinjiang, featuring a spatially homogenous pattern, is closely correlated with the simultaneous meridional negative–positive–negative SST anomalies over the North Atlantic. The North Atlantic tripole SST anomalies can lead to an anomalous high pressure system over the Iran–Pamir Plateau and a northward shift of the West Asian subtropical westerly jet through exciting a wave train propagating from the North Atlantic to Eurasia, which consequently contributes to the occurrence of compound hot and drought events over Xinjiang.