bluuebunny/crossref_metadata_2025 huggingface dataset:
Elementary teachers' self‐regulated learning of science subject matter through teaching experience
Authors: Nixon Ryan S. , Smith Leigh K.
Published: October 2023

Elementary teachers likely have many opportunities to improve their science subject matter knowledge in the context of their everyday work. However, this has not been sufficiently explored in the literature. The purpose of this exploratory study is to investigate teachers' self‐regulated learning of science subject matter knowledge as a result of teaching experience. All teachers in this study recognized and described moments where they determined their subject matter knowledge was inadequate, an important step of self‐regulated learning. Findings also indicate that teachers' recognition of gaps in their knowledge may be influenced by teachers' perceptions of the complexity of their students' questions. In response to recognizing gaps in their knowledge, teachers drew on online resources. They were, however, generally not critical about the quality of these resources. We discuss these observations in relation to teachers' self‐regulated learning of science subject matter through teaching experience.
Parents’ experiences of health literacy in parenting infants at home: a qualitative systematic review protocol
Authors: Sakai Ayano , Ishimaru Mina , Iwata Hiroko , Iwase Seiko , Suzuki Satoko
Published: October 2023

Objective:

This systematic review will identify and synthesize available qualitative evidence regarding parents’ experiences of health literacy in parenting infants at home.

Introduction:

Parental health literacy, which is essential for parents’ and children’s health, is associated with parents’ health knowledge, parenting practices, and children’s health outcomes. Parents face difficulties pertaining to their health literacy skills in daily health education and health care for their infants; therefore, understanding their parenting experience with infants from a health literacy perspective is important for health professionals. This review will evaluate and integrate qualitative evidence regarding parental experiences of health literacy in daily parenting of infants at home.

Inclusion criteria:

This review will include qualitative data from empirical studies describing parents’ experiences of health literacy in parenting infants at home. Parents of infants (0–1 year of age) living at home in Organisation for Economic Co-operation and Development member countries will be included.

Methods:

This review will follow the JBI approach for qualitative systematic reviews. The following databases will be searched for published and unpublished studies: MEDLINE (EBSCOhost), CINAHL (EBSCOhost), PsycINFO (EBSCOhost), and ProQuest Health & Medical Collection (in English and Japanese); Open Access Theses and Dissertations (in English); and Ichushi-Web, CiNii, and the Institutional Repositories Database (in Japanese). Study selection, data extraction, and critical appraisal of the methodological quality of studies will be undertaken by 2 reviewers independently. Data synthesis will be conducted using the meta-aggregation approach, and the synthesized findings will be assessed using the ConQual approach.

Systematic review registration number:

CRD42022345187
Investigaciones y explicaciones sobre corrupción pública
Authors: Peralta Borray Diego Alejandro , Zapata Sebastián
Published: October 2023

Esta investigación tiene como objetivo comprender las relaciones causales que se presentan alrededor del fenómeno de la corrupción pública, y que han sido abordadas en las investigaciones académicas de mayor relevancia. Con este propósito se realizó una revisión de literatura que analizó 156 de los artículos, más los citados distribuidos en 19 países y contenidos en la base de datos Scopus a enero de 2020, que respondían a la búsqueda del término public corruption. Como resultado se identificaron 33 agrupaciones conceptuales que permitieron construir 4 categorías emergentes denominadas explicaciones, de las que se infiere la necesidad de abordar de forma transdisciplinar el fenómeno a partir de la economía, la política, la administración pública y las ciencias humanas. A partir de estas agrupaciones conceptuales se construyeron diagramas causales que muestran la complementariedad y consistencia en los resultados de las investigaciones. Esta revisión se presenta como un punto de partida para los investigadores que deseen ahondar en las discusiones académicas actuales, y los legisladores que quieran enfocar sus esfuerzos a través de políticas públicas que ataquen la corrupción de forma integral.
Tax Avoidance y cumplimiento contable-tributario según las características de las empresas
Authors: Packer Eigenstuhler Dyeniffer , Baú dal Magro Cristian
Published: October 2023

Este estudio tuvo como objetivo verificar la influencia del cumplimiento contable-tributario y las características individuales de las empresas en la práctica de la tax avoidance. Para cumplir con el objetivo de la investigación, metodologicamente, se utilizó estadística multivariante con el uso de regresión lineal múltiple. El análisis se extiende al período de muestra de 2012 a 2018 y se aplica a empresas que cotizan en bolsa de 30 países, totalizando una muestra de 61 673 observaciones. Los hallazgos indican una relación positiva entre la mayor distancia entre las utilidades contables y gravables (incumplimiento fiscal-contable) y la práctica de la tax avoidance, lo que indica que las organizaciones están haciendo uso de una planificación fiscal cada vez más agresiva. En cuanto a la influencia de las características económicas y financieras de las empresas, no hubo significación estadística que evidenciara tal relación con la evasión o elusión fiscal, contrariamente a lo que en el pasado fue un indicador de la práctica de la tax avoidance.
Toward decoupling the effects of kinetic and potential ion energies: Ion flux dependent structural properties of thin (V,Al)N films deposited by pulsed filtered cathodic arc
Authors: Unutulmazsoy Yeliz , Kalanov Dmitry , Oh Kyunghwan , Karimi Aghda Soheil , Gerlach Jürgen W. , Braun Nils , Munnik Frans , Lotnyk Andriy , Schneider Jochen M. , Anders André
Published: October 2023

Pulsed filtered cathodic arc deposition involves formation of energetic multiply charged metal ions, which help to form dense, adherent, and macroparticle-free thin films. Ions possess not only significant kinetic energy, but also potential energy primarily due to their charge, which for cathodic arc plasmas is usually greater than one. While the effects of kinetic ion energy on the growing film are well investigated, the effects of the ions’ potential energy are less known. In the present work, we make a step toward decoupling the contributions of kinetic and potential energies of ions on thin film formation. The potential energy is changed by enhancing the ion charge states via using an external magnetic field at the plasma source. The kinetic energy is adjusted by biasing the arc source (“plasma bias”), which allows us to approximately compensate the differences in kinetic energy, while the substrate and ion energy detector remain at ground. However, application of an external magnetic field also leads to an enhancement of the ion flux and hence the desired complete decoupling of the potential and kinetic energy effects will require further steps. Charge-state-resolved energy distribution functions of ions are measured at the substrate position for different arc source configurations, and thin films are deposited using exactly those configurations. Detailed characterization of the deposited thin films is performed to reveal the correlations of changes in structure with kinetic and potential energies of multiply charged ions. It is observed that the cathode composition (Al:V ratio) strongly affects the formation of the thermodynamically stable wurtzite or the metastable cubic phase. The external magnetic field applied at the arc source is found to greatly alter the plasma and, therefore, to be the primary, easily accessible “tuning knob” to enhance film crystallinity. The effect of “atomic scale heating” provided by the ions’ kinetic and potential energies on the film crystallinity is investigated, and the possibility to deposit crystalline (V,Al)N films without substrate heating is demonstrated. This study shows an approach toward distinguishing the contributions stemming from kinetic and potential energies of ions on the film growth, however, further research is needed to assess and distinguish the additional effect of ion flux intensity (current).
Evolution of β-Ga2O3 to
γ
-Ga2O3 solid-solution epitaxial films after high-temperature annealing
Authors: Jiang Kunyao , Tang Jingyu , Xu Chengchao , Xiao Kelly , Davis Robert F. , Porter Lisa M.
Published: October 2023

Atomic resolution scanning/transmission electron microscopy (S/TEM) and energy-dispersive x-ray (EDX) analysis were used to determine the effects of annealing at 800–1000 °C in air on Ga2O3 films grown on (100) MgAl2O4 at 650 °C via metal-organic chemical vapor deposition. Annealing resulted in the diffusion of Mg and Al into the films concomitantly with the transformation of β-Ga2O3 to γ-Ga2O3 solid solutions. The minimum atomic percent of Al + Mg that corresponded with the transformation was ∼4.6 at. %. Analyses of atomic-scale STEM images and EDX profiles revealed that the Al and Mg atoms in the γ-Ga2O3 solid solutions occupied octahedral sites; whereas the Ga atoms occupied tetrahedral sites. These site preferences may account for the stabilization of the γ-Ga2O3 solid solutions.
Internal Structure of Venus Based on the PREM Model
Authors: Amorim D. O. , Gudkova T. V.
Published: October 2023

Abstract—

Models of the internal structure of Venus have been constructed with a wide range of crustal thickness (30–70 km) and core radius (2800–3500 km). An analysis of the pressure values in the center of the planet allows us to conclude that the presence of a solid inner core is unlikely if the composition and temperature profile of Venus correspond to that of the Earth. Andrade’s rheology was used to take into account the inelasticity of the interior of Venus when calculating the tidal Love numbers and the angle of delay of the tidal hump. Comparison of experimental values of the Love number k2 with the model gives the radius of the core of Venus in the range of 3100–3500 km. It is shown that to determine the characteristic viscosity of the Venusian mantle, the key factor is the determination of the angle of retardation of the tidal bulge: values of 0.9° correspond to low viscosity and high temperature, and 0.4° to high viscosity and low temperature, so the planned measurements of tidal parameters and the moment of inertia of the planet in the VERITAS and EnVision missions will be able to impose restrictions on the distribution of viscosity and temperature in the interior of Venus.
Can Google Trends predict asylum-seekers’ destination choices?
Authors: Qi Haodong , Bircan Tuba
Published: October 2023

Google Trends (GT) collate the volumes of search keywords over time and by geographical location. Such data could, in theory, provide insights into people’s ex ante intentions to migrate, and hence be useful for predictive analysis of future migration. Empirically, however, the predictive power of GT is sensitive, it may vary depending on geographical context, the search keywords selected for analysis, as well as Google’s market share and its users’ characteristics and search behavior, among others. Unlike most previous studies attempting to demonstrate the benefit of using GT for forecasting migration flows, this article addresses a critical but less discussed issue: when GT cannot enhance the performances of migration models. Using EUROSTAT statistics on first-time asylum applications and a set of push-pull indicators gathered from various data sources, we train three classes of gravity models that are commonly used in the migration literature, and examine how the inclusion of GT may affect models’ abilities to predict refugees’ destination choices. The results suggest that the effects of including GT are highly contingent on the complexity of different models. Specifically, GT can only improve the performance of relatively simple models, but not of those augmented by flow Fixed-Effects or by Auto-Regressive effects. These findings call for a more comprehensive analysis of the strengths and limitations of using GT, as well as other digital trace data, in the context of modeling and forecasting migration. It is our hope that this nuanced perspective can spur further innovations in the field, and ultimately bring us closer to a comprehensive modeling framework of human migration.
An SU(15) approach to bifermion classification
Authors: Corianò Claudio , Frampton Paul H. , Melle Dario , Kephart Thomas W. , Yuan Tzu-Chiang
Published: October 2023

One interesting way to extend the Standard Model is the hypothesis of bifermions which are bosons that couple to pairs of quarks and leptons. We point out that [Formula: see text] grand unification gives a natural way to classify bifermions and discuss leptoquarks, biquarks and bileptons. In fact, [Formula: see text] provides an ideal covering group as it contains all possible bifermions within a single model.
A Review of Exosomes in Regenerative Cosmetic Dermatology
Authors: Miller Julia , Chen Grace , Hayag Marie V
Published: October 2023

Exosomes are the small extracellular vesicles secreted by almost all living cell types. They are a main component of cellular communication. To mediate intercellular communication, exosomes transport cellular cargo such as proteins, miRNA, nucleic acids, and various metabolites[Formula: see text]. Although specifics of their role in cellular physiology have yet to be uncovered, interest in exosomes and their functionality has exploded due to their diverse treatment and diagnostic capabilities. Already, numerous studies have proven the safety, efficacy, and therapeutic potential of exosomes in the treatment of cancers, neurodegenerative disorders, cardiovascular illness, and orthopedic diseases1. Due to their small size, high membrane permeability, and modifiability, exosomes are of the utmost therapeutic and diagnostic potential[Formula: see text]. As exosomes promote cellular regeneration, their role in general dermatology as well as cosmetic dermatology has become prominent. In the past few years, cosmetic dermatology research proves the potential of exosomes in the processes of skin rejuvenation, postprocedural care, and dermal maintenance. Some of the most popular modalities of treatment include hair restoration, photorejuvenation, daily maintenance, and antiaging. This paper will discuss the biological function, isolation methods, and therapeutic role of mesenchymal stem cell-and platelet-derived exosomes in cosmetic dermatology.
Triangle-oriented Community Detection Considering Node Features and Network Topology
Authors: Gao Guangliang , Liang Weichao , Yuan Ming , Qian Hanwei , Wang Qun , Cao Jie
Published: October 2023

The joint use of node features and network topology to detect communities is called community detection in attributed networks. Most of the existing work along this line has been carried out through objective function optimization and has proposed numerous approaches. However, they tend to focus only on lower-order details, i.e., capture node features and network topology from node and edge views, and purely seek a higher degree of optimization to guarantee the quality of the found communities, which exacerbates unbalanced communities and free-rider effect. To further clarify and reveal the intrinsic nature of networks, we conduct triangle-oriented community detection considering node features and network topology. Specifically, we first introduce a triangle-based quality metric to preserve higher-order details of node features and network topology, and then formulate so-called two-level constraints to encode lower-order details of node features and network topology. Finally, we develop a local search framework based on optimizing our objective function consisting of the proposed quality metric and two-level constraints to achieve both non-overlapping and overlapping community detection in attributed networks. Extensive experiments demonstrate the effectiveness and efficiency of our framework and its potential in alleviating unbalanced communities and free-rider effect.
Gender Classification System Based on the Behavioral Biometric Modality: Application of Handwritten Text
Authors: Dargan Shaveta , Kumar Munish
Published: October 2023

Forensic Science is a branch of science that deals with the discovery, examination, and analysis of strong elements or evidence involved in the criminal justice system. It involves the use of scientific methods to investigate crimes. The Gender Classification System is closely linked to forensic studies, specifically investigating individuals through their handwriting, known as Behavioral Biometrics. Biometric systems rely on behavioral and physiological traits such as brain-prints, fingerprints, handwritten text, speech, facial attributes, gait information, palm vein patterns, hand geometry, electrocardiograms (ECGs), and more. Gender classification is an intriguing and important aspect within the field of pattern recognition and machine learning. It involves a binary problem of classifying individuals as either male or female. Analyzing the differences in femininity and masculinity behaviors can contribute to the evaluation of biometric-based identification systems. Gender classification has numerous forensic applications, including crime identification, demographic research, forgery detection, security, and surveillance. The main objective of this article is to present the latest survey findings on the gender classification system based on handwritten text, specifically the behavioral biometric modality. It includes an overview of the state-of-the-art work, the general framework, approaches, biometric modalities, and critical analysis. The article concludes with a critical analysis, discussion of open issues, concluding remarks, and future perspectives.
Special Issue on The Workshop on MAthematical performance Modeling and Analysis (MAMA 2023)
Authors: Squillante Mark S.
Published: October 2023

The complexity of computer systems, networks and applications, as well as the advancements in computer technology, continue to grow at a rapid pace. Mathematical analysis, modeling and optimization have been playing, and continue to play, an important role in research studies to investigate fundamental issues and tradeoffs at the core of performance problems in the design and implementation of complex computer systems, networks and applications.
Distributed Rate Scaling in Large-Scale Service Systems
Authors: Rutten Daan , Zubeldia Martin , Mukherjee Debankur
Published: October 2023

We consider a large-scale parallel-server system, where each server dynamically chooses its processing speed in a completely distributed fashion. The goal is to minimize the global cost that is the sum of the average cost of maintaining the respective processing speeds of all servers and a certain non-decreasing function of the sojourn time of tasks. The key challenges arise from the facts that the arrival rate of tasks is unknown and that there is no centralized control or communication among the servers.

Using insights from stochastic approximation, we develop a novel rate-scaling algorithm and prove that the cost of the processing rates under our algorithm converges to the globally optimum value as the system size becomes large. En route, we also analyze the performance of a fully heterogeneous parallel-server system (i.e, where each server has a different processing speed), which might be of independent interest.
Trade-off Analysis in Learning-augmented Algorithms with Societal Design Criteria
Authors: Hajiesmaili Mohammad H.
Published: October 2023

Traditionally, computer systems are designed to optimize classic notions of performance such as flow completion time, cost, etc. The system performance is then typically evaluated by characterizing theoretical bounds in worst-case settings over a single performance metric. In the next generation of computer systems, societal design criteria, such as carbon awareness and fairness, becomes a first-class design goal. However, the classic performance metrics may conflict with societal criteria. Foundational understanding and performance evaluations of systems with these inherent trade-offs lead to novel research questions that could be considered new educational components for performance analysis courses. The classic techniques, e.g., worst-case analysis, for systems with conflicting objectives may lead to the impossibility of results. However, a foundational understanding of the impossibility of results calls for new techniques and tools. In traditional performance evaluation, to understand the foundational limits, typically, it is sufficient to derive lower-bound arguments in worst-case settings. In the new era of system design, lower bounds are inherently about trade-offs between different objectives. Characterizing these trade-offs in settings with multiple design criteria is closer to the notion of Pareto-optimality, which is drastically different from classic lower bounds. With the impossibility of results using classic paradigms, one possible direction is to (re)design systems following the emerging direction of learning-augmented algorithms. With this approach, it might be possible to remove/mitigate the foundational conflict between classic vs. societal metrics using the right predictions. However, the performance evaluation of learning-augmented algorithms calls for a new set of technical questions, which we highlight in this paper.
Making Decisions at Data Plane Speeds
Authors: Narayana Srinivas
Published: October 2023

Feedback control loops to implement self-driving networks constitute data collection to sense the network, and control algorithms to make decisions driving the network. Highquality data is necessary for smart decisions. Yet, highquality data is hard to obtain from the network data plane, due to insufficient visibility and large data volumes stemming from high packet rates. This paper distills principles to collect high-quality data arising from our own research experience: (i) filter and aggregate data as close to the source as possible; (ii) identify broad families of statistics that are measurable with bounded inaccuracy; (iii) don't assume lowlevel data plane software is easy to instrument, but instead (iv) apportion software flexibility by the time scales of the computation; and (v) prefer in-band approaches where possible for timely and efficient reactivity. We call the community to act upon these principles to leverage emerging opportunities using safely-extensible network stacks.
A NetAI Manifesto (Part II): Less Hubris, more Humility
Authors: Willinger Walter , Gupta Arpit , Beltiukov Roman , Guo Wenbo
Published: October 2023

The application of the latest techniques from artificial intelligence (AI) and machine learning (ML) to improve and automate the decision-making required for solving real-world network security and performance problems (NetAI, for short) has generated great excitement among networking researchers. However, network operators have remained very reluctant when it comes to deploying NetAIbased solutions in their production networks. In Part I of this manifesto, we argue that to gain the operators' trust, researchers will have to pursue a more scientific approach towards NetAI than in the past that endeavors the development of explainable and generalizable learning models. In this paper, we go one step further and posit that this "opening up of NetAI research" will require that the largely self-assured hubris about NetAI gives way to a healthy dose humility. Rather than continuing to extol the virtues and "magic" of black-box models that largely obfuscate the critical role of the utilized data play in training these models, concerted research efforts will be needed to design NetAI-driven agents or systems that can be expected to perform well when deployed in production settings and are also required to exhibit strong robustness properties when faced with ambiguous situations and real-world uncertainties. We describe one such effort that is aimed at developing a new ML pipeline for generating trained models that strive to meet these expectations and requirements.
Sympathetic transduction at rest and during cold pressor test in young healthy non-Hispanic Black and White women
Authors: Stephens Brandi Y. , Young Benjamin E. , Nandadeva Damsara , Skow Rachel J. , Greaney Jody L. , Brothers R. Matthew , Fadel Paul J.
Published: October 2023

This study was the first to comprehensively investigate sympathetic vascular transduction and sympathetic and BP reactivity during a cold pressor test in young, healthy BL women. We demonstrated that young BL women do not exhibit exaggerated resting sympathetic vascular transduction and do not have augmented sympathetic or BP reactivity during cold stress compared with their WH counterparts. Collectively, these findings suggest that alterations in sympathetic transduction and reactivity are not apparent in young, healthy BL women.
Integrative physiology of lysine metabolites
Authors: Tan Yifan , Chrysopoulou Maria , Rinschen Markus M.
Published: October 2023

Lysine is an essential amino acid that serves as a building block in protein synthesis. Beside this, the metabolic activity of lysine has only recently been unraveled. Lysine metabolism is tissue specific and is linked to several renal, cardiovascular, and endocrinological diseases through human metabolomics datasets. As a free molecule, lysine takes part in the antioxidant response and engages in protein modifications, and its chemistry shapes both proteome and metabolome. In the proteome, it is an acceptor for a plethora of posttranslational modifications. In the metabolome, it can be modified, conjugated, and degraded. Here, we provide an update on integrative physiology of mammalian lysine metabolites such as α-aminoadipic acid, saccharopine, pipecolic acid, and lysine conjugates such as acetyl-lysine, and sugar-lysine conjugates such as advanced glycation end products. We also comment on their emerging associative and mechanistic links to renal disease, hypertension, diabetes, and cancer.
Data from Kinome reprogramming is a targetable vulnerability in ESR1 fusion-driven breast cancer
Authors: Gou Xuxu , Kim Beom-Jun , Anurag Meenakshi , Lei Jonathan T. , Young Meggie N. , Holt Matthew V. , Fandino Diana , Vollert Craig T. , Singh Purba , Alzubi Mohammad A. , Malovannaya Anna , Dobrolecki Lacey E. , Lewis Michael T. , Li Shunqiang , Foulds Charles E. , Ellis Matthew J.
Published: October 2023

Abstract
Transcriptionally active ESR1 gene fusions (ESR1-TAF) are a potent cause of breast cancer endocrine therapy (ET) resistance. ESR1-TAFs are not directly druggable because the C-terminal estrogen/anti-estrogen binding domain is replaced with translocated in-frame partner gene sequences that confer constitutive transactivation. To discover alternative treatments, a mass spectrometry (MS)-based kinase inhibitor pulldown assay (KIPA) was deployed to identify druggable kinases that are upregulated by diverse ESR1-TAFs. Subsequent explorations of drug sensitivity validated RET kinase as a common therapeutic vulnerability despite remarkable ESR1-TAF C-terminal sequence and structural diversity. Organoids and xenografts from a pan-ET resistant patient-derived xenograft (PDX) model that harbors the ESR1-e6>YAP1 TAF were concordantly inhibited by the selective RET inhibitor pralsetinib to a similar extent as the CDK4/6 inhibitor palbociclib. Together, these findings provide preclinical rationale for clinical evaluation of RET inhibition for the treatment of ESR1-TAF-driven ET resistant breast cancer.
Data from Single-cell characterization of pulmonary nodules implicates suppression of immunosurveillance across early stages of lung adenocarcinoma
Authors: Yanagawa Jane , Tran Linh M. , Salehi-Rad Ramin , Lim Raymond J. , Dumitras Camelia , Fung Eileen , Wallace William D. , Prosper Ashley E. , Fishbein Gregory , Shea Conor , Hong Rui , Kahangi Bitta , Deng John J. , Gower Adam C. , Liu Bin , Campbell Joshua D. , Mazzilli Sarah A. , Beane Jennifer E. , Kadara Humam , Lenburg Marc E. , Spira Avrum E. , Aberle Denise R. , Krysan Kostyantyn , Dubinett Steven M.
Published: October 2023

Abstract
A greater understanding of molecular, cellular, and immunological changes during the early stages of lung adenocarcinoma development could improve diagnostic and therapeutic approaches in patients with pulmonary nodules at risk for lung cancer. To elucidate the immunopathogenesis of early lung tumorigenesis, we evaluated surgically resected pulmonary nodules representing the spectrum of early lung adenocarcinoma as well as associated normal lung tissues utilizing single-cell RNA sequencing and validated the results by flow cytometry and multiplex immunofluorescence. Single-cell transcriptomics revealed a significant decrease in gene expression associated with cytolytic activities of tumor-infiltrating natural killer and natural killer T cells. This was accompanied by a reduction in effector T cells and an increase of CD4+ regulatory T cells in subsolid nodules. An independent set of resected pulmonary nodules consisting of both adenocarcinomas and associated premalignant lesions corroborated the early increment of regulatory T cells in premalignant lesions compared to the associated normal lung tissues by multiplex immunofluorescence. Gene expression analysis indicated that cancer-associated alveolar type 2 cells and fibroblasts may contribute to the deregulation of the extracellular matrix, potentially affecting immune infiltration in subsolid nodules through ligand-receptor interactions. These findings suggest that there is a suppression of immune surveillance across the spectrum of early-stage lung adenocarcinoma.
Data from LncRNA AGPG confers endocrine resistance in breast cancer by promoting E2F1 activity
Authors: Yu Shiyi , Wang Ying , Gong Xue , Fan Zhehao , Wang Zheng , Liang Zhengyan , Wu Rui , Cao Binjie , Wang Ning , Bi Caili , Lv Dan , Sun Haibo
Published: October 2023

Abstract
Resistance to endocrine therapy represents a major concern for patients with estrogen receptor α positive (ERα+) breast cancer. Endocrine therapy resistance is commonly mediated by activated E2F signaling. A better understanding of the mechanisms governing E2F1 activity in resistant cells could reveal strategies for overcoming resistance. Here, we identified the long non-coding RNA (lncRNA) actin gamma 1 pseudogene 25 (AGPG) as a regulator of E2F1 activity in endocrine resistant breast cancer. Expression of EGPG was increased in endocrine-resistant breast cancer cells, which was driven by epigenomic activation of an enhancer. AGPG was also abnormally upregulated in patient breast tumors, especially in the luminal B subtype, and high AGPG expression was associated with poor survival of ERα+ breast cancer patients receiving endocrine therapy. The upregulation of AGPG mediated resistance to endocrine therapy and CDK4/6 inhibition in breast cancer cells. Mechanistically, AGPG physically interacted with PURα, thus releasing E2F1 from PURα and leading to E2F1 signaling activation in ERα+ breast cancer cells. In breast cancer patients, E2F1 target genes were positively and negatively correlated with expression of AGPG and PURα, respectively. Co-administration of chemically modified AGPG siRNA and tamoxifen strongly suppressed tumor growth in endocrine resistant cell line-derived xenografts. Together, these results demonstrate that AGPG can drive endocrine therapy resistance and indicate that it is a promising biomarker and potential therapeutic target in breast cancer.
Data from Socioeconomic Status at Birth and Breast Tissue Composition in Adolescence and Adulthood
Authors: Kehm Rebecca D. , Lilge Lothar , Walter E. Jane , White Melissa , Herbstman Julie B. , Perera Frederica P. , Miller Rachel L. , Terry Mary Beth , Tehranifar Parisa
Published: October 2023

AbstractBackground:
Socioeconomic status (SES) at birth is associated with breast cancer risk. Whether this association is driven by changes in breast tissue composition (BTC) prior to adulthood remains unclear.
Methods:
We used multivariable linear regression models to examine whether SES at birth is associated with BTC in adolescence and adulthood using data from a New York City cohort of daughters (n = 165, 11–20 years) and mothers (n = 160, 29–55 years). We used maternal-reported data on daughters’ household income and maternal education at birth, analyzed individually and in combination (SES index). Women also reported their own mothers’ education at birth. We used optical spectroscopy to evaluate BTC measures that positively (water content, collagen content, optical index) and negatively (lipid content) correlate with mammographic breast density, a recognized breast cancer risk factor.
Results:
Being in the highest versus lowest category of the SES index was associated with lower lipid content [βadjusted (βadj) = −0.80; 95% confidence interval (CI), −1.30 to –0.31] and higher collagen content (βadj = 0.54; 95% CI, 0.09–0.99) in adolescence. In women with a body mass index (BMI) <30 kg/m2, higher maternal education at birth (≥ vs. < high school degree) was associated with lower lipid content (βadj = −0.57; 95% CI, −0.97 to −0.17), higher water content (βadj = 0.70; 95% CI, 0.26–1.14), and higher optical index (βadj = 0.53; 95% CI, 0.10–0.95).
Conclusions:
This study supports that SES at birth is associated with BTC in adolescence and adulthood, although the latter association may depend on adult BMI.
Impact:
Further research is needed to identify the socially patterned early life factors influencing BTC.
Data from Associations between Ambient Air Pollutants and Clonal Hematopoiesis of Indeterminate Potential
Authors: Leiser Claire L. , Whitsel Eric A. , Reiner Alexander , Rich Stephen S. , Rotter Jerome I. , Taylor Kent D. , Tracy Russel P. , Kooperberg Charles , Smith Albert Vernon , Manson JoAnn E. , Mychaleckyj Josyf C. , Bick Alexander G. , Szpiro Adam A. , Kaufman Joel D.
Published: October 2023

AbstractBackground:
Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related somatic mutation associated with incident hematologic cancer. Environmental stressors which, like air pollution, generate oxidative stress at the cellular level, may induce somatic mutations and some mutations may provide a selection advantage for persistence and expansion of specific clones.
Methods:
We used data from the Multi-Ethnic Study of Atherosclerosis (MESA) N = 4,379 and the Women's Health Initiative (WHI) N = 7,701 to estimate cross-sectional associations between annual average air pollution concentrations at participant address the year before blood draw using validated spatiotemporal models. We used covariate-adjusted logistic regression to estimate risk of CHIP per interquartile range increases in particulate matter (PM2.5; 4 μg/m3) and nitrogen dioxide (NO2; 10 ppb) as ORs (95% confidence intervals).
Results:
Prevalence of CHIP at blood draw (variant allele fraction > 2%) was 4.4% and 8.7% in MESA and WHI, respectively. The most common CHIP driver mutation was in DNMT3A. Neither pollutant was associated with CHIP: ORMESA PM2.5 = 1.00 (0.68–1.45), ORMESA NO2 = 1.05 (0.69–1.61), ORWHI PM2.5 = 0.97 (0.86–1.09), ORWHI NO2 = 0.98 (0.88–1.10); or with DNMT3A-driven CHIP.
Conclusions:
We did not find evidence that air pollution contributes to CHIP prevalence in two large observational cohorts.
Impact:
This is the first study to estimate associations between air pollution and CHIP.
Data from Urine pH and Risk of Bladder Cancer in Northern New England
Authors: Fischer Alexander H. , Wong Jason Y.Y. , Baris Dalsu , Koutros Stella , Karagas Margaret R. , Schwenn Molly , Johnson Alison , Alguacil Juan , Silverman Debra T. , Rothman Nathaniel
Published: October 2023

AbstractBackground:
Acidic urine pH is associated with rapid hydrolysis of N-glucuronide conjugates of aromatic amines into metabolites that may undergo metabolism in the bladder lumen to form mutagenic DNA adducts. We previously reported that consistently acidic urine was associated with increased bladder cancer risk in a hospital-based case–control study in Spain. Here, we conducted a separate study in northern New England to replicate these findings.
Methods:
In a large, population-based case–control study conducted in Maine, New Hampshire, and Vermont, we examined bladder cancer risk in relation to consistent urine pH, measured twice daily by participants over 4 consecutive days using dipsticks. In parallel, we collected spot urine samples and conducted laboratory measurements of urinary acidity using a pH meter. Unconditional logistic regression was used to estimate associations, adjusting for age, gender, race, Hispanic status, and state. Analyses were further stratified by smoking status.
Results:
Among 616 urothelial carcinoma cases and 897 controls, urine pH consistently ≤ 6.0 was associated with increased bladder cancer risk (OR = 1.27; 95% confidence interval, 1.02–1.57), with the effect limited to ever-smokers. These findings were supported by analyses of a spot urine, with statistically significant exposure–response relationships for bladder cancer risk overall (Ptrend = 5.1×10−3) and among ever-smokers (Ptrend = 1.2×10−3).
Conclusions:
Consistent with a previous study in Spain, our findings suggest that acidic urine pH is associated with increased bladder cancer risk.
Impact:
Our findings align with experimental results showing that acidic urine pH, which is partly modifiable by lifestyle factors, is linked to hydrolysis of acid-labile conjugates of carcinogenic aromatic amines.
Data from Dietary Fish and n-3 Polyunsaturated Fatty Acid Consumption, and Renal Cell Carcinoma Risk in Japan: The Japan Public Health Center-Based Prospective Study
Authors: Takahashi Michiko , Sobue Tomotaka , Zha Ling , Kitamura Tetsuhisa , Iwasaki Motoki , Inoue Manami , Yamaji Taiki , Tsugane Shoichiro , Sawada Norie
Published: October 2023

AbstractBackground:
Previous epidemiologic studies found inconsistent associations between fish consumption and renal cell carcinoma (RCC). Although the consumption of n-3 polyunsaturated fatty acids (PUFA) was reported to protect against the development of some types of cancer, little is known regarding its association with RCC.
Methods:
We investigated the association between fish and n-3 PUFA consumption and RCC risk using the Japan Public Health Center-based Prospective Study. We examined data from 84,063 eligible Japanese participants aged 45 to 74 years who responded to a validated food frequency questionnaire for Cohort I in 1995 and Cohort II in 1998. The participants were followed-up until 2013. HRs and 95% confidence intervals (CI) were estimated using a multivariable-adjusted Cox proportional hazard model, and the exposure level was categorized into quartiles.
Results:
Among the 1,272,298 person-years of follow-up, 262 cases of newly diagnosed RCC were identified. The multivariate-adjusted HRs for the highest vs. lowest quartile of fish, including shellfish, were (HR = 1.43; 95% CI, 0.98–2.07) and the individual marine n-3 PUFAs were (HR = 1.56; 95% CI, 1.07–2.28; Ptrend = 0.09) for eicosapentenoic acid, (HR = 1.81; 95% CI, 1.27–2.59; Ptrend = 0.01) for docosapentaenoic acid, and (HR = 1.56; 95% CI, 1.07–2.27; Ptrend = 0.09) for docosahexaenoic acid. RCC were further categorized on the basis of diagnosis methods and cancer stage, and the positive correlation did not change substantially.
Conclusions:
We demonstrated that high consumption of n-3 PUFA is associated with RCC risk.
Impact:
The positive association between n-3 PUFA and RCC risk was observed in Japanese who consume higher amounts of fish than Western populations.
Data from Multiomic Mapping of Acquired Chromosome 1 Copy-Number and Structural Variants to Identify Therapeutic Vulnerabilities in Multiple Myeloma
Authors: Boyle Eileen M. , Blaney Patrick , Stoeckle James H. , Wang Yubao , Ghamlouch Hussein , Gagler Dylan , Braunstein Marc , Williams Louis , Tenenbaum Avital , Siegel Ariel , Chen Xiaoyi , Varma Gaurav , Avigan Jason , Li Alexander , Jinsi Monica , Kaminetzsky David , Arbini Arnaldo , Montes Lydia , Corre Jill , Rustad Even H. , Landgren Ola , Maura Francesco , Walker Brian A. , Bauer Michael , Bruno Benedetto , Tsirigos Aristotelis , Davies Faith E. , Morgan Gareth J.
Published: October 2023

AbstractPurpose:
Chromosome 1 (chr1) copy-number abnormalities (CNA) and structural variants (SV) are frequent in newly diagnosed multiple myeloma (NDMM) and are associated with a heterogeneous impact on outcomes, the drivers of which are largely unknown.
Experimental Design:
A multiomic approach comprising CRISPR, gene mapping of CNAs and SVs, methylation, expression, and mutational analysis was used to document the extent of chr1 molecular variants and their impact on pathway utilization.
Results:
We identified two distinct groups of gain(1q): focal gains associated with limited gene-expression changes and a neutral prognosis, and whole-arm gains, which are associated with substantial gene-expression changes, complex genetics, and an adverse prognosis. CRISPR identified a number of dependencies on chr1 but only limited variants associated with acquired CNAs. We identified seven regions of deletion, nine of gain, three of chromothripsis (CT), and two of templated insertion (TI), which contain a number of potential drivers. An additional mechanism involving hypomethylation of genes at 1q may contribute to the aberrant gene expression of a number of genes. Expression changes associated with whole-arm gains were substantial and gene set enrichment analysis identified metabolic processes, apoptotic resistance, signaling via the MAPK pathway, and upregulation of transcription factors as being key drivers of the adverse prognosis associated with these variants.
Conclusions:
Multiple layers of genetic complexity impact the phenotype associated with CNAs on chr1 to generate its associated clinical phenotype. Whole-arm gains of 1q are the critically important prognostic group that deregulate multiple pathways, which may offer therapeutic vulnerabilities.
Data from Learning Individual Survival Models from PanCancer Whole Transcriptome Data
Authors: Kumar Neeraj , Skubleny Daniel , Parkes Michael , Verma Ruchika , Davis Sacha , Kumar Luke , Aissiou Amira , Greiner Russell
Published: October 2023

Abstract
Purpose: Personalized medicine attempts to predict survival time for each patient, based on their individual tumour molecular profile. We investigate whether our survival learner in combination with a dimension reduction method can produce useful survival estimates for a variety of cancer patients. Experimental Design: This paper provides a method that learns a model for predicting the survival time for individual cancer patients from the PanCancer Atlas: given the (16335-dimensional) gene expression profiles from 10173 patients, each having one of 33 cancers, this method uses unsupervised NMF (non-negative matrix factorization) to re-express the gene expression data for each patient in terms of 100 learned NMF Factors. It then feeds these 100 Factors into the MTLR (Multi-Task Logistic Regression) learner to produce cancer-specific models for each of 20 cancers (with >50 uncensored instances); this produces “individual survival distributions” (ISDs), which provide survival probabilities at each future time for each individual patient – which provides a patient’s risk score and estimated survival time. Results: Our NMF-MTLR concordance indices outperformed the VAECox benchmark by 14.9% overall. We achieved optimal survival prediction using pan-cancer NMF in combination with cancer-specific MTLR models. We provide biological interpretation of the NMF model and clinical implications of ISDs for prognosis and therapeutic response prediction. Conclusions: NMF-MTLR provides many benefits over other models: superior model discrimination, superior calibration, meaningful survival time estimates, and accurate probabilistic estimates of survival over time for each individual patient. We advocate for the adoption of these cancer survival models in clinical and research settings.
Data from Safety and Efficacy of Anlotinib Hydrochloride Plus Temozolomide in Patients with Recurrent Glioblastoma
Authors: Xu Qingsheng , Huang Kaiyuan , Meng Xiangqi , Weng Yuxiang , Zhang Luyuan , Bu Linghao , Zheng Xiujue , Cai Jinquan , Zhan Renya , Chen Qun
Published: October 2023

Abstract
Background: Glioblastoma (GBM) is a highly vascularized tumor with few treatment options after disease recurrence. Here, we report the efficacy and safety of anlotinib hydrochloride plus temozolomide in patients with recurrent GBM. Methods: Patients with first definite postsurgical progression of histologically confirmed GBM preceded by standard radiotherapy and temozolomide chemotherapy were eligible for inclusion. All patients received temozolomide (150-200mg/m2, orally, QD, d1-5/4wks) and anlotinib (10mg, orally, QD, d1-14/3wks) until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed 6-month PFS rate by RANO criteria. Result: Twenty-one patients were enrolled between May 2020 and July 2021, with a median age of 55 (range 27-68) years old. According to the RANO criteria, tumor response occurred in 17 patients, of which 9 patients had a complete response, and the objective response rate was 81.0% (95% CI 62.6-99.3). The disease control rate was 95.2% (95% CI 76.2-99.9), with three additional patients achieving a stable disease without tumor progression. The median PFS was 7.3 months (95% CI 4.9-9.7), and the 6-month PFS rate was 61.9% (95% CI 39.3-84.6). The median overall OS was 16.9 months (95% CI 7.8-26.0). The most common adverse events were leukocytopenia (66.7%), thrombocytopenia (38.1%), and hypertriglyceridemia (38.1%). Five patients had nine grade 3 adverse events, with a 23.8% incidence rate. Two patients discontinued therapy due to ischemic stroke (grade 3) and wound dehiscence (grade 1) respectively. No grade 4 or treatment-related deaths occurred in this study. Conclusions: Anlotinib combined with temozolomide is efficacious and tolerated in recurrent GBM patients.