bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tobacco 21 adoption decreased sales of cigarette brands purchased by young people: a translation of population health survey data to gain insight into market data for policy analysis
Authors: Liber Alex C , Xue Zheng , Cahn Zachary , Drope Jeffrey , Stoklosa Michal 
Published: December 2020

IntroductionPolicies raising the minimum age of sale of tobacco products to 21 (T21) proliferated at state and local levels across the USA before a federal policy was adopted. Evidence of the effectiveness of these policies is building and lags implementation. This study exploits demographic patterns of cigarette brand purchasing to evaluate the effectiveness of T21.MethodsTo capture the effect of T21 implementation on cigarette sales, we used universal product code-level data from Nielsen Scantrack data covering January 2015 to October 2019. We used the 2015 to 2018 National Survey on Drug Use and Health to identify cigarette brands where smokers under 21 comprised a disproportionately high (young) and low (old) share of consumption. We fit fixed-effects linear regressions in Nielsen designated market areas to test if sales of young or old cigarette brands were changed by T21. Unadjusted models controlled for time and T21 implementation date. Adjusted models controlled for price, seasonality and unemployment. A permutation test of 5000 randomised placebo T21 policies were fit to determine how well the true date of implementation fit sales data stratified by brand group.ResultsSales of disproportionately young brands declined after T21 implementation. T21 policy implementation dates fit disproportionately young brand sales trends better than 99% of adjusted randomised placebo models. T21 implementation fit disproportionately old brand sales trends better than just 1% of adjusted randomised placebo models.ConclusionThis study adds compelling empirical evidence that T21 decreased purchases of the cigarette brands consumed disproportionately by young people, the policy’s target demographic.
Unphysical properties in a class of interacting dark energy models
Authors: von Marttens R. , Borges H. A. , Carneiro S. , Alcaniz J. S. , Zimdahl W. 
Published: December 2020

AbstractModels with non-gravitational interactions between the dark matter and dark energy components are an alternative to the standard cosmological scenario. These models are characterized by an interaction term, and a frequently used parameterization is $$Q = 3\xi H \rho _{x}$$

Q
=
3
ξ
H

ρ
x

, where H is the Hubble parameter and $$\rho _{x}$$

ρ
x

is the dark energy density. Although recent analyses have reported that this particular scenario provides a potential solution to the $$H_{0}$$

H
0

and $$\sigma _{8}$$

σ
8

tensions for negative values of the interaction parameter $$\xi $$
ξ
, we show here that such an interval of values of $$\xi $$
ξ
leads to a violation of the Weak Energy Condition for the dark matter density, which is accompanied by unphysical instabilities of matter perturbations. Using current observational data we also show that the inclusion of the physical prior $$\xi \ge 0$$

ξ
≥
0

in the statistical analysis alters the parameter selection for this model and discards it as a solution for the $$H_{0}$$

H
0

-tension problem.
Flipped U(1) extended standard model and Majorana dark matter
Authors: Nam Cao H. 
Published: December 2020

AbstractWe propose a general flavor-independent extension of the Standard Model (SM) with the minimal particle content, based on the symmetry $$SU(3)_C\times SU(2)_L\times U(1)_{Y'}\times U(1)_X\times Z_2$$

S
U

(
3
)

C

×
S
U

(
2
)

L

×
U

(
1
)

Y
′

×
U

(
1
)

X

×

Z
2

. In this scenario, the charge operator is identified in terms of the charges of two U(1) gauge symmetries. The light neutrino masses are generated via Type-I seesaw mechanism only with two heavy right-handed neutrinos acquiring their Majorana masses through the $$U(1)_{Y'}\times U(1)_X$$

U

(
1
)

Y
′

×
U

(
1
)

X

symmetry breaking. We study various experimental constraints on the parameters of the model and investigate the phenomenology of the right-handed neutrino dark matter (DM) candidate assigned a $$Z_2$$

Z
2

-odd parity. We find that the most important constraints are the observed DM relic abundance, the current LHC limits, and the ambiguity of the SM neutral gauge boson mass.
Weighing massive neutron star with screening gravity: a look on PSR J0740 + 6620 and GW190814 secondary component
Authors: Nunes Rafael C. , Coelho Jaziel G. , de Araujo José C. N. 
Published: December 2020

AbstractNeutron stars (NSs) are excellent natural laboratories to constrain gravity on strong field regime and nuclear matter in extreme conditions. Motivated by the recent discovery of a compact object with $$2.59^{+0.08}_{-0.09} M_\odot $$

2
.

59

-
0.09

+
0.08

M
⊙

in the binary merger GW190814, if this object was a NS, it serves as a strong constraint on the NS equation of state (EoS), ruling out several soft EoSs favored by GW170817 event. In this work, we revisit the question of the maximum mass of NSs considering a chameleon screening (thin-shell effect) on the NS mass-radius relation, where the microscopic physics inside the NS is given by realistic soft EoSs. We find that from appropriate and reasonable combination of modified gravity, rotation effects and realistic soft EoSs, that it is possible to achieve high masses and explain GW190814 secondary component, and in return also NSs like PSR J0740 + 6620 (the most NS massive confirmed to date). It is shown that gravity can play an important role in estimating maximum mass of NSs, and even with soft EoSs, it is possible to generate very high masses. Therefore, in this competition of hydrostatic equilibrium between gravity and pressure (from EoS choice), some soft EoSs, in principle, cannot be completely ruled out without first taking into account gravitational effects.
AZD0364 Is a Potent and Selective ERK1/2 Inhibitor That Enhances Antitumor Activity inKRAS-Mutant Tumor Models when Combined with the MEK Inhibitor, Selumetinib
Authors: Flemington Vikki , Davies Emma J. , Robinson David , Sandin Linda C. , Delpuech Oona , Zhang Pei , Hanson Lyndsey , Farrington Paul , Bell Sigourney , Falenta Katarzyna , Gibbons Francis D. , Lindsay Nicola , Smith Aaron , Wilson Joanne , Roberts Karen , Tonge Michael , Hopcroft Philip , Willis Sophie E. , Roudier Martine P. , Rooney Claire , Coker Elizabeth A. , Jaaks Patricia , Garnett Mathew J. , Fawell Stephen E. , Jones Clifford D. , Ward Richard A. , Simpson Iain , Cosulich Sabina C. , Pease J. Elizabeth , Smith Paul D. 
Published: December 2020

AbstractThe RAS-regulated RAF–MEK1/2–ERK1/2 (RAS/MAPK) signaling pathway is a major driver in oncogenesis and is frequently dysregulated in human cancers, primarily by mutations in BRAF or RAS genes. The clinical benefit of inhibitors of this pathway as single agents has only been realized in BRAF-mutant melanoma, with limited effect of single-agent pathway inhibitors in KRAS-mutant tumors. Combined inhibition of multiple nodes within this pathway, such as MEK1/2 and ERK1/2, may be necessary to effectively suppress pathway signaling in KRAS-mutant tumors and achieve meaningful clinical benefit. Here, we report the discovery and characterization of AZD0364, a novel, reversible, ATP-competitive ERK1/2 inhibitor with high potency and kinase selectivity. In vitro, AZD0364 treatment resulted in inhibition of proximal and distal biomarkers and reduced proliferation in sensitive BRAF-mutant and KRAS-mutant cell lines. In multiple in vivo xenograft models, AZD0364 showed dose- and time-dependent modulation of ERK1/2-dependent signaling biomarkers resulting in tumor regression in sensitive BRAF- and KRAS-mutant xenografts. We demonstrate that AZD0364 in combination with the MEK1/2 inhibitor, selumetinib (AZD6244 and ARRY142886), enhances efficacy in KRAS-mutant preclinical models that are moderately sensitive or resistant to MEK1/2 inhibition. This combination results in deeper and more durable suppression of the RAS/MAPK signaling pathway that is not achievable with single-agent treatment. The AZD0364 and selumetinib combination also results in significant tumor regressions in multiple KRAS-mutant xenograft models. The combination of ERK1/2 and MEK1/2 inhibition thereby represents a viable clinical approach to target KRAS-mutant tumors.
The HPV and p63 Status in Penile Cancer Are Linked with the Infiltration and Therapeutic Availability of Neutrophils
Authors: Bernhard Muriel Charlotte , Zwick Anabel , Mohr Tobias , Gasparoni Gilles , Khalmurzaev Oybek , Matveev Vsevolod Borisovich , Loertzer Philine , Pryalukhin Alexey , Hartmann Arndt , Geppert Carol-Immanuel , Loertzer Hagen , Wunderlich Heiko , Naumann Carsten Maik , Kalthoff Holger , Junker Kerstin , Smola Sigrun , Lohse Stefan 
Published: December 2020

Abstract
Squamous penile cancer displays a rare human papillomavirus (HPV)–associated tumor entity. Investigations on the molecular pathogenesis of HPV-driven penile cancer are impaired by the rareness of clinical specimens and, in particular, are missing relevant cell culture models. Here, we identified in HPV-positive penile cancer cell lines that HPV16 oncoproteins control TP63 expression by modulating critical regulators, while integration into the TP63 open reading frame facilitates oncogene expression. The resulting feed-forward loop leads to elevated p63 levels that in turn enhance the release of the neutrophil-recruiting chemokine CXCL8. Remarkably, elevated CXCL8 amounts lead to the increased surface exposition of the Fc receptor of human IgA antibodies, FcαRI, on neutrophils and correlated with a higher susceptibility to antibody-dependent neutrophil-mediated cytotoxicity (ADCC) using an EGFR-specific IgA2 antibody. IHC staining of tissue microarrays proved that elevated expression of p63 together with neutrophil infiltration were significantly more frequent in HPV-positive penile cancer displaying a higher tumor grade. In summary, we identified a promising marker profile of patients with penile cancer at higher risk for worse prognosis. However, these patients may benefit from immunotherapeutic approaches efficiently engaging neutrophils for tumor cell killing.
Development of Novel Antibody–Camptothecin Conjugates
Authors: Lyski Ryan D. , Bou Lauren B. , Lau Uland Y. , Meyer David W. , Cochran Julia H. , Okeley Nicole M. , Emmerton Kim K. , Zapata Francisco , Simmons Jessica K. , Trueblood Esther S. , Ortiz David J. , Zaval Margo C. , Snead Katie M. , Jin Steven , Farr Lauren M. , Ryan Maureen C. , Senter Peter D. , Jeffrey Scott C. 
Published: December 2020

Abstract
We have developed a highly active and well-tolerated camptothecin (CPT) drug-linker designed for antibody-mediated drug delivery in which the lead molecule consists of a 7-aminomethyl-10,11-methylenedioxy CPT (CPT1) derivative payload attached to a novel hydrophilic protease-cleavable valine–lysine–glycine tripeptide linker. A defined polyethylene glycol stretcher was included to improve the properties of the drug-linker, facilitating high antibody–drug conjugate (ADC) drug loading, while reducing the propensity for aggregation. A CPT1 ADC with 8 drug-linkers/mAb displayed a pharmacokinetic profile coincident with parental unconjugated antibody and had high serum stability. The ADCs were broadly active against cancer cells in vitro and in mouse xenograft models, giving tumor regressions and complete responses at low (≤3 mg/kg, single administration) doses. Pronounced activities were obtained in both solid and hematologic tumor models and in models of bystander killing activity and multidrug resistance. Payload release studies demonstrated that two CPTs, CPT1 and the corresponding glycine analog (CPT2), were released from a cAC10 ADC by tumor cells. An ADC containing this drug-linker was well tolerated in rats at 60 mg/kg, given weekly four times. Thus, ADCs comprised of this valine–lysine–glycine linker with CPT drug payloads have promise in targeted drug delivery.
Abstract IA02: Host microbiome interactions in health and disease
Authors: Elinav Eran 
Published: December 2020

Abstract
The mammalian intestine contains trillions of microbes, a community that is dominated by members of the domain Bacteria but also includes members of Archaea, Eukarya, and viruses. The vast repertoire of this microbiome functions in ways that benefit the host. The mucosal immune system coevolves with the microbiota beginning at birth, acquiring the capacity to tolerate components of the community while maintaining the capacity to respond to invading pathogens. The gut microbiota is shaped and regulated by multiple factors including our genomic composition, the local intestinal niche, and multiple environmental factors including our nutritional repertoire and biogeographic location. Moreover, it has been recently highlighted that dysregulation of these genetic or environmental factors leads to aberrant host-microbiome interactions, ultimately predisposing to pathologies ranging from chronic inflammation, obesity, the metabolic syndrome, and even cancer. We have identified various possible mechanisms participating in the reciprocal regulation between the host and the intestinal microbial ecosystem and demonstrate that disruption of these factors, in mice and humans, lead to dysbiosis and susceptibility to common multifactorial disease. Understanding the molecular basis of host-microbiome interactions may lead to development of new microbiome-targeting treatments.
Citation Format: Eran Elinav. Host microbiome interactions in health and disease [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr IA02.
Abstract IA23: Impact of metastatic prostate cancer on human bone marrow
Authors: Baryawno Ninib , Kfoury Youmna , Severe Nicolas , Mei Shenglin , Gustafsson Karin , Hirz Taghreed , Brouse Thomas , Scadden Elizabeth W. , Igolkina Anna A. , Choi Bryan D. , Barkas Nikolas , Shin John H. , Saylor Philip J. , Scadden David T. , Sykes David B. , Kharchenko Peter V. 
Published: December 2020

Abstract
Cancer-related mortality due to solid tumor malignancies is overwhelmingly due to the development and progression of metastases. In advanced prostate cancer, metastases most often involve the bone and generally represent incurable disease. It remains unclear what aspects of the bone marrow microenvironment make it hospitable to metastatic dissemination. Similarly, the impact of the metastatic tumor on hematopoiesis and the marrow immune response is poorly understood. We took advantage of rare spinal cord decompression surgeries to profile marrow and metastatic tumors from men with advanced prostate cancer at single-cell resolution. Our analysis contrasts the cellular composition and transcriptional states in matched samples of tumor and liquid bone marrow collected at adjacent vertebral body levels, as well as bone marrow of orthopedic patients without malignancy. Metastatic prostate cancer was associated with hematopoietic suppression and multifaceted immune distortion. There was exhaustion of specific T cell subsets, appearance of inflammatory monocytes and macrophages, and alteration of cytokine profiles. Computational analysis showed association between the presence of specific myeloid subsets and the level of T lymphocyte dysfunction in the tumor fraction. We screened for potential signaling axes that may underlie this interaction. Among them was chemokine CCL20, notably overexpressed by myeloid cells, as was its cognate CCR6 receptor, expressed on T cells. We developed a syngeneic mouse model of bone-metastatic prostate cancer to explore this observation, and demonstrated that disruption of the CCL20-CCR6 axis from either side resulted in significant prolongation of survival. Our results further indicated that this dual overexpression was associated with repressed immune responses. Overall, comparative high-resolution analysis of bone marrow reveals distinct alterations associated with prostate cancer bone metastases that may be amenable to therapeutic targeting with the goal of altering cancer progression.
Citation Format: Ninib Baryawno, Youmna Kfoury, Nicolas Severe, Shenglin Mei, Karin Gustafsson, Taghreed Hirz, Thomas Brouse, Elizabeth W. Scadden, Anna A. Igolkina, Bryan D. Choi, Nikolas Barkas, John H. Shin, Philip J. Saylor, David T. Scadden, David B. Sykes, Peter V. Kharchenko, as part of the Boston Bone Metastasis Consortium. Impact of metastatic prostate cancer on human bone marrow [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr IA23.
Abstract PO-120: MYC drives temporal evolution of small cell lung cancer subtypes by reprogramming neuroendocrine fate
Authors: Ireland Abbie S. , Micinski Alexi M. , Kastner David W. , Guo Bingqian , Wait Sarah J. , Spainhower Kyle B. , Conley Christopher C. , Chen Opal S. , Guthrie Matthew R. , Soltero Danny , Qiao Yi , Huang Xiaomeng , Tarapcsak Szabolcs , Devarakonda Siddhartha , Chalishazar Milind D. , Gertz Jason , Moser Justin C. , Marth Gabor , Puri Sonam , Witt Benjamin L. , Spike Benjamin T. , Oliver Trudy G. 
Published: December 2020

Abstract
Small cell lung cancer (SCLC) is a highly aggressive neuroendocrine tumor that is treated clinically as a single disease with poor outcomes. However, SCLC is recently recognized to comprise multiple molecular subsets with unique therapeutic vulnerabilities. Four distinct subtypes of SCLC have been defined based on expression of lineage-related transcription factors: ASCL1, NEUROD1, POU2F3 or YAP1. The origins of these subtypes remain unknown. We use mouse and human SCLC models with a time-series analysis of single-cell transcriptome profiling to reveal that the oncogene MYC drives the dynamic evolution of SCLC subtypes by activation of Notch signaling. MYC cooperates with Notch signaling to promote a temporal shift from an ASCL1-to-NEUROD1-to-YAP1-positive state from a neuroendocrine cell of origin, whereas MYC promotes POU2F3+ tumors from a distinct cell type. SCLC molecular subtypes are therefore not distinct, but rather represent dynamic stages of MYC-driven tumor evolution. Treatment-naive human SCLC exhibits intratumoral heterogeneity in SCLC subtypes, suggesting this dynamic evolution occurs in patient tumors. These findings demonstrate that genetics, cell of origin, and tumor cell plasticity determine SCLC subtype. Given the reported unique therapeutic vulnerabilities of each subtype, we postulate that SCLC tumors represent a “moving therapeutic target” that may require more general, combinatorial, or plasticity-directed therapeutic approaches to combat this transcriptional flexibility. We anticipate that molecular subsets of other cancer types may also represent dynamic stages of tumor evolution.
Citation Format: Abbie S. Ireland, Alexi M. Micinski, David W. Kastner, Bingqian Guo, Sarah J. Wait, Kyle B. Spainhower, Christopher C. Conley, Opal S. Chen, Matthew R. Guthrie, Danny Soltero, Yi Qiao, Xiaomeng Huang, Szabolcs Tarapcsak, Siddhartha Devarakonda, Milind D. Chalishazar, Jason Gertz, Justin C. Moser, Gabor Marth, Sonam Puri, Benjamin L. Witt, Benjamin T. Spike, Trudy G. Oliver. MYC drives temporal evolution of small cell lung cancer subtypes by reprogramming neuroendocrine fate [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-120.
Abstract PO-016: Putting their money where their mouths are: A review of the literature concerning health research and grant funding organizations and the recruitment of Black women to breast cancer clinical trials
Authors: Ridley-Merriweather Katherine E. 
Published: December 2020

Abstract
Numerous clinical trials exist that focus on addressing treatments that might help improve racial disparities, but the outcomes can be significantly compromised by deficiencies in sample diversity. There is little doubt that increasing the number of Black women represented in clinical trials could positively affect well known adverse racial health statistics. Due to several factors, however, recruiting these women into clinical trials can be a challenging prospect. This review primarily focuses on how Black women are recruited into breast cancer clinical trials and/or treatment protocols, paying particular attention to public and private health organizations and grant-funding agencies that ultimately determine which studies receive funding.
Gaps clearly exist in the literature surrounding the use of communication vehicles and channels to deliver messages these women themselves say they want to hear. This work examines the recruitment of Black women to breast cancer research, identifying themes in the literature where gaps exist. Through illuminating a critical exemplar of the importance of highlighting the needs for increased cross-sectional literature in the fields of communication and psychology, a significant case study is presented as an illustration. Next, some of the industrial/organizational psychology literature on influencing the recruitment of women and racial/ethnic minorities is examined, while suggesting this field may yield some crossover methods (such as incorporating research on identity threat and safety) that may be helpful for addressing the recognized gaps. Finally, suggestions for future applied research opportunities for increasing the participation of Black women in breast cancer research are offered.
Citation Format: Katherine E. Ridley-Merriweather. Putting their money where their mouths are: A review of the literature concerning health research and grant funding organizations and the recruitment of Black women to breast cancer clinical trials [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-016.