bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of feedlot manure on reactive phosphorus in rainfall runoff during the transition from continuous to legacy phases
Authors: Miller J.J. , Beasley B.W. , Owen M.L. , Drury C.F. , Chanasyk D.S. 
Published: January 2021

Little research has compared land application of stockpiled (SM) or composted (CM) beef feedlot manure with straw (ST) or wood-chip (WD) bedding on loss of reactive phosphorus (RP) in runoff. We conducted a 6 yr (2013–2018) rainfall simulation-runoff study and utilized surface (0–5 cm) soil collected from a long-term (since 1998) field experiment on a clay loam soil in southern Alberta, Canada. The treatments consisted of SM or CM with ST or WD bedding applied at 13, 39, and 77 Mg·ha−1 (dry weight), as well as an unamended control and mineral fertilizer treatment. Surface soil was collected from all treatments after 15–17 (C15, C16, C17; 2013–2015) continual annual applications, and then 1–3 yr (L1–L3, 2016–2018) into the legacy phase after manure applications were first discontinued in 2015. The soil was packed into runoff trays, and flow-weighted mean concentrations (FWMCs) and mass loads of RP5 (<5 μm filter) in runoff water were determined during rainfall simulations. Our findings generally supported our null hypothesis of similar RP5 losses for manure type (CM = SM) and bedding (ST = WD) for most years. Successively higher application rates increased RP5 loss by 32%–121%. Termination of long-term applications dramatically reduced FWMCs by 58%–77% and mass loss by 56%–65% from the C17 to L3 years. This suggests an accumulation of soil P during continuous phase and depletion during legacy phase; therefore, lower application rates or termination of applications may reduce RP5 loss in runoff.
Aerial ropeway system — feasibility study in Doha, Qatar
Authors: Tahmasseby Shahram 
Published: January 2021

Aerial ropeway systems, also called gondolas and aerial cable cars, are amongst driverless transportation modes, which are progressively drawing attention in promoting tourism. Aerial ropeway systems have been operated in touristic spots (e.g., over lakes, rivers, and hilly lands) in several countries. Passengers can enjoy a view from above and experience a stress-free and reliable trip. Furthermore, those systems can be exploited as public transportation in urbanized and populated regions. The objective of this article is to investigate the viability of implementing a gondola line over Doha Bay in Qatar as a tourist attraction from marketing, economic, and environmental points of view. In this study, the associated costs (capital, maintenance, and operating) of implementing a monocable detachable gondola technology (MDG) are estimated using international best practices. The economic analysis outcome demonstrates that the revenues generated from fares could offset the required capital investment as well as operating and maintenance costs and hence the proposed gondola could be economically attractive for investors. Moreover, no significant negative impacts and footprint on the environment are anticipated at the exploitation phase of the gondola.
Quark star matter in heavy quark stars
Authors: Chu Peng-Cheng , Zhou Yi , Jiang Yao-Yao , Ma Hong-Yang , Liu He , Zhang Xiao-Min , Li Xiao-Hua 
Published: January 2021

AbstractWe study the thermodynamic properties of asymmetric quark matter and large mass quark stars within the confined-isospin-density-dependent-quark-mass model. We find that the quark matter symmetry energy should be very large in order to describe the recent discovered heavy compact stars PSR J0348+0432 ($$\text {2.01}\pm \text {0.04}M_{\odot }$$

2.01
±
0.04

M
⊙

), MSP J0740+6620 ($$\text {2.14}\pm ^\text {0.10}_\text {0.09}M_{\odot }$$

2.14

±
0.09
0.10

M
⊙

of 68.3$$\%$$
%
credibility interval and $$\text {2.14}\pm ^\text {0.20}_\text {0.18}M_{\odot }$$

2.14

±
0.18
0.20

M
⊙

of 95.4$$\%$$
%
credibility interval) and PSR J2215+5135 (2.27$$\pm ^\text {0.10}_\text {0.09}M_{\odot }$$

±
0.09
0.10

M
⊙

) as QSs. The tidal deformability $$\Lambda _{1.4}$$

Λ

1.4

of the QSs is also investigated in this work, and the result indicates that $$\Lambda _{1.4}$$

Λ

1.4

may depend on the isospin effects and the strength / orientation distribution of the magnetic fields inside the quark stars.
Existence and Uniqueness of Solutions for Fractional Boundary Value Problems under Mild Lipschitz Condition
Authors: Bachar Imed , Mâagli Habib , Eltayeb Hassan 
Published: January 2021

This paper deals with the following boundary value problem

D

α

u

t

=
f

t
,
u

t

,
t
∈

0
,
1

,

u

0

=
u

1

=

D

α
−
3

u

0

=

u

′

1

=
0
,

where

3
<
α
≤
4
,

D

α

is the Riemann-Liouville fractional derivative, and the nonlinearity

f
,

which could be singular at both

t
=
0

and

t
=
1
,

is required to be continuous on

0
,
1

×
ℝ

satisfying a mild Lipschitz assumption. Based on the Banach fixed point theorem on an appropriate space, we prove that this problem possesses a unique continuous solution

u

satisfying

u

t

≤
c
ω

t

,
for

t
∈

0
,
1

and

c
>
0
,

where

ω

t

≔

t

α
−
2

1
−
t

2

.
Light at Night and Risk of Pancreatic Cancer in the NIH-AARP Diet and Health Study
Authors: Xiao Qian , Jones Rena R. , James Peter , Stolzenberg-Solomon Rachael Z. 
Published: January 2021

Abstract

Circadian disruption may play a role in carcinogenesis. Recent research suggests that light at night (LAN), a circadian disruptor, may be a risk factor for cancer. Moreover, LAN has been linked to obesity and diabetes, two risk factors for pancreatic ductal adenocarcinoma (PDAC). Here we examine the relationship between LAN and PDAC in an epidemiologic study of 464,371 participants from the NIH-AARP Diet and Health Study. LAN was estimated from satellite imagery at baseline (1996), and incident primary PDAC cases were ascertained from state cancer registries. Cox proportional hazards models were used to estimate HRs and two-sided 95% confidence intervals (CI) for the association between quintiles of LAN and PDAC in the overall population stratified by sex. Over up to 16.2 years of follow-up, a total of 2,502 incident PDAC were identified in the cohort. Higher estimated LAN exposure was associated with an elevated PDAC risk. Compared with those living in areas in the lowest LAN quintile, those in areas in the highest quintile had a 27% increase PDAC risk [HR (95% CI), 1.24 (1.03–1.49)], with similar risk for men [1.21 (0.96–1.53)] and women [1.28 (0.94–1.75)]. In addition, stronger associations were observed in normal and overweight groups compared with the obese group (Pinteraction = 0.03). Our results support the hypothesis that LAN and circadian disruption may be risk factors for PDAC.

Significance:
Our study suggests that higher LAN is a risk factor for pancreatic cancer, contributing to the growing literature that demonstrates the potentially adverse health effects of light pollution.
Estrogen Receptor β-Mediated Inhibition of Actin-Based Cell Migration Suppresses Metastasis of Inflammatory Breast Cancer
Authors: Thomas Christoforos , Karagounis Ilias V. , Srivastava Ratnesh K. , Vrettos Nicholas , Nikolos Fotis , Francois Noëlle , Huang Menggui , Gong Siliang , Long Qi , Kumar Sushil , Koumenis Constantinos , Krishnamurthy Savitri , Ueno Naoto T. , Chakrabarti Rumela , Maity Amit 
Published: January 2021

Abstract

Inflammatory breast cancer (IBC) is a highly metastatic breast carcinoma with high frequency of estrogen receptor α (ERα) negativity. Here we explored the role of the second ER subtype, ERβ, and report expression in IBC tumors and its correlation with reduced metastasis. Ablation of ERβ in IBC cells promoted cell migration and activated gene networks that control actin reorganization, including G-protein–coupled receptors and downstream effectors that activate Rho GTPases. Analysis of preclinical mouse models of IBC revealed decreased metastasis of IBC tumors when ERβ was expressed or activated by chemical agonists. Our findings support a tumor-suppressive role of ERβ by demonstrating the ability of the receptor to inhibit dissemination of IBC cells and prevent metastasis. On the basis of these findings, we propose ERβ as a potentially novel biomarker and therapeutic target that can inhibit IBC metastasis and reduce its associated mortality.

Significance:
These findings demonstrate the capacity of ERβ to elicit antimetastatic effects in highly aggressive inflammatory breast cancer and propose ERβ and the identified associated genes as potential therapeutic targets in this disease.
Heterogeneity and Clonal Evolution of Acquired PARP Inhibitor Resistance in TP53- and BRCA1-Deficient Cells
Authors: Färkkilä Anniina , Rodríguez Alfredo , Oikkonen Jaana , Gulhan Doga C. , Nguyen Huy , Domínguez Julieta , Ramos Sandra , Mills Caitlin E. , Pérez-Villatoro Fernando , Lazaro Jean-Bernard , Zhou Jia , Clairmont Connor S. , Moreau Lisa A. , Park Peter J. , Sorger Peter K. , Hautaniemi Sampsa , Frias Sara , D'Andrea Alan D. 
Published: January 2021

Abstract

Homologous recombination (HR)-deficient cancers are sensitive to poly-ADP ribose polymerase inhibitors (PARPi), which have shown clinical efficacy in the treatment of high-grade serous cancers (HGSC). However, the majority of patients will relapse, and acquired PARPi resistance is emerging as a pressing clinical problem. Here we generated seven single-cell clones with acquired PARPi resistance derived from a PARPi-sensitive TP53−/− and BRCA1−/− epithelial cell line generated using CRISPR/Cas9. These clones showed diverse resistance mechanisms, and some clones presented with multiple mechanisms of resistance at the same time. Genomic analysis of the clones revealed unique transcriptional and mutational profiles and increased genomic instability in comparison with a PARPi-sensitive cell line. Clonal evolutionary analyses suggested that acquired PARPi resistance arose via clonal selection from an intrinsically unstable and heterogenous cell population in the sensitive cell line, which contained preexisting drug-tolerant cells. Similarly, clonal and spatial heterogeneity in tumor biopsies from a clinical patient with BRCA1-mutant HGSC with acquired PARPi resistance was observed. In an imaging-based drug screening, the clones showed heterogenous responses to targeted therapeutic agents, indicating that not all PARPi-resistant clones can be targeted with just one therapy. Furthermore, PARPi-resistant clones showed mechanism-dependent vulnerabilities to the selected agents, demonstrating that a deeper understanding on the mechanisms of resistance could lead to improved targeting and biomarkers for HGSC with acquired PARPi resistance.

Significance:
This study shows that BRCA1-deficient cells can give rise to multiple genomically and functionally heterogenous PARPi-resistant clones, which are associated with various vulnerabilities that can be targeted in a mechanism-specific manner.
Association of Inflammatory and Insulinemic Potential of Diet and Lifestyle with Risk of Hepatocellular Carcinoma
Authors: Yang Wanshui , Sui Jing , Zhao Longgang , Ma Yanan , Tabung Fred K. , Simon Tracey G. , Lee Dong Hoon , Zeng Xufen , Nguyen Long H. , Meyerhardt Jeffrey A. , Chan Andrew T. , Giovannucci Edward L. , Zhang Xuehong 
Published: January 2021

Abstract

Background:
We prospectively examined the extent to which greater inflammatory and insulinemic potential of diet and lifestyle are associated with the risk of developing hepatocellular carcinoma (HCC) in two nationwide cohorts.

Methods:
Five kinds of pattern scores, including the empirical dietary inflammatory pattern (EDIP), empirical dietary index for hyperinsulinemia (EDIH) and insulin resistance (EDIR), empirical lifestyle pattern score for hyperinsulinemia (ELIH) and insulin resistance (ELIR) were calculated. Multivariable hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox regression.

Results:
After an average follow-up of 25.6 years among 119,316 participants, 142 incident HCC cases were documented. Higher adherence to EDIP (HR by comparing extreme tertiles: 2.03; 95% CI, 1.31–3.16; Ptrend = 0.001), EDIH (HR, 1.61; 95% CI, 1.06–2.43; Ptrend = 0.02), and EDIR (HR, 1.62; 95% CI: 1.08–2.42; Ptrend = 0.02) was associated with increased risk of HCC. Likewise, participants with higher scores of ELIH (HR, 1.89; 95% CI, 1.25–2.87; Ptrend = 0.001) and ELIR (HR, 2.05; 95% CI, 1.34–3.14, Ptrend = 0.0004) had higher risk of developing HCC. Additional adjustment for diabetes mellitus and/or body mass index attenuated the magnitude of the associations, indicating that diabetes and/or adiposity may partly mediate the association of these patterns with HCC risk.

Conclusions:
Our findings suggest that inflammation and insulin resistance/hyperinsulinemia are potential mechanisms linking dietary or lifestyle factors and HCC development.

Impact:
Inflammation and insulin resistance/hyperinsulinemia may partly mediate the association of diet and other lifestyles with HCC development, and interventions to reduce the adverse effect of pro-inflammatory and hyperinsulinemic diet and lifestyle may reduce HCC risk.
Detection of Aneuploidy in Cerebrospinal Fluid from Patients with Breast Cancer Can Improve Diagnosis of Leptomeningeal Metastases
Authors: Angus Lindsay , Deger Teoman , Jager Agnes , Martens John W.M. , de Weerd Vanja , van Heuvel Irene , van den Bent Martin J. , Sillevis Smitt Peter A.E. , Kros Johan M. , Bindels Eric M.J. , Heitzer Ellen , Sleijfer Stefan , Jongen Joost L.M. , Wilting Saskia M. 
Published: January 2021

Abstract

Purpose:
Detection of leptomeningeal metastasis is hampered by limited sensitivities of currently used techniques: MRI and cytology of cerebrospinal fluid (CSF). Detection of cell-free tumor DNA in CSF has been proposed as a tumor-specific candidate to detect leptomeningeal metastasis at an earlier stage. The aim of this study was to investigate mutation and aneuploidy status in CSF-derived cell-free DNA (cfDNA) of patients with breast cancer with a clinical suspicion of leptomeningeal metastasis.

Experimental Design:
cfDNA was isolated from stored remnant CSF and analyzed by targeted next-generation sequencing (NGS; n = 30) and the modified fast aneuploidy screening test-sequencing system (mFAST-SeqS; n = 121). The latter method employs selective amplification of long interspaced nuclear elements sequences that are present throughout the genome and allow for fast and cheap detection of aneuploidy. We compared these results with the gold standard to diagnose leptomeningeal metastasis: cytology.

Results:
Leptomeningeal metastasis was cytology proven in 13 of 121 patients. Low DNA yields resulted in insufficient molecular coverage of NGS for the majority of samples (success rate, 8/30). The mFAST-SeqS method, successful in 112 of 121 (93%) samples, detected genome-wide aneuploidy in 24 patients. Ten of these patients had cytology-proven leptomeningeal metastasis; 8 additional patients were either concurrently diagnosed with central nervous system metastases by radiological means or developed these soon after the lumbar puncture. The remaining six cases were suspected of leptomeningeal metastasis, but could not be confirmed by cytology or imaging. Aneuploidy was associated with development of leptomeningeal metastasis and significantly worse overall survival.

Conclusions:
Aneuploidy in CSF-derived cfDNA may provide a promising biomarker to improve timely detection of leptomeningeal metastasis.
Phase I Trial of Encapsulated Rapamycin in Patients with Prostate Cancer Under Active Surveillance to Prevent Progression
Authors: Kemp Bohan Phillip M. , Chick Robert C. , O'Shea Anne E. , Vreeland Timothy J. , Hickerson Annelies T. , Cindass Jessica L. , Ensley Daniel C. , Hale Diane , Clifton Guy T. , Sohn Vance Y. , Thompson Ian M. , Peoples George E. , Liss Michael A. 
Published: January 2021

Abstract
No approved medical therapies prevent progression of low-grade prostate cancer. Rapamycin inhibits cell proliferation and augments immune responses, producing an antitumor effect. Encapsulated rapamycin (eRapa) incorporates rapamycin into a pH-sensitive polymer, ensuring consistent dosing. Here, we present results from a phase I trial evaluating the safety and tolerability of eRapa in patients with prostate cancer. Patients with Gleason ≤7 (3+4) disease (low and intermediate risk) under active surveillance were enrolled in a 3+3 study with three eRapa dosing cohorts (cohort 1, 0.5 mg/week; cohort 2, 1 mg/week; and cohort 3, 0.5 mg/day). Patients were treated for 3 months and followed for an additional 3 months to assess safety, pharmacokinetics, quality of life (QoL), immune response, and disease progression. Fourteen patients (cohort 1, n = 3; cohort 2, n = 3; and cohort 3, n = 8) were enrolled. In cohort 3, one dose-limiting toxicity (DLT; neutropenia) and two non-DLT grade 1–2 adverse events (AE) occurred that resulted in patient withdrawal. All AEs in cohorts 1 and 2 were grade 1. Peak serum rapamycin concentration was 7.1 ng/mL after a 1 mg dose. Stable trough levels (∼2 ng/mL) developed after 48–72 hours. Daily dosing mildly worsened QoL, although QoL recovered after treatment cessation in all categories, except fatigue. Weekly dosing increased naïve T-cell populations. Daily dosing increased central memory cell populations and exhaustion markers. No disease progression was observed. In conclusion, treatment with eRapa was safe and well-tolerated. Daily dosing produced higher frequencies of lower grade toxicities and transient worsening of QoL, while weekly dosing impacted immune response. Future studies will verify clinical benefit and long-term tolerability.
Prevention Relevance: There is an unmet medical need for a well-tolerated treatment capable of delaying progression of newly diagnosed low-grade prostate cancer. This treatment would potentially obviate the need for future surgical intervention and improve the perception of active surveillance as a more acceptable option among this patient population.
Germline Pathogenic Variants in the Ataxia Telangiectasia Mutated (ATM) Gene are Associated with High and Moderate Risks for Multiple Cancers
Authors: Hall Michael J. , Bernhisel Ryan , Hughes Elisha , Larson Katie , Rosenthal Eric T. , Singh Nanda A. , Lancaster Johnathan M. , Kurian Allison W. 
Published: January 2021

AbstractPathogenic variants (PVs) in ATM are relatively common, but the scope and magnitude of risk remains uncertain. This study aimed to estimate ATM PV cancer risks independent of family cancer history. This analysis included patients referred for hereditary cancer testing with a multi-gene panel (N = 627,742). Cancer risks for ATM PV carriers (N = 4,607) were adjusted for family history using multivariable logistic regression and reported as ORs with 95% confidence intervals (CIs). Subanalyses of the c.7271T&gt;G missense PV were conducted. Moderate-to-high risks for pancreatic (OR, 4.21; 95% CI, 3.24–5.47), prostate (OR, 2.58; 95% CI, 1.93–3.44), gastric (OR, 2.97; 95% CI, 1.66–5.31), and invasive ductal breast (OR, 2.03; 95% CI, 1.89–2.19) cancers were estimated for ATM PV carriers. Notably, c.7271T&gt;G was associated with higher invasive ductal breast cancer risk (OR, 3.76; 95% CI, 2.76–5.12) than other missense and truncating ATM PVs. Low-to-moderate risks were seen for ductal carcinoma in situ (OR, 1.80; 95% CI, 1.61–2.02), male breast cancer (OR, 1.72; 95% CI, 1.08–2.75), ovarian cancer (OR, 1.57; 95% CI, 1.35–1.83), colorectal cancer (OR, 1.49; 95% CI, 1.24–1.79), and melanoma (OR, 1.46; 95% CI, 1.18–1.81). ATM PVs are associated with multiple cancer risks and, while professional society guidelines support that carriers are eligible for increased breast and pancreatic cancer screening, increased screening for prostate and gastric cancer may also be warranted. c.7271T&gt;G is associated with high risk for breast cancer, with a 3- to 4-fold risk increase that supports consideration of strategies for prevention and/or early detection.Prevention Relevance:This study estimated risks for multiple cancers associated with ATM pathogenic variants independent of family history. These results indicate that some common variants may be associated with higher breast cancer risks than previously appreciated and increased screening for prostate and gastric cancer may be warranted for carriers of ATM pathogenic variants.
β2M Signals Monocytes Through Non-Canonical TGFβ Receptor Signal Transduction
Authors: Hilt Zachary T. , Maurya Preeti , Tesoro Laura , Pariser Daphne N. , Ture Sara K. , Cleary Simon J. , Looney Mark R. , McGrath Kathleen E. , Morrell Craig N. 
Published: January 2021

Rationale:
Circulating monocytes can have proinflammatory or proreparative phenotypes. The endogenous signaling molecules and pathways that regulate monocyte polarization in vivo are poorly understood. We have shown that platelet-derived β2M (β-2 microglobulin) and TGF-β (transforming growth factor β) have opposing effects on monocytes by inducing inflammatory and reparative phenotypes, respectively, but each bind and signal through the same receptor. We now define the signaling pathways involved.

Objective:
To determine the molecular mechanisms and signal transduction pathways by which β2M and TGF-β regulate monocyte responses both in vitro and in vivo.

Methods and Results:
Wild-type– (WT) and platelet-specific β2M knockout mice were treated intravenously with either β2M or TGF-β to increase plasma concentrations to those in cardiovascular diseases. Elevated plasma β2M increased proinflammatory monocytes, while increased plasma TGFβ increased proreparative monocytes. TGF-βR (TGF-β receptor) inhibition blunted monocyte responses to both β2M and TGF-β in vivo. Using imaging flow cytometry, we found that β2M decreased monocyte SMAD2/3 nuclear localization, while TGF-β promoted SMAD nuclear translocation but decreased noncanonical/inflammatory (JNK [jun kinase] and NF-κB [nuclear factor-κB] nuclear localization). This was confirmed in vitro using both imaging flow cytometry and immunoblots. β2M, but not TGF-β, promoted ubiquitination of SMAD3 and SMAD4, that inhibited their nuclear trafficking. Inhibition of ubiquitin ligase activity blocked noncanonical SMAD-independent monocyte signaling and skewed monocytes towards a proreparative monocyte response.

Conclusions:
Our findings indicate that elevated plasma β2M and TGF-β dichotomously polarize monocytes. Furthermore, these immune molecules share a common receptor but induce SMAD-dependent canonical signaling (TGF-β) versus noncanonical SMAD-independent signaling (β2M) in a ubiquitin ligase dependent manner. This work has broad implications as β2M is increased in several inflammatory conditions, while TGF-β is increased in fibrotic diseases.

Graphic Abstract:

A
graphic abstract
is available for this article.