bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cosmology in 5D and 4D Einstein–Gauss–Bonnet gravity
Authors: Gómez F. , Lepe S. , Orozco V. C. , Salgado P. 
Published: October 2022

AbstractWe consider the five-dimensional Einstein–Gauss–Bonnet gravity, which can be obtained by means of an appropriate choice of coefficients in the five-dimensional Lanczos–Lovelock gravity theory. The Einstein–Gauss–Bonnet field equations for the Friedmann–Lemaître–Robertson–Walker metric are found as well as some of their solutions. The hyperbolicity of the corresponding equations of motion is discussed. A four-dimensional gravity action is obtained from the Gauss–Bonnet gravity using the Randall–Sundrum compactification procedure and then it is studied the implications of the compactification procedure in the cosmological solutions. The same procedure is used to obtain gravity in four dimensions from the five-dimensional AdS–Chern–Simons gravity to then study some cosmological solutions. Some aspects of the construction of the four-dimensional action gravity, as well as a brief review of Lovelock gravity in 5D are considered in an Appendix.
Gravitational form factors of the delta resonance in chiral EFT
Authors: Alharazin H. , Epelbaum E. , Gegelia J. , Meißner U.-G. , Sun B.-D. 
Published: October 2022

AbstractThe leading one-loop corrections to the gravitational form factors of the delta resonance are calculated in the framework of chiral effective field theory. Various contributions to the energy–momentum tensor and the renormalization of the low-energy constants are worked out. Using the small scale expansion, expressions for static quantities are obtained and the real and imaginary parts of the gravitational form factors are calculated numerically.
The high-density equation of state in heavy-ion collisions: constraints from proton flow
Authors: Steinheimer Jan , Motornenko Anton , Sorensen Agnieszka , Nara Yasushi , Koch Volker , Bleicher Marcus 
Published: October 2022

AbstractA set of different equations of state is implemented in the molecular dynamics part of a non-equilibrium transport simulation (UrQMD) of heavy-ion collisions. It is shown how different flow observables are affected by the density dependence of the equation of state. In particular, the effects of a phase transition at high density are explored, including an expected reduction in mean $$m_T$$

m
T

. We also show that an increase in $$v_2$$

v
2

is characteristic for a strong softening of the equation of state. The phase transitions with a low coexistence density, $$n_{\text {CE}}<4 n_0$$

n
CE

<
4

n
0

, show a distinct minimum in the slope of the directed flow as a function of the beam energy, which would be a clear experimental signal. By comparing our results with experimental data, we can exclude any strong phase transition at densities below $$4n_0$$

4

n
0

.
Defactinib, Pembrolizumab, and Gemcitabine in Patients with Advanced Treatment Refractory Pancreatic Cancer: A Phase I Dose Escalation and Expansion Study
Authors: Wang-Gillam Andrea , Lim Kian-Huat , McWilliams Robert , Suresh Rama , Lockhart Albert C. , Brown Amberly , Breden Marcus , Belle Jad I. , Herndon John , Bogner Savannah J. , Pedersen Katrina , Tan Benjamin , Boice Nicholas , Acharya Abhi , Abdiannia Mina , Gao Feng , Yoon Harry H. , Zhu Mojun , Trikalinos Nikolaos A. , Ratner Lee , Aranha Olivia , Hawkins William G. , Herzog Brett H. , DeNardo David G. 
Published: October 2022

Abstract

Purpose:
Targeting focal adhesion kinase (FAK) renders checkpoint immunotherapy effective in pancreatic ductal adenocarcinoma (PDAC) mouse model. Defactinib is a highly potent oral FAK inhibitor that has a tolerable safety profile.

Patients and Methods:
We conducted a multicenter, open-label, phase I study with dose escalation and expansion phases. In dose escalation, patients with refractory solid tumors were treated at five escalating dose levels of defactinib and gemcitabine to identify a recommended phase II dose (RP2D). In expansion phase, patients with metastatic PDAC who progressed on frontline treatment (refractory cohort) or had stable disease (SD) after at least 4 months of standard gemcitabine/nab-paclitaxel (maintenance cohort) were treated at RP2D. Pre- and posttreatment tumor biopsies were performed to evaluate tumor immunity.

Results:
The triple drug combination was well-tolerated, with no dose-limiting toxicities. Among 20 treated patients with refractory PDAC, the disease control rate (DCR) was 80%, with one partial response (PR) and 15 SDs, and the median progression-free survival (PFS) and overall survival (OS) were 3.6 and 7.8 months, respectively. Among 10 evaluable patients in the maintenance cohort, DCR was 70% with one PR and six SDs. Three patients with SD came off study due to treatment- or disease-related complications. The median PFS and OS on study treatment were 5.0 and 8.3 months, respectively.

Conclusions:
The combination of defactinib, pembrolizumab, and gemcitabine was well-tolerated and safe, had promising preliminary efficacy, and showed biomarker activity in infiltrative T lymphocytes. Efficacy of this strategy may require incorporation of more potent chemotherapy in future studies.
Phase I Dose Escalation Study of Topical Bexarotene in Women at High Risk for Breast Cancer
Authors: Thomas Parijatham S. , Patel Anisha B. , Lee J. Jack , Liu Diane D. , Hernandez Mike , Muzzio Miguel , Contreras Alejandro , Sepeda Valerie , Mays Carrie , Weber Diane , Vornik Lana A. , Khan Seema A. , Dimond Eileen , Heckman-Stoddard Brandy M. , Perloff Marjorie , Brown Powel H. 
Published: October 2022

Abstract
Agents that can reduce the incidence of hormone receptor negative breast cancer are currently lacking. Rexinoids such as bexarotene significantly reduced mammary tumor development in preclinical mouse models. Oral bexarotene in BRCA mutation carriers significantly decreased cyclin D1 in breast cells, suggesting biological activity on breast tissue. This study evaluated topical bexarotene 1% gel applied to one unaffected breast in women at high risk for breast cancer for 4 weeks to assess safety and toxicity. Secondary objectives included assessment of bexarotene concentrations in the plasma and breast tissue. In the dose escalation phase, women were assigned to one of three different dose levels: 10 mg (1 mL) every other day, 10 mg (1 mL) daily, 20 mg (2 mL) daily. Dose-limiting toxicity (DLT) was defined as a grade 2 skin adverse event for at least 6 days or any grade 3 or 4 adverse event related to study drug. A total of 14 women were enrolled with 10 participants at the every other day dose level and 4 participants at daily dosing. Two skin DLTs were experienced at daily dosing and therefore further enrollment was discontinued per protocol. An additional 10 participants were enrolled at the MTD as part of the dose expansion phase. These individuals tolerated the treatment with minimal adverse events. Maculopapular rash at the treatment site was the most common adverse event related to study drug and resolved within a few days of discontinuation. Bexarotene was detectable in breast tissue at the 10 mg daily every other day dose.

Prevention Relevance:
Bexarotene is a rexinoid that has been shown to prevent mammary tumors in mouse models but oral dosing has toxicities. This phase I study evaluates topical bexarotene, as a potential chemoprevention agent, for safety and toxicity in high-risk women for breast cancer.
Quantitative Phosphoproteomics of the Angiotensin AT
2
-Receptor Signaling Network Identifies HDAC1 (Histone-Deacetylase-1) and p53 as Mediators of Antiproliferation and Apoptosis
Authors: Peluso A. Augusto , Kempf Stefan J. , Verano-Braga Thiago , Rodrigues-Ribeiro Lucas , Johansen Lene Egedal , Hansen Mie Rytz , Kitlen Gitte , Haugaard Andreas Houe , Sumners Colin , Ditzel Henrik J. , Santos Robson A. , Bader Michael , Larsen Martin R. , Steckelings U. Muscha 
Published: October 2022

Background:

Angiotensin AT
2
-receptor signaling is atypical for a G-protein coupled receptor and incompletely understood. To obtain novel insights into AT
2
-receptor signaling, we mapped changes in the phosphorylation status of the entire proteome of human aortic endothelial cells in response to AT
2
-receptor stimulation.

Methods:
Phosphorylation status of human aortic endothelial cells after stimulation with C21 (1 µM; 0, 1, 3, 5, 20 minutes) was determined utilizing time-resolved quantitative phosphoproteomics. Specific changes in protein phosphorylation and acetylation were confirmed by Western Blotting. Functional tests included resazurin assay for cell proliferation, and caspase 3/7 luminescence assay or FACS analysis of annexin V expression for apoptosis.

Results:

AT
2
-receptor stimulation significantly altered the phosphorylation status of 172 proteins (46% phosphorylations, 54% dephosphorylations). Bioinformatic analysis revealed a cluster of phospho-modified proteins involved in antiproliferation and apoptosis. Among these proteins, HDAC1 (histone-deacetylase-1) was dephosphorylated at serine
421/423
involving serine/threonine phosphatases. Resulting HDAC1 inhibition led to p53 acetylation and activation. AT
2
-receptor stimulation induced antiproliferation and apoptosis, which were absent when cells were co-incubated with the p53 inhibitor pifithrin-α, thus indicating p53-dependence of these AT
2
-receptor mediated functions.

Conclusions:

Contrary to the prevailing view that AT
2
-receptor signaling largely involves phosphatases, our study revealed significant involvement of kinases. HDAC1 inhibition and resulting p53 activation were identified as novel, AT
2
-receptor coupled signaling mechanisms. Furthermore, the study created an openly available dataset of AT
2
-receptor induced phospho-modified proteins, which has the potential to be the basis for further discoveries of currently unknown, AT
2
-receptor coupled signaling mechanisms.
Changes of the CYP11B2 Expressing Zona Glomerulosa in Human Adrenals From Birth to 40 Years of Age
Authors: van de Wiel Elle , Chaman Baz Amir-Hossein , Küsters Benno , Mukai Kuniaki , van Bonzel Lidia , van Erp Merijn , Deinum Jaap , Langenhuijsen Johan 
Published: October 2022

Background:
Aldosterone synthase (CYP11B2) antibodies for immunohistochemistry, enables to visualize aldosterone-producing zona glomerulosa (ZG), aldosterone-producing micronodules, and aldosterone-producing adenomas. The architecture of the ZG differs in old versus young age but the evolution of the changes is not well known. The pathogenesis of aldosterone-producing micronodules and aldosterone-producing adenomas is still unclear and research on the ZG in young populations is limited. In this study, we elucidate changes in human ZG with age by quantifying the CYP11B2 expression.

Methods:
We collected 83 human adrenal glands from 57 autopsy cases aged 0 to 40 years old. In 26 cases, both adrenals were available. We performed immunohistochemistry targeting CYP11B2 and quantified the relative CYP11B2 expressing area, CYP11B2 continuity, the mean gap length between CYP11B2-expressing areas and the maximum extension of CYP11B2 area (depth).

Results:
We found a negative correlation between age and the relative CYP11B2 expressing area, a negative correlation between age and CYP11B2 continuity, a positive correlation between age and mean gap length, and a positive correlation between age and maximum CYP11B2 depth. The changes in expression patterns of relative CYP11B2 expressing area, CYP11B2 continuity and mean gap length were seen in both adrenals of the same autopsy case.

Conclusions:
The decline of relative CYP11B2 expressing ZG area and continuity may indicate involution of the ZG, which is supported by an increase of gaps and maximum CYP11B2 depth indicating clustering, comparable to formation of aldosterone-producing micronodules. The similarities in both adrenals from the same case indicate that these changes occur bilaterally.
Association of Cardiovascular Health Score Trajectory With Incident Myocardial Infarction in Hypertensive Patients
Authors: Huang Zegui , Chen Zekai , Wang Xianxuan , Ding Xiong , Cai Zefeng , Li Weijian , Cai Zhiwei , Lan Yulong , Chen Guanzhi , Fang Wei , Wu Shouling , Chen Youren 
Published: October 2022

Background:
The association between changes in cardiovascular health score (CHS) over time and myocardial infarction (MI) risk in hypertensive patients remains unclear.

Method:
This was a prospective study comprising 17 374 hypertensive patients from the Kailuan study cohort who underwent 3 surveys and were identified to be free of MI, stroke, or cancer from 2006 to 2010. CHS consisted of 7 cardiovascular health metrics (plasma glucose, total cholesterol, blood pressure, smoking, body mass index, physical activity, salt intake), ranging from 0 (worst) to 13 (best) in the study. CHS trajectories were developed during 2006 to 2010 to predict the MI risk from 2010 to 2020. Additionally, the Cox proportional hazard model was established to calculate the hazard ratio and 95% CI of incident MI in different trajectory groups.

Result:
This study identified the 5 CHS trajectories from 2006 to 2010: low-stable (n=1161; range, 4.7–4.5), moderate-decreasing (n=3928; decreased from 6.9 to 6.0), moderate-increasing (n=1014; increased from 5.6 to 7.8), high-stable I (n=7940; range, 8.1–8.2), and high-stable II (n=3331; range, 9.2–9.7). During the median follow-up of 10.04 years, 288 incident MI cases were identified. After adjusting for potential confounders, compared with low-stable group, the hazard ratio and 95% CI of MI were 0.24 (0.15–0.40) for high-stable II, 0.36 (0.24–0.54) for high-stable I, 0.46 (0.25–0.83) for moderate-increasing, and 0.61 (0.41–0.90) for moderate-decreasing, respectively.

Conclusions:
In hypertensive patients, high-stable CHS or improvement in CHS is associated with a lower risk of incident MI, when compared with low-stable CHS trajectory over time.
Genetic Engineering of Lymphangiogenesis in Skin Does Not Affect Blood Pressure in Mouse Models of Salt-Sensitive Hypertension
Authors: Thowsen Irene Matre , Reikvam Tore , Skogstrand Trude , Samuelsson Anne-Maj , Müller Dominik N. , Tenstad Olav , Alitalo Kari , Karlsen Tine , Wiig Helge 
Published: October 2022

Background:
Recent studies have indicated that sodium storage is influenced by macrophages that secrete VEGF-C (vascular endothelial growth factor) during salt stress thus stimulating lymphangiogenesis, thereby acting as a buffer against increased blood pressure (BP). We aimed to explore the role of dermal lymphatics in BP and sodium homeostasis. Our hypothesis was that mice with reduced dermal lymphatic vessels were more prone to develop salt-sensitive hypertension, and that mice with hyperplastic vessels were protected.

Methods:

Mice with either hypoplastic (Chy), absent (K14-VEGFR3 [vascular endothelial growth factor receptor 3]-Ig), or hyperplastic (K14-VEGF-C) dermal lymphatic vessels and littermate controls were given high-salt diet (4% NaCl in the chow), deoxycorticosterone acetate (DOCA)-salt diet and 1% saline to drink or nitric oxide blocker diet L-N
G
-nitro arginine methyl ester (followed by high salt diet). BP was measured by telemetric recording, and tissue sodium content by ion chromatography.

Results:
In contrast to previous studies, high salt diet did not induce an increase in BP or sodium storage in any of the mouse strains investigated. DOCA-salt, on the other hand, gave an increase in BP in Chy and K14-VEGFR3-Ig not different from their corresponding WT controls. DOCA induced salt storage in skin and muscle, but to the same extent in mice with dysfunctional lymphatic vessels and WT controls. Lymph flow as assessed by tracer washout was not affected by the diet in any of the mouse strains.

Conclusions:
Our results suggest that dermal lymphatic vessels are not involved in salt storage or blood pressure regulation in these mouse models of salt-sensitive hypertension.
BCAM Deficiency May Contribute to Preeclampsia by Suppressing the PIK3R6/p-STAT3 Signaling
Authors: Liu Min , Liao Lingyun , Gao Yijie , Yin Yangxue , Wei Xiaohong , Xu Qin , Gao Linbo , Zhou Rong 
Published: October 2022

Background:
Preeclampsia is a pregnancy syndrome that may utilize multiple pathogenic mechanisms. Insufficient trophoblast invasion and impaired uterine spiral artery remodeling are believed to be the pathological basis; yet the underlying mechanisms remain largely unclear.

Methods:
The placental BCAM (basal cell adhesion molecule) expression and important clinical indicators were detected and correlation analysis was performed. MiRNAs directly targeting BCAM were predicted and further verified by dual-luciferase reporter gene, and the downstream molecular mechanisms of BCAM were investigated in both HTR-8/SVneo and JAR cells. In addition, pregnant/nonpregnant rats were treated with adenoviruses containing BCAM shRNA genes (Ad-shBCAM) on gestational 9.5 days to detect the preeclamptic features.

Results:
The BCAM is highly expressed on the trophoblast membrane and decreased in the preeclamptic placentae. In HTR-8/SVneo and JAR cells, BCAM knockdown inhibited trophoblast proliferation, migration, and invasion, and suppressed phosphorylation on Y705 of STAT3 dependent on the downregulation of PIK3R6. Moreover, miR-199a-5p mediated the degradation of BCAM and also inhibited trophoblast proliferation, migration, and invasion. In vivo, BCAM deficiency induced a preeclampsia-like phenotype included elevated systolic blood pressure, proteinuria, impaired morphology and function of multiple organs (placenta, liver, and kidney), and fetal growth restriction. The expression of placenta BCAM/PIK3R6/p-STAT3 signaling was also downregulated in this preeclampsia rat model.

Conclusions:
MiR-199a-5p mediated–BCAM deficiency contributes to the suppression of trophoblast proliferation, migration, and invasion by inhibiting PIK3R6/p-STAT3 signaling, which may lead to poor placentation and result in preeclampsia-like phenotypes. Our study provides a new academic perspective on the pathogenesis of preeclampsia.
From Peace Talks to Parliaments: The Microprocesses Propelling Women into Formal Politics Following War
Authors: Anderson Miriam J. , Valade Marc Y. 
Published: October 2022

Abstract
Women’s legislative representation often increases following armed conflict. Although various studies suggest a relationship between gender-inclusive peace negotiations and better outcomes for women, we know little about the processes linking these phenomena. Using social network analysis and drawing on qualitative interviews, we examine women’s participation in Burundi’s peace negotiations (1998–2000) and their increased political participation in post-accord national politics (2000–2005). We find that women’s civil society built social networks reliant on cross-ethnic collaboration and the support of international actors during the peace negotiations. With the aid of those networks, they successfully entered formal politics and passed pro-women legislation, where they developed cross-party alliances and maintained close relationships with civil society, increasing their effectiveness in parliament. This case suggests that evolving social networks are a crucial component of the explanation for women’s increased participation in politics during times of transition from conflict to peace.
Navigating the Religious in the Cosmopolitan
Authors: Chaoui Saleh 
Published: October 2022

Abstract
Sweetness in the Belly (2005) explores a new space which problematizes the intersections between religion, cosmopolitanism, and displacement. Camilla Gibb employs the trope of the journey to trace the ways in which the female protagonist, Lilly, transforms in a transnational context. The narrative depicts multiple journeys that Lilly undertakes between the West and the East. Such geographical displacements are pivotal to her complex spiritual self-discovery. Lilly, a white Ethiopian Muslim, embraces Sufi Islam which helps her resist forms of alienation and discrimination. Therefore, as I argue in this paper, religion can be a constitutive component in the formation of female cosmopolitan subjectivity. Understanding cosmopolitanism as a disposition that is not necessarily secular in its orientation, this article investigates the transformative role of religion in the debates surrounding “new cosmopolitanism.” I argue that through Lilly’s journey, the narrative depicts religion as a central feature of cosmopolitan identity which disrupts the orientalist bent associated with East/West dichotomies.
Clinical Predictors of Symptom Improvement Following Eustachian Tube Balloon Dilation
Authors: Yang Hong-Ho , Alonso Jose , Ishiyama Akira , Gopen Quinton S. , Suh Jeffrey D. , Wang Marilene B. , Wells Christine , Wung Vivian , Lee Jivianne T. 
Published: October 2022

Objective: This study aims to identify clinical predictors of treatment response to Eustachian Tube Balloon Dilation (ETBD) as measured by changes in Eustachian Tube Dysfunction Questionnaire-7 (ETDQ-7) scores. Methods: One hundred thirteen patients who underwent ETBD at an institution from 2017 to 2021 completed ETDQ-7 pre- and post-operatively. We conducted multivariable regression analyses with ETDQ-7 normalization (<2.1 post-op), minimum clinically important difference (MCID) (>0.5 pre-op – post-op), and quantitative improvement in ETDQ-7 score as outcome variables. Pre-operative ETDQ-7 score, tympanogram type, chronic otitis media, chronic rhinosinusitis (CRS), inferior turbinate hypertrophy, deviated septum, allergic rhinitis, and rhinorrhea were included as covariates. Models controlled for age, sex, ethnicity, prior ear or sinus surgery, and follow-up duration. Results: The mean age was 49 years old. 51% were females, and all patients had pre-operative ETDQ-7 above 2.1. After a mean follow-up period of 13 months, 77% achieved MCID and 37% had normalized. Higher pre-operative ETDQ-7 score was associated with greater ETDQ-7 score improvement ( B = 0.60, 95% CI = [0.37, 0.83]) and greater odds of achieving MCID (aOR = 1.65; 95% CI = [1.06, 2.59]). A history of CRS improved chances of achieving MCID (aOR = 4.53; 95% CI = [1.11, 18.55]) and a history of chronic otitis media predicted increased odds of ETDQ-7 normalization (aOR = 2.88; 95% CI = [1.09, 7.58]). Conclusions: Our findings suggest that ETBD was highly effective among patients with pre-operative ETDQ-7 above 2.1. Furthermore, higher pre-operative ETDQ-7 score, CRS, and chronic otitis media predicted more favorable symptomatic benefit from ETBD. These factors may be important to consider when counseling potential candidates for this procedure.