bluuebunny/crossref_metadata_2025_split huggingface dataset:
Constraining Palatini–Horndeski theory with gravitational waves after GW170817
Authors: Dong Yu-Qi , Liu Yu-Qiang , Liu Yu-Xiao 
Published: August 2023

AbstractIn this paper, we investigate the possible parameter space of Palatini–Horndeski theory with gravitational waves in a spatially flat Universe. We develop a general method for obtaining the speed of gravitational waves in the Palatini formalism in the cosmological background and we find that if the theory satisfies the following condition: in any spatially flat cosmological background, the tensor gravitational wave speed is the speed of light c, then only $$S = \int d^4x \sqrt{-g} \big [K(\phi ,X)-G_{3}(\phi ,X){{\tilde{\Box }}}\phi +G_{4}(\phi ){\tilde{R}}\big ]$$

S
=
∫

d
4

x

-
g

[

K

(
ϕ
,
X
)

-

G
3

(
ϕ
,
X
)

□
~

ϕ
+

G
4

(
ϕ
)

R
~

]

is left as the possible action in Palatini–Horndeski theory. We also find that when $$G_{5}(\phi ,X)\ne 0$$

G
5

(
ϕ
,
X
)

≠
0

, the tensor part of the connection will propagate and there are two different tensor gravitational wave speeds.
Quasinormal modes of black holes in f(Q) gravity
Authors: Gogoi Dhruba Jyoti , Övgün Ali , Koussour M. 
Published: August 2023

AbstractIn this work, we have studied the quasinormal modes of a black hole in a model of the type $$f(Q)=\underset{n}{\sum }a_{n}\left( Q-Q_{0}\right) ^{n} $$

f

(
Q
)

=

∑
n

a
n

Q
-

Q
0

n

in f(Q) gravity by using a recently introduced method known as Bernstein spectral method and confirmed the validity of the method with the help of well known Padé averaged higher order WKB approximation method. Here we have considered scalar perturbation and electromagnetic perturbation in the black hole spacetime and obtained the corresponding quasinormal modes. We see that for a non-vanishing nonmetricity scalar $$Q_0$$

Q
0

, quasinormal frequencies in scalar perturbation are greater than those in electromagnetic perturbation scenarios. On the other hand, the damping rate of gravitational waves is higher for electromagnetic perturbation. To confirm the quasinormal mode behaviour, we have also investigated the time domain profiles for both types of perturbations.
Breast Cancer–Secreted Factors Promote Lung Metastasis by Signaling Systemically to Induce a Fibrotic Premetastatic Niche
Authors: Cohen Noam , Mundhe Dhanashree , Deasy Sarah K. , Adler Omer , Ershaid Nour , Shami Tamar , Levi-Galibov Oshrat , Wassermann Rina , Scherz-Shouval Ruth , Erez Neta 
Published: August 2023

Abstract

Metastatic cancer is largely incurable and is the main cause of cancer-related deaths. The metastatic microenvironment facilitates formation of metastases. Cancer-associated fibroblasts (CAF) are crucial players in generating a hospitable metastatic niche by mediating an inflammatory microenvironment. Fibroblasts also play a central role in modifying the architecture and stiffness of the extracellular matrix (ECM). Resolving the early changes in the metastatic niche could help identify approaches to inhibit metastatic progression. Here, we demonstrate in mouse models of spontaneous breast cancer pulmonary metastasis that fibrotic changes and rewiring of lung fibroblasts occurred at premetastatic stages, suggesting systemic influence by the primary tumor. Activin A (ActA), a TGFβ superfamily member, was secreted from breast tumors and its levels in the blood were highly elevated in tumor-bearing mice. ActA upregulated the expression of profibrotic factors in lung fibroblasts, leading to enhanced collagen deposition in the lung premetastatic niche. ActA signaling was functionally important for lung metastasis, as genetic targeting of ActA in breast cancer cells significantly attenuated lung metastasis and improved survival. Moreover, high levels of ActA in human patients with breast cancer were associated with lung metastatic relapse and poor survival. This study uncovers a novel mechanism by which breast cancer cells systemically rewire the stromal microenvironment in the metastatic niche to facilitate pulmonary metastasis.

Significance:
ActA mediates cross-talk between breast cancer cells and cancer-associated fibroblasts in the lung metastatic niche that enhances fibrosis and metastasis, implicating ActA as a potential therapeutic target to inhibit metastatic relapse.
Estrogen Receptor and Immune Checkpoint Inhibitors: New Partners in Lung Cancer?
Authors: Valencia Karmele , Montuenga Luis M. , Calvo Alfonso 
Published: August 2023

SummaryThe influence of sex on immunotherapy response in patients with non–small cell lung cancer (NSCLC) had been studied with no clear conclusions. An article in this issue reports that a key determinant of response is not sex but the existence of a 17β-estradiol/ERα/PDL1 signaling loop in NSCLC. This intriguing result opens new therapeutic options.See related article by Anobile et al., p. 3958
Dual Immune Checkpoint Blockade Induces Analogous Alterations in the Dysfunctional CD8+ T-cell and Activated Treg Compartment
Authors: van der Leun Anne M. , Traets Joleen J.H. , Vos Joris L. , Elbers Joris B.W. , Patiwael Sanne , Qiao Xiaohang , Machuca-Ostos Mercedes , Thommen Daniela S. , Haanen John B.A.G. , Schumacher Ton N.M. , Zuur Charlotte L. 
Published: August 2023

Abstract

To dissect the effect of neoadjuvant PD-1 and CTLA4 blockade on intratumoral T cells in treatment-naive head and neck squamous cell carcinoma, we analyzed primary tumor immune infiltrates from responding and nonresponding patients. At baseline, a higher ratio between active (4-1BB/OX40+) and inactive regulatory CD4+ T cells was associated with immunotherapy response. Furthermore, upon therapy, this active regulatory T-cell (Treg) population showed a profound decrease in responding patients. In an analogous process, intratumoral dysfunctional CD8+ T cells displayed decreased expression of activity and dysfunction-related genes in responding patients, whereas in clinical nonresponders, natural killer cells showed an increased cytotoxic profile early upon treatment. These data reveal immunologic changes in response to dual PD-1/CTLA4 blockade, including a parallel remodeling of presumed tumor-reactive Treg and CD8+ T-cell compartments in responding patients, and indicate that the presence of activated Tregs at baseline may be associated with response.

Significance:
In head and neck squamous cell carcinoma, neoadjuvant PD-1/CTLA4 blockade has shown substantial response rates (20%–35%). As recognition of tumor antigens by T cells appears to be a critical driver of therapy response, a better understanding of alterations in T-cell state that are associated with response and resistance is of importance.
This article is featured in Selected Articles from This Issue, p. 2109
Is Height
2.7
Appropriate for Indexation of Left Ventricular Mass in Healthy Adolescents? The Importance of Sex Differences
Authors: Taylor Hannah C. M. , Chaturvedi Nishi , Davey Smith George , Ferreira Diana L. S. , Fraser Abigail , Howe Laura D. , Hughes Alun D. , Lawlor Debbie A. , Timpson Nic J. , Park Chloe M. 
Published: August 2023

BACKGROUND:

Left ventricular mass (LVM) is an important predictor of cardiovascular risk. In adolescence, LVM is commonly indexed to height
2.7
, although some evidence suggests that this may not fully account for sex differences.

METHODS:
We investigated appropriate allometric scaling of LVM to height, total lean mass, and body surface area, in a UK birth cohort of 2039 healthy adolescents (17±1 years). Allometric relationships were determined by linear regression stratified by sex, following log transformation of x and y variables [log(y)=a+b×log(x)], b is the allometric exponent.

RESULTS:
Log (LVM) showed linear relationships with log(height) and log(lean mass). Biased estimates of slope resulted when the sexes were pooled. The exponents were lower than the conventional estimate of 2.7 for males (mean [95% CI]=1.66 [1.30–2.03]) and females (1.58 [1.27–1.90]). When LVM was indexed to lean mass, the exponent was 1.16 (1.05–1.26) for males and 1.07 (0.97–1.16) for females. When LVM was indexed to estimated body surface area, the exponent was 1.53 (1.40–1.66) for males and 1.34 (1.24–1.45) for females.

CONCLUSIONS:
Allometric exponents derived from pooled data, including men and women without adjustment for sex were biased, possibly due to sex differences in body composition. We suggest that when assessing LVM, clinicians should consider body size, body composition, sex, and age. Our observations may also have implications for the identification of young individuals with cardiac hypertrophy.
Prognostic Impact of On-Treatment Cumulative Ambulatory Blood Pressures for Adverse Macro- and Microvascular Outcomes in Individuals With Type 2 Diabetes: The Rio de Janeiro Type 2 Diabetes Cohort
Authors: Cardoso Claudia R.L. , Leite Nathalie C. , Salles Gil F. 
Published: August 2023

BACKGROUND:
The prognostic value of on-treatment mean cumulative ambulatory blood pressures (BPs) in type 2 diabetes has never been investigated. We aimed to assess it in a prospective cohort of 647 individuals with type 2 diabetes.

METHODS:
Clinic-office and ambulatory BPs were measured at baseline and serially during follow-up. Multivariable Cox analyses assessed the associations between baseline and mean cumulative BPs with the occurrence of cardiovascular events, major adverse cardiovascular events, all-cause and cardiovascular mortality, and microvascular outcomes (microalbuminuria, renal failure, retinopathy, and peripheral neuropathy). C statistics and the integrated discrimination improvement (IDI) index evaluated the improvement in risk discrimination by using cumulative ambulatory BPs instead of baseline BPs.

RESULTS:
Over a median follow-up of 10.6 years, there were 202 cardiovascular events (163 major adverse cardiovascular events), 254 all-cause deaths (118 cardiovascular); 125 individuals had microalbuminuria development/progression, 104 developed advanced renal failure, 159 had retinopathy, and 174 individuals had peripheral neuropathy development/progression. The risks associated with mean cumulative ambulatory BPs were in general higher than those associated with baseline BPs, particularly for cardiovascular (HR, 1.42 versus 1.25 for increments of 1 SD in 24-hour systolic blood pressure) and mortality outcomes (1.56 versus 1.26). Compared with cumulative clinic BPs, mean cumulative ambulatory BPs improved risk discrimination for most outcomes, with IDIs from 11% to 14% for major adverse cardiovascular events and mortality up to 24% to 26% for microalbuminuria and neuropathy.

Conclusions:
Compared with clinic-office BPs, mean cumulative ambulatory BPs during follow-up improve risk discrimination for most complications and mortality in individuals with type 2 diabetes. Serial ambulatory BP monitoring shall be more widely used in clinical management.
Cardiovascular Outcomes of Coronary Computed Tomography Angiography Versus Functional Testing in Suspected Coronary Syndromes: Real‐World Evidence From the Nationwide Cohort
Authors: Jo Jinhwan , Cha Min Jae , Lee Hee Jeong , Kim William D. , Kim Jinseob , Ha Kyung Eun , Kim Subin , Shim Chi Young , Hong Geu‐Ru , Ha Jong‐Won , Cho Iksung 
Published: August 2023

Background
Real‐world evidence for the selection of gatekeeping studies in patients with suspected coronary syndromes is limited.

Methods and Results

We identified 27 036 patients who underwent coronary computed tomography angiography (CCTA), single‐photon emission computed tomography, and the treadmill test for suspected coronary syndromes from the Korean National Health Insurance Service–National Sample Cohort between 2006 and 2014. The primary end point was a composite of cardiac death and myocardial infarction, and the secondary end point was a composite of the primary end point and revascularization. During a median follow‐up of 5.4 years, the risk of both primary and secondary end points was significantly higher in the single‐photon emission computed tomography group (hazard ratio [HR], 1.81 [95% CI, 1.34–2.45]; and HR, 1.42 [95% CI, 1.22–1.66]), but significantly lower in the treadmill test group (HR, 0.53 [95% CI, 0.42–0.67]; and HR, 0.69 [95% CI, 0.62–0.76]) compared with the CCTA group. After balancing baseline risk factors, there was no significant difference in the primary end point in those with single‐photon emission computed tomography (HR, 1.11 [95% CI, 0.78–1.57];
P
=0.58) or treadmill test (HR, 0.84 [95% CI, 0.65–1.08];
P
=0.18) groups, compared with the CCTA group. The event rate of the secondary end point was significantly lower in the treadmill test group than in the CCTA group (HR, 0.87 [95% CI, 0.78–0.96];
P
=0.008).

Conclusions
Compared with functional testing, initial CCTA was not associated with a lower rate of cardiac death or myocardial infarction when used as an initial diagnostic test for patients with suspected coronary syndromes.
Revisiting the Smoking Paradox in Acute Ischemic Stroke Patients: Findings From the Chinese Stroke Center Alliance Study
Authors: Hu Guoliang , Gu Hongqiu , Jiang Yingyu , Yang Xin , Jiang Yong , Wang Chunjuan , Li Zixiao , Wang Yongjun , Wang Yilong 
Published: August 2023

Background
Smoking is a well‐established risk factor for the development of acute ischemic stroke (AIS). However, the “smoker's paradox” suggests that it is associated with favorable clinical outcomes following stroke. We aimed to reevaluate the association between smoking and in‐hospital outcomes in patients with AIS in contemporary practice.

Methods and Results

A total of 649 610 inpatients with AIS from 1476 participating hospitals in the Chinese Stroke Center Alliance were included. In‐hospital outcomes measurement included all‐cause mortality, discharge against medical advice, and complications. Multivariable logistic regression models adjusting for baseline characteristics, clinical profiles at presentation, and in‐hospital management were used to evaluate the association between smoking and in‐hospital outcomes. A propensity score–matched analysis was also conducted. Of these patients with AIS, 36.8% (n=238 912) were smokers. Smokers were younger, had fewer comorbidities, and had slightly lower rates of adverse in‐hospital outcomes than nonsmokers (all‐cause death or discharge against medical advice: 6.0% versus 6.1%; in‐hospital complications: 14.5% versus 15.1%). Multivariable analysis revealed that smoking was associated with higher risk of adverse in‐hospital outcomes (all‐cause death or discharge against medical advice: odds ratio [OR], 1.05 [95% CI, 1.02–1.08];
P
<0.001; complications: OR, 1.06 [95% CI, 1.04–1.08];
P
<0.001). The excess risk of adverse in‐hospital outcomes remained in smoking patients with AIS after propensity score‐matching analysis (all‐cause death or discharge against medical advice: OR, 1.04 [95% CI, 1.00–1.08];
P
=0.034; complications: OR, 1.05 [95% CI, 1.03–1.08];
P
<0.001).

Conclusions
Smoking was associated with increased risk of adverse in‐hospital outcomes among patients with AIS in contemporary practice, reinforcing the importance of smoking cessation in patients with AIS.
Periodontal Disease Treatment After Stroke or Transient Ischemic Attack: The PREMIERS Study, a Randomized Clinical Trial
Authors: Sen Souvik , Curtis James , Hicklin David , Nichols Cynthia , Glover Saundra , Merchant Anwar T. , Hardin James W. , Logue Makenzie , Meyer Jaclyn , Mason Emma , Huang David Y. , Susin Cristiano , Moss Kevin , Beck James 
Published: August 2023

BACKGROUND:
Patients with stroke/transient ischemic attack and periodontal disease (PD) are at increased risk for cardiovascular events. PD treatments that can improve stroke risk factors were tested if they might assist patients with cerebrovascular disease.

METHODS:
In this multicenter phase II trial, patients with stroke/transient ischemic attack and moderately severe PD were randomly assigned to intensive or standard PD treatment arms. The primary outcome measure was a composite of death, myocardial infarction, and recurrent stroke, as well as adverse events. Secondary outcome included changes in stroke risk factors.

RESULTS:

A total of 1209 patients with stroke/transient ischemic attack were screened, of whom 481 met the PD eligibility criteria; 280 patients were randomized to intensive arm (n=140) and standard arm (n=140). In 12-month period, primary outcome occurred in 11 (8%) in the intensive arm and 17 (12%) in the standard arm. The intensive arm was nonsuperior to the standard arm (hazard ratio, 0.65 [95% CI, 0.30–1.38]) with similar rates of adverse events (sepsis 2.1% versus 0.7%; dental bleeding 1.4% versus 0%; and infective endocarditis 0.7% versus 0%). Secondary-outcome improvements were noted in both arms with diastolic blood pressure and high-density lipoprotein cholesterol (
P
<0.05).

CONCLUSIONS:
In patients with recent stroke/transient ischemic attack and PD, intensive PD treatment was not superior to standard PD treatment in prevention of stroke/myocardial infarction/death. Fewer events were noted in the intensive arm and the 2 arms were comparable in the safety outcomes. Secondary-outcome measures showed a trend toward improvement, with significant changes noted in diastolic blood pressure and high-density lipoprotein in both the treatment arms.
Toward a Typology of Environmental Cooperation in Postconflict Settings: The Case of Jordan and Israel
Authors: Kedem Rina , Feitelson Eran , Halasah Suleiman , Teff-Seker Yael 
Published: August 2023

Abstract
Mismatches between natural systems and political boundaries often hamper environmental management and conservation efforts. As the number of transboundary environmental cooperation (TEC) initiatives increases, it becomes imperative to establish a systematic scale for analyzing such initiatives. In this article, we advance a TEC typology and apply it to the Israeli–Jordanian case. The typology includes categories of TEC initiatives and their placement on a transaction cost ladder. This typology allows for analyses of the organizational scale, societal influence, and duration of TEC initiatives. A total of sixty TEC initiatives were analyzed in an iterative process. TEC initiatives between Israel and Jordan were found largely to bear low transaction costs. The suggested typology provides an assessment tool to a large number of initiatives and a baseline for further in-depth investigation of the causal relations between environmental cooperation, peace, and conflict and may be applied to conflictual contexts at various stages.
Features of Local Finite-Amplitude Wave Activity during Extreme Cold Waves over Eastern China
Authors: Shi Ning , Ekwacu Samuel , Fu Shiyi , Song Jian , Xing Shaoying 
Published: August 2023

Abstract
The frequent occurrence of extreme cold waves under climate change has attracted widespread attention. Based on the Japanese 55-year Reanalysis daily dataset from 1958 to 2021, we use a newly developed dynamic metric, the local finite-amplitude wave activity (LWA), to explore the precursory signals, outburst conditions, and key dynamic features of extreme cold waves over eastern China from the perspective of synoptic climatology. The statistical results show that approximately 40% of extreme cold waves have the following features. First, the formation of significant positive LWA anomalies over the Balkhash–Baikal region is an evident precursory signal, which is accompanied by significant cold surface air temperature anomalies that accumulate over mid- and high-latitude Eurasia. Second, the appearance of extreme positive LWA anomalies over the region east of Lake Baikal (ELB) is necessary for subsequent outbursts of extreme cold waves. These extreme positive LWA anomalies indicate the meridionally enhanced planetary trough over East Asia and advection of the accumulated cold air masses southeastward to eastern China. Third, the evident positive change in the LWA anomalies over the ELB is mainly attributable to the convergence of the zonal LWA flux due to the zonal wind in the eddy-free state and Stokes drift flux over the eastern area of the ELB and the convergence of the meridional eddy heat flux over the western area. This study demonstrates that the LWA could be used as a simple and feasible metric for monitoring and forecasting extreme cold waves.

Significance Statement
Enhanced waviness in circulation usually occurs before and during the outburst of extreme cold waves over eastern China. With a state-of-the-art diagnostic tool, the local finite-amplitude wave activity (LWA), the present study reveals both precursory signals and outburst conditions of these extreme cold events from the perspective of synoptic climatology. This study not only deepens our understanding of the dynamic process for extreme cold events over eastern China but also offers a method for monitoring and forecasting those extreme events. Our work also provides a method for studying other extreme climate events that are closely related to large-amplitude circulation waviness over the middle and high latitudes.
Observationally Constrained Projections of Twenty-First-Century Regional Warming in the Extratropical Northern Hemisphere
Authors: Liang Yongxiao , Gillett Nathan P. , Monahan Adam H. 
Published: August 2023

Abstract
Physically based observational constraint methods can effectively reduce uncertainty in global warming projections but have not been widely applied at regional scales. We first develop and apply multivariate linear regression models for constraining projections of surface air temperature averaged over subcontinental regions in the extratropical Northern Hemisphere, based on a set of potential constraints including climatological metrics derived from tropical and subtropical low-level cloud and global average past warming trend, as well as a set of regional climate metrics previously used in the literature. We evaluate the performance of the multivariate linear regression models based on cross-validated tests using output from phases 5 and 6 of the Coupled Model Intercomparison Projects (CMIP). We find that linear regression models using global-scale low-cloud metrics alone perform more robustly than linear regression models using the past global mean warming trend or regional climate metrics as constraints. These results, while favoring global constraints over the set of regional constraints considered, do not preclude the existence of even better regional constraints for particular regions. Through model-based cross-validation, the projections constrained using low-level cloud metrics exhibit more accurate best estimate projections, narrower uncertainty ranges, and more reliable uncertainty estimates in most Northern Hemisphere regions when compared with unconstrained projections. Application of the approach to climate projections based on both Shared Socioeconomic Pathway (SSP) 1-2.6 and SSP5-8.5 using observed low-cloud metrics results in considerably narrower 5%–95% uncertainty ranges of twenty-first-century warming over subcontinental Northern Hemisphere land regions compared to unconstrained projections.