bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of acute dietary nitrate supplementation on oxygen delivery/consumption and limit of tolerance during progressive forearm exercise in men: a randomized crossover trial
Authors: Fenuta Alyssa M. , Drouin Patrick J. , Kohoko Zach I.N. , Lynn Mytchel J.T. , Tschakovsky Michael E. 
Published: January 2024

Beetroot juice (BRJ) supplementation increases nitric oxide bioavailability with hypoxia and acidosis, characteristics of high-intensity exercise. We investigated whether BRJ improved forearm oxygen delivery:demand matching in an intensity-dependent manner. Healthy men (21 ± 2.5 years) participated in a randomized crossover trial between October 2017 and May 2018 (Queen's University, Kingston, ON, Canada). Participants completed a forearm incremental exercise test to limit of tolerance (IET-LOT) 2.5 h post placebo (PL) versus BRJ (2 completed PL/BRJ vs. 9 completed BRJ/PL) within a 2-week period. Data are presented as mean ± standard deviation. There was a significant main effect of drink (PL < BRJ; P = 0.042, ηp2 = 0.385) and drink × intensity interaction for arteriovenous oxygen difference (PL < BRJ; P = 0.03; ηp2= 0.197; 20%–50% and 90% LOT). BRJ did not influence oxygen delivery ( P = 0.893, ηp2 = 0.002), forearm blood flow ( P = 0.589, ηp2 = 0.03) (forearm vascular conductance ( P = 0.262, ηp2 = 0.124), mean arterial pressure ( P = 0.254,ηp2 = 0.128)), oxygen consumption ( P = 0.194, ηp2 = 0.179) or LOT ( P = 0.432, d = 0.247). In healthy men, BRJ did not improve forearm oxygen delivery (vasodilatory or pressor response) during IET-LOT. Increased arteriovenous oxygen difference at submaximal intensities did not significantly influence oxygen consumption or performance across the entire range of forearm exercise intensities. This study adds to the growing body of evidence that BRJ does not influence small muscle mass blood flow in humans regardless of exercise intensity.
Research on energy-absorption active control method for large deformation of tunnel surrounding rock through multi-fault fracture zone
Authors: Tao Zhigang , Mao Yuting , Sun Jihao , Zhang Xiaoyu , Huo Shusen , He Manchao 
Published: January 2024

To study the problems of large deformation of surrounding rock and water-rich dense fracture zones during tunnel construction through fault fracture zone, the NPR (Negative Poisson’s Ratio) anchor cable control method is studied based on the Tabaiyi Tunnel. First, the mechanical deformation mechanism of surrounding rock is analyzed by geological conditions, lithology and strength of surrounding rock, and different surrounding rock zones are obtained. Then, based on the self-developed high-prestressed NPR anchor cable, the tunnel prevention and control measures are designed. The high-stress NPR anchor net technology is used to support the common large deformation and fault fracture zone, while in the water-rich dense fracture zones, the combined support of double gradient grouting technology and high-stress NPR anchor net technology is adopted. Finally, to evaluate the control effect of the support design scheme, the deformation of surrounding rock, the axial force of NPR anchor cable, and the pressure of steel arch are monitored in real time. The results show that the high-stress NPR anchor net technology can effectively control the large deformation of tunnel surrounding rock caused by fault zone. In addition, in the water-rich zones, the double gradient grouting technology can provide sufficient anchoring force for the NPR anchor cable. The two technologies control the maximum deformation of surrounding rock within 300 mm and realize the stability of tunnel primary support.
Multi-state Dirac stars
Authors: Liang Chen , Ren Ji-Rong , Sun Shi-Xian , Wang Yong-Qiang 
Published: January 2024

AbstractIn this paper, we construct the multi-state Dirac stars (MSDSs) consisting of two pairs of Dirac fields. The two pairs of Dirac fields are in the ground state and the first excited state, respectively, with opposite spins to ensure that the system possesses spherical symmetry. We discuss the solutions of the MSDSs under synchronized and nonsynchronized frequencies. By varying the ratio of masses between the two sets of Dirac fields, different branches of solutions can be obtained. Furthermore, we analyze the characteristics of the various MSDSs solutions and analyze the relationship between the ADM mass M of the MSDSs and the synchronized and nonsynchronized frequencies. Subsequently, we calculate the binding energy $$E_B$$

E
B

of the MSDSs and discuss the stability of the solutions. Then, we investigated the solutions of the MSDSs under the single particle condition. Finally, we discuss the feasibility of simulating the dark matter halos using MSDSs.
A simpler proof of Sternfeld’s Theorem
Authors: Dzhenzher S. 
Published: January 2024

In Sternfeld’s work on Kolmogorov’s Superposition Theorem appeared the combinatorial–geometric notion of a basic set and a certain kind of arrays. A subset [Formula: see text] is basic if any continuous function [Formula: see text] could be represented as the sum of compositions of continuous functions [Formula: see text] and projections to the coordinate axes. The definition of a Sternfeld array is presented in this paper. Sternfeld’s Arrays Theorem. If a closed bounded subset[Formula: see text] contains Sternfeld arrays of arbitrary large size then[Formula: see text] is not basic. The paper provides a simpler proof of this theorem.
Correlation between the Total Dose of Follicle-Stimulating Hormone and Cumulative Live Birth Rate in Women Undergoing in Vitro Fertilization
Authors: Le Long Ho , Ho Ngoc Anh Vu , Duong Toan , Ho Manh Tuong , Vuong Ngoc Lan 
Published: January 2024

Background: Follicle-stimulating hormone (FSH) is widely used during assisted reproductive therapy to facilitate the development of multiple follicles. In turn, the number of oocytes retrieved has been shown to relate to the live birth rate. This retrospective study investigated the correlation between the total FSH dose used and the cumulative live birth rate in individuals who had undergone in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). Methods: This retrospective study included women undergoing IVF/ICSI using a gonadotropin-releasing hormone antagonist protocol who had a regular menstrual cycle and an expected normal response to ovarian stimulation. Cumulative live birth rate was defined as the first live birth following the use of all fresh and frozen transfers of embryos derived from one stimulated IVF/ICSI cycle. Results: The analysis included 7,130 stimulated cycles in 6,517 individuals (9,138 transfers). The mean age, antral follicle count, and anti-Müllerian hormone level were [Formula: see text], [Formula: see text], and [Formula: see text][Formula: see text]ng/ml, respectively. The mean total FSH dose, total number of oocytes retrieved, and total FSH dose per oocyte retrieved were [Formula: see text] IU, [Formula: see text], and [Formula: see text] IU, respectively. There was a significant negative correlation between the total FSH dosage and the cumulative live birth rate in women aged [Formula: see text] years ([Formula: see text], 95% confidence interval [−0.14, −0.08]; [Formula: see text]) and in those aged [Formula: see text] years ([Formula: see text], 95% confidence interval [−0.11, −0.02]; [Formula: see text]). Conclusions: The cumulative live birth rate decreased as the total FSH dose increased. These findings suggest that physicians may wish to avoid prescribing a high dose of FSH in women undergoing IVF/ICSI who are predicted not to have a poor response.
AXL/WRNIP1 Mediates Replication Stress Response and Promotes Therapy Resistance and Metachronous Metastasis in HER2+ Breast Cancer
Authors: Marquez-Palencia Mauricio , Reza Herrera Luis , Parida Pravat Kumar , Ghosh Suvranil , Kim Kangsan , Das Nikitha M. , Gonzalez-Ericsson Paula I. , Sanders Melinda E. , Mobley Bret C. , Diegeler Sebastian , Aguilera Todd A. , Peng Yan , Lewis Cheryl M. , Arteaga Carlos L. , Hanker Ariella B. , Whitehurst Angelique W. , Lorens James B. , Brekken Rolf A. , Davis Anthony J. , Malladi Srinivas 
Published: January 2024

Abstract

Therapy resistance and metastatic progression are primary causes of cancer-related mortality. Disseminated tumor cells possess adaptive traits that enable them to reprogram their metabolism, maintain stemness, and resist cell death, facilitating their persistence to drive recurrence. The survival of disseminated tumor cells also depends on their ability to modulate replication stress in response to therapy while colonizing inhospitable microenvironments. In this study, we discovered that the nuclear translocation of AXL, a TAM receptor tyrosine kinase, and its interaction with WRNIP1, a DNA replication stress response factor, promotes the survival of HER2+ breast cancer cells that are resistant to HER2-targeted therapy and metastasize to the brain. In preclinical models, knocking down or pharmacologically inhibiting AXL or WRNIP1 attenuated protection of stalled replication forks. Furthermore, deficiency or inhibition of AXL and WRNIP1 also prolonged metastatic latency and delayed relapse. Together, these findings suggest that targeting the replication stress response, which is a shared adaptive mechanism in therapy-resistant and metastasis-initiating cells, could reduce metachronous metastasis and enhance the response to standard-of-care therapies.

Significance:
Nuclear AXL and WRNIP1 interact and mediate replication stress response, promote therapy resistance, and support metastatic progression, indicating that targeting the AXL/WRNIP1 axis is a potentially viable therapeutic strategy for breast cancer.
Body Weight Correlates with Molecular Variances in Patients with Cancer
Authors: Huang Fengyuan , Xu Peng , Yue Zongliang , Song Yuwei , Hu Kaili , Zhao Xinyang , Gao Min , Chong Zechen 
Published: January 2024

Abstract

Overweight and obesity are identified by a high body mass index (BMI) and carry significant health risks due to associated comorbidities. Although epidemiologic data connect overweight/obesity with 13 cancer types, a better understanding of the molecular mechanisms underlying this correlation is needed to improve prevention and treatment strategies. In this study, we conducted a comprehensive analysis of molecular differences between overweight or obese patients and normal weight patients across 14 different cancer types from The Cancer Genome Atlas. Using the propensity score weighting algorithm to control for confounding factors, obesity-specific mutational features were identified, such as higher mutation burden in rectal cancer and biased mutational signatures in other cancers. Differentially expressed genes (DEG) in tumors from patients with overweight/obesity were predominantly upregulated and enriched in inflammatory and hormone-related pathways. These DEGs were significantly associated with survival rates in various cancer types, highlighting the impact of elevated body fat on gene expression profiles and clinical outcomes in patients with cancer. Interestingly, while high BMI seemed to have a negative impact on most cancer types, the normal weight–biased mutational and gene expression patterns indicated overweight/obesity may be beneficial in endometrial cancer, suggesting the presence of an “obesity paradox” in this context. Body fat also significantly impacted the tumor microenvironment by modulating immune cell infiltration, underscoring the importance of understanding the interplay between weight and immune response in cancer progression. Together, this study systematically elucidates the molecular differences corresponding to body weight in multiple cancer types, offering potentially critical insights for developing precision therapy for patients with cancer.

Significance:
Elucidation of the complex interplay between body weight and the molecular landscape of cancer could potentially guide tailored therapies and improve patient management amid the global obesity crisis.
One CD4+TCR and One CD8+TCR Targeting Autochthonous Neoantigens Are Essential and Sufficient for Tumor Eradication
Authors: Wolf Steven P. , Anastasopoulou Vasiliki , Drousch Kimberley , Diehl Markus I. , Engels Boris , Yew Poh Yin , Kiyotani Kazuma , Nakamura Yusuke , Schreiber Karin , Schreiber Hans , Leisegang Matthias 
Published: January 2024

Abstract

Purpose:
To achieve eradication of solid tumors, we examined how many neoantigens need to be targeted with how many T-cell receptors (TCR) by which type of T cells.

Experimental Design:
Unmanipulated, naturally expressed (autochthonous) neoantigens were targeted with adoptively transferred TCR-engineered autologous T cells (TCR-therapy). TCR-therapy used CD8+ T-cell subsets engineered with TCRs isolated from CD8+ T cells (CD8+TCR-therapy), CD4+ T-cell subsets engineered with TCRs isolated from CD4+ T cells (CD4+TCR-therapy), or combinations of both. The targeted tumors were established for at least 3 weeks and derived from primary autochthonous cancer cell cultures, resembling natural solid tumors and their heterogeneity as found in humans.

Results:
Relapse was common with CD8+TCR-therapy even when targeting multiple different autochthonous neoantigens on heterogeneous solid tumors. CD8+TCR-therapy was only effective against homogenous tumors artificially derived from a cancer cell clone. In contrast, a combination of CD8+TCR-therapy with CD4+TCR-therapy, each targeting one neoantigen, eradicated large and established solid tumors of natural heterogeneity. CD4+TCR-therapy targeted a mutant neoantigen on tumor stroma while direct cancer cell recognition by CD8+TCR-therapy was essential for cure. In vitro data were consistent with elimination of cancer cells requiring a four-cell cluster composed of TCR-engineered CD4+ and CD8+ T cells together with antigen-presenting cells and cancer cells.

Conclusions:
Two cancer-specific TCRs can be essential and sufficient to eradicate heterogeneous solid tumors expressing unmanipulated, autochthonous targets. We demonstrate that simplifications to adoptive TCR-therapy are possible without compromising efficacy.
A Genomic Link From Heart Failure to Atrial Fibrillation Risk: FOG2 Modulates a TBX5/GATA4-Dependent Atrial Gene Regulatory Network
Authors: Broman Michael T. , Nadadur Rangarajan D. , Perez-Cervantes Carlos , Burnicka-Turek Ozanna , Lazarevic Sonja , Gams Anna , Laforest Brigitte , Steimle Jeffrey D. , Iddir Sabrina , Wang Zhezhen , Smith Linsin , Mazurek Stefan R. , Olivey Harold E. , Zhou Pingzhu , Gadek Margaret , Shen Kaitlyn M. , Khan Zoheb , Theisen Joshua W.M. , Yang Xinan H. , Ikegami Kohta , Efimov Igor R. , Pu William T. , Weber Christopher R. , McNally Elizabeth M. , Svensson Eric C. , Moskowitz Ivan P. 
Published: January 2024

BACKGROUND:

The relationship between heart failure (HF) and atrial fibrillation (AF) is clear, with up to half of patients with HF progressing to AF. The pathophysiological basis of AF in the context of HF is presumed to result from atrial remodeling. Upregulation of the transcription factor FOG2 (friend of GATA2; encoded by
ZFPM2
) is observed in human ventricles during HF and causes HF in mice.

METHODS:
FOG2 expression was assessed in human atria. The effect of adult-specific FOG2 overexpression in the mouse heart was evaluated by whole animal electrophysiology, in vivo organ electrophysiology, cellular electrophysiology, calcium flux, mouse genetic interactions, gene expression, and genomic function, including a novel approach for defining functional transcription factor interactions based on overlapping effects on enhancer noncoding transcription.

RESULTS:

FOG2 is significantly upregulated in the human atria during HF. Adult cardiomyocyte-specific FOG2 overexpression in mice caused primary spontaneous AF before the development of HF or atrial remodeling. FOG2 overexpression generated arrhythmia substrate and trigger in cardiomyocytes, including calcium cycling defects. We found that FOG2 repressed atrial gene expression promoted by TBX5. FOG2 bound a subset of GATA4 and TBX5 co-bound genomic locations, defining a shared atrial gene regulatory network. FOG2 repressed TBX5-dependent transcription from a subset of co-bound enhancers, including a conserved enhancer at the
Atp2a2
locus. Atrial rhythm abnormalities in mice caused by
Tbx5
haploinsufficiency were rescued by
Zfpm2
haploinsufficiency.

CONCLUSIONS:
Transcriptional changes in the atria observed in human HF directly antagonize the atrial rhythm gene regulatory network, providing a genomic link between HF and AF risk independent of atrial remodeling.
Trade-war Tariffs and Supply Chain Trade
Authors: Swenson Deborah L. 
Published: January 2024

Abstract
Although Chinese exports to the United States hit an all-time high in 2022, it would be incorrect to conclude that the U.S.–China trade war had no effects on trade. By exploiting fine product-level information on trade war tariffs, this paper demonstrates how the trade war diminished China's exports to the United States in tariff-impeded products, while expanding opportunities for exports from other countries in a fashion that had some systematic characteristics. First, the impact of the trade war tariffs was not immediate, as trade responses took place with a lag. Second, the responses to trade-war tariffs were heterogenous across countries and regions, with finer distinctions by product categories. Finally, trade that could be viewed as highly tied to global value chains (GVCs), such as trade in information and communication technology products, exhibited stronger reactions to the imposition of trade-war tariffs. These responses, and their implications for the organization of global supply chains, are discussed considering current trade concerns.
Tropospheric Thermal Forcing of the Stratosphere through Quasi-Balanced Dynamics
Authors: Lin Jonathan , Emanuel Kerry 
Published: January 2024

Abstract
The steady response of the stratosphere to tropospheric thermal forcing via an SST perturbation is considered in two separate theoretical models. It is first shown that an SST anomaly imposes a geopotential anomaly at the tropopause. Solutions to the linearized quasigeostrophic potential vorticity equations are then used to show that the vertical length scale of a tropopause geopotential anomaly is initially shallow, but significantly increased by diabatic heating from radiative relaxation. This process is a quasi-balanced response of the stratosphere to tropospheric forcing. A previously developed, coupled troposphere–stratosphere model is then introduced and modified. Solutions under steady, zonally symmetric SST forcing in the linear β-plane model show that the upward stratospheric penetration of the corresponding tropopause geopotential anomaly is controlled by two nondimensional parameters: 1) a dynamical aspect ratio and 2) a ratio between tropospheric and stratospheric drag. The meridional scale of the SST anomaly, radiative relaxation rate, and wave drag all significantly modulate these nondimensional parameters. Under Earthlike estimates of the nondimensional parameters, the theoretical model predicts stratospheric temperature anomalies 2–3 larger in magnitude than that in the boundary layer, approximately in line with observational data. Using reanalysis data, the spatial variability of temperature anomalies in the troposphere is shown to have remarkable coherence with that of the lower stratosphere, which further supports the existence of a quasi-balanced response of the stratosphere to SST forcing. These findings suggest that besides mechanical and radiative forcing, there is a third way the stratosphere can be forced—through the tropopause via tropospheric thermal forcing.

Significance Statement
Upward motion in the tropical stratosphere, the layer of atmosphere above where most weather occurs, is thought to be controlled by weather disturbances that propagate upward and dissipate in the stratosphere. The strength of this upward motion is important since it sets the global distribution of ozone. We formulate and use simple mathematical models to show the vertical motion in the stratosphere can also depend on the warming in the troposphere, the layer of atmosphere where humans live. We use the theory as an explanation for our observations of inverse correlations between the ocean temperature and the stratosphere temperature. These findings suggest that local stratospheric cooling may be coupled to local tropospheric warming.
Asymmetry of the Distribution of Vertical Velocities of the Extratropical Atmosphere in Theory, Models, and Reanalysis
Authors: Kohl Matthieu , O’Gorman Paul A. 
Published: January 2024

Abstract
The vertical velocity distribution in the atmosphere is asymmetric with stronger upward than downward motion. This asymmetry is important for the distribution of precipitation and its extremes and for an effective static stability that has been used to represent the effects of latent heating on extratropical eddies. Idealized GCM simulations show that the asymmetry increases as the climate warms, but current moist dynamical theories based around small-amplitude modes greatly overestimate the increase in asymmetry with warming found in the simulations. Here, we first analyze the changes in asymmetry with warming using numerical inversions of a moist quasigeostrophic omega equation applied to output from the idealized GCM. The inversions show that increases in the asymmetry with warming in the GCM simulations are primarily related to decreases in moist static stability on the left-hand side of the moist omega equation, whereas the dynamical forcing on the right-hand side of the omega equation is unskewed and contributes little to the asymmetry of the vertical velocity distribution. By contrast, increases in asymmetry with warming for small-amplitude modes are related to changes in both moist static stability and dynamical forcing leading to enhanced asymmetry in warm climates. We distill these insights into a toy model of the moist omega equation that is solved for a given moist static stability and wavenumber of the dynamical forcing. In comparison to modal theory, the toy model better reproduces the slow increase of the asymmetry with climate warming in the idealized GCM simulations and over the seasonal cycle from winter to summer in reanalysis.

Significance Statement
Upward velocities are stronger than downward velocities in the atmosphere, and this asymmetry is important for the distribution of precipitation because precipitation is linked to upward motion. An important and open question is what sets this asymmetry and how much it increases as the climate warms. Past work has shown that current theories greatly overestimate the increase in asymmetry with warming in idealized simulations. In this work, we develop a more complete theory and show that it is able to better reproduce the slow increase of the asymmetry with warming that is found over the seasonal cycle from winter to summer and in idealized simulations of warming climates.