bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thermal false vacuum decay in (1+1) dimensions: Evidence for nonequilibrium dynamics
Authors: Pîrvu Dalila , Shkerin Andrey , Sibiryakov Sergey 
Published: November 2024

In this paper, we numerically study the evolution of a classical real scalar field in [Formula: see text] dimensions with initial conditions describing thermal fluctuations around a metastable vacuum. We track false vacuum decay in real time and compare several observables to the predictions of the standard Euclidean formalism. We find agreement for the shape of the critical bubble and the exponential suppression of the decay rate. However, the decay rate prefactor is almost an order of magnitude lower than the predicted value. We argue that this signals a breakdown of thermal equilibrium during the bubble nucleation. In addition, the inefficient thermalization in the system biases the properties of the statistical ensemble and leads to further decrease of the decay rate with time. We substantiate our interpretation with a suite of stochastic field simulations with controlled thermalization time. By varying this time, we find that the predictions of the standard equilibrium formalism are recovered when it is sufficiently short. We propose an upper bound on the thermalization time that must be satisfied in order to ensure the applicability of the Euclidean rate calculation. We discuss that this bound is unavoidably violated in common single-field models, irrespective of the number of space–time dimensions, implying that deviations from equilibrium in these models cannot be neglected. In theories with multiple fields, the bound may or may not hold, depending on the setup details. We investigate one more signature of nonequilibrium dynamics — coherent oscillonic precursors to the critical bubble nucleation. We show that they get suppressed in the stochastic dynamical simulations when the thermalization time is reduced.
Hemodynamic Alterations in Cardiac Function Among Patients With Stroke and SARS‐CoV‐2 Infection: A Retrospective Cohort Study
Authors: Zhou Mingchao , Zha Fubing , Zhao Liuyang , Li Dongxia , Luo Jiao , Wang Yao , Liu Fang , Zhou Jing , Zhang Zeyu , Zou Yucong , Xiong Feng , Hou Dianrui , Li Fei , He Mingjun , Zhu Yongjie , Wang Yulong 
Published: November 2024

Objective: Cardiovascular complications associated with COVID‐19 are being increasingly recognized. They include potential long‐term effects on the heart, although how these complications manifest in patients with stroke who are already vulnerable to cardiovascular issues is lacking. This study addressed this gap by investigating the influence of SARS‐CoV‐2 infection on cardiac hemodynamic changes in inpatients with stroke, thereby providing valuable insights into the management of cardiac complications in this population.Methods: This retrospective cohort study enrolled inpatients with stroke who did or did not experience SARS‐CoV‐2 infection in Shenzhen Second People’s Hospital. Clinical information, hemodynamics data, serum myocardial enzyme levels, functional levels, including Barthel index, and Longshi scale assessment (bedridden, domestic, and community) were extracted from clinical records. An independent sample t‐test and the Mann–Whitney U test were used for comparison between groups. Multiple logistic regression analysis was used to identify indicators associated with decline in cardiac function in patients with stroke post‐COVID‐19.Results: Eighty‐three patients with stroke (average age of 66.0 ± 15.5 years) were recruited (42 patients in the study group and 41 in the control group). No significant difference in general characteristics was observed between the groups. The ejection fraction (EF, 56.45 ± 12.46 vs. 47.64 ± 14.76, p = 0.04) was decreased, and the end‐diastolic volume (EDV, 142.74 ± 80.00 vs. 193.34 ± 140.17, p = 0.001) was increased significantly in patients infected with SARS‐CoV‐2 compared with the noninfected participants. SARS‐CoV‐2 infection was an independent risk factor for EF (−10%) decrease (OR: 5.205, 95% CI: 1.621–16.720, p = 0.006). The risk of cardiac function decline among bedridden infected patients was 15.43 times higher than that of uninfected nonbedridden patients (OR: 15.430, 95% CI: 1.402–169.805, p = 0.025).Conclusion: Patients who are bedridden after stroke face a higher potential risk of cardiac hemodynamic impairment following SARS‐CoV‐2 infection, emphasizing the need for meticulous hemodynamic monitoring during treatment and rehabilitation of these patients to prevent any potential cardiovascular complications.Trial Registration: ClinicalTrials.gov identifier: ChiCTR2300071376.
Predictive Factors for the Efficacy of Radioactive Iodine Treatment of Graves’ Disease
Authors: Feng Wenwen , Shi He , Yang Yanli , Liu Jing , Chen Shiying , Ren Minghui , Li Yajie , Liu Wei , Cui Dai 
Published: November 2024

Objective: The utilization of radioactive iodine‐131I (RAI) has long been established as a cost‐effective and conventional treatment for managing Graves’ disease (GD). However, the accurate prediction of the clinical response to RAI treatment remains difficult. The successful resolution of GD through RAI therapy is typically characterized by the induction of hypothyroidism or euthyroidism. Thus, the principal aim of this study was to identify plausible predictors of RAI efficacy in the treatment of GD.Methods: The clinical data of 613 GD patients, who underwent RAI treatment for the first time, were retrospectively analyzed, including age, gender, duration of hyperthyroidism, presence or absence of ocular signs, thyroid volume, thyroid weight, thyroid function (FT3, FT4, and TSH), radioactive iodine uptake (RAIU) at 2 h/6 h/24 h (2‐h/6‐h/24‐h RAIU) prior to RAI treatment, the highest RAIU (RAIUmax), and administered activity of 131I and 131I activity per gram of thyroid tissue. Success of RAI treatment was defined as achieving hypothyroidism or euthyroidism for more than 1 year after the initial treatment. Univariate and multivariate logistics regression analyses were conducted to identify factors that influence the efficacy of RAI treatment for GD. And at last, based on the results of the multivariate logistic regression analysis, a nomogram model was established.Results: In this study, the success rate of RAI treatment for GD was 91.2% (559/613). Univariate analysis demonstrated that several factors, including age (p = 0.005), thyroid volume (p = 0.001), thyroid‐stimulating hormone (TSH, p = 0.042), ratio of RAIU at 6 h to 24 h (6‐h/24‐h RAIU, p = 0.048), total 131I activity (p = 0.026), and 131I activity per gram of thyroid tissue (p = 0.001), were significantly associated with treatment outcome. Multivariate logistic regression analysis indicated thyroid volume and 131I activity per gram of thyroid tissue as significant independent predictors of radioactive iodine therapy (RIT) efficacy. The area under the ROC curve of the established nomogram model was 0.769 (95% confidence interval [CI]: 0.692–0.846), indicating that the model has good discriminatory ability.Conclusion: Calculated‐dose RAI is effective in the treatment of GD. The smaller thyroid volume and the higher 131I activity per gram of thyroid tissue are predictors of RAI efficacy in the treatment of GD.
Loss of CDKN2A Enhances the Efficacy of Immunotherapy in EGFR-Mutant Non–Small Cell Lung Cancer
Authors: Wang Simeng , Lai Jia-Cheng , Li Yu , Tang Chengfang , Lu Jiajia , Han Min , Ye Xianjiang , Jia Lina , Cui Wei , Yang Jingyu , Wu Chunfu , Wang Lihui 
Published: November 2024

Abstract
Mutant EGFR is a common driver of non–small cell lung cancer (NSCLC). Although mutant EGFR has been reported to limit the efficacy of immunotherapy, a subset of patients with EGFR-mutant NSCLC benefit from treatment with immune checkpoint inhibitors. A better understanding of how co-occurring genomic alterations in oncogenic driver genes impact immunotherapy efficacy may provide a more complete understanding of cancer heterogeneity and identify biomarkers of response. Here, we investigated the effects of frequent EGFR co-mutations in EGFR-mutant lung cancer models and identified loss-of-function mutation of CDKN2A as a potential sensitizer to anti–PD-1 treatment in vitro and in vivo. Mechanistically, CDKN2A loss impacted the composition of the tumor immune microenvironment by promoting the expression of PD-L2 through reduced ubiquitination of c-MYC, and mutant EGFR cooperating to upregulate c-MYC and PD-L2 by activating the MAPK pathway. Blocking PD-L2 induced antitumor immune responses mediated by CD8+ T cells in EGFR/CDKN2A co-mutated lung cancer. Importantly, a small-molecule PD-L2 inhibitor, zinc undecylenate, remodeled the tumor immune microenvironment of EGFR/CDKN2A co-mutant tumors and enhanced the antitumor efficacy of EGFR tyrosine kinase inhibitors. Collectively, these results identify EGFR/CDKN2A co-mutation as a distinct subtype of NSCLC that shows superior sensitivity to immune checkpoint blockade and reveals a potential combined therapeutic strategy for treating this NSCLC subtype.
Significance: Upregulation of c-MYC driven by co-mutation of CDKN2A and EGFR increases PD-L2 to abrogate CD8+ T-cell activity in lung cancer, which confers sensitivity to PD-L2 blockade in combination with tyrosine kinase inhibitors.
TIPE Inhibits Ferroptosis in Colorectal Cancer Cells by Regulating MGST1/ALOX5
Authors: Yan Changxiu , Yu Shengnan , Zhang Jing , Li Zhen , Lin Zeyang , Zhang Shiying , Li Haoyang , Ye Zhijian , Huang Jiyi , Ye Yuhan , Zhuang Guohong 
Published: November 2024

Abstract
TIPE is a protein highly expressed in various cancers that promotes ferroptosis in colorectal cancer cells. Ferroptosis is a nonapoptotic cell death caused by lipid peroxidation, and microsomal glutathione transferase 1 (MGST1) is a critical enzyme that resists lipid peroxidation. This study explored how TIPE regulates MGST1 expression to inhibit ferroptosis and promote colorectal cancer proliferation. TIPE was highly expressed in colorectal cancer tissues and positively correlated with the proliferation of human colorectal cancer cells. We measured levels of reactive oxygen species and lipid reactive oxygen species in colorectal cancer cells with differential expression of TIPE and detected ferroptosis using transmission electron microscopy. Bioinformatics analysis revealed a positive correlation of expression patterns between TIPE and MGST1 in colorectal cancer. TIPE regulated the expression of MGST1 by activating the phosphorylation of ERK1/2. Coimmunoprecipitation revealed binding between MGST1 and ALOX5. This binding inhibited the phosphorylation of ALOX5, inhibiting ferroptosis and promoting the proliferation of colorectal cancer cells. A tumor formation experiment in nude mice supported our findings that TIPE regulates the proliferation of colorectal cancer by regulating ferroptosis.
Implications: TIPE inhibits colorectal cancer ferroptosis via an MGST1–ALOX5 interaction to promote colorectal cancer proliferation. These findings suggest future colorectal cancer treatment strategies.
Combination CXCR4 and PD-1 Blockade Enhances Intratumoral Dendritic Cell Activation and Immune Responses Against Hepatocellular Carcinoma
Authors: Morita Satoru , Lei Pin-Ji , Shigeta Kohei , Ando Tomofumi , Kobayashi Tatsuya , Kikuchi Hiroto , Matsui Aya , Huang Peigen , Pittet Mikael J. , Duda Dan G. 
Published: November 2024

Abstract
Immune checkpoint inhibitors have revolutionized the treatment of unresectable hepatocellular carcinoma (HCC), but their impressive efficacy is seen in just a fraction of patients. One key mechanism of immunotherapy resistance is the paucity of dendritic cells (DC) in liver malignancies. In this study, we tested combination blockade of PD-1 and CXCR4, a receptor for CXCL12, a pleiotropic factor that mediates immunosuppression in tumors. Using orthotopic grafted and autochthonous HCC models with underlying liver damage, we evaluated treatment feasibility and efficacy. In addition, we examined the effects of treatment using immunofluorescence, flow cytometric analysis of DCs in vivo and in vitro, and RNA sequencing. The combination anti-CXCR4 and anti–PD-1 therapy was safe and significantly inhibited tumor growth and prolonged survival in all murine preclinical models of HCC tested. The combination treatment successfully reprogrammed antigen-presenting cells, revealing the potential role of conventional type 1 DCs (cDC1) in the HCC microenvironment. Moreover, DC reprogramming enhanced anticancer immunity by facilitating CD8+ T-cell accumulation and activation in the HCC tissue. The effectiveness of anti-CXCR4/PD-1 therapy was compromised entirely in Batf3 knockout mice deficient in cDC1s. Thus, combined CXCR4/PD-1 blockade can reprogram intratumoral cDC1s and holds the potential to potentiate antitumor immune response against HCC.
IL1RAP Blockade With a Monoclonal Antibody Reduces Cardiac Inflammation and Preserves Heart Function in Viral and Autoimmune Myocarditis
Authors: Lema Diego A. , Jakobsson Gabriel , Daoud Abdel , Elias David , Talor Monica V. , Rattik Sara , Grönberg Caitríona , Kalinoski Hannah , Jaensson Gyllenbäck Elin , Wang Nadan , Liberg David , Schiopu Alexandru , Čiháková Daniela 
Published: November 2024

BACKGROUND:
Currently, there are no therapies targeting specific pathogenic pathways in myocarditis. IL (interleukin)-1 blockade has shown promise in preclinical studies and case reports. We hypothesized that blockade of IL1RAP (IL-1 receptor accessory protein), a shared subunit of the IL-1, IL-33, and IL-36 receptors, could be more efficient than IL-1 blockade alone.

METHODS:
We induced coxsackievirus B3 (CVB3)–mediated or experimental autoimmune myocarditis (EAM) in BALB/c mice, followed by treatment with an Fc (fragment crystallizable)-modified mIgG2a mouse anti-mouse IL1RAP monoclonal antibody (mCAN10). Myocarditis severity and immune infiltration were assessed by histology and flow cytometry. Cardiac function was measured by echocardiography. We used spatial transcriptomics (Visium 10× Genomics) to compare the gene expression landscape in the hearts of mCAN10-treated versus control mice.

RESULTS:

IL1RAP blockade reduced CVB3 and EAM severity. In EAM, the treatment prevented deterioration of cardiac function, measured on day 42 post-disease induction (left ventricular ejection fraction: 56.5% versus 51.0% in isotype controls [
P
=0.002] and versus 51.4% in mice treated with anti-IL-1β antibodies alone [
P
=0.003]; n=10–11 mice per group). In the CVB3 model, mCAN10 did not impede viral clearance from the heart and significantly lowered the numbers of CD4
+
(cluster of differentiation 4) T cells (
P
=0.025), inflammatory Ly6C
+
CCR2
+
(lymphocyte antigen 6 complex, locus C/C-C motif chemokine receptor 2) monocytes (
P
=0.038), neutrophils (
P
=0.001) and eosinophils (
P
<0.001) infiltrating the myocardium. The spatial transcriptomic analysis revealed reduced canonical IL-1 signaling and chemokine expression in cardiac immune foci in CVB3-infected mice treated with IL1RAP blockade.

CONCLUSIONS:
Blocking IL1RAP reduces acute CVB3 myocarditis and EAM severity and preserves cardiac function in EAM. We conclude that IL1RAP blockade is a potential therapeutic strategy in viral and autoimmune myocarditis.
The Context, Logic, and Perpetuation of Violence
Authors: Haase Dwight 
Published: November 2024

Abstract
This article attempts to explain why the current conflict in Gaza has happened through a brief history of conflicts in Gaza since 2005 and a discussion of more recent events, focusing on conditions such as inequality, dependency, political repression, ethnic divisions, and previous incidents of violence. The article also reflects on the US response to the situation, concluding that domestic political agendas and the influence of special interests have perpetuated the Gaza crisis.
The Legal Landscape of Freedom of Association in Canada: The Complex Path to Half of a Constitutional Freedom
Authors: Newman Dwight 
Published: November 2024

Abstract
Part of a special issue setting out the shape of freedom of association in jurisdictions around the world, this article analyzes freedom of association in Canada. It argues that freedom of association in Canada has struggled toward being half a freedom. Early union-context case law saw it significantly constrained in judicial interpretation, though that has changed in recent years. Today, those judicial interpretations continue to face possible parliamentary response under distinctive constitutional arrangements in Canada, and they have not yet animated a case law on association outside the union context, though that now has more potential. So, association remains in the position of being a half-freedom, though this landscape could change in the years to come.
Pluriversal Autonomies Beyond Development: Towards an Intercultural, Decolonial and Ecological Buen Vivir as an Alternative to the 2030 Agenda in Abya Yala/Latin America
Authors: Garcia-Arias Jorge , Cuestas-Caza Javier 
Published: November 2024

This article employs Critical Development Studies to analyze the international political economy of the 2030 Agenda for Sustainable Development and address how the main elements that sustain and characterize it turn it into “another brick in the wall” of the hegemonic development paradigm (neoliberal, neo-developmentalist, neocolonial, privatized, inequitable, and environmentally predatory). It further analyzes how this 2030 Agenda contributed to the process of ‘enclosure of development’ in Abya Yala/Latin America (AY/LA). We then employ decolonial thought and pluriversal perspectives to contest this hegemonic vision and imagine an intercultural, decolonial and ecological buen vivir or “good living” (BV-IDE) as an autonomist alternative to the 2030A model for AY/LA, and address three contemporary experiences in Colombia, Ecuador, and Central America. En este trabajo, partiendo de una perspectiva de Estudios Críticos del Desarrollo y tras un análisis de economía política internacional crítica de la Agenda 2030 de Desarrollo Sostenible, mostramos cómo los ejes principales que la sostienen y atraviesan la convierten en ‘otro ladrillo en el muro’ del paradigma de desarrollo hegemónico (neoliberal, neodesarrollista, neocolonial, privatizado, inequitativo, y ecológicamente depredador), y cómo dicha Agenda 2030 ha contribuido al proceso de ‘cercamiento del desarrollo’, también en Abya Yala/América Latina (AY/AL). Como respuesta a esta visión hegemónica proponemos, desde los aportes del pensamiento decolonial y las perspectivas pluriversales, imaginar un buen vivir intercultural, decolonial y ecologista (BV-IDE) como alternativa autonomista al modelo de la 2030A para AY/AL, y presentamos tres experiencias contemporáneas, en Colombia, Ecuador y Centroamérica, conectadas con nuestra propuesta.
Stroke due to small-vessel disease and migraine: A case–control study of a young adult with ischemic stroke population
Authors: Cloet Faustin , Gueyraud Gabriel , Lerebours Fleur , Munio Mélanie , Larrue Vincent , Gollion Cédric 
Published: November 2024

Background Migraine with aura (MWA) is a risk factor for stroke, but the mechanisms underlying this association remain unclear. Our aim was to assess the association between MWA and cerebral small-vessel disease (CSVD) ischemic stroke after adjustment for vascular risk factors in a population of young patients hospitalized for a first-ever ischemic stroke. Methods Patients aged 18–54 years consecutively hospitalized for a first-ever acute ischemic stroke at the neurovascular unit of our university hospital between January 2017 and July 2021 were included in this retrospective cohort study. CSVD lesions were assessed and classified according to ASCOD (Atherosclerosis, Small-Vessel Disease, Cardiac pathology, Others causes, Dissection) classification criteria. Results In total, 646 patients were included (median (SD) age, 44.03 (9.01) years; 61.8% male) including 115 patients with MWA and 110 patients with migraine without aura (MWoA). Grade S1, potentially causal, CSVD lesions were significantly less frequent in patients with MWA (odds ratio (OR) = 0.35, 95% cofdence interval (CI)  =  0.13–0.95, p = 0.048) compared to non-migraine patients in univariate analysis. Logistic regression adjusting for vascular risk factors showed no significant association of CSVD of any grade (S1, S2 or S3 vs. S0) with migraine: OR = 0.78, 95% CI = 0.48–1.28, p = 0.34; MWoA: OR = 0.81, 95% CI = 0.42–1.47, p = 0.51; and MWA: OR = 0.84, 95% CI = 0.43–1.56, p = 0.60, as well as no association of grade S1 CSVD lesions with migraine: OR = 0.91, 95% CI = 0.40–1.92, p = 0.81; MWoA: OR = 1.11, 95% CI = 0.42–2.64, p = 0.81; and MWA: OR = 0.72, 95% CI = 0.20–1.98, p = 0.56. Conclusions In a retrospective study including almost 650 young adults hospitalized for a first ischemic stroke, MWA was not associated with CSVD cause of stroke after adjustment for vascular risk factors.
Higher BMI Is Associated With Wound Breakdown Following Resection of Haglund Deformity
Authors: Morrissette Kali J. , Kutzer Katherine M. , Krez Alexandra N. , Wu Kevin A. , Hinton Zoe W. , Anastasio Albert T. , Hanselman Andrew E. , Schweitzer Karl M. , Adams Samuel B. , Easley Mark E. , Nunley James A. , Amendola Ned 
Published: November 2024

Background: Haglund deformity is characterized by an enlarged posterosuperior calcaneus, often with inflammation of the retrocalcaneal bursa and Achilles tendon. This study aims to determine if obesity is associated with an increased rate of complications after Haglund resection. Methods: A retrospective review was conducted on patients who underwent surgical resection for Haglund deformity from January 2015 to December 2023 at a single academic center. The patient cohort was initially stratified by body mass index (BMI) into normal (BMI < 25), overweight (25 ≤ BMI < 30), and obese (BMI ≥ 30). For those classified as obese, further subclassification was performed using the standard system: obesity class I (mild obesity) = BMI 30.0-34.9; obesity class II (moderate obesity) = BMI 35.0-39.9; and obesity class III (severe obesity) = BMI ≥40.0. Data on demographics, surgical techniques, and weightbearing were collected and analyzed. Postoperative complications were compared between groups. Results: Of the 370 patients included in this study, 20 (5.4%) were classified as normal, 77 (20.8%) were overweight, and 273 (73.8%) were obese. Within the cohort of patients with obesity, 96 (35.2%) were classified as obesity class I, 96 (35.2%) as obesity class II, and 81 (29.7%) as obesity class III. The obese group had a higher proportion of females (70.0%) and Black/African American race (24.5%), and a higher prevalence of diabetes mellitus (22.0%) and American Society of Anesthesiologists scores compared with other groups. Additionally, analysis within the obesity subclassifications revealed significant differences in smoking status, with a higher proportion of nonsmokers as obesity class increased (58.3% in class I, 76.0% in class II, and 79.0% in class III; P = .01). Follow-up duration averaged 10.5 months, with wound breakdown rates significantly higher in the obese group vs the overweight or normal groups (11.0% vs 2.6% vs 0.0%, P = .02). No significant differences in wound complications or outcomes were observed between patients based on different obesity subclassifications. Conclusion: Our findings demonstrate that after Haglund resection, obese patients have a higher risk of complications, particularly wound breakdown. This underscores the necessity of careful patient selection and perioperative optimization.