bluuebunny/crossref_metadata_2025_split huggingface dataset:
Russia and the United States in the Arctic: from Competition to Confrontation
Authors: Raikov Yu. A. 
Published: June 2022

Abstract
The rivalry of great powers for hegemony and influence that has unfolded in the modern multipolar world is increasingly evident in the Arctic, a strategically important region of the world and exceptionally rich in natural resources. Тhe attractiveness of the Arctic and the competition of great powers around it are growing due to the objective changes taking place in the Far North in four important areas (technology, economy, climate, and law), contributing to the economic development of the region. The clash of interests, primarily between the United States and Russia, is leading to an increase in military and political tension, turning the once abandoned peripheral region of the Far North into a zone of increased information, as well as political, and, most importantly, military activity of the superpowers. This article analyzes the increased popularity of the Arctic topic in the foreign policy of the United States and Russia, which is associated with climate warming, the accelerated melting of glaciers in the Arctic, the prospect of opening new sea routes, and the growing activity of the Arctic and other states, primarily China, in the region. Against the background of recent international events related to the Arctic, the Arctic direction of the foreign policy of Washington, Moscow, and Beijing is considered. The emphasis is placed on its military‒political component, given that the growing political tension in the Arctic can lead to a new generation of armed conflicts and exacerbate the situation not only in the Northern region but also in the international arena as a whole. The situation is aggravated by the fact that there are no recognized norms of international law in the Arctic regarding the Arctic states’ ownership of concrete vast sectors of the Arctic Ocean and islands in its aquatic area. The delimitation of maritime boundaries and the determination of rights to economic activities here remain the main problem. Political tension is growing.
Peasants and Power in 1917: the Localization of the Revolution
Authors: Kabytov P. , Kabytova N. 
Published: June 2022

Abstract
This article analyzes the relationship between the peasants and the authorities during the Great Russian Revolution. The stages in the study of this problem are highlighted. When considering the mechanism of formation of power structures in rural areas, the specifics of sociopolitical associations in the countryside, which differed from those in the city, are revealed. The self-organization of the rural world manifested itself in the creation of grassroots peasant committees that implemented communal forms of popular representation. The organizing role of the provincial and district peasant congresses, which the peasants endowed with law-making powers, is shown. The reasons for the support of the peasants, both by community members and small owners, of Soviet power are revealed, the ways of its constitution on the ground are considered, and the use of power without justification of the traditional folk values is proved.
Advances in the management of idiopathic pulmonary fibrosis and progressive pulmonary fibrosis
Authors: Liu Gabrielle Y , Budinger G R Scott , Dematte Jane E 
Published: June 2022

ABSTRACTSimilarly to idiopathic pulmonary fibrosis (IPF), other interstitial lung diseases can develop progressive pulmonary fibrosis (PPF) characterized by declining lung function, a poor response to immunomodulatory therapies, and early mortality. The pathophysiology of disordered lung repair involves common downstream pathways that lead to pulmonary fibrosis in both IPF and PPF. The antifibrotic drugs, such as nintedanib, are indicated for the treatment of IPF and PPF, and new therapies are being evaluated in clinical trials. Clinical, radiographic, and molecular biomarkers are needed to identify patients with PPF and subgroups of patients likely to respond to specific therapies. This article reviews the evidence supporting the use of specific therapies in patients with IPF and PPF, discusses agents being considered in clinical trials, and considers potential biomarkers based on disease pathogenesis that might be used to provide a personalized approach to care.
Association between democratic governance and excess mortality during the COVID-19 pandemic: an observational study
Authors: Jain Vageesh , Clarke Jonathan , Beaney Thomas 
Published: June 2022

BackgroundExcess mortality has been used to assess the overall health impact of COVID-19 across countries. Democracies aim to build trust in government and enable checks and balances on decision making, which may be useful in a pandemic. But during the pandemic, they have been criticised as being hesitant to enforce restrictive public health measures.MethodsThrough linking open-access datasets we constructed univariable and multivariable linear regression models investigating the association between country V-Dem Liberal Democracy Indices (LDI), representing strength of democratic governance and excess mortality rates, from January 2020 to September 2021. We adjusted for several important confounders and conducted a range of sensitivity analyses to assess the robustness of our findings.ResultsAcross 78 countries, 4.19 million deaths million excess deaths were recorded. On multivariable regression, a one-point increase in V-Dem LDI was associated with a decrease in excess mortality of 2.18 per 100 000 (p=0.004), after accounting for age, gender, wealth and universal health coverage. This association was only partially attenuated by COVID-19 vaccination rates and remained robust in all sensitivity analyses.ConclusionsDemocratic governance may have played an important role in mitigating the overall health impact of COVID-19 across countries. This study strengthens the case to broaden the scope of traditional pandemic risk assessment and discussions on preparedness.
A no-go theorem for scalar fields with couplings from Ginzburg–Landau models
Authors: Liu Guohua , Peng Yan 
Published: June 2022

AbstractRecently Hod proved a no-go theorem that static scalar fields cannot form spherically symmetric boson stars in the asymptotically flat background. On the other side, scalar fields can be coupled to the gradient according to next-to-leading order Ginzburg–Landau models. In the present work, we extend Hod’s discussions by considering couplings between static scalar fields and the field gradient. For a non-negative coupling parameter, we show that there is no asymptotically flat spherically symmetric boson stars made of coupled static scalar fields.
Efficacy and Safety of Ripretinib in Chinese Patients with Advanced Gastrointestinal Stromal Tumors as a Fourth- or Later-Line Therapy: A Multicenter, Single-Arm, Open-Label Phase II Study
Authors: Li Jian , Cai Shirong , Zhou Yongjian , Zhang Jun , Zhou Ye , Cao Hui , Wu Xin , Deng Yanhong , Huang Zhao , Dong Juan , Shen Lin 
Published: June 2022

Abstract

Purpose:
This is a phase II multicenter, single-arm, open-label study assessing the efficacy, safety, and pharmacokinetics (PK) of ripretinib in Chinese patients with advanced gastrointestinal stromal tumor (GIST) as a fourth- or later-line therapy. It was designed to show consistency with the phase III INVICTUS study.

Patients and Methods:
Patients with disease progression on (or intolerance to) prior imatinib, sunitinib, and at least one other drug were recruited to receive ripretinib 150 mg once daily continuously in 28-day cycles. The primary endpoint was progression-free survival (PFS) based on independent radiologic review (IRR). Secondary efficacy endpoints included objective response rate (ORR) based on IRR and overall survival. Safety endpoints included the incidence and severity of adverse events (AE).

Results:
Between April 2020 and August 2020, 39 patients were enrolled. All were included in the safety analysis while 38 were included in the efficacy analysis. By primary data cut-off (February 26, 2021), the median PFS [90% confidence interval (CI)] was 7.2 (2.9–7.3) months; the lower bound of the 90% CI exceeded 1 month, fulfilling the standard of bridging success. The ORR (95% CI) based on IRR was 18.4% (7.7%–34.3%). Treatment-related treatment-emergent AEs (TRAE) were reported in 37 (94.9%) patients. The majority of TRAEs were of grade 1/2. A total of 6 patients (15.4%) experienced grade 3/4 TRAEs.

Conclusions:
The results demonstrated that ripretinib can clinically improve the outcomes of Chinese patients with advanced GIST as a fourth- or later-line therapy. The efficacy, safety, and PK profiles of ripretinib are consistent with those in the global patient population.
Superkine IL-2 and IL-33 Armored CAR T Cells Reshape the Tumor Microenvironment and Reduce Growth of Multiple Solid Tumors
Authors: Brog Rachel A. , Ferry Shannon L. , Schiebout Courtney T. , Messier Cameron M. , Cook W. James , Abdullah Leena , Zou Jia , Kumar Prathna , Sentman Charles L. , Frost H. Robert , Huang Yina H. 
Published: June 2022

Abstract

Chimeric-antigen receptor (CAR) T-cell therapy has shown remarkable efficacy against hematologic tumors. Yet, CAR T-cell therapy has had little success against solid tumors due to obstacles presented by the tumor microenvironment (TME) of these cancers. Here, we show that CAR T cells armored with the engineered IL-2 superkine Super2 and IL-33 were able to promote tumor control as a single-agent therapy. IFNγ and perforin were dispensable for the effects of Super2- and IL-33-armored CAR T cells. Super2 and IL-33 synergized to shift leukocyte proportions in the TME and to recruit and activate a broad repertoire of endogenous innate and adaptive immune cells including tumor-specific T cells. However, depletion of CD8+ T cells or NK cells did not disrupt tumor control, suggesting that broad immune activation compensated for loss of individual cell subsets. Thus, we have shown that Super2 and IL-33 CAR T cells can promote antitumor immunity in multiple solid tumor models and can potentially overcome antigen loss, highlighting the potential of this universal CAR T-cell platform for the treatment of solid tumors.
T-cell Receptor Gene Therapy Clinically Targeting aTP53Public Neoantigen
Authors: Klebanoff Christopher A. 
Published: June 2022

AbstractT-cell receptors (TCR) are an antigen receptor class that can uniquely respond to epitopes resulting from cytosolic and intranuclear proteins. In this issue, Kim and colleagues report the first successful application of TCR gene therapy targeting a shared, or public, neoantigen resulting from a TP53 hotspot mutation. These results establish clinical proof of concept that an off-the-shelf TCR targeting a recurrent mutation in a molecular driver of oncogenesis can benefit patients with metastatic cancer.See related article by Kim et al., p. 932 (4) .
Bcl-xL Inhibition RadiosensitizesPIK3CA/PTENWild-type Triple-negative Breast Cancers with Low Mcl-1 Expression
Authors: Pesch Andrea M. , Chandler Benjamin C. , Michmerhuizen Anna R. , Carter Hannah M. , Hirsh Nicole H. , Wilder-Romans Kari , Liu Meilan , Ward Tanner , Ritter Cassandra L. , Nino Charles A. , Jungles Kassidy M. , Pierce Lori J. , Rae James M. , Speers Corey W. 
Published: June 2022

Patients with radioresistant breast cancers, including a large percentage of women with triple-negative breast cancer (TNBC), demonstrate limited response to radiation and increased locoregional recurrence; thus, strategies to increase the efficacy of radiation in TNBC are critically needed. We demonstrate that pan Bcl-2 family inhibition [ABT-263, radiation enhancement ratio (rER): 1.52–1.56] or Bcl-xL–specific inhibition (WEHI-539, A-1331852; rER: 1.31–2.00) radiosensitized wild-type PIK3CA/PTEN TNBC (MDA-MB-231, CAL-120) but failed to radiosensitize PIK3CA/PTEN-mutant TNBC (rER: 0.90–1.07; MDA-MB-468, CAL-51, SUM-159). Specific inhibition of Bcl-2 or Mcl-1 did not induce radiosensitization, regardless of PIK3CA/PTEN status (rER: 0.95–1.07). In wild-type PIK3CA/PTEN TNBC, pan Bcl-2 family inhibition or Bcl-xL–specific inhibition with radiation led to increased levels of apoptosis (P &lt; 0.001) and an increase in cleaved PARP and cleaved caspase 3. CRISPR-mediated PTEN knockout in wild-type PIK3CA/PTEN MDA-MB-231 and CAL-120 cells induced expression of pAKT/Akt and Mcl-1 and abolished Bcl-xL inhibitor–mediated radiosensitization (rER: 0.94–1.07). Similarly, Mcl-1 overexpression abolished radiosensitization in MDA-MB-231 and CAL-120 cells (rER: 1.02–1.04) but transient MCL1 knockdown in CAL-51 cells promoted Bcl-xL inhibitor–mediated radiosensitization (rER: 2.35 ± 0.05). In vivo, ABT-263 or A-1331852 in combination with radiation decreased tumor growth and increased tumor-tripling time (P &lt; 0.0001) in PIK3CA/PTEN wild-type TNBC cell line and patient-derived xenografts. Collectively, this study provides the preclinical rationale for early-phase clinical trials testing the safety, tolerability, and efficacy of Bcl-xL inhibition and radiation in women with wild-type PIK3CA/PTEN wild-type TNBC at high risk for recurrence.Significance:This study proposes a novel strategy for the treatment of radioresistant TNBCs using FDA-approved compounds that target apoptosis to improve local disease control in this patient population.
Patent Ductus Arteriosus Stent Versus Surgical Aortopulmonary Shunt for Initial Palliation of Cyanotic Congenital Heart Disease with Ductal‐Dependent Pulmonary Blood Flow: A Systematic Review and Meta‐Analysis
Authors: Tseng Stephanie Y. , Truong Vien T. , Peck Daniel , Kandi Sneha , Brayer Samuel , Jason Don P. , Mazur Wojciech , Hill Garick D. , Ashfaq Awais , Goldstein Bryan H. , Alsaied Tarek 
Published: June 2022

Background
In patients with ductal‐dependent pulmonary blood flow, initial palliation includes catheter‐based patent ductus arteriosus (PDA) stent or surgical aortopulmonary shunt (APS). This meta‐analysis aimed to compare outcomes between PDA stent and APS.

Methods and Results

A comprehensive literature search yielded six retrospective observational studies. Pooled adjusted hazard ratios (HR) were included to control for covariates and assess time to event analysis. Of 757 patients, 243 (32.1%) underwent PDA stent and 514 (67.9%) underwent APS. Pulmonary atresia with intact ventricular septum and expected biventricular repair were more common with PDA stent compared with APS (39.6% versus 21.2%,
P
<0.001 and 57.9% versus 46.6%,
P
=0.007, respectively). There was no statistically significant difference in mortality between PDA stent and APS (HR, 0.71; [95% CI, 0.26–1.93];
P
=0.50). PDA stent was associated with lower risk of postprocedural complications (odds ratio [OR], 0.45; [95% CI, 0.25–0.81];
P
=0.008), mechanical circulatory support (OR, 0.27; [95% CI, 0.09–0.79];
P
=0.02), and shorter intensive care unit length of stay (−4.03 days; [95% CI, −5.99 to −2.07];
P
<0.001), hospital length of stay (−5.54 days; [95% CI, −9.20 to −1.88];
P
=0.003), and duration of mechanical ventilation (−3.41 days; [95% CI, −5.29 to −1.52];
P
<0.001). There was no difference in pulmonary artery growth or hazard of unplanned reintereventions.

Conclusions
PDA stent has a similar hazard of mortality compared with APS. Benefits to PDA stent include shorter duration of mechanical ventilation, shorter hospital length of stay, and fewer complications. Differences in patient characteristics exist with more patients with pulmonary atresia with intact ventricular septum and expected biventricular repair undergoing PDA stent.
Neuropeptide‐Y Levels in ST‐Segment–Elevation Myocardial Infarction: Relationship With Coronary Microvascular Function, Heart Failure, and Mortality
Authors: Gibbs Thomas , Tapoulal Nidi , Shanmuganathan Mayooran , Burrage Matthew K. , Borlotti Alessandra , Banning Adrian P. , Choudhury Robin P. , Neubauer Stefan , Kharbanda Rajesh K. , Ferreira Vanessa M. , Channon Keith M. , Herring Neil , Channon Keith M. , Ferreira Vanessa M. , De Maria Giovanni Luigi , Dawkins Sam , Lucking Andrew , Langrish Jeremy P. , Banning Adrian P. , Kharbanda Rajesh K. , Choudhury Robin P. 
Published: June 2022

Background
The sympathetic cotransmitter, neuropeptide Y (NPY), is released into the coronary sinus during ST‐segment–elevation myocardial infarction and can constrict the coronary microvasculature. We sought to establish whether peripheral venous (PV) NPY levels, which are easy to obtain and measure, are associated with microvascular obstruction, myocardial recovery, and prognosis.

Methods and Results

NPY levels were measured immediately after primary percutaneous coronary intervention and compared with angiographic and cardiovascular magnetic resonance indexes of microvascular function. Patients were prospectively followed up for 6.4 (interquartile range, 4.1–8.0) years. PV (n=163) and coronary sinus (n=68) NPY levels were significantly correlated (
r
=0.92;
P
<0.001) and associated with multiple coronary and imaging parameters of microvascular function and infarct size (such as coronary flow reserve, acute myocardial edema, left ventricular ejection fraction, and late gadolinium enhancement 6 months later). We therefore assessed the prognostic value of PV NPY during follow‐up, where 34 patients (20.7%) developed heart failure or died. Kaplan‐Meier survival analysis demonstrated that high PV NPY levels (>21.4 pg/mL by binary recursive partitioning) were associated with increased incidence of heart failure and mortality (hazard ratio, 3.49 [95% CI, 1.65–7.4];
P
<0.001). This relationship was maintained after adjustment for age, cardiovascular risk factors, and previous myocardial infarction.

Conclusions
Both PV and coronary sinus NPY levels correlate with microvascular function and infarct size after ST‐segment–elevation myocardial infarction. PV NPY levels are associated with the subsequent development of heart failure or mortality and may therefore be a useful prognostic marker. Further research is required to validate these findings.
Impact of Managing Provider Type on Severe Aortic Stenosis Management and Mortality
Authors: Pellikka Patricia A. , Padang Ratnasari , Scott Christopher G. , Murphy Shannon M. E. , Fabunmi Rosalind , Thaden Jeremy J. 
Published: June 2022

Background
Many patients with symptomatic severe aortic stenosis do not undergo aortic valve replacement (AVR) despite clinical guidelines. This study analyzed the association of managing provider type with cardiac specialist follow‐up, AVR, and mortality for patients with newly diagnosed severe aortic stenosis (sAS).

Methods and Results

We identified adults with newly diagnosed sAS per echocardiography performed between January 2017 and March 2019 using Optum electronic health record data. We then selected from those meeting all eligibility criteria patients managed by a primary care provider (n=1707 [25%]) or cardiac specialist (n=5039 [75%]). We evaluated the association of managing provider type with cardiac specialist follow‐up, AVR, and mortality, as well as the independent association of cardiac specialist follow‐up and AVR with mortality, within 1 year of echocardiography detecting sAS. A subgroup analysis was limited to patients with symptomatic sAS. Patient characteristics and comorbidities at baseline were used for covariate‐adjusted cause‐specific and multivariable Cox proportional hazard models assessing group differences in outcomes by managing provider type. An adjusted Cox proportional hazard model with additional time‐dependent covariates for follow‐up and AVR was used to assess these practices' association with mortality. Within 1 year of echocardiography detecting sAS, data revealed that primary care provider management was associated with lower rates of cardiac specialist follow‐up (hazard ratio [HR], 0.47 [95% CI, 0.43–0.50],
P
<0.0001) and AVR (HR, 0.58 [95% CI, 0.53–0.64],
P
<0.0001) and with higher 1‐year mortality (HR, 1.45 [95% CI, 1.26–1.66],
P
<0.0001). Cardiac specialist follow‐up and AVR were independently associated with lower mortality (follow‐up: HR, 0.55 [95% CI, 0.48–0.63],
P
<0.0001; AVR: HR, 0.70 [95% CI, 0.60–0.83],
P
<0.0001). Results were similar for patients with symptomatic sAS. All analyses were adjusted for baseline patient characteristics and comorbidities.

Conclusions
For patients newly diagnosed with sAS, we observed differences in rates of cardiac specialist follow‐up and AVR and risk of mortality between primary care provider‐ versus cardiologist‐managed patients with sAS. In addition, a lower likelihood of receiving follow‐up and AVR was independently associated with higher mortality.
Colchicine Ameliorates Dilated Cardiomyopathy Via SIRT2‐Mediated Suppression of NLRP3 Inflammasome Activation
Authors: Sun Xuan , Duan Junfeng , Gong Chenyi , Feng Yuting , Hu Jiaxin , Gu Rong , Xu Biao 
Published: June 2022

Background
Dilated cardiomyopathy remains a leading cause of heart failure worldwide. Immune inflammation response is recognized as a significant player in the progression of heart failure; however, immunomodulatory strategies remain a long‐term challenge. Colchicine, a potent anti‐inflammatory drug, has many benefits in ischemic cardiovascular events, but its role in nonischemic heart failure remains unclear.

Methods and Results
Doxorubicin administration was used to establish a murine dilated cardiomyopathy model, and colchicine or saline was orally given. At the end point, cardiac function and fibrosis were measured to investigate the effects of colchicine. Inflammatory cytokine levels, neutrophil recruitment, and NLRP3 (NOD‐like receptor protein 3) inflammasome activation were detected to evaluate the inflammatory response. Furthermore, to examine the downstream target of colchicine, SIRT2 (Sirtuin 2) was pharmacologically inhibited in vitro; thus, changes in the NLRP3 inflammasome were detected by immunoblotting. These results showed that murine cardiac function was significantly improved and fibrosis was significantly alleviated after colchicine treatment. Moreover, the infiltration of neutrophils and the levels of inflammatory cytokines in the failing myocardium were both decreased by colchicine treatment. Mechanistically, colchicine upregulated the expression of SIRT2, leading to the inactivation of the NLRP3 inflammasome in an NLRP3 deacetylated manner. Conversely, the inhibition of SIRT2 attenuated the suppressive effect of colchicine on NLRP3 inflammasome activation.

Conclusions
This study indicated that colchicine could be a promising therapeutic candidate for dilated cardiomyopathy and other nonischemic heart failure associated with the inflammatory response.