bluuebunny/crossref_metadata_2025_split huggingface dataset:
Symmetric wormholes in Einstein-vector–Gauss–Bonnet theory
Authors: Barton Simon , Kiefer Claus , Kleihaus Burkhard , Kunz Jutta 
Published: September 2022

AbstractWe construct wormholes in Einstein-vector–Gauss–Bonnet theory where a real massless vector field is coupled to the higher curvature Gauss–Bonnet invariant. We consider three coupling functions which depend on the square of the vector field. The respective domains of existence of wormholes possess as their boundaries (i) black holes, (ii) solutions with a singular throat, (iii) solutions with a degenerate throat and (iv) solutions with cusp singularities. Depending on the coupling function wormhole solutions can feature a single throat or an equator surrounded by a double throat. The wormhole solutions need a thin shell of matter at the throat, in order to be symmetrically continued into the second asymptotically flat region. These wormhole spacetimes allow for bound and unbound particle motion as well as light rings.
Schottky’s forgotten step to the Ising model
Authors: Folk Reinhard , Holovatch Yurij 
Published: September 2022

AbstractA longstanding problem in natural science and later in physics was the understanding of the existence of ferromagnetism and its disappearance under heating to high temperatures. Although a qualitative description was possible by the Curie–Weiss theory, it was obvious that a microscopic model was necessary to explain the tendency of the elementary magnetons to prefer parallel ordering at low temperatures. Such a model was proposed in 1922 by Schottky within the old Bohr–Sommerfeld quantum mechanics and claimed to explain the high values of the Curie temperatures of certain ferromagnets. Based on this idea Ising formulated a new model for ferromagnetism in solids. Simultaneously the old quantum mechanics was replaced by new concepts of Heisenberg and Schrödinger and the discovery of spin. Thus Schottky’s idea was outperformed and finally replaced in 1928 by Heisenberg exchange interaction. This led to a reformulation of Ising’s model by Pauli at the Solvay conference in 1930. Nevertheless one might consider Schottky’s idea as a forerunner of this development explaining and asserting that the main point is the Coulomb energy leading to the essential interaction of neighboring elementary magnets.
Group analysis, invariance results, exact solutions and conservation laws of the perturbed fractional Boussinesq equation
Authors: Lashkarian Elham , Motamednezhad Ahmad , Hejazi S. Reza 
Published: September 2022

The scope of this work is based on symmetry analysis of perturbed fractional Boussinesq equation. For beginning the group formalism, invariance properties and conservation laws of the nonlinear perturbed fractional Boussinesq equation have been explored generally. This method was first described by Lukashchuk [Commun. Nonlinear Sci. Numer. Simul. 68 (2019) 147–159]. The key subject is that when the order of fractional derivative in a fractional differential equation (FDE) is nearly integers, we can approximate it to a perturbed integer-order differential equation with a small perturbation parameter. For obtaining the results, perturbed and unperturbed symmetries are computed. Then, the methodology of reduction is applied for finding some new solutions by the symmetry operators of the equation. These solutions are obtained by the similarity transformations of the symmetries. Another exact solution will be found with constructing one-dimensional optimal system of the symmetries. Finally, the meaning of nonlinear self-adjointness concept is attended in order to find conservation laws with informal Lagrangians.
Genomic Characteristics and Single-Cell Profiles After Immunotherapy in Fumarate Hydratase-Deficient Renal Cell Carcinoma
Authors: Dong Pei , Zhang Xinyue , Peng Yulu , Zhang Yijun , Liu Ruiqi , Li Yilin , Pan Qiwen , Wei Wensu , Guo Shengjie , Zhang Zhiling , Han Hui , Zhou Fangjian , Liu Yang , He Liru 
Published: September 2022

Abstract

Purpose:
Fumarate hydratase–deficient renal cell carcinoma (FHRCC) is highly malignant, but the urgent need for effective treatment remains unmet. We aimed to analyze the genomic characteristics and microenvironment of FHRCC and the cause of heterogeneous response to immune checkpoint inhibitor (ICI)-based treatment at single-cell level.

Experimental Design:
Whole-exome sequencing and IHC staining analyses were performed in 30 advanced FHRCC patients. Single-cell RNA sequencing following ICI-based treatment was conducted in 4 patients. The clinical characteristics, therapeutic effect, and follow-up data were analyzed.

Results:
The median tumor mutation burden was only 0.14 mutations per megabase. IHC staining showed an immune-active tumor microenvironment characterized by extensive CD8+ T-cell infiltration. ATM expression was inversely correlated with percentage of tumor-infiltrating CD8+ T cells. Trajectory analysis indicated gradually upregulated exhausted markers and an increased apoptotic trend of CD8+ T cells despite continuous exposure to ICI-based treatment. ICI-based treatment was associated with improved overall response rate (17.6% vs. 0%, P = 0.046) and disease control rate (DCR; 64.7% vs. 12.5%, P = 0.004) compared with tyrosine kinase inhibitor. Among patients with germline mutation, the ORR (16.7% vs. 0%, P = 0.086) and the DCR (66.7% vs. 14.3%, P = 0.011) were higher after ICI-based treatment.

Conclusions:
Immune infiltration is frequent in FHRCC. ICI-based treatment is a promising regimen, and treatment response depends on the functional status of tumor-infiltrating lymphocytes. ICI-based treatment cannot reverse the exhaustion of CD8+ T cells in patients with progressive disease, highlighting the need for additional therapeutic strategies.
Ewing Sarcoma and Osteosarcoma Have Distinct Immune Signatures and Intercellular Communication Networks
Authors: Cillo Anthony R. , Mukherjee Elina , Bailey Nathanael G. , Onkar Sayali , Daley Jessica , Salgado Claudia , Li Xiang , Liu Dongyan , Ranganathan Sarangarajan , Burgess Melissa , Sembrat John , Weiss Kurt , Watters Rebecca , Bruno Tullia C. , Vignali Dario A.A. , Bailey Kelly M. 
Published: September 2022

Abstract

Purpose:
Ewing sarcoma and osteosarcoma are primary bone sarcomas occurring most commonly in adolescents. Metastatic and relapsed disease are associated with dismal prognosis. Although effective for some soft tissue sarcomas, current immunotherapeutic approaches for the treatment of bone sarcomas have been largely ineffective, necessitating a deeper understanding of bone sarcoma immunobiology.

Experimental Design:
Multiplex immunofluorescence analysis of immune infiltration in relapsed versus primary disease was conducted. To better understand immune states and drivers of immune infiltration, especially during disease progression, we performed single-cell RNA sequencing (scRNAseq) of immune populations from paired blood and bone sarcoma tumor samples.

Results:
Our multiplex immunofluorescence analysis revealed increased immune infiltration in relapsed versus primary disease in both Ewing sarcoma and osteosarcoma. scRNAseq analyses revealed terminally exhausted CD8+ T cells expressing co-inhibitory receptors in osteosarcoma and an effector T-cell subpopulation in Ewing sarcoma. In addition, distinct subsets of CD14+CD16+ macrophages were present in Ewing sarcoma and osteosarcoma. To determine pathways driving tumor immune infiltration, we conducted intercellular communication analyses and uncovered shared mechanisms of immune infiltration driven by CD14+CD16+ macrophages and unique pathways of immune infiltration driven by CXCL10 and CXCL12 in osteosarcoma.

Conclusions:
Our study provides preclinical rationale for future investigation of specific immunotherapeutic targets upon relapse and provides an invaluable resource of immunologic data from bone sarcomas.
The C-terminus of Gain-of-Function Mutant p53 R273H Is Required for Association with PARP1 and Poly-ADP-Ribose
Authors: Lundine Devon , Annor George K. , Chavez Valery , Maimos Styliana , Syed Zafar , Jiang Shuhong , Ellison Viola , Bargonetti Jill 
Published: September 2022

Abstract

The TP53 gene is mutated in 80% of triple-negative breast cancers. Cells that harbor the hot-spot p53 gene mutation R273H produce an oncogenic mutant p53 (mtp53) that enhances cell proliferative and metastatic properties. The enhanced activities of mtp53 are collectively referred to as gain-of-function (GOF), and may include transcription-independent chromatin-based activities shared with wild-type p53 (wtp53) such as association with replicating DNA and DNA replication associated proteins like PARP1. However, how mtp53 upregulates cell proliferation is not well understood. wtp53 interacts with PARP1 using a portion of its C-terminus. The wtp53 oligomerization and far C-terminal domain (CTD) located within the C-terminus constitute putative GOF-associated domains, because mtp53 R273H expressing breast cancer cells lacking both domains manifest slow proliferation phenotypes. We addressed if the C-terminal region of mtp53 R273H is important for chromatin interaction and breast cancer cell proliferation using CRISPR-Cas9 mutated MDA-MB-468 cells endogenously expressing mtp53 R273H C-terminal deleted isoforms (R273HΔ381–388 and R273HΔ347–393). The mtp53 R273HΔ347–393 lacks the CTD and a portion of the oligomerization domain. We observed that cells harboring mtp53 R273HΔ347–393 (compared with mtp53 R273H full-length) manifest a significant reduction in chromatin, PARP1, poly-ADP-ribose (PAR), and replicating DNA binding. These cells also exhibited impaired response to hydroxyurea replicative stress, decreased sensitivity to the PARP-trapping drug combination temozolomide–talazoparib, and increased phosphorylated 53BP1 foci, suggesting reduced Okazaki fragment processing.

Implications:
The C-terminal region of mtp53 confers GOF activity that mediates mtp53–PARP1 and PAR interactions assisting DNA replication, thus implicating new biomarkers for PARP inhibitor therapy.
Anti-spike T-cell and Antibody Responses to SARS-CoV-2 mRNA Vaccines in Patients with Hematologic Malignancies
Authors: Greenberger Lee M. , Saltzman Larry A. , Gruenbaum Lore M. , Xu Jun , Reddy Sneha T. , Senefeld Jonathon W. , Johnson Patrick W. , Fields Paul A. , Sanders Catherine , DeGennaro Louis J. , Nichols Gwen L. 
Published: September 2022

Abstract

The anti-spike T-cell and antibody responses to SARS-CoV-2 mRNA vaccines in patients with B-cell malignancies were examined in a real-world setting. A next-generation sequencing (NGS)–based molecular assay was used to assess SARS-CoV-2–specific T-cell responses. After the second dose, 58% (166/284) of seropositive and 45% (99/221) of seronegative patients display anti-spike T cells. The percentage of patients who displayed T-cell response was higher among patients receiving mRNA-1273 vaccines compared with those receiving BNT162b2 vaccines. After the third vaccination, 40% (137/342) of patients seroconverted, although only 22% displayed sufficient antibody levels associated with the production of neutralizing antibodies. 97% (717/738) of patients who were seropositive before the third dose had markedly elevated anti-spike antibody levels. Anti-spike antibody levels, but not T-cell responses, were depressed by B cell–directed therapies. Vaccinated patients with B-cell malignancies with a poor response to SARS-CoV-2 vaccines may remain vulnerable to COVID-19 infections.

Significance:
This study represents the first investigation of SARS-CoV-2–specific immune responses to vaccination in a patient registry using an NGS-based method for T-cell receptor repertoire–based analysis combined with anti-spike antibody assessments. Vaccinated patients with B cell–derived hematologic malignancies are likely at higher risk of infection or severe COVID-19.
This article is highlighted in the In This Issue feature, p. 476
Urban Spatial Accessibility of Primary Care and Hypertension Control and Awareness on Chicago’s South Side: A Study From the COMPASS Cohort
Authors: Luo Jiajun , Kibriya Muhammad G. , Zakin Paul , Craver Andrew , Connellan Liz , Tasmin Saira , Polonsky Tamar , Kim Karen , Ahsan Habibul , Aschebrook-Kilfoy Briseis 
Published: September 2022

Background:
Understanding the relationship between hypertension and spatial accessibility of primary care can inform interventions to improve hypertension control and awareness, especially among disadvantaged populations. This study aims to investigate the association between spatial accessibility of primary care and hypertension control and awareness.

Methods:
Participant data from the COMPASS (Chicago Multiethnic Prevention and Surveillance Study) between 2013 and 2019 were analyzed. All participants were geocoded. Locations of primary care providers in Chicago were obtained from MAPSCorps. A score was generated for spatial accessibility of primary care using an enhanced 2-step floating catchment area method. A higher score indicates greater accessibility. Measured hypertension was defined as systolic blood pressure ≥130 mm Hg or diastolic blood pressure ≥80 mm Hg. Logistic regression was used to estimate odds ratio and 95% CI for hypertension status in relation to accessibility score quartiles.

Results:

Five thousand ninety-six participants (mean age, 53.4±10.8) were included. The study population was predominantly non-Hispanic black (84.0%), over 53% reported an annual household income <$15 000, and 37.3% were obese. Measured hypertension prevalence was 78.7% in this population, among which 37.7% were uncontrolled and 41.0% were unaware. A higher accessibility score was associated with lower measured hypertension prevalence. In fully adjusted models, compared with the first (lowest) quartile of accessibility score, the odds ratio strengthened from 0.82 (95% CI, 0.67–1.01) for the second quartile to 0.75 (95% CI, 0.62–0.91) for the third quartile, and further to 0.73 (95% CI, 0.60–0.89) for the fourth (highest) quartile. The increasing trend had a
P
<0.01. Similar associations were observed for both uncontrolled and unaware hypertensions. When stratified by neighborhood socioeconomic status, a higher accessibility score was associated with lower rates of unaware hypertension in both disadvantaged and nondisadvantaged neighborhoods.

Conclusions:
Better spatial accessibility of primary care is associated with improved hypertension awareness and control.
Nonadherence by Serum Drug Analyses in Resistant Hypertension: 7‐Year Follow‐Up of Patients Considered Adherent by Directly Observed Therapy
Authors: Halvorsen Lene V. , Bergland Ola U. , Søraas Camilla L. , Larstorp Anne Cecilie K. , Hjørnholm Ulla , Kjær Vibeke N. , Kringen Marianne K. , Clasen Per‐Erik , Haldsrud Renate , Kjeldsen Sverre E. , Rostrup Morten , Fadl Elmula Fadl Elmula M. , Opdal Mimi S. , Høieggen Aud 
Published: September 2022

Background
Measurement of serum concentrations of drugs is a novelty found useful in detecting poor drug adherence in patients taking ≥2 antihypertensive agents. Regarding patients with treatment‐resistant hypertension, we previously based our assessment on directly observed therapy. The present study aimed to investigate whether serum drug measurements in patients with resistant hypertension offer additional information regarding drug adherence, beyond that of initial assessment with directly observed therapy.

Methods and Results

Nineteen patients assumed to have true treatment‐resistant hypertension and adherence to antihypertensive drugs based on directly observed therapy were investigated repeatedly through 7 years. Serum concentrations of antihypertensive drugs were measured by ultra‐high‐performance liquid chromatography–tandem mass spectrometry from blood samples taken at baseline, 6‐month, 3‐year, and 7‐year visits. Cytochrome P450 polymorphisms, self‐reported adherence and beliefs about medicine were performed as supplement investigations. Seven patients (37%) were redefined as nonadherent based on their serum concentrations during follow‐up. All patients reported high adherence to medications. Nonadherent patients expressed lower necessity and higher concerns regarding intake of antihypertensive medication (
P
=0.003). Cytochrome P450 polymorphisms affecting metabolism of antihypertensive drugs were found in 16 patients (84%), 21% were poor metabolizers, and none were ultra‐rapid metabolizers. Six of 7 patients redefined as nonadherent had cytochrome P450 polymorphisms, however, not explaining the low serum drug concentrations measured in these patients.

Conclusions
Our data suggest that repeated measurements of serum concentrations of antihypertensive drugs revealed nonadherence in one‐third of patients previously evaluated as adherent and treatment resistant by directly observed therapy, thereby improving the accuracy of adherence evaluation.

Registration

URL:
https://www.clinicaltrials.gov
; unique identifier: NCT01673516.
Clinical Outcomes of Rhythm Control Strategies for Asymptomatic Atrial Fibrillation According to the Quality‐of‐Life Score: The CODE‐AF (Comparison Study of Drugs for Symptom Control and Complication Prevention of Atrial Fibrillation) Registry
Authors: Kim Ju Youn , Park Hyoung‐Seob , Park Hyung Wook , Choi Eue‐Keun , Park Jin‐Kyu , Kim Jin‐Bae , Kang Ki‐Woon , Shim Jaemin , Joung Boyoung , Park Kyoung‐Min 
Published: September 2022

Background
Atrial fibrillation (AF) is associated with an increased risk of poor cardiovascular outcomes; appropriate rhythm control can reduce the incidence of these adverse events. Therefore, catheter ablation is recommended in symptomatic patients with AF. The aims of this study were to compare AF‐related outcomes according to a baseline symptom scale score and to determine the best treatment strategy for asymptomatic patients with AF.

Methods and Results

This study enrolled all patients who completed a baseline Atrial Fibrillation Effect on Quality‐of‐Life (AFEQT) survey in a prospective observational registry. The patients were divided into 2 groups according to AFEQT score at baseline; scores ≤80 were defined as symptomatic, whereas scores >80 represented asymptomatic patients. The primary outcome was defined as a composite of hospitalization for heart failure, ischemic stroke, or cardiac death. This study included 1515 patients (mean age: 65.7±10.5 years; 998 [65.9%] men). The survival curve showed a poorer outcome in the symptomatic group compared with the asymptomatic group (log‐rank
P
=0.04). Rhythm control led to a significantly lower risk of a composite outcome in asymptomatic patients (hazard ratio [HR], 0.47 [95% CI, 0.27–0.84],
P
=0.01). Rhythm control was associated with more favorable composite outcomes in the asymptomatic group with paroxysmal AF, left atrium diameter ≤50 mm, and CHA
2
DS
2
‐VASc score ≥3.

Conclusions
Symptomatic patients with AF experienced more adverse outcomes compared with asymptomatic patients. In asymptomatic patients with AF, a strategy of rhythm control improved the outcomes, especially with paroxysmal AF, smaller left atrium size, or higher stroke risk.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT02786095.
Effects of Nicorandil Administration on Infarct Size in Patients With ST‐Segment–Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: The CHANGE Trial
Authors: Qian Geng , Zhang Ying , Dong Wei , Jiang Zi‐Chao , Li Tao , Cheng Liu‐Quan , Zou Yu‐Ting , Jiang Xiao‐Si , Zhou Hao , A Xin , Li Ping , Chen Mu‐Lei , Su Xi , Tian Jin‐Wen , Shi Bei , Li Zong‐Zhuang , Wu Yan‐Qing , Li Yong‐Jun , Chen Yun‐Dai 
Published: September 2022

Background
Nicorandil was reported to improve microvascular dysfunction and reduce reperfusion injury when administered before primary percutaneous coronary intervention. In this multicenter, prospective, randomized, double‐blind clinical trial (CHANGE [Effects of Nicorandil Administration on Infarct Size in Patients With ST‐Segment–Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention]), we investigated the effects of nicorandil administration on infarct size in patients with ST‐segment–elevation myocardial infarction treated with primary percutaneous coronary intervention.

Methods and Results

A total of 238 patients with ST‐segment–elevation myocardial infarction were randomized to receive intravenous nicorandil (n=120) or placebo (n=118) before reperfusion. Patients in the nicorandil group received a 6‐mg intravenous bolus of nicorandil followed by continuous infusion at a rate of 6 mg/h. Patients in the placebo group received the same dose of placebo. The predefined primary end point was infarct size on cardiac magnetic resonance (CMR) imaging performed at 5 to 7 days and 6 months after reperfusion. CMR imaging was performed in 201 patients (84%). Infarct size on CMR imaging at 5 to 7 days after reperfusion was significantly smaller in the nicorandil group compared with the placebo (control) group (26.5±17.1 g versus 32.4±19.3 g;
P
=0.022), and the effect remained significant on long‐term CMR imaging at 6 months after reperfusion (19.5±14.4 g versus 25.7±15.4 g;
P
=0.008). The incidence of no‐reflow/slow‐flow phenomenon during primary percutaneous coronary intervention was much lower in the nicorandil group (9.2% [11/120] versus 26.3% [31/118];
P
=0.001), and thus, complete ST‐segment resolution was more frequently observed in the nicorandil group (90.8% [109/120] versus 78.0% [92/118];
P
=0.006). Left ventricular ejection fraction on CMR imaging was significantly higher in the nicorandil group than in the placebo group at both 5 to 7 days (47.0±10.2% versus 43.3±10.0%;
P
=0.011) and 6 months (50.1±9.7% versus 46.4±8.5%;
P
=0.009) after reperfusion.

Conclusions
In the present trial, administration of nicorandil before primary percutaneous coronary intervention led to improved myocardial perfusion grade, increased left ventricular ejection fraction, and reduced myocardial infarct size in patients with ST‐segment–elevation myocardial infarction.

Registration

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT03445728.
Impact of Socioeconomic Status and Residence Distance on Infant Heart Disease Outcomes in Canada
Authors: Olugbuyi Oluwayomi , Smith Christopher , Kaul Padma , Dover Douglas C. , Mackie Andrew S. , Islam Sunjidatul , Eckersley Luke , Hornberger Lisa K. 
Published: September 2022

Background
Socioeconomic status (SES) impacts clinical outcomes associated with severe congenital heart disease (sCHD). We examined the impact of SES and remoteness of residence (RoR) on congenital heart disease (CHD) outcomes in Canada, a jurisdiction with universal health insurance.

Methods and Results

All infants born in Canada (excluding Quebec) from 2008 to 2018 and hospitalized with CHD requiring intervention in the first year were identified. Neighborhood level SES income quintiles were calculated, and RoR was categorized as residing <100 km, 100 to 299 km, or >300 km from the closest of 7 cardiac surgical programs. In‐hospital mortality at <1 year was the primary outcome, adjusted for preterm birth, low birth weight, and extracardiac pathology. Among 7711 infants, 4485 (58
.
2%) had moderate CHD (mCHD) and 3226 (41.8%) had sCHD. Overall mortality rate was 10.5%, with higher rates in sCHD than mCHD (13.3% versus 8.5%, respectively). More CHD infants were in the lowest compared with the highest SES category (27.1% versus 15.0%, respectively). The distribution of CHD across RoR categories was 52.3%, 21.3%, and 26.4% for <100 km, 100 to 299 km, and >300 km, respectively. Although SES and RoR had no impact on sCHD mortality, infants with mCHD living >300 km had a higher risk of mortality relative to those living <100 km (adjusted odds ratio [aOR], 1.43 [95% CI, 1.11–1.84]). Infants with mCHD within the lowest SES quintile and living farthest away had the highest risk for mortality (aOR, 1.74 [95% CI, 1.08–2.81]).

Conclusions
In Canada, neither RoR nor SES had an impact on outcomes of infants with sCHD. Greater RoR, however, may contribute to higher risk of mortality among infants with mCHD.