bluuebunny/crossref_metadata_2025_split huggingface dataset:
SU(3) analysis of fully-light tetraquarks in heavy meson weak decays
Authors: Shi Yu-Ji , Xing Ye , Zhao Zhen-Xing 
Published: February 2021

AbstractWe perform a SU(3) analysis for both semi-leptonic and non-leptonic heavy meson weak decays into a pseudoscalar meson and a fully-light tetraquark in 10 or 27 representation. A reduction of the SU(3) representation tensor for the fully-light tetraquarks is produced and all the flavor components for each representation tensor are listed. The decay channels we analysis include $$B/D \rightarrow U/T~P~l\nu $$

B
/
D
→
U
/
T

P

l
ν

, $$B/D \rightarrow U/T~P $$

B
/
D
→
U
/
T

P

and $$B_c \rightarrow U/T~P/D$$

B
c

→
U
/
T

P
/
D

, with U/T represents a fully-light tetraquark in 10 or 27 representation and P is a pseudoscalar meson. Finally, among these results we list all the golden decay channels which are expected to have more possibilities to be observed in experiments.
SMARCA2 Is a Novel Interactor of NSD2 and Regulates Prometastatic PTP4A3 through Chromatin Remodeling in t(4;14) Multiple Myeloma
Authors: Chong Phyllis S.Y. , Chooi Jing Yuan , Lim Julia S.L. , Toh Sabrina Hui Min , Tan Tuan Zea , Chng Wee-Joo 
Published: February 2021

Abstract

NSD2 is the primary oncogenic driver in t(4;14) multiple myeloma. Using SILAC-based mass spectrometry, we demonstrate a novel role of NSD2 in chromatin remodeling through its interaction with the SWI/SNF ATPase subunit SMARCA2. SMARCA2 was primarily expressed in t(4;14) myeloma cells, and its interaction with NSD2 was noncanonical and independent of the SWI/SNF complex. RNA sequencing identified PTP4A3 as a downstream target of NSD2 and mapped NSD2–SMARCA2 complex on PTP4A3 promoter. This led to a focal increase in the permissive H3K36me2 mark and transcriptional activation of PTP4A3. High levels of PTP4A3 maintained MYC expression and correlated with a 54-gene MYC signature in t(4;14) multiple myeloma. Importantly, this mechanism was druggable by targeting the bromodomain of SMARCA2 using the specific BET inhibitor PFI-3, leading to the displacement of NSD2 from PTP4A3 promoter and inhibiting t(4;14) myeloma cell viability. In vivo, treatment with PFI-3 reduced the growth of t(4;14) xenograft tumors. Together, our study reveals an interplay between histone-modifying enzymes and chromatin remodelers in the regulation of myeloma-specific genes that can be clinically intervened.

Significance:
This study uncovers a novel, SWI/SNF–independent interaction between SMARCA2 and NSD2 that facilitates chromatin remodeling and transcriptional regulation of oncogenes in t(4;14) multiple myeloma, revealing a therapeutic vulnerability targetable by BET inhibition.
Spatial Analysis and Clinical Significance of HLA Class-I and Class-II Subunit Expression in Non–Small Cell Lung Cancer
Authors: Datar Ila J. , Hauc Sacha C. , Desai Shruti , Gianino Nicole , Henick Brian , Liu Yuting , Syrigos Kostas , Rimm David L. , Kavathas Paula , Ferrone Soldano , Schalper Kurt A. 
Published: February 2021

AbstractPurpose:To analyze the distribution, associated immune contexture, and clinical significance of human leukocyte antigen (HLA) class-I and HLA class-II subunits in non–small cell lung cancer (NSCLC).Experimental Design:Using spatially resolved and quantitative multiplexed immunofluorescence we studied the tumor/stromal tissue distribution, cancer cell–specific defects, and clinicopathologic/survival associations of β2 microglobulin (β2M), HLA-A, and HLA-B,-C heavy chains, as well as HLA class-II β chain in &gt;700 immunotherapy-naïve NSCLCs from four independent cohorts. Genomic analysis of HLA genes in NSCLC was performed using two publicly available cohorts.Results:Cancer cell–specific downregulation of HLA markers was identified in 30.4% of cases. β2M was downregulated in 9.8% (70/714), HLA-A in 9% (65/722), HLA-B,-C in 12.1% (87/719), and HLA class-II in 17.7% (127/717) of evaluable samples. Concurrent downregulation of β2M, HLA-B,-C, and HLA class-II was commonly identified. Deleterious mutations in HLA genes were detected in &lt;5% of lung malignancies. Tumors with cancer cell–specific β2M downregulation displayed reduced T cells and increased natural killer (NK)–cell infiltration. Samples with cancer cell HLA-A downregulation displayed modest increase in CD8+ T cells and NK-cell infiltration. Samples with cancer cell–selective HLA-B,-C or HLA class-II downregulation displayed reduced T cells and NK-cell infiltration. There was limited association of the markers with clinicopathologic variables and KRAS/EGFR mutations. Cancer cell–selective downregulation of the HLA subunits was associated with shorter overall survival.Conclusions:Our results reveal frequent and differential defects in HLA class-I and HLA class-II protein subunit expression in immunotherapy-naïve NSCLCs associated with distinct tumor microenvironment composition and patient survival.
Eligibility in Cancer Clinical Research: The Intersection of Discovery, Generalizability, Beneficence, and Justice
Authors: Giantonio Bruce J. 
Published: February 2021

Abstract
Eligibility criteria in clinical trials limit the study population for safety and scientific purposes. The American Society of Clinical Oncology and The Friends of Cancer Research collaboration reconsidered common eligibility criteria in cancer trials and found many to be unnecessarily restrictive. The current recommendations further their efforts to facilitate accrual and improve the generalizability of research results to practice.
See related articles, p. 2394, 2400, 2408, 2416, 2424, and 2430
Modified Hypoxia-Inducible Factor Expression in CD8+ T Cells Increases Antitumor Efficacy
Authors: Veliça Pedro , Cunha Pedro P. , Vojnovic Nikola , Foskolou Iosifina Petrina , Bargiela David , Gojkovic Milos , Rundqvist Helene , Johnson Randall S. 
Published: February 2021

Abstract
Adoptive transfer of antitumor cytotoxic T cells is an emerging form of cancer immunotherapy. A key challenge to expanding the utility of adoptive cell therapies is how to enhance the survival and function of the transferred T cells. Immune-cell survival requires adaptation to different microenvironments and particularly to the hypoxic milieu of solid tumors. The hypoxia-inducible factor (HIF) transcription factors are an essential aspect of this adaptation. In this study, we undertook experiments to define structural determinants of HIF that potentiate antitumor efficacy in cytotoxic T cells. We first created retroviral vectors to deliver ectopic expression of HIF1α and HIF2α in mouse CD8+ T cells, together or individually and with or without sensitivity to the oxygen-dependent HIFα inhibitors Von Hippel–Lindau and factor-inhibiting HIF (FIH). HIF2α, but not HIF1α, drove broad transcriptional changes in CD8+ T cells, resulting in increased cytotoxic differentiation and cytolytic function against tumor targets. A specific mutation replacing the hydroxyl group–acceptor site for FIH in HIF2α gave rise to the most effective antitumor T cells after adoptive transfer in vivo. In addition, codelivering an FIH-insensitive form of HIF2α with an anti-CD19 chimeric antigen receptor greatly enhanced cytolytic function of human CD8+ T cells against lymphoma cells both in vitro and in a xenograft adoptive transfer model. These experiments point to a means to increase the antitumor efficacy of therapeutic CD8+ T cells via ectopic expression of the HIF transcription factor.
See related Spotlight on p. 364
Ceramide Scores Predict Cardiovascular Risk in the Community
Authors: Vasile Vlad C. , Meeusen Jeffrey W. , Medina Inojosa Jose R. , Donato Leslie J. , Scott Christopher G. , Hyun Meredith S. , Vinciguerra Manlio , Rodeheffer Richard R. , Lopez-Jimenez Francisco , Jaffe Allan S. 
Published: February 2021

Objective:
Cardiovascular disease remains a leading cause of mortality worldwide. Ceramide scores have been associated with adverse outcomes in patients with established coronary artery disease. The prognostic value of ceramide score has not been assessed in the general population. We tested the hypothesis that ceramide scores are associated with major adverse cardiac events (MACE) in a community-based cohort with average coronary artery disease burden at enrollment.

Approach and results:
In a prospective community-based cohort, we performed passive follow-up using a record linkage system to ascertain the composite outcome of MACE, defined as acute myocardial infarction, coronary revascularization (bypass grafting or percutaneous intervention), stroke, or death. Ceramides were analyzed as log-transformed continuous variables, ratios or scores, and quartiles with adjustment for confounders. We analyzed 1131 subjects, 52% females, mean age±(SD) 64±9 years. After a median follow-up of 13.3 years (Q1, 12.7; Q3, 14.4), 486 patients experienced a MACE: myocardial infarction (80), coronary artery bypass surgery (34), percutaneous coronary intervention (62), stroke (94), and all-cause death (362). Ceramide ratios were significantly associated with MACE independently of LDL-c (low-density lipoprotein cholesterol) and conventional coronary artery disease risk factors. Those in the highest quartile of ceramide score had nearly 1.5-fold risk of MACE, hazard ratio, 1.47 (95% CI, 1.12–1.92). There was a dose-response association across quartiles of ceramide ratios and MACE.

Conclusions:
Elevated ceramide score is a robust predictor of cardiovascular disease and MACE in the community. The risk conferred by the ceramide score has a dose-response behavior and is independent of conventional risk factors.
Platelet Quiescence in Patients With Acute Coronary Syndrome Undergoing Coronary Artery Bypass Graft Surgery
Authors: Sarathy Kiran , Wells George A. , Singh Kuljit , Couture Etienne , Chong Aun Yeong , Rubens Fraser , Lordkipanidzé Marie , Tanguay Jean‐François , So Derek 
Published: February 2021

Background
The optimal antiplatelet strategy for patients with acute coronary syndromes who require coronary artery bypass surgery remains unclear. While a more potent antiplatelet regimen will predispose to perioperative bleeding, it is hypothesized that through “platelet quiescence,” ischemic protection conferred by such therapy may provide a net clinical benefit.

Methods and Results

We compared patients undergoing coronary artery bypass surgery who were treated with a more potent antiplatelet inhibition strategy with those with a less potent inhibition through a meta‐analysis. The primary outcome was all‐cause mortality after bypass surgery. The analysis identified 4 studies in which the antiplatelet regimen was randomized and 6 studies that were nonrandomized. Combining all studies, there was an overall higher mortality with weaker strategies compared with more potent strategies (odds ratio, 1.38; 95% CI, 1.03–1.85;
P
=0.03).

Conclusions
Our findings support the concept of platelet quiescence, in reducing mortality for patients with acute coronary syndrome requiring coronary artery bypass surgery. This suggests the routine up‐front use of potent antiplatelet regimens in acute coronary syndrome, irrespective of likelihood of coronary artery bypass graft.
Impact of Medical Castration on Malignant Arrhythmias in Patients With Prostate Cancer
Authors: Hasegawa Kanae , Ito Hideaki , Kaseno Kenichi , Miyazaki Shinsuke , Shiomi Yuichiro , Tama Naoto , Ikeda Hiroyuki , Ishida Kentaro , Uzui Hiroyasu , Ohno Seiko , Horie Minoru , Yokoyama Osamu , Tada Hiroshi 
Published: February 2021

Background
Medical castration, gonadotropin‐releasing hormone agonists, and antiandrogens have been widely applied as a treatment for prostate cancer. Sex steroid hormones influence cardiac ion channels. However, few studies have examined the proarrhythmic properties of medical castration.

Methods and Results

This study included 149 patients who underwent medical castration using gonadotropin‐releasing hormones with/without antiandrogen for prostate cancer. The changes in the ECG findings during the therapy and associations of the electrocardiographic findings with malignant arrhythmias were studied. The QT and corrected QT (QTc) intervals prolonged during the therapy compared with baseline (QT, 394±32 to 406±39 ms [
P
<0.001]; QTc, 416±27 to 439±31 ms [
P
<0.001]). The QTc interval was prolonged in 119 (79.9%) patients during the therapy compared with baseline. In 2 (1.3%) patients who had no structural heart disease, torsade de pointes (TdP) and ventricular fibrillation (VF) occurred ≥6 months after starting the therapy. In patients with TdP/VF, the increase in the QTc interval from the pretreatment value was >80 ms. However, in patients without TdP/VF, the prevalence of an increase in the QTc interval from the pretreatment value of >50 ms was 11%, and an increase in the QTc interval from the pretreatment value >80 ms was found in only 4 (3%) patients.

Conclusions
Medical castration prolongs the QT/QTc intervals in most patients with prostate cancer, and it could cause TdP/VFs even in patients with no risk of QT prolongation before the therapy. An increase in the QTc interval from the pretreatment value >50 ms might become a predictor of TdP/VF. Much attention should be paid to the QTc interval throughout all periods of medical castration to prevent malignant arrhythmias.
Heart Failure, Atrioventricular Block, and Ventricular Tachycardia in Sarcoidosis
Authors: Rosenthal David G. , Fang Christina D. , Groh Christopher A. , Nah Gregory , Vittinghoff Eric , Dewland Thomas A. , Vedantham Vasanth , Marcus Gregory M. 
Published: February 2021

Background
Sarcoidosis is a granulomatous disease usually affecting the lungs, although cardiac morbidity may be common. The risk of these outcomes and the characteristics that predict them remain largely unknown. This study investigates the epidemiology of heart failure, atrioventricular block, and ventricular tachycardia among patients with and without sarcoidosis.

Methods and Results
We identified California residents aged ≥21 years using the Office of Statewide Health Planning and Development ambulatory surgery, emergency, or inpatient databases from 2005 to 2015. The risk of sarcoidosis on incident heart failure, atrioventricular block, and ventricular tachycardia were each determined. Linkage to the Social Security Death Index was used to ascertain overall mortality. Among 22 527 964 California residents, 19 762 patients with sarcoidosis (0.09%) were identified. Sarcoidosis was the strongest predictor of heart failure (hazard ratio [HR], 11.2; 95% CI, 10.7–11.7), atrioventricular block (HR, 117.7; 95% CI, 103.3–134.0), and ventricular tachycardia (HR, 26.1; 95% CI, 24.2–28.1) identified among all risk factors. The presence of any cardiac involvement best predicted each outcome. Approximately 22% (95% CI, 18%–26%) of the relationship between sarcoidosis and increased mortality was explained by the presence of at least 1 of these cardiovascular outcomes.

Conclusions
The magnitude of risk associated with sarcoidosis as a predictor of heart failure, atrioventricular block, and ventricular tachycardia, exceeds all established risk factors. Surveillance for and anticipation of these outcomes among patients with sarcoidosis is indicated, and consideration of a sarcoidosis diagnosis may be prudent among patients with heart failure, atrioventricular block, or ventricular tachycardia.
Outcomes of Surgical Mitral and Aortic Valve Replacements Among Kidney Transplant Candidates: Implications for Valve Selection
Authors: Ngendahimana David K. , Deo Salil V. , Sundaram Varun , Lentine Krista L. , Herzog Charles A. , Al Dahabreh Laith , Srinivas Titte R. , Chavin Kenneth D. , Sarabu Nagaraju 
Published: February 2021

Background
Limited literature exists that evaluated outcomes of kidney transplant–eligible patients who are having dialysis and who are undergoing valve replacement. Our main objective in this study was to compare mortality, reoperation, and bleeding episodes between bioprosthetic and mechanical valve procedures among kidney transplant–eligible patients who are having dialysis.

Methods and Results
We studied 887 and 1925 dialysis patients from the United States Renal Data System, who underwent mitral valve replacement and aortic valve replacement (AVR) after being waitlisted for a kidney transplant (2000–2015), respectively. Time to death, time to reoperation, and time to bleeding requiring hospitalizations were compared separately for AVR and mitral valve replacement. Kaplan–Meier survival curves, Cox proportional hazards model for time to death, accelerated time to event model for time to reoperation, and counting process model for time to recurrent bleeding were used. There were no differences in mortality (hazard ratio [HR], 0.92; 95% CI, 0.77–1.09) or risk of reoperation or risk of significant bleeding events between bioprosthetic and mechanical mitral valve replacement. However, mechanical AVR was associated with a modestly significant less hazard of death (HR, 0.83; 95% CI, 0.74–0.94) compared with bioprosthetic AVR. There were no differences in time to reoperation, or time to significant bleeding events between bioprosthetic and mechanical AVR.

Conclusions
For kidney transplant waitlisted patients who are on dialysis and who are undergoing surgical valve replacement, bioprosthetic and mechanical valves have comparable survival, reoperation rates, and bleeding episodes requiring hospitalizations at both mitral and aortic locations. These findings emphasize that an individualized informed decision is recommended when choosing the type of valve for this special group of patients having dialysis.
Kallikrein‐1 Blockade Inhibits Aortic Expansion in a Mouse Model and Reduces Prostaglandin E2 Secretion From Human Aortic Aneurysm Explants
Authors: Moran Corey S. , Biros Erik , Krishna Smriti M. , Morton Susan K. , Sexton Daniel J. , Golledge Jonathan 
Published: February 2021

Background

Abdominal aortic aneurysm (AAA) is an important cause of mortality in older adults. The kinin B2 receptor agonist, bradykinin, has been implicated in AAA pathogenesis through promoting inflammation. Bradykinin is generated from high‐ and low‐molecular‐weight kininogen by the serine protease kallikrein‐1. The aims of this study were first to examine the effect of neutralizing kallikrein‐1 on AAA development in a mouse model and second to test how blocking kallikrein‐1 affected cyclooxygenase‐2 and prostaglandin E
2
in human AAA explants.

Methods and Results

Neutralization of kallikrein‐1 in apolipoprotein E‐deficient (

ApoE
−/−

) mice via administration of a blocking antibody inhibited suprarenal aorta expansion in response to angiotensin (Ang) II infusion. Kallikrein‐1 neutralization decreased suprarenal aorta concentrations of bradykinin and prostaglandin E
2
and reduced cyclooxygenase‐2 activity. Kallikrein‐1 neutralization also decreased protein kinase B and extracellular signal‐regulated kinase 1/2 phosphorylation and reduced levels of active matrix metalloproteinase 2 and matrix metalloproteinase 9. Kallikrein‐1 blocking antibody reduced levels of cyclooxygenase‐2 and secretion of prostaglandin E
2
and active matrix metalloproteinase 2 and matrix metalloproteinase 9 from human AAA explants and vascular smooth muscle cells exposed to activated neutrophils.

Conclusions
These findings suggest that kallikrein‐1 neutralization could be a treatment target for AAA.
Comparative Effectiveness and Safety of Non–Vitamin K Antagonist Oral Anticoagulants in Atrial Fibrillation Patients
Authors: Zhu Wengen , Ye Zi , Chen Shilan , Wu Dexi , He Jiangui , Dong Yugang , Lip Gregory Y.H. , Liu Chen 
Published: February 2021

Background and Purpose:
Several observational studies have compared the effect of the non–vitamin K antagonist oral anticoagulants to each other in patients with atrial fibrillation. However, confounding by indication is a major problem when comparing non–vitamin K antagonist oral anticoagulant treatments in some of these studies. This meta-analysis was conducted to compare the effectiveness and safety between non–vitamin K antagonist oral anticoagulant and non–vitamin K antagonist oral anticoagulant by only including the propensity score matching studies.

Methods:
We systematically searched the PubMed and Ovid databases until May 2020 to identify relevant observational studies. Hazard ratios (HRs) and 95% CIs of the reported outcomes were collected and then pooled by a random-effects model complemented with an inverse variance heterogeneity or quality effects model.

Results:
A total of 17 retrospective cohort studies were included in this meta-analysis. Compared with dabigatran use, the use of rivaroxaban was significantly associated with increased risks of stroke or systemic embolism (HR, 1.16 [95% CI, 1.05–1.29]) and major bleeding (HR, 1.32 [95% CI, 1.24–1.41]), whereas the use of apixaban was associated with a reduced risk of major bleeding (HR, 0.78 [95% CI, 0.67–0.90]) but not stroke or systemic embolism (HR, 0.84 [95% CI, 0.56–1.28]). Compared with rivaroxaban use, the use of apixaban was associated with a decreased risk of major bleeding (HR, 0.63 [95% CI, 0.54–0.73]) but not stroke or systemic embolism (HR, 0.83 [95% CI, 0.67–1.04]). Reanalyses with the inverse variance heterogeneity or quality effects model produced similar results as the random-effects model.

Conclusions:
Current observational comparisons with propensity score matching methods suggest that apixaban might be a better choice compared with dabigatran or rivaroxaban for stroke prevention in atrial fibrillation patients.
Trends in Incidence of Intracranial and Spinal Arteriovenous Shunts
Authors: Murai Satoshi , Hiramatsu Masafumi , Suzuki Etsuji , Ishibashi Ryota , Takai Hiroki , Miyazaki Yuko , Takasugi Yuji , Yamaoka Yoko , Nishi Kazuhiko , Takahashi Yu , Haruma Jun , Hishikawa Tomohito , Yasuhara Takao , Chin Masaki , Matsubara Shunji , Uno Masaaki , Tokunaga Koji , Sugiu Kenji , Date Isao ,   on behalf of the Okayama Cranial and Spinal A-V Shunts (OCSS) Study Group
Published: February 2021

Background and Purpose:
To date, the incidence of intracranial and spinal arteriovenous shunts has not been thoroughly investigated. We aimed to clarify recent trends in the rates of intracranial and spinal arteriovenous shunts in Japan.

Methods:
We conducted multicenter hospital-based surveillance at 8 core hospitals in Okayama Prefecture between April 1, 2009 and March 31, 2019. Patients who lived in Okayama and were diagnosed with cerebral arteriovenous malformations, dural arteriovenous fistulas (DAVFs), or spinal arteriovenous shunts (SAVSs) were enrolled. The incidence and temporal trends of each disease were calculated.

Results:
Among a total of 393 cranial and spinal arteriovenous shunts, 201 (51.1%) cases of DAVF, 155 (39.4%) cases of cerebral arteriovenous malformation, and 34 (8.7%) cases of SAVS were identified. The crude incidence rates between 2009 and 2019 were 2.040 per 100 000 person-years for all arteriovenous shunts, 0.805 for cerebral arteriovenous malformation, 1.044 for DAVF, and 0.177 for SAVS. The incidence of all types tended to increase over the decade, with a notable increase in incidence starting in 2012. Even after adjusting for population aging, the incidence of nonaggressive DAVF increased 6.0-fold while that of SAVS increased 4.4-fold from 2010 to 2018.

Conclusions:
In contrast to previous studies, we found that the incidence of DAVF is higher than that of cerebral arteriovenous malformation. Even after adjusting for population aging, all of the disease types tended to increase in incidence over the last decade, with an especially prominent increase in SAVSs and nonaggressive DAVFs. Various factors including population aging may affect an increase in DAVF and SAVS.