bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Interplay between Slow-Cycling, Chemoresistant Cancer Cells and Fibroblasts Creates a Proinflammatory Niche for Tumor Progression
Authors: Cho Jaebeom , Lee Hyo-Jong , Hwang Su Jung , Min Hye-Young , Kang Han Na , Park A-Young , Hyun Seung Yeob , Sim Jeong Yeon , Lee Ho Jin , Jang Hyun-Ji , Suh Young-Ah , Hong Sungyoul , Shin Young Kee , Kim Hye Ryun , Lee Ho-Young 
Published: March 2020

AbstractQuiescent cancer cells are believed to cause cancer progression after chemotherapy through unknown mechanisms. We show here that human non–small cell lung cancer (NSCLC) cell line-derived, quiescent-like, slow-cycling cancer cells (SCC) and residual patient-derived xenograft (PDX) tumors after chemotherapy experience activating transcription factor 6 (ATF6)-mediated upregulation of various cytokines, which acts in a paracrine manner to recruit fibroblasts. Cancer-associated fibroblasts (CAF) underwent transcriptional upregulation of COX2 and type I collagen (Col-I), which subsequently triggered a slow-to-active cycling switch in SCC through prostaglandin E2 (PGE2)- and integrin/Src-mediated signaling pathways, leading to cancer progression. Both antagonism of ATF6 and cotargeting of Src/COX2 effectively suppressed cytokine production and slow-to-active cell cycling transition in SCC, withholding cancer progression. Expression of COX2 and Col-I and activation of Src were observed in patients with NSCLC who progressed while receiving chemotherapy. Public data analysis revealed significant association between COL1A1 and SRC expression and NSCLC relapse. Overall, these findings indicate that a proinflammatory niche created by the interplay between SCC and CAF triggers tumor progression.Significance:Cotargeting COX2 and Src may be an effective strategy to prevent cancer progression after chemotherapy.
A Feedback Loop Comprising EGF/TGFα Sustains TFCP2-Mediated Breast Cancer Progression
Authors: Zhao Yi , Kaushik Neha , Kang Jae-Hyeok , Kaushik Nagendra Kumar , Son Seung Han , Uddin Nizam , Kim Min-Jung , Kim Chul Geun , Lee Su-Jae 
Published: March 2020

Abstract

Stemness and epithelial–mesenchymal transition (EMT) are two fundamental characteristics of metastasis that are controlled by diverse regulatory factors, including transcription factors. Compared with other subtypes of breast cancer, basal-type or triple-negative breast cancer (TNBC) has high frequencies of tumor relapse. However, the role of alpha-globin transcription factor CP2 (TFCP2) has not been reported as an oncogenic driver in those breast cancers. Here, we show that TFCP2 is a potent factor essential for EMT, stemness, and metastasis in breast cancer. TFCP2 directly bound promoters of EGF and TGFα to regulate their expression and stimulate autocrine signaling via EGFR. These findings indicate that TFCP2 is a new antimetastatic target and reveal a novel regulatory mechanism in which a positive feedback loop comprising EGF/TGFα and AKT can control malignant breast cancer progression.

Significance:
TFCP2 is a new antimetastatic target that controls TNBC progression via a positive feedback loop between EGF/TGFα and the AKT signaling axis.
T-Cell Infiltration and Adaptive Treg Resistance in Response to Androgen Deprivation With or Without Vaccination in Localized Prostate Cancer
Authors: Obradovic Aleksandar Z. , Dallos Matthew C. , Zahurak Marianna L. , Partin Alan W. , Schaeffer Edward M. , Ross Ashley E. , Allaf Mohamad E. , Nirschl Thomas R. , Liu David , Chapman Carolyn G. , O'Neal Tanya , Cao Haiyi , Durham Jennifer N. , Guner Gunes , Baena-Del Valle Javier A. , Ertunc Onur , De Marzo Angelo M. , Antonarakis Emmanuel S. , Drake Charles G. 
Published: March 2020

Abstract

Purpose:
Previous studies suggest that androgen deprivation therapy (ADT) promotes antitumor immunity in prostate cancer. Whether a vaccine-based approach can augment this effect remains unknown.

Patients and Methods:
We conducted a neoadjuvant, randomized study to quantify the immunologic effects of a GM-CSF–secreting allogeneic cellular vaccine in combination with low-dose cyclophosphamide (Cy/GVAX) followed by degarelix versus degarelix alone in patients with high-risk localized prostate adenocarcinoma who were planned for radical prostatectomy.

Results:
Both Cy/GVAX plus degarelix and degarelix alone led to significant increases in intratumoral CD8+ T-cell infiltration and PD-L1 expression as compared with a cohort of untreated, matched controls. However, the CD8+ T-cell infiltrate was accompanied by a proportional increase in regulatory T cells (Treg), suggesting that adaptive Treg resistance may dampen the immunogenicity of ADT. Although Cy/GVAX followed by degarelix was associated with a modest improvement in time-to-PSA progression and time-to-next treatment, as well as an increase in PD-L1, there was no difference in the CD8+ T-cell infiltrate as compared with degarelix alone. Gene expression profiling demonstrated that CHIT1, a macrophage marker, was differentially upregulated with Cy/GVAX plus degarelix compared with degarelix alone.

Conclusions:
Our results highlight that ADT with or without Cy/GVAX induces a complex immune response within the prostate tumor microenvironment. These data have important implications for combining ADT with immunotherapy. In particular, our finding that ADT increases both CD8+ T cells and Tregs supports the development of regimens combining ADT with Treg-depleting agents in the treatment of prostate cancer.
Trends in Infective Endocarditis Hospitalizations, Characteristics, and Valve Operations in Patients With Opioid Use Disorders in the United States: 2005–2014
Authors: Mori Makoto , Brown Kelly J. , Bin Mahmood Syed Usman , Geirsson Arnar , Mangi Abeel A. 
Published: March 2020

Background
To evaluate changes in patient characteristics and outcomes for infective endocarditis (IE) related to opioid use disorder (OUD), we used the National (Nationwide) Inpatient Sample (NIS) to characterize the trend in hospitalizations for patients with IE with and without OUD and those treated medically and surgically.

Methods and Results

Temporal trends in hospitalization characteristics for patients with IE with and without OUD and those treated medically and surgically were estimated via the NIS data in 2005–2014. Hospitalizations for OUD and IE increased from 119 to 202 and from 12 to 15 cases per 100 000 between 2005 and 2014, respectively. Hospitalizations with OUD among all IE hospitalizations increased from 6.3% in 2005 to 11.6% in 2014. Among all IE hospitalizations, patients being admitted for IE in the setting of OUD were younger compared with the cohort of IE without OUD (aged 37.6±0.21 years versus 60.9±0.16 years). Myocardial infarction, diabetes mellitus, chronic kidney disease, peripheral vascular disease, and heart failure were more common in patients without OUD. The OUD cohort more frequently had liver disease (46.0% versus 10.8%) and immunosuppressed status (4.3% versus 2.1%). Valve operations for IE accounted for 10.2% of all valve operations in 2005, and this increased to 12.7% in 2014. These proportions were similar between OUD (11.4%) and non‐OUD (11.1%) cohorts. Operative mortality was lower in patients with OUD (4.3% versus 9.4%,
P
<0.001).

Conclusions
IE associated with OUD has a distinct phenotype and has become more prevalent. Surgical outcomes are favorable and operations were performed in similar proportions of patients who had IE with OUD compared with patients who had IE without OUD.
Determinants of Sudden Cardiac Death in Adult Patients With Eisenmenger Syndrome
Authors: Chiriac Anca , Riley David C. , Russell Matthew , Moore Jeremy P. , Padmanabhan Deepak , Hodge David O. , Spiegel Matthew R. , Vargas Emily R. , Phillips Sabrina D. , Ammash Naser M. , Madhavan Malini , Asirvatham Samuel J. , McLeod Christopher J. 
Published: March 2020

Background

Patients with Eisenmenger syndrome are known to have a high incidence of sudden cardiac death (
SCD
), yet the underlying causes are not well understood. We sought to define the predictors of
SCD
in this population.

Methods and Results

A retrospective analysis of all patients with Eisenmenger syndrome from 2 large tertiary referral centers was performed. ECGs, prolonged ambulatory recordings, echocardiograms, and clinical histories were reviewed; and the cause of death was identified. A total of 246 patients (85 [34.6%] men) with a mean age of 37.3 (±14.2) years were followed up for a median of 7 years. Over the study period, 136 patients died, with 40 experiencing
SCD
and 74 experiencing cardiac death (sudden and nonsudden). Age, atrial fibrillation, prolonged
QRS
duration, complete heart block, right atrial enlargement, right bundle branch block, increased right atrial pressure, impaired biventricular function, and the presence of a pacemaker were associated with increased risk of
SCD
, whereas advanced pulmonary hypertension therapies were protective. Atrial fibrillation (11.45‐fold increased risk;
P
<0.001) and
QRS
duration ≥120 ms (2.06‐fold increased risk;
P
=0.034) remained significant predictors of
SCD
in the multivariate analysis, whereas advanced pulmonary hypertension therapies were strongly protective against
SCD
(
P
<0.001).

Conclusions

Atrial arrhythmias, impaired ventricular function, and conduction system disease were associated with increased risk of
SCD
in this cohort of patients with Eisenmenger syndrome, providing an opportunity for early risk stratification and potential intervention. Clinical heart failure symptoms (New York Heart Association class ≥
II
) were predictive of increased mortality but not of
SCD
, suggesting a potential arrhythmic cause behind
SCD
.
Associations of Serum Dickkopf‐1 and Sclerostin With Cardiovascular Events: Results From the Prospective Bruneck Study
Authors: Klingenschmid Gerhard , Tschiderer Lena , Himmler Gottfried , Rungger Gregorio , Brugger Stefan , Santer Peter , Willeit Johann , Kiechl Stefan , Willeit Peter 
Published: March 2020

Background

Dickkopf‐1 and sclerostin have been implicated in atherosclerosis and vascular calcification. We aimed to quantify the association of their serum levels with incident cardiovascular disease (
CVD
) in the general population.

Methods and Results

Among 706 participants of the prospective, population‐based Bruneck Study, mean±SD of serum levels were 44.5±14.7 pmol/L for dickkopf‐1 and 47.1±17.5 pmol/L for sclerostin. The primary outcome was a composite
CVD
end point composed of ischemic or hemorrhagic stroke, transient ischemic attack, myocardial infarction, angina pectoris, peripheral vascular disease, and revascularization procedures. Over a median follow‐up duration of 15.6 years, 179
CVD
events occurred. For the primary
CVD
outcome, multivariable‐adjusted hazard ratios (
HR
s) per SD higher level were 1.20 for dickkopf‐1 (95%
CI
, 1.02–1.42;
P
=0.028) and 0.92 for sclerostin (95%
CI,
0.78–1.08;
P
=0.286). Secondary outcome analyses revealed that the association of dickkopf‐1 was primarily driven by ischemic and hemorrhagic stroke (67 events;
HR,
1.37; 95%
CI,
1.06–1.78;
P
=0.017), whereas no increase in risk was observed for transient ischemic attack (22 events;
HR,
0.87; 95%
CI,
0.53–1.44;
P
=0.593), myocardial infarction (45 events;
HR,
1.10; 95% CI, 0.78–1.54;
P
=0.598), or for other
CVD
(45 events;
HR,
1.25; 95%
CI,
0.88–1.76;
P
=0.209).

Conclusions

In this prospective, population‐based study, elevated baseline levels of dickkopf‐1, but not sclerostin, were independently associated with incident cardiovascular events, which was mainly driven by stroke. Our findings support the hypothesis of a role of dickkopf‐1 in the pathogenesis of
CVD
.
Cumulative Lifetime Burden of Cardiovascular Disease From Early Exposure to Air Pollution
Authors: Kim Juyong Brian , Prunicki Mary , Haddad Francois , Dant Christopher , Sampath Vanitha , Patel Rushali , Smith Eric , Akdis Cezmi , Balmes John , Snyder Michael P. , Wu Joseph C. , Nadeau Kari C. 
Published: March 2020

Abstract
The disease burden associated with air pollution continues to grow. The World Health Organization (WHO) estimates ≈7 million people worldwide die yearly from exposure to polluted air, half of which—3.3 million—are attributable to cardiovascular disease (CVD), greater than from major modifiable CVD risks including smoking, hypertension, hyperlipidemia, and diabetes mellitus. This serious and growing health threat is attributed to increasing urbanization of the world's populations with consequent exposure to polluted air. Especially vulnerable are the elderly, patients with pre‐existing CVD, and children. The cumulative lifetime burden in children is particularly of concern because their rapidly developing cardiopulmonary systems are more susceptible to damage and they spend more time outdoors and therefore inhale more pollutants. World Health Organization estimates that 93% of the world's children aged <15 years—1.8 billion children—breathe air that puts their health and development at risk. Here, we present growing scientific evidence, including from our own group, that chronic exposure to air pollution early in life is directly linked to development of major CVD risks, including obesity, hypertension, and metabolic disorders. In this review, we surveyed the literature for current knowledge of how pollution exposure early in life adversely impacts cardiovascular phenotypes, and lay the foundation for early intervention and other strategies that can help prevent this damage. We also discuss the need for better guidelines and additional research to validate exposure metrics and interventions that will ultimately help healthcare providers reduce the growing burden of CVD from pollution.
Association Between Intensive Care Unit Usage and Long‐Term Medication Adherence, Mortality, and Readmission Among Initially Stable Patients With Non–ST‐Segment–Elevation Myocardial Infarction
Authors: Fanaroff Alexander C. , Chen Anita Y. , van Diepen Sean , Peterson Eric D. , Wang Tracy Y. 
Published: March 2020

Background

Hospitals in the United States vary in their use of intensive care units (
ICU
s) for hemodynamically stable patients with non–
ST
‐segment–elevation myocardial infarction (
NSTEMI
). The association between
ICU
use and long‐term outcomes after
NSTEMI
is unknown.

Methods and Results

Using data from the National Cardiovascular Data Registry linked to Medicare claims, we identified 65 256
NSTEMI
patients aged ≥ 65 years without cardiogenic shock or cardiac arrest on presentation between 2011 and 2014. We compared 1‐year medication non‐adherence, cardiovascular readmission, and mortality across hospitals by
ICU
use using multivariable regression models. Among 520 hospitals, 154 (29.6%) were high
ICU
users (>70% of stable
NSTEMI
patients admitted to
ICU
), 270 (51.9%) were intermediate (30%–70%), and 196 (37.7%) were low (<30%). Compared with low
ICU
usage hospitals, no differences were observed in the risks of 1‐year medication non‐adherence (adjusted odds ratio 1.08, 95%
CI
, 0.97–1.21), mortality (adjusted hazard ratio 1.06, 95%
CI
, 0.98–1.15), and cardiovascular readmission (adjusted hazard ratio 0.99, 95% CI, 0.95–1.04) at high usage hospitals. Patients hospitalized at intermediate
ICU
usage hospitals had lower rates of evidence‐based therapy and diagnostic catheterization within 24 hours of hospital arrival, and higher risks of 1‐year mortality (adjusted hazard ratio 1.07, 95%
CI
, 1.02–1.12) and medication non‐adherence (adjusted odds ratio 1.09, 95%
CI
, 1.02–1.15) compared with low
ICU
usage hospitals.

Conclusions

Routine
ICU
use is unlikely to be beneficial for hemodynamically stable
NSTEMI
patients; medication adherence, long‐term mortality, and cardiovascular readmission did not differ for high
ICU
usage hospitals compared with hospitals with low
ICU
usage rates.
Atrial Fibrillation-Associated Ischemic Stroke Patients With Prior Anticoagulation Have Higher Risk for Recurrent Stroke
Authors: Tanaka Kanta , Koga Masatoshi , Lee Keon-Joo , Kim Beom Joon , Park Eun Lyeong , Lee Juneyoung , Mizoguchi Tadataka , Yoshimura Sohei , Cha Jae-Kwan , Lee Byung-Chul , Nakahara Jin , Suzuki Norihiro , Bae Hee-Joon , Toyoda Kazunori ,   for the CRCS-K Investigators and the SAMURAI Study Investigators
Published: March 2020

Background and Purpose—
Ischemic stroke associated with nonvalvular atrial fibrillation (NVAF) despite prior anticoagulation may indicate underlying problems that nullify the stroke-preventing effects of oral anticoagulants. We aimed to evaluate the risk for recurrent stroke in patients with NVAF with prior anticoagulation, compared with that in patients without prior anticoagulation.

Methods—
This study comprised pooled individual patient data on NVAF-associated acute ischemic stroke or transient ischemic attack from 2011 to 2014 arising from the Clinical Research Collaboration for Stroke in Korea (15 South Korean stroke centers) and the Stroke Acute Management With Urgent Risk-Factor Assessment and Improvement-NVAF registry (18 Japanese stroke centers). Data on 4841 eligible patients from the Clinical Research Collaboration for Stroke in Korea registry were pooled with data on all patients (n=1192) in the Stroke Acute Management with Urgent Risk-factor Assessment and Improvement-NVAF registry. The primary outcome was recurrent ischemic stroke. The secondary outcomes were hemorrhagic stroke and all-cause death. Outcome events were captured up to 1 year after the index event.

Results—
Among the 6033 patients in the full cohort, 5645 patients were analyzed, of whom 1129 patients (20.0%) had received prior anticoagulation. Median age was 75 years (interquartile range, 69–81 years), and 2649 patients (46.9%) were women. Follow-up data of 4617 patient-years (median follow-up 365 days, interquartile range 335–365 days) were available. The cumulative incidence of recurrent ischemic stroke in patients with prior anticoagulation was 5.3% (60/1129), compared with the 2.9% (130/4516) incidence in patients without prior anticoagulation. The risk for recurrent ischemic stroke was higher in patients with prior anticoagulation than in those without (multivariable Cox shared-frailty model, hazard ratio 1.50 [95% CI, 1.02–2.21]). No significant differences in the risks for hemorrhagic stroke and mortality were seen between the 2 groups.

Conclusions—
The risk for recurrent ischemic stroke may be higher in NVAF-associated stroke patients with prior anticoagulation than in those without prior anticoagulation.

Registration—

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01581502.
The Discriminative Kalman Filter for Bayesian Filtering with Nonlinear and Nongaussian Observation Models
Authors: Burkhart Michael C. , Brandman David M. , Franco Brian , Hochberg Leigh R. , Harrison Matthew T. 
Published: March 2020

AbstractThe Kalman filter provides a simple and efficient algorithm to compute the posterior distribution for state-space models where both the latent state and measurement models are linear and gaussian. Extensions to the Kalman filter, including the extended and unscented Kalman filters, incorporate linearizations for models where the observation model p(observation|state) is nonlinear. We argue that in many cases, a model for p(state|observation) proves both easier to learn and more accurate for latent state estimation.Approximating p(state|observation) as gaussian leads to a new filtering algorithm, the discriminative Kalman filter (DKF), which can perform well even when p(observation|state) is highly nonlinear and/or nongaussian. The approximation, motivated by the Bernstein–von Mises theorem, improves as the dimensionality of the observations increases. The DKF has computational complexity similar to the Kalman filter, allowing it in some cases to perform much faster than particle filters with similar precision, while better accounting for nonlinear and nongaussian observation models than Kalman-based extensions.When the observation model must be learned from training data prior to filtering, off-the-shelf nonlinear and nonparametric regression techniques can provide a gaussian model for p(observation|state) that cleanly integrates with the DKF. As part of the BrainGate2 clinical trial, we successfully implemented gaussian process regression with the DKF framework in a brain-computer interface to provide real-time, closed-loop cursor control to a person with a complete spinal cord injury. In this letter, we explore the theory underlying the DKF, exhibit some illustrative examples, and outline potential extensions.
A new species of Ogyrides (Decapoda, Caridea, Ogyrididae) from Kuwait
Authors: De Grave Sammy , Al-Kandari Manal , Anker Arthur 
Published: March 2020

Abstract
A new species of telescope shrimp, Ogyrides sindibadi sp. nov. is described from Kuwait. The new species is morphologically similar to O. striaticauda Kemp, 1915, originally described from Chilka Lake (India), but can be distinguished by the shape of the scaphocerite, the much longer dactylus of the third pereiopod, as well as the shape of the distal margin of the telson.
A Great Little Man: The Shadow of Jair Bolsonaro
Authors: Webber Jeffery R. 
Published: March 2020

Abstract
This editorial perspective attempts to explain the recent rise of Jair Bolsonaro to the presidency in Brazil and to characterise, at least in a preliminary fashion, the nature of the new regime one year into Bolsonaro’s rule. The core argument is that Bolsonaro represents a weak and internally-fragmented far-right regime, with unenthusiastic and declining popular support. Dominant sections of international and domestic capital operating in Brazil lent Bolsonaro electoral backing as a last way out of economic and political crisis, but so far, the new government has failed in sufficiently guaranteeing their most important interests and the markets are withdrawing approval. Themes covered include the political paralysis of the new regime, the social bases of Bolsonarismo, the nature of the current state–capital relation, and the role of evangelical Pentecostalism in far-right Brazilian politics today. A biographical portrait of Bolsonaro is provided, alongside a mapping of the dominant factions of the new administration. Finally, an assessment of the economic outlook in Brazil is developed, together with speculation as to the likely political consequences in the short- to medium-term future.
On the Prehistory of Cretan Icon Painting
Authors: Bacci Michele 
Published: March 2020

Abstract
The present paper offers some thoughts on the complex issue of Italianate elements in Cretan icon painting by emphasizing the extent to which they can be considered to stem from motifs worked out in the mid-to-late fourteenth century in the wider, fluid space between Venice and the Eastern Mediterranean. It focuses on a cluster of Marian panels that, on account of their mixed Byzantine and Western character, have been hitherto confined to the margins of art-historical research and improperly labeled as works of a so-called “Adriatic” school. The critical reassessment of these works illuminates the ways in which innovative compositional, iconographic, and stylistic solutions were developed by masters well acquainted with both Palaiologan and Venetian art, and reproduced in a chain of replicas, some of which can be reasonably attributed to Cretan workshops.