bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validating Wave 1 (2014) Urinary Cotinine and TNE-2 Cut-points for Differentiating Wave 4 (2017) Cigarette Use from Non-use in the United States Using Data from the PATH Study
Authors: Edwards Kathryn C. , Khan Asia , Sharma Eva , Wang Lanqing , Feng June , Blount Benjamin C. , Sosnoff Connie S. , Smith Danielle M. , Goniewicz Maciej L. , Pearson Jennifer , Villanti Andrea C. , Delnevo Cristine D. , Bover-Manderski Michelle T. , Hatsukami Dorothy K. , Niaura Raymond , Everard Colm , Kimmel Heather L. , Duffy Kara , Rostron Brian L. , Del Valle-Pinero Arseima Y. , van Bemmel Dana M. , Stanton Cassandra A. , Hyland Andrew 
Published: June 2023

Abstract

Background:
Sex and racial/ethnic identity-specific cut-points for validating tobacco use using Wave 1 (W1) of the Population Assessment of Tobacco and Health (PATH) Study were published in 2020. The current study establishes predictive validity of the W1 (2014) urinary cotinine and total nicotine equivalents-2 (TNE-2) cut-points on estimating Wave 4 (W4; 2017) tobacco use.

Methods:
For exclusive and polytobacco cigarette use, weighted prevalence estimates based on W4 self-report alone and with exceeding the W1 cut-point were calculated to identify the percentage missed without biochemical verification. Sensitivity and specificity of W1 cut-points on W4 self-reported tobacco use status were examined. ROC curves were used to determine the optimal W4 cut-points to distinguish past 30-day users from non-users, and evaluate whether the cut-points significantly differed from W1.

Results:
Agreement between W4 self-reported use and exceeding the W1 cut-points was high overall and when stratified by demographic subgroups (0.7%–4.4% of use was missed if relying on self-report alone). The predictive validity of using the W1 cut-points to classify exclusive cigarette and polytobacco cigarette use at W4 was high (&gt;90% sensitivity and specificity, except among polytobacco Hispanic smokers). Cut-points derived using W4 data did not significantly differ from the W1-derived cut-points [e.g., W1 exclusive = 40.5 ng/mL cotinine (95% confidence interval, CI: 26.1–62.8), W4 exclusive = 29.9 ng/mL cotinine (95% CI: 13.5–66.4)], among most demographic subgroups.

Conclusions:
The W1 cut-points remain valid for biochemical verification of self-reported tobacco use in W4.

Impact:
Findings from can be used in clinical and epidemiologic studies to reduce misclassification of cigarette smoking status.
CCRL2 Expression by Specialized Lung Capillary Endothelial Cells Controls NK-cell Homing in Lung Cancer
Authors: Sozio Francesca , Schioppa Tiziana , Laffranchi Mattia , Salvi Valentina , Tamassia Nicola , Bianchetto-Aguilera Francisco M. , Tiberio Laura , Bonecchi Raffaella , Bosisio Daniela , Parmentier Marc , Bottazzi Barbara , Leone Roberto , Russo Eleonora , Bernardini Giovanni , Garofalo Stefano , Limatola Cristina , Gismondi Angela , Sciumè Giuseppe , Mantovani Alberto , Del Prete Annalisa , Sozzani Silvano 
Published: June 2023

Abstract
Patterns of receptors for chemotactic factors regulate the homing of leukocytes to tissues. Here we report that the CCRL2/chemerin/CMKLR1 axis represents a selective pathway for the homing of natural killer (NK) cells to the lung. C–C motif chemokine receptor-like 2 (CCRL2) is a nonsignaling seven-transmembrane domain receptor able to control lung tumor growth. CCRL2 constitutive or conditional endothelial cell targeted ablation, or deletion of its ligand chemerin, were found to promote tumor progression in a Kras/p53Flox lung cancer cell model. This phenotype was dependent on the reduced recruitment of CD27– CD11b+ mature NK cells. Other chemotactic receptors identified in lung-infiltrating NK cells by single-cell RNA sequencing (scRNA-seq), such as Cxcr3, Cx3cr1, and S1pr5, were found to be dispensable in the regulation of NK-cell infiltration of the lung and lung tumor growth. scRNA-seq identified CCRL2 as the hallmark of general alveolar lung capillary endothelial cells. CCRL2 expression was epigenetically regulated in lung endothelium and it was upregulated by the demethylating agent 5-aza-2′-deoxycytidine (5-Aza). In vivo administration of low doses of 5-Aza induced CCRL2 upregulation, increased recruitment of NK cells, and reduced lung tumor growth. These results identify CCRL2 as an NK-cell lung homing molecule that has the potential to be exploited to promote NK cell–mediated lung immune surveillance.
Elevating Omophoita octoguttata elytralis Bechyné, 1956 (Coleoptera: Chrysomelidae: Galerucinae: Alticini) to species
Authors: Begha Bruno Piotrovski , Santos Mateus Henrique , Prado Laura Rocha 
Published: June 2023

An updated morphological description for Omophoita elytralis (Bechyné, 1956), stat. nov., is presented, including the first account of the genitalia for this species. The separation Omophoita elytralis from O. octoguttata (Fabricius, 1775) is supported by differences found in the median lobe of males, elytral tegument uniform in color (not patterned), and their allopatric geographical distribution.
Novel Strategy to Combat the Procoagulant Phenotype in Heparin-Induced Thrombocytopenia Using 12-LOX Inhibition
Authors: Renna Stephanie A. , Zhao Xuefei , Kunapuli Satya P. , Ma Peisong , Holinstat Michael , Boxer Matthew B. , Maloney David J. , Michael James V. , McKenzie Steven E. 
Published: June 2023

BACKGROUND:
Heparin-induced thrombocytopenia (HIT) is a major concern for all individuals that undergo cardiac bypass surgeries or require prolonged heparin exposure. HIT is a life- and limb-threatening adverse drug reaction with an immune response following the formation of ultra-large immune complexes that drive platelet activation through the receptor FcγRIIA. Thrombotic events remain high following the standard of care treatment with anticoagulants, while increasing risk of bleeding complications. This study sought to investigate a novel approach to treatment of HIT. Recent reports demonstrate increased procoagulant activity in HIT; however, these reports required analysis ex vivo, and relevance in vivo remains unclear.

METHODS:

Using human and mouse model systems, we investigated the cooperativity of PARs (protease-activated receptors) and FcγRIIA in HIT. We challenged humanized FcγRIIA transgenic mice with or without endogenous mouse Par4 (denoted as IIA-Par4
+/+
or IIA-Par4
−
/−
, respectively) with a well-established model IgG immune complex (anti [α]-CD9). Furthermore, we assessed the procoagulant phenotype and efficacy to treat HIT utilizing inhibitor of 12-LOX (12[S]-lipoxygenase), VLX-1005, previously reported to decrease platelet activation downstream of FcγRIIA and PAR4, using the triple allele HIT mouse model.

RESULTS:

IIA-Par4
+/+
mice given αCD9 were severely thrombocytopenic, with extensive platelet-fibrin deposition in the lung. In contrast, IIA-Par4
−/−
mice had negligible thrombocytopenia or pulmonary platelet-fibrin thrombi. We observed that pharmacological inhibition of 12-LOX resulted in a significant reduction in both platelet procoagulant phenotype ex vivo, and thrombocytopenia and thrombosis in our humanized mouse model of HIT in vivo.

CONCLUSIONS:
These data demonstrate for the first time the need for dual platelet receptor (PAR and FcγRIIA) stimulation for fibrin formation in HIT in vivo. These results extend our understanding of HIT pathophysiology and provide a scientific rationale for targeting the procoagulant phenotype as a possible therapeutic strategy in HIT.
TGF-β1/SMAD3 Regulates Programmed Cell Death 5 That Suppresses Cardiac Fibrosis Post–Myocardial Infarction by Inhibiting HDAC3
Authors: Weng Lin , Ye Jingjing , Yang Fenghe , Jia Shi , Leng Minghong , Jia Bo , Xu Chunling , Zhao Yang , Liu Ruxia , Xiong Yufei , Zhou Yiqing , Zhao Junhui , Zheng Ming 
Published: June 2023

BACKGROUND:
Progressive cardiac fibrosis leads to ventricular wall stiffness, cardiac dysfunction, and eventually heart failure, but the underlying mechanism remains unexplored. PDCD5 (programmed cell death 5) ubiquitously expresses in tissues, including the heart; however, the role of PDCD5 in cardiac fibrosis is largely unknown. Therefore, this study aims at exploring the possible role and underlying mechanisms of PDCD5 in the pathogenesis of cardiac fibrosis.

METHODS AND RESULTS:
PDCD5 levels were found to be elevated in the serum obtained from patients with cardiac fibrosis, in fibrotic mice heart tissues after myocardial infarction, and in cardiac fibroblasts stimulated by Ang II (angiotensin II)- or TGF-β1 (transforming growth factor-β1). Overexpression of PDCD5 in cardiac fibroblasts or treatment with PDCD5 protein reduced the expression of profibrogenic proteins in response to TGF-β1 stimulation, while knockdown of PDCD5 increased fibrotic responses. It has been demonstrated that SMAD3, a protein that is also known as mothers against decapentaplegic homolog 3, directly upregulated PDCD5 during cardiac fibrosis. Subsequently, the increased PDCD5 promoted HDAC3 (histone deacetylase 3) ubiquitination, thus, inhibiting HDAC3 to reduce fibrotic responses. Fibroblast-specific knock-in of PDCD5 in mice ameliorated cardiac fibrosis after myocardial infarction and enhanced cardiac function, and these protective effects were eliminated by AAV9-mediated HDAC3 overexpression.

CONCLUSIONS:
The findings of this study demonstrated that PDCD5 is upregulated by SMAD3 during cardiac fibrosis, which subsequently ameliorated progressive fibrosis and cardiac dysfunction through HDAC3 inhibition. Thus, this study suggests that PDCD5 functions as a negative feedback factor on fibrotic signaling pathways and might serve as a potential therapeutic target to suppress the progression of fibrotic responses.
Cross‐Sectional Validation of a Novel Computed Tomography‐Based Carotid Mean Calcium Density Measurement
Authors: Cahalane Rachel , Akyildiz Ali , Kavousi Maryam , Vernooij Meike W. , Ikram M. Kamran , Gijsen Frank , Bos Daniel 
Published: June 2023

Background
The purpose of this study was to validate a technique for measuring mean calcium density and to determine associations of cardiovascular risk factors with carotid calcium density.

Methods and Results

We performed a cross‐sectional study in a random sample of 100 stroke‐free participants from the population‐based Rotterdam Study. The mean calcium density of the combined left and right carotid bifurcations was quantified with a threshold of 130 Hounsfield Units (HU) using a novel density technique. To validate the methodology, carotid calcium volumes acquired using the technique in the current study were compared with measurements computed using dedicated clinical software (semiautomatic technique based on a threshold of ≥130 HU). Next, we investigated the associations of participant demographics, total calcium volume, and known cardiovascular risk factors (hypertension, diabetes, hypercholesterolemia, obesity, and smoking status) with the newly derived mean carotid calcium density measurement using linear regression analyses. Calcium volumes obtained with the 2 methods showed a high agreement (intraclass correlation coefficient=0.99,
P
<0.001), underlining the validity of the density technique. The total calcium volume was statistically significantly associated with the mean calcium density (cardiovascular risk factors adjusted model (B: 0.48 [95% CI, 0.30–0.66],
P
<0.001). We also found an association between hypercholesterolemia and mean calcium density (0.46 [0.09–0.83],
P
=0.017). No other significant associations were found between participant demographics or cardiovascular risk factors and mean carotid calcium density.

Conclusions
We demonstrated the feasibility of a carotid calcium density measurement technique. The data warrant a subsequent longitudinal study to determine the association between carotid calcium density and the risk of cerebrovascular events.
Variation in Risk‐Standardized Acute Admission Rates Among Patients With Heart Failure in Accountable Care Organizations: Implications for Quality Measurement
Authors: Chuzi Sarah , Lindenauer Peter K. , Faridi Kamal , Priya Aruna , Pekow Penelope S. , D'Aunno Thomas , Mazor Kathleen M. , Stefan Mihaela S. , Spatz Erica S. , Gilstrap Lauren , Werner Rachel M. , Lagu Tara 
Published: June 2023

Background
Accountable care organizations (ACOs) aim to improve health care quality and reduce costs, including among patients with heart failure (HF). However, variation across ACOs in admission rates for patients with HF and associated factors are not well described.

Methods and Results
We identified Medicare fee‐for‐service beneficiaries with HF who were assigned to a Medicare Shared Savings Program ACO in 2017 and survived ≥30 days into 2018. We calculated risk‐standardized acute admission rates across ACOs, assigned ACOs to 1 of 3 performance categories, and examined associations between ACO characteristics and performance categories. Among 1 232 222 beneficiaries with HF, 283 795 (mean age, 81 years; 54% women; 86% White; 78% urban) were assigned to 1 of 467 Medicare Shared Savings Program ACOs. Across ACOs, the median risk‐standardized acute admission rate was 87 admissions per 100 people, ranging from 61 (minimum) to 109 (maximum) admissions per 100 beneficiaries. Compared to the overall average, 13% of ACOs performed better on risk‐standardized acute admission rates, 72% were no different, and 14% performed worse. Most ACOs with better performance had fewer Black beneficiaries and were not hospital affiliated. Most ACOs that performed worse than average were large, located in the Northeast, had a hospital affiliation, and had a lower proportion of primary care providers.

Conclusions
Admissions are common among beneficiaries with HF in ACOs, and there is variation in risk‐standardized acute admission rates across ACOs. ACO performance was associated with certain ACO characteristics. Future studies should attempt to elucidate the relationship between ACO structure and characteristics and admission risk.
Improvement in the Prediction of Cerebrovascular Events With White Matter Hyperintensity
Authors: de Havenon Adam , Smith Eric E. , Sharma Richa , Falcone Guido J. , Bangad Aaron , Prabhakaran Shyam , Sheth Kevin N. 
Published: June 2023

Background
It remains unclear if white matter hyperintensity (WMH) on magnetic resonance imaging adds relevant cerebrovascular prognostic information beyond vascular risk factors and demographics alone.

Methods and Results

We performed a post hoc analysis of hypertensive individuals in SPRINT‐MIND (Systolic Blood Pressure Intervention Trial–Memory and Cognition in Decreased Hypertension). The primary outcome was incident stroke or cognitive impairment (mild cognitive impairment or dementia). We fit logistic regression models with the predictors of Atherosclerotic Cardiovascular Disease Risk Score, age, sex, race, education, current cigarette smoking, and the SPRINT‐MIND randomization arm. WMH was subsequently included in the model to determine if it improved area under the receiver operating curve using the DeLong test. We used a structural equation model to determine the indirect effect on the primary outcome mediated through WMH. We included 727 individuals (mean age at baseline 67.7±8.4 years, 61.1% were men, 62.6% were non‐Hispanic White, and mean years of follow‐up was 3.6±0.9). Of the 727 individuals, 67 (9.2%) developed incident stroke or cognitive decline. The area under the receiver operating curve of the baseline model (without WMH) was 0.75 (95% CI, 0.70–0.81), and after the addition of WMH it increased to 0.81 (95% CI, 0.76–0.86) (
P
=0.004 for difference). The mediation analysis showed that 26.3% of the vascular risk's effect on the primary outcome is indirectly mediated through WMH.

Conclusions
In adult hypertensive individuals, we found that the addition of WMH to models predicting incident stroke or cognitive impairment improved the prognostic ability above vascular risk and demographics alone to a level consistent with excellent prediction.

Registration Information

REGISTRATION:
URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01206062.
Age‐Related Trends in the Predictive Value of Carotid Intima‐Media Thickness for Cardiovascular Death: A Prospective Population‐Based Cohort Study
Authors: Ge Jinzhuo , Jing Fuyu , Ji Runqing , Tian Aoxi , Su Xiaoming , Li Wei , He Guangda , Pu Boxuan , Lei Lubi , Lu Jiapeng , Li Jing 
Published: June 2023

Background
The age‐related trends in the predictive ability of carotid intima‐media thickness (CIMT) for cardiovascular risk remain unclear. We aimed to identify the age‐related trends in the predictive value of CIMT for cardiovascular death.

Methods and Results

In a prospective cohort of adults aged 35 to 75 years without history of cardiovascular disease who were enrolled between 2014 and 2020, we measured CIMT at baseline and collected the vital status and cause of death. We divided the study population into 4 age groups (35–44, 45–54, 55–64, and 65–75 years). Competing risk models were fitted to estimate the associations between CIMT and cardiovascular death. The added values of CIMT in prediction were assessed by the differences of the Harrell's concordance index and the net reclassification improvement index. We included 369 478 adults and followed them for a median of 4.7 years. A total of 4723 (1.28%) cardiovascular deaths occurred. After adjusting for the traditional risk factors, the hazard ratios for CIMT
mean
per SD decreased with age, from 1.27 (95% CI, 1.17–1.37) in the 35 to 44 years age group to 1.14 (95% CI, 1.10–1.19) in the 65 to 75 years age group (
P
for interaction <0.01). Meanwhile, the net reclassification improvement indexes for CIMT
mean
were attenuated with age, from 22.60% (95% CI, 15.56%–29.64%) in the 35 to 44 years age group to 7.00% (95% CI, −6.82% to 20.83%) in the 65 to 75 years age group. Similar results were found for maximum CIMT in all age groups.

Conclusions
CIMT may improve cardiovascular risk prediction in the young and middle‐aged populations, rather than those aged ≥55 years.
Incidence, Relevant Patient Factors, and Clinical Outcomes of the Misdiagnosis of ST‐Segment–Elevation Myocardial Infarction: Results From the Korea Acute Myocardial Infarction Registry
Authors: Cho Kyung Hoon , Shin Min‐Ho , Kim Min Chul , Sim Doo Sun , Hong Young Joon , Kim Ju Han , Ahn Youngkeun , Kim Hyo‐Soo , Hur Seung‐Ho , Lee Sang Rok , Hwang Jin‐Yong , Oh Seok Kyu , Cha Kwang Soo , Jeong Myung Ho ,   the Korea Acute Myocardial Infarction Registry (KAMIR) Investigators*
Published: June 2023

Background
Data on the incidence, relevant patient factors, and clinical outcomes of the misdiagnosis of ST‐segment–elevation myocardial infarction (STEMI) in the modern era of percutaneous coronary intervention are limited.

Methods and Results

Data from KAMIR (Korea Acute Myocardial Infarction Registry) between November 2011 and June 2020 were analyzed. Out of 28 470 patients with acute myocardial infarction, 11 796 were eventually diagnosed with STEMI following a coronary angiogram. They were classified into 2 groups: patients with an initial working diagnosis of STEMI before starting the initial treatment and patients with an initial working diagnosis of non‐STEMI (misdiagnosed group). Out of 11 796 patients with a final diagnosis of STEMI, 165 (1.4%) were misdiagnosed. The door‐to‐angiography time in the misdiagnosed group was 5 times longer than that in the timely diagnosed group (median 220 [interquartile range {IQR}, 66–1177] versus 43 [IQR, 31–58] minutes;
P
<0.001). In a multivariable adjustments model, patients with a history of heart failure, atypical chest pain, anemia, or symptom‐to‐door time ≥4 hours had significantly higher odds, whereas those with systolic blood pressure <100 mm Hg or anterior ST elevation or left bundle‐branch block on ECG had lower odds of STEMI misdiagnosis. For patients with culprit lesions in the left anterior descending artery (n=5838), the adjusted 1‐year mortality risk for STEMI misdiagnosis was 1.84 (95% CI, 1.01–3.38).

Conclusions
Misdiagnosis of STEMI is not rare and is associated with a significant delay in coronary angiography, resulting in increased 1‐year mortality for patients with culprit lesions in the left anterior descending artery.
Treatment of Slow‐Flow After Primary Percutaneous Coronary Intervention With Flow‐Mediated Hyperemia: The Randomized RAIN‐FLOW Study
Authors: Gomez‐Lara Josep , Gracida Montserrat , Rivero Fernando , Gutiérrez‐Barrios Alejandro , Muntané‐Carol Guillem , Romaguera Rafael , Fuentes Lara , Marcano Ana , Roura Gerard , Ferreiro José Luis , Teruel Luis , Brugaletta Salvatore , Alfonso Fernando , Comín‐Colet Josep , Gomez‐Hospital Joan‐Antoni 
Published: June 2023

Background
ST‐segment–elevation myocardial infarction complicated with no reflow after primary percutaneous coronary intervention is associated with adverse outcomes. Although several hyperemic drugs have been shown to improve the Thrombolysis in Myocardial Infarction flow, optimal treatment of no reflow remains unsettled. Saline infusion at 20 mL/min via a dedicated microcatheter causes (flow‐mediated) hyperemia. The objective is to compare the efficacy of pharmacologic versus flow‐mediated hyperemia in patients with ST‐segment–elevation myocardial infarction complicated with no reflow.

Methods and Results

In the RAIN‐FLOW (Treatment of Slow‐Flow After Primary Percutaneous Coronary Intervention With Flow‐Mediated Hyperemia) study, 67 patients with ST‐segment–elevation myocardial infarction and no reflow were randomized to receive either pharmacologic‐mediated hyperemia with intracoronary adenosine or nitroprusside (n=30) versus flow‐mediated hyperemia (n=37). The angiographic corrected Thrombolysis in Myocardial Infarction frame count and the minimal microcirculatory resistance, as assessed with intracoronary pressure‐thermistor wire, dedicated microcatheter, and thermodilution techniques, were compared after study interventions. Both Thrombolysis in Myocardial Infarction frame count(40.2±23.1 versus 39.2±20.7;
P
=0.858) and minimal microcirculatory resistance (753.6±661.5 versus 993.3±740.8 Wood units;
P
=0.174) were similar between groups. Thrombolysis in Myocardial Infarction 3 flow was observed in 26.7% versus 27.0% (
P
=0.899). Flow‐mediated hyperemia showed 2 different thermodilution patterns during saline infusion indicative of the severity of the no reflow phenomenon. In‐hospital death and nonfatal heart failure were observed in 10.4% and 26.9%, respectively.

Conclusions
Both treatments showed similar (and limited) efficacy restoring coronary flow. Flow‐mediated hyperemia with thermodilution pattern assessment allowed the simultaneous characterization of the no reflow degree and response to hyperemia. No reflow was associated with a high rate of adverse outcomes. Further research is warranted to prevent and to treat no reflow in patients with ST‐segment–elevation myocardial infarction.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT04685941.