bluuebunny/crossref_metadata_2025_split huggingface dataset:
CDK4/6 Inhibitor PD 0332991 Sensitizes Acute Myeloid Leukemia to Cytarabine-Mediated Cytotoxicity
Authors: Yang Chenyi , Boyson Cynthia A. , Di Liberto Maurizio , Huang Xiangao , Hannah Jeffrey , Dorn David C. , Moore Malcolm A.S. , Chen-Kiang Selina , Zhou Pengbo 
Published: March 2015

AbstractCyclin-dependent kinase (CDK)4 and CDK6 are frequently overexpressed or hyperactivated in human cancers. Targeting CDK4/CDK6 in combination with cytotoxic killing therefore represents a rational approach to cancer therapy. By selective inhibition of CDK4/CDK6 with PD 0332991, which leads to early G1 arrest and synchronous S-phase entry upon release of the G1 block, we have developed a novel strategy to prime acute myeloid leukemia (AML) cells for cytotoxic killing by cytarabine (Ara-C). This sensitization is achieved in part through enrichment of S-phase cells, which maximizes the AML populations for Ara-C incorporation into replicating DNA to elicit DNA damage. Moreover, PD 0332991 triggered apoptosis of AML cells through inhibition of the homeobox (HOX)A9 oncogene expression, reducing the transcription of its target PIM1. Reduced PIM1 synthesis attenuates PIM1-mediated phosphorylation of the proapoptotic BAD and activates BAD-dependent apoptosis. In vivo, timely inhibition of CDK4/CDK6 by PD 0332991 and release profoundly suppresses tumor growth in response to reduced doses of Ara-C in a xenograft AML model. Collectively, these data suggest selective and reversible inhibition of CDK4/CDK6 as an effective means to enhance Ara-C killing of AML cells at reduced doses, which has implications for the treatment of elderly AML patients who are unable to tolerate high-dose Ara-C therapy. Cancer Res; 75(9); 1838–45. ©2015 AACR.
Opportunities for Translational Epidemiology: The Important Role of Observational Studies to Advance Precision Oncology
Authors: Marrone Michael , Schilsky Richard L. , Liu Geoff , Khoury Muin J. , Freedman Andrew N. 
Published: March 2015

Abstract
Within current oncology practice, several genomic applications are being used to inform treatment decisions with molecularly targeted therapies in breast, lung, colorectal, melanoma, and other cancers. This commentary introduces a conceptual framework connecting the full spectrum of biomedical research disciplines, including fundamental laboratory research, clinical trials, and observational studies in the translation of genomic applications into clinical practice. The conceptual framework illustrates the contribution that well-designed observational epidemiologic studies provide to the successful translation of these applications, and characterizes the role observational epidemiology plays in driving the dynamic and iterative bench-to-bedside, and bedside-to-bench translation continuum. We also discuss how the principles of this conceptual model, emphasizing integration of multidisciplinary research, can be applied to the evolving paradigm in “precision oncology” focusing on multiplex tumor sequencing, and we identify opportunities for observational studies to contribute to the successful and efficient translation of this paradigm.Cancer Epidemiol Biomarkers Prev; 24(3); 484–9. ©2015 AACR.
Targeting ETV1 in Gastrointestinal Stromal Tumors: Tripping the Circuit Breaker in GIST?
Authors: Duensing Anette 
Published: March 2015

Abstract
Summary: Activating mutations in the KIT or PDGFRA receptor tyrosine kinase genes are the key oncogenic drivers in the majority of gastrointestinal stromal tumors (GIST), but novel results now show that aberrant kinase signaling is potentiated by a positive feedback circuit that involves the ETS transcription factor ETV1. Targeting ETV1 can disrupt this circuit and represents a promising new therapeutic approach for the treatment of GISTs. Cancer Discov; 5(3); 231–3. ©2015 AACR.
See related article by Ran and colleagues, p. 304
Relationship of Cigarette Smoking With Inflammation and Subclinical Vascular Disease
Authors: McEvoy John W. , Nasir Khurram , DeFilippis Andrew P. , Lima Joao A.C. , Bluemke David A. , Hundley W. Gregory , Barr R. Graham , Budoff Matthew J. , Szklo Moyses , Navas-Acien Ana , Polak Joseph F. , Blumenthal Roger S. , Post Wendy S. , Blaha Michael J. 
Published: March 2015

Objective—
We sought to assess the impact of smoking status, cumulative pack-years, and time since cessation (the latter in former smokers only) on 3 important domains of cardiovascular disease: inflammation, vascular dynamics and function, and subclinical atherosclerosis.

Approach and Results—

The Multi-Ethnic Study of Atherosclerosis (MESA) cohort enrolled 6814 adults without prior cardiovascular disease. Smoking variables were determined by self-report and confirmed with urinary cotinine. We examined cross-sectional associations between smoking parameters and (1) inflammatory biomarkers (high-sensitivity C-reactive protein [hsCRP], interleukin-6, and fibrinogen); (2) vascular dynamics and function (brachial flow-mediated dilation and carotid distensibility by ultrasound, as well as aortic distensibility by MRI); and (3) subclinical atherosclerosis (coronary artery calcification, carotid intima–media thickness, and ankle-brachial index). We identified 3218 never smokers, 2607 former smokers, and 971 current smokers. Mean age was 62 years and 47% were male. There was no consistent association between smoking and vascular distensibility or flow-mediated dilation outcomes. However, compared with never smokers, the adjusted association between current smoking and measures of either inflammation or subclinical atherosclerosis was consistently stronger than for former smoking (eg, odds ratio for hsCRP>2 mg/L of 1.7 [95% confidence interval, 1.5–2.1] versus 1.2 [1.1–1.4], odds ratio for coronary artery calcification>0 of 1.8 [1.5–2.1] versus 1.4 [1.2–1.6], respectively). Similar associations were seen for interleukin-6, fibrinogen, carotid intima–media thickness, and ankle-brachial index. A monotonic association was also found between higher pack-year quartiles and increasing inflammatory markers. Furthermore, current smokers with hsCRP>2 mg/L were more likely to have increased carotid intima–media thickness, abnormal ankle-brachial index, and coronary artery calcification>75th percentile for age, sex, and race (relative to smokers with hsCRP<2 mg/L, interaction
P
<0.05 for all 3 outcomes). In contrast, time since quitting in former smokers was independently associated with lower inflammation and atherosclerosis (eg, odds ratio for hsCRP>2 mg/L of 0.91 [0.88–0.95] and odds ratio for coronary artery calcification>0 of 0.94 [0.90–0.97] for every 5-year cessation interval).

Conclusions—
These findings expand our understanding of the harmful effects of smoking and help explain the cardiovascular benefits of smoking cessation.
Cell Adhesion Mediated by VCAM–ITGα9 Interactions Enables Lymphatic Development
Authors: Yang Yiqing , Enis David , Zheng Hui , Chia Stephanie , Yang Jisheng , Chen Mei , Dhillon Veerpal , Papayannapoulou Thalia , Kahn Mark L. 
Published: March 2015

Objective—
Adhesive ligand–receptor interactions play key roles in blood vessel angiogenesis but remain poorly characterized during lymphatic vessel growth. In this study, we use genetic approaches in both fish and mice to address the roles of cell surface integrin ligand vascular cell adhesion molecule (VCAM) and its 2 receptors, integrins α9 and α4, during lymphatic vascular development.

Approach and Results—

Conditional deletion of the
Vcam
gene was used to test VCAM function in lymphatic growth in midgestation mice. Morpholino knockdown and cRNA rescue of the 2 zebrafish vcam alleles, as well as integrins α9 and 4, were used to test the role of these ligands and receptors during lymphatic growth in the developing fish. We show that VCAM is essential for lymphatic development in the zebrafish embryo and that integrin α9 (Itgα9) rather than Itgα4 is the required VCAM receptor in the developing fish. VCAM is expressed along lines of lymphatic migration in the mouse intestine, but its loss only retards lymphatic growth.

Conclusions—
These studies reveal an unexpected role for cell–cell adhesion mediated by Itgα9–VCAM interactions during lymphatic development in the fish but not in the mouse. We propose that the relative importance of cellular adhesive ligands is magnified under conditions of rapid tissue growth when the cell number increases faster than cell matrix, such as in the early zebrafish embryo.
Five-Year Follow-Up After Catheter Ablation of Persistent Atrial Fibrillation Using the Stepwise Approach and Prognostic Factors for Success
Authors: Schreiber Doreen , Rostock Thomas , Fröhlich Max , Sultan Arian , Servatius Helge , Hoffmann Boris A. , Lüker Jakob , Berner Imke , Schäffer Benjamin , Wegscheider Karl , Lezius Susanne , Willems Stephan , Steven Daniel 
Published: March 2015

Background—
In the meantime, catheter ablation is widely used for the treatment of persistent atrial fibrillation (AF). There is a paucity of data about long-term outcomes. This study evaluates (1) 5-year single and multiple procedure success and (2) prognostic factors for arrhythmia recurrences after catheter ablation of persistent AF using the stepwise approach aiming at AF termination.

Methods and Results—

A total of 549 patients with persistent AF underwent de novo catheter ablation using the stepwise approach (2007–2009). A total of 493 patients were included (Holter ECGs ≥every 6 months). Mean follow-up was 59±16 months with 2.1±1.1 procedures per patient. Single and multiple procedure success rates were 20.1% and 55.9%, respectively (80% off antiarrhythmic drug). Antiarrhythmic drug–free multiple procedure success was 46%. Long-term recurrences (n=171) were paroxysmal AF in 48 patients (28%) and persistent AF/atrial tachycardia in 123 patients (72%). Multivariable recurrent event analysis revealed the following factors favoring arrhythmia recurrence: failure to terminate AF during index procedure (hazard ratio [HR], 1.279; 95% confidence interval [CI], 1.093–1.497;
P
=0.002), number of procedures (HR, 1.154; 95% CI, 1.051–1.267;
P
=0.003), female sex (HR, 1.263; 95% CI, 1.027–1.553;
P
=0.027), and the presence of structural heart disease (HR, 1.236; 95% CI, 1.003–1.524;
P
=0.047). AF termination was correlated with a higher rate of consecutive procedures because of atrial tachycardia recurrences (
P
=0.003; HR, 1.71; 95% CI, 1.20–2.43).

Conclusions—
Catheter ablation of persistent AF using the stepwise approach provides limited long-term freedom of arrhythmias often requiring multiple procedures. AF termination, the number of procedures, sex, and the presence of structural heart disease correlate with outcome success. AF termination is associated with consecutive atrial tachycardia procedures.
Temporal Trends in Revascularization Strategy and Outcomes in Left Main Coronary Artery Stenosis
Authors: Park Seung-Jung , Ahn Jung-Min , Kim Young-Hak , Park Duk-Woo , Yun Sung-Cheol , Yoon Sung-Han , Park Hyun Woo , Chang Mineok , Lee Jong-Young , Kang Soo-Jin , Lee Seung-Whan , Lee Cheol Whan , Park Seong-Wook 
Published: March 2015

Background—
Changes over time in revascularization strategies and outcomes among patients with unprotected left main coronary artery stenosis remain largely unknown.

Methods and Results—

A total of 2618 consecutive patients with unprotected left main coronary artery stenosis who underwent revascularization were identified from the ASAN Medical Center-Left MAIN Revascularization registry and classified by time periods: bare metal stent (wave 1, 1995–1998), early drug-eluting stents (wave 2, 2003–2006), and late drug-eluting stents (wave 3, 2007–2010). Primary end point was major adverse cerebrocardiovascular events (the composite of death, myocardial infarction, repeat revascularization, and stroke). During the study period, 1124 patients underwent percutaneous coronary intervention (PCI) and 1494 patients underwent coronary artery bypass grafting. The proportion of PCI significantly increased from 35% to 52% between waves 1 and 3. In patients receiving PCI, the risk-adjusted incidence rate of major adverse cerebro-cardiovascular events decreased from 20.18 cases per 100 person-years in wave 1 to 6.77 cases per 100 person-years in wave 3 (
P
<0.001 for trend). Death, the composite of death, myocardial infarction, stroke, and repeat revascularization were also significantly decreased by 40%, 35%, and 46%, respectively. The risk-adjusted incidence rate of major adverse cerebrocardiovascular events did not change in patients receiving coronary artery bypass grafting. The difference major adverse cerebrocardiovascular events risk between PCI and coronary artery bypass grafting progressively reduced (adjusted hazard ratio [95% confidence interval], 0.33 [0.23–0.47]; 0.53 [0.35–0.80]; and 1.01 [0.68–1.49] from wave 1 to wave 3.

Conclusions—
The outcomes of unprotected left main coronary artery PCI have significantly improved over time. In addition, more patients received PCI for unprotected left main coronary artery stenosis in recent years.
Association Between Newborn Birth Weight and the Risk of Postpartum Maternal Venous Thromboembolism
Authors: Blondon Marc , Quon Bradley S. , Harrington Laura B. , Bounameaux Henri , Smith Nicholas L. 
Published: March 2015

Background—
Postpartum venous thromboembolism (VTE) is a potentially fatal and preventable event leading to substantial short- and long-term morbidity. We sought to evaluate whether the delivery of term newborns of low or high birth weight was associated with greater risks of VTE.

Methods and Results—

In a population-based case–control study conducted in Washington State from 1987 through 2011, cases of hospitalized VTE within 3 months of delivery were identified by using selected
International Classification of Diseases, Ninth Revision, Clinical Modification
codes. Controls were randomly selected postpartum women without VTE, matched on birth year. Birth weight and other maternal and pregnancy characteristics were extracted from birth certificate data. Among term live singleton deliveries, we compared the risk of VTE for mothers of newborns of low and high birth weights (<2500 g and >4000 g, respectively) versus mothers of newborns of normal birth weight (2500–4000 g). Logistic regression models were adjusted for maternal age, race, education, body mass index, parity, delivery methods, gestational length, smoking, gestational diabetes mellitus, and preeclampsia. Patients with VTE (n=547) were older, had a higher body mass index, and experienced more pregnancy-related complications than controls (n=9482). In comparison with mothers of newborns with normal birth weight, mothers of newborns with low birth weight had a 3-fold increased risk of VTE, which persisted after multivariable adjustment (odds ratio, 2.98; 95% confidence interval, 1.80–4.93). Mothers of newborns with high birth weight had only a slightly increased risk of VTE, which was attenuated after multivariable adjustment (odds ratio, 1.26; 95% confidence interval, 0.99–1.61).

Conclusions—
The delivery of a newborn with low birth weight is associated with a 3-fold increased risk of maternal postpartum VTE. This should be considered when assessing VTE risk at delivery.
Validity of Shape as a Predictive Biomarker of Final Infarct Volume in Acute Ischemic Stroke
Authors: Frindel Carole , Rouanet Anaïs , Giacalone Mathilde , Cho Tae-Hee , Østergaard Leif , Fiehler Jens , Pedraza Salvador , Baron Jean-Claude , Wiart Marlène , Berthezène Yves , Nighoghossian Norbert , Rousseau David 
Published: March 2015

Background and Purpose—
This study examines whether lesion shape documented on magnetic resonance diffusion-weighted imaging during acute stroke improves the prediction of the final infarct volume compared with lesion volume only.

Methods—
Diffusion-weighted imaging data and clinical information were retrospectively reviewed in 110 consecutive patients who underwent (n=67) or not (n=43) thrombolytic therapy for acute ischemic stroke. Three-dimensional shape analysis was performed on admission diffusion-weighted imaging data and 5 shape descriptors were developed. Final infarct volume was measured on T2-fluid-attenuated inversion recovery imaging data performed 30 days after stroke.

Results—

Shape analysis of acute ischemic lesion and more specifically the ratio of the bounding box volume to the lesion volume before thrombolytic treatment improved the prediction of the final infarct for patients undergoing thrombolysis (
R
2
=0.86 in model with volume;
R
2
=0.98 in model with volume and shape).

Conclusions—
Our findings suggest that lesion shape contains important predictive information and reflects important environmental factors that might determine the progression of ischemia from the core.
Quantitative Assessment of Changes in Cerebral Arteriovenous Malformation Hemodynamics After Embolization
Authors: Alaraj Ali , Amin-Hanjani Sepideh , Shakur Sophia F. , Aletich Victor A. , Ivanov Alexander , Carlson Andrew P. , Oh Gerald , Charbel Fady T. 
Published: March 2015

Background and Purpose—
Embolization reduces flow in arteriovenous malformations (AVMs) before surgical resection, but achievement of this goal is determined subjectively from angiograms. Here, we quantify effects of embolization on AVM flow.

Methods—
Records of patients who underwent AVM embolization at our institution between 2007 and 2013 and had flow rates obtained pre- and postembolization using quantitative magnetic resonance angiography were retrospectively reviewed. Total flow was estimated as aggregate flow within primary arterial feeders or flow in single draining veins.

Results—

Twenty-one patients were included (mean age 35 years, 24% hemorrhagic presentation) with Spetzler–Martin grades 1 to 4. Fifty-four total embolization sessions were performed. The mean AVM flow was 403.4±262.4 mL/min at baseline, 285.3±246.4 mL/min after single session (29% drop,
P
<0.001), and 102.0±103.3 mL/min after all sessions of embolization (75% drop,
P
<0.001). Total number of pedicles embolized (
P
<0.001) and embolization of an intranidal fistula during any session (
P
=0.002) were significantly associated with total decreased flow postembolization. On multivariate analysis, total pedicles embolized was predictive of total flow drop (
P
<0.001). However, pedicles embolized per session did not correlate with flow drop related to that session (
P
=0.44).

Conclusions—
AVM flow changes after embolization can be measured using quantitative magnetic resonance angiography. The total number of pedicles embolized after multiple embolization sessions was predictive of final flow, indicating this parameter is the best angiographic marker of a hemodynamically successful intervention. The number of pedicles embolized per session, however, did not correlate with flow drop in that session, likely because of flow redistribution after partial embolization.
Additional Diagnostic Value of Computed Tomography Perfusion for Detection of Acute Ischemic Stroke in the Posterior Circulation
Authors: van der Hoeven Erik J.R.J. , Dankbaar Jan Willem , Algra Ale , Vos Jan Albert , Niesten Joris M. , van Seeters Tom , van der Schaaf Irene C. , Schonewille Wouter J. , Kappelle L. Jaap , Velthuis Birgitta K. 
Published: March 2015

Background and Purpose—
Detection of acute infarction in the posterior circulation is challenging. We aimed to determine the additional value of tomograpy (CT) perfusion to noncontrast CT and CT angiography source images for infarct detection and localization in patients suspected of acute ischemic posterior circulation stroke.

Methods—

Patients with suspected acute ischemic posterior circulation stroke were selected from the Dutch acute Stroke Trial (DUST) study. Patients underwent noncontrast CT, CT angiography, and CT perfusion within 9 hours after stroke onset and CT or MRI on follow-up. Images were evaluated for signs and location of ischemia. Discrimination of 3 hierarchical logistic regression models (noncontrast CT [A], added CT angiography source images [B], and CT perfusion [C]) was compared with
C
-statistics.

Results—

Of 88 patients, 76 (86%) had a clinical diagnosis of ischemic stroke on discharge and 42 patients (48%) showed a posterior circulation infarct on follow-up imaging. Model C (area under the curve from the receiver operating characteristic curve=0.86; 95% confidence interval, 0.77–0.94) predicted an infarct in the posterior circulation territory better than models A (area under the curve from the receiver operating characteristic curve=0.64; 95% confidence interval, 0.53–0.76;
P
C versus A
<0.001) and B (area under the curve from the receiver operating characteristic curve=0.68; 95% confidence interval, 0.56–0.79;
P
C versus B
<0.001).

Conclusions—
CT perfusion has significant additional diagnostic values to noncontrast CT and CT angiography source images for detecting ischemic changes in patients suspected of acute posterior circulation stroke.
Abundance, relative growth and fecundity of Emerita rathbunae Schmitt, 1935 (Decapoda, Anomura, Hippidae) in the S.E. Gulf of California, Mexico
Authors: Ríos-Elósegui Daniela , Hendrickx Michel E. 
Published: March 2015

Specimens of the mole crabEmerita rathbunaeSchmitt, 1935, were collected during a one-year period along two sandy beaches in the S.E. Gulf of California, Mexico. A total of 2171 specimens were examined. Only 8% of the collected females were ovigerous. The large majority of males (95%) were collected in the sand as “free living” males, while the rest (39 individuals) were “dwarf males”, with developed genital papilla, 95% of which were found attached to females. Density for pooled samples reached an overall maximum of 309.8 orgs/m2in February and a minimum in April (65.0 orgs/m2). Females always outnumbered males, except in February. Ovigerous females were observed in the first half of the study period (February to September). Proportions of males were very similar throughout the study period, while indeterminate specimens were proportionally more abundant in its second half. Relationships between CW and CL for both males and females were highly correlated and isometric. Relationships between size and weight were highly correlated in both males and non-ovigerous females for pooled samples or for each sampling zone, and in each case growth was isometric. The number of eggs per ovigerous female varied considerably, from 910 to 22 866, and the relationship between number of eggs per batch and body size was poorly correlated. In the study area,E. rathbunaeappears to have a rather restricted reproduction period. A larger series of data combined with the analysis of other environmental factors, such as beach profiles, current patterns and primary productivity, might bring some additional information on this species biology and ecology. Due to the key role that mole crabs play in the food web of sandy beaches, special attention should be provided to this particular habitat.
A new species of cirolanid isopod (Peracarida, Isopoda) collected from Cenote Aerolito, Cozumel Island, northwestern Caribbean
Authors: Ortiz Manuel , Cházaro-Olvera Sergio 
Published: March 2015

A new species ofCirolanaLeach, 1818, collected from Cenote Aerolito, Cozumel Island, Mexican Caribbean, is described.Cirolana(Anopsilana)adrianisp. nov. has a body 2.7× as long as wide, widest at pereonites 5-6; cephalon smooth, with small rostral point; pereonites without tubercles or ridges; antenna 2 not surpassing back of segment 2 of pereon; pleonite 4 lacking free ventrolateral margins; pleotelson as long as wide, smooth, with 9 distal robust setae; appendix masculina extremely long, 2× as long as endopod of pleopod 2. The main differences between the new species and the marine speciesCirolana(Anopsilana)jonesi(Kensley, 1987) andC.(A.)sinu(Kensley & Schotte, 1994), as well as the stygobitic speciesC.(A.)yucatanaBotosaneanu & Iliffe, 2000, the most similar known species ofCirolana(Anopsilana) in the region, are described. This is the second isopod of the genusCirolanarecorded from the karstic systems of the Yucatan Peninsula.