bluuebunny/crossref_metadata_2025_split huggingface dataset:
Value of an Exercise Workload ≥10 Metabolic Equivalents for Predicting Inducible Myocardial Ischemia
Authors: Peteiro Jesús , Bouzas-Mosquera Alberto , Broullón Francisco , Martinez Dolores , Yañez Juan , Castro-Beiras Alfonso 
Published: September 2013

Background—
We sought to identify extensive ischemia on exercise echocardiography (ExE) relative to workload in patients without known coronary artery disease and to investigate whether ExE is useful in predicting outcomes in those with high exercise capacity (≥10 metabolic equivalents [METs]) plus a maximal test (≥85% of their maximal age-predicted heart rate [MAPHR]).

Methods and Results—

The analysis was performed on 4269 patients who underwent ExE, of whom 3995 achieved ≥85% of their MAPHR. These patients were divided according to the reached workload (<7, 7–9, or ≥10 METs) and compared for ExE results. Outcomes in the group achieving ≥10 METs plus ≥85% of their MAPHR (n=2221) were specifically assessed. Ischemia was defined as new/worsening wall motion abnormalities with exercise. ExE results were different between groups because the METs were lower. Still, among patients achieving ≥10 METs plus ≥85% of their MAPHR, 9.3% had extensive ischemia and 6% multiterritory disease. During follow-up in this subgroup, 108 patients died and 42 had a major cardiac event. Annualized mortality and major cardiac event rates were 0.84% and 0.32% in patients without ischemia versus 2.26% and 0.84% in those with ischemia, respectively (
P
<0.001 and
P
=0.002, respectively). Ischemia was an independent predictor of mortality (hazard ratio, 1.88; 95% confidence interval, 1.23–2.89;
P
=0.004) and major cardiac event (hazard ratio, 2.39; 95% confidence interval, 1.22–4.71;
P
=0.01).

Conclusions—
Patients without known coronary artery disease achieving ≥10 METs plus ≥85% of their MAPHR may still have ischemia. However, the low event rates even in those with ischemia limit the usefulness of imaging for assessing outcomes in this group.
Valvuloarterial Impedance, But Not Aortic Stenosis Severity, Predicts Syncope in Patients With Aortic Stenosis
Authors: Harada Kenji , Saitoh Takeji , Tanaka Jun , Shibayama Kentaro , Berdejo Javier , Shiota Takahiro 
Published: September 2013

Background—
The presence of syncope in patients with aortic valve stenosis (AS) predicts a grave prognosis. However, the evaluation of AS severity has been limited to valve-specific factors such as aortic valve area and mean transaortic pressure gradient. Recently, valvuloarterial impedance (Zva) was proposed for the estimation of global left ventricular afterload. Therefore, because predictors of syncope in patients with AS have not been investigated in recent years, we assessed the effect of clinical characteristics and echocardiographic parameters, including Zva, on syncope in patients with AS.

Methods and Results—

We retrospectively studied 451 patients with moderate and severe AS without low left ventricular ejection fraction (<40%). Patients with syncope (n=79; 18%) had higher Zva (5.1±0.9 versus 4.4±0.9 mm Hg/mL per m
2
;
P
<0.001) than those without (n=372; 82%). However, no significant differences existed in the mean transaortic pressure gradient (
P
=0.076) or the aortic valve area (
P
=0.160) between the 2 groups. In the multivariable analysis, only Zva was an independent predictor of syncope in patients with AS (odds ratio, 2.02; 95% confidence interval, 1.54–2.64;
P
<0.001). However, systolic blood pressure, relative wall thickness, the early transmitral flow velocity to peak early diastolic mitral annular velocity ratio, and mean transaortic pressure gradient were not identified as independent predictors. Receiver operating characteristic curve analysis identified Zva ≥4.7 mm Hg/mL per m
2
as the cutoff value associated with syncope in patients with AS.

Conclusions—
Our study suggests that high Zva, but not conventional parameters of AS, identifies AS patients with an increased risk of syncope.
Cardiac Magnetic Resonance Postcontrast T1 Time Is Associated With Outcome in Patients With Heart Failure and Preserved Ejection Fraction
Authors: Mascherbauer Julia , Marzluf Beatrice A. , Tufaro Caroline , Pfaffenberger Stefan , Graf Alexandra , Wexberg Paul , Panzenböck Adelheid , Jakowitsch Johannes , Bangert Christine , Laimer Daniela , Schreiber Catharina , Karakus Gültekin , Hülsmann Martin , Pacher Richard , Lang Irene M. , Maurer Gerald , Bonderman Diana 
Published: September 2013

Background—
The underlying pathophysiology of heart failure with preserved ejection fraction (HFPEF) is incompletely understood, but myocardial extracellular matrix accumulation is thought to play a major role. Our aims were to estimate myocardial extracellular matrix using cardiac magnetic resonance T1 mapping and to assess the relationship between pathobiology/pathophysiology and prognosis.

Methods and Results—

Patients with suspected HFPEF (n=100) were enrolled in this prospective, observational study. Confirmatory diagnostic tests, cardiac magnetic resonance imaging including T1 mapping, and invasive hemodynamic assessments were performed at baseline. Sixty-one patients with confirmed HFPEF entered a longitudinal outcome-monitoring phase (mean, 22.9±5.0 months), during which 16 had a cardiac event. Cardiac magnetic resonance T1 time (hazard ratio, 0.99; 95% confidence interval, 0.98–0.99;
P
=0.046), left atrial area (hazard ratio, 1.08; 95% confidence interval, 1.03–1.13;
P
<0.01), and pulmonary vascular resistance (hazard ratio, 1.01; 95% confidence interval, 1.00–1.01;
P
=0.03) were significantly associated with cardiac events. Patients with T1 times below the median (<388.3 ms) were at greater risk of cardiac events than the rest of the group (
P
<0.01). Extracellular matrix of left ventricular biopsies (n=9), quantified by TissueFAXS technology correlated with T1 time (
R
=0.98;
P
<0.01). T1 time also correlated with right ventricular–pulmonary arterial coupling (pulmonary vascular resistance:
R
=−0.36;
P
<0.01; right ventricular ejection fraction:
R
=0.28;
P
=0.01).

Conclusions—
In the present preliminary study, cardiac magnetic resonance postcontrast T1 time is associated with prognosis in HFPEF, suggesting postcontrast T1 as possible biomarker for HFPEF.
Rhodamine-Loaded Intercellular Adhesion Molecule–1-targeted Microbubbles for Dual-Modality Imaging Under Controlled Shear Stresses
Authors: Wu Zhuojun , Curaj Adelina , Fokong Stanley , Liehn Elisa A. , Weber Christian , Lammers Twan , Kiessling Fabian , Zandvoort van Marc 
Published: September 2013

Background—
The ability to image incipient atherosclerosis is based on the early events taking place at the endothelial level. We hypothesized that the expression of intercellular adhesion molecule-1 even in vessels with high flow rates can be imaged at the molecular level using 2 complementary imaging techniques: 2-photon laser scanning microscopy and contrast-enhanced ultrasound.

Methods and Results—

Using 2-photon laser scanning microscopy and contrast-enhanced ultrasound, intercellular adhesion molecule-1–targeted and rhodamine-loaded microbubbles were shown to be specifically bound to tumor necrosis factor-α–stimulated human umbilical vein endothelial cells and murine carotid arteries (44 wild-type mice) at shear stresses ranging from 1.25 to 120 dyn/cm
2
. Intercellular adhesion molecule-1–targeted and rhodamine-loaded microbubbles bound 8× more efficient (
P
=0.016) to stimulated human umbilical vein endothelial cells than to unstimulated cells and 14× more than nontargeted microbubbles (
P
=0.016). In excised carotids, binding efficiency did not decrease significantly when increasing the flow rate from 0.25 to 0.6 mL/min. Higher flow rates (0.8 and 1 mL/min) showed significantly reduced microbubbles retention, by 38% (
P
=0.03) and 55% (
P
=0.03), respectively. Ex vivo results were translatable in vivo, confirming that intercellular adhesion molecule-1–targeted and rhodamine-loaded microbubbles are able to bind specifically to the inflamed carotid artery endothelia under physiological flow conditions and to be noninvasively detected using contrast-enhanced ultrasound.

Conclusions—
Our data provide groundwork for the implementation of molecular ultrasound imaging in vessels with high shear stress and flow rates, as well as for the future development of image-guided therapeutic interventions, and multiphoton microscopy as the appropriate method of validation.
Innate Immune Interleukin-1 Receptor–Associated Kinase 4 Exacerbates Viral Myocarditis by Reducing CCR5
+
CD11b
+
Monocyte Migration and Impairing Interferon Production
Authors: Valaperti Alan , Nishii Mototsugu , Liu Youan , Naito Kotaro , Chan Megan , Zhang Liyong , Skurk Carsten , Schultheiss Heinz-Peter , Wells George A. , Eriksson Urs , Liu Peter P. 
Published: September 2013

Background—
Viral myocarditis follows a fatal course in ≈30% of patients. Interleukin-1 receptor–associated kinase 4 (IRAK4), a major nodal signal transducer in innate immunity, can play a pivotal role in host inflammatory response. We sought to determine how IRAK4 modulates inflammation and outcome in a mouse model of viral myocarditis.

Methods and Results—

Myocarditis was induced after intraperitoneal inoculation of coxsackievirus B3 into C57Bl/6 IRAK4-deficient mice and their littermate controls. Mortality and viral proliferation were markedly reduced in IRAK4
−/−
mice compared with their IRAK4
+/+
littermates. Disease resistance of IRAK4
−/−
mice paralleled increased amounts of protective heart-infiltrating CCR5
+
monocytes/macrophages and enhanced interferon-α and interferon-γ production 2 days after infection. Competitive bone marrow chimera demonstrated that intact IRAK4 function inhibited heart-specific migration of bone marrow–derived CCR5
+
cells. Mechanistically, lack of IRAK4 resulted in interferon regulatory factor 5 homodimerization via reduced melanoma differentiation-associated protein 5 degradation and enhanced Stat1 and Stat5 phosphorylation. Consequently, antiviral interferon-α and interferon-γ production, as well as CCR5
+
cell recruitment, increased, whereas the overall proinflammatory response was drastically reduced in the absence of IRAK4.

Conclusions—

Innate immunity signal transducer IRAK4 exacerbates viral myocarditis through inhibition of interferon production and reduced mobilization of protective CCR5
+
monocytes/macrophages to the heart. The combination of IRAK4 inhibitors and antiviral adjuvants may become an attractive therapeutic approach against viral myocarditis in the future.
FTY720 Ameliorates Acute Ischemic Stroke in Mice by Reducing Thrombo-Inflammation but Not by Direct Neuroprotection
Authors: Kraft Peter , Göb Eva , Schuhmann Michael K. , Göbel Kerstin , Deppermann Carsten , Thielmann Ina , Herrmann Alexander M. , Lorenz Kristina , Brede Marc , Stoll Guido , Meuth Sven G. , Nieswandt Bernhard , Pfeilschifter Waltraud , Kleinschnitz Christoph 
Published: September 2013

Background and Purpose—
Lymphocytes are important players in the pathophysiology of acute ischemic stroke. The interaction of lymphocytes with endothelial cells and platelets, termed thrombo-inflammation, fosters microvascular dysfunction and secondary infarct growth. FTY720, a sphingosine-1-phosphate receptor modulator, blocks the egress of lymphocytes from lymphoid organs and has been shown to reduce ischemic neurodegeneration; however, the underlying mechanisms are unclear. We investigated the mode of FTY720 action in models of cerebral ischemia.

Methods—

Transient middle cerebral artery occlusion (tMCAO) was induced in wild-type and lymphocyte-deficient
Rag1

−/−

mice treated with FTY720 (1 mg/kg) or vehicle immediately before reperfusion. Stroke outcome was assessed 24 hours later. Immune cells in the blood and brain were counted by flow cytometry. The integrity of the blood–brain barrier was analyzed using Evans Blue dye. Thrombus formation was determined by immunohistochemistry and Western blot, and was correlated with cerebral perfusion.

Results—

FTY720 significantly reduced stroke size and improved functional outcome in wild-type mice on day 1 and day 3 after transient middle cerebral artery occlusion. This protective effect was lost in lymphocyte-deficient
Rag1

−/−

mice and in cultured neurons subjected to hypoxia. Less lymphocytes were present in the cerebral vasculature of FTY720-treated wild-type mice, which in turn reduced thrombosis and increased cerebral perfusion. In contrast, FTY720 was unable to prevent blood–brain barrier breakdown and transendothelial immune cell trafficking after transient middle cerebral artery occlusion.

Conclusions—

Induction of lymphocytopenia and concomitant reduction of microvascular thrombosis are key modes of FTY720 action in stroke. In contrast, our findings in
Rag1

−/−

mice and cultured neurons argue against direct neuroprotective effects of FTY720.
Why the Intellect Cannot Have a Bodily Organ: De Anima 3.4
Authors: Cohoe Caleb 
Published: September 2013

Abstract
I reconstruct Aristotle’s reasons for thinking that the intellect cannot have a bodily organ. I present Aristotle’s account of the ‘aboutness’ or intentionality of cognitive states, both perceptual and intellectual. On my interpretation, Aristotle’s account is based around the notion of cognitive powers taking on forms in a special preservative way. Based on this account, Aristotle argues that no physical structure could enable a bodily part or combination of bodily parts to produce or determine the full range of forms that the human intellect can understand. For Aristotle, cognitive powers with bodily organs are always spatio-temporally limited, but the understanding is not. Aristotle claims that our understanding applies to all instances of the thing understood wherever and whenever they exist. On Aristotle’s own account the intellect in its nature is only ‘potential’, it does not actually possess any form. Thus nothing prevents it from possessing all forms.
Roles of Synoptic to Quasi-Biweekly Disturbances in Generating the Summer 2003 Heavy Rainfall in East China
Authors: Liu Hong-Bo , Yang Jing , Zhang Da-Lin , Wang Bin 
Published: September 2013

Abstract
During the mei-yu season of the summer of 2003, the Yangtze and Huai River basin (YHRB) encountered anomalously heavy rainfall, and the northern YHRB (nYHRB) suffered a severe flood because of five continuous extreme rainfall events. A spectral analysis of daily rainfall data over YHRB reveals two dominant frequency modes: one peak on day 14 and the other on day 4 (i.e., the quasi-biweekly and synoptic-scale mode, respectively). Results indicate that the two scales of disturbances contributed southwesterly and northeasterly anomalies, respectively, to the mei-yu frontal convergence over the southern YHRB (sYHRB) at the peak wet phase. An analysis of bandpass-filtered circulations shows that the lower and upper regions of the troposphere were fully coupled at the quasi-biweekly scale, and a lower-level cyclonic anomaly over sYHRB was phase locked with an anticyclonic anomaly over the Philippines. At the synoptic scale, the strong northeasterly components of an anticyclonic anomaly with a deep cold and dry layer helped generate the heavy rainfall over sYHRB. Results also indicate the passages of five synoptic-scale disturbances during the nYHRB rainfall. Like the sYHRB rainfall, these disturbances originated from the periodical generations of cyclonic and anticyclonic anomalies at the downstream of the Tibetan Plateau. The nYHRB rainfalls were generated as these disturbances moved northeastward under the influence of monsoonal flows and higher-latitude eastward-propagating Rossby wave trains. It is concluded that the sYHRB heavy rainfall resulted from the superposition of quasi-biweekly and synoptic-scale disturbances, whereas the intermittent passages of five synoptic-scale disturbances led to the flooding rainfall over nYHRB.
Are Arrested and Non-Arrested Serial Offenders Different? A Test of Spatial Offending Patterns Using DNA Found at Crime Scenes
Authors: Lammers Marre 
Published: September 2013

Objectives: Compare the spatial offending patterns of arrested offenders to that of non-arrested offenders, in order to assess selection bias in arrest data. Method: Data used for this study are from the Dutch DNA database for criminal cases. DNA allows reliable linkage of serial crimes committed by the same offender, whether or not the offender has ever been arrested. Spatial offending patterns of arrested and non-arrested offenders are measured by calculating the mean intercrime distance (MICD) of the offense locations. Survival analysis is performed to study whether the MICD has an influence on the duration until arrest. Results: No large differences are found between the MICD of arrested offenders and the MICD of non-arrested offenders. The MICD does not affect the duration until arrest. Conclusions: Because no differences in the MICDs are found between the arrested and non-arrested offenders, arrest data are probably less selective than has been suspected in the past, and results based on these data are unlikely to be strongly biased.
Superficial Medial Collateral Ligament Anatomic Augmented Repair Versus Anatomic Reconstruction
Authors: Wijdicks Coen A. , Michalski Max P. , Rasmussen Matthew T. , Goldsmith Mary T. , Kennedy Nicholas I. , Lind Martin , Engebretsen Lars , LaPrade Robert F. 
Published: September 2013

Background: When surgical intervention is required for a grade 3 superficial medial collateral ligament (sMCL) tear, there is no consensus on the optimal surgical treatment. Anatomic augmented repairs and anatomic reconstructions for treatment of grade 3 sMCL tears have not been biomechanically validated or compared. Hypothesis: Anatomic sMCL augmented repairs and anatomic sMCL reconstruction techniques will reproduce equivalent knee kinematics when compared with the intact state, while creating significant improvements in translational and rotational laxity compared with the sMCL sectioned state. Study Design: Controlled laboratory study. Methods: Eighteen match-paired, fresh-frozen cadaveric knees (average age, 52.6 years; range, 40-59 years) were each used to test laxity of an intact sMCL, a deficient sMCL, and either an anatomic augmented repair or an anatomic reconstruction. Knees were biomechanically tested in a 6 degrees of freedom robotic system, which included valgus rotation, internal and external rotation, simulated pivot shift, and coupled anterior drawer with external rotation. Results: Anatomic augmented repairs and anatomic reconstructions had significantly less medial joint gapping than the sectioned state at all tested flexion angles and showed significant reductions in valgus rotation compared with the sectioned state at all flexion angles. No significant differences between the anatomic augmented repair and anatomic reconstruction were found for any test performed. Despite the similar behavior between the 2 reconstruction groups, neither technique was able to reproduce the intact state. Conclusion: Anatomic sMCL augmented repairs and anatomic sMCL reconstructions were not significantly different when tested at time zero. Both the anatomic augmented repair and the anatomic reconstruction were able to improve knee stability and provide less than 2 mm of medial joint gapping at 0° and 20° of flexion. Clinical Significance: These results suggest that both an anatomic sMCL augmented repair and an anatomic sMCL reconstruction improve knee kinematics compared with a deficient sMCL and provide equivalent joint stability.
Risk Factors for Meniscectomy After Meniscal Repair
Authors: Lyman Stephen , Hidaka Chisa , Valdez Ana S. , Hetsroni Iftach , Pan Ting Jung , Do Huong , Dunn Warren R. , Marx Robert G. 
Published: September 2013

Background: Previous research suggests that a substantial percentage of meniscal repairs fail, resulting in a subsequent meniscectomy. Risk factors for failure have been investigated using small cohorts, providing ambiguous results. Purpose: To measure the frequency of and elucidate risk factors for subsequent meniscectomies after meniscal repair using a large study population from multiple surgical centers. Study Design: Case-control study; Level of evidence, 3. Methods: A total of 9529 patients who underwent 9609 outpatient meniscal repairs between 2003 and 2010 were identified from a statewide database of all ambulatory surgery in New York. Patients who subsequently underwent a meniscectomy were then identified. A Cox regression analysis was used to calculate the hazard ratio and 95% confidence intervals. The model included patient age, sex, comorbidities, concomitant arthroscopic procedures, laterality of the meniscus, and surgeon’s yearly meniscal repair volume. Results: The overall frequency of subsequent meniscectomies was 8.9%. Patients were at a decreased risk for subsequent meniscectomies if they underwent a concomitant anterior cruciate ligament (ACL) reconstruction ( P < .001). Patients undergoing isolated meniscal repairs (without concomitant ACL reconstruction) were at a decreased risk if they were older ( P < .001), had a lateral meniscal injury ( P = .002), or were operated on by a surgeon with a higher annual meniscal repair volume (>24 cases/year; P < .001). Conclusion: A meniscectomy after meniscal repair is performed infrequently, supporting the notion that repairing a meniscus is a safe and effective procedure in the long term. The risk for undergoing subsequent meniscectomies is decreased in patients undergoing a concomitant ACL reconstruction, in cases of isolated meniscal repairs for patients of older age, and in patients undergoing meniscal repair by surgeons with a high case volume.
Hyperbranched cyclic and multicyclic poly(etherketone)s by polycondensation of isosorbide and isomannide with 2,6,4′-trifluorobenzophenone and 1,3,5-tris(4-fluorobenzoyl) benzene
Authors: Bennour Haythem , Medimagh Raouf , Fildier Aurélie , Raffin Guy , Hangouet Marie , Chatti Saber , Zina Mongia Said , Kricheldorf Hans R. 
Published: September 2013

1,3,5-Tris(4-fluorobenzoyl)benzene (TFBB) and 2,6,4′-trifluorobenzophenone (TFB) were polycondensed with isosorbide and isomanide. All polycondensations were performed in a mixture of dimethyl sulfoxide and toluene with potassium carbonate as promotor. Optimal concentration to avoid gelation was set at 0.06 mol L−1. The different cyclization tendencies on the basis of monomers conformations are discussed. In the TFB series, the feed ratio isosorbide/TFB was varied from 1.0:1.0 to 1.5:1.0. A majority of linear and hyperbranched species were identified as main reaction products by matrix-assisted laser desorption/ionization–time-of-flight mass spectrometry regardless of the diol with slight cyclization tendency for isomannide. When TFBB was polycondensed with isosorbide, the cyclization tendency was significantly improved. The products obtained at a feed ratio of 1.41/1.0 and 1.51/1.0 were rich in cyclic and multicyclic species. More interesting results were obtained from the polycondensation of TFBB and isomannide, giving rise majoritarily to cyclic, bicyclic, and multicyclic species. Differential scanning calorimetric measurements indicated high glass transition temperature (around 200°C).