bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does PTEN Loss Impair DNA Double-Strand Break Repair by Homologous Recombination?
Authors: Hunt Clayton R. , Gupta Arun , Horikoshi Nobuo , Pandita Tej K. 
Published: December 2011

Abstract
The tumor suppressor PTEN is frequently lost in cancer cells, resulting in altered radiation and drug sensitivity. However, the role of PTEN in DNA repair is controversial. Detailed studies in prostate cancer cells now indicate PTEN does not regulate RAD51 expression or homologous recombination and is not a biomarker for PARP inhibitor sensitivity. Clin Cancer Res; 18(4); 920–2. ©2011 AACR.
Contractile Dysfunction Irrespective of the Mutant Protein in Human Hypertrophic Cardiomyopathy With Normal Systolic Function
Authors: van Dijk Sabine J. , Paalberends E. Rosalie , Najafi Aref , Michels Michelle , Sadayappan Sakthivel , Carrier Lucie , Boontje Nicky M. , Kuster Diederik W.D. , van Slegtenhorst Marjon , Dooijes Dennis , dos Remedios Cris , ten Cate Folkert J. , Stienen Ger J.M. , van der Velden Jolanda 
Published: December 2011

Background—
Hypertrophic cardiomyopathy (HCM), typically characterized by asymmetrical left ventricular hypertrophy, frequently is caused by mutations in sarcomeric proteins. We studied if changes in sarcomeric properties in HCM depend on the underlying protein mutation.

Methods and Results—

Comparisons were made between cardiac samples from patients carrying a
MYBPC3
mutation (MYBPC3
mut
; n=17), mutation negative HCM patients without an identified sarcomere mutation (HCM
mn
; n=11), and nonfailing donors (n=12). All patients had normal systolic function, but impaired diastolic function. Protein expression of myosin binding protein C (cMyBP-C) was significantly lower in MYBPC3
mut
by 33±5%, and similar in HCM
mn
compared with donor. cMyBP-C phosphorylation in MYBPC3
mut
was similar to donor, whereas it was significantly lower in HCM
mn
. Troponin I phosphorylation was lower in both patient groups compared with donor. Force measurements in single permeabilized cardiomyocytes demonstrated comparable sarcomeric dysfunction in both patient groups characterized by lower maximal force generating capacity in MYBPC3
mut
and HCM
mn,
compared with donor (26.4±2.9, 28.0±3.7, and 37.2±2.3 kN/m
2
, respectively), and higher myofilament Ca
2+
-sensitivity (EC
50
=2.5±0.2, 2.4±0.2, and 3.0±0.2 μmol/L, respectively). The sarcomere length-dependent increase in Ca
2+
-sensitivity was significantly smaller in both patient groups compared with donor (ΔEC
50
: 0.46±0.04, 0.37±0.05, and 0.75±0.07 μmol/L, respectively). Protein kinase A treatment restored myofilament Ca
2+
-sensitivity and length-dependent activation in both patient groups to donor values.

Conclusions—

Changes in sarcomere function reflect the clinical HCM phenotype rather than the specific
MYBPC3
mutation. Hypocontractile sarcomeres are a common deficit in human HCM with normal systolic left ventricular function and may contribute to HCM disease progression.
Reference Values for Normal Pulmonary Artery Dimensions by Noncontrast Cardiac Computed Tomography
Authors: Truong Quynh A. , Massaro Joseph M. , Rogers Ian S. , Mahabadi Amir A. , Kriegel Matthias F. , Fox Caroline S. , O'Donnell Christopher J. , Hoffmann Udo 
Published: December 2011

Background—
Main pulmonary artery diameter (mPA) and ratio of mPA to ascending aorta diameter (ratio PA) derived from chest CT are commonly reported in clinical practice. We determined the age- and sex-specific distribution and normal reference values for mPA and ratio PA by CT in an asymptomatic community-based population.

Methods and Results—

In 3171 men and women (mean age, 51±10 years; 51% men) from the Framingham Heart Study, a noncontrast, ECG-gated, 8-slice cardiac multidetector CT was performed. We measured the mPA and transverse axial diameter of the ascending aorta at the level of the bifurcation of the right pulmonary artery and calculated the ratio PA. We defined the healthy referent cohort (n=706) as those without obesity, hypertension, current and past smokers, chronic obstructive pulmonary disease, history of pulmonary embolism, diabetics, cardiovascular disease, and heart valve surgery. The mean mPA diameter in the overall cohort was 25.1±2.8 mm and mean ratio PA was 0.77±0.09. The sex-specific 90th percentile cutoff value for mPA diameter was 28.9 mm in men and 26.9 mm in women and was associated with increase risk for self-reported dyspnea (adjusted odds ratio, 1.31;
P
=0.02). The 90th percentile cutoff value for ratio PA of the healthy referent group was 0.91, similar between sexes but decreased with increasing age (range, 0.82–0.94), though not associated with dyspnea.

Conclusions—
For simplicity, we established 29 mm in men and 27 mm in women as sex-specific normative reference values for mPA and 0.9 for ratio PA.
Short-Term Outcomes of Acute Myocardial Infarction in Patients With Acute Kidney Injury
Authors: Fox Caroline S. , Muntner Paul , Chen Anita Y. , Alexander Karen P. , Roe Matthew T. , Wiviott Stephen D. 
Published: December 2011

Background—
Acute kidney injury (AKI) is a risk factor for long-term adverse outcomes, including acute myocardial infarction and death. However, the relationship between severity of AKI and in-hospital outcomes in the setting of acute myocardial infarction has not been well documented.

Methods and Results—
The study population (n=59 970) was drawn from the Acute Coronary Treatment and Intervention Outcomes Network (ACTION) Registry–Get With the Guidelines (GWTG), a nationwide sample of myocardial infarction patients admitted to 383 hospitals in the United States between July 2008 and September 2009. AKI was defined using absolute changes in serum creatinine (SCr; peak SCr minus admission SCr) and categorized as no AKI (SCr change, <0.3 mg/dL), mild AKI (SCr change, 0.3–<0.5 mg/dL), moderate AKI (SCr change, 0.5–<1.0 mg/dL), and severe AKI (SCr change, ≥1.0 mg/dL). Overall, 16.1% had AKI, including 6.5% with mild AKI, 5.6% with moderate AKI, and 4.0% with severe AKI. In-hospital mortality rates for those with mild, moderate, and severe AKI were 6.6%, 14.2%, and 31.8% compared with 2.1% in those without AKI. The odds ratios for in-hospital death were 2.4 (95% confidence interval, 2.0–2.7), 4.5 (95% confidence interval, 3.9–5.1), and 12.6 (95% confidence interval, 11.1–14.3) for mild, moderate, and severe AKI compared with those without AKI. Although patients with AKI were less likely to undergo early invasive care or to receive antiplatelet therapies, rates of major bleeding ranged from 8.4% (no AKI) to 32.7% (severe AKI).

Conclusion—
AKI is common and associated with mortality and bleeding, underscoring the importance of efforts to identify risk factors and to prevent AKI in acute myocardial infarction care.
ST-Elevation Acute Coronary Syndromes in the Platelet Inhibition and Patient Outcomes (PLATO) Trial
Authors: Armstrong Paul W. , Siha Hany , Fu Yuling , Westerhout Cynthia M. , Steg Ph. Gabriel , James Stefan K. , Storey Robert F. , Horrow Jay , Katus Hugo , Clemmensen Peter , Harrington Robert A. , Wallentin Lars 
Published: December 2011

Background—
Ticagrelor, when compared with clopidogrel, reduced the 12-month risk of vascular death/myocardial infarction and stroke in patients with ST-elevation acute coronary syndromes intended to undergo primary percutaneous coronary intervention in the PLATelet inhibition and patient Outcomes (PLATO) trial. This prespecified ECG substudy explored whether ticagrelor's association with vascular death and myocardial infarction within 1 year would be amplified by (1) the extent of baseline ST shift and (2) subsequently associated with fewer residual ST changes at hospital discharge.

Methods and Results—

ECGs were evaluated centrally in a core laboratory in 3122 ticagrelor- and 3084 clopidogrel-assigned patients having at least 1 mm ST-elevation in 2 contiguous leads as identified by site investigators on the qualifying ECG. Patients with greater ST-segment shift at baseline had higher rates of vascular death/myocardial infarction within 1 year. Among those who also had an ECG at hospital discharge (n=4798), patients with ≥50% ΣST-deviation (ΣST-dev) resolution had higher event-free survival than those with incomplete resolution (6.4% versus 8.8%, adjusted hazard ratio 0.69 (0.54–0.88),
P
=0.003). The extent of ΣST-dev resolution was similar irrespective of treatment assignment. The benefit of ticagrelor versus clopidogrel on clinical events was consistent irrespective of the extent of baseline ΣST-dev (
P
(interaction)=0.728). When stratified according to conventional times from symptom onset, ie, ≤3 hours, 3 to 6 hours, >6 hours, the extent of baseline ΣST-dev declined progressively over time. As time from symptom onset increased beyond 3 hours, the benefit of ticagrelor appeared to be more pronounced; however, the interaction between time and treatment was not significant (
P
=0.175).

Conclusions—
Ticagrelor did not modify ΣST-dev resolution at discharge nor was its benefit affected by the extent of baseline ΣST-dev. These hypothesis-generating observations suggest that the main effects of ticagrelor may not relate to the rapidity or the completeness of acute reperfusion, but rather the prevention of recurrent vascular events by more powerful platelet inhibition or other mechanisms.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00391872.
Six-Month Versus 12-Month Dual Antiplatelet Therapy After Implantation of Drug-Eluting Stents
Authors: Gwon Hyeon-Cheol , Hahn Joo-Yong , Park Kyung Woo , Song Young Bin , Chae In-Ho , Lim Do-Sun , Han Kyoo-Rok , Choi Jin-Ho , Choi Seung-Hyuk , Kang Hyun-Jae , Koo Bon-Kwon , Ahn Taehoon , Yoon Jung-Han , Jeong Myung-Ho , Hong Taek-Jong , Chung Woo-Young , Choi Young-Jin , Hur Seung-Ho , Kwon Hyuck-Moon , Jeon Dong-Woon , Kim Byung-Ok , Park Si-Hoon , Lee Nam-Ho , Jeon Hui-Kyung , Jang Yangsoo , Kim Hyo-Soo 
Published: December 2011

Background—
The optimal duration of dual antiplatelet therapy (DAPT) after implantation of drug-eluting coronary stents remains undetermined. We aimed to test whether 6-month DAPT would be noninferior to 12-month DAPT after implantation of drug-eluting stents.

Methods and Results—

We randomly assigned 1443 patients undergoing implantation of drug-eluting stents to receive 6- or 12-month DAPT (in a 1:1 ratio). The primary end point was a target vessel failure, defined as the composite of cardiac death, myocardial infarction, or ischemia-driven target vessel revascularization at 12 months. Rates of target vessel failure at 12 months were 4.8% in the 6-month DAPT group and 4.3% in the 12-month DAPT group (the upper limit of 1-sided 95% confidence interval, 2.4%;
P
=0.001 for noninferiority with a predefined noninferiority margin of 4.0%). Although stent thrombosis tended to occur more frequently in the 6-month DAPT group than in the 12-month group (0.9% versus 0.1%; hazard ratio, 6.02; 95% confidence interval, 0.72–49.96;
P
=0.10), the risk of death or myocardial infarction did not differ in the 2 groups (2.4% versus 1.9%; hazard ratio, 1.21; 95% confidence interval, 0.60–2.47;
P
=0.58). In the prespecified subgroup analysis, target vessel failure occurred more frequently in the 6-month DAPT group than in the 12-month group (hazard ratio, 3.16; 95% confidence interval, 1.42–7.03;
P
=0.005) among diabetic patients.

Conclusions—
Six-month DAPT did not increase the risk of target vessel failure at 12 months after implantation of drug-eluting stents compared with 12-month DAPT. However, the noninferiority margin was wide, and the study was underpowered for death or myocardial infarction. Our results need to be confirmed in larger trials.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00698607.
Collagenase Total Occlusion-1 (CTO-1) Trial
Authors: Strauss Bradley H. , Osherov Azriel B. , Radhakrishnan Sam , Mancini G.B. John , Manners Allison , Sparkes John D. , Chisholm Robert J. 
Published: December 2011

Background—
Percutaneous interventions for chronic total occlusions have low success rates, primarily because of failure of guide wire crossing. Collagen-rich matrix constitutes the main barrier to chronic total occlusion crossing. In preclinical studies, local delivery of a bacterial collagenase formulation improved guide wire crossing. The Collagenase Total Occlusion-1 (CTO-1) Trial is a phase I, dose-escalation trial to assess the safety and efficacy of collagenase therapy to facilitate guide wire crossing in coronary artery chronic occlusions.

Methods and Results—

Twenty subjects with ≥1 previous failure of chronic total occlusion guide wire crossing were enrolled at 2 sites. Subjects were treated in 4 distinct cohorts of 5 patients, with escalation of collagenase dose in each cohort from 300 to 1200 μg. Collagenase was locally delivered into the occlusions with either an over-the-wire balloon system (n=8) or a fine-cross microcatheter (n=12) for a period of 30 minutes. Subjects were brought back to the catheterization laboratory for guide wire crossing and angioplasty the next day. Guide wire crossing was successfully achieved in 15 subjects (75%). A soft-tip guide wire (Whisper, Pilot-50, Fielder XT) was either the sole or predominant guide wire used in 75% of successful crossings. Non–ST-segment–elevation myocardial infarctions occurred in 3 patients as a result of side-branch ischemia during stenting. Computed tomographic angiography at 3 months showed no late complications and patent stents in successfully treated chronic total occlusion. Anginal improvement occurred with a reduction in Canadian Cardiovascular Society class from baseline to 3 months (2.5±0.6 versus 0.9±0.9;
P
<0.001).

Conclusion—
Local delivery of collagenase into coronary chronic total occlusion is feasible and safe with encouraging guide wire crossing results in previously failed cases. Larger clinical trials are required to determine efficacy.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01271335.
Evaluation of Multiple Biomarkers of Cardiovascular Stress for Risk Prediction and Guiding Medical Therapy in Patients With Stable Coronary Disease
Authors: Sabatine Marc S. , Morrow David A. , de Lemos James A. , Omland Torbjorn , Sloan Sarah , Jarolim Petr , Solomon Scott D. , Pfeffer Marc A. , Braunwald Eugene 
Published: December 2011

Background—
Circulating biomarkers can offer insight into subclinical cardiovascular stress and thus have the potential to aid in risk stratification and tailoring of therapy.

Methods and Results—

We measured plasma levels of 4 cardiovascular biomarkers, midregional pro-atrial natriuretic peptide (MR-proANP), midregional pro-adrenomedullin (MR-proADM), C-terminal pro-endothelin-1 (CT-proET-1), and copeptin, in 3717 patients with stable coronary artery disease and preserved left ventricular ejection fraction who were randomized to trandolapril or placebo as part of the Prevention of Events With Angiotensin Converting Enzyme (PEACE) trial. After adjustment for clinical cardiovascular risk predictors and left ventricular ejection fraction, elevated levels of MR-proANP, MR-proADM, and CT-proET-1 were independently associated with the risk of cardiovascular death or heart failure (hazard ratios per 1-SD increase in log-transformed biomarker levels of 1.97, 1.48, and 1.47, respectively;
P
≤0.002 for each biomarker). These 3 biomarkers also significantly improved metrics of discrimination when added to a clinical model. Trandolapril significantly reduced the risk of cardiovascular death or heart failure in patients who had elevated levels of ≥2 biomarkers (hazard ratio, 0.53; 95% confidence interval, 0.36–0.80), whereas there was no benefit in patients with elevated levels of 0 or 1 biomarker (hazard ratio, 1.09; 95% confidence interval, 0.74–1.59;
P
interaction
=0.012).

Conclusions—
In patients with stable coronary artery disease and preserved left ventricular ejection fraction, our results suggest that elevated levels of novel biomarkers of cardiovascular stress may help identify patients who are at higher risk of cardiovascular death and heart failure and may be useful to select patients who derive significant benefit from angiotensin-converting enzyme inhibitor therapy.
Assisted Breathing
Authors: Graham Amanda Jane 
Published: December 2011

The Colombian artist Oscar Muñoz’s Aliento (Breath)—10 steel discs, photoserigraph with grease—is an experiment with materials. On the surface it is minimalist—art about the surface of art, the stuff art is made of. Yet Muñoz’s surfaces are deceiving, for his images become clear only when viewers breathe on them. With a breath, sepia photographs of desaparecidos—young Colombian men proclaimed “disappeared” by their government—appear and momentarily return viewers’ gaze. As the condensation fades on the mirror-like metal, so do the images. Here the aesthetic disappearance parallels the corporeal-political one. For a moment, viewers recognize the “Other” in their own reflections and in so doing begin to comprehend how Muñoz’s piece forces the repetition of the moment of encounter and in the process uncovers hidden truths. La obra Aliento del artista colombiano Oscar Muñoz (10 discos de metal, fotoserigrafía con grasa) es un experimento con materiales. Superficialmente se trata de un trabajo minimalista—arte que habla sobre las superficies del arte y los materiales que la componen. Pero las superficies de Muñoz son engañosas, ya que las imágenes sólo aparecen debidamente cuando el espectador respira sobre ellas. Un aliento revela momentáneamente fotografías en sepia de jóvenes colombianos declarados desaparecidos por su gobierno. Conforme la condensación se esfuma del metal especular, las imágenes también se desvanecen y la desaparición estética hace eco al desvanecimiento corpóreo y político. Por un instante, el espectador reconoce al “Otro” en su propio reflejo y comienza así a entender las maneras en las que la obra de Muñoz obliga a repetir el momento del encuentro, develando en el proceso verdades ocultas.
Comparison of postdischarge physiotherapy versus usual care following primary total knee arthroplasty for osteoarthritis: an exploratory pilot randomized clinical trial
Authors: Lowe Catherine J Minns , Barker Karen L , Holder Roger , Sackley Catherine M 
Published: December 2011

Objective: To evaluate a pilot trial of a postdischarge physiotherapy intervention to improve patient function versus usual physiotherapy in patients undergoing total knee arthroplasty aiming to assess: recruitment rate, feasibility and acceptability of the intervention and control, suitability of outcomes, retention and adverse events and to inform sample size calculation for a definitive trial. Design: Exploratory pilot randomized controlled trial using independent assessment. Setting: Mixed urban and rural, UK. Participants: Patients undergoing primary, elective unilateral knee arthroplasty for osteoarthritis. Intervention: Two additional home physiotherapy visits of functional weight-bearing exercises, functional task-specific training versus treatment as usual. Main outcome: Oxford Knee Score at 12 months. Secondary outcomes: completion rates, adverse events, Knee Injury and Osteoarthritis Outcome Score, leg extensor power, timed 10-m walk, timed sit-to-stand, resource use diaries. Assessments completed at baseline (pre-operatively), 3, 6 and 12 months. Results: Of 181 eligible participants 107 (59.1%) were randomized over 13 months, one participant withdrew, no adverse events. Intervention group n = 56 (mean age 67.8), control group n = 51 (mean age 70.8). The difference in mean change of Oxford Knee Scores between groups (intervention – control) at 12 months was 0.2 (95% confidence interval (CI) –3.8, 4.2), P = 0.94. Patient diaries revealed non-trial additional physiotherapy requires improved measurement. Conclusions: Successful recruitment and retention rates were achieved. The intervention appeared feasible and acceptable but may be suboptimal in intensity given recent research. A sample size of 1271 participants would be required for a fully powered randomized controlled trial using the main outcome. However new outcomes, potentially of greater validity and responsiveness, require consideration.
The DRESS trial: a feasibility randomized controlled trial of a neuropsychological approach to dressing therapy for stroke inpatients
Authors: Walker Marion F , Sunderland Alan , Fletcher-Smith Joanna , Drummond Avril , Logan Pip , Edmans Judi A , Garvey Katherine , Dineen Robert A , Ince Paul , Horne Jane , Fisher Rebecca J , Taylor Jenny L 
Published: December 2011

Objective: To investigate two approaches to treating patients with persistent dressing problems and cognitive difficulties following stroke. Design: Pilot randomized controlled trial. Setting: Inpatient stroke rehabilitation service. Subjects: Seventy consecutive stroke patients with persistent dressing problems and accompanying cognitive difficulties at two weeks after their stroke. Interventions: Patients were randomly allocated to six weeks of either a systematic neuropsychological approach, based on analysis of dressing problems and further cognitive testing, or to the control group who received conventional (functional) dressing practice. Both groups received treatment three times a week in accordance with two separately prepared manuals. Main measures: Nottingham Stroke Dressing Assessment (NSDA), Line Cancellation, 10-hole peg transfer test, Object Decision, Gesture Imitation. Patients were assessed at six weeks after randomization by an independent assessor masked to group allocation. Results: Both neuropsychological and functional groups improved performance on the NSDA over the treatment period (31% and 22%, respectively) but there was no significant difference between groups at six weeks. However, the neuropsychological group showed a significantly greater improvement on a line cancellation test of visual neglect ( t(62) = 2.1, P < 0.05) and a planned subanalysis for those with right hemisphere damage showed a trend towards better dressing outcome ( P = 0.07, one-tailed). Conclusions: Results demonstrate the potential benefits of a systematic neuropsychological approach to dressing therapy, particularly for patients with right hemisphere damage. This study suggests the need for a phase III study evaluating the efficacy of a systematic neuropsychological approach in treating dressing difficulties, targeting patients with right hemisphere stroke and visuospatial impairments.