bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selective BCL-2 Inhibition by ABT-199 Causes On-Target Cell Death in Acute Myeloid Leukemia
Authors: Pan Rongqing , Hogdal Leah J. , Benito Juliana M. , Bucci Donna , Han Lina , Borthakur Gautam , Cortes Jorge , DeAngelo Daniel J. , Debose LaKeisha , Mu Hong , Döhner Hartmut , Gaidzik Verena I. , Galinsky Ilene , Golfman Leonard S. , Haferlach Torsten , Harutyunyan Karine G. , Hu Jianhua , Leverson Joel D. , Marcucci Guido , Müschen Markus , Newman Rachel , Park Eugene , Ruvolo Peter P. , Ruvolo Vivian , Ryan Jeremy , Schindela Sonja , Zweidler-McKay Patrick , Stone Richard M. , Kantarjian Hagop , Andreeff Michael , Konopleva Marina , Letai Anthony G. 
Published: December 2013

Abstract
B-cell leukemia/lymphoma 2 (BCL-2) prevents commitment to programmed cell death at the mitochondrion. It remains a challenge to identify those tumors that are best treated by inhibition of BCL-2. Here, we demonstrate that acute myeloid leukemia (AML) cell lines, primary patient samples, and murine primary xenografts are very sensitive to treatment with the selective BCL-2 antagonist ABT-199. In primary patient cells, the median IC50 was approximately 10 nmol/L, and cell death occurred within 2 hours. Our ex vivo sensitivity results compare favorably with those observed for chronic lymphocytic leukemia, a disease for which ABT-199 has demonstrated consistent activity in clinical trials. Moreover, mitochondrial studies using BH3 profiling demonstrate activity at the mitochondrion that correlates well with cytotoxicity, supporting an on-target mitochondrial mechanism of action. Our protein and BH3 profiling studies provide promising tools that can be tested as predictive biomarkers in any clinical trial of ABT-199 in AML.
Significance: Although targeting BCL-2 has largely been investigated in lymphoid cancers, we present preclinical results of targeting BCL-2 in AML. These results support clinical testing of the small-molecule BCL-2 antagonist ABT-199 in AML, accompanied by testing of predictive biomarkers used in this study. Cancer Discov; 4(3); 362–75. ©2013 AACR.
See related commentary by Hockenbery, p. 278
This article is highlighted in the In This Issue feature, p. 259
Changes in Geographic Variation in the Use of Percutaneous Coronary Intervention for Stable Ischemic Heart Disease After Publication of the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) Trial
Authors: Mohan Arun V. , Fazel Reza , Huang Pei-Hsiu , Shen Yu-Chu , Howard David 
Published: December 2013

Background—
Clinical uncertainty is cited as a cause of geographic variation. However, little is known about the effect of comparative effectiveness research on variation. We examined whether geographic variation in the use of percutaneous coronary intervention (PCI) for stable ischemic heart disease (SIHD) declined after publication of the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial.

Methods and Results—

We examined changes in utilization and geographic variation in 67 hospital referral regions using the State Inpatient Databases. We compared age- and sex-adjusted rates of PCI for SIHD before (2006) and after (2008) publication of the COURAGE trial and compared those with contemporaneous changes in PCI volume for acute coronary syndrome. A total of 272 659 PCIs for SIHD from 526 hospitals were included in the analysis. After the publication of the COURAGE trial, PCI volume for SIHD declined by 25% (
P
<0.001) and decreased by 12% for acute coronary syndrome (
P
<0.001). This was predominantly attributable to changes in hospital referral regions with the highest levels of utilization pre-COURAGE trial (35% decline in the highest tertile versus 18% in the lowest). As measured by the systematic component of variation, there was substantial geographic variation in the use of PCI for SIHD preceding the publication of the COURAGE trial. Variation declined by 28% (0.53 versus 0.40) after publication, but geographic variation remained higher for SIHD than acute coronary syndrome (0.40 versus 0.17).

Conclusions—
There was a substantial decline in the use of and geographic variation in PCI for SIHD after the publication of the COURAGE trial. However, geographic variation in the use of PCI for SIHD remained high.
Cortical Photothrombotic Infarcts Impair the Recall of Previously Acquired Memories but Spare the Formation of New Ones
Authors: Diederich Kai , Schmidt Antje , Strecker Jan-Kolja , Schäbitz Wolf-Rüdiger , Schilling Matthias , Minnerup Jens 
Published: December 2013

Background and Purpose—
Despite a high incidence of poststroke dementia, there is no specific treatment for this condition. Because the evaluation of poststroke cognitive deficits in animal models of stroke is exceedingly challenging, the preclinical evaluation of candidate drugs is limited. We aimed to explore the impact of small cortical photothrombotic strokes on poststroke cognition, thereby assessing the suitability of this experimental stroke model for the investigation of cognitive impairment after stroke.

Methods—
Photothrombotic cortical infarcts were induced in 19 adult male Wistar rats. Nineteen sham-operated animals served as controls. Using the Morris water maze, we analyzed the impact of photothrombotic stroke on both the acquisition of new memories and the recall of previously acquired memories. The cylinder test, the adhesive tape removal test, and the rotarod test were performed to investigate sensorimotor deficits.

Results—

Photothrombotic stroke significantly impaired the recall of previously acquired memories (
P
<0.05), whereas the acquisition of new memories remained largely intact. The analysis of the animals’ swimming speed in the water maze and the rotarod test showed no confounding motor impairments after photothrombotic stroke. The adhesive tape removal test and the cylinder test revealed mild sensorimotor deficits in lesioned animals (
P
<0.05).

Conclusions—
Photothrombotic cortical infarcts impair the recall of memories acquired before stroke, whereas the formation of new memories remains unimpaired. The observed deficits in the water maze are not confounded by disturbed motor functions. Overall, experimental photothrombotic strokes are well suited for the investigation of specific cognitive impairments after stroke.
Multiyear Volume, Liquid Freshwater, and Sea Ice Transports through Davis Strait, 2004–10*
Authors: Curry B. , Lee C. M. , Petrie B. , Moritz R. E. , Kwok R. 
Published: December 2013

Abstract
Davis Strait is a primary gateway for freshwater exchange between the Arctic and North Atlantic Oceans including freshwater contributions from west Greenland and Canadian Arctic Archipelago glacial melt. Data from six years (2004–10) of continuous measurements collected by a full-strait moored array and concurrent high-resolution Seaglider surveys are used to estimate volume and liquid freshwater transports through Davis Strait, with respective annual averages of −1.6 ± 0.5 Sverdrups (Sv; 1 Sv ≡ 106 m3 s−1) and −93 ± 6 mSv (negative sign indicates southward transport). Sea ice export contributes an additional −10 ± 1 mSv of freshwater transport, estimated using satellite ice area transport and moored upward-looking sonar ice thickness measurements. Interannual and annual variability of the net transports are large, with average annual volume and liquid freshwater transport standard deviations of 0.7 Sv and 17 mSv and with interannual standard deviations of 0.3 Sv and 15 mSv. Moreover, there are no clear trends in the net transports over the 6-yr period. However, salinity in the upper 250 m between Baffin Island and midstrait decreases starting in September 2009 and remains below average through August 2010, but appears to return to normal by the end of 2010. This freshening event, likely caused by changes in arctic freshwater storage, is not apparent in the liquid freshwater transport time series due to a reduction in southward volume transport in 2009–10. Reanalysis of Davis Strait mooring data from the period 1987–90, compared to the 2004–10 measurements, reveals less arctic outflow and warmer, more saline North Atlantic inflow during the most recent period.
Positive Display Polarity Is Particularly Advantageous for Small Character Sizes
Authors: Piepenbrock Cosima , Mayr Susanne , Buchner Axel 
Published: December 2013

Objective: To test the display luminance hypothesis of the positive polarity advantage and gain insights for display design, the joint effects of display polarity and character size were assessed with a proofreading task. Background: Studies have shown that dark characters on light background (positive polarity) lead to better legibility than do light characters on dark background (negative polarity), presumably due to the typically higher display luminance of positive polarity presentations. Method: Participants performed a proofreading task with black text on white background or white text on black background. Texts were presented in four character sizes (8, 10, 12, and 14 pt; corresponding to 0.22°, 0.25°, 0.31°, and 0.34° of vertical visual angle). Results: A positive polarity advantage was observed in proofreading performance. Importantly, the positive polarity advantage linearly increased with decreasing character size. Conclusion: The findings are in line with the assumption that the typically higher luminance of positive polarity displays leads to an improved perception of detail. Application: The implications seem important for the design of text on such displays as those of computers, automotive control and entertainment systems, and smartphones that are increasingly used for the consumption of text-based media and communication. The sizes of these displays are limited, and it is tempting to use small font sizes to convey as much information as possible. Especially with small font sizes, negative polarity displays should be avoided.
Impact of beta-blockade premedication on image quality of ECG-gated thoracic aorta CT angiography
Authors: Entezari Pegah , Collins Jeremy , Chalian Hamid , Tore Huseyin Gurkan , Carr James , Yaghmai Vahid 
Published: December 2013

Background Thoracic aortic aneurysm is one of the most common aorta pathologies worldwide, which is commonly evaluated by computed tomography angiography (CTA). One of the routine methods to improve the image quality of CTA is heart rate reduction prior to study by beta-blockade administration. Purpose To assess the effect of beta-blockade on image quality of the ascending aorta in electrocardiography (ECG)-gated dual-source CTA (DSCTA) images. Material and Methods In this retrospective study, ECG-gated thoracic aorta CTA images of 40 patients without beta-blocker administration were compared with ECG-gated images of 40 patients with beta-blockade. Images of the aorta were analyzed objectively and subjectively at three levels: sinus of Valsalva (sinus), sinotubular junction (STJ), and mid ascending aorta (MAA). Quantitative sharpness index (SI) and signal-to-noise ratio (SNR) were calculated and two radiologists evaluated the image quality using a 3-point scale. Results Mean heart rate in beta-blocker and non-beta-blocker groups was 61.7 beats per minute (bpm) (range, 58.1–63.9 bpm) and 72.9 bpm (range, 69.3–84.1 bpm), respectively ( P <0.05). Aorta wall SI, SNR, and subjective grading were comparable between the two groups at all three levels ( P >0.05). Conclusion Beta-blocker premedication may not be necessary for imaging of ascending aorta with ECG-gated DSCTA.
Changes in matrix metalloproteinase-9 levels during progression of atrial fibrillation
Authors: Li Mingjiang , Yang Guokang , Xie Bin , Babu Kamesh , Huang Congxin 
Published: December 2013

Objectives: To observe levels of matrix metalloproteinase (MMP)-9 and evaluate their significance in various stages of idiopathic atrial fibrillation (AF). Methods: Patients with idiopathic AF were recruited into this prospective study and classified into one of three groups according to stage of disease progression: paroxysmal AF; persistent AF; permanent AF. Healthy individuals were enrolled as control subjects. Serum levels of MMP-9 in all four groups were determined using a double-antibody sandwich enzyme-linked immunosorbent assay. Results: Each AF group included 25 patients; 40 healthy individuals were included as controls. MMP-9 levels in the three AF groups were significantly higher than in the control group: 168.72 ± 25.970, 201.36 ± 31.26 and 253.20 ± 22.99 ng/ml for the paroxysmal, persistent and permanent AF groups respectively, versus 76.80 ± 14.90 ng/ml for the control group. MMP-9 levels increased with idiopathic AF disease progression ( P < 0.05). Conclusions: An elevated MMP-9 level appears to be associated with a diagnosis of AF. MMP-9 levels appear to increase in relation to the stage of idiopathic AF progression.
Mental health among left-behind preschool-aged children: Preliminary survey of its status and associated risk factors in rural China
Authors: Tao Xu-Wei , Guan Hong-Yan , Zhao Ya-Ru , Fan Zhao-Yang 
Published: December 2013

Objective A large proportion of preschoolers have been left behind due to parental migration in rural China. We conducted a preliminary cross-sectional survey to investigate the mental health of these left-behind preschool-aged children (LBPC) and associated risk factors. Methods A total of 750 LBPC, comprising 217 and 433 children left behind as a result of migration of either or both parents, respectively, and 100 controls were enrolled from two counties in Anhui province, China. Their caregivers completed questionnaires on demographics, the Family Support Scale, the Parenting Self-efficacy Scale and the Preschool-aged Child Mental Health Scale. Results There were no significant differences in mental outcomes among the three groups. However, male LBPC who were younger, fostered by caregivers with lower levels of life satisfaction and parenting efficacy, and came from poorer families with less social support, experienced more mental health problems than other children. Conclusions LBPC did not have worse mental well-being than their control counterparts, but some subpopulations were at potential risk of mental health problems compared with other LBPC. More research on other underlying factors and strategies to prevent the development of psychopathology is urgently needed.
A Survey of Community Pharmacists and Final-Year Student Pharmacists and their Perception of Psychotherapeutic Agents
Authors: McKee Brian D. , Larose-Pierre Margareth , Rappa Leonard R. 
Published: December 2013

Introduction: The World Health Organization has estimated that as many as 450 million people worldwide have mental disorders. More than 44 million people in the United States have a mental disorder annually, estimating the annual direct costs of mental illness to exceed US$69 billion. Psychotherapeutic agents are used to treat mental illnesses and improve quality of life. The purpose of the study is to assess the knowledge and knowledge perception of community pharmacists and final-year student pharmacists regarding psychotherapeutic agents dispensed to their community of patients with mental illness. Methods: A survey was distributed to pharmacists and final-year student pharmacists regarding psychotherapeutic agents. Results: In all, 100 pharmacists and 40 final-year student pharmacists completed the survey. Upon analysis of surveys returned by pharmacists, knowledge deficiency was assessed regarding anxiolytics and mood stabilizers. The analysis of student participant surveys demonstrated knowledge deficiency regarding antidepressants and anxiolytics. Conclusions: Final-year student pharmacists would benefit from the curricular incorporation of courses and advanced pharmacy practice experiences in Psychiatry. Community pharmacists caring for customers with psychiatric disorders should take advantage of continuing education series that highlight updates and new developments regarding psychotherapeutic agents in order to improve clinical outcomes of patients.
Short-term Results of Total Ankle Arthroplasty for End-stage Ankle Arthritis With Severe Varus Deformity
Authors: Sung Ki-Sun , Ahn Jungtae , Lee Keun-Ho , Chun Tae-Hwan 
Published: December 2013

Background: Many authors have reported that an ankle varus deformity more than 10 to 15 degrees may be the cause of failures in total ankle arthroplasty. Our study aim was to analyze short-term outcomes of total ankle arthroplasty with additional procedures accompanied by more than 20 degrees of varus deformity. Methods: Among the patients who received total ankle arthroplasty for end-stage osteoarthritis between June 2006 and May 2012, 103 cases that were followed for more than 6 months were reviewed. Depending on the degree of varus deformity, 24 cases with more than 20 degrees of coronal deformity were allocated into group A, and 79 cases with less than 20 degrees were allocated into group B. Soft tissue balancing, bony realignment osteotomy, and subtalar arthrodesis were also performed intraoperatively. The American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scale, visual analogue scale (VAS) for pain, and ankle range of motion (ROM) were analyzed preoperatively and postoperatively. Subjective satisfaction of the patients (excellent, good, fair, or poor) and complications (major or minor) were identified. Results: The average AOFAS and VAS scores significantly improved in both groups ( P < .001), but there was no significant difference between the groups. Patients’ subjective satisfaction levels also improved in both groups. Conclusion: Short-term follow-up of total ankle arthroplasty, according to the degree of varus deformity, revealed clinically satisfactory progress in both groups without significant differences. There were no significant differences between the 2 groups in postoperative complications and early implant failures. Level of Evidence: Level III, comparative series.
Causes of successful medico-legal claims following amputation
Authors: Toolan Caroline C , Cartwright-Terry Matthew , Scurr James RH , Smout Jonathan D 
Published: December 2013

Introduction The causes of successful medico-legal claims following amputation were reviewed. Methods A retrospective analysis of claims handled by the National Health Service Litigation Authority, from 2005 to August 2010, was performed. Under the Freedom of Information Act, the National Health Service Litigation Authority provided limited details on closed claims, settled with damages, following a search of their database with the term “amputation.” No demographic data were provided. Results During this period, 174 claims were settled by the National Health Service Litigation Authority, who paid out more than £36.3 million. The causes of the claims were the need for a lower limb amputation due to a delay in the diagnosis and or treatment of arterial ischaemia (56), an iatrogenic injury (15), the development of preventable pressure sores (15), the delay and or failure to diagnose a limb malignancy (6) and the delay in the management of an infected pseudo-aneurysm (1). Complications following orthopaedic surgery resulted in 25 successful claims as did the delayed diagnosis or mismanagement of 10 lower limb fractures. Additional claims followed the amputation of the wrong toe (1), a retained foreign body (2), an unnecessary amputation (4), inadequate consent (4), failure to provide thrombo-prophylaxis following amputation resulting in death (2) and a diathermy burn injury during an amputation (1). Delay in the diagnosis of and/or failure to manage an injury or infection resulted in 21 upper limb amputations. There was insufficient information provided in the remaining 11 claims to determine how the claim related to an amputation procedure. The largest single payout for damages (£1.9 million) resulted from the failure to diagnose and treat a femoral artery injury following a road traffic accident leading to an eventual below knee amputation. Conclusion Delays in the diagnosis and or treatment of arterial ischaemia were the commonest reasons for a settled claim. Lessons can be learnt from potentially preventable cases that can be incorporated in medical education and training programs with the aim of reducing both amputation rates and litigation costs.
Central and statistical data monitoring in the Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage (CRASH-2) trial
Authors: Edwards Phil , Shakur Haleema , Barnetson Lin , Prieto David , Evans Stephen , Roberts Ian 
Published: December 2013

Background The purpose of monitoring in clinical trials is to ensure the rights, safety, and well-being of trial patients and the accuracy of the trial data. In the Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage (CRASH-2) trial, which recruited over 20,000 adult trauma patients worldwide, the nature and extent of monitoring was based on a risk assessment undertaken before recruitment started. Purpose We report the methods used for central and statistical monitoring in the CRASH-2 trial and explain how central monitoring was used to target on-site investigations. Methods To ensure that trial participants met the inclusion criteria, we monitored event rates for the primary (death) and secondary outcomes (blood transfusion given). We monitored four quantitative variables (systolic blood pressure (SBP), heart rate (HR), respiratory rate, and capillary refill time) as indicators of the severity of bleeding. We used the coefficient of variation (CV) to identify sites with too much or too little variability. To ensure the accuracy of the data on side effects, we monitored thromboembolic events at each site. Sites with higher or lower than expected event rates were identified for further evaluation. Results A total of 274 sites recruited patients: 145 sites recruited ≥20; patients, and 52 sites recruited ≥100 patients. Sites with low case fatality and low blood transfusion rates were found to be including patients with relatively mild haemorrhage. One site with a high rate of thromboembolic events was found to be using clinical judgement alone. Measurements of SBP and HR varied by about one-fifth of their average value, and capillary refill time measurements varied by around one-third of their average; between-site variation was lowest for blood pressure. Limitations A comparison of mean and median CV indicated that the distributions are slightly skewed to the right. Our simple approach to calculating 95% confidence intervals for the CV may be improved by using a logarithmic transformation of CV for each variable. Conclusions Central and statistical monitoring of data can be used to monitor clinical trials, particularly large, pragmatic, international trials where 100% on-site monitoring is neither necessary nor cost-effective. In the CRASH-2 trial, re-education about trial protocol and the development of guidance helped resolve the issues identified during monitoring.
Eltrombopag restores trilineage hematopoiesis in refractory severe aplastic anemia that can be sustained on discontinuation of drug
Authors: Desmond Ronan , Townsley Danielle M. , Dumitriu Bogdan , Olnes Matthew J. , Scheinberg Phillip , Bevans Margaret , Parikh Ankur R. , Broder Kinneret , Calvo Katherine R. , Wu Colin O. , Young Neal S. , Dunbar Cynthia E. 
Published: December 2013

Key Points
Eltrombopag promotes hematopoiesis in patients with severe aplastic anemia by stimulating stem and progenitor cells. Eltrombopag can be discontinued safely in robust responders with maintenance of hematopoiesis.