bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Growing Arsenal of ATP-Competitive and Allosteric Inhibitors of BCR–ABL
Authors: Hantschel Oliver , Grebien Florian , Superti-Furga Giulio 
Published: September 2012

Abstract
The BCR–ABL fusion kinase is the driving mutation of chronic myelogenous leukemias and is also expressed in a subset of acute lymphoblastic leukemias. Recent advances in elucidating the structure, regulation, and signaling of BCR–ABL have led to the identification of allosteric sites that are distant from the ATP-binding pocket and are critical for BCR–ABL–dependent oncogenic transformation. Here, we review the available data regarding the molecular mechanism of action and the specificity of ATP-competitive tyrosine kinase inhibitors targeting BCR–ABL. In addition, we discuss how targeting of allosteric sites could provide new opportunities to inhibit resistant BCR–ABL mutants, either alone or in combination with conventional ATP-competitive inhibitors. Cancer Res; 72(19); 4890–5. ©2012 AACR.
Cytomegalovirus Infection Leads to Pleomorphic Rhabdomyosarcomas in Trp53+/− Mice
Authors: Price Richard L. , Bingmer Katherine , Harkins Lualhati , Iwenofu O. Hans , Kwon Chang-Hyuk , Cook Charles , Pelloski Christopher , Chiocca E. Antonio 
Published: September 2012

Abstract
Cytomegalovirus (CMV) has been detected in several human cancers, but it has not proven to be oncogenic. However, recent studies have suggested mechanisms through which cytomegalovirus may modulate the tumor environment, encouraging its study as a positive modifier of tumorigenesis. In this study, we investigated the effects of cytomegalovirus infection in Trp53 heterozygous mice. Animals were infected with murine cytomegalovirus (MCMV) after birth at 2 days (P2) or 4 weeks of age and then monitored for tumor formation. Mice injected at 2 days of age developed tumors at a high frequency (43%) by 9 months of age. In contrast, only 3% of mock-infected or mice infected at 4 weeks developed tumors. The majority of tumors from P2 MCMV–infected mice were pleomorphic rhabdomyosarcomas (RMS) harboring MCMV DNA, RNA, and protein. An examination of clinical cases revealed that human RMS (embryonal, alveolar, and pleomorphic) harbored human cytomegalovirus IE1 and pp65 protein as well as viral RNA. Taken together, our findings offer support for the hypothesis that cytomegalovirus contributes to the development of pleomorphic RMS in the context of Trp53 mutation, a situation that occurs with high frequency in human RMS. Cancer Res; 72(22); 5669–74. ©2012 AACR.
Myosin Cross-Bridge Dynamics in Patients With Hypertension and Concentric Left Ventricular Remodeling
Authors: Donaldson Cameron , Palmer Bradley M. , Zile Michael , Maughan David W. , Ikonomidis John S. , Granzier Henk , Meyer Markus , VanBuren Peter , LeWinter Martin M. 
Published: September 2012

Background—
Hypertension (HTN) causes concentric left ventricular remodeling, defined as an increased relative wall thickness or overt left ventricular hypertrophy, and associated diastolic dysfunction. HTN and concentric remodeling are also common precursors to heart failure with a preserved ejection fraction. It is not known whether the myofilament contributes to diastolic dysfunction in patients with concentric remodeling.

Methods and Results—

Intraoperative myocardial biopsies were obtained in 15 male patients undergoing coronary bypass grafting, all with normal left ventricular ejection fraction and wall motion. Eight patients had a history of HTN and concentric remodeling. Seven without HTN or remodeling served as controls. Myocardial strips were dissected and demembranated with detergent. Isometric tension was measured and sinusoidal length perturbation analysis performed at sarcomere length 2.2 μm and pCa 8 to 4.5. Sinusoidal analysis provides estimates of cross-bridge dynamics, including rate constants of attachment and detachment and cross-bridge attachment time. The normalized isometric tension–pCa relation was similar in HTN and controls. However, cross-bridge attachment time was significantly prolonged at submaximal [Ca
2+
] (pCa ≥6.5) in HTN patients. Analysis of protein phosphorylation revealed ≈25% reduction in phosphorylation of troponin I in HTN patients (
P
<0.05).

Conclusions—

Compared with controls, patients with HTN and concentric remodeling display prolonged cross-bridge attachment time at submaximal [Ca
2+
] without a change in the tension–pCa relation. Prolonged cross-bridge attachment time implicates altered cross-bridge dynamics as a cause of slowed relaxation in these patients. This finding was associated with reduced phosphorylation of troponin I, suggesting decreased phosphorylation of protein kinase A/G sites as a mechanism.
Pathological Role of Serum- and Glucocorticoid-Regulated Kinase 1 in Adverse Ventricular Remodeling
Authors: Das Saumya , Aiba Takeshi , Rosenberg Michael , Hessler Katherine , Xiao Chunyang , Quintero Pablo A. , Ottaviano Filomena G. , Knight Ashley C. , Graham Evan L. , Boström Pontus , Morissette Michael R. , del Monte Federica , Begley Michael J. , Cantley Lewis C. , Ellinor Patrick T. , Tomaselli Gordon F. , Rosenzweig Anthony 
Published: September 2012

Background—
Heart failure is a growing cause of morbidity and mortality. Cardiac phosphatidylinositol 3-kinase signaling promotes cardiomyocyte survival and function, but it is paradoxically activated in heart failure, suggesting that chronic activation of this pathway may become maladaptive. Here, we investigated the downstream phosphatidylinositol 3-kinase effector, serum- and glucocorticoid-regulated kinase-1 (SGK1), in heart failure and its complications.

Methods and Results—
We found that cardiac SGK1 is activated in human and murine heart failure. We investigated the role of SGK1 in the heart by using cardiac-specific expression of constitutively active or dominant-negative SGK1. Cardiac-specific activation of SGK1 in mice increased mortality, cardiac dysfunction, and ventricular arrhythmias. The proarrhythmic effects of SGK1 were linked to biochemical and functional changes in the cardiac sodium channel and could be reversed by treatment with ranolazine, a blocker of the late sodium current. Conversely, cardiac-specific inhibition of SGK1 protected mice after hemodynamic stress from fibrosis, heart failure, and sodium channel alterations.

Conclusions—
SGK1 appears both necessary and sufficient for key features of adverse ventricular remodeling and may provide a novel therapeutic target in cardiac disease.
A Systematic Review of Simulators in Otolaryngology
Authors: Javia Luv , Deutsch Ellen S. 
Published: September 2012

ObjectiveTo conduct a systematic review of published articles that describe simulators that could be used in otolaryngology for education, skill acquisition, and/or skill improvement.Data SourcesOvid and Embase databases searched July 14, 2011.Review MethodsThree hundred fifty‐three abstracts were independently reviewed by both authors, then 154 eligible articles were reviewed by both authors, and 95 articles were categorized by organ system (eg, otologic); type of simulator (eg, physical, virtual); whether the simulator was a prototype, could be purchased, or was constructed; validation; and level of learning assessment. Discrepancies were resolved by re‐review and discussion.ResultsIn addition to 11 overview articles, 28 articles described 16 otology simulators, most of which are virtual and prototypes. Ninteen articles described 10 sinus/rhinology simulators; most are virtual surgery simulators and prototypes. Eight articles described 8 oral cavity simulators, and 8 articles described neck simulators. Seventeen articles described 13 bronchoscopy simulators; several are full‐body high‐technology manikins adapted from other purposes. Five articles described eclectic simulators, including some for learning nontechnical and teamwork skills. Half of the simulators have been validated. Learning levels were often not assessed or assessment was limited to the learners’ perceptions.ConclusionA wide variety of simulators are available or under development. Lack of unified validation concepts and limited descriptions restricted our ability to assess model characteristics, availability, and validation. Simulators are emerging as powerful tools to facilitate learning; this review may provide a platform for discussion and refinement of the information reported and analyzed in evaluating simulators.
Safety of training and assessment in operating theatres – a systematic review and meta-analysis
Authors: Ahmed K , Ashrafian H , Harling L , Patel VM , Rao C , Darzi A , Hanna GB , Punjabi P , Athanasiou T 
Published: September 2012

Objective: Procedural outcomes can be used to assess the performance of specialists and trainees. This article establishes a systematic evidence base for the safety of training in the operating theatre. It also explores the possibility of using early, intermediate and late procedural outcomes of cardiac surgical operations to evaluate the performance of the clinicians and the healthcare system. Methods: Medline, EMBASE and PsycINFO databases were searched. Comparative studies evaluating quality indicators of cardiac surgical procedures (coronary artery bypass grafting (CABG) and valve surgery) were included. Guidelines from the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) were used. Results: Fourteen studies met the inclusion criteria. For CABG, meta-analysis of outcomes did not show any significant differences between the technical and non-technical skills of trainees versus specialists apart from bypass time (less for specialists) and intensive care unit (ICU) length of stay (less for trainees). Studies reporting outcomes on valve surgery also did not report any statistically significant differences amongst the outcomes. Conclusion: This systematic review did not discern any significant differences between the procedural outcomes of trainees and specialists, which indicates that trainees are safe to operate under senior supervision. In addition, this article recommends that various procedural outcomes can be used to evaluate the performance of clinicians and healthcare systems. Prospective studies need to be performed, taking into account the specific contribution of trainees and specialists during the procedure. This will give a clearer indication of safety and performance of trainees and specialists in the operating theatre.
How important is resilience among family members supporting relatives with traumatic brain injury or spinal cord injury?
Authors: Simpson Grahame , Jones Kate 
Published: September 2012

Objective: To investigate the relationship between resilience and affective state, caregiver burden and caregiving strategies among family members of people with traumatic brain or spinal cord injury. Design: An observational prospective cross-sectional study. Setting: Inpatient and community rehabilitation services. Subjects: Convenience sample of 61 family respondents aged 18 years or older at the time of the study and supporting a relative with severe traumatic brain injury ( n = 30) or spinal cord injury ( n= 31). Main measures: Resilience Scale, Positive And Negative Affect Schedule, Caregiver Burden Scale, Functional Independence Measure, Carer’s Assessment of Managing Index. Results: Correlational analyses found a significant positive association between family resilience scores and positive affect ( rs = 0.67), and a significant negative association with negative affect ( rs = −0.47) and caregiver burden scores ( rs = −0.47). No association was found between family resilience scores and their relative’s severity of functional impairment. Family members with high resilience scores rated four carer strategies as significantly more helpful than family members with low resilience scores. Between-groups analyses (families supporting relative with traumatic brain injury vs. spinal cord injury) found no significant differences in ratings of the perceived helpfulness of carer strategies once Bonferroni correction for multiple tests was applied. Conclusions: Self-rated resilience correlated positively with positive affect, and negatively with negative affect and caregiver burden. These results are consistent with resilience theories which propose that people with high resilience are more likely to display positive adaptation when faced by significant adversity.
Arthroscopic Rotator Cuff Repair Using Modified Mason-Allen Medial Row Stitch
Authors: Rhee Yong Girl , Cho Nam Su , Parke Chong Suck 
Published: September 2012

Background: When using a method of suture bridge technique, there may be a possibility of strangulation of the rotator cuff tendon at the medial row. The style of knots chosen to secure the medial row might conceivably be a factor to reduce this possibility. Purpose: To compare the clinical results and repair integrity of arthroscopic rotator cuff repair between a knotless and a conventional knot-tying suture bridge technique for patients with full-thickness rotator cuff tears and to evaluate retear patterns in the cases with structural failure after arthroscopic repair by magnetic resonance imaging (MRI). Study Design: Cohort study; Level of evidence, 2. Methods: After arthroscopic repair for medium-sized rotator cuff tears, 110 patients available for postoperative MRI evaluation at least 6 months were enrolled in this study. According to the repair technique, 51 shoulders were enrolled in a knotless suture bridge technique group (group A) and 59 shoulders in a conventional knot-tying suture bridge technique group (group B). The mean age at the time of the operation was 61.0 years (range, 44-68 years) in group A and 57.6 years (range, 45-70 years) in group B. The mean follow-up period was 21.2 months (range, 12-34 months) and 22.1 months (range, 13-32 months), respectively. Results: The Constant score of group A increased from the preoperative mean of 65.2 points to 79.1 points at the last follow-up ( P < .001). The corresponding figures for group B improved from 66.6 points to 76.3 points ( P < .001). The preoperative Shoulder Rating Scale of the University of California at Los Angeles (UCLA) score was 21.1 points in group A and 18.3 points in group B. The UCLA score at the last follow-up was 31.0 points in group A and 27.9 points in group B ( P < .001, P < .001). Retear rate was significantly lower in group A (5.9%) than group B (18.6%) ( P < .001). In group B, retear occurred at the musculotendinous junction in 72.7%, but group A had no medial cuff failure. Conclusion: In arthroscopic suture bridge repair of full-thickness rotator cuff tears, clinical results of both a knotless and a conventional knot-tying group showed improvement without significant difference between the 2 groups. However, the knotless group had a significantly lower retear rate compared with the conventional knot-tying group. A knotless suture bridge technique could be a new supplementary repair technique to conventional technique.
Return to Play and Future ACL Injury Risk After ACL Reconstruction in Soccer Athletes From the Multicenter Orthopaedic Outcomes Network (MOON) Group
Authors: Brophy Robert H. , Schmitz Leah , Wright Rick W. , Dunn Warren R. , Parker Richard D. , Andrish Jack T. , McCarty Eric C. , Spindler Kurt P. 
Published: September 2012

Background: There is limited information on outcomes and return to play (RTP) after anterior cruciate ligament reconstruction (ACLR) in soccer athletes. Purpose: The purpose of this study was to (1) test the hypotheses that player sex, side of injury, and graft choice do not influence RTP and (2) define the risk for future ACL injury in soccer players after ACLR. Study Design: Cohort study; Level of evidence, 3. Methods: Soccer players in a prospective cohort were contacted to determine RTP after ACLR. Information regarding if and when they returned to play, their current playing status, the primary reason they stopped playing soccer (if relevant), and incidence of subsequent ACL surgery was recorded. Results: Initially, 72% of 100 soccer athletes (55 male, 45 female) with a mean age of 24.2 years at the time of ACLR returned to soccer. At average follow-up of 7.0 years, 36% were still playing, a significant decrease compared with initial RTP ( P < .0001). Based on multivariate analysis, older athletes ( P = .006) and females ( P = .037) were less likely to return to play. Twelve soccer athletes had undergone further ACL surgery, including 9 on the contralateral knee and 3 on the ipsilateral knee. In a univariate analysis, females were more likely to have future ACL surgery (20% vs 5.5%, P = .03). Soccer athletes who underwent ACLR on their nondominant limb had a higher future rate of contralateral ACLR (16%) than soccer athletes who underwent ACLR on their dominant limb (3.5%) ( P = .03). Conclusion: Younger and male soccer players are more likely to return to play after ACL reconstruction. Return to soccer after ACLR declines over time. ACLR on the nondominant limb potentially places the dominant limb at risk for future ACL injury.
Competing Paradigms of Competition
Authors: Bahçe Serdal , Eres Benan 
Published: September 2012

This study aims at the empirical investigation of the different conceptualizations of competition with the data available for Turkish manufacturing from 1980 to 2001. The analysis specifically takes into account the classical/Marxian view of competition, which rigorously recognizes the dynamic and turbulent nature of capitalist competition and is based on the concept of “regulating capital.” Time series analysis is conducted in order to test for the persistence of profit rate differentials among 3-digit classification of the manufacturing industries. The analysis, by differentiating between the intra- and inter-industry competition, addresses the classical/Marxian emphasis on the inter-industry trends of equalization. For this purpose, industry-based data instead of firm-based data are used. Lastly, the incremental rate of profit as the return to regulating capital is taken as the basis for establishing what is actually equalized in the course of competitive process. The analysis is conducted both for the average and incremental rates of return for a comparative view. The results show that while the average rate of profit shows significant persistence in most of the industries, the incremental rate does not. These results are in accordance with the classical/Marxian long-run center of gravity dynamics. JEL Classifications: B12, B51, D41, D49, L10, L60
Patulin in apple juice and its risk assessments on albino mice
Authors: Al-Hazmi Mansour A 
Published: September 2012

The contamination of apple juice with patulin mycotoxin is a major risk factor in food safety. This study focuses to assess the biochemical and histopathological effects of patulin in apple juice samples collected from different outlets retailing in Jeddah, Kingdom of Saudi Arabia. On the basis of the selected dose level, 152.5 ppb patulin/ml was administered daily orally for up to 6 weeks to male albino mice. The exposure to contaminated samples revealed significant elevation of all the studied blood parameters (alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase activities as well as creatinine, urea and uric acid contents). On the other hand, and with regard to the accumulated neuronal toxicity of the tested dose level, the toxic signs were recorded as significant increase in the aggressive and locomotor behavioral changes. In addition, the brain areas monoamines concentration revealed variable increased changes. The potential maximal changes in norepinephrine, dopamine and serotonin5-hydroxytryptamine levels attained in cortex, hypothalamus, striatum, hippocampus, midbrain and pons and medulla were assessed. Moreover, the histological examination revealed degeneration and necrosis in liver tissues and degenerated glomeruli and hemorrhage between the tubules of the cortical region in kidney tissues. The study declared that patulin-contaminated (152.5 ppb) apple juice exhibited liver, kidney and neurotoxicological effects in 6 weeks orally administered mice.
‘Theory of mind’ III: the unbearable idea of other minds
Authors: Plastow Michael 
Published: September 2012

Objective: In order to give an alternative explanation for the phenomena described by ‘theory of mind’, this topic is approached firstly by an examination of literary productions and then by reference to psychoanalysis. Conclusions: In literature there are many references to the apprehension of the other in terms of a mirror image of the self. The difficulty of grasping the other is described in a passage by the author Ian McEwan as ‘the unbearable idea of other minds’. The notion that this difficulty can in part be overcome through both spoken and written language is also salient in the novels examined here. The concept of an entrapment within one’s image of oneself was elaborated by Freud in his notion of narcissism. Lacan further developed this notion as foundational in one’s relation to the other, but clarified that such mirroring relations to others are always imbued with jealousy and rivalry. Lacan’s notion of “paranoid knowledge”, an imagined knowledge of what the other is thinking, is precisely a ‘theory of mind’ that is able to account for the way one subject attempts, and ultimately fails, to read the mind of another.
An exploration of the ability of routine outcome measurement to represent clinically meaningful information regarding individual consumers
Authors: McKay Rod , Coombs Tim 
Published: September 2012

Objective: Evidence that feedback on outcome measures can improve consumer outcomes is building but clinician engagement remains inconsistent. Clinicians can interpret and utilize familiar measures but have difficulty in relating to routine outcome measures like the Health of the Nation Outcomes Scales (HoNOS). This paper aims to explore and illustrate how these measures can represent clinically meaningful information regarding individual consumers. Method: Exploration of the aspects of individual clinical states and scenarios that can be represented using the HoNOS and Kessler-10 (K-10) will be used to illustrate their utility in clinical practice. Results: Routine outcome measures have the capacity to represent aspects of consumer symptoms, individual functioning and the need for support relevant to clinical care. These measures may be considered using pattern recognition and reflective practice to answer the following questions. Have we adequately assessed the consumer? Is there agreement between the consumer and clinician? Has anything changed? Conclusions: While it may be difficult to relate to the total scores on outcome measures, information from within such measures, individual items and subscales can be presented in a manner that is clinically meaningful. Where clinicians are familiar with the measures, this ability is already being used. The challenge is to make it ‘routine’.