bluuebunny/crossref_metadata_2025_split huggingface dataset:
The relationship of femoral neck shaft angle and adiposity to greater trochanteric pain syndrome in women. A case control morphology and anthropometric study
Authors: Fearon AM , Stephens S , Cook JL , Smith PN , Neeman T , Cormick W , Scarvell JM 
Published: May 2012

ObjectiveTo evaluate if pelvic or hip width predisposed women to developing greater trochanteric pain syndrome (GTPS).DesignProspective case control study.ParticipantsFour groups were included in the study: those gluteal tendon reconstructions (n=31, GTR), those with conservatively managed GTPS (n=29), those with hip osteoarthritis (n=20, OA) and 22 asymptomatic participants (ASC).MethodsAnterior-posterior pelvic x-rays were evaluated for femoral neck shaft angle; acetabular index, and width at the lateral acetabulum, and the superior and lateral aspects of the greater trochanter. Body mass index, and waist, hip and greater trochanter girth were measured. Data were analysed using a one-way analysis of variance (ANOVA; posthoc Scheffe analysis), then multivariate analysis.ResultsThe GTR group had a lower femoral neck shaft angle than the other groups (p=0.007). The OR (95% CI) of having a neck shaft angle of less than 134°, relative to the ASC group: GTR=3.33 (1.26 to 8.85); GTPS=1.4 (0.52 to 3.75); OA=0.85 (0.28 to 2.61). The OR of GTR relative to GTPS was 2.4 (1.01 to 5.6). No group difference was found for acetabular or greater trochanter width. Greater trochanter girth produced the only anthropometric group difference (mean (95% CI) in cm) GTR=103.8 (100.3 to 107.3), GTPS=105.9 (100.2 to 111.6), OA=100.3 (97.7 to 103.9), ASC=99.1 (94.7 to 103.5), (ANOVA: p=0.036). Multivariate analysis confirmed adiposity is associated with GTPS.ConclusionA lower neck shaft angle is a risk factor for, and adiposity is associated with, GTPS in women.
Changes in knee joint biomechanics following balance and technique training and a season of Australian football
Authors: Donnelly Cyril J , Elliott Bruce C , Doyle Tim L A , Finch Caroline F , Dempsey Alasdair R , Lloyd David G 
Published: May 2012

PurposeDetermine if balance and technique training (BTT) implemented adjunct to normal Australian football (AF) training reduces external knee loading during sidestepping. Additionally, the authors determined if an athlete's knee joint kinematics and kinetics change over a season of AF.MethodologyEight amateur-level AF clubs (n=1,001 males) volunteered to participate in either 28 weeks of BTT or a ‘sham’ training (ST) adjunct to their normal preseason and regular training. A subset of 34 athletes (BTT, n=20; ST, n=14) were recruited for biomechanical testing in weeks 1–7 and 18–25 of the 28-week training intervention. During biomechanical testing, participants completed a series running, preplanned (PpSS) and unplanned sidestepping (UnSS) tasks. A linear mixed model (α=0.05) was used to determine if knee kinematics and peak moments during PpSS and UnSS were influenced by BTT and/or a season of AF.ResultsBoth training groups significantly (p=0.025) decreased their peak internal-rotation knee moments during PpSS, and significantly (p=0.022) increased their peak valgus knee moments during UnSS following their respective training interventions.ConclusionsBTT was not effective in changing an athlete's knee joint biomechanics during sidestepping when conducted in ‘real-world’ training environments. Following normal AF training, the players had different changes to their knee joint biomechanics during both preplanned and unplanned sidestepping. When performing an unplanned sidestepping task in the latter half of a playing season, athletes are at an increased risk of ACL injury. The authors therefore recommend both sidestepping tasks are performed during biomechanical testing when assessing the effectiveness of prophylactic training protocols.
Unrecognised ringside concussive injury in amateur boxers
Authors: Moriarity James M , Pietrzak Robert H , Kutcher Jeffrey S , Clausen Margaretha Helen , McAward Kevin , Darby David G 
Published: May 2012

ObjectivesConcussion is common in contact sports such as boxing. Diagnosis of concussion depends on symptom report or recognition of clinical features, and true incidence may be underestimated. Persistent morbidity is a possible risk of repeated or unrecognised concussion. This study aimed to evaluate pre and postbout cognitive performance in motivated amateur boxers in order to detect objective evidence of unrecognised cognitive impairment suggestive of concussive injury.MethodsThe study employed a prospective and observational design. Participants were amateur boxers who won at least one bout in a single elimination competition. Optimal preparticipation performance using a computerised cognitive assessment tool (CCAT, Axon Sports) and no significant deterioration in cognitive performance within 24 h postbout were required to compete. All boxers were screened for clinical evidence of concussion by a ringside physician.ResultsOf approximately 200 competing boxers, 96 were eligible having won at least one of the total 160 bouts. Mean age was 21.3 (SD 1.9) years (range 18.5–29.7). Of these, 17 (10.6%) failed their first postbout CCAT, with 12 (71%) passing a repeat test. Of the five remaining boxers, there were two boxers (1.3% of bouts) not suspected of a concussion after their bouts, who showed evolving slowing in cognitive performance typical of a concussion.ConclusionsCognitive impairment, as detected by subtle deterioration in reaction time measures, can occur in amateur boxers postbout that is not recognised at ringside. Although the vast majority of bouts were conducted safely, unrecognised injury may occur and be detectable using objective computerised cognitive assessment.
Implicit dynamic frames
Authors: Smans Jan , Jacobs Bart , Piessens Frank 
Published: May 2012

An important, challenging problem in the verification of imperative programs with shared, mutable state is the frame problem in the presence of data abstraction. That is, one must be able to specify and verify upper bounds on the set of memory locations a method can read and write without exposing that method's implementation.
Separation logic is now widely considered the most promising solution to this problem. However, unlike conventional verification approaches, separation logic assertions cannot mention heap-dependent expressions from the host programming language, such as method calls familiar to many developers. Moreover, separation logic-based verifiers are often based on symbolic execution. These symbolic execution-based verifiers typically do not support non-separating conjunction, and some of them rely on the developer to explicitly fold and unfold predicate definitions. Furthermore, several researchers have wondered whether it is possible to use verification condition generation and standard first-order provers instead of symbolic execution to automatically verify conformance with a separation logic specification.

In this article, we propose a variant of separation logic called
implicit dynamic frames
that supports heap-dependent expressions inside assertions. Conformance with an implicit dynamic frames specification can be checked by proving the validity of a number of first-order verification conditions. To show that these verification conditions can be discharged automatically by standard first-order provers, we have implemented our approach in a verifier prototype and have used this prototype to verify several challenging examples from related work. Our prototype automatically folds and unfolds predicate definitions, as required, during the proof and can reason about non-separating conjunction which is used in the specifications of some of these examples. Finally, we prove the soundness of the approach.
T-Regulatory Cells: Key Players in Tumor Immune Escape and Angiogenesis
Authors: Facciabene Andrea , Motz Gregory T. , Coukos George 
Published: May 2012

AbstractT-regulatory cells (Tregs) are found infiltrating tumors in a vast array of tumor types, and tumor-infiltrating Tregs are often associated with a poor clinical outcome. Tregs are potent immunosuppressive cells of the immune system that promote progression of cancer through their ability to limit antitumor immunity and promote angiogenesis. Here, we discuss the ways in which Tregs suppress the antitumor immune response and elaborate on our recent discovery that Tregs make significant direct contributions to tumor angiogenesis. Further, we highlight several current therapies aimed at eliminating Tregs in cancer patients. Given the multifaceted role of Tregs in cancer, a greater understanding of their functions will ultimately strengthen future therapies. Cancer Res; 72(9); 2162–71. ©2012 AACR.
Epigenetic Resensitization to Platinum in Ovarian Cancer
Authors: Matei Daniela , Fang Fang , Shen Changyu , Schilder Jeanne , Arnold Alesha , Zeng Yan , Berry William A. , Huang Tim , Nephew Kenneth P. 
Published: May 2012

Abstract
Preclinical studies have shown that hypomethylating agents reverse platinum resistance in ovarian cancer. In this phase II clinical trial, based upon the results of our phase I dose defining study, we tested the clinical and biologic activity of low-dose decitabine administered before carboplatin in platinum-resistant ovarian cancer patients. Among 17 patients with heavily pretreated and platinum-resistant ovarian cancer, the regimen induced a 35% objective response rate (RR) and progression-free survival (PFS) of 10.2 months, with nine patients (53%) free of progression at 6 months. Global and gene-specific DNA demethylation was achieved in peripheral blood mononuclear cells and tumors. The number of demethylated genes was greater (P &lt; 0.05) in tumor biopsies from patients with PFS more than 6 versus less than 6 months (311 vs. 244 genes). Pathways enriched at baseline in tumors from patients with PFS more than 6 months included cytokine–cytokine receptor interactions, drug transporters, and mitogen-activated protein kinase, toll-like receptor and Jak-STAT signaling pathways, whereas those enriched in demethylated genes after decitabine treatment included pathways involved in cancer, Wnt signaling, and apoptosis (P &lt; 0.01). Demethylation of MLH1, RASSF1A, HOXA10, and HOXA11 in tumors positively correlated with PFS (P &lt; 0.05). Together, the results of this study suggest that low-dose decitabine altered DNA methylation of genes and cancer pathways, restoring sensitivity to carboplatin in patients with heavily pretreated ovarian cancer and resulting in a high RR and prolonged PFS. Cancer Res; 72(9); 2197–205. ©2012 AACR.
Crizotinib for ALK-Rearranged Non–Small Cell Lung Cancer: A New Targeted Therapy for a New Target
Authors: Gandhi Leena , Jänne Pasi A. 
Published: May 2012

Abstract
Crizotinib (PF02341066, Xalkori; Pfizer) was recently approved by the U.S. Food and Drug Administration for treatment of ALK-positive non–small cell lung cancer (NSCLC) as defined by a jointly approved diagnostic test using a break-apart fluorescence in situ hybridization assay. The approval was based on dramatic response rates in ALK-positive NSCLC patients of 54% to 61% in phase I and II trials. To date, the overall disease control rates in these trials are close to 90%. Progression-free survival approaches 10 months. This review focuses on the ALK-inhibitory activity of crizotinib in preclinical and clinical trials that led to approval, as well as the diagnostic methods to classify patients with ALK-positive NSCLC. Although these patients represent a small subset of all patients with NSCLC, the rapid time course from identification of this unique target to an approved targeted therapy with striking benefit serves as a paradigm for the development of targeted therapeutics in an era of personalized medicine. Clin Cancer Res; 18(14); 3737–42. ©2012 AACR.
Ribonucleotide Reductase Large Subunit (RRM1) Gene Expression May Predict Efficacy of Adjuvant Mitotane in Adrenocortical Cancer
Authors: Volante Marco , Terzolo Massimo , Fassnacht Martin , Rapa Ida , Germano Antonina , Sbiera Silviu , Daffara Fulvia , Sperone Paola , Scagliotti Giorgio , Allolio Bruno , Papotti Mauro , Berruti Alfredo 
Published: May 2012

Abstract
Purpose: Mitotane is the most broadly used systemic therapy for adrenocortical carcinoma (ACC), but its mechanism of action and possible predictors of treatment response are currently poorly defined. Our aim was to evaluate the gene expression of ribonucleotide reductase large subunit 1 (RRM1) and excision repair cross-complementation group 1 (ERCC1) in ACC as potential biomarkers for clinical outcome and response to mitotane.
Experimental Design: Forty-five and 47 tissue samples from two cohorts (Orbassano, Italy; Wuerzburg, Germany) of completely resected ACC were centrally analyzed using real-time PCR for RRM1 and ERCC1 expression. Fifty-four patients received surgery alone and 38 received adjuvant mitotane after surgery. Clinical and pathologic features were highly comparable in the two series. H295R and SW-13 ACC cell lines were also used for pharmacologic tests.
Results: ERCC1 gene expression was not associated to clinical outcome. In contrast, high RRM1 gene expression was associated to shorter disease-free survival (DFS) and overall survival at both univariate and multivariate analysis. In patients with low RRM1 gene expression, adjuvant mitotane was associated with improved DFS, whereas this effect was lost in cases with high RMM1 expression. In vitro mitotane induced strong up regulation of RRM1 transcription (up to 25-fold increase) in mitotane-insensitive SW-13 but not in mitotane-sensitive H295R cells. Furthermore, RRM1 silencing in SW-13 cells induced sensitivity to mitotane.
Conclusion: Our in vitro and in vivo data indicate that RRM1 gene expression is functionally associated to mitotane sensitivity and support a possible role of RRM1 determination as a novel molecular biomarker predicting response to adjuvant mitotane in ACC. Clin Cancer Res; 18(12); 3452–61. ©2012 AACR.
LY2109761 Attenuates Radiation-Induced Pulmonary Murine Fibrosis via Reversal of TGF-β and BMP-Associated Proinflammatory and Proangiogenic Signals
Authors: Flechsig Paul , Dadrich Monika , Bickelhaupt Sebastian , Jenne Jürgen , Hauser Kai , Timke Carmen , Peschke Peter , Hahn Eric W. , Gröne Hermann-Josef , Yingling Jonathan , Lahn Michael , Wirkner Ute , Huber Peter E. 
Published: May 2012

Abstract
Purpose: Radiotherapy is used for the treatment of lung cancer, but at the same time induces acute pneumonitis and subsequent pulmonary fibrosis, where TGF-β signaling is considered to play an important role.
Experimental Design: We irradiated thoraces of C57BL/6 mice (single dose, 20 Gy) and administered them a novel small-molecule TGF-β receptor I serine/threonine kinase inhibitor (LY2109761) orally for 4 weeks before, during, or after radiation. Noninvasive lung imaging including volume computed tomography (VCT) and MRI was conducted 6, 16, and 20 weeks after irradiation and was correlated to histologic findings. Expression profiling analysis and protein analysis was conducted in human primary fibroblasts.
Results: Radiation alone induced acute pulmonary inflammation and lung fibrosis after 16 weeks associated with reduced life span. VCT, MRI, and histology showed that LY2109761 markedly reduced inflammation and pulmonary fibrosis resulting in prolonged survival. Mechanistically, we found that LY2109761 reduced p-SMAD2 and p-SMAD1 expression, and transcriptomics revealed that LY2109761 suppressed expression of genes involved in canonical and noncanonical TGF-β signaling and downstream signaling of bone morphogenetic proteins (BMP). LY2109761 also suppressed radiation-induced inflammatory [e.g., interleukin (IL)-6, IL-7R, IL-8] and proangiogenic genes (e.g., ID1) indicating that LY2109761 achieves its antifibrotic effect by suppressing radiation-induced proinflammatory, proangiogenic, and profibrotic signals.
Conclusion: Small-molecule inhibitors of the TGF-β receptor I kinase may offer a promising approach to treat or attenuate radiation-induced lung toxicity or other diseases associated with fibrosis. Clin Cancer Res; 18(13); 3616–27. ©2012 AACR.
A Phase I Pharmacokinetic and Pharmacodynamic Study of CHR-3996, an Oral Class I Selective Histone Deacetylase Inhibitor in Refractory Solid Tumors
Authors: Banerji Udai , van Doorn Leni , Papadatos-Pastos Dionysis , Kristeleit Rebecca , Debnam Phillip , Tall Matthew , Stewart Adam , Raynaud Florence , Garrett Michelle Dawn , Toal Martin , Hooftman Leon , De Bono Johann Sebastian , Verweij Jaap , Eskens Ferry ALM 
Published: May 2012

Abstract
Purpose: This clinical trial investigated the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) profile of CHR-3996, a selective class I histone deacetylase inhibitor.
Patients and Methods: CHR-3996 was administered orally once a day. This phase I trial used a 3+3 dose-escalation design. PK profiles were analyzed by liquid chromatography–tandem mass spectroscopic methods and PD studies were conducted using ELISA studying histone H3 acetylation in peripheral blood mononuclear cells.
Results: Thirty-nine patients were treated at dose levels of 5 mg (n = 3), 10 mg (n = 4), 20 mg (n = 3), 40 mg (n = 10), 80 mg (n = 10), 120 mg (n = 4), and 160 mg (n = 5) administered orally once daily. The dose-limiting toxicities seen were thrombocytopenia (160 mg), fatigue (80 and 120 mg), plasma creatinine elevation (80 and 120 mg), and atrial fibrillation (40 mg). The area under the curve was proportional to the administered dose and a maximal plasma concentration of 259 ng/mL at a dose of 40 mg exceeded the concentrations required for antitumor efficacy in preclinical models. Target inhibition measured by quantification of histone acetylation was shown at doses of 10 mg/d and was maximal at 40 mg. A partial response was seen in one patient with metastatic acinar pancreatic carcinoma.
Conclusions: Taking the toxicity and PK/PD profile into consideration, the recommended phase II dose (RP2D) is 40 mg/d. At this dose, CHR-3996 has a favorable toxicologic, PK, and PD profile. CHR-3996 has shown preliminary clinical activity and should be evaluated in further clinical trials. Clin Cancer Res; 18(9); 2687–94. ©2012 AACR.
Acquisition of Resistance of Pancreatic Cancer Cells to 2-Methoxyestradiol Is Associated with the Upregulation of Manganese Superoxide Dismutase
Authors: Zhou Jianhong , Du Yuchun 
Published: May 2012

Abstract
Acquired resistance of cancer cells to anticancer drugs or ionizing radiation (IR) is one of the major obstacles in cancer treatment. Pancreatic cancer is an exceptional aggressive cancer, and acquired drug resistance in this cancer is common. Reactive oxygen species (ROS) play an essential role in cell apoptosis, which is a key mechanism by which radio- or chemotherapy induce cell killing. Mitochondria are the major source of ROS in cells. Thus, alterations in the expression of mitochondrial proteins, involved in ROS production or scavenging, may be closely linked to the resistance of cancer cells to radio- or chemotherapy. In the present study, we generated a stable cell line by exposing pancreatic cancer cells to increasing concentrations of ROS-inducing, anticancer compound 2-methoxyestradiol (2-ME) over a 3-month period. The resulting cell line showed strong resistance to 2-ME and contained an elevated level of ROS. We then used a comparative proteomics method to profile the differential expression of mitochondrial proteins between the parental and the resistant cells. One protein identified to be upregulated in the resistant cells was manganese superoxide dismutase (SOD2), a mitochondrial protein that converts superoxide radicals to hydrogen peroxides. Silencing of SOD2 resensitized the resistant cells to 2-ME, and overexpression of SOD2 led the parental cells to 2-ME resistance. In addition, the 2-ME–resistant cells also showed resistance to IR. Our results suggest that upregulation of SOD2 expression is an important mechanism by which pancreatic cancer cells acquire resistance to ROS-inducing, anticancer drugs, and potentially also to IR. Mol Cancer Res; 10(6); 768–77. ©2012 AACR.
A Detailed Normal-Mode Energetics of the General Circulation of the Atmosphere
Authors: Marques C. A. F. , Castanheira J. M. 
Published: May 2012

Abstract
An energetics formulation is here introduced that enables an explicit evaluation for the conversion rates between available potential energy and kinetic energy, the nonlinear interactions of both energy forms, and their generation and dissipation rates, in both the zonal wavenumber and vertical mode domains. The conversion rates between available potential energy and kinetic energy are further decomposed into the contributions by the rotational (Rossby) and divergent (gravity) components of the circulation field. The computed energy terms allow one to formulate a detailed energy cycle describing the flow of energy among the zonal mean and eddy components, and also among the barotropic and baroclinic components. This new energetics formulation is a development of the 3D normal-mode energetics scheme. The new formulation is applied on an assessment of the energetics of winter (December–February) circulation in the 40-yr ECMWF Re-Analysis (ERA-40), the 25-yr Japan Meteorological Agency Reanalysis (JRA-25), and the NCEP–Department of Energy Reanalysis 2 (NCEP-R2) datasets.
Second Language Listening and Unfamiliar Proper Names: Comprehension Barrier?
Authors: Kobeleva Polina P. 
Published: May 2012

This study examines whether unfamiliar proper names affect English as a second language (ESL) learners’ listening comprehension. A total of 110 intermediate to advanced ESL learners participated; comprehension of a short news text was tested under two conditions, Names Known (all proper names pre-taught in advance) and Names Unknown (all proper names unfamiliar prior to listening). The Names Known group performed significantly better than the Names Unknown group on two measures, true-false-don’t know statements and open-ended questions. The effect of unfamiliar proper names on comprehension remained statistically significant after the listening proficiency variable was controlled. Listeners in the Names Unknown treatment were able to derive 44.8% of information about the referents of proper names from context but they could not identify all the referents successfully. Unfamiliar proper names evidently hinder comprehension, which was also supported by the participants’ task difficulty ratings. When proper names were familiar, participants rated all comprehension tasks as easier to do and self-reported higher comprehension success. In contrast, when proper names were unfamiliar, participants rated all comprehension tasks as harder to do and self-reported a lower amount of comprehension. It has long been established that vocabulary knowledge is a prerequisite to successful comprehension. This study confirms that, similarly to common vocabulary, the presence of unfamiliar proper names decreases the ESL learners’ chances of understanding spoken English. Implications of the findings for second language learning and testing are discussed. It is recommended that teachers be flexible when setting up listening exercises and use different techniques depending on the depth of understanding the learners are supposed to achieve. If the instructional goal is listening for gist, proper names will unlikely affect the outcomes of the activity. However, if detailed and precise understanding is required, then it is unrealistic to expect ESL listeners to cope with unfamiliar proper names ‘on the spot’ without assistance or preparation. It is also advisable to avoid unfamiliar proper names in a testing situation because they may cause unwarranted anxiety and reflect negatively on the ESL listeners’ performance.