bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting a Nation’s Olympic-Qualifying Swimmers
Authors: Allen Sian V. , Vandenbogaerde Tom J. , Pyne David B. , Hopkins Will G. 
Published: October 2014

Talent identification and development typically involve allocation of resources toward athletes selected on the basis of early-career performance.Purpose:To compare 4 methods for early-career selection of Australia’s 2012 Olympic-qualifying swimmers.Methods:Performance times from 5738 Australian swimmers in individual Olympic events at 101 competitions from 2000 to 2012 were analyzed as percentages of world-record times using 4 methods that retrospectively simulated early selection of swimmers into a talent-development squad. For all methods, squad-selection thresholds were set to include 90% of Olympic qualifiers. One method used each swimmer’s given-year performance for selection, while the others predicted each swimmer’s 2012 performance. The predictive methods were regression and neural-network modeling using given-year performance and age and quadratic trajectories derived using mixed modeling of each swimmer’s annual best career performances up to the given year. All methods were applied to swimmers in 2007 and repeated for each subsequent year through 2011.Results:The regression model produced squad sizes of 562, 552, 188, 140, and 93 for the years 2007 through 2011. Corresponding proportions of the squads consisting of Olympic qualifiers were 11%, 11%, 32%, 43%, and 66%. Neural-network modeling produced similar outcomes, but the other methods were less effective. Swimming Australia’s actual squads ranged from 91 to 67 swimmers but included only 50−74% of Olympic qualifiers.Conclusions:Large talent-development squads are required to include most eventual Olympic qualifiers. Criteria additional to age and performance are needed to improve early selection of swimmers to talent-development squads.
What Are Athletes' Perceptions of Rehabilitation Outcome 1 Year After Hip Arthroscopy?
Authors: Carter Danielle Lovett , Kennedy Norelee 
Published: October 2014

Background:Hip arthroscopy is a minimally invasive surgical procedure. Femoroacetabular impingement (FAI) is being increasingly recognized as a cause of hip pain in athletes and is a growing indication for arthroscopic surgery. Few studies have attempted to address patient views on outcome after arthroscopy, and no qualitative studies have been carried out to date.Objectives:To explore athletes' perceptions of rehabilitation outcome, the rehabilitative process, and return to sport and to gain insight into factors that affected this process.Methodology:A retrospective qualitative approach was adopted using semistructured interviews. Eight eligible participants were interviewed. Each had been treated with hip arthroscopy for FAI from September to November 2010. Data were audiotaped, transcribed verbatim, and analyzed using thematic analysis.Results:Three main themes emerged. (1) The ability to participate in sport; athletes were relatively satisfied with outcome despite some limitations in sporting ability. (2) Perceptions of hip problems; there was a lack of understanding and an association of hip problems with older people among the general public. (3) Athletes' perception of rehabilitation; athletes were dissatisfied with the rehabilitation and sought greater physiotherapy input.Conclusions:Overall, athletes were relatively satisfied with their outcome 1 y after hip arthroscopy, despite some having to adapt their sporting activities. Key areas that need to be addressed in future research include factors affecting outcomes of hip arthroscopy, longer-term outcomes, perception of FAI among the public and health practitioners, and the development of a standardized evidence-based rehabilitation protocol.
Pilicide ec240 Disrupts Virulence Circuits in Uropathogenic Escherichia coli
Authors: Greene Sarah E. , Pinkner Jerome S. , Chorell Erik , Dodson Karen W. , Shaffer Carrie L. , Conover Matt S. , Livny Jonathan , Hadjifrangiskou Maria , Almqvist Fredrik , Hultgren Scott J. 
Published: October 2014

ABSTRACT

Chaperone-usher pathway (CUP) pili are extracellular organelles produced by Gram-negative bacteria that mediate bacterial pathogenesis. Small-molecule inhibitors of CUP pili, termed pilicides, were rationally designed and shown to inhibit type 1 or P piliation. Here, we show that pilicide ec240 decreased the levels of type 1, P, and S piliation. Transcriptomic and proteomic analyses using the cystitis isolate UTI89 revealed that ec240 dysregulated CUP pili and decreased motility. Paradoxically, the transcript levels of P and S pilus genes were increased during growth in ec240, even though the level of P and S piliation decreased. In contrast, the most downregulated transcripts after growth in ec240 were from the type 1 pilus genes. Type 1 pilus expression is controlled by inversion of the
fimS
promoter element, which can oscillate between phase on and phase off orientations. ec240 induced the
fimS
phase off orientation, and this effect was necessary for the majority of ec240’s inhibition of type 1 piliation. ec240 increased levels of the transcriptional regulators SfaB and PapB, which were shown to induce the
fimS
promoter phase off orientation. Furthermore, the effect of ec240 on motility was abolished in the absence of the SfaB, PapB, SfaX, and PapX regulators. In contrast to the effects of ec240, deletion of the type 1 pilus operon led to increased S and P piliation and motility. Thus, ec240 dysregulated several uropathogenic
Escherichia coli
(UPEC) virulence factors through different mechanisms and independent of its effects on type 1 pilus biogenesis and may have potential as an antivirulence compound.

IMPORTANCE
CUP pili and flagella play active roles in the pathogenesis of a variety of Gram-negative bacterial infections, including urinary tract infections mediated by UPEC. These are extremely common infections that are often recurrent and increasingly caused by antibiotic-resistant organisms. Preventing piliation and motility through altered regulation and assembly of these important virulence factors could aid in the development of novel therapeutics. This study increases our understanding of the regulation of these virulence factors, providing new avenues by which to target their expression.
How does a combined preoperative and postoperative rehabilitation programme influence the outcome of ACL reconstruction 2 years after surgery? A comparison between patients in the Delaware-Oslo ACL Cohort and the Norwegian National Knee Ligament Registry
Authors: Grindem H , Granan L P , Risberg M A , Engebretsen L , Snyder-Mackler L , Eitzen I 
Published: October 2014

BackgroundPreoperative knee function is associated with successful postoperative outcome after anterior cruciate ligament reconstruction (ACLR). However, there are few longer term studies of patients who underwent progressive preoperative and postoperative rehabilitation compared to usual care.ObjectivesTo compare preoperative and 2 year postoperative patient-reported outcomes (PROs) in patients undergoing progressive preoperative and postoperative rehabilitation at a sports medicine clinic compared with usual care.MethodsWe included patients aged 16–40 years undergoing primary unilateral ACLR. The preoperative and 2 year postoperative Knee Injury and Osteoarthritis Outcome Score (KOOS) of 84 patients undergoing progressive preoperative and postoperative rehabilitation at a sports medicine clinic (Norwegian Research Center for Active Rehabilitation (NAR) cohort) were compared with the scores of 2690 patients from the Norwegian National Knee Ligament Registry (NKLR). The analyses were adjusted for sex, age, months from injury to surgery and cartilage/meniscus injury at ACLR.ResultsThe NAR cohort had significantly better preoperative KOOS in all subscales, with clinically relevant differences (>10 points) observed in KOOS Pain, activities of daily living (ADL), Sports and Quality of Life. At 2 years, the NAR cohort still had significantly better KOOS with clinically relevant differences in KOOS Symptoms, Sports and Quality of Life. At 2 years, 85.7–94% of the patients in the NAR cohort scored within the normative range of the different KOOS subscales, compared to 51.4–75.8% of the patients in the NKLR.ConclusionsPatients in a prospective cohort who underwent progressive preoperative and postoperative rehabilitation at a sports medicine clinic showed superior patient-reported outcomes both preoperatively and 2 years postoperatively compared to patients in the NKLR who received usual care.
Does topical Amethocaine cream increase first-time successful cannulation in children compared with a eutectic mixture of local anaesthetics (EMLA) cream? A systematic review and meta-analysis of randomised controlled trials
Authors: Pywell Alison , Xyrichis Andreas 
Published: October 2014

BackgroundCannulation of children is often required for administration of intravenous fluids and medications, but can cause pain and anxiety. Amethocaine and a eutectic mixture of local anaesthetics (EMLA) cream are two of the most commonly used local anaesthetic creams.ObjectiveTo examine the evidence for the superiority of Amethocaine cream compared with EMLA cream in facilitating successful first-time cannulation in children.MethodA systematic search was undertaken in MEDLINE and EMBASE in June 2014. Studies examining cannulation, undertaken with children and providing data about first-time cannulation success rates were considered for inclusion. Three randomised controlled trials met the inclusion criteria and were included in the meta-analysis. Data extraction was undertaken independently by the two authors using predefined data fields.ResultsPooled analysis was based on a random effects model. Low statistical heterogeneity was observed. Amethocaine cream increased the likelihood of successful first-time cannulation (RR 1.046, CI 0.975 to 1.122), although this did not reach statistical significance (p=0.211).ConclusionsAmethocaine cream does not appear to significantly facilitate successful first-time cannulation. Lack of precision and design weaknesses of the included studies hinder the formation of a strong recommendation for either cream.ImplicationsBased on the evidence reviewed here and considering analgesic properties and cost-savings associated with both creams, a weak recommendation can be issued in favour of Amethocaine cream for cannulation in children based on high-quality evidence but where the treatment choice will depend on other factors including cost and provider preference.
Gamification as a tool for enhancing graduate medical education
Authors: Nevin Christa R , Westfall Andrew O , Rodriguez J Martin , Dempsey Donald M , Cherrington Andrea , Roy Brita , Patel Mukesh , Willig James H 
Published: October 2014

Abstract

Introduction
The last decade has seen many changes in graduate medical education training in the USA, most notably the implementation of duty hour standards for residents by the Accreditation Council of Graduate Medical Education. As educators are left to balance more limited time available between patient care and resident education, new methods to augment traditional graduate medical education are needed.

Objectives
To assess acceptance and use of a novel gamification-based medical knowledge software among internal medicine residents and to determine retention of information presented to participants by this medical knowledge software.

Methods
We designed and developed software using principles of gamification to deliver a web-based medical knowledge competition among internal medicine residents at the University of Alabama (UA) at Birmingham and UA at Huntsville in 2012–2013. Residents participated individually and in teams. Participants accessed daily questions and tracked their online leaderboard competition scores through any internet-enabled device. We completed focus groups to assess participant acceptance and analysed software use, retention of knowledge and factors associated with loss of participants (attrition).

Results
Acceptance: In focus groups, residents (n=17) reported leaderboards were the most important motivator of participation. Use: 16 427 questions were completed: 28.8% on Saturdays/Sundays, 53.1% between 17:00 and 08:00. Retention of knowledge: 1046 paired responses (for repeated questions) were collected. Correct responses increased by 11.9% (p&lt;0.0001) on retest. Differences per time since question introduction, trainee level and style of play were observed. Attrition: In ordinal regression analyses, completing more questions (0.80 per 10% increase; 0.70 to 0.93) decreased, while postgraduate year 3 class (4.25; 1.44 to 12.55) and non-daily play (4.51; 1.50 to 13.58) increased odds of attrition.

Conclusions
Our software-enabled, gamification-based educational intervention was well accepted among our millennial learners. Coupling software with gamification and analysis of trainee use and engagement data can be used to develop strategies to augment learning in time-constrained educational settings.
MAP2K1 (MEK1) Mutations Define a Distinct Subset of Lung Adenocarcinoma Associated with Smoking
Authors: Arcila Maria E. , Drilon Alexander , Sylvester Brooke E. , Lovly Christine M. , Borsu Laetitia , Reva Boris , Kris Mark G. , Solit David B. , Ladanyi Marc 
Published: October 2014

Abstract
Purpose: Genetic alterations affecting the MAPK/ERK pathway are common in lung adenocarcinoma (LAD). Early steps of the signaling pathway are most often affected with EGFR, KRAS, and BRAF mutations encompassing more than 70% of all alterations. Somatic mutations in MEK1, located downstream of BRAF, are rare and remain poorly defined as a distinct molecular subset.
Experimental Design: Tumors harboring MEK1 mutations were identified through targeted screening of a large LAD cohort concurrently interrogated for recurrent mutations in MEK1, EGFR, KRAS, BRAF, ERBB2/HER2, NRAS, PIK3CA, and AKT. Additional cases were identified through a search of publically available cancer genomic datasets. Mutations were correlated with patient characteristics and treatment outcomes. Overall survival was compared with stage-matched patients with KRAS- and EGFR-mutant LADs.
Results: We identified 36 MEK1-mutated cases among 6,024 LAD (0.6%; 95% confidence interval, 0.42–0.85). The majority of patients were smokers (97%, n = 35/36). There was no association with age, sex, race, or stage. The most common mutations were K57N (64%, 23/36) followed by Q56P (19%, 7/36), all mutually exclusive with other driver mutations in the targeted panel. Transversions G:C&gt;T:A were predominant (89%, 31/35), in keeping with smoking-associated DNA damage. Additional less common somatic mutations were identified in the kinase domain, all of which are predicted to converge into a single interaction area based on in silico 3D modeling.
Conclusions: MEK1 mutations define a distinct subset of lung cancers (∼1%) with potential sensitivity to MEK inhibitors. Mutations are predominantly transversions, in keeping with a strong association with smoking. Clin Cancer Res; 21(8); 1935–43. ©2014 AACR.
The NOTCH Ligand JAGGED2 Promotes Pancreatic Cancer Metastasis Independent of NOTCH Signaling Activation
Authors: Hu Yufeng , Su Hexiu , Li Xu , Guo Guoli , Cheng Ling , Qin Renyi , Qing Guoliang , Liu Hudan 
Published: October 2014

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and lethal disease with a high rate of metastasis. Numerous signaling events have been implicated in the molecular pathogenesis of this neoplasm. Aberrantly high expression of JAGGED2, one of the NOTCH ligands, often occurs in human PDAC. However, what role JAGGED2 plays in the disease development and whether JAGGED2 executes its function through activating NOTCH signaling remain to be determined. We report here that JAGGED2 plays a critical role in promoting PDAC metastasis in vitro and in vivo. Depletion of JAGGED2, but not its homolog JAGGED1, profoundly inhibited both migration and invasion without influencing cell proliferation. Furthermore, reconstitution of JAGGED2 expression rescued the migratory defect. Surprisingly, neither pharmacologic nor genetic inhibition of NOTCH downstream signaling resulted in obvious defect in metastasis. Instead, depletion of NOTCH1 expression per se gave rise to migratory defects similar to JAGGED2 ablation. Moreover, blockade of ligand–receptor interaction by a specific JAGGED2-Fc fusion protein dramatically inhibited PDAC cell migration, suggesting that tumor metastasis relies on physical interactions of JAGGED2-NOTCH1 but not Notch downstream signaling activation. Taken together, our data reveal a novel role of NOTCH in regulation of PDAC metastasis, and identify JAGGED2 as a critical mediator in this event. These findings also provide rationale for developing small molecules or biologic agents targeting JAGGED2 for therapeutic intervention. Mol Cancer Ther; 14(1); 289–97. ©2014 AACR.
Anticancer Activity of a Novel Selective CYP17A1 Inhibitor in Preclinical Models of Castrate-Resistant Prostate Cancer
Authors: Toren Paul J. , Kim Soojin , Pham Steven , Mangalji Azzra , Adomat Hans , Guns Emma S. Tomlinson , Zoubeidi Amina , Moore William , Gleave Martin E. 
Published: October 2014

Abstract
VT-464 is a novel, nonsteroidal, small-molecule CYP17A1 inhibitor with 17,20-lyase selectivity. This study evaluates the anticancer activity of VT-464 compared with abiraterone (ABI) in castrate-resistant prostate cancer cell lines and xenograft models that are enzalutamide (ENZ)-responsive (C4-2) or ENZ-resistant (MR49C, MR49F). In vitro, androgen receptor (AR) transactivation was assessed by probasin luciferase reporter, whereas AR and AR-regulated genes and steroidogenic pathway enzymes were assessed by Western blot and/or qRT-PCR. The MR49F xenograft model was used to compare effects of oral VT-464 treatment to vehicle and abiraterone acetate (AA). Steroid concentrations were measured using LC-MS chromatography. VT-464 demonstrated a greater decrease in AR transactivation compared with ABI in C4-2 and both ENZ-resistant cell lines. At the gene and protein level, VT-464 suppressed the AR axis to a greater extent compared with ABI. Gene transcripts StAR, CYP17A1, HSD17B3, and SRD5A1 increased following treatment with ABI and to a greater extent with VT-464. In vivo, intratumoral androgen levels were significantly lower after VT-464 or AA treatment compared with vehicle, with the greatest decrease seen with VT-464. Similarly, tumor growth inhibition and PSA decrease trends were greater with VT-464 than with AA. Finally, an AR-antagonist effect of VT-464 independent of CYP17A1 inhibition was observed using luciferase reporter assays, and a direct interaction was confirmed using an AR ligand binding domain biolayer interferometry. These preclinical results suggest greater suppression of the AR axis with VT-464 than ABI that is likely due to both superior selective suppression of androgen synthesis and AR antagonism. Mol Cancer Ther; 14(1); 59–69. ©2014 AACR.
Mast Cells Boost Myeloid-Derived Suppressor Cell Activity and Contribute to the Development of Tumor-Favoring Microenvironment
Authors: Danelli Luca , Frossi Barbara , Gri Giorgia , Mion Francesca , Guarnotta Carla , Bongiovanni Lucia , Tripodo Claudio , Mariuzzi Laura , Marzinotto Stefania , Rigoni Alice , Blank Ulrich , Colombo Mario P. , Pucillo Carlo E. 
Published: October 2014

Abstract
Inflammation plays crucial roles at different stages of tumor development and may lead to the failure of immune surveillance and immunotherapy. Myeloid-derived suppressor cells (MDSC) are one of the major components of the immune-suppressive network that favors tumor growth, and their interaction with mast cells is emerging as critical for the outcome of the tumor-associated immune response. Herein, we showed the occurrence of cell-to-cell interactions between MDSCs and mast cells in the mucosa of patients with colon carcinoma and in the colon and spleen of tumor-bearing mice. Furthermore, we demonstrated that the CT-26 colon cancer cells induced the accumulation of CD11b+Gr1+ immature MDSCs and the recruitment of protumoral mast cells at the tumor site. Using ex vivo analyses, we showed that mast cells have the ability to increase the suppressive properties of spleen-derived monocytic MDSCs, through a mechanism involving IFNγ and nitric oxide production. In addition, we demonstrated that the CD40:CD40L cross-talk between the two cell populations is responsible for the instauration of a proinflammatory microenvironment and for the increase in the production of mediators that can further support MDSC mobilization and tumor growth. In light of these results, interfering with the MDSC:mast cell axis could be a promising approach to abrogate MDSC-related immune suppression and to improve the antitumor immune response. Cancer Immunol Res; 3(1); 85–95. ©2014 AACR.
Catabolic Signaling and Muscle Wasting After Acute Ischemic Stroke in Mice
Authors: Springer Jochen , Schust Susanne , Peske Katrin , Tschirner Anika , Rex Andre , Engel Odilo , Scherbakov Nadja , Meisel Andreas , von Haehling Stephan , Boschmann Michael , Anker Stefan D. , Dirnagl Ulrich , Doehner Wolfram 
Published: October 2014

Background and Purpose—
Muscle wasting is a common complication accompanying stroke. Although it is known to impair poststroke recovery, the mechanisms of subacute catabolism after stroke have not been investigated in detail. The aim of this study is to investigate mechanisms of local and systemic catabolism and muscle wasting (sarcopenia) in a model of ischemic stroke systematically.

Methods—
Changes in body composition and catabolic activation in muscle tissue were studied in a mouse model of acute cerebral ischemia (temporal occlusion of the middle cerebral artery). Tissue wasting (nuclear magnetic resonance spectroscopy), tissue catabolism (caspases-3 and -6, myostatin), and proteasome activity were assessed. Food intake, activity levels, and energy expenditure were assessed, and putative mechanisms of postischemic wasting were tested with appropriate interventions.

Results—
Severe weight loss in stroke animals (day 3: weight loss, –21.7%) encompassed wasting of muscle (–12%; skeletal and myocardium) and fat tissue (–27%). Catabolic signaling and proteasome activity were higher in stroke animals in the contralateral and in the ipsilateral leg. Cerebral infarct severity correlated with catabolic activity only in the contralateral leg but not in the ipsilateral leg. Lower energy expenditure in stroke animals together with normal food intake and activity levels suggests compensatory mechanisms to regain weight. Interventions (high caloric feeding, β-receptor blockade, and antibiotic treatment) failed to prevent proteolytic activation and muscle wasting.

Conclusions—
Catabolic pathways of muscle tissue are activated after stroke. Impaired feeding, sympathetic overactivation, or infection cannot fully explain this catabolic activation. Wasting of the target muscle of the disrupted innervation correlated to severity of brain injury. Our data indicate the presence of a stroke-specific sarcopenia.