bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II Study of the MEK1/MEK2 Inhibitor Trametinib in Patients With Metastatic BRAF-Mutant Cutaneous Melanoma Previously Treated With or Without a BRAF Inhibitor
Authors: Kim Kevin B. , Kefford Richard , Pavlick Anna C. , Infante Jeffrey R. , Ribas Antoni , Sosman Jeffrey A. , Fecher Leslie A. , Millward Michael , McArthur Grant A. , Hwu Patrick , Gonzalez Rene , Ott Patrick A. , Long Georgina V. , Gardner Olivia S. , Ouellet Daniele , Xu Yanmei , DeMarini Douglas J. , Le Ngocdiep T. , Patel Kiran , Lewis Karl D. 
Published: December 2012

Purpose BRAF mutations promote melanoma cell proliferation and survival primarily through activation of MEK. The purpose of this study was to determine the response rate (RR) for the selective, allosteric MEK1/MEK2 inhibitor trametinib (GSK1120212), in patients with metastatic BRAF-mutant melanoma. Patients and Methods This was an open-label, two-stage, phase II study with two cohorts. Patients with metastatic BRAF-mutant melanoma previously treated with a BRAF inhibitor (cohort A) or treated with chemotherapy and/or immunotherapy (BRAF-inhibitor naive; cohort B) were enrolled. Patients received 2 mg of trametinib orally once daily. Results In cohort A (n = 40), there were no confirmed objective responses and 11 patients (28%) with stable disease (SD); the median progression-free survival (PFS) was 1.8 months. In cohort B (n = 57), there was one (2%) complete response, 13 (23%) partial responses (PRs), and 29 patients (51%) with SD (confirmed RR, 25%); the median PFS was 4.0 months. One patient each with BRAF K601E and BRAF V600R had prolonged PR. The most frequent treatment-related adverse events for all patients were skin-related toxicity, nausea, peripheral edema, diarrhea, pruritis, and fatigue. No cutaneous squamous cell carcinoma was observed. Conclusion Trametinib was well tolerated. Significant clinical activity was observed in BRAF-inhibitor–naive patients previously treated with chemotherapy and/or immunotherapy. Minimal clinical activity was observed as sequential therapy in patients previously treated with a BRAF inhibitor. Together, these data suggest that BRAF-inhibitor resistance mechanisms likely confer resistance to MEK-inhibitor monotherapy. These data support further evaluation of trametinib in BRAF-inhibitor–naive BRAF-mutant melanoma, including rarer forms of BRAF-mutant melanoma.
Association of Nutrient-Dense Snack Combinations With Calories and Vegetable Intake
Authors: Wansink Brian , Shimizu Mitsuru , Brumberg Adam 
Published: December 2012

BACKGROUND:
With other factors such as general diet and insufficient exercise, eating non–nutrient dense snack foods such as potato chips contributes to childhood obesity. We examined whether children consumed fewer calories when offered high-nutrient dense snacks consisting of cheese and vegetables than children who were offered non–nutrient dense snacks (ie, potato chips).

METHODS:
Two hundred one children (115 girls) entering the third to sixth grades were randomly assigned to 1 of 4 snacking conditions: (1) potato chips only, (2) cheese-only, (3) vegetables only, and (4) cheese and vegetables. Children were allowed to eat snacks freely provided while watching 45-minute TV programs. Satiety was measured before they started eating snacks, in the middle of the study, and 20 minutes after they finished eating the snacks. Parents completed a questionnaire regarding their family environment.

RESULTS:
Children consumed 72% fewer calories when eating a combined snack compared with when they were served potato chips, P &lt; .001. Children who ate the combination snack needed significantly fewer calories to achieve satiety than those who ate potato chips, P &lt; .001. The effects of the snack conditions on caloric intake were more pronounced among overweight or obese children (P = .02) and those from low-involvement families (P = .049)

CONCLUSIONS:
The combination snack of vegetables and cheese can be an effective means for children to reduce caloric intake while snacking. The effect was more pronounced among children who were overweight or obese and children from low-involvement families.
Detection of Kingella kingae Osteoarticular Infections in Children by Oropharyngeal Swab PCR
Authors: Ceroni Dimitri , Dubois-Ferriere Victor , Cherkaoui Abdessalam , Gesuele Renzi , Combescure Christophe , Lamah Léopold , Manzano Sergio , Hibbs Jonathan , Schrenzel Jacques 
Published: December 2012

OBJECTIVE:
The purpose of this study was to investigate if oropharyngeal swab polymerase chain reaction (PCR) could predict osteoarticular infection (OAI) due to Kingella kingae in young children.

METHODS:
One hundred twenty-three consecutive children aged 6 to 48 months presenting with atraumatic osteoarticular complaints were prospectively studied. All had a clinical evaluation, imaging, and blood samples. Blood and oropharyngeal specimens were tested with a PCR assay specific for K kingae. OAI was defined as bone, joint, or blood detection of pathogenic bacteria, or MRI consistent with infection in the absence of positive microbiology. K kingae OAI was defined by blood, bone, or synovial fluid positivity for the organism by culture or PCR.

RESULTS:
Forty children met the OAI case definition; 30 had K kingae OAI, 1 had another organism, and 9 had no microbiologic diagnosis. All 30 oropharyngeal swabs from the K kingae case patients and 8 swabs from the 84 patients without OAI or with OAI caused by another organism were positive. The sensitivity and specificity of the oropharyngeal swab PCR assay for K kingae were 100% and 90.5%, respectively.

CONCLUSIONS:
Detection of K kingae DNA in oropharyngeal swabs of children with clinical findings of OAI is predictive of K kingae OAI. If these findings are replicated in other settings, detection of K kingae by oropharyngeal swab PCR could improve the recognition of OAI.
Duration of Abdominal Obesity Beginning in Young Adulthood and Incident Diabetes Through Middle Age
Authors: Reis Jared P. , Hankinson Arlene L. , Loria Catherine M. , Lewis Cora E. , Powell-Wiley Tiffany , Wei Gina S. , Liu Kiang 
Published: December 2012

OBJECTIVE
To examine whether the duration of abdominal obesity determined prospectively using measured waist circumference (WC) is associated with the development of new-onset diabetes independent of the degree of abdominal adiposity.

RESEARCH DESIGN AND METHODS
The Coronary Artery Risk Development in Young Adults Study is a multicenter, community-based, longitudinal cohort study of 5,115 white and black adults aged 18–30 years in 1985 to 1986. Years spent abdominally obese were calculated for participants without abdominal obesity (WC &gt;102 cm in men and &gt;88 cm in women) or diabetes at baseline (n = 4,092) and was based upon repeat measurements conducted 2, 5, 7, 10, 15, 20, and 25 years later.

RESULTS
Over 25 years, 392 participants developed incident diabetes. Overall, following adjustment for demographics, family history of diabetes, study center, and time varying WC, energy intake, physical activity, smoking, and alcohol, each additional year of abdominal obesity was associated with a 4% higher risk of developing diabetes [hazard ratio (HR) 1.04 (95% CI 1.02–1.07)]. However, a quadratic model best represented the data. HRs for 0, 1–5, 6–10, 11–15, 16–20, and &gt;20 years of abdominal obesity were 1.00 (referent), 2.06 (1.43–2.98), 3.45 (2.28–5.22), 3.43 (2.28–5.22), 2.80 (1.73–4.54), and 2.91 (1.60–5.29), respectively; P-quadratic &lt; 0.001.

CONCLUSIONS
Longer duration of abdominal obesity was associated with substantially higher risk for diabetes independent of the degree of abdominal adiposity. Preventing or at least delaying the onset of abdominal obesity in young adulthood may lower the risk of developing diabetes through middle age.
Outcome of Modified Kidner Procedure with Subtalar Arthroereisis for Painful Accessory Navicular Associated with Planovalgus Deformity
Authors: Garras David N. , Hansen Patricia L. , Miller Adam G. , Raikin Steven Mark. 
Published: December 2012

Background: Type II accessory naviculars are frequently associated with planovalgus deformity. Operative treatment for patients recalcitrant to nonoperative treatment involves resection, with or without takedown, and reattachment of the tibialis posterior tendon as described by Kidner. This does not address the planovalgus deformity. The authors hypothesized that adding a subtalar arthroereisis to the Kidner procedure would lead to improvement of pain and function and correction of the deformity. Methods: Institutional Review Board-approved, prospectively collected data were reviewed for 20 patients (23 feet), who underwent a combined modified Kidner and subtalar arthroereisis for painful type II accessory navicular with planovalgus deformity recalcitrant to nonoperative treatment. The average age at the time of surgery was 18 years. Patients were evaluated preoperatively and at final follow-up clinically, radiographically, and via the visual analog pain scale (VAPS), the American Orthopaedic Foot and Ankle Society (AOFAS) ankle hindfoot score, and a satisfaction rating. Mean follow-up was 53.9 months. Results: The mean AOFAS scores improved from 53 preoperatively to 95 at final follow-up and the mean VAPS score decreased from 7.4 preoperatively to 1.7 at final follow-up. Radiographically, the average Meary's angle improved from 18.5° apex plantar preoperatively to 3° apex plantar on weight-bearing lateral radiographs, and the average talar head uncoverage percentage on weight-bearing anteroposterior radiographs improved from 24% preoperatively to 3%. Nineteen of 20 patients reported good or excellent results. Three patients required implant removal because of pain; no recurrence of planovalgus deformity occurred after implant removal. No patients developed subtalar arthritis. Conclusion: The modified Kidner procedure combined with a subtalar arthroereisis resulted in significant pain and functional improvement. The deformity correction obtained at surgery was maintained even if the arthroereisis plug was removed. The extra-articular plug did not lead to subtalar arthritis. Level of Evidence: IV, Case Series
Outcome of Medial Displacement Calcaneal Osteotomy for Correction of Adult-Acquired Flatfoot
Authors: Niki Hisateru , Hirano Takaaki , Okada Hirokazu , Beppu Moroe 
Published: December 2012

Background: The results of medial displacement calcaneal osteotomy (MDCO) with flexor digitorum longus (FDL) tendon transfer were reviewed, as well as postoperative radiographic changes, to determine quantitative x-ray-based indications for MDCO with FDL tendon transfer in cases of adult-acquired flatfoot. Materials and Methods: Twenty-five patients, ages 42 to 71 years, underwent MDCO with FDL tendon transfer for stage II posterior tibial tendon dysfunction. Follow-up was 2.6 to 10.2 years. Preoperative and postoperative Japanese Society for Surgery of the Foot (JSSF), Foot Function Index, and SF-36 scores and physical and radiographic findings were compared. Eight measures of foot alignment were obtained from weight-bearing radiographs at 3, 6, 9, and 12 months after surgery and every 6 months thereafter. Differences in scores and values over time were analyzed statistically. Results: Average JSSF scores improved from 59 preoperatively to 91.3 postoperatively ( p < .001). The only x-ray parameters that improved significantly and showed maintenance of the surgical correction were the lateral talometatarsal (LTMT) and tibiocalcaneal (TBC) angles. With preoperative LTMT and TBC angles of >25° and >15°, respectively, correction was inadequate. Conclusions: It was concluded that indications for MDCO with FDL tendon transfer in cases of adult-acquired flatfoot are a preoperative LTMT angle of <25° and hindfoot coronal alignment (TBC angle) of <15°. Level of Evidence: IV, Case Series
Accompagner plutôt qu'enseigner le business plan : bilan d'une expérimentation pédagogique
Authors: Verzat Caroline , Granger Benoît 
Published: December 2012

Résumé Le business plan est un dispositif controversé dans l’enseignement de l’entrepreneuriat. Une expérimentation réalisée auprès d’étudiants de 3 e année de Bachelor à Novancia est ici présentée et discutée. Le dispositif mis en œuvre apparait comme un « entre-deux » original entre le monde académique et le monde professionnel, à la frontière du business plan et du business model. Il met en œuvre un processus d’accompagnement sur mesure dans un groupe bienveillant, qui autorise davantage le développement d’identités entrepreneuriales que la création d’entreprises par les étudiants.
Three-Dimensional Visualization of the Mouse Thymus Organization in Health and Immunodeficiency
Authors: Irla Magali , Guenot Jeanne , Sealy Gregg , Reith Walter , Imhof Beat A. , Sergé Arnauld 
Published: December 2012

Abstract
Lymphoid organs exhibit complex structures tightly related to their function. Surprisingly, although the thymic medulla constitutes a specialized microenvironment dedicated to the induction of T cell tolerance, its three-dimensional topology remains largely elusive because it has been studied mainly in two dimensions using thymic sections. To overcome this limitation, we have developed an automated method for full organ reconstruction in three dimensions, allowing visualization of intact mouse lymphoid organs from a collection of immunolabeled slices. We validated full organ reconstruction in three dimensions by reconstructing the well-characterized structure of skin-draining lymph nodes, before revisiting the complex and poorly described corticomedullary organization of the thymus. Wild-type thymi contain ∼200 small medullae that are connected to or separated from a major medullary compartment. In contrast, thymi of immunodeficient Rag2−/− mice exhibit only ∼20 small, unconnected medullary islets. Upon total body irradiation, medullary complexity was partially reduced and then recovered upon bone marrow transplantation. This intricate topology presents fractal properties, resulting in a considerable corticomedullary area. This feature ensures short distances between cortex and medulla, hence efficient thymocyte migration, as assessed by mathematical models. Remarkably, this junction is enriched, particularly in neonates, in medullary thymic epithelial cells expressing the autoimmune regulator. The emergence of a major medullary compartment is induced by CD4+ thymocytes via CD80/86 and lymphotoxin-α signals. This comprehensive three-dimensional view of the medulla emphasizes a complex topology favoring efficient interactions between developing T cells and autoimmune regulator–positive medullary thymic epithelial cells, a key process for central tolerance induction.
IL-33 Induces a Hyporesponsive Phenotype in Human and Mouse Mast Cells
Authors: Jung Mi-Yeon , Smrž Daniel , Desai Avanti , Bandara Geethani , Ito Tomonobu , Iwaki Shoko , Kang Jeong-Han , Andrade Marcus V. , Hilderbrand Susana C. , Brown Jared M. , Beaven Michael A. , Metcalfe Dean D. , Gilfillan Alasdair M. 
Published: December 2012

Abstract
IL-33 is elevated in afflicted tissues of patients with mast cell (MC)–dependent chronic allergic diseases. Based on its acute effects on mouse MCs, IL-33 is thought to play a role in the pathogenesis of allergic disease through MC activation. However, the manifestations of prolonged IL-33 exposure on human MC function, which best reflect the conditions associated with chronic allergic disease, are unknown. In this study, we found that long-term exposure of human and mouse MCs to IL-33 results in a substantial reduction of MC activation in response to Ag. This reduction required &gt;72 h exposure to IL-33 for onset and 1–2 wk for reversion following IL-33 removal. This hyporesponsive phenotype was determined to be a consequence of MyD88-dependent attenuation of signaling processes necessary for MC activation, including Ag-mediated calcium mobilization and cytoskeletal reorganization, potentially as a consequence of downregulation of the expression of phospholipase Cγ1 and Hck. These findings suggest that IL-33 may play a protective, rather than a causative, role in MC activation under chronic conditions and, furthermore, reveal regulated plasticity in the MC activation phenotype. The ability to downregulate MC activation in this manner may provide alternative approaches for treatment of MC-driven disease.
Cutting Edge: Chronic Inflammatory Liver Disease in Mice Expressing a CD28-Specific Ligand
Authors: Corse Emily , Gottschalk Rachel A. , Park Joon Seok , Sepulveda Manuel A. , Loke P’ng , Sullivan Timothy J. , Johnson Linda K. , Allison James P. 
Published: December 2012

Abstract
Inflammation of the normally tolerant liver microenvironment precedes the development of chronic liver disease. Study of the pathogenesis of autoimmune liver diseases, such as autoimmune hepatitis (AIH), has been hampered by a lack of autochthonous chronic animal models. Through our studies of T cell costimulation, we generated transgenic mice expressing a ligand specific for the CD28 receptor, which normally shares ligands with the related inhibitory receptor CTLA-4. The mice spontaneously develop chronic inflammatory liver disease with several pathologies found in AIH, including elevated serum aminotransferases in the context of normal alkaline phosphatase and bilirubin levels, lymphocytic inflammation, focal necrosis, oval cell hyperplasia, and fibrosis. The prevalence of IFN-γ–producing CD8+ T cells in the livers of transgenic mice suggests a role for autoimmune cytotoxicity in the chronic disease state. The CD28 ligand–specific transgenic mice will facilitate evaluation of CD8+ T cell function in liver disease pathologies found in AIH.
The Accuracy of Magnetic Resonance Arthrography in Hip Arthroscopic Labral Revision Surgery
Authors: Aprato Alessandro , Jayasekera Narlaka , Villar Richard N. 
Published: December 2012

The interpretation of a magnetic resonance arthrogram (MRA) after a labral tear has been surgically treated can be challenging and there is no published evidence on its accuracy. The aim of this study was to evaluate the MRA accuracy in identifying labral pathology after hip arthroscopy. We reviewed 60 patients who had undergone a revision hip arthroscopy. Patients were divided into two groups. First, a study group (n = 40), which included patients who had undergone arthroscopic labral surgery at index operation. Secondly, there was a control group (n = 20), for patients who had not undergone labral surgery at index procedure. Findings regarding labral pathologies at MRA and at revision surgery were recorded. Sensitivity for MRA after hip arthroscopy was 53% and 71% in the study and control groups, respectively; specificity was 50% and 92%, positive predictive value was 81% and 83%, negative predictive value was 21% and 86% and accuracy was 53% and 85%. We conclude that the MRA is not reliable after hip arthroscopy where a labral tear has been addressed. When a labral tear has been repaired or partial labral excision has been performed, a postoperative MRA may inaccurately diagnose the presence of a persistent, recurrent, or unhealed tear.
Assessing Academic/Intellectual Skills in Keene State College's Integrative Studies Program
Authors: Rancourt Ann Marie 
Published: December 2012

Abstract
Key to the design of Keene State College's Integrative Studies Program (ISP) was the intention to create a program based on a conceptual framework. The framework came from AAC&U's Greater Expectations Report (2002) in which the essential learning outcomes for a liberal education were identified. In 2007 the program was implemented. The program has three sets of outcomes (intellectual skills, perspectives and interdisciplinary outcomes, and integrative outcomes). The focus of this article will be on the development of our process and on the assessment of intellectual skills.
The Butter Printer:
Authors: Keyser Catherine 
Published: December 2012

ABSTRACT
This essay follows the trope of industrial and convenience food in the work of middlebrow periodical humorists Robert Benchley, Margaret Fishback, and Ogden Nash. I argue that this trope reflects authorial anxieties and aspirations about the modern media's role in shaping consumer appetites and tastes. “Taste” takes on figurative connotations as these humorists meditate on modern foods in order to account for the place of mass production and commercialism within literary culture. Whether addressing chewing gum, soda fountains, or iceberg lettuce, these periodical writers confront the intimacy and ubiquity of modernity's changes and their professional implication in those changes.
Splendid Little Papers from the “Splendid Little War”:
Authors: Berkey James 
Published: December 2012

ABSTRACT
“Splendid Little Papers” recovers a forgotten moment in the print culture history of U.S. empire by examining a handful of newspapers and periodicals—Bounding Billow, American Soldier, Manila Outpost, and Volunteer—that were founded and written by and for U.S. soldiers in the Philippines and Cuba during the Spanish-American War. Foregrounding their status as periodicals, this essay argues that soldier papers used the formal technologies of print to remap the nation's relationship with the world and in the process helped their readers see themselves as part of an imagined community of empire.
An Engaged Mass Audience? The Provocations of a Popular Front Slick, Direction (1937–1945)
Authors: Rozendal Michael 
Published: December 2012

ABSTRACT
Exploding the bounds of the little journal in light of the emerging mass market, Direction (1937–45) used lush design and high production values to synthesize both the radical communities of the early thirties and the foundational magazines of American modernism—the Masses, Little Review, and Poetry. A glossy, Popular Front magazine with iconic visuals by Paul Rand, Direction helped to launch American graphic design and to define the distinctive style of midcentury modernism. Inspired by the federal New Deal programs, Direction sought to decouple literature from the market, foster emerging artists, and empower readers as writers.