bluuebunny/crossref_metadata_2025_split huggingface dataset:
RAS Mutations Are Associated With the Development of Cutaneous Squamous Cell Tumors in Patients Treated With RAF Inhibitors
Authors: Oberholzer Patrick A. , Kee Damien , Dziunycz Piotr , Sucker Antje , Kamsukom Nyam , Jones Robert , Roden Christine , Chalk Clinton J. , Ardlie Kristin , Palescandolo Emanuele , Piris Adriano , MacConaill Laura E. , Robert Caroline , Hofbauer Günther F.L. , McArthur Grant A. , Schadendorf Dirk , Garraway Levi A. 
Published: November 2011

Purpose RAF inhibitors are effective against melanomas with BRAF V600E mutations but may induce keratoacanthomas (KAs) and cutaneous squamous cell carcinomas (cSCCs). The potential of these agents to promote secondary malignancies is concerning. We analyzed cSCC and KA lesions for genetic mutations in an attempt to identify an underlying mechanism for their formation. Methods Four international centers contributed 237 KA or cSCC tumor samples from patients receiving an RAF inhibitor (either vemurafenib or sorafenib; n = 19) or immunosuppression therapy (n = 53) or tumors that developed spontaneously (n = 165). Each sample was profiled for 396 known somatic mutations across 33 cancer-related genes by using a mass spectrometric–based genotyping platform. Results Mutations were detected in 16% of tumors (38 of 237), with five tumors harboring two mutations. Mutations in TP53, CDKN2A, HRAS, KRAS, and PIK3CA were previously described in squamous cell tumors. Mutations in MYC, FGFR3, and VHL were identified for the first time. A higher frequency of activating RAS mutations was found in tumors from patients treated with an RAF inhibitor versus populations treated with a non–RAF inhibitor (21.1% v 3.2%; P < .01), although overall mutation rates between treatment groups were similar (RAF inhibitor, 21.1%; immunosuppression, 18.9%; and spontaneous, 17.6%; P = not significant). Tumor histology (KA v cSCC), tumor site (head and neck v other), patient age (≤ 70 v > 70 years), and sex had no significant impact on mutation rate or type. Conclusion Squamous cell tumors from patients treated with an RAF inhibitor have a distinct mutational profile that supports a mechanism of therapy-induced tumorigenesis in RAS-primed cells. Conceivably, cotargeting of MEK together with RAF may reduce or prevent formation of these tumors.
Assessment of BCR-ABL1 Transcript Levels at 3 Months Is the Only Requirement for Predicting Outcome for Patients With Chronic Myeloid Leukemia Treated With Tyrosine Kinase Inhibitors
Authors: Marin David , Ibrahim Amr R. , Lucas Claire , Gerrard Gareth , Wang Lihui , Szydlo Richard M. , Clark Richard E. , Apperley Jane F. , Milojkovic Dragana , Bua Marco , Pavlu Jiri , Paliompeis Christos , Reid Alistair , Rezvani Katayoun , Goldman John M. , Foroni Letizia 
Published: November 2011

Purpose We studied BCR-ABL1 transcript levels in patients with chronic myeloid leukemia in chronic phase (CML-CP) at 3, 6, and 12 months after starting imatinib to identify molecular milestones that would predict for overall survival (OS) and other outcomes more reliably than serial marrow cytogenetics. Patients and Methods We analyzed 282 patients with CML-CP who received imatinib 400 mg/d as first-line therapy followed by dasatinib or nilotinib if treatment with imatinib failed. We used a receiver operating characteristic curve to identify the cutoffs in transcript levels at 3, 6, and 12 months that would best predict patient outcome. We validated our findings in an independent cohort of 95 patients treated elsewhere. Results Patients with transcript levels of more than 9.84% (n = 68) at 3 months had significantly lower 8-year probabilities of OS (56.9% v 93.3%; P < .001), progression-free survival, cumulative incidence of complete cytogenetic response, and complete molecular response than those with higher transcript levels. Similarly, transcript levels of more than 1.67% (n = 87) at 6 months and more than 0.53% (n = 93) at 12 months identified high-risk patients. However, transcript levels at 3 months were the most strongly predictive for the various outcomes. When we compared OS for the groups defined molecularly at 6 and 12 months with the usual cytogenetic milestones, categorization by transcript numbers was the only independent predictor for OS (relative risk, 0.207; P < .001 and relative risk, 0.158; P < .001, respectively). Conclusion A single measurement of BCR-ABL1 transcripts performed at 3 months is the best way to identify patients destined to fare poorly, thereby allowing early clinical intervention.
STD and HIV Testing Behaviors Among Black And Puerto Rican Young Adults
Authors: Carter Marion W. , Kraft Joan Marie , Hatfield‐Timajchy Kendra , Hock‐Long Linda , Hogben Matthew 
Published: November 2011

CONTEXT: Given the high rates of infection among urban young adults, STD and HIV testing promotion is a public health priority. To inform future testing efforts, lifetime and recent testing behaviors of this population within casual and serious relationships should be better understood.
METHODS: Data from a 2007–2008 study conducted in select neighborhoods in Hartford and Philadelphia were used to examine self‐reported STD and HIV testing behaviors and attitudes among 483 sexually active black and Puerto Rican young adults aged 18–25. Multivariate ordered logit regression analyses were conducted to assess characteristics associated with lifetime number of STD tests.
RESULTS: More than eight in 10 participants reported having been tested for STDs, and a similar proportion for HIV, most of them multiple times. Nineteen percent had ever had an STD diagnosis. A majority—86%—perceived their risk of STD infection in the next year as “not at all likely.” Sixty‐one percent of those in serious relationships reported that both partners had been tested, compared with 25% of those in casual relationships. Characteristics associated with higher lifetime number of STD tests were being female (odds ratio, 2.2), being from Philadelphia (2.5), being black (1.5), having lived with two or more serious partners (1.7) and having ever received an STD diagnosis (2.3).
DISCUSSION: Despite their risks, participants did not perceive themselves to be at risk of STDs. However, they did report testing repeatedly. Testing was highly acceptable, particularly within serious relationships. Questions about the timing of testing initiation and repeat testing merit attention for the benefits of widespread testing to be fully realized.
Effects of fibrates on C-reactive protein concentrations: a meta-analysis of randomized controlled trials
Authors: Hao Yongchen , Zhang Huan , Yang Xueli , Wang Lu , Gu Dongfeng 
Published: November 2011

AbstractThe effects of fibrates on C-reactive protein (CRP) are controversial. This meta-analysis was conducted to synthesize the available clinical trial evidence and summarize the effects of fibrates on CRP concentrations. In addition, this study assessed the relationship between changes in CRP and lipid measures.A systematic search was conducted of randomized controlled trials on the effects of fibrates on CRP concentrations in the PubMed, Embase and Cochrane Library Database up to January 2011. A meta-analysis was performed using a random effect model. Meta-regression analysis was employed to assess the relationships between average change in CRP and lipid profiles.Sixteen randomized controlled trials were included in the meta-analysis. Compared with placebo, treatment with fibrates significantly decreased CRP concentrations (weighted mean difference –0.47 mg/L, 95% confidence interval –0.93 to –0.01 mg/L, p=0.046). Fibrates significantly reduced CRP concentrations in trials with a higher baseline CRP concentrations (≥3 mg/L). There was a significant correlation between change in CRP and change in high-density lipoprotein cholesterol (regression coefficient or slope=–2.03, 95% CI –3.20 to –0.87, p=0.001).Fibrates can reduce CRP concentrations and change in CRP was correlated with change in high-density lipoprotein cholesterol but not with triglyceride. These findings suggest that patients with dyslipidemia could benefit from fibrates treatment by CRP lowering and this benefit is associated with lipid profile improving.
Centralizer of an idempotent in a reductive monoid
Authors: Putcha Mohan S. 
Published: November 2011

Abstract
Let M be a reductive monoid. If e is an idempotent in M, we prove that the centralizer M(e) of e in M is a regular monoid with a finite graded poset of 𝒥-classes. We compute this poset explicitly when M is of canonical or dual canonical type and e is the relevant pivotal idempotent.
31 Year Evolution of the Rotating-Platform Total Knee Replacment: Coping With “Spinout” and Wear
Authors: Buechel Frederick F. , Buechel Frederick F. , Helbig Thomas E. , Pappas Michael J. 
Published: November 2011

Abstract
Low-contact-stress rotating-platform knee replacements were the original mobile-bearing knees developed by the senior authors in 1978 to improve fixation and minimize wear, however, 1-2 % experienced “spin-out” and wear resulting in the development of a third generation rotating platform (Buechel-Pappas, or B-P) in 1991. The purpose of this study is to evaluate design modifications incorporated into the B-P device based upon clinical outcomes. Clinical results of the initial 310 cementless B-P rotating platform total knee replacements in 257 patients were analyzed using a strict knee scoring scale. Of that group, 259 total knees in 206 patients were followed for 2–18 years (mean: 7.6 years). The titanium alloy metallic implants had a 10 μm thick titanium nitride (TiN) coating on all bearing and fixation surfaces and sintered-bead porous-coating, pore size of 350 microns, on all fixation surfaces. The rotating-platform bearing allowed 45° of internal and external rotation with further rotation limited by a stop pin on the tibial component to block complete rotary subluxation/dislocation of the bearing in the event of significant flexion instability or rotational trauma. The study showed 86.4 % excellent, 12.3 % good, 0.3 % fair, and 1.0 % poor results using a strict knee scoring scale. Complications requiring revision included tibial component loosening in 2 super-obese (BMI &gt;50), osteoarthritic patients (0.6%) and 1 late deep infection (0.3%) in a rheumatoid patient after 3.3 years. There were no cases of bearing wear, subluxation, or dislocation seen. Radiographic analysis, using &gt;2 mm lucency in any implant zone, demonstrated 0 % of radiolucencies around femoral components, 2.6 % around tibial components, and 0 % around patella components. Survivorship, using an end point of revision for wear or component loosening was 99.4 % at the 18-year interval.
Kardiovaskuläre Variabilitätsanalysen zur Risikostratifizierung nach Herzoperationen
Authors: Malberg Hagen , Wessel Niels , Bauernschmitt Robert , Zaunseder Sebastian , Kurths Jürgen , Bretthauer Georg 
Published: November 2011

ZusammenfassungMethoden zur Charakterisierung der kardiovaskulären Regulation wurden angewendet, um den Heilungsverlauf und das Risiko bei herzchirurgischen Patienten zu untersuchen. Dabei wurde der Zeitverlauf während der ersten 24 Stunden nach der Herzoperation, der präoperative autonome Status des Patienten und die Beeinflussung verschiedener Operationstechniken auf das postoperative kardiovaskuläre Regulationsverhalten untersucht. Die Ergebnisse deuten darauf hin, daß diese Bereiche in zukünftige Verfahren zur Risikostratifizierung bei herzchirurgischen Patienten einbezogen werden sollten.
Parent Participation and Physician-Parent Communication During Informed Consent in Child Leukemia
Authors: Cousino Melissa , Hazen Rebecca , Yamokoski Amy , Miller Victoria , Zyzanski Stephen , Drotar Dennis , Kodish Eric 
Published: November 2011

OBJECTIVE:
In this study we evaluated the effectiveness of a physician-directed intervention at enhancing positive physician behaviors and communication strategies during informed consent conferences (ICCs) for pediatric acute leukemia clinical trials.

PATIENTS AND METHODS:
Physicians at 2 large pediatric hospitals were recruited to participate in a physician-directed intervention (PDI), which included 1 full-day seminar and successive half-day booster sessions. ICCs were then observed, audiotaped, coded, and analyzed to evaluate the effectiveness of the intervention. Data also were collected at 2 control sites. Between 2003 and 2007, 59 ICCs were observed and analyzed.

RESULTS:
Significant group differences were found in physician rapport-building behaviors. Physicians in the PDI + booster session group engaged in greater rapport-building than did physicians in the PDI group who did not attend booster sessions and physicians in the control group. No group differences were detected for physician partnership-building. In addition, parents in the PDI + booster session group engaged in more general communication and study-related communication, and mothers in the PDI groups asked significantly more questions per minute than did mothers in the control group.

CONCLUSIONS:
These results provide support for the effectiveness of the PDI at enhancing positive physician behaviors. Booster-session attendance is a critical component of physician-directed interventions to improve parental participation and physician-parent communication during ICCs.
Adaptive geographical clines in the growth and defense of a native plant
Authors: Woods Ellen C. , Hastings Amy P. , Turley Nash E. , Heard Stephen B. , Agrawal Anurag A. 
Published: November 2011

Broad‐scale geographical gradients in the abiotic environment and interspecific interactions should select for clinal adaptation. How trait clines evolve has recently received increased attention because of anticipated climate change and the importance of rapid evolution in invasive species. This issue is particularly relevant for clines in growth and defense of plants, because both sets of traits are closely tied to fitness and because such sessile organisms experience strong local selection. Yet despite widespread recognition that growth and defense traits are intertwined, the general issue of their joint clinal evolution is not well resolved.To address heritable clinal variation and adaptation of growth and defense traits of common milkweed (Asclepias syriaca), we planted seed from 22 populations encompassing the species' latitudinal range in common gardens near the range center (New York) and toward the range edges (New Brunswick and North Carolina). Populations were differentiated in 13 traits, and six traits showed genetically based latitudinal clines. Higher‐latitude populations had earlier phenology, lower shoot biomass, more root buds and clonal growth, higher root‐to‐shoot ratio, and greater latex production. The cline in shoot biomass was consistent in all three locations. Selection on phenology was reversed in New Brunswick and North Carolina, with early genotypes favored in the north but not the south. We found no clines in foliar trichomes or toxic cardenolides. Annual precipitation of source populations explained variation in phenology, clonal growth, root‐to‐shoot ratio, and latex. Across four traits measured in New Brunswick and North Carolina, we found garden‐by‐latitude (and garden‐by‐precipitation) interactions, indicating plasticity in genetically based trait clines.In the two gardens with substantial herbivory (New York and North Carolina), northern populations showed higher resistance to insects. Resistance to aphids was driven by trichomes and water content, while resistance to monarch caterpillars was driven by latex. However, surveys of natural populations indicated that leaf damage and insect diversity on milkweed are low at the geographical extremes (New Brunswick and North Carolina) and higher toward the range center. We speculate that milkweed plants evolved clines in growth traits in response to climate, and that this set the template for tolerance to herbivory, which subsequently shaped the evolution of defensive traits.
Radiographic Periodontal Bone Loss in Chronic Kidney Disease
Authors: Messier Marie‐Danielle , Emde Karin , Stern Leonard , Radhakrishnan Jai , Vernocchi Linda , Cheng Bin , Angelopoulos Christos , Papapanou Panos N. 
Published: November 2011

Background: We examined the extent and severity of radiographic periodontal bone loss in patients with different stages of chronic kidney disease (CKD) and explored a potential dose–response relationship between bone loss and CKD‐related biomarkers.Methods: Panoramic radiographs were obtained from 129 CKD patients (78 males and 51 females; mean age: 63.5 years, range: 24 to 91 years), including 63 patients undergoing dialysis for an average of 3.3 years (range: 0.5 to 14 years). Glomerular filtration rate (GFR), dialysis dose, and levels of serum biomarkers were obtained through a hospital database. Interproximal bone loss was assessed as a percentage of root length.Results: Twenty‐nine participants were edentulous (23.8% of those on dialysis versus 21.2% of those with residual kidney function; χ2 test, P = 0.724). The extent of bone loss was higher among dialysis patients (analysis of variance [ANOVA], P = 0.007), but no clear dose–response association between CKD stage and extent was evident. GFR, dialysis dose, and levels of serum biomarkers did not differ between edentulous and dentate individuals, and only serum albumin was lower in patients with extensive bone loss (ANOVA, P = 0.030). After adjusting for dialysis status, the severity of bone loss was positively associated with glucose levels (multiple regression, P = 0.019) and white blood cell count (P = 0.032), whereas the number of teeth present was positively associated with plasma phosphorus (P = 0.008) and negatively with glucose levels (P = 0.011).Conclusion: Despite a higher extent of bone loss in dialysis patients, the lack of a dose–response association between bone loss and CKD stage or the levels of CKD‐related serum biomarkers underscores the complex relationship between the two conditions.
Measurement of Atherosclerosis Markers in Patients With Periodontitis: A Case‐Control Study
Authors: López‐Jornet P. , Berná‐Mestre J.D. , Berná‐Serna J.D. , Camacho‐Alonso F. , Fernandez‐Millan S. , Reus‐Pintado M. 
Published: November 2011

Background: It is suggested that periodontitis enhances the process of vascular inflammation leading to atherosclerosis. The present study explores the effect of periodontitis in relation to the clinical and ultrasound markers of carotid atherosclerosis.Methods: Sixty systemically healthy patients >45 years of age (30 with chronic periodontitis and 30 without periodontitis) were studied in a university dental school. Traditional cardiovascular risk factors for atherosclerosis were evaluated. Carotid intima‐media thickness (IMT) was assessed by ultrasound.Results: The internal carotid IMT was 0.77 and 0.81 mm in the periodontal disease and control groups, respectively, with no statistically significant differences between the two groups (P = 0.538). There were significant differences in the presence of carotid atheroma plaques and the severity of periodontitis (P = 0.003). In the logistic regression analysis, significant differences in terms of age and periodontitis were recorded in relation to the presence of atheroma plaques in the carotid intima.Conclusion: The severity of periodontitis was seen to influence the presence of carotid atheroma plaques.
CD84 Negatively Regulates IgE High-Affinity Receptor Signaling in Human Mast Cells
Authors: Álvarez-Errico Damiana , Oliver-Vila Irene , Ainsua-Enrich Erola , Gilfillan Alasdair M. , Picado César , Sayós Joan , Martín Margarita 
Published: November 2011

Abstract
CD84 is a self-binding receptor from the CD150 (or signaling lymphocyte activation molecule [SLAM]) family that is broadly expressed in hematopoietic cells. It has been described that the adaptors SLAM-associated protein (SAP) and EWS-FLI1–activated transcript 2 (EAT-2) are critical for CD150 family members’ signaling and function. We observed that human mast cells express CD84 but lack SAP or EAT-2, that CD84 is tyrosine phosphorylated upon FcεRI engagement, and that the release of granule contents is reduced when FcεRI is coengaged with CD84 in LAD2 and human CD34+-derived mast cells. In addition, we observed that the release of IL-8 and GM-CSF was also reduced in FcεRI/CD84-costimulated cells as compared with FcεRI/Ig control. To understand how CD84 downregulates FcεRI-mediated function, we analyzed signaling pathways affected by CD84 in human mast cells. Our results showed that CD84 dampens FcεRI-mediated calcium mobilization after its co-cross–linking with the receptor. Furthermore, FcεRI-mediated Syk–linker for activation of T cells–phospholipase C-γ1 axis activity is downregulated after CD84 stimulation, compared with FcεRI/Ig control. The inhibitory kinase Fes phosphorylates mainly the inhibitory motif for CD84. Moreover, Fes, which has been described to become phosphorylated after substrate binding, also gets phosphorylated when coexpressed with CD84. Consistently, Fes was observed to be more phosphorylated after CD84 and FcεRI co-cross–linking. The phosphorylation of the protein phosphatase Src homology region 2 domain-containing phosphatase-1 also increases after CD84 and FcεRI coengagement. Taken together, our results show that CD84 is highly expressed in mast cells and that it contributes to the regulation of FcεRI signaling in SAP- and EAT-2–independent and Fes- and Src homology region 2 domain-containing phosphatase-1–dependent mechanisms.
Cofilin-Mediated F-Actin Severing Is Regulated by the Rap GTPase and Controls the Cytoskeletal Dynamics That Drive Lymphocyte Spreading and BCR Microcluster Formation
Authors: Freeman Spencer A. , Lei Victor , Dang-Lawson May , Mizuno Kensaku , Roskelley Calvin D. , Gold Michael R. 
Published: November 2011

Abstract
When lymphocytes encounter APCs bearing cognate Ag, they spread across the surface of the APC to scan for additional Ags. This is followed by membrane contraction and the formation of Ag receptor microclusters that initiate the signaling reactions that lead to lymphocyte activation. Breakdown of the submembrane cytoskeleton is likely to be required for the cytoskeleton reorganization that drives cell spreading and for removing physical barriers that limit Ag receptor mobility. In this report, we show that Ag receptor signaling via the Rap GTPases promotes the dephosphorylation and activation of the actin-severing protein cofilin and that this results in increased severing of cellular actin filaments. Moreover, we show that this cofilin-mediated actin severing is critical for the changes in actin dynamics that drive B and T cell spreading, for the formation of BCR microclusters, and for the increased mobility of BCR microclusters within the plasma membrane after BCR engagement. Finally, using a model APC, we show that activation of this Rap–cofilin signaling module controls the amount of Ag that is gathered into BCR microclusters and that this is directly related to the magnitude of the resulting BCR signaling that is initiated during B cell–APC interactions. Thus, Rap-dependent activation of cofilin is critical for the early cytoskeletal changes and BCR reorganization that are involved in APC-dependent lymphocyte activation.