bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Two Measures of Micrometastatic Disease on Clinical Outcomes in Patients with Newly Diagnosed Ewing Sarcoma: A Report from the Children's Oncology Group
Authors: Vo Kieuhoa T. , Edwards Jeremy V. , Epling C. Lorrie , Sinclair Elizabeth , Hawkins Douglas S. , Grier Holcombe E. , Janeway Katherine A. , Barnette Phillip , McIlvaine Elizabeth , Krailo Mark D. , Barkauskas Donald A. , Matthay Katherine K. , Womer Richard B. , Gorlick Richard G. , Lessnick Stephen L. , Mackall Crystal L. , DuBois Steven G. 
Published: February 2016

Abstract
Purpose: Flow cytometry and RT-PCR can detect occult Ewing sarcoma cells in the blood and bone marrow. These techniques were used to evaluate the prognostic significance of micrometastatic disease in Ewing sarcoma.
Experimental Design: Newly diagnosed patients with Ewing sarcoma were enrolled on two prospective multicenter studies. In the flow cytometry cohort, patients were defined as “positive” for bone marrow micrometastatic disease if their CD99+/CD45− values were above the upper limit in 22 control patients. In the PCR cohort, RT-PCR on blood or bone marrow samples classified the patients as “positive” or “negative” for EWSR1/FLI1 translocations. The association between micrometastatic disease burden with clinical features and outcome was assessed. Coexpression of insulin-like growth factor-1 receptor (IGF-1R) on detected tumor cells was performed in a subset of flow cytometry samples.
Results: The median total bone marrow CD99+CD45− percent was 0.0012% (range 0%–1.10%) in the flow cytometry cohort, with 14 of 109 (12.8%) of Ewing sarcoma patients defined as “positive.” In the PCR cohort, 19.6% (44/225) patients were “positive” for any EWSR1/FLI1 translocation in blood or bone marrow. There were no differences in baseline clinical features or event-free or overall survival between patients classified as “positive” versus “negative” by either method. CD99+CD45− cells had significantly higher IGF-1R expression compared with CD45+ hematopoietic cells (mean geometric mean fluorescence intensity 982.7 vs. 190.9; P &lt; 0.001).
Conclusions: The detection of micrometastatic disease at initial diagnosis by flow cytometry or RT-PCR is not associated with outcome in newly diagnosed patients with Ewing sarcoma. Flow cytometry provides a tool to characterize occult micrometastatic tumor cells for proteins of interest. Clin Cancer Res; 22(14); 3643–50. ©2016 AACR.
Linalool-Incorporated Nanoparticles as a Novel Anticancer Agent for Epithelial Ovarian Carcinoma
Authors: Han Hee Dong , Cho Young-Jae , Cho Sung Keun , Byeon Yeongseon , Jeon Hat Nim , Kim Hye-Sun , Kim Byoung-Gie , Bae Duk-Soo , Lopez-Berestein Gabriel , Sood Anil K. , Shin Byung Cheol , Park Yeong-Min , Lee Jeong-Won 
Published: February 2016

Abstract
Although cytotoxic chemotherapy is widely used against epithelial ovarian cancer (EOC), adverse side effects and emergence of resistance can limit its utility. Therefore, new drugs with systemic delivery platforms are urgently needed for this disease. In this study, we developed linalool-incorporated nanoparticles (LIN-NP) as a novel anticancer agent. We prepared LIN-NPs by the self-assembly water-in-oil-in-water (w/o/w) emulsion method. LIN-NP–mediated cytotoxicity and apoptosis was assessed in EOC cells, and the role of reactive oxygen species (ROS) generation as the mechanism of action was evaluated. In addition, therapeutic efficacy of LIN-NP was assessed in cell lines and patient-derived xenograft (PDX) models for EOC. LIN-NPs had significant cytotoxicity and apoptotic activity against EOC cells, including A2780, HeyA8, and SKOV3ip1. LIN-NP treatment increased apoptosis in EOC cells through ROS generation and a subsequent decrease in mitochondrial membrane potential and increase in caspase-3 levels. In addition, 100 mg/kg LIN-NPs significantly decreased tumor weight in the HeyA8 (P &lt; 0.001) and SKOV3ip1 (P = 0.006) in vivo models. Although treatment with 50 mg/kg LIN-NP did not decrease tumor weight compared with the control group, combination treatment with paclitaxel significantly decreased tumor weight compared with paclitaxel alone in SKOV3ip1 xenografts (P = 0.004) and the patient-derived xenograft model (P = 0.020). We have developed LIN-NPs that induce ROS generation as a novel anticancer agent for EOC. These findings have broad applications for cancer therapy. Mol Cancer Ther; 15(4); 618–27. ©2016 AACR.
A Critical Role of miR-144 in Diffuse Large B-cell Lymphoma Proliferation and Invasion
Authors: Wang Haiying , Wang Aihong , Hu Zhenbo , Xu Xin , Liu Zhiqiang , Wang Zhanju 
Published: February 2016

Abstract
MicroRNAs are endogenous noncoding RNAs that play important roles in a wide variety of biologic processes such as apoptosis, development, aging, and tumorigenesis. The B-cell lymphoma 6 (BCL6) transcriptional repressor has emerged as a critical therapeutic target in diffuse large B-cell lymphomas (DLBCL), but the mechanisms regulating BCL6 are still unclear. In the current study, we screened the microRNA expression profiles in DLBCL specimens and cell lines by qRT-PCR and found that the expression of miR-144 was significantly downregulated in DLBCL tissues and cell lines and negatively correlated with BCL6 expression. We further demonstrated that BCL6 was the direct target gene of miR-144, and miR-144 suppressed the expression of BCL6 via binding the 3′untranslated region of BCL6 mRNA. Biologically, forced expression of miR-144 significantly attenuated cell proliferation and invasion of OCI-Ly3 cells in vitro, and the tumor-suppressor effect of miR-144 was also confirmed using a xenograft mouse model in vivo. Taken together, our results reveal that miR-144 regulates BCL6 in DLBCL and provide a rationale for developing strategies that target miR-144 as a therapeutic intervention for DLBCL. Cancer Immunol Res; 4(4); 337–44. ©2016 AACR.
Percutaneous Transluminal Angioplasty and Drug-Eluting Stents for Infrapopliteal Lesions in Critical Limb Ischemia (PADI) Trial
Authors: Spreen Marlon I. , Martens Jasper M. , Hansen Bettina E. , Knippenberg Bob , Verhey Elke , van Dijk Lukas C. , de Vries Jean-Paul P.M. , Vos Jan-Albert , de Borst Gert Jan , Vonken Evert-Jan P.A. , Wever Jan J. , Statius van Eps Randolph G. , Mali Willem P.Th.M. , van Overhagen Hans 
Published: February 2016

Background—
Endovascular infrapopliteal treatment of patients with critical limb ischemia using percutaneous transluminal angioplasty (PTA) and bail-out bare metal stenting (BMS) is hampered by restenosis. In interventional cardiology, drug-eluting stents (DES) have shown better patency rates and are standard practice nowadays. An investigator-initiated, multicenter, randomized trial was conducted to assess whether DES also improve patency and clinical outcome of infrapopliteal lesions.

Methods and Results—

Adults with critical limb ischemia (Rutherford category ≥4) and infrapopliteal lesions were randomized to receive PTA±BMS or DES with paclitaxel. Primary end point was 6-month primary binary patency of treated lesions, defined as ≤50% stenosis on computed tomographic angiography. Stenosis >50%, retreatment, major amputation, and critical limb ischemia–related death were regarded as treatment failure. Severity of failure was assessed with an ordinal score, ranging from vessel stenosis through occlusion to the clinical failures. Seventy-four limbs (73 patients) were treated with DES and 66 limbs (64 patients) received PTA±BMS. Six-month patency rates were 48.0% for DES and 35.1% for PTA±BMS (
P
=0.096) in the modified-intention-to-treat and 51.9% and 35.1% (
P
=0.037) in the per-protocol analysis. The ordinal score showed significantly worse treatment failure for PTA±BMS versus DES (
P
=0.041). The observed major amputation rate remained lower in the DES group until 2 years post-treatment, with a trend toward significance (
P
=0.066). Less minor amputations occurred after DES until 6 months post-treatment (
P
=0.03).

Conclusions—
In patients with critical limb ischemia caused by infrapopliteal lesions, DES provide better 6-month patency rates and less amputations after 6 and 12 months compared with PTA±BMS.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00471289.
Additions, deletions and changes to the Ecuadorian Lycopodiaceae
Authors: Øllgaard Benjamin 
Published: February 2016

This paper is an update of the list of Lycopodiaceae known from Ecuador, resulting from field and herbarium activities after the publication of the family in Flora of Ecuador (Øllgaard 1988). Several taxa have been recognized or recorded as new to the country or new to science after 1988. Two are deleted due to misidentification or absence in spite of expectation. Two species are described as new to science here. The list is arranged alphabetically according to the recent classification presented in Øllgaard & Windisch (2014).
Potential Value of Expert Elicitation for Determining Differential Credibility of Regional Climate Change Simulations: An Exercise with the NARCCAP co-PIs for the Southwest Monsoon Region of North America
Authors: Mearns Linda O. , Bukovsky Melissa S. , Schweizer Vanessa J. 
Published: February 2016

Abstract
In this brief article, we report the initial results of an expert elicitation with the co-PIs (regional climate modelers) of the North American Regional Climate Change Assessment Program regarding their evaluation of the relative quality of regional climate model simulations focusing on the subregion dominated by the North American monsoon (NAM). We assumed that an expert elicitation framework might reveal interesting beliefs and understanding that would be different from what would be obtained from calculating quantitative metrics associated with model quality.
The simulations considered were of six regional climate models (RCMs) that used NCEP Reanalysis 2 as boundary conditions for the years 1980–2004. The domain covers most of North America and adjacent oceans. The seven participating regional modelers were asked to complete surveys on their background beliefs about model credibility and their judgments regarding the quality of the six models based on a series of plots of variables related to the NAM (e.g., temperature, winds, humidity, moisture flux, precipitation). The specific RCMs were not identified.
We also compared the results of the expert elicitation with those obtained from using a series of metrics developed to evaluate a European collection of climate model simulations. The results proved to be quite different in the two cases.
The results of this exercise proved very enlightening regarding regional modelers’ perceptions of model quality and their beliefs about how this information should or should not be used. Based on these pilot study results, we believe a more complete study is warranted.
Evaluation of the Weather Research and Forecasting Model in the Durance Valley Complex Terrain during the KASCADE Field Campaign
Authors: Kalverla Peter Christiaan , Duine Gert-Jan , Steeneveld Gert-Jan , Hedde Thierry 
Published: February 2016

AbstractIn the winter of 2012/13, the Katabatic Winds and Stability over Cadarache for the Dispersion of Effluents (KASCADE) observational campaign was carried out in southeastern France to characterize the wind and thermodynamic structure of the (stable) planetary boundary layer (PBL). Data were collected with two micrometeorological towers, a sodar, a tethered balloon, and radiosoundings. Here, this dataset is used to evaluate the representation of the boundary layer in the Weather Research and Forecasting (WRF) Model. In general, it is found that diurnal temperature range (DTR) is largely underestimated, there is a strong negative bias in both longwave radiation components, and evapotranspiration is overestimated. An illustrative case is subjected to a thorough model-physics evaluation. First, five PBL parameterization schemes and two land surface schemes are employed. A marginal sensitivity to PBL parameterization is found, and the sophisticated Noah land surface model represents the extremes in skin temperature better than does a more simple thermal diffusion scheme. In a second stage, sensitivity tests for land surface–atmosphere coupling (through parameterization of z0h/z0m), initial soil moisture content, and radiation parameterization were performed. Relatively strong surface coupling and low soil moisture content result in a larger sensible heat flux, deeper PBL, and larger DTR. The larger sensible heat flux is not supported by the observations, however. It turns out that, for the selected case, a combination of subsidence and warm-air advection is not accurately simulated, but this inaccuracy cannot fully explain the discrepancies found in the WRF simulations. The results of the sensitivity analysis reiterate the important role of initial soil moisture values.
Reducing Operational Hurricane Intensity Forecast Errors during Eyewall Replacement Cycles
Authors: Kossin James P. , DeMaria Mark 
Published: February 2016

Abstract
Eyewall replacement cycles (ERCs) are fairly common events in tropical cyclones (TCs) of hurricane intensity or greater and typically cause large and sometimes rapid changes in the intensity evolution of the TC. Although the details of the intensity evolution associated with ERCs appear to have some dependence on the ambient environmental conditions that the TCs move through, these dependencies can also be quite different than those of TCs that are not undergoing an ERC. For example, the Statistical Hurricane Prediction Scheme (SHIPS), which is used in National Hurricane Center operations and provides intensity forecast skill that is, on average, equal to or greater than deterministic numerical model skill, typically identifies an environment that is not indicative of weakening during the onset and subsequent evolution of an ERC. Contrarily, a period of substantial weakening does typically begin near the onset of an ERC, and this disparity can cause large SHIPS intensity forecast errors. Here, a simple model based on a climatology of ERC intensity change is introduced and tested against SHIPS. It is found that the application of the model can reduce intensity forecast error substantially when applied at, or shortly after, the onset of ERC weakening.
Effect of Radiofrequency Thermal Ablation Treatment on Nasal Ciliary Motility
Authors: Rosato Chiara , Pagliuca Giulio , Martellucci Salvatore , de Vincentiis Marco , Greco Antonio , Fusconi Massimo , De Virgilio Armando , Gallipoli Camilla , Simonelli Marilia , Gallo Andrea 
Published: February 2016

ObjectiveTo investigate the efficacy of nasal ciliary motility after radiofrequency ablation treatment in patients with isolated inferior turbinate hypertrophy and to clarify how long until normal ciliary function is restored.Study DesignProspective, single‐group, pretest‐posttest design.SettingAcademic tertiary care medical center.Subjects and MethodsThis study involved 34 adult patients affected by nasal obstruction due to inferior turbinate hypertrophy who underwent radiofrequency ablation treatment between June and December 2014. Diagnosis was assessed according to clinical history, nasal endoscopy, and active anterior rhinomanometry. Cytologic samples were collected by nasal scraping before surgery and 1, 2, and 3 months after surgery. Ciliary motility was evaluated by nasal cytology with phase‐contrast microscopy. Functional aspects of nasal mucosa were studied, with a focus on 3 parameters: (1) nasal mucociliary clearance, assessed by saccharin nasal transit time test; (2) percentage of ciliated cell motility, measured as the ratio between cells with motility and cells without motility; and (3) efficacy of ciliary motility, measured as the ratio between cells with valid motility and cells with hypovalid motility.ResultsCiliary motility and ciliary efficacy showed a significant reduction after 1 and 2 months from surgery, returning to normal values within 3 months. No significant changes in saccharin nasal transit time were recorded during the follow‐up.ConclusionsThe outcomes of this study suggest that radiofrequency ablation treatment causes ciliary motility changes of nasal mucosa that are completely restored after at least 3 months after surgery. These cytologic abnormalities do not affect nasal functionality.
Definitive Surgical Therapy after Open Neck Biopsy for HPV‐Related Oropharyngeal Cancer
Authors: Zenga Joseph , Graboyes Evan M. , Haughey Bruce H. , Paniello Randal C. , Mehrad Mitra , Lewis James S. , Thorstad Wade L. , Nussenbaum Brian , Rich Jason T. 
Published: February 2016

ObjectiveTo determine the impact of prior open neck biopsy on the prognosis of patients with human papillomavirus (HPV)–related oropharyngeal squamous cell carcinoma (OPSCC) who are subsequently treated with a definitive surgical paradigm, including adjuvant therapy when indicated.Study DesignRetrospective cohort.SettingTertiary care university hospital.Subjects and MethodsPatients with open neck biopsies who were treated with definitive surgery, with or without adjuvant therapy, for HPV‐related OPSCC between 1998 and 2012 were compared with a matched control group who did not undergo open neck biopsy. Outcomes were disease‐free survival, overall survival, disease‐specific survival, incidence of tumor deposit in dermal scar, patterns of recurrence, and neck dissection complications.ResultsForty‐five patients who underwent open neck biopsy were compared with 90 matched controls. Tumor deposits in dermal scars from the prior open neck biopsy were found in 3 patients (7%) during completion neck dissection. Overall complications of the neck dissection were not significantly increased in the open biopsy group over matched controls (20% vs 12%, respectively; P >. 05). Five‐year Kaplan‐Meier estimates for disease‐free survival, overall survival, and disease‐specific survival were not significantly different between the open biopsy and control groups (93% vs 91%, 98% vs 97%, 98% vs 99%, respectively; all P >. 05). Recurrence rates were also not significantly different between groups.ConclusionsPatients with HPV‐related OPSCC who have undergone a prior open neck biopsy can be successfully treated with a definitive surgical paradigm. Although needle biopsy is preferable to establish a diagnosis, previous open neck biopsy does not affect prognosis in these patients.
Application of Lean Sigma to the Audiology Clinic at a Large Academic Center
Authors: Huddle Matthew G. , Tirabassi Amy , Turner Laurie , Lee Emily , Ries Kathryn , Lin Sandra Y. 
Published: February 2016

ObjectiveTo apply Lean Sigma—a quality improvement strategy to eliminate waste and reduce variation and defects—to improve audiology scheduling and utilization in a large tertiary care referral center. The project goals included an increase in utilization rates of audiology block time and a reduction in appointment lead time.Study DesignProspective quality improvement study.SettingAcademic tertiary care center.SubjectsAll patients scheduling audiology clinic visits July 2013 to July 2014.MethodsValue stream mapping was performed for the audiology scheduling process, and wasteful steps were identified for elimination. Interventions included a 2‐week block release, audiology template revision, and reduction of underutilized blocks. Schedule utilization and lead time for new patient diagnostic audiogram were measured for 5 months postintervention and compared with 5 months preintervention. Overall, 2995 preintervention and 3714 postintervention booked appointments were analyzed.ResultsBlock utilization increased from 77% to 90% after intervention (P <. 0001). Utilization of joint‐with‐provider visits increased from 39% to 67% (P <. 0001). Booked appointments increased from 2995 to 3714, with joint‐with‐provider booked appointments increasing from 317 to 1193. Appointment lead time averaged 24 days postintervention, compared with 29 days preintervention (P =. 06). Average monthly relative value units measured 13,321 preintervention and 14,778 postintervention (P =. 09).ConclusionLean Sigma techniques were successfully used to increase appointment block utilization and streamline scheduling practices.
Region specific contribution of ASIC2 to acidosis-and ischemia-induced neuronal injury
Authors: Jiang Nan , Wu Junjun , Leng Tiandong , Yang Tao , Zhou Yufan , Jiang Qian , Wang Bin , Hu Youjia , Ji Yong-hua , Simon Roger P , Chu Xiang-ping , Xiong Zhi-Gang , Zha Xiang-ming 
Published: February 2016

Acidosis in the brain plays a critical role in neuronal injury in neurological diseases, including brain ischemia. One key mediator of acidosis-induced neuronal injury is the acid-sensing ion channels (ASICs). Current literature has focused on ASIC1a when studying acid signaling. The importance of ASIC2, which is also widely expressed in the brain, has not been appreciated. We found here a region-specific effect of ASIC2 on acid-mediated responses. Deleting ASIC2 reduced acid-activated current in cortical and striatal neurons, but had no significant effect in cerebellar granule neurons. In addition, we demonstrated that ASIC2 was important for ASIC1a expression, and that ASIC2a but not 2b facilitated ASIC1a surface trafficking in the brain. Further, we showed that ASIC2 deletion attenuated acidosis/ischemia-induced neuronal injury in organotypic hippocampal slices but had no effect in organotypic cerebellar slices. Consistent with an injurious role of ASIC2, we showed that ASIC2 deletion significantly protected the mouse brain from ischemic damage in vivo. These data suggest a critical region-specific contribution of ASIC2 to neuronal injury and reveal an important functional difference between ASIC2a and 2b in the brain.
Optimal detection of scapholunate ligament tears with MRI
Authors: Greditzer Harry G , Zeidenberg Joshua , Kam Check C , Gray Robert R , Clifford Paul D , Mintz Douglas N , Jose Jean 
Published: February 2016

Background Scapholunate interosseous ligament (SLIL) injuries can often be difficult to detect using magnetic resonance imaging (MRI), especially with older 1.0 and 1.5 Tesla magnets. Wrist arthroscopy is the gold standard for diagnosis of SLIL injuries, but is an invasive procedure with associated risks. Purpose To assess whether SLIL injuries can be more accurately detected using axial MRI sequences instead of coronal sequences. Material and Methods An institutional review board approved retrospective analysis of arthroscopic wrist surgeries performed at our institution. Patients that had a preoperative MRI performed at our university center using a 1.5 Tesla scanner with a dedicated wrist coil were included in the study. Three fellowship-trained musculoskeletal radiologists reviewed the axial sequences and coronal sequences independently. The accuracy of the coronal and axial sequences was compared with the arthroscopic/surgical findings. Result Twenty-six patients met the inclusion criteria. The sensitivity for SLIL tears was 79% and 65% for the axial and coronal sequences, respectively. The specificity was 82% for the axial and 69% for the coronal sequences, respectively. The positive and negative predictive values for the axial sequences were 76% and 84% respectively, compared to 68% and 71% for the coronal sequences, a statistically significant difference. Conclusion SLIL tears are more readily detectable on axial MRI sequences than coronal. Clinically, patients with radial-sided wrist pain and suspicion for SLIL tears should have the axial sequences scrutinized carefully. An otherwise normal study with the axial sequence being degraded by motion or other MRI artifacts might need repeat imaging.