bluuebunny/crossref_metadata_2025_split huggingface dataset:
Noninvasive Detection of Response and Resistance in EGFR-Mutant Lung Cancer Using Quantitative Next-Generation Genotyping of Cell-Free Plasma DNA
Authors: Oxnard Geoffrey R. , Paweletz Cloud P. , Kuang Yanan , Mach Stacy L. , O'Connell Allison , Messineo Melissa M. , Luke Jason J. , Butaney Mohit , Kirschmeier Paul , Jackman David M. , Jänne Pasi A. 
Published: January 2014

Abstract
Purpose: Tumor genotyping using cell-free plasma DNA (cfDNA) has the potential to allow noninvasive assessment of tumor biology, yet many existing assays are cumbersome and vulnerable to false-positive results. We sought to determine whether droplet digital PCR (ddPCR) of cfDNA would allow highly specific and quantitative assessment of tumor genotype.
Experimental Design: ddPCR assays for EGFR, KRAS, and BRAF mutations were developed using plasma collected from patients with advanced lung cancer or melanoma of a known tumor genotype. Sensitivity and specificity were determined using cancers with nonoverlapping genotypes as positive and negative controls. Serial assessment of response and resistance was studied in patients with EGFR-mutant lung cancer on a prospective trial of erlotinib.
Results: We identified a reference range for EGFR L858R and exon 19 deletions in specimens from KRAS-mutant lung cancer, allowing identification of candidate thresholds with high sensitivity and 100% specificity. Received operative characteristic curve analysis of four assays demonstrated an area under the curve in the range of 0.80 to 0.94. Sensitivity improved in specimens with optimal cfDNA concentrations. Serial plasma genotyping of EGFR-mutant lung cancer on erlotinib demonstrated pretreatment detection of EGFR mutations, complete plasma response in most cases, and increasing levels of EGFR T790M emerging before objective progression.
Conclusions: Noninvasive genotyping of cfDNA using ddPCR demonstrates assay qualities that could allow effective translation into a clinical diagnostic. Serial quantification of plasma genotype allows noninvasive assessment of response and resistance, including detection of resistance mutations up to 16 weeks before radiographic progression. Clin Cancer Res; 20(6); 1698–705. ©2014 AACR.
Masitinib Antagonizes ATP-Binding Cassette Subfamily C Member 10–Mediated Paclitaxel Resistance: A Preclinical Study
Authors: Kathawala Rishil J. , Sodani Kamlesh , Chen Kang , Patel Atish , Abuznait Alaa H. , Anreddy Nagaraju , Sun Yue-Li , Kaddoumi Amal , Ashby Charles R. , Chen Zhe-Sheng 
Published: January 2014

Abstract
Paclitaxel displays clinical activity against a wide variety of solid tumors. However, resistance to paclitaxel significantly attenuates the response to chemotherapy. The ABC transporter subfamily C member 10 (ABCC10), also known as multidrug resistance protein 7 (MRP7) efflux transporter, is a major mediator of paclitaxel resistance. In this study, we show that masitinib, a small molecule stem-cell growth factor receptor (c-Kit) tyrosine kinase inhibitor, at nontoxic concentrations, significantly attenuates paclitaxel resistance in HEK293 cells transfected with ABCC10. Our in vitro studies indicated that masitinib (2.5 μmol/L) enhanced the intracellular accumulation and decreased the efflux of paclitaxel by inhibiting the ABCC10 transport activity without altering the expression level of ABCC10 protein. Furthermore, masitinib, in combination with paclitaxel, significantly inhibited the growth of ABCC10-expressing tumors in nude athymic mice in vivo. Masitinib administration also resulted in a significant increase in the levels of paclitaxel in the plasma, tumors, and lungs compared with paclitaxel alone. In conclusion, the combination of paclitaxel and masitinib could serve as a novel and useful therapeutic strategy to reverse paclitaxel resistance mediated by ABCC10. Mol Cancer Ther; 13(3); 714–23. ©2014 AACR.
Curcumin: A Double Hit on Malignant Mesothelioma
Authors: Miller Jill M. , Thompson Joyce K. , MacPherson Maximilian B. , Beuschel Stacie L. , Westbom Catherine M. , Sayan Mutlay , Shukla Arti 
Published: January 2014

Abstract
Inflammation is a key mediator in the development of malignant mesothelioma, which has a dismal prognosis and poor therapeutic strategies. Curcumin, a naturally occurring polyphenol in turmeric, has been shown to possess anticarcinogenic properties through its anti-inflammatory effects. Inflammasomes, a component of inflammation, control the activation of caspase-1 leading to pyroptosis and processing of proinflammatory cytokines, interleukin (IL)-1β and IL-18. In the present study, we investigate the role of curcumin in pyroptotic cell death of malignant mesothelioma cells. Using in vitro models with mouse and human malignant mesothelioma cells, curcumin is shown to induce pyroptosis through activation of caspase-1 and increased release of high-mobility group box 1 (HMGB1) without processing of IL-1β and IL-18. Absence of IL-1β processing in response to curcumin-mediated caspase-1 activation is attributed to blockade of pro-IL-1β priming through inhibition of the NF-κB pathway. Furthermore, curcumin's cytotoxicity in malignant mesothelioma cells is demonstrated to be dependent on pyroptosis as inhibition of caspase-1 resulted in protection against curcumin-induced cell death. We also demonstrate that curcumin-mediated caspase-1 activation is oxidant dependent by using N-acetyl-L-cysteine (NAC) to inhibit pyroptosis. PCR array analysis using the human inflammasome template revealed that curcumin significantly downregulated levels of inflammasome-related gene expression involved in inflammation, e.g., NF-κB, toll-like receptors (TLR), and IL-1β. Our data indicate that curcumin has a double effect on malignant mesothelioma cells through induction of pyroptosis while subsequently protecting against inflammation. Cancer Prev Res; 7(3); 330–40. ©2014 AACR.
Roles of fibrin α- and γ-chain specific cross-linking by FXIIIa in fibrin structure and function
Authors: Duval Cédric , Allan Peter , Connell Simon D. A. , Ridger Victoria C. , Philippou Helen , Ariëns Robert A. S. 
Published: January 2014

SummaryFactor XIII is responsible for the cross-linking of fibrin γ-chains in the early stages of clot formation, whilst α-chain cross-linking occurs at a slower rate. Although γ- and α-chain cross-linking was previously shown to contribute to clot stiffness, the role of cross-linking of both chains in determining clot structure is currently unknown. Therefore, the aim of this study was to determine the role of individual α- and γ-chain cross-linking during clot formation, and its effects on clot structure. We made use of a recombinant fibrinogen (γQ398N/Q399N/K406R), which does not allow for y-chain cross-linking. In the absence of cross-linking, intact D-D interface was shown to play a potential role in fibre appearance time, clot stiffness and elasticity. Cross-linking of the fibrin α-chain played a role in the thickening of the fibrin fibres over time, and decreased lysis rate in the absence of α2-antiplasmin. We also showed that α-chain cross-linking played a role in the timing of fibre appearance, straightening fibres, increasing clot stiffness and reducing clot deformation. Cross-linking of the γ-chain played a role in fibrin fibre appearance time and fibre density. Our results show that α- and γ-chain cross-linking play independent and specific roles in fibrin clot formation and structure.
Relationship between Snow Extent and Midlatitude Disturbance Centers
Authors: Rydzik Matthew , Desai Ankur R. 
Published: January 2014

Abstract
A relationship between midlatitude cyclone (MLC) tracks and snow-cover extent has been discussed in the literature over the last 50 years but not explicitly analyzed with high-resolution and long-term observations of both. Large-scale modeling studies have hinted that areas near the edge of the snow extent support enhanced baroclinicity because of differences in surface albedo and moisture fluxes. In this study, the relationship between snow-cover extent and midlatitude disturbance (MLD) trajectories is investigated across North America using objectively analyzed midlatitude disturbance trajectories and snow-cover extent from the North American Regional Reanalysis (NARR) for 1979–2010. MLDs include low-level mesoscale disturbances through midlatitude cyclones. A high-resolution MLD database is developed from sea level pressure minima that are tracked through subsequent 3-h time steps, and a simple algorithm is developed that identified the southern edge of the snow-cover extent. A robust enhanced frequency of MLDs in a region 50–350 km south of the snow-cover extent is found. The region of enhanced MLD frequency coincides with the region of maximum low-level baroclinicity. These observations support hypotheses of an internal feedback in which the snow-cover extent is leading the disturbance tracks through surface heat and moisture fluxes. Further, these results aid in the understanding of how midlatitude disturbance tracks may shift in a changing climate in response to snow-cover trends.
Impact of Dominant Breaking Waves on Air–Sea Momentum Exchange and Boundary Layer Turbulence at High Winds
Authors: Suzuki Nobuhiro , Hara Tetsu , Sullivan Peter P. 
Published: January 2014

Abstract
Large-eddy simulation (LES) is used to investigate how dominant breaking waves in the ocean under hurricane-force winds affect the drag and near-surface airflow turbulence. The LES explicitly resolves the wake turbulence produced by dominant-scale breakers. Effects of unresolved roughness such as short breakers, nonbreaking waves, and sea foam are modeled as the subgrid-scale drag. Compared to the laboratory conditions previously studied using the same method, dominant-scale breakers in open-ocean conditions are less frequent, and the subgrid-scale drag is more significant. Nevertheless, dominant-scale breakers are more fully exposed to high winds and produce more intense wakes individually. As a result, they support a large portion of the total drag and significantly influence the turbulence for many ocean conditions that are likely to occur. The intense wake turbulence is characterized by flow separation, upward bursts of wind, and upward flux of the turbulent kinetic energy (TKE), all of which may influence sea spray dispersion. Similarly to the findings in the laboratory conditions, high production of wake turbulence shortcuts the inertial energy cascade, causes high TKE dissipation, and contributes to the reduction of the drag coefficient. The results also indicate that if the drag coefficient decreases with increasing wind at very high winds, as some recent observations suggest, then the unresolved roughness must also decrease.
Can formulation affect tryptophan depletion results? Hints from studies in experimental panic
Authors: Sobczak Sjacko , Schruers Koen 
Published: January 2014

Rationale: Acute Tryptophan Depletion (ATD) is a specific serotonergic challenge tool. Central serotonergic effects of different ATD procedures are possibly not those that are usually assumed. Objectives: In this paper we review data of ATD in an experimental fear model to investigate whether and how methodological differences may affect fear outcomes. Next we point to discrepancies of studies in our laboratory in order to test the hypotheses formulated in the review. Methods: Literature was searched in PubMed and MEDLINE and studies of our laboratory were compared. Results: Eight studies were included in the review: five in patients with panic disorder, three in healthy individuals. Methodologically the studies in our laboratory were quite similar except for the applied ATD mixtures. Conclusions: ATD exerts fear-enhancing effects in patients with panic disorders, more than in healthy individuals. However, our findings are inconclusive. The discrepant findings of studies in our laboratory can possibly be explained by differences in the ATD mixtures used. We suggest mechanisms as to how these might have affected the central availability of tryptophan and hence serotonin.
Pharmacological treatment strategies in obsessive compulsive disorder: A cross-sectional view in nine international OCD centers
Authors: Van Ameringen Michael , Simpson William , Patterson Beth , Dell’Osso Bernardo , Fineberg Naomi , Hollander Eric , Hranov Luchezar , Hranov Georgi , Lochner Christine , Karamustafalioglu Oguz , Marazziti Donatella , Menchon Jose M , Nicolini Humberto , Pallanti Stefano , Stein Dan J , Zohar Joseph 
Published: January 2014

Objective: It is unknown what next-step strategies are being used in clinical practice for patients with obsessive–compulsive disorder (OCD) who do not respond to first-line treatment. As part of a cross-sectional study of OCD, treatment and symptom information was collected. Method: Consecutive OCD out-patients in nine international centers were evaluated by self-report measures and clinical/structured interviews. OCD symptom severity was evaluated by the Yale Brown Obsessive Compulsive Scale (YBOCS) and Clinical Global Impression–Severity Scale (CGI-S). Clinical response to current treatment was evaluated by the CGI-Improvement Scale (CGI-I ≤ 2). Results: In total, 361 participants reported taking medication; 77.6% were taking a selective serotonin reuptake inhibitor; 50% reported use of at least one augmentation strategy. Antipsychotics were most often prescribed as augmenters (30.3%), followed by benzodiazepines (24.9%) and antidepressants (21.9%). No differences in OCD symptom severity were found between patients taking different classes of augmentation agents. Conclusions: Results from this international cross-sectional study indicate that current OCD treatment is in line with evidence-based treatment guidelines. Although augmentation strategies are widely used, no significant differences in OCD symptom severity were found between monotherapy and augmentation or between different therapeutic agents.
RNA granule component TDRD7 gene polymorphisms in a Han Chinese population with age-related cataract
Authors: Zheng Can , Wu Min , He Chun-Yan , An Xiao-Ju , Sun Min , Chen Chun-Lin , Ye Jian 
Published: January 2014

Objectives To examine whether polymorphisms in the RNA granule component tudor domain-containing protein 7 ( TDRD7) gene are associated with susceptibility to age-related cataract (ARC) in a Han Chinese population. Methods Patients with ARC, and age-, sex- and ethnically-matched healthy control subjects were enrolled in the study. Five single nucleotide polymorphisms (SNPs) within the TDRD7 gene, rs1462091, rs11793735, rs10981985, rs2045732 and rs1462089, were genotyped using a SNaPshot® Multiplex Kit. Results The study included 271 control subjects and 218 patients with ARC. The rs10981985 SNP was associated with ARC in dominant (odds ratio [OR] 0.561, 95% confidence interval [CI] 0.388, 0.809) and allele dose (OR 0.619, 95% CI 0.455, 0.841) genetic models. The rs10981985 A allele frequency was lower in patients with cortical ARC than in control subjects (OR 0.502, 95% CI 0.315, 0.801). The rs10981985 polymorphism was significantly associated with cortical ARC in a dominant genetic model (OR 0.431, 95% CI 0.251, 0.740). Conclusions The present study suggests that the rs10981985 G → A variant within the TDRD7 gene may protect against cortical ARC in a Han Chinese population.
The Burden of Song
Authors: Dairianathan Eugene 
Published: January 2014

Studies involving popular music songs have tended to overlook issues of language and music, especially when explorations between music and language reiterate questions ‘about the linguistic mediation of musical and especially timbral discourse, and connections between the singing voice and place, class, ethnicity, and identity’, which augur for a place for music ‘for the study of the mental, semiotic, communicative, expressive and discursive roles of language’ ( Feld et al. 2004 , p. 321). Consequently, choice of language in songs of popular music overlook use and user value in language not only as cultural marker but also socially constituted demarcation within communities of practice, especially when Anglophone discourses meet musical discourses. This attention (or lack) recalls Gayatri Spivak’s ( 1993 , p. 134) articulation of the concept of ‘burden’ of the teaching of English in India but has special relevance here. In this article, I draw on my work on Rudra, a local melodic Death Metal group in Singapore, who identify their creative endeavour as Vedic Metal since their songs are seen to f/use English and Sanskrit text/s. I examine their practice in relation to Spivak’s concept of burden.
Creating Space for Where Ancestors Once Walked
Authors: Hughes Diane , Keith Sarah 
Published: January 2014

Using music and voice to express cultural identity is a tradition inherent in musical communities throughout the world. Today, while traditions can be affected by popular culture and modern technologies, contemporary practices in music production and aesthetics can aid in communicating and sustaining cultural heritage. Taiwan has a diverse cultural makeup being a former colonial territory and now home to descendants of mainland Chinese immigrants together with its own indigenous peoples. This article explores the music of contemporary Taiwanese indigenous singers of Amis heritage. Specifically, the music and production techniques in recordings of two female singer–songwriters, Ado Kaliting Pacidal and Ilid Kaolo, are explored. Pacidal and Kaolo combine the Amis language and themes of aboriginal identity with a range of contemporary musical styles, narratives and production techniques. For our analysis, we draw on cultural musicology in terms of lyrical and musical expression, and focus on how production techniques and aesthetics (including processing and treatment of the voice, effects and mixing) are used to enhance that expression. In doing so, we draw attention to the relationship between contemporary music production and cultural significance. We conclude by determining how space is created for ‘where the ancestors once walked’ ( Pacidal 2012a ).
Neutrophil to Lymphocyte Ratio is Predictor of Atrial Fibrillation Recurrence After Cardioversion With Amiodarone
Authors: Karavelioğlu Yusuf , Karapınar Hekim , Yüksel Murat , Memiç Kadriye , Sarak Taner , Kurt Recep , Yilmaz Ahmet 
Published: January 2014

Background: In this study, our aim is to examine the role of the neutrophil to lymphocyte ratio (NLR) in the predictions of recurrence under long-term follow-up in patients whose sinus rhythms (SRs) were restored with amiodarone in acute atrial fibrillation (AF). Methods: Retrospectively, patients with acute AF, which successfully converted to the SR with amiodarone treatment, were recruited into the study. Patients experiencing the first AF attack were enrolled to the study and followed up for 5 years (median 23 months, 25-75 percentiles 12-24 months). Neutrophil to lymphocyte ratio was computed as absolute neutrophil count divided by lymphocyte count. Results: A total of 218 patients were recruited into the study and followed up for 21.6 ± 13.9 months; 87 (40%) patients had ≥1 recurrent AF attack within this period. The follow-up of 131 (60%) patients resulted in persisted SR without any other AF attack. Groups were similar in terms of age and gender. Left atrium (LA) diameter and NLR were increased, and platelet count and lymphocyte count were decreased in patients with AF recurrence in univariate analysis ( P < .05 for all). Only LA diameter (for per mm, 1.077 [1.021-1.136], P = .006) and NLR (1.584 [1.197-2.095], P = .001) were independent predictors of AF recurrence in the multivariate analysis. Conclusion: Increased NLR is a marker of increased inflammation and may serve as simple, cheap, and readily available predictors of recurrence in the long-term follow-up of patients admitted with acute AF and successfully converted to SR with amiodarone.
The Story of a Nation
Authors: Chandorkar Leena 
Published: January 2014

Social historians have pointed to the importance of autobiography in nation building. Nehru’s autobiography is no different. It is in fact a detailed account of India’s freedom movement. Nehru sees no contradiction at all between the cultural and political growth of the individual and the experience of history. Unlike Gandhi’s autobiography though, Nehru prefers to concentrate on his public life, the events around him, and the maturing of his intellectual thought and ideology. Philip Lejeune, one of the foremost names in autobiography studies, places the concept of confession at the heart of the autobiographical domain. This valorisation of the confession of intimate details in order to produce an ‘honest’ autobiography is also questionable because it implies that one equates ‘confession’ with acknowledgement of suppressed desires and unacceptable behaviour. This dichotomy of Public/Private does not always work in the case of autobiographies written by public figures. My article argues that though the Public and the Private are tightly interlinked in Nehru’s autobiography, a closer reading teases out their complex dynamics and the unexpected admissions of loneliness in the book are what ultimately humanises the subject/author of the book.
Safe mobilization of CD34+ cells in adults with β-thalassemia and validation of effective globin gene transfer for clinical investigation
Authors: Boulad Farid , Wang Xiuyan , Qu Jinrong , Taylor Clare , Ferro Leda , Karponi Garyfalia , Bartido Shirley , Giardina Patricia , Heller Glenn , Prockop Susan E. , Maggio Aurelio , Sadelain Michel , Rivière Isabelle 
Published: January 2014

Key Points
Safe mobilization of CD34+ cells in adults with β-thalassemia and effective transduction with a globin vector under cGMP conditions. Stable vector copy number and β-globin expression in BFU-Es derived from engrafted CD34+ HPCs 6 months post-transplant in NSG mice.
Potential side effect of propofol and sevoflurane for anesthesia of anti-NMDA-R encephalitis
Authors: Lapébie François-Xavier , Kennel Céline , Magy Laurent , Projetti Fabrice , Honnorat Jérôme , Pichon Nicolas , Vignon Philippe , François Bruno 
Published: January 2014

Abstract

Background
Many anesthetic drugs interact with the NMDA receptor and may therefore alter the clinical presentation of anti-NMDA-R encephalitis.

Case presentation
A 24-year-old woman was admitted to hospital for decreased consciousness and hyperthermia. Cerebrospinal fluid analysis revealed lymphocytic pleocytosis, and elevated protein. Cultures were negative. Patient state worsened with agitation, facial dyskinesia, ocular deviation, and limb dystonia. Diagnosis of anti-NMDA-R encephalitis was evidenced by specific antibodies. High doses of methylprednisolone were administered. CT scan disclosed an ovarian teratoma and tumor resection was scheduled under anesthesia with propofol, sufentanil, atracurium and sevoflurane. Sedation after surgery was maintained with propofol. Rapidly after surgery, patient’s condition deteriorated with increase of dyskinesias, and two tonic-clonic generalized seizure events.

Conclusion
In patients with anti-NMDA-R encephalitis, anesthesia using benzodiazepines, opiates and curares, which fail to interfere with the NMDA pathway, should be preferred.