bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glutamatergic Pathway Targeting in Melanoma: Single-Agent and Combinatorial Therapies
Authors: Lee Hwa Jin , Wall Brian A. , Wangari-Talbot Janet , Shin Seung-Shick , Rosenberg Stephen , Chan Joseph L-K. , Namkoong Jin , Goydos James S. , Chen Suzie 
Published: August 2011

Abstract
Purpose: Melanoma is a heterogeneous disease where monotherapies are likely to fail due to variations in genomic signatures. B-RAF inhibitors have been clinically inadequate but response might be augmented with combination therapies targeting multiple signaling pathways. We investigate the preclinical efficacy of combining the multikinase inhibitor sorafenib or the mutated B-RAF inhibitor PLX4720 with riluzole, an inhibitor of glutamate release that antagonizes metabotropic glutamate receptor 1 (GRM1) signaling in melanoma cells.
Experimental Design: Melanoma cell lines that express GRM1 and either wild-type B-RAF or mutated B-RAF were treated with riluzole, sorafenib, PLX4720, or the combination of riluzole either with sorafenib or with PLX4720. Extracellular glutamate levels were determined by glutamate release assays. MTT assays and cell-cycle analysis show effects of the compounds on proliferation, viability, and cell-cycle profiles. Western immunoblotting and immunohistochemical staining showed apoptotic markers. Consequences on mitogen-activated protein kinase pathway were assessed by Western immunoblotting. Xenograft tumor models were used to determine the efficacy of the compounds in vivo.
Results: The combination of riluzole with sorafenib exhibited enhanced antitumor activities in GRM1-expressing melanoma cells harboring either wild-type or mutated B-RAF. The combination of riluzole with PLX4720 showed lessened efficacy compared with the combination of riluzole and sorafenib in suppressing the growth of GRM1-expressing cells harboring the B-RAFV600E mutation.
Conclusions: The combination of riluzole with sorafenib seems potent in suppressing tumor proliferation in vitro and in vivo in GRM1-expressing melanoma cells regardless of B-RAF genotype and may be a viable therapeutic clinical combination. Clin Cancer Res; 17(22); 7080–92. ©2011 AACR.
Parallel Anticancer Drug Development and Molecular Stratification to Qualify Predictive Biomarkers: Dealing with Obstacles Hindering Progress
Authors: Garcia Victor Moreno , Cassier Philippe A. , de Bono Johann 
Published: August 2011

Abstract
Current anticancer drug development still largely follows the classic designs developed for chemotherapeutic agents over the past 4 to 5 decades, remaining slow, costly, and inefficient, with continuing high risks of costly late drug attrition. A Pharmacologic Audit Trail has been described to decrease these risks, incorporating pharmacokinetic, pharmacodynamic, intermediate efficacy endpoints, as well as patient stratification molecular biomarkers. Molecular biomarker–based patient selection in hypothesis-testing early clinical trials is critical to clinically qualify putative predictive biomarkers for rationally designed, molecularly targeted drugs as early as possible. Nevertheless, major concerns have been raised about the impact of using such biomarkers in early trials, in view of the costs and time involved to develop multiple certified assays for clinical use. The rapid evolution of novel technologies of utility to this field, such as next-generation sequencing and circulating tumor-cell isolation, makes these valid concerns of critical importance. We therefore propose a more efficient parallel predictive biomarker and clinical anticancer drug development process to deal with the obstacles hindering progress. Cancer Discovery; 1(3); 207–12. © 2011 AACR.
Functional Subtyping of Breast Cancer
Authors: Beijersbergen Roderick L. , Bernards René 
Published: August 2011

Abstract
Breast cancers can be subdivided in several different ways. In this issue, Brough and colleagues describe a functional subtyping of breast cancers based on their responses to specific perturbations. Cancer Discovery; 1(3); 205–6. © 2011 AACR.
Commentary on Brough et al., p. 260.
The Influence of the Cloud Shell on Tracer Budget Measurements of LES Cloud Entrainment
Authors: Dawe Jordan T. , Austin Philip H. 
Published: August 2011

AbstractDirect measurements of rates of entrainment into and detrainment from cumulus cloud cores obtained from LES model cloud fields produce values twice as large as those produced from tracer budget calculations. This difference can be explained by two effects: the presence of a shell of air around the cloud cores that is moister than the mean environment and air at the edge of the cloud core that is drier than the mean core, and the tendency for the mean tracer values of the entrained fluid to be greater than the mean tracer values of the cloud shell. Preferential entrainment of shell air that is moving upward faster than the mean shell creates strong vertical momentum fluxes into the cumulus cloud core, thereby making the assumption that cumulus cloud cores entrain fluid with zero vertical momentum incorrect. Variability in the properties of the moist cloud shell has strong impacts on entrainment values inferred from tracer budget calculations. These results indicate that the dynamics of the cloud shell should be included in parameterization of cumulus clouds used in general circulation models.
Estimating the lifetime economic burden of stroke according to the age of onset in South Korea: a cost of illness study
Authors: Kang Hye-Young , Lim Seung-Ji , Suh Hae Sun , Liew Danny 
Published: August 2011

AbstractBackgroundThe recently-observed trend towards younger stroke patients in Korea raises economic concerns, including erosion of the workforce. We compared per-person lifetime costs of stroke according to the age of stroke onset from the Korean societal perspective.MethodsA state-transition Markov model consisted of three health states ('post primary stroke event', 'alive post stroke', and 'dead') was developed to simulate the natural history of stroke. The transition probabilities for fatal and non-fatal recurrent stroke by age and gender and for non-stroke causes of death were derived from the national epidemiologic data of the Korean Health Insurance Review and Assessment Services and data from the Danish Monitoring Trends in Cardiovascular Disease study. We used an incidence-based approach to estimate the long-term costs of stroke. The model captured stroke-related costs including costs within the health sector, patients' out-of-pocket costs outside the health sector, and costs resulting from loss of productivity due to morbidity and premature death using a human capital approach. Average insurance-covered costs occurring within the health sector were estimated from the National Health Insurance claims database. Other costs were estimated based on the national epidemiologic data and literature. All costs are presented in 2008 Korean currency values (Korean won = KRW).ResultsThe lifetime costs of stroke were estimated to be: 200.7, 81.9, and 16.4 million Korean won (1,200 KRW is approximately equal to one US dollar) for men who suffered a first stroke at age 45, 55 and 65 years, respectively, and 75.7, 39.2, and 19.3 million KRW for women at the same age. While stroke occurring among Koreans aged 45 to 64 years accounted for only 30% of the total disease incidence, this age group incurred 75% of the total national lifetime costs of stroke.ConclusionsA higher lifetime burden and increasing incidence of stroke among younger Koreans highlight the need for more effective strategies for the prevention and management of stroke especially for people between 40 and 60 years of ages.
A new modified block iterative algorithm for uniformly quasi-ϕ-asymptotically nonexpansive mappings and a system of generalized mixed equilibrium problems
Authors: Saewan Siwaporn , Kumam Poom 
Published: August 2011

AbstractIn this paper, we introduce a new modified block iterative algorithm for finding a common element of the set of common fixed points of an infinite family of closed and uniformly quasi-ϕ-asymptotically nonexpansive mappings, the set of the variational inequality for an α-inverse-strongly monotone operator, and the set of solutions of a system of generalized mixed equilibrium problems. We obtain a strong convergence theorem for the sequences generated by this process in a 2-uniformly convex and uniformly smooth Banach space. Our results extend and improve ones from several earlier works.2000 MSC: 47H05; 47H09; 47H10.
Population-Based Study of Competing Mortality in Head and Neck Cancer
Authors: Rose Brent S. , Jeong Jong-Hyeon , Nath Sameer K. , Lu Sharon M. , Mell Loren K. 
Published: August 2011

Purpose Patients with head and neck cancer (HNC) are at high risk of death resulting from noncancer causes and second malignancies (ie, competing mortality). Variation in competing mortality risk complicates individual treatment choices and design and interpretation of clinical studies. Methods Using the Surveillance, Epidemiology, and End Results registry, we identified 34,568 patients with nonmetastatic squamous cell carcinoma of the head and neck diagnosed between 1994 and 2003. We developed a multivariable competing-risk regression model to stratify patients according to competing mortality risk and evaluate the impact of this risk on power loss in clinical studies. Results The 5-year cumulative incidences of all-cause mortality, HNC-specific mortality, and competing mortality were 51.3% (95% CI, 50.8% to 51.9%), 23.8% (95% CI, 23.3% to 24.2%), and 27.6% (95% CI, 26.8% to 28.3%), respectively. Factors associated with increased competing mortality were increasing age, male sex, black race, unmarried status, localized disease, higher socioeconomic status, nonsurgical treatment, and hypopharyngeal, nasopharyngeal, and oral cavity subsites. The 5-year cumulative incidences of competing mortality for patients in low-, medium-, and high-risk score tertiles were 20.0% (95% CI, 18.8% to 21.3%), 27.7% (95% CI, 26.3% to 29.1%), and 33.7% (95% CI, 32.2% to 35.2%), respectively. Compared with patients with low competing mortality risk, relative sample sizes required to show benefit of a treatment regarding all-cause mortality were 12% and 42% higher in the medium- and high-risk groups, respectively. Conclusion Multiple factors affect risk of competing mortality among patients with HNC. Risk stratification would be useful to identify patients most likely to benefit from treatment intensification.
“Ein seltsam Spielen”: Narrative, Performance, and Impossible Voice in Mahler's Das klagende Lied
Authors: Lee Sherry 
Published: August 2011

Abstract
A quest, a murder, and musical retribution through a dead body part that sings: these are the elements of the folktale known as “The Singing Bone,” a traditional narrative that appears in numerous versions in both oral and literary European traditions. For decades, this tale has drawn the special attention of folklorists because of the remarkable and indeed sensational role played in it by music: its narrative reflects a fascinating ideology of the cultural power of music as the voice of the oppressed, while its musical interludes, chilling spectral songs sung by the bone of the murder victim, invoke the potent and at times unsettling effects of musical performance. Gustav Mahler's first large-scale work, Das klagende Lied, takes up this extraordinary narrative and translates its exceptional features into poetry and musical sound in a manner that especially foregrounds and amplifies the effects of a performing presence in both textual and musical dimensions. Mahler's narrative ballad is a multivoiced text whose temporal and vocal shifts create oscillations between narrative and drama, telling and enactment, giving rise to a remarkable instability of utterance from which repeated evocations of sound and voice emerge. Its musical setting delivers a discourse that similarly exhibits explicit moments of performance, temporal suspension, and sonic dislocation in both voices and orchestra. This extreme volatility of utterance and its resultant effects of presence become the means of the work's embodiment of its own narrative content, such that, in performance, it evokes an experience of the radical sonic rupture that is the story's theme—a theme that reverberates powerfully throughout Mahler's oeuvre.
Somatic mutations in NKX2–5, GATA4, and HAND1 are not a common cause of tetralogy of Fallot or hypoplastic left heart
Authors: Esposito Giorgia , Butler Tanya L. , Blue Gillian M. , Cole Andrew D. , Sholler Gary F. , Kirk Edwin P. , Grossfeld Paul , Perryman Benjamin M. , Harvey Richard P. , Winlaw David S. 
Published: August 2011

AbstractThe majority of congenital heart disease (CHD) occurs as a sporadic finding, with a minority of cases associated with a known genetic abnormality. Combinations of genetic and environmental factors are implicated, with the recent and intriguing hypothesis that an apparently high rate of somatic mutations might explain some sporadic CHD. We used samples of right ventricular myocardium from patients undergoing surgical repair of tetralogy of Fallot (TOF) and hypoplastic left heart (HLH) to examine the incidence of somatic mutation in cardiac tissue. TOF is a common form of cyanotic CHD, occurring in 3.3 per 10,000 live births. HLH is a rare defect in which the left side of the heart is severely under‐developed. Both are severe malformations whose genetic etiology is largely unknown. We carried out direct sequence analysis of the NKX2–5 and GATA4 genes from fresh frozen cardiac tissues and matched blood samples of nine TOF patients. Analysis of NKX2–5, GATA4, and HAND1 was performed from cardiac tissue of 24 HLH patients and three matched blood samples. No somatic or germline mutations were identified in the TOF or HLH patients. Although limited by sample size, our study suggests that somatic mutations in NKX2–5 and GATA4 are not a common cause of isolated TOF or HLH. © 2011 Wiley‐Liss, Inc.
Unraveling Gold(I)‐Specific Action Towards Peptidic Disulfide Cleavage: A DFT Investigation
Authors: Dumont Elise , Michel Carine , Sautet Philippe 
Published: August 2011

AbstractGround‐state disulfide dissociation is a target of prime importance in structural biochemistry. A main difficulty consists in avoiding competition with carbon–sulfur and backbone scission pathways. In tandem mass spectrometry, such selectivity is afforded using transition elements or coinage‐metal ions as catalyst. Yet, the underlying gas‐phase mechanistic details remain poorly understood. Gold(I)‐assisted disulfide cleavage is investigated by means of DFT calculations, to elucidate the highly selective and specific catalytic action of this transition‐metal cation, a most promising one in tandem mass spectrometry. The preferential cleavage of sulfur–sulfur versus carbon–sulfur linkages on dimethyldisulfide, taken as a prototypical aliphatic compound, is rationalized on the basis of molecular orbital arguments. Secondly, it is revealed that the disulfide dissociation profile is dramatically impacted by a peptidic environment. Calculations on l,l‐cystine derivatives show two main factors: the topological frustration for an embedded ‐CH2SSCH2‐ motif induces a 5 kcal mol−1 penalty, whereas electrophilic assistance via complexation of nitrogen and oxygen atoms lowers activation barriers by a factor of 3. SS weakening is both thermodynamically and kinetically driven by the versatile coordination mode of gold(I). The influence of amine‐terminus group protonation is finally sketched: it gives rise to an intermediate reactivity. This study sheds lights on the key action of the peptidic environment in tuning the dissociation profile in the presence of this transition‐metal monocation.
In vivo flow cytometry of circulating clots using negative photothermal and photoacoustic contrasts
Authors: Galanzha Ekaterina I. , Sarimollaoglu Mustafa , Nedosekin Dmitry A. , Keyrouz Salah G. , Mehta Jawahar L. , Zharov Vladimir P. 
Published: August 2011

AbstractConventional photothermal (PT) and photoacousic (PA) imaging, spectroscopy, and cytometry are preferentially based on positive PT/PA effects, when signals are above background. Here, we introduce PT/PA technique based on detection of negative signals below background. Among various new applications, we propose label‐free in vivo flow cytometry of circulating clots. No method has been developed for the early detection of clots of different compositions as a source of thromboembolism including ischemia at strokes and myocardial infarction. When a low‐absorbing, platelet‐rich clot passes a laser‐irradiated vessel volume, a transient decrease in local absorption results in an ultrasharp negative PA hole in blood background. Using this phenomenon alone or in combination with positive contrasts, we demonstrated identification of white, red, and mixed clots on a mouse model of myocardial infarction and human blood. The concentration and size of clots were measured with threshold down to few clots in the entire circulation with size as low as 20 μm. This multiparameter diagnostic platform using portable personal high‐speed flow cytometer with negative dynamic contrast mode has potential to real‐time defining risk factors for cardiovascular diseases, and for prognosis and prevention of stroke or use clot count as a marker of therapy efficacy. Possibility for label‐free detection of platelets, leukocytes, tumor cells or targeting themby negative PA probes (e.g., nonabsorbing beads or bubbles) is also highlighted. © 2011 International Society for Advancement of Cytometry
Risk of sinonasal‐cutaneous fistula after treatment for advanced sinonasal cancer
Authors: Cianchetti Marco , Varvares Mark A. , Deschler Daniel G. , Liebsch Nobert J. , Wang Jing J. , Chan Annie W. 
Published: August 2011

AbstractBackground and ObjectivesTo determine the rate and the risk factors for sinonasal‐cutaneous fistula formation after treatment for sinonasal malignancy.MethodsBetween 1991 and 2002, 99 patients with advanced sinonasal malignancy received radiation therapy +/− surgery. Primary site was maxillary sinus in 30, ethmoid sinus in 19, nasal cavity in 32, nasopharynx in 3, and sphenoid sinus in 15 patients. Eighty‐two percent of patients had T4 disease. Sixty‐eight percent of patients had undergone surgical resection. Median follow‐up was 70.6 months.ResultsEight patients developed ≥ grade 3 sinonasal‐cutaneous fistulas at a median time of 3.8 months after radiation. The overall rates of developing ≥ grade 3 fistulas in the entire group at 2 and 5 years were 6% and 10%, respectively. The fistulas were in the medial canthus in seven patients and in the infraorbital region in one patient. Fistulas developed exclusively along the transfacial incision scar and in patients whose tumors extended to the subcutaneous tissues. In univariate analysis, squamous cell carcinoma histology (P = 0.008), ≤ T4a primary tumor category (P = 0.02), and transfacial incision (P = 0.02) were associated with increased risk of fistula formation.ConclusionsHistologic subtype, T category, and quality of the skin and the underlying supporting tissues after transfacial incision are risk factors for sinonasal‐cutaneous fistula formation. J. Surg. Oncol. 2012; 105:261–265. © 2011 Wiley Periodicals, Inc.
Hybrid Polymeric Nanomaterials for siRNA Delivery and Imaging
Authors: Mok Hyejung , Park Tae Gwan 
Published: August 2011

AbstractA combined nanomaterials‐based approach for simultaneous therapy and molecular imaging has powerful potential for efficient treatment and monitoring the prognosis of incurable diseases such as malignant tumors or degenerative diseases. Recent developments of hybrid polymeric nanomaterials for siRNA delivery and imaging are highlighted. A particular focus is on various conjugation and formulation strategies of how to incorporate siRNA and imaging agents onto the surface of functionally active polymer‐coated inorganic nanomaterials such as iron oxide, gold, and quantum‐dot nanoparticles for theranostic applications. These multifunctional nanocarriers may allow real‐time tracking of siRNA as well as visualization of its therapeutic effects in vitro and in vivo.magnified image
Bone marrow transplant options and preferences in a sickle cell anemia cohort on chronic transfusions
Authors: Hansbury Eileen N. , Schultz William H. , Ware Russell E. , Aygun Banu 
Published: August 2011

AbstractBackgroundBone marrow transplantation (BMT) using human leukocyte antigen (HLA)‐matched sibling donors can be curative for children with sickle cell anemia (SCA). However, minimal data exist regarding availability of HLA‐identical matched siblings for transplant‐eligible children, and family interest in pursuing transplantation.MethodsWe retrospectively analyzed a pediatric SCA cohort receiving chronic transfusions between July 2004 and January 2011. Data were analyzed regarding the number of full siblings and half‐siblings, availability, and family interest in HLA testing the full siblings, and interest in proceeding with HLA‐matched transplantation.ResultsAmong 113 patients, 46 (41%) had at least 1 full sibling and 40 (35%) had an unaffected full sibling who could serve as a BMT donor. The families of 23 of these patients (58%) agreed to HLA‐type sibling, 8 of whom (35%) were matched. Transfusion indications for families agreeing to HLA typing included stroke (46%) abnormal TCD (29%), acute chest syndrome (21%), and other CNS reasons (4%). Common reasons to decline HLA typing or transplantation included fear of the process, toxicities of the procedure, and comfort with current quality of life on transfusions. Only 8 of 113 (7%) were eligible for matched BMT, and only 3 (3%) underwent HLA‐matched transplantation. Two unmatched children received haploidentical transplantation.ConclusionsMost families of children with SCA on chronic transfusions choose to proceed with HLA typing. However, when a matched sibling was identified, most families declined to proceed with matched‐sibling transplantation. Discussing BMT as a treatment option, offering HLA typing and identifying barriers may improve acceptance of this treatment modality. Pediatr Blood Cancer 2012; 58: 611–615. © 2011 Wiley Periodicals, Inc.