bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective functional outcomes in sequential population based cohorts of stage III/ IV oropharyngeal carcinoma patients treated with 3D conformal vs. intensity modulated radiotherapy
Authors: Kerr Paul , Myers Candace L , Butler James , Alessa Mohamed , Lambert Pascal , Cooke Andrew L 
Published: May 2015

Background and purpose To compare early (3 and 6 month) and later (12 and 24 month) functional outcomes of stage III and IV (M0) oropharyngeal squamous cancer patients treated in sequential cohorts with 3D conformal (3DCRT) or intensity modulated radiotherapy (IMRT). Patients and methods 200 patients in sequential population based cohorts of 83 and 117 patients treated at a single institution with 3DCRT and then IMRT respectively were prospectively assessed at pre-treatment and 3, 6, 12 and 24 months post treatment. A standard functional outcomes protocol including performance status (KPS, ECOG), 3 Performance Status scales for Head and Neck (PSS-HN), the Royal Brisbane Hospital Outcome Measure for Swallowing (RBHOMS), Voice Handicap Index-10 (VHI-10) and self-rated xerostomia were applied. Results Mean age at diagnosis was 59 years. The primary site was base of tongue in 77 and tonsil or soft palate in 123 patients. Median follow up was 2.5 years for the second cohort. Concomitant therapy was used in 159 (79.5%). Overall survival at 3 years was 75.6% and 71.5% for IMRT and 3DCRT cohorts respectively (not significant). A multiple imputation technique was used to estimate missing values in order to avoid a healthy patient bias. KPS and ECOG reached nadirs at 3 to 6 months but approached baseline values at 12 to 24 months and did not differ by treatment. The 3 PSS-HN scales, Eating in Public (p < 0.001), Understandability of Speech (p = 0.009) and Oral Diet Texture (p = 0.002) and all showed significantly better outcomes in favor of IMRT. The RBHOMS showed a difference in favor of IMRT which appeared during 3 to 6 months (p < 0.001). The VHI-10 also showed a difference in favor of IMRT (p = 0.015). Self-rated xerostomia did not differ at 3 and 6 months but was significantly better in favor of IMRT after 12 months p = 0.005 Conclusions A prospectively administered functional outcomes protocol showed meaningful differences in favor of IMRT over 3DCRT early (3–6 months) and later (12–24 months) in the treatment of oropharyngeal carcinoma with equivalent survival. These data support the adoption of IMRT as the standard radiation treatment method for patients with stage III and IV (M0) oropharyngeal squamous carcinoma. KPS and ECOG may not be sensitive to oropharyngeal cancer patients’ functional outcomes by treatment.
Big data and deep data in scanning and electron microscopies: deriving functionality from multidimensional data sets
Authors: Belianinov Alex , Vasudevan Rama , Strelcov Evgheni , Steed Chad , Yang Sang Mo , Tselev Alexander , Jesse Stephen , Biegalski Michael , Shipman Galen , Symons Christopher , Borisevich Albina , Archibald Rick , Kalinin Sergei 
Published: May 2015

AbstractThe development of electron and scanning probe microscopies in the second half of the twentieth century has produced spectacular images of the internal structure and composition of matter with nanometer, molecular, and atomic resolution. Largely, this progress was enabled by computer-assisted methods of microscope operation, data acquisition, and analysis. Advances in imaging technology in the beginning of the twenty-first century have opened the proverbial floodgates on the availability of high-veracity information on structure and functionality. From the hardware perspective, high-resolution imaging methods now routinely resolve atomic positions with approximately picometer precision, allowing for quantitative measurements of individual bond lengths and angles. Similarly, functional imaging often leads to multidimensional data sets containing partial or full information on properties of interest, acquired as a function of multiple parameters (time, temperature, or other external stimuli). Here, we review several recent applications of the big and deep data analysis methods to visualize, compress, and translate this multidimensional structural and functional data into physically and chemically relevant information.
Genetic and cellular dissection of the activation of AM14 rheumatoid factor B cells in a mouse model of lupus
Authors: Sang Allison , Zheng Ying Yi , Choi Seung-Chul , Zeumer Leilani , Morel Laurence 
Published: May 2015

Abstract
The RF-specific AM14 tg BCR has been used as a model to dissect the mechanisms of B cell tolerance to ICs containing nucleic acids. We have shown previously that AM14 RF B cells break tolerance in the TC mouse model of lupus through the dual engagement of the AM14 BCR and TLR9. In this study, we showed that neither the expression of Sle1 or Sle2 susceptibility loci alone was sufficient to activate AM14 RF B cells, suggesting that the production of antichromatin IgG2aa autoAg mediated by Sle1 and an intrinsically higher B cell activation mediated by Sle2 were required. We also showed that the B6 genetic background enhanced the selection of AM14 RF B cells to the MZB cell compartment regardless of the expression of the Sle loci and therefore, of their activation into AFCs. Furthermore, some AM14 RF B cells were selected into the B-1a compartment, where they did not differentiate into AFCs. Therefore, it is unlikely that the selection of AM14 RF B cells to the MZB or B-1a cell compartments in TC.AM14a mice is responsible for their breach of tolerance. Finally, we showed that the presence of expression of Sle1 in non-tg cells, most likely T cells, is necessary for the activation of AM14 RF B cells into AFCs. Overall, these results suggest a threshold model of activation of AM14 RF B cells on the B6 background with additive genetic and cellular contribution of multiple sources.
Prediagnostic Sex Steroid Hormones in Relation to Male Breast Cancer Risk
Authors: Brinton Louise A. , Key Tim J. , Kolonel Laurence N. , Michels Karin B. , Sesso Howard D. , Ursin Giske , Van Den Eeden Stephen K. , Wood Shannon N. , Falk Roni T. , Parisi Dominick , Guillemette Chantal , Caron Patrick , Turcotte Véronique , Habel Laurel A. , Isaacs Claudine J. , Riboli Elio , Weiderpass Elisabete , Cook Michael B. 
Published: May 2015

Purpose Although previous studies have implicated a variety of hormone-related risk factors in the etiology of male breast cancers, no previous studies have examined the effects of endogenous hormones. Patients and Methods Within the Male Breast Cancer Pooling Project, an international consortium comprising 21 case-control and cohort investigations, a subset of seven prospective cohort studies were able to contribute prediagnostic serum or plasma samples for hormone quantitation. Using a nested case-control design, multivariable unconditional logistic regression analyses estimated odds ratios and 95% CIs for associations between male breast cancer risk and 11 individual estrogens and androgens, as well as selected ratios of these analytes. Results Data from 101 cases and 217 matched controls were analyzed. After adjustment for age and date of blood draw, race, and body mass index, androgens were found to be largely unrelated to risk, but circulating estradiol levels showed a significant association. Men in the highest quartile had an odds ratio of 2.47 (95% CI, 1.10 to 5.58) compared with those in the lowest quartile (trend P = .06). Assessment of estradiol as a ratio to various individual androgens or sum of androgens showed no further enhancement of risk. These relations were not significantly modified by either age or body mass index, although estradiol was slightly more strongly related to breast cancers occurring among younger (age < 67 years) than older men. Conclusion Our results support the notion of an important role for estradiol in the etiology of male breast cancers, similar to female breast cancers.
Course and Predictors of Cognitive Function in Patients With Prostate Cancer Receiving Androgen-Deprivation Therapy: A Controlled Comparison
Authors: Gonzalez Brian D. , Jim Heather S.L. , Booth-Jones Margaret , Small Brent J. , Sutton Steven K. , Lin Hui-Yi , Park Jong Y. , Spiess Philippe E. , Fishman Mayer N. , Jacobsen Paul B. 
Published: May 2015

Purpose Men receiving androgen-deprivation therapy (ADT) for prostate cancer may be at risk for cognitive impairment; however, evidence is mixed in the existing literature. Our study examined the impact of ADT on impaired cognitive performance and explored potential demographic and genetic predictors of impaired performance. Patients and Methods Patients with prostate cancer were assessed before or within 21 days of starting ADT (n = 58) and 6 and 12 months later. Age- and education-matched patients with prostate cancer treated with prostatectomy only (n = 84) and men without prostate cancer (n = 88) were assessed at similar intervals. Participants provided baseline blood samples for genotyping. Mean-level cognitive performance was compared using mixed models; cognitive impairment was compared using generalized estimating equations. Results ADT recipients demonstrated higher rates of impaired cognitive performance over time relative to all controls (P = .01). Groups did not differ at baseline (P > .05); however, ADT recipients were more likely to demonstrate impaired performance within 6 and 12 months (P for both comparisons < .05). Baseline age, cognitive reserve, depressive symptoms, fatigue, and hot flash interference did not moderate the impact of ADT on impaired cognitive performance (P for all comparisons ≥ .09). In exploratory genetic analyses, GNB3 single-nucleotide polymorphism rs1047776 was associated with increased rates of impaired performance over time in the ADT group (P < .001). Conclusion Men treated with ADT were more likely to demonstrate impaired cognitive performance within 6 months after starting ADT relative to matched controls and to continue to do so within 12 months after starting ADT. If confirmed, findings may have implications for patient education regarding the risks and benefits of ADT.
Phase I Study of Single-Agent AZD1775 (MK-1775), a Wee1 Kinase Inhibitor, in Patients With Refractory Solid Tumors
Authors: Do Khanh , Wilsker Deborah , Ji Jiuping , Zlott Jennifer , Freshwater Tomoko , Kinders Robert J. , Collins Jerry , Chen Alice P. , Doroshow James H. , Kummar Shivaani 
Published: May 2015

Purpose Wee1 tyrosine kinase phosphorylates and inactivates cyclin-dependent kinase (Cdk) 1/2 in response to DNA damage. AZD1775 is a first-in-class inhibitor of Wee1 kinase with single-agent antitumor activity in preclinical models. We conducted a phase I study of single-agent AZD1775 in adult patients with refractory solid tumors to determine its maximum-tolerated dose (MTD), pharmacokinetics, and modulation of phosphorylated Tyr15-Cdk (pY15-Cdk) and phosphorylated histone H2AX (γH2AX) levels in paired tumor biopsies. Patients and Methods AZD1775 was administered orally twice per day over 2.5 days per week for up to 2 weeks per 21-day cycle (3 + 3 design). At the MTD, paired tumor biopsies were obtained at baseline and after the fifth dose to determine pY15-Cdk and γH2AX levels. Six patients with BRCA-mutant solid tumors were also enrolled at the MTD. Results Twenty-five patients were enrolled. The MTD was established as 225 mg twice per day orally over 2.5 days per week for 2 weeks per 21-day cycle. Confirmed partial responses were observed in two patients carrying BRCA mutations: one with head and neck cancer and one with ovarian cancer. Common toxicities were myelosuppression and diarrhea. Dose-limiting toxicities were supraventricular tachyarrhythmia and myelosuppression. Accumulation of drug (t1/2 approximately 11 hours) was observed. Reduction in pY15-Cdk levels (two of five paired biopsies) and increases in γH2AX levels (three of five paired biopsies) were demonstrated. Conclusion This is the first report of AZD1775 single-agent activity in patients carrying BRCA mutations. Proof-of-mechanism was demonstrated by target modulation and DNA damage response in paired tumor biopsies.
The cuticle modulates ultraviolet reflectance of avian eggshells
Authors: Fecheyr-Lippens Daphne C. , Igic Branislav , D'Alba Liliana , Hanley Daniel , Verdes Aida , Holford Mande , Waterhouse Geoffrey I. N. , Grim Tomas , Hauber Mark E. , Shawkey Matthew D. 
Published: May 2015

ABSTRACT
Avian eggshells are variedly coloured, yet only two pigments, biliverdin and protoporphyrin IX, are known to contribute to the dramatic diversity of their colours. By contrast, the contributions of structural or other chemical components of the eggshell are poorly understood. For example, unpigmented eggshells, which appear white to the human eye, vary in their ultraviolet (UV) reflectance, which may be detectable by birds. We investigated the proximate mechanisms for the variation in UV-reflectance of unpigmented bird eggshells using spectrophotometry, electron microscopy, chemical analyses, and experimental manipulations. We specifically tested how UV-reflectance is affected by the eggshell cuticle, the outermost layer of most avian eggshells. The chemical dissolution of the outer eggshell layers, including the cuticle, increased UV-reflectance for only eggshells that contained a cuticle. Our findings demonstrate that the outer eggshell layers, including the cuticle, absorb UV-light, probably because they contain higher levels of organic components and other chemicals, such as calcium phosphates, compared to the predominantly calcite-based eggshell matrix. These data highlight the need to examine factors other than the known pigments in studies of avian eggshell colour.
Syntheses and Catalytic Ability of Sugar-Incorporated N-Heterocyclic Carbene Pincer Pd Complexes Possessing Various N-Substituents
Authors: Imanaka Yosuke , Hashimoto Hideki , Nishioka Takanori 
Published: May 2015

Abstract
Exploration of catalysts for organic reactions in water, which is a nontoxic and nonexplosive liquid, has been studied to achieve environmentally friendly chemical processes. For such a purpose, we utilized click chemistry to incorporate sugar units into transition-metal complexes affording water-soluble complexes. In this study, a series of palladium complexes with C–C–N pincer ligands, each of which consisted of two N-heterocyclic carbenes (NHCs) and a triazole moiety with a d-glucopyranosyl unit were synthesized. These complexes possess various N-substituents, namely, methyl, isopropyl, benzyl, or d-glucopyranosyl units on the terminal NHC moieties. The diastereoselectivity in the formation of the complexes and their catalytic ability toward the Suzuki–Miyaura cross-coupling reactions in water exhibited clear N-substituent effects. The tridentate ligand with an acetylated d-glucopyranosyl unit on the terminal NHC moiety led to high diastereoselectivity in the formation of its complex, while each of the other ligands with achiral substituents on the terminal NHC units afforded both of the diastereomers with low selectivity. Catalytic reactions using the complexes were examined for the Suzuki–Miyaura cross-coupling reactions of phenylboronic acid and 4′-bromoacetophenone in water. The complex possessing an isopropyl group on the terminal NHC moiety exhibited excellent catalytic activity with TON (800000), which is comparable to the best value reported for a similar reaction.
Oxygen Consumption of Contractile C2C12 Myotubes Investigated by Scanning Electrochemical Microscopy
Authors: Igaki Yuki , Mizutani Fumio , Yasukawa Tomoyuki 
Published: May 2015

Abstract
The oxygen consumption of single contractile myotubes was investigated by amperometric monitoring of the reduction current for oxygen using scanning electrochemical microscope (SECM) equipped with Pt microelectrode. The contraction of myotubes was induced by the application of electric pulse stimulation. The reduction current for oxygen immediately decreased after application of the electric pluses with 1.0 Hz and almost reached steady state because the activity of the oxygen consumption by respiration increased due to the contraction of myotubes accompanied with a consumption of energy.
Scalable and adaptive online joins
Authors: Elseidy Mohammed , Elguindy Abdallah , Vitorovic Aleksandar , Koch Christoph 
Published: May 2015

Scalable join processing in a parallel shared-nothing environment requires a partitioning policy that evenly distributes the processing load while minimizing the size of state maintained and number of messages communicated. Previous research proposes static partitioning schemes that require statistics beforehand. In an online or streaming environment in which no statistics about the workload are known, traditional static approaches perform poorly.
This paper presents a novel parallel online dataflow join operator that supports arbitrary join predicates. The proposed operator continuously adjusts itself to the data dynamics through adaptive dataflow routing and state repartitioning. The operator is resilient to data skew, maintains high throughput rates, avoids blocking behavior during state repartitioning, takes an eventual consistency approach for maintaining its local state, and behaves strongly consistently as a black-box dataflow operator. We prove that the operator ensures a constant competitive ratio 3:75 in data distribution optimality and that the cost of processing an input tuple is amortized constant, taking into account adaptivity costs. Our evaluation demonstrates that our operator outperforms the state-of-the-art static partitioning schemes in resource utilization, throughput, and execution time.
Storage management in AsterixDB
Authors: Alsubaiee Sattam , Behm Alexander , Borkar Vinayak , Heilbron Zachary , Kim Young-Seok , Carey Michael J. , Dreseler Markus , Li Chen 
Published: May 2015

Social networks, online communities, mobile devices, and instant messaging applications generate complex, unstructured data at a high rate, resulting in large volumes of data. This poses new challenges for data management systems that aim to ingest, store, index, and analyze such data efficiently. In response, we released the first public version of AsterixDB, an open-source Big Data Management System (BDMS), in June of 2013. This paper describes the storage management layer of AsterixDB, providing a detailed description of its ingestion-oriented approach to local storage and a set of initial measurements of its ingestion-related performance characteristics.
In order to support high frequency insertions, AsterixDB has wholly adopted Log-Structured Merge-trees as the storage technology for all of its index structures. We describe how the AsterixDB software framework enables "LSM-ification" (conversion from an in-place update, disk-based data structure to a deferred-update, append-only data structure) of any kind of index structure that supports certain primitive operations, enabling the index to ingest data efficiently. We also describe how AsterixDB ensures the ACID properties for operations involving multiple heterogeneous LSM-based indexes. Lastly, we highlight the challenges related to managing the resources of a system when many LSM indexes are used concurrently and present AsterixDB's initial solution.
Reducing database locking contention through multi-version concurrency
Authors: Sadoghi Mohammad , Canim Mustafa , Bhattacharjee Bishwaranjan , Nagel Fabian , Ross Kenneth A. 
Published: May 2015

In multi-version databases, updates and deletions of records by transactions require appending a new record to tables rather than performing in-place updates. This mechanism incurs non-negligible performance overhead in the presence of multiple indexes on a table, where changes need to be propagated to all indexes. Additionally, an uncommitted record update will block other active transactions from using the index to fetch the most recently committed values for the updated record. In general, in order to support snapshot isolation and/or multi-version concurrency, either each active transaction is forced to search a database temporary area (e.g., roll-back segments) to fetch old values of desired records, or each transaction is forced to scan the entire table to find the older versions of the record in a multi-version database (in the absence of specialized temporal indexes).
In this work, we describe a novel kV-Indirection structure to enable efficient (parallelizable) optimistic and pessimistic multi-version concurrency control by utilizing the old versions of records (at most two versions of each record) to provide direct access to the recent changes of records without the need of temporal indexes. As a result, our technique results in higher degree of concurrency by reducing the clashes between readers and writers of data and avoiding extended lock delays. We have a working prototype of our concurrency model and kV-Indirection structure in a commercial database and conducted an extensive evaluation to demonstrate the benefits of our multi-version concurrency control, and we obtained orders of magnitude speed up over the single-version concurrency control.
Faster visual analytics through pixel-perfect aggregation
Authors: Jugel Uwe , Jerzak Zbigniew , Hackenbroich Gregor , Markl Volker 
Published: May 2015

State-of-the-art visual data analysis tools ignore bandwidth limitations. They fetch millions of records of high-volume time series data from an underlying RDBMS to eventually draw only a few thousand pixels on the screen.
In this work, we demonstrate a pixel-aware big data visualization system that dynamically adapts the number of data points transmitted and thus the data rate, while preserving pixel-perfect visualizations. We show how to carefully select the data points to fetch for each pixel of a visualization, using a visualization-driven data aggregation that models the visualization process. Defining all required data reduction operators at the query level, our system trades off a few milliseconds of query execution time for dozens of seconds of data transfer time. The results are significantly reduced response times and a near real-time visualization of millions of data points.
Using our pixel-aware system, the audience will be able to enjoy the speed and ease of big data visualizations and learn about the scientific background of our system through an interactive evaluation component, allowing the visitor to measure, visualize, and compare competing visualization-related data reduction techniques.