bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB-215: Combination studies using PI3K isoform-selective inhibitors in PTEN-deficient cancer cells
Authors: Blackwell Christina , De Young. M. Phillip 
Published: July 2016

Abstract
A large and growing body of evidence indicates that dysregulation of phosphoinositide 3-kinase (PI3K) pathway signaling activity is necessary for cancer cell survival, most commonly as a result of genetic defects causing a deficiency of the tumor suppressor PTEN or activating mutations or amplification of PIK3CA (PI3Kα). In the context of PTEN-deficient cancer cells, it appears that in most cases PI3Kβ (PIK3CB) and not PI3Kα is required for PI3K survival signaling. GSK2636771 is a potent, orally bioavailable, selective ATP-competitive inhibitor of PI3Kβ with single digit nanomolar potency. It possesses &gt;10-fold selectivity over PI3Kδ and &gt;1000-fold selectivity over other lipid/atypical kinases including PI3Kα and mTOR. In this study, western blot analysis was performed to assess phosphorylation changes to AKT, ERK, and S6 proteins in 21 tumor cell lines of various histologies and genetic backgrounds treated with GSK2636771. PTEN deficiency (lack of PTEN protein expression) was the best marker to predict response to PI3Kβ inhibition based on reduction of phospho-AKT levels. Some of these “responsive” cells also harbored other genetic alterations such as amplified and/or mutated (V600E) BRAF, NF1 mutations, or EGFR amplification. For example, inhibition of PI3Kβ resulted in partial reduction of phospho-AKT and phospho-S6 levels in PTEN-deficient A2058, MDA-MB-468, and LNCAP cells, whereas PI3Kα inhibition by BYL719 treatment had no effect on AKT, ERK, and S6 phosphorylation. In PTEN-deficient, PIK3CA (E542K) mutant CAL-51 cells, the opposite was observed: GSK2636771 had no effect on phospho levels of AKT, ERK, and S6, but BYL719 treatment caused reductions of phospho-AKT and phospho-S6. Interestingly, when both isoforms were inhibited, the effects on phospho-AKT and phospho-S6 levels were more pronounced in all four cell lines, suggesting that these compounds may synergize to inhibit PI3K signaling. Combination treatment of both inhibitors had modest effects on cell growth in LNCAP cells, although it was observed that 6-day GSK2636771 treatment pulsed with BYL719 for 2 days in LNCAP provided similar antiproliferative effects as co-treatment of both molecules for 6 days. This may suggest that pulsing BYL719 with constant GSK2636771 treatment may be effective at inhibiting tumor growth in vivo while minimizing the on target toxicity that has been observed with sustained PI3Kα inhibition.
Citation Format: Christina Blackwell, M. Phillip De Young. Combination studies using PI3K isoform-selective inhibitors in PTEN-deficient cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-215.
Abstract LB-236: Self-renewal of CD133hi cells by IL6/Notch3 signaling regulates endocrine resistance in metastatic breast cancers
Authors: Sansone Pasquale , Claudio Ceccarelli , Berishaj Marjan , Chang Qing , Vinagolu Rajasekhar , Perna Fabiana , Bowman Robert , Vidone Michele , Daly Laura , Nnoli Jennifer , Santini Donatella , Mario Taffurelli , Shih Natalie , Feldman Michael , Mao Jun James , Colameco Christopher , Chen Jinbo , DeMichele Angela , Fabbri Nicola , Healey John , Cricca Monica , Gasparre Giuseppe , Lyden David , Bonafe Massimiliano , Bromberg Jacqueline F. 
Published: July 2016

Abstract
The mechanisms of metastatic progression from hormonal therapy (HT)-induced tumour dormancy to hormonal therapy resistance is largely unknown in luminal breast cancer. Analysis of clinical specimens revealed the enrichment of CD133hi/ERlo cancer cells in primary tumours following neo-adjuvant endocrine therapy and in HT refractory metastatic disease. We developed spontaneous experimental models of metastatic luminal breast cancer and determined that endocrine therapy can promote the generation of HT- resistant, self-renewing CD133hi/ERlo/IL6hicells. Dual pharmacological inhibition of IL6R-IL6 (tocilizumab) and ER (HT) abrogated the establishment of CD133hi/ERlo/IL6hi cancer stem cells (CSCs), restoring endocrine sensitivity to hormone-refractory metastatic disease, in both experimental and patient-derived endocrine-resistant bone metastasis. Hormonal therapy, initially abrogated oxidative phosphorylation (OXPHOS) generating dormant (self-renewal deficient-CD133hi/ERlo/OXPHOSlo) cancer cells, These cells exited metabolic dormancy via an IL6 driven feed-forward ERlo-IL6hi-Notchhi loop, activating OXPHOS, in the absence of ER activity. Importantly, the inhibition of IL6R/IL6-Notch pathways switched the self-renewal of CD133hi CSCs, from an IL6/Notch-dependent one to an ER-dependent one, through the re-expression of ER. Thus, HT induces an OXPHOS metabolic editing of luminal breast cancers, paradoxically establishing HT-driven self-renewal of dormant CD133hi/ERlo cells mediating metastatic progression, which is sensitive to dual targeted therapy.
Citation Format: Pasquale Sansone, Ceccarelli Claudio, Marjan Berishaj, Qing Chang, Rajasekhar Vinagolu, Fabiana Perna, Robert Bowman, Michele Vidone, Laura Daly, Jennifer Nnoli, Donatella Santini, Taffurelli Mario, Natalie Shih, Michael Feldman, Jun James Mao, Christopher Colameco, Jinbo Chen, Angela DeMichele, Nicola Fabbri, John Healey, Monica Cricca, Giuseppe Gasparre, David Lyden, Massimiliano Bonafe, Jacqueline F. Bromberg. Self-renewal of CD133hi cells by IL6/Notch3 signaling regulates endocrine resistance in metastatic breast cancers. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-236.
Abstract LB-365: Novel susceptibility loci for colorectal cancer: Findings from the colorectal transdisciplinary (CORECT) study OncoArray analysis
Authors: Schmit Stephanie L. , Schumacher Fredrick R. , Edlund Christopher K. , Gong Jian , Rennert Gad , Zheng Wei , Le Marchand Loic , Peters Ulrike , Casey Graham , Hsu Li , Gruber Stephen B. , Conti David V. ,   CORECT, GECCO, CCFR, ACCC, and MEC
Published: July 2016

Abstract
Genome-wide association studies (GWAS) have identified 58 susceptibility alleles across 37 regions associated with the incidence of colorectal cancer (CRC) with P&lt;5E-08, yet much of the disease's familial risk remains to be explained. In its first phase, the Colorectal Transdisciplinary (CORECT) study, in collaboration with the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colon Cancer Family Registry (CCFR), the Asian Colorectal Cancer Consortium (ACCC) and the Multiethnic Cohort (MEC), identified 6 of these loci based on 18,299 cases and 19,656 controls. The CORECT consortium recently completed genotyping on approximately 26,000 cases and 18,000 controls using the Illumina Infinium® OncoArray platform with the goals of 1) identifying novel overall and ethnic-specific susceptibility alleles and 2) fine-mapping known CRC risk loci. Newly genotyped samples represent multiple ethnic groups and include individuals primarily of European (75%), Asian (19%) and Hispanic (2.5%) origins. Combining both phases of CORECT, this study constitutes the largest GWAS meta-analysis of CRC to date. Here, we present European-specific results derived from genetically-defined Europeans genotyped on the OncoArray (16,456 cases and 10,442 controls), CORECT Phase I (5,584 cases and 5,329 controls), and CCFR/GECCO (12,715 cases and 14,327 controls), for a total of 34,755 cases and 30,098 controls. OncoArray genotype data were imputed to the 1000 Genomes Phase III reference panel, and summary results from logistic regression adjusting for age, sex, global ancestry, and study-specific covariates were combined in a fixed-effects inverse variance-weighted meta-analysis. Preliminary results indicate at least 10 new low-penetrance risk variants that reach genome-wide significance (P&lt;5E-08) and that are independent of known risk loci. Further, fine-mapping of well-established CRC susceptibility regions is underway. This investigation provides additional insight into the etiology of CRC and informs future risk modeling efforts.
Citation Format: Stephanie L. Schmit, Fredrick R. Schumacher, Christopher K. Edlund, Jian Gong, Gad Rennert, Wei Zheng, Loic Le Marchand, Ulrike Peters, Graham Casey, Li Hsu, Stephen B. Gruber, David V. Conti, CORECT, GECCO, CCFR, ACCC, and MEC. Novel susceptibility loci for colorectal cancer: Findings from the colorectal transdisciplinary (CORECT) study OncoArray analysis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-365.
Seed germination studies on Gymnacranthera canarica (King) Warb. - a Vulnerable tree species of a highly threatened Myristica swamp ecosystem
Authors: Keshavachandra K. , Krishnakumar G. 
Published: July 2016

Gymnacranthera canarica (King) Warb. is an exclusive Myristica swamp species endemic to the Western Ghats. The Myristica swamp is a Critically Endangered ecosystem. Studies were carried out to assess the viability, germination and storage behaviour of Gymnacranthera canarica seeds. In the present study, it was observed that seeds have shown an initiation of germination after two weeks. A maximum of 90% germination was recorded when the initial moisture content was 38.04 ± 1.75 %. A decreased percentage (3%) was observed when the moisture content reached 14.26 ± 2.3 after 70 days of storage. Seeds failed to germinate beyond this moisture level. A desiccation study showed recalcitrant behaviour and seeds can be stored in lab conditions for up to two and half months.
An updated checklist of shrimps on the Indian coast
Authors: Samuel Vijay Kumar Deepak , Sreeraj Chemmencheri Ramakrishnan , Krishnan Pandian , Parthiban Chermapandi , Sekar Veeramuthu , Chamundeeswari Kanagaraj , Immanuel Titus , Shesdev Patro , Purvaja Ramachandran , Ramesh Ramachandran 
Published: July 2016

This study reports an updated checklist of marine shrimps found along the Indian coast, including the Lakshadweep and the Andaman & Nicobar Islands. A total of 364 species classified under 128 genera belonging to the order Decapoda is reported, thus adding 27 species to the existing checklist of 337 species. Marine shrimps are classified under two suborders of the order Decapoda, viz., Dendrobranchiata and Pleocyemata, and the two suborders account for 155 (42.6 %) and 209 species (57.4 %) of these 364 species, respectively. Pleocyemata is represented by three infraorders, viz., Axiidea, Caridea and Stenopodidea, while Caridea has a maximum of 199 reported species. Among the 12 superfamilies, Penaeoidea contributed to 38.13% (135 species) followed by Paleaemonidea with 18.07% (64 species). All other superfamilies were found to contribute less than 12%. Superfamilies, Bresilloidea and Psalidopodoidea had only single species representatives (0.28% each). The final list was compiled after reviewing all existing literature including monographs, catalogues, checklists, websites and fishery reports. The scientific names were validated with the World Register of Marine Species (WoRMS) database. A total of 25 issues were identified from the previous checklist out of which 19 species have been updated with the correct, accepted names and six species have been removed from the previous list.
Bats (Mammalia: Chiroptera) of the southeastern Truong Son Mountains, Quang Ngai Province, Vietnam
Authors: Son Nguyen Truong , O'shea Thomas J. , Gore Jeffery A. , Csorba Gabor , Tu Vuong Tan , Oshida Tatsuo , Endo Hideki , Motokawa Masaharu 
Published: July 2016

Bat communities of mainland Southeast Asia can be highly diverse. Many are under threat. Despite this, regional faunal composition is not well documented for many areas, including regions of Vietnam. We assessed the biodiversity of bats in a watershed protection forest in the southeastern Truong Son (Annamite) Mountains, southwestern Quang Ngai Province, Vietnam in 2011–2013. Twenty species of insectivorous bats were documented including a high diversity of Murina species Tube-nosed Bats. Diversity and abundance indices were compared with that recorded previously in two nature reserves and one national park in Vietnam, and were higher or comparable in several measures despite the lack of a karst substrate for roosts. Reproduction in the insectivorous bat fauna coincided with the early rainy season. In the late dry season, pregnant females of several species were observed but volant juveniles were not present, whereas in the early wet season adult females were lactating or post-lactating and volant juveniles of nine species were detected. We recorded echolocation calls of 14 bat species; for each species, we compared features of calls with those reported previously in other Asian localities. For some species we found discrepancies in call metrics among studies, perhaps suggesting a greater hidden biodiversity of bats in Southeast Asia.
Frequency, Type, and Volume of Leisure-Time Physical Activity and Risk of Coronary Heart Disease in Young Women
Authors: Chomistek Andrea K. , Henschel Beate , Eliassen A. Heather , Mukamal Kenneth J. , Rimm Eric B. 
Published: July 2016

Background:
The inverse association between physical activity and coronary heart disease (CHD) risk has primarily been shown in studies of middle-aged and older adults. Evidence for the benefits of frequency, type, and volume of leisure-time physical activity in young women is limited.

Methods:
We conducted a prospective analysis among 97 230 women aged 27 to 44 years at baseline in 1991. Leisure-time physical activity was assessed biennially by questionnaire. Cox proportional hazards models were used to examine the associations between physical activity frequency, type, and volume, and CHD risk.

Results:

During 20 years of follow-up, we documented 544 incident CHD cases. In multivariable-adjusted models, the hazard ratio (95% confidence interval) of CHD comparing ≥30 with <1 metabolic equivalent of task-hours/wk of physical activity was 0.75 (0.57–0.99) (
P
, trend=0.01). Brisk walking alone was also associated with significantly lower CHD risk. Physical activity frequency was not associated with CHD risk when models also included overall activity volume. Finally, the association was not modified by body mass index (kg/m
2
) (
P
, interaction=0.70). Active women (≥30 metabolic equivalent of task-hours/wk) with body mass index<25 kg/m
2
had 0.52 (95% confidence interval, 0.35–0.78) times the rate of CHD in comparison with women who were obese (body mass index≥30 kg/m
2
) and inactive (physical activity <1 metabolic equivalent of task-hours/wk).

Conclusions:
These prospective data suggest that total volume of leisure-time physical activity is associated with lower risk of incident CHD among young women. In addition, this association was not modified by weight, emphasizing that it is important for normal weight, overweight, and obese women to be physically active.
The Influence of Topography on Convective Storm Environments in the Eastern United States as Deduced from the HRRR
Authors: Katona Branden , Markowski Paul , Alexander Curtis , Benjamin Stanley 
Published: July 2016

Abstract
Relatively little is known about how topography affects convective storms. The first step toward understanding these effects is to investigate how topography affects storm environments. Unfortunately, the effects of topography on convective environments are not easily observed directly. Instead, it is necessary to resort to using output from the High-Resolution Rapid Refresh (HRRR). The HRRR’s 3-km grid spacing can resolve some of the larger-scale topographic effects. Popular convective storm forecasting parameters obtained from the HRRR are averaged on convective days from February to September 2013–15. It is surmised that most of the day-to-day variability attributable to synoptic- and mesoscale meteorological influences is removed by averaging; the remaining horizontal heterogeneity in parameters related to instability and vertical wind shear is due to the hemispheric-scale meridional temperature and pressure gradient, and likely also topographic influences, especially where recurring longitudinal variations in instability, wind shear, etc. are found. Anomalies are sensitive to the ambient low-level wind direction (i.e., whether winds are locally blowing upslope or downslope), especially for parameters that depend on the low-level vertical shear. The statistical significance of local maxima and minima is demonstrated by comparing the amplitudes of the anomalies to bootstrapped estimates of the standard errors.
Comparing the main compositional activities in a study of eight composers
Authors: Roels Hans 
Published: July 2016

This article addresses the problem of comparing individual creative processes in music composition, across aesthetic visions, research concepts, data collection and analysis methods. Eight professional composers are studied in a real-world setting in search of broad compositional activities that are both common to the composers studied and that are meaningful for individual compositional processes. To compare individual creative processes, the analytic route, specifically the last analysis phases of the research process, is made as transparent as possible. The need for a synthesis phase is clarified by presenting two visual syntheses, apart from four textual synthesis themes: an “events time line” – a general chronological account of salient compositional activities – and a “music in progress” visualization, displaying the development of the new composition. To apply similar criteria in the analysis of eight creative processes, an analysis framework is proposed, consisting of four main compositional activities (planning, exploring, writing and rewriting) and three attributes (productivity, level of musical abstraction and creativity). The results of the study show how the eight processes are individually characterized by a specific configuration, that is, the four main compositional activities appear in a selective presence, chronological order and hierarchy. Although no activities or strategies common to all eight composers were found, some configurations were also recognized in creative processes outside the current study. Finally, indications are discussed that general models of compositional processes and actions, such as evaluating, may be related to specific configurations of the four main activities.
Developing the next generation of quality improvers: An evaluation of a region wide structured support quality improvement training programme
Authors: Bethune Rob , Dahill Mark , Finucane Katherine , Van Hamel Clare , Watson Joanne , Woodhead Patricia 
Published: July 2016

Introduction Despite an increasing and widespread understanding of the importance of quality improvement in healthcare, medical students and junior doctors receive variable training in improvement methods. The South West Foundation Doctor quality improvement programme attempted to equip junior doctors with the skills to develop and improve healthcare services. Methods A questionnaire-based evaluation was undertaken of a cohort of first-year doctors who took part in a 9-month quality improvement educational intervention. The study was conducted across a whole training region with some of the hospitals running the quality improvement educational intervention and one acting as the natural control cohort. A previously validated questionnaire was sent out at the start and end of their first year. Results In questions related to attitudes to all domains of quality improvement first-year doctors consider it an important part of their role as doctors to improve the quality of healthcare. However, they do not think they are equipped with the skills to do this improvement. During their first year as doctors, these self-reported skills increased dramatically in the hospitals that took part in the programme but not in the single hospital that did not run the programme. Conclusion First-year doctors consider improving the quality of healthcare to be an important part of their job. This can be contrasted to their self-reported skills related to quality improvement when they start their first year. In hospitals that run a structured, supported experiential quality improvement programme, these self-reported skills increase statistically significantly.
Introduction of the identification, situation, background, assessment, recommendations tool to improve the quality of information transfer during medical handover in intensive care
Authors: Ramasubbu Benjamin , Stewart Emma , Spiritoso Rosalba 
Published: July 2016

Objective To audit the quality and safety of the current doctor-to-doctor handover of patient information in our Cardiothoracic Intensive Care Unit. If deficient, to implement a validated handover tool to improve the quality of the handover process. Methods In Cycle 1 we observed the verbal handover and reviewed the written handover information transferred for 50 consecutive patients in St George’s Hospital Cardiothoracic Intensive Care Unit. For each patient’s handover, we assessed whether each section of the Identification, Situation, Background, Assessment, Recommendations tool was used on a scale of 0–2. Zero if no information in that category was transferred, one if the information was partially transferred and two if all relevant information was transferred. Each patient’s handover received a score from 0 to 10 and thus, each cycle a total score of 0–500. Following the implementation of the Identification, Situation, Background, Assessment, Recommendations handover tool in our Intensive Care Unit in Cycle 2, we re-observed the handover process for another 50 consecutive patients hence, completing the audit cycle. Results There was a significant difference between the total scores from Cycle 1 and 2 (263/500 versus 457/500, p < 0.001). The median handover score for Cycle 1 was 5/10 (interquartile range 4–6). The median handover score for Cycle 2 was 9/10 (interquartile range 9–10). Patient handover scores increased significantly between Cycle 1 and 2, U = 13.5, p < 0.001. Conclusions The introduction of a standardised handover template (Identification, Situation, Background, Assessment, Recommendations tool) has improved the quality and safety of the doctor-to-doctor handover of patient information in our Intensive Care Unit.