bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract SY15-04: Angiogenesis revisited: Endothelial cell metabolism as a target
Authors: Carmeliet Peter 
Published: August 2015

Abstract
Angiogenesis, the growth of new blood vessels, plays a crucial role in numerous diseases, including cancer. Anti-angiogenesis therapies have been developed to starve cancer cells from nutrients. Clinically approved anti-angiogenic drugs prolong the survival of cancer patients, but their success is limited by intrinsic refractoriness and acquired resistance. New strategies are thus needed to block tumor angiogenesis via alternative mechanisms. We recently reported that PFKFB3-driven glycolysis regulates the endothelial cell function and identity during vessel sprouting, even capable of overruling the potent activity of Notch, and that its loss in endothelial cells causes vascular hypobranching defects. Moreover, partial and transient reduction of glycolysis by blocking PFKFB3 reduced pathological angiogenesis in several disease models. Ongoing studies explore the role of lipid and amino acid metabolism in vessel sprouting, and assess the therapeutic potential of targeting these metabolic pathways for anti-angiogenic therapy.
Citation Format: Peter Carmeliet. Angiogenesis revisited: Endothelial cell metabolism as a target. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr SY15-04. doi:10.1158/1538-7445.AM2015-SY15-04
Abstract SY16-02: Clinical whole exome interpretation for precision cancer medicine
Authors: Van Allen Eliezer M. 
Published: August 2015

Abstract
Translating whole exome sequencing (WES) for prospective clinical use may impact the care of cancer patients. However, since this approach greatly expands the quantity of genomic data generated for an individual patient, multiple innovations are necessary for clinical implementation. These include clinical analysis and interpretation of large scale WES data, effective representation of WES data in a clinical environment for physician consumption, and development of knowledge-sharing platforms to ensure effective curation of clinically relevant variants. Here, we describe heuristic methods for the clinical interpretation of WES data. We also discuss approaches that may facilitate physician understanding of WES data in a clinical setting. Finally, we review existing knowledge bases and emerging mechanisms for crowdsourcing variant curation that may enable prospective WES-scale genomic profiling. Overall, this methodology may inform the widespread implementation of precision cancer medicine.
Citation Format: Eliezer M. Van Allen. Clinical whole exome interpretation for precision cancer medicine. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr SY16-02. doi:10.1158/1538-7445.AM2015-SY16-02
Abstract SY36-03: Intraoperative molecular imaging with protease-activated fluorescent imaging agents
Authors: Whitley Melodi J. , Cardona Diana M. , Blazer Dan G. , Hwang Shelley , Greenup Rachel A. , Mosca Paul J. , Cahill Joan , Mito Jeffrey K. , Cuneo Kyle C. , Larrier Nicole , O'Reilly Erin , Spasojevic Ivan , Riedel Richard F. , Eward William C. , Griffith Linda G. , Bawendi Moungi G. , Ferrer Jorge , Strasfeld David B. , Lee W. David , Brigman Brian , Kirsch David G. 
Published: August 2015

Abstract
Intra-operative detection of residual cancer in the tumor bed can be used to decrease the risk of a positive surgical margin, reduce the rate of re-excision, and tailor adjuvant therapy. LUM015 is a pegylated protease-activated imaging agent containing a near infrared fluorophore and quencher attached by a polypeptide linker. Using mouse models of soft tissue sarcoma (STS), we showed that LUM015 selectively localizes to the tumor and upon cleavage of the linker by proteases in the tissue, the quencher is released, allowing fluorescence to be detected.
We recently completed a phase I clinical trial to test the safety of LUM015 in human patients with cancer. This open-label nonrandomized trial compared 3 dose cohorts (0.5, 1.0, and 1.5 mg/kg) of LUM015 in order to determine a safe dose of LUM015 that labels tumors in humans. A total of 15 subjects, 12 with STS and 3 with breast cancer, received IV LUM015 prior to surgical resection without any adverse pharmacological activity (APA). Quantitative fluorescence imaging of the resected tissues revealed that tumor fluorescence was significantly higher than corresponding normal tissue from the same patient (p&lt;0.0001) with a mean tumor to normal fluorescence ratio of 5.4. Furthermore, within the study population, the distribution of tumor fluorescence values was significantly higher than those recorded for fat or muscle (p&lt;0.009).
We conducted comparative analyses of LUM015 pharmacodynamics in mouse and human subjects showing that biodistribution into tumors and activation by proteases is conserved across species. These studies revealed the presence of a novel, small molecule metabolite that correlates strongly with tissue fluorescence. Additional in vivo studies in mice and in vitro studies with mouse and human tissues showed that LUM015 is selectively distributed to and accumulates in tumors to result in increased fluorescence when compared to normal tissues.
Citation Format: Melodi J. Whitley, Diana M. Cardona, Dan G. Blazer, Shelley Hwang, Rachel A. Greenup, Paul J. Mosca, Joan Cahill, Jeffrey K. Mito, Kyle C. Cuneo, Nicole Larrier, Erin O'Reilly, Ivan Spasojevic, Richard F. Riedel, William C. Eward, Linda G. Griffith, Moungi G. Bawendi, Jorge Ferrer, David B. Strasfeld, W. David Lee, Brian Brigman, David G. Kirsch. Intraoperative molecular imaging with protease-activated fluorescent imaging agents. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr SY36-03. doi:10.1158/1538-7445.AM2015-SY36-03
Abstract SY42-03: One carbon metabolism and cancer
Authors: Maddocks Oliver , Labuschagne Christiaan , Vousden Karen H. 
Published: August 2015

Abstract
Cancer cells adapt their metabolism to allow for growth and proliferation, while maintaining survival under conditions of fluctuating nutrient availability. Recent studies have shown that cancer cells are highly dependent on the non-essential amino acid serine. We have found a key requirement for serine is to maintain the one carbon cycle needed for nucleotide synthesis. Serine depletion impedes nucleotide synthesis and inhibits proliferation, a response that can be rescued by providing glycine and one-carbon units in the form of formate. More recently, we have been examining the fate of serine and the effect of serine depletion on other pathways that require one-carbon metabolism, such as NADPH production and the methionine cycle. We found that the adaptation to serine starvation involves diversion of glycolytic intermediates into the de novo SSP, resulting in a greater dependence on OXPHOS to provide energy. Interestingly, the serine produced during this period of adaptation is channeled into antioxidant defense through generation of both glutathione and NADPH, to help buffer the ROS produced from this increase in OXPHOS. Defects in the ability to make this adaptation and limit ROS, as seen in cells lacking p53, impedes the ability of cells to cope with a loss of exogenous serine.
Serine is also required to support the S-adenosyl methionine (SAM) cycle, although surprisingly we have found that this reflected a requirement for ATP rather than one-carbon units. As a consequence, serine depletion caused a decrease in the conversion of methionine to SAM and a rapid remodeling of DNA methylation. We are currently examining the consequences on gene specific methylation and expression.
Funded by CR-UK and ERC
Citation Format: Oliver Maddocks, Christiaan Labuschagne, Karen H. Vousden. One carbon metabolism and cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr SY42-03. doi:10.1158/1538-7445.AM2015-SY42-03
Abstract SY43-02: Mismatch repair, gut microbiota, and the etiology of colon cancer
Authors: Martin Alberto 
Published: August 2015

Abstract
The etiology of colorectal cancer (CRC) has been linked to deficiencies in mismatch repair and adenomatous polyposis coli (APC) proteins, diet, inflammatory processes, and gut microbiota. However, the mechanism through which the microbiota synergizes with these etiologic factors to promote CRC is not clear. We report that altering the microbiota composition reduces CRC in APC(Min/+)Msh2-/- and APC(Min/+)Mlh1-/- mice, and that a diet reduced in carbohydrates phenocopies this effect. Gut microbes did not induce CRC in these mice through an inflammatory response or the production of DNA mutagens but rather by providing carbohydrate-derived metabolites such as butyrate that fuels hyperproliferation of Msh2-/- and Mlh1-/- colon epithelial cells. Further, we provide evidence that the mismatch repair pathway has a role in regulating β-catenin activity and potentially modulating the differentiation of transit-amplifying cells in the colon. These data show that mismatch repair deficiency sensitizes colon epithelial cells to transformation by gut microbiota, and thereby provide an explanation for the interaction between microbiota, diet, and mismatch repair deficiency in CRC induction.
Citation Format: Alberto Martin. Mismatch repair, gut microbiota, and the etiology of colon cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr SY43-02. doi:10.1158/1538-7445.AM2015-SY43-02
Association Between Use of Statins and Mortality in Patients With Heart Failure and Ejection Fraction of ≥50%
Authors: Alehagen Urban , Benson Lina , Edner Magnus , Dahlström Ulf , Lund Lars H. 
Published: August 2015

Background—
The pathophysiology of heart failure with preserved ejection fraction is poorly understood, but may involve a systemic proinflammatory state. Therefore, statins might improve outcomes in patients with heart failure with preserved ejection fraction defined as ≥50%.

Methods and Results—

Of 46 959 unique patients in the prospective Swedish Heart Failure Registry, 9140 patients had heart failure and ejection fraction ≥50% (age 77±11 years, 54.0% women), and of these, 3427 (37.5%) were treated with statins. Propensity scores for statin treatment were derived from 40 baseline variables. The association between statin use and primary (all-cause mortality) and secondary (separately, cardiovascular mortality, and combined all-cause mortality or cardiovascular hospitalization) end points was assessed with Cox regressions in a population matched 1:1 based on age and propensity score. In the matched population, 1-year survival was 85.1% for statin-treated versus 80.9% for untreated patients (hazard ratio, 0.80; 95% confidence interval, 0.72–0.89;
P
<0.001). Statins were also associated with reduced cardiovascular death (hazard ratio, 0.86; 95% confidence interval, 0.75–0.98;
P
=0.026) and composite all-cause mortality or cardiovascular hospitalization (hazard ratio, 0.89; 95% confidence interval, 0.82–0.96;
P
=0.003).

Conclusions—
In heart failure with ejection fraction ≥50%, the use of statins was associated with improved outcomes. The mechanisms should be evaluated and the effects tested in a randomized trial.
Effects of Postconditioning on Neurogenesis and Angiogenesis During the Recovery Phase After Focal Cerebral Ischemia
Authors: Esposito Elga , Hayakawa Kazuhide , Maki Takakuni , Arai Ken , Lo Eng H. 
Published: August 2015

Background and Purpose—
Postconditioning may be a clinically feasible way to protect the brain after a stroke. However, its effects during the recovery phase post stroke remain to be fully elucidated. Here, we examine the hypothesis that ischemic postconditioning amplifies neurogenesis and angiogenesis during stroke recovery.

Methods—
Male Sprague–Dawley rats were subjected to 100-minute transient middle cerebral artery occlusion (MCAO) or postconditioning (100-minute middle cerebral artery occlusion plus 10-minute reperfusion plus 10-minute reocclusion). After 2 weeks, infarct volumes, behavioral outcomes, and immunohistochemical markers of neurogenesis and angiogenesis were quantified.

Results—
Postconditioning significantly reduced infarction and improved neurological outcomes. Concomitantly, brains subjected to postconditioning showed an increase in doublecortin/BrdU and collagen-IV/Ki67-positive cells.

Conclusions—
These results suggest that therapeutic effects of postconditioning may involve the promotion of neurogenesis and angiogenic remodeling during the recovery phase after focal cerebral ischemia.
Variability of Hawaiian Winter Rainfall during La Niña Events since 1956
Authors: O’Connor Christopher F. , Chu Pao-Shin , Hsu Pang-Chi , Kodama Kevin 
Published: August 2015

Abstract
Rainfall in Hawaii during La Niña years has undergone abnormal variability since the early 1980s. Traditionally, Hawaii receives greater-than-normal precipitation during the La Niña wet seasons. Recently, La Niña years have experienced less-than-normal rainfall. A drying trend in Hawaiian precipitation during La Niña years is evident. A changepoint analysis determined that the shift in precipitation occurred in 1983, forming the two epochs used for comparison in this study. The first epoch (E1) runs from 1956 to 1982 and the second epoch (E2) from 1983 to 2010. Location-specific changes in rainfall anomalies from E1 to E2 throughout the Hawaiian Islands are examined, illustrating that the greatest difference in rainfall between epochs is found on the climatologically drier sides (i.e., south and west) of the islands. Variations in tropical sea surface temperatures and circulation features in the northern Pacific Ocean have changed during La Niña wet seasons, thus changing La Niña–year rainfall.
The strengthening, broadening, and westward shifting of the eastern North Pacific subtropical high, coupled with an eastward elongation and intensification of the subtropical jet stream, are two main influences when considering the lack of precipitation during the recent La Niña wet seasons. Moisture transport analysis shows that variations in circulation structures play a dominant role in the reduction of moisture flux convergence in the Hawaiian region during the second epoch. Additionally, a storm-track analysis reveals that the changes found in the aforementioned circulation features are creating a less favorable environment for the development of Kona lows and midlatitude fronts in the vicinity of Hawaii.
Determinants of attitudes towards professional mental health care, informal help and self-reliance in people with subclinical depression
Authors: van Zoonen Kim , Kleiboer Annet , Cuijpers Pim , Smit Jan , Penninx Brenda , Verhaak Peter , Beekman Aartjan 
Published: August 2015

Background: Although little is known about which people with subclinical depression should receive care to prevent the onset of depression, it is clear that remediating symptoms of depression is important. However, depending on the beliefs people hold about help, some people will seek professional help, while others seek informal help or solve problems on their own. Aims: This study examined associations between attitudes about help and socio-demographic variables, mastery, severity of depressive symptoms, accessibility to care, and health care utilization at baseline and 4-year follow-up. Methods: Data were derived from a large cohort study, the Netherlands Study of Depression and Anxiety (NESDA). A total of 235 respondents with subclinical depression completed questionnaires at baseline and follow-up. Attitude was assessed using a short version of the ‘Trust in mental health care’ questionnaire. Results: Positive attitude towards professional care was associated with being male, younger age, higher mastery and easy accessibility to care. Positive attitude towards informal help was associated with higher mastery and unemployment. Older age, less accessibility to care and lower mastery were associated with positive attitude towards self-reliance. A change in care utilization was associated with positive attitudes towards professional care at follow-up. Conclusions: People differ in the way they cope with symptoms which may influence their preferred care. Higher levels of mastery were positively associated with professional and informal care, but negatively associated with self-reliance. Both age and mastery showed relatively large effect sizes.
Experience of a Small British Pacing Centre between 1994 and 2000: Some Answers to the Problem of Low UK Implantation Rates
Authors: D'Souza R. , Dawson F , Kerr F. 
Published: August 2015

Raigmore is a district general hospital offering a permanent pacemaker service to its catchment population of 233,500. This report reviews the pacemaker practice over a seven year period (1994 to 2000) and makes a comparison with the national database and other hospitals in the UK. The records of all patients receiving new implantions for the period under observation were reviewed retrospectively. Data collected included number of patients paced each year, age, sex, indications and complications. In the 84 months studied 3/71 patients received new permanent pacemakers (the mean age was 74 years and 51% were male). The most common presenting symptoms were syncope (62%), dizzy spells (24%), and heart failure (11.5%). The most common indication for permanent pacemaker insertion was complete atrioventricular block (58%) followed by sick sinus syndrome (20%). The implantation rate was 419.3/million population /year in 2000. Pacemaker modes used were appropriate and the early and late complication rates were low (2.7%). This current audit demonstrates continued growth of the service with low-complication rates and implantation rates which approach those in Western Europe and North America.
Isolated Langerhans Cell Histiocytosis Bone Lesion in Pediatric Patients
Authors: Bezdjian Aren , Alarfaj Abdullah A. , Varma Namrata , Daniel Sam J. 
Published: August 2015

ObjectiveThe present study reviewed all cases reported of isolated Langerhans cell histiocytosis bone lesions in the head and neck of pediatric patients. The objective was to create a treatment algorithm to facilitate the diagnosis and management of these lesions.Data SourcesEligible articles were identified through a comprehensive search of the following electronic databases: PubMed, Ovid Medline, Embase, and Cochrane Library.Review MethodsTwo authors independently reviewed the titles and abstracts retrieved by the electronic search concordant with the criteria for study eligibility. The lists of articles from each author were jointly reviewed and a common list created. All relevant articles were reviewed in hard copies and as full texts to justify inclusion.ResultsA total of 201 patients (67% male, mean age: 8.1 ± 4.3 years) were included from 45 studies. Clinical presentations included swelling (64%), pain (9%), or both (18%). The skull (61%) and the orbit (24%) were the most common location for isolated bone lesions in the head and neck. The most frequently documented management option was resection, followed by observation, chemotherapy, and intralesional steroid injection.ConclusionsDue to its rarity and variability in presentation and severity, treatment of these lesions has yet to be standardized. Based on the review, a diagnosis and treatment algorithm was created for head and neck surgeons when encountering these types of lesions.
Ex vivo simulation of cardiopulmonary bypass with human blood for hemocompatibility testing
Authors: Teligui Leylah , Dalmayrac Emilie , Corbeau Jean-Jacques , Bouquet Emmanuelle , Godon Alban , Denommé Anne-Sophie , Binuani Partrice , Verron Laurence , Boer Christa , Baufreton Christophe 
Published: August 2015

Object: Experimental circuits for biomaterial surface testing are frequently limited by the tested blood volume, composition of the circuit, flow conditions and the use of animal blood. This report describes an ex vivo set-up for simulated cardiopulmonary bypass with human blood perfusion. We investigated the clinical generalizability of the observed effects on hematological and metabolic parameters and the hemocompatibility of the system. Methods: The simulated cardiopulmonary bypass circuit consisted of a heparin-coated tubing system connected to an oxygenator and a venous reservoir. Normothermic flow of blood obtained from healthy donors was maintained at 2.4 L/min/m2 by a roller pump. Heparin was dosed to obtain a target activated clotting time (ACT) ⩾500 s. Blood was drawn at baseline and 0, 10, 60 and 120 minutes following the initiation of blood flow to determine hematological and metabolic parameters and the hemocompatibility of the extracorporeal system. Data were analyzed using repeated measures ANOVA. Results: Two hours of blood perfusion resulted in a small, but clinically unimportant reduction in hematocrit, whereas hemoglobin levels and red blood cell, platelet and leukocyte counts remained stable. There was a significant increase in ACT throughout the experiment. While pO2 levels and the pH remained unaltered during the experiment, pCO2 values decreased from 51 ± 6 mmHg at T0 to 41 ± 3 mmHg at T120 (p<0.001). Simulated cardiopulmonary bypass induced a two-fold increase in C3a (p=0.001) while tissue factor was decreased from 44 ± 14 pg/mL at T0 to 38 ± 13 pg/mL at T120 (p=0.009). Levels of CD40L, prothrombin fragment 1+2, β-thromboglobulin and factor VIIa remained stable over time. Conclusion: The ex vivo set-up for simulated cardiopulmonary bypass mimicked the clinical cardiosurgical setting. Exposure of fresh donor blood to the extracorporeal circuit showed a good hemocompatibility, indicated by maintained hematological parameters and a mild immune response.
Do parties converge to the electoral mean in all political systems?
Authors: Gallego Maria , Schofield Norman 
Published: August 2015

Many formal models suggest that parties or candidates should locate at the electoral mean. Yet, there is no consistent evidence of such convergence across political systems. Schofield’s (2007) Valence Theorem proves that when valence differences across parties are large, there is non-convergence to the mean. Convergence to the mean depends on the value of the convergence coefficient, c. When c is high there is significant centrifugal tendency acting on the parties and when c is low there is a significant centripetal tendency acting on the parties. In this paper we apply the stochastic valence model of elections in various countries under different political regimes and use the convergence coefficient of these elections to classify political systems. Our results show that the convergence coefficient varies across elections in a country, across countries using the same political system and across political regimes. For countries using proportional representation, namely Israel, Turkey and Poland, the centrifugal tendency is very high and parties move away from the mean. In the majoritarian polities of the United States and the UK, parties are located at the mean, as the centrifugal tendency is very low. In anocracies, the autocrat imposes limitations on how far from the origin the opposition parties can move but the equilibrium is fragile.