bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Gebra–Magia Complex: mass-transport processes reworking trough-mouth fans in the Central Bransfield Basin (Antarctica)
Authors: Casas D. , García M. , Bohoyo F. , Maldonado A. , Ercilla G. 
Published: June 2017

Abstract
The Gebra–Magia Complex is an important example of a submarine mass-movement composite located on the lower continental slope of the Antarctic Peninsula (Central Bransfield Basin). Continuous instability dynamics over time is inferred to have affected the palaeo-trough-mouth fans present in the study area.
The depositional architecture and the outstanding relief of the Gebra Valley, which is the most striking morphological feature in the area, determine the asymmetrical morphology of the complex. This complex is characterized, from east to west, by an open-slope margin flanking the sidewall of the Gebra Valley, the Gebra Valley itself and a SW margin that is connected to the Magia area by a large scar approximately 7.8 km to the SW.
The Gebra Valley is a Quaternary debris valley resulting from repeated large-scale mass-transport and cut-and-fill processes. In contrast, the Magia area is dominated by unchannelized sedimentary instability processes, resulting in a different sedimentary architecture and morphology. The near-surface sediments in the Gebra–Magia Complex document the continuous occurrence of recent mass movements, as also evidenced by flows transported downslope as unchannelized or channelized flows.
Climate and tectonic activity are considered the primary factors controlling the development of the complex.
5-HT causes splanchnic venodilation
Authors: Seitz Bridget M. , Orer Hakan S. , Krieger-Burke Teresa , Darios Emma S. , Thompson Janice M. , Fink Gregory D. , Watts Stephanie W. 
Published: June 2017

Serotonin [5-hydroxytryptamine (5-HT)] causes relaxation of the isolated superior mesenteric vein, a splanchnic blood vessel, through activation of the 5-HT7receptor. As part of studies designed to identify the mechanism(s) through which chronic (≥24 h) infusion of 5-HT lowers blood pressure, we tested the hypothesis that 5-HT causes in vitro and in vivo splanchnic venodilation that is 5-HT7receptor dependent. In tissue baths for measurement of isometric contraction, the portal vein and abdominal inferior vena cava relaxed to 5-HT and the 5-HT1/7receptor agonist 5-carboxamidotryptamine; relaxation was abolished by the 5-HT7receptor antagonist SB-269970. Western blot analyses showed that the abdominal inferior vena cava and portal vein express 5-HT7receptor protein. In contrast, the thoracic vena cava, outside the splanchnic circulation, did not relax to serotonergic agonists and exhibited minimal expression of the 5-HT7receptor. Male Sprague-Dawley rats with chronically implanted radiotelemetry transmitters underwent repeated ultrasound imaging of abdominal vessels. After baseline imaging, minipumps containing vehicle (saline) or 5-HT (25 μg·kg−1·min−1) were implanted. Twenty-four hours later, venous diameters were increased in rats with 5-HT-infusion (percent increase from baseline: superior mesenteric vein, 17.5 ± 1.9; portal vein, 17.7 ± 1.8; and abdominal inferior vena cava, 46.9 ± 8.0) while arterial pressure was decreased (~13 mmHg). Measures returned to baseline after infusion termination. In a separate group of animals, treatment with SB-269970 (3 mg/kg iv) prevented the splanchnic venodilation and fall in blood pressure during 24 h of 5-HT infusion. Thus, 5-HT causes 5-HT7receptor-dependent splanchnic venous dilation associated with a fall in blood pressure.NEW & NOTEWORTHY This research is noteworthy because it combines and links, through the 5-HT7receptor, an in vitro observation (venorelaxation) with in vivo events (venodilation and fall in blood pressure). This supports the idea that splanchnic venodilation plays a role in blood pressure regulation.
The Alkylating Chemotherapeutic Temozolomide Induces Metabolic Stress in IDH1-Mutant Cancers and Potentiates NAD+ Depletion–Mediated Cytotoxicity
Authors: Tateishi Kensuke , Higuchi Fumi , Miller Julie J. , Koerner Mara V.A. , Lelic Nina , Shankar Ganesh M. , Tanaka Shota , Fisher David E. , Batchelor Tracy T. , Iafrate A. John , Wakimoto Hiroaki , Chi Andrew S. , Cahill Daniel P. 
Published: June 2017

Abstract
IDH1-mutant gliomas are dependent upon the canonical coenzyme NAD+ for survival. It is known that PARP activation consumes NAD+ during base excision repair (BER) of chemotherapy-induced DNA damage. We therefore hypothesized that a strategy combining NAD+ biosynthesis inhibitors with the alkylating chemotherapeutic agent temozolomide could potentiate NAD+ depletion–mediated cytotoxicity in mutant IDH1 cancer cells. To investigate the impact of temozolomide on NAD+ metabolism, patient-derived xenografts and engineered mutant IDH1-expressing cell lines were exposed to temozolomide, in vitro and in vivo, both alone and in combination with nicotinamide phosphoribosyltransferase (NAMPT) inhibitors, which block NAD+ biosynthesis. The acute time period (&lt;3 hours) after temozolomide treatment displayed a burst of NAD+ consumption driven by PARP activation. In IDH1-mutant–expressing cells, this consumption reduced further the abnormally lowered basal steady-state levels of NAD+, introducing a window of hypervulnerability to NAD+ biosynthesis inhibitors. This effect was selective for IDH1-mutant cells and independent of methylguanine methyltransferase or mismatch repair status, which are known rate-limiting mediators of adjuvant temozolomide genotoxic sensitivity. Combined temozolomide and NAMPT inhibition in an in vivo IDH1-mutant cancer model exhibited enhanced efficacy compared with each agent alone. Thus, we find IDH1-mutant cancers have distinct metabolic stress responses to chemotherapy-induced DNA damage and that combination regimens targeting nonredundant NAD+ pathways yield potent anticancer efficacy in vivo. Such targeting of convergent metabolic pathways in genetically selected cancers could minimize treatment toxicity and improve durability of response to therapy. Cancer Res; 77(15); 4102–15. ©2017 AACR.
Colorectal Cancer Screening: How Health Gains and Cost-Effectiveness Vary by Ethnic Group, the Impact on Health Inequalities, and the Optimal Age Range to Screen
Authors: McLeod Melissa , Kvizhinadze Giorgi , Boyd Matt , Barendregt Jan , Sarfati Diana , Wilson Nick , Blakely Tony 
Published: June 2017

Abstract
Background: Screening programs consistently underserve indigenous populations despite a higher overall burden of cancer. In this study, we explore the likely health gains and cost-effectiveness of a national colorectal cancer screening program for the indigenous Māori population of New Zealand (NZ).
Methods: A Markov model estimated: health benefits (quality-adjusted life-year; QALY), costs, and cost-effectiveness of biennial immunochemical fecal occult blood testing (FOBTi) of 50- to 74-year-olds from 2011. Input parameters came from literature reviews, the NZ Bowel Screening Programme Pilot, and NZ linked health datasets. Equity analyses substituted non-Māori values for Māori values of background (noncolorectal cancer) morbidity and mortality, colorectal cancer survival and incidence, screening coverage, and stage-specific survival. We measured the change in “quality-adjusted life expectancy” (QALE) as a result of the intervention.
Results: Based upon a threshold of GDP per capita (NZ$45,000), colorectal cancer screening in NZ using FOBTi is cost-effective: NZ$2,930 (US$1,970) per QALY gained [95% uncertainty interval: cost saving to $6,850 (US$4,610)]. Modeled health gains per capita for Māori were less than for non-Māori: half for 50- to 54-year-olds (0.031 QALYs per person for Māori vs. 0.058 for non-Māori), and a fifth (0.003 c.f. 0.016) for 70- to 74-year-olds and ethnic inequalities in QALE increased with colorectal cancer screening.
Conclusions: Colorectal cancer screening in NZ using FOBTi is likely to be cost-effective but risks increasing inequalities in health for Māori.
Impact: To avoid or mitigate the generation of further health inequalities, attention should be given to underserved population groups when planning and implementing screening programs. Cancer Epidemiol Biomarkers Prev; 26(9); 1391–400. ©2017 AACR.
How Many Deaths from Colorectal Cancer Can Be Prevented by 2030? A Scenario-Based Quantification of Risk Factor Modification, Screening, and Treatment in Norway
Authors: Skyrud Katrine Damgaard , Myklebust Tor Åge , Bray Freddie , Eriksen Morten Tandberg , de Lange Thomas , Larsen Inger Kristin , Møller Bjørn 
Published: June 2017

Abstract
Background: Colorectal cancer mortality can be reduced through risk factor modification (adherence to lifestyle recommendations), screening, and improved treatment. This study estimated the potential of these three strategies to modify colorectal cancer mortality rates in Norway.
Methods: The potential reduction in colorectal cancer mortality due to risk factor modification was estimated using the software Prevent, assuming that 50% of the population in Norway—who do not adhere to the various recommendations concerning prevention of smoking, physical activity, body weight, and intake of alcohol, red/processed meat, and fiber—started to follow the recommendations. The impact of screening was quantified assuming implementation of national flexible sigmoidoscopy screening with 50% attendance. The reduction in colorectal cancer mortality due to improved treatment was calculated assuming that 50% of the linear (positive) trend in colorectal cancer survival would continue to persist in future years.
Results: Risk factor modification would decrease colorectal cancer mortality by 11% (corresponding to 227 prevented deaths: 142 men, 85 women) by 2030. Screening and improved treatment in Norway would reduce colorectal cancer mortality by 7% (149 prevented deaths) and 12% (268 prevented deaths), respectively, by 2030. Overall, the combined effect of all three strategies would reduce colorectal cancer mortality by 27% (604 prevented deaths) by 2030.
Conclusions: Risk factor modification, screening, and treatment all have considerable potential to reduce colorectal cancer mortality by 2030, with the largest potential reduction observed for improved treatment and risk factor modification.
Impact: The estimation of these health impact measures provides useful information that can be applied in public health decision-making. Cancer Epidemiol Biomarkers Prev; 26(9); 1420–6. ©2017 AACR.
Optimization of RAS/BRAF Mutational Analysis Confirms Improvement in Patient Selection for Clinical Benefit to Anti-EGFR Treatment in Metastatic Colorectal Cancer
Authors: Santos Cristina , Azuara Daniel , Garcia-Carbonero Rocio , Alfonso Pilar Garcia , Carrato Alfredo , Elez Mª Elena , Gomez Auxiliadora , Losa Ferran , Montagut Clara , Massuti Bartomeu , Navarro Valenti , Varela Mar , Lopez-Doriga Adriana , Moreno Victor , Valladares Manuel , Manzano Jose Luis , Vieitez Jose Maria , Aranda Enrique , Sanjuan Xavier , Tabernero Josep , Capella Gabriel , Salazar Ramon 
Published: June 2017

Abstract
In metastatic colorectal cancer (mCRC), recent studies have shown the importance to accurately quantify low-abundance mutations of the RAS pathway because anti-EGFR therapy may depend on certain mutation thresholds. We aimed to evaluate the added predictive value of an extended RAS panel testing using two commercial assays and a highly sensitive and quantitative digital PCR (dPCR). Tumor samples from 583 mCRC patients treated with anti–EGFR- (n = 255) or bevacizumab- (n = 328) based therapies from several clinical trials and retrospective series from the TTD/RTICC Spanish network were analyzed by cobas, therascreen, and dPCR. We evaluated concordance between techniques using the Cohen kappa index. Response rate, progression-free survival (PFS), and overall survival (OS) were correlated to the mutational status and the mutant allele fraction (MAF). Concordance between techniques was high when analyzing RAS and BRAF (Cohen kappa index around 0.75). We observed an inverse correlation between MAF and response in the anti-EGFR cohort (P &lt; 0.001). Likelihood ratio analysis showed that a fraction of 1% or higher of any mutated alleles offered the best predictive value. PFS and OS were significantly longer in RAS/BRAF wild-type patients, independently of the technique. However, the predictability of both PFS and OS were higher when we considered a threshold of 1% in the RAS scenario (HR = 1.53; CI 95%, 1.12–2.09 for PFS, and HR = 1.9; CI 95%, 1.33–2.72 for OS). Although the rate of mutations observed among techniques is different, RAS and BRAF mutational analysis improved prediction of response to anti-EGFR therapy. Additionally, dPCR with a threshold of 1% outperformed the other platforms. Mol Cancer Ther; 16(9); 1999–2007. ©2017 AACR.
Antegrade Dissection and Reentry as Part of the Hybrid Chronic Total Occlusion Revascularization Strategy
Authors: Maeremans Joren , Dens Jo , Spratt James C. , Bagnall Alan J. , Stuijfzand Wynand , Nap Alexander , Agostoni Pierfrancesco , Wilson William , Hanratty Colm G. , Wilson Simon , Faurie Benjamin , Avran Alexandre , Bressollette Erwan , Egred Mohaned , Knaapen Paul , Walsh Simon , Smith Dave , Chase Alexander , Smith William H.T. , Harcombe Alun , Kayaert Peter , Smith Elliot J. , Kelly Paul , Irving John , McEntegart Margaret B. , Strange Julian W 
Published: June 2017

Background—
Development of the CrossBoss and Stingray devices for antegrade dissection and reentry (ADR) of chronic total occlusions has improved historically suboptimal outcomes. However, the outcomes, safety, and failure modes of the technique have to be studied in a larger patient cohort. This preplanned substudy of the RECHARGE registry (Registry of CrossBoss and Hybrid Procedures in France, the Netherlands, Belgium and United Kingdom) aims to evaluate the value and use of ADR and determine its future position in contemporary chronic total occlusion intervention.

Methods and Results—
Patients were selected if an ADR strategy was applied. Outcomes, safety, and failure modes of the technique were assessed. The ADR technique was used in 23% (n=292/1253) of the RECHARGE registry and was mainly applied for complex lesions (Japanese chronic total occlusion score=2.7±1.1). ADR was the primary strategy in 30% (n=88/292), of which 67% were successful. Bail-out ADR strategies were successful in 63% (n=133/210). The Controlled ADR (ie, combined CrossBoss-Stingray) subtype was applied most frequently (32%; n=93/292) and successfully (81%; n=75/93). Overall per-lesion success rate was 78% (n=229/292), after use of additional bail-out strategies. The inability to reach the distal target zone (n=48/100) or to reenter (n=43/100) most commonly led to failure. ADR-associated major events occurred in 3.4% (n=10/292).

Conclusions—
Although mostly applied as a bail-out strategy for complex lesions, the frequency, outcomes, and low complication rate of the ADR technique and its subtypes confirm the benefit and value of the technique in hybrid chronic total occlusion percutaneous coronary intervention, especially when antegrade wiring or retrograde approaches are not feasible.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT02075372.
Effect of Obesity and Underweight Status on Perioperative Outcomes of Congenital Heart Operations in Children, Adolescents, and Young Adults
Authors: O’Byrne Michael L. , Kim Sunghee , Hornik Christoph P. , Yerokun Babatunde A. , Matsouaka Roland A. , Jacobs Jeffrey P. , Jacobs Marshall L. , Jonas Richard A. 
Published: June 2017

Background:
Extreme body mass index (BMI; either very high or very low) has been associated with increased risk of adverse perioperative outcome in adults undergoing cardiac surgery. The effect of BMI on perioperative outcomes in congenital heart disease patients has not been evaluated.

Methods:
A multicenter retrospective cohort study was performed studying patients 10 to 35 years of age undergoing a congenital heart disease operation in the Society of Thoracic Surgeons Congenital Heart Surgery Database between January 1, 2010, and December 31, 2015. The primary outcomes were operative mortality and a composite outcome (1 or more of operative mortality, major adverse event, prolonged hospital length of stay, and wound infection/dehiscence). The associations between age- and sex-adjusted BMI percentiles and these outcomes were assessed, with adjustment for patient-level risk factors, with multivariate logistic regression.

Results:

Of 18 337 patients (118 centers), 16% were obese, 15% were overweight, 53% were normal weight, 7% were underweight, and 9% were severely underweight. Observed risks of operative mortality (
P
=0.04) and composite outcome (
P
<0.0001) were higher in severely underweight and obese subjects. Severely underweight BMI was associated with increased unplanned cardiac operation and reoperation for bleeding. Obesity was associated with increased risk of wound infection. In multivariable analysis, the association between BMI and operative mortality was no longer significant. Obese (odds ratio, 1.28;
P
=0.008), severely underweight (odds ratio, 1.29;
P
<0.0001), and underweight (odds ratio, 1.39;
P
=0.002) subjects were associated with increased risk of composite outcome.

Conclusions:
Obesity and underweight BMI were associated with increased risk of composite adverse outcome independently of other risk factors. Further research is necessary to determine whether BMI represents a modifiable risk factor for perioperative outcome.
Secondary Prevention of Cardiovascular Disease in Patients With Type 2 Diabetes Mellitus
Authors: Pagidipati Neha J. , Navar Ann Marie , Pieper Karen S. , Green Jennifer B. , Bethel M. Angelyn , Armstrong Paul W. , Josse Robert G. , McGuire Darren K. , Lokhnygina Yuliya , Cornel Jan H. , Halvorsen Sigrun , Strandberg Timo E. , Delibasi Tuncay , Holman Rury R. , Peterson Eric D. 
Published: June 2017

Background:
Intensive risk factor modification significantly improves outcomes for patients with diabetes mellitus and cardiovascular disease. However, the degree to which secondary prevention treatment goals are achieved in international clinical practice is unknown.

Methods:
Attainment of 5 secondary prevention parameters—aspirin use, lipid control (low-density lipoprotein cholesterol <70 mg/dL or statin therapy), blood pressure control (<140 mm Hg systolic, <90 mm Hg diastolic), angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use, and nonsmoking status—was evaluated among 13 616 patients from 38 countries with diabetes mellitus and known cardiovascular disease at entry into TECOS (Trial Evaluating Cardiovascular Outcomes With Sitagliptin). Logistic regression was used to evaluate the association between individual and regional factors and secondary prevention achievement at baseline. Cox proportional hazards regression analysis was used to determine the association between baseline secondary prevention achievement and cardiovascular death, myocardial infarction, or stroke.

Results:
Overall, 29.9% of patients with diabetes mellitus and cardiovascular disease achieved all 5 secondary prevention parameters at baseline, although 71.8% achieved at least 4 parameters. North America had the highest proportion (41.2%), whereas Western Europe, Eastern Europe, and Latin America had proportions of ≈25%. Individually, blood pressure control (57.9%) had the lowest overall attainment, whereas nonsmoking status had the highest (89%). Over a median 3.0 years of follow-up, a higher baseline secondary prevention score was associated with improved outcomes in a step-wise graded relationship (adjusted hazard ratio, 0.60; 95% confidence interval, 0.47–0.77 for those patients achieving all 5 measures versus those achieving ≤2).

Conclusions:
In an international trial population, significant opportunities exist to improve the quality of cardiovascular secondary prevention care among patients with diabetes mellitus and cardiovascular disease, which in turn could lead to reduced risk of downstream cardiovascular events.

Clinical Trial Registration:

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00790205.
Prediction of Recurrent Stroke or Transient Ischemic Attack After Noncardiogenic Posterior Circulation Ischemic Stroke
Authors: Zhang Changqing , Wang Yilong , Zhao Xingquan , Liu Liping , Wang ChunXue , Pu Yuehua , Zou Xinying , Pan Yuesong , Wong Ka Sing , Wang Yongjun 
Published: June 2017

Background and Purpose—
Posterior circulation ischemic stroke (IS) is generally considered an illness with a poor prognosis. However, there are no effective rating scales to predict recurrent stroke following it. Therefore, our aim was to identify clinical or radiological measures that could assist in predicting recurrent cerebral ischemic episodes.

Methods—
We prospectively enrolled 723 noncardiogenic posterior circulation IS patients with onset of symptoms <7 days. Stroke risk factors, admission symptoms and signs, topographical distribution and responsible cerebral artery of acute infarcts, and any recurrent IS or transient ischemic attack (TIA) within 1 year were assessed. Cox regression was used to identify risk factors associated with recurrent IS or TIA within the year after posterior circulation IS.

Results—

A total of 40 patients (5.5%) had recurrent IS or TIA within 1 year of posterior circulation IS. Multivariate Cox regression identified chief complaint with dysphagia (hazard ratio [HR], 4.16; 95% confidence interval [CI], 1.69–10.2;
P
=0.002), repeated TIAs within 3 months before the stroke (HR, 15.4; 95% CI, 5.55–42.5;
P
<0.0001), responsible artery stenosis ≥70% (HR, 7.91; 95% CI, 1.00–62.6;
P
=0.05), multisector infarcts (HR, 5.38; 95% CI, 1.25–23.3;
P
=0.02), and not on antithrombotics treatment at discharge (HR, 3.06; 95% CI, 1.09–8.58;
P
=0.03) as independent predictors of recurrent IS or TIA.

Conclusions—
Some posterior circulation IS patients are at higher risk for recurrent IS or TIA. Urgent assessment and preventive treatment should be offered to these patients as soon as possible.
Contributors to the Excess Stroke Mortality in Rural Areas in the United States
Authors: Howard George , Kleindorfer Dawn O. , Cushman Mary , Long D. Leann , Jasne Adam , Judd Suzanne E. , Higginbotham John C. , Howard Virginia J. 
Published: June 2017

Background and Purpose—
Stroke mortality is 30% higher in the rural United States. This could be because of either higher incidence or higher case fatality from stroke in rural areas.

Methods—
The urban–rural status of 23 280 stroke-free participants recruited between 2003 and 2007 in the REGARDS study (Reasons for Geographic and Racial Differences in Stroke) was classified using the Rural–Urban Commuting Area scheme as residing in urban, large rural town/city, or small rural town or isolated areas. The risk of incident stroke was assessed using proportional hazards analysis, and case fatality (death within 30 days of stroke) was assessed using logistic regression. Models were adjusted for demographics, traditional stroke risk factors, and measures of socioeconomic status.

Results—

After adjustment for demographic factors and relative to urban areas, stroke incidence was 1.23-times higher (95% confidence intervals, 1.01–1.51) in large rural town/cities and 1.30-times higher (95% confidence intervals, 1.03–1.62) in small rural towns or isolated areas. Adjustment for risk factors and socioeconomic status only modestly attenuated this association, and the association became marginally nonsignificant (
P
=0.071). There was no association of rural–urban status with case fatality (
P
>0.47).

Conclusions—
The higher stroke mortality in rural regions seemed to be attributable to higher stroke incidence rather than case fatality. A higher prevalence of risk factors and lower socioeconomic status only modestly contributed to the increased risk of incident stroke risk in rural areas. There was no evidence of higher case fatality in rural areas.