bluuebunny/crossref_metadata_2025_split huggingface dataset:
Break-up and seafloor spreading domains in the NE Atlantic
Authors: Gaina Carmen , Nasuti Aziz , Kimbell Geoffrey S. , Blischke Anett 
Published: February 2017

Abstract
An updated magnetic anomaly grid of the NE Atlantic and an improved database of magnetic anomaly and fracture zone identifications allow the kinematic history of this region to be revisited. At break-up time, continental rupture occurred parallel to the Mesozoic rift axes in the south, but obliquely to the previous rifting trend in the north, probably due to the proximity of the Iceland plume at 57–54 Ma.
The new oceanic lithosphere age grid is based on 30 isochrons (C) from C24n old (53.93 Ma) to C1n old (0.78 Ma), and documents ridge reorganizations in the SE Lofoten Basin, the Jan Mayen Fracture Zone region, in Iceland and offshore Faroe Islands. Updated continent–ocean boundaries, including the Jan Mayen microcontinent, and detailed kinematics of the Eocene–Present Greenland–Eurasia relative motions are included in this model.
Variations in the subduction regime in the NE Pacific could have caused the sudden northwards motion of Greenland and subsequent Eurekan deformation. These events caused seafloor spreading changes in the neighbouring Labrador Sea and a decrease in spreading rates in the NE Atlantic. Boundaries between major oceanic crustal domains were formed when the European Plate changed its absolute motion direction, probably caused by successive adjustments along its southern boundary.

Supplementary material:
Figures showing the long wavelength of the NAG-TEC magnetic anomaly grid, detailed magnetic anomalies and isochrons, and a Table documenting aeromagnetic surveys for NAG-TEC magnetic compilation are available at
https://doi.org/10.6084/m9.figshare.c.3661925
Cardiac Med1 deletion promotes early lethality, cardiac remodeling, and transcriptional reprogramming
Authors: Spitler Kathryn M. , Ponce Jessica M. , Oudit Gavin Y. , Hall Duane D. , Grueter Chad E. 
Published: February 2017

The mediator complex, a multisubunit nuclear complex, plays an integral role in regulating gene expression by acting as a bridge between transcription factors and RNA polymerase II. Genetic deletion of mediator subunit 1 (Med1) results in embryonic lethality, due in large part to impaired cardiac development. We first established that Med1 is dynamically expressed in cardiac development and disease, with marked upregulation of Med1 in both human and murine failing hearts. To determine if Med1 deficiency protects against cardiac stress, we generated two cardiac-specific Med1 knockout mouse models in which Med1 is conditionally deleted (Med1cKO mice) or inducibly deleted in adult mice (Med1cKO-MCM mice). In both models, cardiac deletion of Med1 resulted in early lethality accompanied by pronounced changes in cardiac function, including left ventricular dilation, decreased ejection fraction, and pathological structural remodeling. We next defined how Med1 deficiency alters the cardiac transcriptional profile using RNA-sequencing analysis. Med1cKO mice demonstrated significant dysregulation of genes related to cardiac metabolism, in particular genes that are coordinated by the transcription factors Pgc1α, Pparα, and Errα. Consistent with the roles of these transcription factors in regulation of mitochondrial genes, we observed significant alterations in mitochondrial size, mitochondrial gene expression, complex activity, and electron transport chain expression under Med1 deficiency. Taken together, these data identify Med1 as an important regulator of vital cardiac gene expression and maintenance of normal heart function.NEW & NOTEWORTHY Disruption of transcriptional gene expression is a hallmark of dilated cardiomyopathy; however, its etiology is not well understood. Cardiac-specific deletion of the transcriptional coactivator mediator subunit 1 (Med1) results in dilated cardiomyopathy, decreased cardiac function, and lethality. Med1 deletion disrupted cardiac mitochondrial and metabolic gene expression patterns.
Intrinsic Resistance of Solid Tumors to Immune Checkpoint Blockade Therapy
Authors: Zhao Xianda , Subramanian Subbaya 
Published: February 2017

Abstract
Immune checkpoint blockade therapy (ICBT), which blocks negative immune-activating signals and maintains the antitumor response, has elicited a remarkable clinical response in certain cancer patients. However, intrinsic resistance (i.e., insensitivity of the tumors to therapy) remains a daunting challenge. The efficacy of ICBT is tightly modulated by the function of each step in the antitumor immunity cycle. Mechanistically, the number of mutations determines tumor immunogenicity. The properties of the tumor microenvironment control T-cell infiltration, distribution, and function in tumor tissues. Low tumor immunogenicity and a strong immunosuppressive tumor microenvironment cause significant intrinsic resistance to ICBT. With our evolving understanding of intrinsic resistance, people have successfully tested, in preclinical models, treatments targeting specific resistance mechanisms to sensitize ICBT-resistant tumors. Translation of those preclinical findings to the clinical arena will help generate personalized ICBT strategies that target tumor-specific resistance mechanisms. Progress in the new personalized ICBT strategies will expand the reach of immunotherapy to more cancer types, thus enabling more patients to benefit. Cancer Res; 77(4); 817–22. ©2017 AACR.
Estradiol Promotes Breast Cancer Cell Migration via Recruitment and Activation of Neutrophils
Authors: Vazquez Rodriguez Gabriela , Abrahamsson Annelie , Jensen Lasse Dahl Ejby , Dabrosin Charlotta 
Published: February 2017

Abstract
Estradiol (E2) plays a key role in breast cancer progression. Most breast cancer recurrences express the estrogen receptor (ER), but nearly 50% of patients are resistant to antiestrogen therapy. Novel therapeutic targets of ER-positive breast cancers are needed. Protumoral neutrophils expressing the lymphocyte function-associated antigen 1 (LFA-1) integrin may mediate cancer metastasis, and TGFβ1 is the major chemoattractant for neutrophils. The role of E2 in neutrophil–ER+ breast cancer cell interactions is unknown. We studied this in vivo using murine breast cancers in immunocompetent mice and human breast cancers in nude mice. Cell dissemination was evaluated in a zebrafish model, and microdialysis of breast cancer patients was performed. In vitro studies were done with mammosphere cultures of breast cancer cells and human neutrophils. We found that E2 increased the number of LFA-1+ neutrophils recruited to the invasive edge of mouse tumors, increased TGFβ1 secretion and promoted neutrophil infiltration in mammospheres, and induced overexpression of LFA-1 in neutrophils. In zebrafish, in the presence of E2, neutrophils increased dissemination of ER+ breast cancer cells via LFA-1 and TGFβ1, thus causing noninvasive cancer cells to be highly metastatic. Time-lapse imaging in zebrafish revealed close interactions of neutrophils with cancer cells, which drove breast cancer metastasis. We also found that extracellular TGFβ1 was overproduced in human breast cancer tissue compared with adjacent normal breast tissue. Thus, E2 can regulate immune/cancer cell interactions in tumor microenvironments. Our results indicate that extracellular TGFβ1 is a relevant target in human breast cancer. Cancer Immunol Res; 5(3); 234–47. ©2017 AACR.
NK-Cell Recruitment Is Necessary for Eradication of Peritoneal Carcinomatosis with an IL12-Expressing Maraba Virus Cellular Vaccine
Authors: Alkayyal Almohanad A. , Tai Lee-Hwa , Kennedy Michael A. , de Souza Christiano Tanese , Zhang Jiqing , Lefebvre Charles , Sahi Shalini , Ananth Abhirami A. , Mahmoud Ahmad Bakur , Makrigiannis Andrew P. , Cron Greg O. , Macdonald Blair , Marginean E. Celia , Stojdl David F. , Bell John C. , Auer Rebecca C. 
Published: February 2017

AbstractDespite improvements in chemotherapy and radical surgical debulking, peritoneal carcinomatosis (PC) remains among the most common causes of death from abdominal cancers. Immunotherapies have been effective for selected solid malignancies, but their potential in PC has been little explored. Here, we report that intraperitoneal injection of an infected cell vaccine (ICV), consisting of autologous tumor cells infected ex vivo with an oncolytic Maraba MG1 virus expressing IL12, promotes the migration of activated natural killer (NK) cells to the peritoneal cavity in response to the secretion of IFNγ-induced protein-10 (IP-10) from dendritic cells. The recruitment of cytotoxic, IFNγ-secreting NK cells was associated with reduced tumor burden and improved survival in a colon cancer model of PC. Even in mice with bulky PC (tumors &gt; 8 mm), a complete radiologic response was demonstrated within 8 to14 weeks, associated with 100% long-term survival. The impact of MG1-IL12-ICV upon NK-cell recruitment and function observed in the murine system was recapitulated in human lymphocytes exposed to human tumor cell lines infected with MG1-IL12. These findings suggest that an MG1-IL12-ICV is a promising therapy that could provide benefit to the thousands of patients diagnosed with PC each year. Cancer Immunol Res; 5(3); 211–21. ©2017 AACR.
Serum Chloride and Sodium Interplay in Patients With Acute Myocardial Infarction and Heart Failure With Reduced Ejection Fraction
Authors: Ferreira João Pedro , Girerd Nicolas , Duarte Kevin , Coiro Stefano , McMurray John J. V. , Dargie Henry J. , Pitt Bertram , Dickstein Kenneth , Testani Jeffrey M. , Zannad Faiez , Rossignol Patrick 
Published: February 2017

Background—
Serum chloride levels were recently found to be independently associated with mortality in heart failure (HF).

Methods and Results—

We investigated the relationship between serum chloride and clinical outcomes in 7195 subjects with acute myocardial infarction complicated by reduced left ventricular function and HF. The studied outcomes were all-cause mortality, cardiovascular mortality, and hospitalization for HF. Both chloride and sodium had a nonlinear association with the studied outcomes (
P
<0.05 for linearity). Patients in the lowest chloride tertile (chloride ≤100) were older, had more comorbidities, and had lower sodium levels (
P
<0.05 for all). Serum chloride showed a significant interaction with sodium with regard to all studied outcomes (
P
for interaction <0.05 for all). The lowest chloride tertile (≤100 mmol/L) was associated with increased mortality rates in the context of lower sodium (≤138 mmol/L; adjusted hazard ratio [95% confidence interval] for all-cause mortality=1.42 (1.14–1.77);
P
=0.002), whereas in the context of higher sodium levels (>141 mmol/L), the association with mortality was lost. Spline-transformed chloride and its interaction with sodium did not add significant prognostic information on top of other well-established prognostic variables (
P
>0.05 for all outcomes).

Conclusions—
In post–myocardial infarction with systolic dysfunction and HF, low serum chloride was associated with mortality (but not hospitalization for HF) in the setting of lower sodium. Overall, chloride and its interaction with sodium did not add clinically relevant prognostic information on top of other well-established prognostic variables. Taken together, these data support an integrated and critical consideration of chloride and sodium interplay.
Aortic Waveform Analysis to Individualize Treatment in Heart Failure
Authors: Wohlfahrt Peter , Melenovsky Vojtech , Redfield Margaret M. , Olson Thomas P. , Lin Grace , Abdelmoneim Sahar S. , Hametner Bernhard , Wassertheurer Siegfried , Borlaug Barry A. 
Published: February 2017

Background—
Afterload reduction is a cornerstone in the management of patients with heart failure (HF) and reduced ejection fraction. However, arterial load and the effect of HF therapies on afterload might vary between individuals. Tailoring vasoactive medicines to patients with HF based upon better understanding of arterial afterload may enable better individualization of therapy.

Methods and Results—

Subjects with HF and reduced ejection fraction underwent aggressive titration of vasoactive HF therapies with assessment of central aortic waveforms analyzed using pulse wave, wave separation, and arterial reservoir models. Clinical response to treatment was assessed using the 6-minute walk test distance, which increased in 25 subjects and decreased or remained unchanged in 13. Subjects with improvement on therapy displayed higher aortic pressure wave pulsatility (central pulse pressure [PP], reflected pressure wave, and reservoir pressure) at study entry compared with subjects without improvement (all
P
<0.05). Parameters derived by the arterial analysis methods were strongly correlated with one another and displayed similar ability to predict improvement. Aortic pressure pulsatility significantly decreased in subjects with functional improvement, whereas no change was observed in patients without functional improvement (
P
for interaction <0.05). These differences in arterial load at baseline and on therapy were not apparent from conventional brachial artery cuff pressure assessments.

Conclusions—
Increased aortic pressure wave pulsatility and greater decrease in pulsatility on treatment are associated with functional improvement in patients with HF and reduced ejection fraction receiving aggressive vasodilator titration. These differences are not identifiable using brachial cuff pressures. Central aortic waveform analysis may enable better individualization of vasoactive therapies in chronic HF and reduced ejection fraction.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00588692.
Surgical Indication for Chronic Aortic Dissection in Descending Thoracic and Thoracoabdominal Aorta
Authors: Oda Tatsuya , Minatoya Kenji , Sasaki Hiroaki , Tanaka Hiroshi , Seike Yoshimasa , Itonaga Tatsuya , Inoue Yosuke , Higashi Masahiro , Nishimura Kunihiro , Kobayashi Junjiro 
Published: February 2017

Background—
To address the lack of information about the size of ruptures associated with chronic dissection in the descending and thoracoabdominal aorta, we evaluated the natural history of this pathology.

Methods and Results—
We analyzed data from 571 patients (mean age, 69.4±11.6 years) with unrepaired chronic aortic dissection in the descending or thoracoabdominal aorta with a maximal aortic diameter of ≥3.5 cm from 2007 to 2014. This was a cross-sectional study. Data on the timing of computed tomographic scan were as follows: for ruptured cases: at the time of rupture; for nonruptured cases: the initial aortic diameter. Patients with connective tissue disorders were excluded. The primary end point was evidence of aortic rupture on computed tomographic images. The median maximal diameter was 4.3 cm (limits, 3.5–9.0 cm) for all aortas and 5.6 cm (n=31; limits, 3.6–8.0 cm) for ruptured aortas. For aortic diameters of 4.0 to 4.4, 4.5 to 4.9, 5.0 to 5.4, 5.5 to 5.9, and 6.0 to 6.4 cm, the incidence of rupture was 0%, 3.3%, 15.3%, 18.8%, and 28.6%, respectively. The risk factors for rupture were absence of hypertension, chronic heart failure, chronic-phase dissection, and Yale index.

Conclusions—
The risk of aortic rupture increased with an aortic diameter of ≥5.0 cm in patients with chronic aortic dissection in the descending or thoracoabdominal aorta. We would recommend 5.0 cm as an acceptable size for elective resection of subacute or chronic aortic dissection in the descending or thoracoabdominal aorta.
High-Sensitive Cardiac Troponin T as an Early Biochemical Signature for Clinical and Subclinical Heart Failure
Authors: Seliger Stephen L. , Hong Susie N. , Christenson Robert H. , Kronmal Richard , Daniels Lori B. , Lima Joao A.C. , de Lemos James A. , Bertoni Alain , deFilippi Christopher R. 
Published: February 2017

Background:
Although small elevations of high-sensitive cardiac troponin T (hs-cTnT) are associated with incident heart failure (HF) in the general population, the underlying mechanisms are not well defined. Evaluating the association of hs-cTnT with replacement fibrosis and progression of structural heart disease before symptoms is fundamental to understanding the potential of this biomarker in a HF prevention strategy.

Methods:
We measured hs-cTnT at baseline among 4986 participants in MESA (Multi-Ethnic Study of Atherosclerosis), a cohort initially free of overt cardiovascular disease (CVD). Cardiac magnetic resonance imaging was performed at baseline. Repeat cardiac magnetic resonance was performed 10 years later among 2831 participants who remained free of interim CVD events; of these, 1723 received gadolinium-enhanced cardiac magnetic resonance for characterization of replacement fibrosis by late gadolinium enhancement. Progression of subclinical CVD was defined by 10-year change in left ventricular structure and function. Associations of hs-cTnT with incident HF, CV-related mortality, and coronary heart disease were estimated using Cox regression models.

Results:
Late gadolinium enhancement for replacement fibrosis was detectable in 6.3% participants without interim CVD events by follow-up cardiac magnetic resonance. A graded association was observed between higher baseline hs-cTnT categories and late gadolinium enhancement (≥7.42 ng/L versus <limit of detection [<3 ng/L]; adjusted odds ratio, 2.87; 95% confidence interval, 1.38–5.94). Higher hs-cTnT was also associated with a greater probability of an increase in LV mass >12% (highest category versus <limit of detection; odds ratio, 1.50; 95% confidence interval, 1.09–2.07), but not with decline in left ventricular ejection fraction. The risk of incident HF was greater for higher hs-cTnT (≥8.81 ng/L versus <limit of detection; adjusted hazards ratio, 5.59; 95% CI, 2.97–10.68).

Conclusions:
hs-cTnT levels are associated with replacement fibrosis and progressive changes in left ventricular structure in CVD-free adults, findings that may precede HF symptoms by years. Minor elevations of hs-cTnT may represent a biochemical signature of early subclinical cardiac disease, providing an opportunity for targeted preventive interventions.
Thoracic Aortic Aneurysm Growth: Role of Sex and Aneurysm Etiology
Authors: Cheung Katie , Boodhwani Munir , Chan Kwan‐Leung , Beauchesne Luc , Dick Alexander , Coutinho Thais 
Published: February 2017

Background

Thoracic aortic aneurysm (
TAA
) outcomes are worse in women than men, although reasons for sex differences are unknown. Because faster
TAA
growth is a risk factor for acute aortic syndromes, we sought to determine the role of sex and aneurysm etiology on
TAA
growth.

Methods and Results

Eighty‐two consecutive unoperated subjects with
TAA
who had serial aneurysm measurements were recruited. In multivariable linear regression the association of female sex with aneurysm growth rate was assessed after adjustment for potential confounders. We also tested the interaction term sex×aneurysm etiology in the prediction of
TAA
growth. Seventy‐four percent of subjects were men; mean±
SD
age was 62.4±11.9 years in men and 67.7±10.7 years in women (
P
=0.06). Forty‐seven (57%) subjects had degenerative
TAA
s, and the remainder had heritable
TAA
s. Absolute baseline aneurysm size and follow‐up time were not different between men and women. Aneurysm growth rate was 1.19±1.15 mm/y in women and 0.59±0.66 mm/y in men (
P
=0.02). Female sex remained significantly associated with greater aneurysm growth in multivariable analyses (β±
SE
: 0.35±0.12,
P
=0.005). In addition, female sex was associated with faster
TAA
growth only among those with degenerative
TAA
(β±
SE
: 0.33±0.08,
P
=0.0002) and not among those with heritable
TAA
(
P
=0.79), with a significant sex×etiology interaction (
P
=0.001).

Conclusions

TAA
growth rates are greater in women than men, and this difference is specific to women with degenerative
TAA
s. Our findings may explain sex differences in
TAA
outcomes and provide a foundation for future investigations of this topic.
Implications of Blood Pressure Measurement Technique for Implementation of Systolic Blood Pressure Intervention Trial (SPRINT)
Authors: Agarwal Rajiv 
Published: February 2017

Background

Cardiovascular morbidity and mortality was reduced by 25% when blood pressure (
BP
) was targeted to 120 mm Hg systolic compared with 140 mm Hg systolic in Systolic Blood Pressure Intervention Trial (SPRINT); however,
BP
was measured using a research technique.
SPRINT
specified 5 minutes of seated rest in a quiet room followed by 3 oscillometric measurements without an observer in the room. The relationship of this research‐grade methodology to routine
BP
measurements is not known.

Methods and Results

Among 275 people with chronic kidney disease who had
BP
<140/90 mm Hg when they came to the clinic, we measured
BP
as in
SPRINT
and recorded
BP
on the same day without specification of seated rest. Compared with routine measurement, the research‐grade systolic
BP
was 12.7 mm Hg lower with wide limits of agreement (−46.1 to 20.7 mm Hg). Research grade systolic
BP
was 7.9 mm Hg lower than daytime ambulatory systolic
BP
and had wide agreement limits (−33.2 to 17.4 mm Hg). Whereas the routine, research‐grade, and daytime ambulatory systolic
BP
were all related to echocardiographic left ventricular hypertrophy, the strength of the relationship between research‐grade and daytime ambulatory systolic
BP
to left ventricular hypertrophy was similar and stronger than the strength of the relationship between routine systolic
BP
and left ventricular hypertrophy.

Conclusions

Taken together, these results suggest that translation of the
SPRINT
results will require measurement of
BP
as performed in that trial. Instead of an algebraic manipulation of routine clinic measurements, the
SPRINT
methodology of
BP
measurement would be needed at minimum if implementation of the
SPRINT
results were to be deployed in the population at large.
Technology and Economic Development: The Schumpeterian Legacy
Authors: Evangelista Rinaldo 
Published: February 2017

The main argument put forward in the paper is that the recent neo-Schumpeterian literature, while providing fundamental contributions to our understanding of innovation, has contributed to the emergence of an optimistic reading of the relationship between technology, economy, and society, with technology able to guarantee strong economic growth and social welfare. It is also argued that such an “optimistic bias” has been associated with a dominant supply-side and micro-based view of the technology–economy relationships. JEL Classification: B52; O10; O30