bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of heparin on secondary brain injury in patients with subarachnoid hemorrhage: an additional ‘H’ therapy in vasospasm treatment
Authors: Bruder Markus , Won Sae-Yeon , Kashefiolasl Sepide , Wagner Marlies , Brawanski Nina , Dinc Nazife , Seifert Volker , Konczalla Juergen 
Published: February 2017

ObjectiveSecondary brain injury leads to high morbidity and mortality rates in patients with aneurysmal subarachnoid hemorrhage (aSAH). However, evidence-based treatment strategies are sparse. Since heparin has various effects on neuroinflammation, microthromboembolism and vasomotor function, our objective was to determine whether heparin can be used as a multitarget prophylactic agent to ameliorate morbidity in SAH.MethodsBetween June 1999 and December 2014, 718 patients received endovascular treatment after rupture of an intracranial aneurysm at our institution; 197 of them were treated with continuous unfractionated heparin in therapeutic dosages after the endovascular procedure. We performed a matched pair analysis to evaluate the effect of heparin on cerebral vasospasm (CVS), cerebral infarction (CI), and outcome.ResultsThe rate of severe CVS was significantly reduced in the heparin group compared with the control group (14.2% vs 25.4%; p=0.005). CI and multiple ischemic lesions were less often present in patients with heparin treatment. These effects were enhanced if patients were treated with heparin for >48 hours, but the difference was not significant. Favorable outcome at 6-month follow-up was achieved in 69% in the heparin group and in 65% in the control group.ConclusionsPatients receiving unfractionated continuous heparin after endovascular aneurysm occlusion have a significant reduction in the rate of severe CVS, have CI less often, and tend to have a favorable outcome more often. Our findings support the potential beneficial effects of heparin as a multitarget therapy in patients with SAH, resulting in an additional ‘H’ therapy in vasospasm treatment.
The Cargo Protein MAP17 (PDZK1IP1) Regulates the Cancer Stem Cell Pool Activating the Notch Pathway by Abducting NUMB
Authors: Garcia-Heredia Jose Manuel , Lucena-Cacace Antonio , Verdugo-Sivianes Eva M. , Pérez Marco , Carnero Amancio 
Published: February 2017

Abstract
Purpose: Cancer stem cells (CSC) are self-renewing tumor cells, with the ability to generate diverse differentiated tumor cell subpopulations. They differ from normal stem cells in the deregulation of the mechanisms that normally control stem cell physiology. CSCs are the origin of metastasis and highly resistant to therapy. Therefore, the understanding of the CSC origin and deregulated pathways is important for tumor control.
Experimental Design: We have included experiments in vitro, in cell lines and tumors of different origins. We have used patient-derived xenografts (PDX) and public transcriptomic databases of human tumors.
Results: MAP17 (PDZKIP1), a small cargo protein overexpressed in tumors, interacts with NUMB through the PDZ-binding domain activating the Notch pathway, leading to an increase in stem cell factors and cancer-initiating–like cells. Identical behavior was mimicked by inhibiting NUMB. Conversely, MAP17 downregulation in a tumor cell line constitutively expressing this gene led to Notch pathway inactivation and a marked reduction of stemness. In PDX models, MAP17 levels directly correlated with tumorsphere formation capability. Finally, in human colon, breast, or lung there is a strong correlation of MAP17 expression with a signature of Notch and stem cell genes.
Conclusions: MAP17 overexpression activates Notch pathway by sequestering NUMB. High levels of MAP17 correlated with tumorsphere formation and Notch and Stem gene transcription. Its direct modification causes direct alteration of tumorsphere number and Notch and Stem pathway transcription. This defines a new mechanism of Notch pathway activation and Stem cell pool increase that may be active in a large percentage of tumors. Clin Cancer Res; 23(14); 3871–83. ©2017 AACR.
Factors Associated With Left Atrial Remodeling in the General Population
Authors: Oliver Walter , Matthews Gwendolyn , Ayers Colby R. , Garg Sonia , Gupta Sachin , Neeland Ian J. , Drazner Mark H. , Berry Jarett D. , Matulevicius Susan , de Lemos James A. 
Published: February 2017

Background—
Although contributors to remodeling of the left ventricle (LV) have been well studied in general population cohorts, few data are available describing factors influencing changes in left atrial (LA) structure.

Methods and Results—

Maximum LA volume was determined by cardiac magnetic resonance imaging among 748 participants in the Dallas Heart Study at 2 visits a mean of 8 years apart. Associations of changes in LA volume (ΔLAV) with traditional risk factors, biomarkers, LV geometry, and remodeling by cardiac magnetic resonance imaging and detailed measurements of global and regional adiposity (by magnetic resonance imaging and dual-energy x ray absorptiometry) were assessed using multivariable linear regression. Greater ΔLAV was independently associated with black and Hispanic race/ethnicity, change in systolic blood pressure, LV mass and ΔLV mass, N-terminal probrain natriuretic peptide and change in N-terminal probrain natriuretic peptide, and body mass index (
P
<0.05 for each). In subanalyses, the associations of ΔLAV with LV mass parameters were driven by associations with baseline and ΔLV end diastolic volume (
P
<0.0001 for each) and not wall thickness (
P
=0.21). Associations of ΔLAV with body mass index were explained exclusively by associations with visceral fat mass (
P
=0.002), with no association seen between ΔLAV and subcutaneous abdominal fat (
P
=0.47) or lower body fat (
P
=0.30).

Conclusions—
Left atrial dilatation in the population is more common in black and Hispanic than in white individuals and is associated with parallel changes in the LV. LA dilatation may be mediated by blood pressure control and the development of visceral adiposity.
Loss of Endothelial CXCR7 Impairs Vascular Homeostasis and Cardiac Remodeling After Myocardial Infarction
Authors: Hao Huifeng , Hu Sheng , Chen Hong , Bu Dawei , Zhu Liyuan , Xu Chuansheng , Chu Fei , Huo Xingyu , Tang Yue , Sun Xiaogang , Ding Bi-Sen , Liu De-Pei , Hu Shengshou , Wang Miao 
Published: February 2017

Background:

Genome-wide association studies identified the association of the
CXCL12
genetic locus (which encodes the chemokine CXCL12, also known as stromal cell–derived factor 1) with coronary artery disease and myocardial infarction (MI). Unlike CXCR4, the classic receptor for CXCL12, the function of CXCR7 (the most recently identified receptor) in vascular responses to injury and in MI remains unclear.

Methods:

Tissue expression of CXCR7 was examined in arteries from mice and humans. Mice that harbored floxed
CXCR7
and
Cdh5
-promoter driven
CreERT2
were treated with tamoxifen to induce endothelium-restricted deletion of CXCR7. The resulting conditional knockout mice and littermate controls were studied for arterial response to angioplasty wire injury and cardiac response to coronary artery ligation. The role of CXCR7 in endothelial cell proliferation and angiogenesis was determined in vitro with cells from mice and humans. The effects of adenoviral delivery of
CXCR7
gene and pharmacological activation of CXCR7 were evaluated in mice subjected to MI.

Results:

Injured arteries from both humans and mice exhibited endothelial CXCR7 expression. Conditional endothelial CXCR7 deletion promoted neointimal formation without altering plasma lipid levels after endothelial injury and exacerbated heart functional impairment after MI, with increased both mortality and infarct sizes. Mechanistically, the exacerbated responses in vascular and cardiac remodeling are attributable to the key role of CXCR7 in promoting endothelial proliferation and angiogenesis. Impressively, the impaired post-MI cardiac remodeling occurred with elevated levels of CXCL12, which was previously thought to mediate cardiac protection by exclusively engaging its cognate receptor, CXCR4. In addition, both
CXCR7
gene delivery via left ventricular injection and treatment with a CXCR7 agonist offered cardiac protection after MI.

Conclusions:
CXCR7 represents a novel regulator of vascular homeostasis that functions in the endothelial compartment with sufficient capacity to affect cardiac function and remodeling after MI. Activation of CXCR7 may have therapeutic potential for clinical restenosis after percutaneous coronary intervention and for heart remodeling after MI.
Prognostic Significance of Plasma High‐Sensitivity C‐Reactive Protein in Patients With Hypertrophic Cardiomyopathy
Authors: Zhu Ling , Zou Yubao , Wang Yilu , Luo Xiaoliang , Sun Kai , Wang Hu , Jia Lei , Liu Yan , Zou Juan , Yuan Zuyi , Hui Rutai , Kang Lianming , Song Lei , Wang Jizheng 
Published: February 2017

Background

Elevated high‐sensitivity C‐reactive protein (hs
CRP
) has been associated with increased risks of adverse outcomes of various cardiovascular diseases. The relationship between hs
CRP
and the prognosis of hypertrophic cardiomyopathy remains to be evaluated.

Methods and Results

The study used an observational cohort methodology. A total of 490 patients were enrolled in the Fuwai Hospital from 2001 to 2011 and were followed for 3.7±2.0 years. According to the risk category of hs
CRP
, subjects in the high hs
CRP
group (>3.0 mg/L) had a higher risk of developing adverse events than the low hs
CRP
group (<1.0 mg/L): cardiovascular death (adjusted hazard ratios[
HR
] 5.41, 95%
CI
1.96–14.93,
P
=0.001), all‐cause mortality (adjusted
HR
4.78, 95%
CI
1.99–11.47,
P
<0.001), sudden cardiac death (adjusted
HR
11.29, 95%
CI
1.38–92.20,
P
=0.024), and heart failure–related death (adjusted
HR
4.38, 95%
CI
1.15–16.60,
P
=0.030). Similarly, the continuous variable of hs
CRP
was also an independent predictor for adverse outcomes: cardiovascular death (adjusted
HR
1.15, 95%
CI
1.06–1.25,
P
=0.001), all‐cause mortality (adjusted
HR
1.17, 95%
CI
1.09–1.26,
P
<0.001), sudden cardiac death (adjusted
HR
1.20, 95%
CI
1.06–1.36,
P
=0.003), and heart failure–related death (adjusted
HR
1.15, 95%
CI
1.02–1.30,
P
=0.020).

Conclusions

Our results indicate that elevated plasma hs
CRP
is associated with increased risk for adverse outcomes in patients with hypertrophic cardiomyopathy.
Outcomes of Physician‐Staffed Versus Non‐Physician‐Staffed Helicopter Transport for ST‐Elevation Myocardial Infarction
Authors: Gunnarsson Sverrir I. , Mitchell Joseph , Busch Mary S. , Larson Brenda , Gharacholou S. Michael , Li Zhanhai , Raval Amish N. 
Published: February 2017

Background

The effect of physician‐staffed helicopter emergency medical service (
HEMS
) on
ST
‐elevation myocardial infarction (
STEMI
) patient transfer is unknown. The purpose of this study was to evaluate the characteristics and outcomes of physician‐staffed
HEMS
(Physician‐
HEMS
) versus non‐physician‐staffed (Standard‐
HEMS
) in patients with
STEMI
.

Methods and Results

We studied 398
STEMI
patients transferred by either Physician‐
HEMS
(n=327) or Standard‐
HEMS
(n=71) for primary or rescue percutaneous coronary intervention at 2 hospitals between 2006 and 2014. Data were collected from electronic medical records and each institution's contribution to the National Cardiovascular Data Registry. Baseline characteristics were similar between groups. Median electrocardiogram‐to‐balloon time was longer for the Standard‐
HEMS
group than for the Physician‐
HEMS
group (118 vs 107 minutes;
P
=0.002). The Standard‐
HEMS
group was more likely than the Physician‐
HEMS
group to receive nitroglycerin (37% vs 15%;
P
<0.001) and opioid analgesics (42.3% vs 21.7%;
P
<0.001) during transport. In‐hospital adverse outcomes, including cardiac arrest, cardiogenic shock, and serious arrhythmias, were more common in the Standard‐
HEMS
group (25.4% vs 11.3%;
P
=0.002). After adjusting for age, sex, Killip class, and transport time, patients transferred by Standard‐
HEMS
had increased risk of any serious in‐hospital adverse event (odds ratio=2.91; 95%
CI
=1.39–6.06;
P
=0.004). In‐hospital mortality was not statistically different between the 2 groups (9.9% in the Standard‐
HEMS
group vs 4.9% in the Physician‐
HEMS
group;
P
=0.104).

Conclusions

Patients with
STEMI
transported by Standard‐
HEMS
had longer transport times, higher rates of nitroglycerin and opioid administration, and higher rates of adjusted in‐hospital events. Efforts to better understand optimal transport strategies in
STEMI
patients are needed.
Development of Coronary Pulse Wave Velocity: New Pathophysiological Insight Into Coronary Artery Disease
Authors: Harbaoui Brahim , Courand Pierre‐Yves , Cividjian Andrei , Lantelme Pierre 
Published: February 2017

Background

Although aortic stiffness assessed by pulse wave velocity (
PWV
) is a strong predictor of coronary artery disease, the significance of local coronary stiffness has never been tackled. The first objective of this study was to describe a method of measuring coronary
PWV
(Co
PWV
) invasively and to describe its determinants. The second objective was to assess both Co
PWV
and aortic
PWV
in patients presenting with acute coronary syndromes or stable coronary artery disease.

Methods and Results

In 53 patients, Co
PWV
was measured from the delay in pressure wave and distance traveled as a pressure wire was withdrawn from the distal to the proximal coronary segment. Similarly, aortic
PWV
was measured invasively when the wire was pulled across the ascending aorta; carotid–femoral
PWV
was also measured noninvasively using the SphygmoCor system (AtCor Medical). Mean Co
PWV
was 10.3±6.1 m/s. Determinants of increased Co
PWV
were fractional flow reserve, diastolic blood pressure, and previous stent implantation in the recorded artery. Co
PWV
was lower in patients with acute coronary syndromes versus stable coronary artery disease (7.6±3 versus 11.5±6.4 m/s;
P
=0.02), and this persisted after adjustment for confounders. In contrast, aortic stiffness, assessed by aortic and carotid–femoral
PWV
, did not differ significantly.

Conclusions

Co
PWV
seems associated with acute coronary events more closely than aortic
PWV
. High coronary compliance, whether per se or because it leads to a distal shift in compliance mismatch, may expose vulnerable plaques to high cyclic stretch. Co
PWV
is a new tool to assess local compliance at the coronary level; it paves the way for a new field of research.
Similar birth-cohort patterns in Crohn’s disease and multiple sclerosis
Authors: Sonnenberg Amnon , Ajdacic-Gross Vladeta 
Published: February 2017

Background: The etiology of Crohn’s disease and multiple sclerosis is unknown. Genetic susceptibility and environmental factors are believed to play a role in both diseases. Objectives: To compare the long-term time trends of the two diseases and thus gain insight about their etiology. Methods: We analyzed mortality data of Crohn’s disease and multiple sclerosis from Canada, England, Italy, the Netherlands, Switzerland, and the United States during the past 60 years. Age–period–cohort (APC) analyses based on logit models served to disentangle the separate influences of age, period, and cohort effects on the overall time trends. Results: The long-term time trends of Crohn’s disease and multiple sclerosis have been shaped by strikingly similar birth-cohort patterns. In both diseases alike, mortality increased in all generations born prior to 1910. It peaked among generations born between 1910 and 1930 and then declined in all subsequent generations. Similar birth-cohort patterns of Crohn’s disease and multiple sclerosis were found in each country analyzed separately. Conclusion: The birth-cohort patterns indicate that the development of Crohn’s disease and multiple sclerosis is influenced by exposure to environmental risk factors during an early period of life. These environmental risk factors may be similar or even identical in Crohn’s disease and multiple sclerosis.
Assessment of the expectancy, seriousness and severity of adverse drug reactions reported for chronic obstructive pulmonary disease therapy
Authors: Petrova Guenka , Stoimenova Assena , Dimitrova Maria , Kamusheva Maria , Petrova Daniela , Georgiev Ognian 
Published: February 2017

Introduction: Adverse drug reactions can cause increased morbidity and mortality, and therefore information needs to be studied systematically. Little is known about the adverse drug reactions for chronic obstructive pulmonary disease therapy. The goal of this study is to assess the expectedness, seriousness and severity of adverse drug reactions during chronic obstructive pulmonary disease therapy based on their reporting in the national pharmacovigilance system. Methods: This was a prospective, observational, 1-year, real-life study about the pharmacotherapy of a sample of 390 chronic obstructive pulmonary disease patients. Prescribed medicines were systematized and national pharmacovigilance databases were searched for reported adverse drug reactions. The expectedness was evaluated through the review of the summary of product characteristics, the seriousness was evaluated by the clinicians based on the life threatening nature of the adverse drug reactions, and the severity was evaluated through Hartwig’s Severity Assessment Scale. Descriptive statistics of the reported adverse drug reactions was performed and the relative risk of developing an adverse drug reaction with all international non-proprietary names included in the analysis was calculated. Results: Results confirm that the chronic obstructive pulmonary disease is a disease with high appearance of adverse drug reactions, and causes many additional costs to the healthcare system. Unexpected and severe adverse drug reactions are frequent. A total of 4.8% of adverse drug reactions were evaluated as life threatening. Majority of adverse drug reactions are classified in Levels 1 (32.6%), 2 (26.4%) and 3 (19%) according to Hartwig’s Severity Assessment Scale. Approximately 22% of reported adverse drug reactions affect people’s everyday life to a greater extent and require additional therapy which might further increase the risk. The relative risk of developing an adverse drug reaction was highest for novphyllin (relative risk = 0.65), followed by aclidinium bromide (relative risk = 0.09). Both indacaterol and salbutamol are with a relative risk of 0.07. Conclusion: In conclusion, the medicines for chronic obstructive pulmonary disease cause many serious adverse drug reactions, most of them were unexpected, lacking in the short product characteristics. Appropriate reporting of adverse drug reactions is necessary to decrease the risk of patients and healthcare system.
Depth of invasion and GLUT-1 as risk predictors in oral squamous cell carcinoma
Authors: Ganvir Sindhu M , Bamane Swati A , Katkade Shashikant P , Khobragade Pratima G , Hazarey Vinay P , Gosavi Suchitra R 
Published: February 2017

Object: Predictor of the risk of subclinical nodal metastasis in early oral cancer would be of significant benefit in determining the need for elective neck dissection or adjuvant therapy. Depth of invasion (DOI) and glucose transporter (GLUT-1) expression have been assigned an independent prognostic significance in predicting the risk of nodal metastasis. The present study has been undertaken to evaluate the mechanisms linking GLUT-1 expression to DOI in progressive grades of oral squamous cell carcinoma (OSCC). Method: The GLUT-1 expression was analysed by immunohistochemistry, and its association with the DOI was assessed in 90 patients in progressive histological grades of OSCC. Result: We hypothesized that OSCC characterized by high frequency of lymph node metastasis, distant metastasis, or local recurrences showed highly significant statistical correlation of DOI with the GLUT-1 over expression at the invasion front in progressive histological grades of OSCC, thereby revealing their potential role in predicting both tumour aggressiveness and prognosis. Conclusion: The correlation of these two parameters, that is, DOI with GLUT-1 over expression at the invasion front, used simultaneously in progressive histological grades of OSCC, might have a significant prognostic value by highlighting those cases that should be subjected to further lymph node assessment, thereby predicting their risk of occult metastasis, assisting in the selection of patients requiring more aggressive therapy.
The microenvironment in human myeloid malignancies: emerging concepts and therapeutic implications
Authors: Medyouf Hind 
Published: February 2017

Abstract
Similar to their healthy counterpart, malignant hematopoietic stem cells in myeloid malignancies, such as myeloproliferative neoplasms, myelodysplastic syndromes, and acute myeloid leukemia, reside in a highly complex and dynamic cellular microenvironment in the bone marrow. This environment provides key regulatory signals for and tightly controls cardinal features of hematopoietic stem cells (HSCs), including self-renewal, quiescence, differentiation, and migration. These features are essential to maintaining cellular homeostasis and blood regeneration throughout life. A large number of studies have extensively addressed the composition of the bone marrow niche in mouse models, as well as the cellular and molecular communication modalities at play under both normal and pathogenic situations. Although instrumental to interrogating the complex composition of the HSC niche and dissecting the niche remodeling processes that appear to actively contribute to leukemogenesis, these models may not fully recapitulate the human system due to immunophenotypic, architectural, and functional inter-species variability. This review summarizes several aspects related to the human hematopoietic niche: (1) its anatomical structure, composition, and function in normal hematopoiesis; (2) its alteration and functional relevance in the context of chronic and acute myeloid malignancies; (3) age-related niche changes and their suspected impact on hematopoiesis; (4) ongoing efforts to develop new models to study niche-leukemic cell interaction in human myeloid malignancies; and finally, (5) how the knowledge gained into leukemic stem cell (LSC) niche dependencies might be exploited to devise novel therapeutic strategies that aim at disrupting essential niche-LSC interactions or improve the regenerative ability of the disease-associated hematopoietic niche.
Brincidofovir is highly efficacious in controlling adenoviremia in pediatric recipients of hematopoietic cell transplant
Authors: Hiwarkar Prashant , Amrolia Persis , Sivaprakasam Ponni , Lum Su Han , Doss Hemalatha , O’Rafferty Ciara , Petterson Toni , Patrick Katharine , Silva Juliana , Slatter Mary , Lawson Sarah , Rao Kanchan , Steward Colin , Gassas Adam , Veys Paul , Wynn Robert 
Published: February 2017

Key PointsBrincidofovir has superior antiadenoviral activity and safety profile compared with cidofovir. Brincidofovir is highly efficacious in controlling adenoviremia during the lymphopenic phase of HCT.
RETRACTED ARTICLE: New applications of Schrödingerean Green potential to boundary behaviors of superharmonic functions
Authors: Lai Kai , Mu Jing , Wang Hong 
Published: February 2017

AbstractBy using the Schrödingerean continuation theorem due to Li (Bound. Value Probl. 2015:242, 2015), we obtain some new results for boundary value problems of Schrödingerean Green potentials. As new applications, the boundary behaviors of superharmonic functions at infinity are also obtained.