bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum Neprilysin and Recurrent Admissions in Patients With Heart Failure
Authors: Núñez Julio , Núñez Eduardo , Barallat Jaume , Bodí Vicent , Miñana Gema , Pastor M. Cruz , Sanchis Juan , Lupón Josep , Bayes‐Genis Antoni 
Published: September 2017

Background

Our aim was to evaluate the association between the soluble form of neprilysin (
sNEP
) levels and long‐term all‐cause, cardiovascular, and acute heart failure (
AHF
) recurrent admissions in an ambulatory cohort of patients with heart failure.
sNEP
has emerged as a new biomarker with promising implications for prognosis and therapy in patients with heart failure. Reducing the recurrent admission rate of heart failure patients has become an important target of public health planning strategies.

Methods and Results

We measured
sNEP
levels in 1021 consecutive ambulatory heart failure patients. End points were the number of all‐cause, cardiovascular, and
AHF
hospitalizations during follow‐up. We used covariate‐adjusted incidence rate ratios to identify associations. At a median follow‐up of 3.4 years (interquartile range: 1.8–5.7), 391 (38.3%) patients died, 477 (46.7%) patients had 1901 all‐cause admissions, 324 (31.7%) patients had 770 cardiovascular admissions, and 218 (21.4%) patients had 488
AHF
admissions. The medians for
sNEP
and amino‐terminal pro‐brain natriuretic peptide were 0.64 ng/mL (interquartile range: 0.39–1.22) and 1248 pg/mL (interquartile range: 538–2825), respectively. In a multivariate setting, the adjusted incidence rate ratios for the top (>1.22 ng/mL) versus the bottom (≤0.39 ng/mL) quartiles of
sNEP
were 1.37 (95% confidence interval: 1.03–1.82),
P
=0.032; 1.51 (95% confidence interval: 1.10–2.06),
P
=0.010; and 1.51 (95% confidence interval: 1.05–2.16),
P
=0.026 for all‐cause, cardiovascular, and
AHF
admissions, respectively.

Conclusions

Elevated
sNEP
levels predicted an increased risk of recurrent all‐cause, cardiovascular, and
AHF
admissions in ambulatory patients with heart failure.
A Systems Biology Approach to Investigating Sex Differences in Cardiac Hypertrophy
Authors: Harrington Josephine , Fillmore Natasha , Gao Shouguo , Yang Yanqin , Zhang Xue , Liu Poching , Stoehr Andrea , Chen Ye , Springer Danielle , Zhu Jun , Wang Xujing , Murphy Elizabeth 
Published: September 2017

Background
Heart failure preceded by hypertrophy is a leading cause of death, and sex differences in hypertrophy are well known, although the basis for these sex differences is poorly understood.

Methods and Results

This study used a systems biology approach to investigate mechanisms underlying sex differences in cardiac hypertrophy. Male and female mice were treated for 2 and 3 weeks with angiotensin
II
to induce hypertrophy. Sex differences in cardiac hypertrophy were apparent after 3 weeks of treatment.
RNA
sequencing was performed on hearts, and sex differences in
mRNA
expression at baseline and following hypertrophy were observed, as well as within‐sex differences between baseline and hypertrophy. Sex differences in
mRNA
were substantial at baseline and reduced somewhat with hypertrophy, as the
mRNA
differences induced by hypertrophy tended to overwhelm the sex differences. We performed an integrative analysis to identify
mRNA
networks that were differentially regulated in the 2 sexes by hypertrophy and obtained a network centered on
PPAR
α (peroxisome proliferator‐activated receptor α). Mouse experiments further showed that acute inhibition of
PPAR
α blocked sex differences in the development of hypertrophy.

Conclusions

The data in this study suggest that
PPAR
α is involved in the sex‐dimorphic regulation of cardiac hypertrophy.
Three‐dimensional Integrated Functional, Structural, and Computational Mapping to Define the Structural “Fingerprints” of Heart‐Specific Atrial Fibrillation Drivers in Human Heart Ex Vivo
Authors: Zhao Jichao , Hansen Brian J. , Wang Yufeng , Csepe Thomas A. , Sul Lidiya V. , Tang Alan , Yuan Yiming , Li Ning , Bratasz Anna , Powell Kimerly A. , Kilic Ahmet , Mohler Peter J. , Janssen Paul M. L. , Weiss Raul , Simonetti Orlando P. , Hummel John D. , Fedorov Vadim V. 
Published: September 2017

Background

Structural remodeling of human atria plays a key role in sustaining atrial fibrillation (
AF
), but insufficient quantitative analysis of human atrial structure impedes the treatment of
AF
. We aimed to develop a novel 3‐dimensional (3D) structural and computational simulation analysis tool that could reveal the structural contributors to human reentrant
AF
drivers.

Methods and Results

High‐resolution panoramic epicardial optical mapping of the coronary‐perfused explanted intact human atria (63‐year‐old woman, chronic hypertension, heart weight 608 g) was conducted during sinus rhythm and sustained
AF
maintained by spatially stable reentrant
AF
drivers in the left and right atrium. The whole atria (107×61×85 mm
3
) were then imaged with contrast‐enhancement
MRI
(9.4 T, 180×180×360‐μm
3
resolution). The entire 3D human atria were analyzed for wall thickness (0.4–11.7 mm), myofiber orientations, and transmural fibrosis (36.9% subendocardium; 14.2% midwall; 3.4% subepicardium). The 3D computational analysis revealed that a specific combination of wall thickness and fibrosis ranges were primarily present in the optically defined
AF
driver regions versus nondriver tissue. Finally, a 3D human heart–specific atrial computer model was developed by integrating 3D structural and functional mapping data to test
AF
induction, maintenance, and ablation strategies. This 3D model reproduced the optically defined reentrant
AF
drivers, which were uninducible when fibrosis and myofiber anisotropy were removed from the model.

Conclusions

Our novel 3D computational high‐resolution framework may be used to quantitatively analyze structural substrates, such as wall thickness, myofiber orientation, and fibrosis, underlying localized
AF
drivers, and aid the development of new patient‐specific treatments.
Sirtuin 3 Deficiency Accelerates Hypertensive Cardiac Remodeling by Impairing Angiogenesis
Authors: Wei Tong , Huang Gaojian , Gao Jing , Huang Chenglin , Sun Mengwei , Wu Jian , Bu Juan , Shen Weili 
Published: September 2017

Background

Emerging evidence indicates that impaired angiogenesis may contribute to hypertension‐induced cardiac remodeling. The nicotinamide adenine dinucleotide–dependent deacetylase Sirtuin 3 (
SIRT
3) has the potential to modulate angiogenesis, but this has not been confirmed. As such, the aim of this study was to examine the relationship between
SIRT
3‐mediated angiogenesis and cardiac remodeling.

Methods and Results

Our experiments were performed on
SIRT
3 knockout and age‐matched wild‐type mice infused with angiotensin
II
(1400 ng/kg per minute) or saline for 14 days. After angiotensin
II
infusion,
SIRT
3 knockout mice developed more severe microvascular rarefaction and functional hypoxia in cardiac tissues compared with wild‐type mice. These events were concomitant with mitochondrial dysfunction and enhanced collagen I and collagen
III
expression, leading to cardiac fibrosis. Silencing
SIRT
3 facilitated angiotensin
II
–induced aberrant Pink/Parkin acetylation and impaired mitophagy, while excessive mitochondrial reactive oxygen species generation limited angiogenic capacity in primary mouse cardiac microvascular endothelial cells. Moreover,
SIRT
3 overexpression in cardiac microvascular endothelial cells enhanced Pink/Parkin‐mediated mitophagy, attenuated mitochondrial reactive oxygen species generation, and restored vessel sprouting and tube formation. In parallel, endothelial cell–specific
SIRT
3 transgenic mice showed decreased fibrosis, as well as improved cardiac function and microvascular network, compared with wild‐type mice with similar stimuli.

Conclusions

Collectively, these findings suggest that
SIRT
3 could promote angiogenesis through attenuating mitochondrial dysfunction caused by defective mitophagy.
Mortality Implications of Appropriate Implantable Cardioverter Defibrillator Therapy in Secondary Prevention Patients: Contrasting Mortality in Primary Prevention Patients From a Prospective Population‐Based Registry
Authors: Almehmadi Fahad , Porta‐Sánchez Andreu , Ha Andrew C. T. , Fischer Hadas D. , Wang Xuesong , Austin Peter C. , Lee Douglas S. , Nanthakumar Kumaraswamy 
Published: September 2017

Background

We sought to examine the mortality impact of appropriate implantable cardioverter defibrillator (
ICD
) therapy between patients who received
ICD
for primary versus secondary prevention purposes.

Methods and Results

From a prospective, population‐based registry, we identified 7020 patients who underwent de novo
ICD
implantation between February 2007 and May 2012 in Ontario, Canada. The primary outcome was all‐cause mortality. We used multivariable Cox proportional hazard modeling to adjust for differences in baseline characteristics and analyzed the mortality impact of first appropriate
ICD
therapy (shock and antitachycardia pacing [
ATP
]) as a time‐varying covariate. There were 1929 (27.5%) patients who received
ICD
s for secondary prevention purposes. The median follow‐up period was 5.02 years. Compared with those with secondary prevention
ICD
s, patients with primary prevention
ICD
s had more medical comorbidities, and lower ejection fraction. Patients who experienced appropriate
ICD
shock or
ATP
had greater risk of death compared with those who did not, irrespective of implant indication. In the primary prevention group, the adjusted hazard ratios of death for appropriate shock and
ATP
were 2.00 (95%
CI
: 1.72–2.33) and 1.73 (95%
CI
: 1.52–1.97), respectively. In the secondary prevention group, the adjusted hazard ratios of death for appropriate
ICD
shock and
ATP
were 1.46 (95%
CI
: 1.20–1.77) and 1.38 (95%
CI
: 1.16–1.64), respectively.

Conclusions

Despite having a more favorable clinical profile, occurrence of appropriate
ICD
shock or
ATP
in patients with secondary prevention
ICD
s was associated with similar magnitudes of mortality risk as those with primary prevention
ICD
s. A heightened degree of care is warranted for all patients who experience appropriate
ICD
shock or
ATP
therapy.
Cardiovascular Adverse Events in Patients With Cancer Treated With Bevacizumab: A Meta‐Analysis of More Than 20 000 Patients
Authors: Totzeck Matthias , Mincu Raluca Ileana , Rassaf Tienush 
Published: September 2017

Background
The monoclonal antibody bevacizumab effectively inhibits angiogenesis in several types of cancers by blocking vascular endothelial growth factor. However, life‐threatening cardiovascular adverse effects could limit its use and may warrant specific follow‐up strategies.

Methods and Results

We systematically searched MEDLINE, Cochrane,
EMBASE
, and Web of Science for randomized controlled trials published until November 2016 that assessed patients with cancer treated with or without bevacizumab in addition to standard chemotherapy. A total of 20 050 patients with a broad range of cancer types from 22 studies were included in this analysis (10 394 in the bevacizumab group and 9656 in the control group). The risks of arterial and venous adverse events were higher in the bevacizumab groups (relative risk [RR], 1.37; 95%
CI
, 1.10–1.70 [
P
=0.004] and
RR
, 1.29; 95%
CI
, 1.12–1.47 [
P
<0.001], respectively), and more arterial adverse events occurred in patients taking high‐dose bevacizumab regimens. Bevacizumab treatment was associated with the highest risk of cardiac and cerebral ischemia in the high‐dose bevacizumab groups (
RR
, 4.4; 95%
CI
, 1.59–12.70 [
P
=0.004] and
RR
, 6.67; 95%
CI
, 2.17–20.66 [
P
=0.001], respectively). In addition, the risk of bleeding and arterial hypertension were higher in the bevacizumab groups (
RR
, 2.74; 95%
CI
, 2.38–3.15 [
P
<0.001] and
RR
, 4.73; 95%
CI
, 4.15–5.39 [
P
<0.00001], respectively), with higher values for patiens taking high‐dose regimens.

Conclusions
Treatment with bevacizumab increases the risk of arterial adverse events, particularly cardiac and cerebral ischemia, venous adverse events, bleeding, and arterial hypertension. This risk is additionally increased with high doses of bevacizumab. Further studies should determine the appropriate options for cardio‐oncology management.

Clinical Trial Registration

URL
:
https://www.crd.york.ac.uk
. Unique identifier:
PROSPERO
(
CRD
42016054305).
Effect of Multifactorial Treatment Targets and Relative Importance of Hemoglobin A1c, Blood Pressure, and Low‐Density Lipoprotein‐Cholesterol on Cardiovascular Diseases in Chinese Primary Care Patients With Type 2 Diabetes Mellitus: A Population‐Based Retrospective Cohort Study
Authors: Wan Eric Yuk Fai , Fung Colman Siu Cheung , Yu Esther Yee Tak , Chin Weng Yee , Fong Daniel Yee Tak , Chan Anca Ka Chun , Lam Cindy Lo Kuen 
Published: September 2017

Background

The relative effect of hemoglobin A1c, blood pressure, and low‐density lipoprotein‐cholesterol (
LDL
‐C) (“
ABC
” factors) on the prevention of cardiovascular diseases (
CVD
) among patients with type 2 diabetes mellitus is poorly understood. This study aimed to evaluate the association of key clinical parameters on
CVD
risk using a multifactorial optimal control approach in Chinese primary care patients with type 2 diabetes mellitus.

Methods and Results

A population‐based retrospective cohort study was conducted on 144 271 Chinese type 2 diabetes mellitus primary care patients, aged 18 to 79 and without prior clinical diagnosis of
CVD
in 2008–2011. Cox regressions were conducted to examine the association between the combinations of
ABC
targets (hemoglobin A1c <7%, blood pressure <130/90 mm Hg, and
LDL
‐C <2.6 mmol/L) and risks of
CVD
(overall), coronary heart disease, stroke, and heart failure. Achieving more
ABC
targets incrementally reduced the incidence of total
CVD
and individual disease including coronary heart disease, stroke, and heart failure, irrespective of other patient characteristics. Compared with suboptimal control in all
ABC
levels, achieving any 1, 2, and all 3
ABC
targets reduced the relative risk of
CVD
by 13% to 42%, 31% to 52%, and 55%, respectively. Among those achieving only 1
ABC
target,
LDL
‐C reduction was associated with the greatest
CVD
risk reduction (42%), followed by blood pressure reduction (18%), and hemoglobin A1c reduction (13%).

Conclusions

To achieve the greatest risk reduction for the incidence of
CVD
, the ultimate goal of treatment should be to achieve target control of hemoglobin A1c, blood pressure, and
LDL
‐C. If it is not possible to achieve all 3 targets, efforts should be prioritized on treating the
LDL
‐C to minimize
CVD
risk.
Stones in the Landscape: Memory and Postmemory in the Yiddish Poems of David Fram
Authors: Frankel Hazel 
Published: September 2017

Abstract
Until the Holocaust in Lithuania annihilated 90% of its community between 1941 and 1944, Yiddish was a fully lived language with its own rich history and literature. David Fram escaped the genocide, having left his shtetl, the market town of Ponevezh in 1927. Once in South Africa, committed to the preservation of his mameloshn, his mother tongue, he created a rich body of Yiddish poetry. Though little known, his poems offer insights into the understanding of a particular Jewish survivor testimony as well as into the Lithuanian Holocaust more generally. Through detailed analysis of specific poems, this paper argues for their continued relevance, providing a valuable space for an account of aspects of memory and postmemory. In making them available to a wider audience through my own translations and transliterations in this small act of retrieval, my hope is to preserve a literary heritage and to memorialize a lost world.
The Republic of Korea-Pacific Islands Climate Prediction Services Project
Authors: Sohn Soo-Jin , Kim WonMoo , Yoo Jin Ho , Lee Yun-Young , Oh Sang Myeong , Kim Bo Ra , Lee Hyunrok , Kim Sangcheol , Seuseu Sunny , Pelesikoti Netatua 
Published: September 2017

Abstract
Seasonal prediction provides critical information for the tropical Pacific region, where the economy and livelihood is highly dependent on climate variability. While the highest skills of dynamical prediction systems are usually found in the tropical Pacific, National Hydrological and Meteorological Services (NHMS) in the Pacific Islands Countries (PICs) do not take full advantage of such scientific achievements. The Republic of Korea-Pacific Islands Climate Prediction Services (ROK-PI CliPS) project aims to help PICs produce regionally tailored climate prediction information using a dynamical seasonal prediction system. The project is being jointly implemented by the APEC Climate Center (APCC) and the Secretariat of the Pacific Regional Environment Programme (SPREP), in close collaboration with NHMSs in PICs. The regionally tailored, dynamical-statistical hybrid climate prediction system uses predictors that were identified through communications with NHMSs. The predictors were selected based on the empirical physical relationship of the local climate fluctuations, indicated by multi-institutional and multimodel ensembles. This hybrid system makes full use of dynamical seasonal predictions, which have not been commonly utilized in current operation in PICs. In accordance with system development, additional efforts have been made for PIC NHMSs to build capacity by increasing their knowledge and skill needed to develop such methodologies and systems. Nonetheless, the successive and strategic efforts to sustain and further improve climate predictions in the Pacific Islands region are required.
Examining the Value of Global Seasonal Reference Evapotranspiration Forecasts to Support FEWS NET’s Food Insecurity Outlooks
Authors: Shukla Shraddhanand , McEvoy Daniel , Hobbins Mike , Husak Greg , Huntington Justin , Funk Chris , Macharia Denis , Verdin James 
Published: September 2017

AbstractThe Famine Early Warning Systems Network (FEWS NET) team provides food insecurity outlooks for several developing countries in Africa, central Asia, and Central America. This study describes development of a new global reference evapotranspiration (ET0) seasonal reforecast and skill evaluation with a particular emphasis on the potential use of this dataset by FEWS NET to support food insecurity early warning. The ET0 reforecasts span the 1982–2009 period and are calculated following the American Society for Civil Engineers formulation of the Penman–Monteith method driven by seasonal climate forecasts of monthly mean temperature, humidity, wind speed, and solar radiation from the National Centers for Environmental Prediction CFSv2 model and the National Aeronautics and Space Administration GEOS-5 model. The skill evaluation, using deterministic and probabilistic scores, focuses on the December–February (DJF), March–May (MAM), June–August (JJA), and September–November seasons. The results indicate that ET0 forecasts are a promising tool for early warning of drought and food insecurity. Globally, the regions where forecasts are most skillful (correlation > 0.35 at leads of 2 months) include the western United States, northern parts of South America, parts of the Sahel region, and southern Africa. The FEWS NET regions where forecasts are most skillful (correlation > 0.35 at lead 3) include northern sub-Saharan Africa (DJF; dry season), Central America (DJF; dry season), parts of East Africa (JJA; wet season), southern Africa (JJA; dry season), and central Asia (MAM; wet season). A case study over parts of East Africa for the JJA season shows that ET0 forecasts in combination with the precipitation forecasts would have provided early warning of recent severe drought events (e.g., in 2002, 2004, 2009) that contributed to substantial food insecurity in the region.
Obesity as a Predictor of Delayed Lactogenesis II
Authors: Preusting Irma , Brumley Jessica , Odibo Linda , Spatz Diane L. , Louis Judette M. 
Published: September 2017

Background: Lactogenesis II is the onset of copious milk production. A delay in this has been associated with an increased risk of formula supplementation and early cessation of breastfeeding. Prepregnancy obesity has also been associated with decreased breastfeeding rates and early cessation. Research aim: This study aimed to evaluate the effect of prepregnancy obesity on self-reported delayed lactogenesis II. Methods: We conducted a prospective observational cohort study of 216 women with a singleton pregnancy and who planned to breastfeed. We compared the onset of lactogenesis II between women with a body mass index (BMI) < 30 kg/m2 and women with a BMI ≥ 30 kg/m2. Using multivariate logistic regression analyses, we assessed the relationship between maternal BMI and delay of lactogenesis II. Results: The prevalence of delayed lactogenesis II among women with prepregnancy BMI < 30 kg/m2 and BMI ≥ 30 kg/m2 was 46.4% and 57.9%, respectively. Delayed lactogenesis II occurred more frequently among women who were obese at the time of delivery ( p < .05). After controlling for the covariates, age, prepregnancy BMI, and gestational weight gain were positively associated with delayed lactogenesis II. Conclusion: Prepregnancy obesity and excessive gestational weight gain are associated with an increased risk of delayed lactogenesis II. Women who are at risk for delay in lactogenesis II and early breastfeeding cessation will need targeted interventions and support for them to achieve their personal breastfeeding goals.
Repeated faecal occult blood testing is associated with decreased advanced colorectal cancer risk: A population-based study
Authors: James Paul D , Rabeneck Linda , Yun Lingsong , Paszat Lawrence , Baxter Nancy N , Govindarajan Anand , Antonova Lilia , Tinmouth Jill M 
Published: September 2017

Objective To evaluate the association between repeated faecal occult blood testing and advanced colorectal cancer risk at population level in Canada. Methods A retrospective cohort study of all Ontario residents aged 56–74 diagnosed with colorectal cancer from 1 April 2007 to 31 March 2010, identified using health administrative data. The primary outcome was stage IV colorectal cancer, and primary exposure was faecal occult blood testing use within five years prior to colorectal cancer diagnosis. Patients were categorized into four mutually exclusive groups based on their exposure to faecal occult blood testing in the five years prior to colorectal cancer diagnosis: none, pre-diagnostic, repeated, and sporadic. Logistic regression was utilized to adjust for confounders. Results Of 7753 patients (median age 66, interquartile range 61–70, 62% male) identified, 1694 (22%) presented with stage I, 2056 (27%) with stage II, 2428 (31%) with stage III, and 1575 (20%) with stage IV colorectal cancer. There were 4092 (53%) with no record of prior faecal occult blood testing, 1485 (19%) classified as pre-diagnostic, 1693 (22%) as sporadic, and 483 (6%) as repeated faecal occult blood testing. After adjusting for confounders, patients who had repeated faecal occult blood testing were significantly less likely to present with stage IV colorectal cancer at diagnosis (Odds ratio 0.46, 95% Confidence Interval 0.34–0.62) than those with no prior faecal occult blood testing. Conclusions Repeated faecal occult blood testing is associated with a decreased risk of advanced colorectal cancer. Our findings support the use of organized screening programmes that employ repeated faecal occult blood testing to improve colorectal cancer outcomes at population level.