bluuebunny/crossref_metadata_2025_split huggingface dataset:
More- Versus Less-Intensive Lipid-Lowering Therapy
Authors: Toyota Toshiaki , Morimoto Takeshi , Yamashita Yugo , Shiomi Hiroki , Kato Takao , Makiyama Takeru , Nakagawa Yasuaki , Saito Naritatsu , Shizuta Satoshi , Ono Koh , Kimura Takeshi 
Published: August 2019

Background:
It has not been yet adequately addressed whether the addition of the nonstatin LDL-C (low-density lipoprotein cholesterol)-lowering agents on top of statins has the same magnitude of risk reduction in the cardiovascular events as compared with more-intensive statin therapy.

Methods and Results:

We performed a systematic review and meta-analysis of RCTs (randomized controlled trials) comparing more- versus less-intensive lipid-lowering therapy (LLT) on clinical outcomes in patients with atherosclerotic cardiovascular risk. We included 23 studies involving 133 037 patients (more-intensive LLT: 67 691 patients and less-intensive LLT: 65 346 patients). We evaluated 3 types of more- versus less-intensive LLT including more versus less statins (57 672 patients), combination therapy of ezetimibe versus statins alone (20 688 patients), or a PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitor with statins versus statins alone (54 677 patients). The odds for major adverse cardiovascular events (MACE; equivalent to the composite of coronary heart death, nonfatal myocardial infarction, stroke, or coronary revascularization) were significantly lower in the more-intensive LLT group compared with the less-intensive LLT group in the entire study population (odds ratio, 0.84; 95% CI, 0.79–0.88;
P
<0.001), and in all the 3 categories of more-intensive LLT strategies (more-intensive statin therapy: odds ratio, 0.83; 95% CI, 0.76–0.90;
P
<0.001, ezetimibe: odds ratio, 0.90; 95% CI, 0.85–0.96;
P
<0.001, and PCSK9 inhibitors: odds ratio, 0.81; 95% CI, 0.73–0.90;
P
<0.001) with numerically greater relative odds reduction by more-intensive statin therapy and PCSK9 inhibitors than by ezetimibe. Odds reduction for MACE per 20 mg/dL LDL-C reduction was also different across the 3 types of more-intensive LLT (more-intensive statin therapy: 17.4%, ezetimibe: 11.0%, and PCSK9 inhibitors: 6.6%).

Conclusions:
In this meta-analysis, more-intensive LLT as compared with less-intensive LLT was associated with significant odds reduction for MACE in the entire study population and in all the 3 categories of more-intensive LLT such as more-intensive statin therapy, ezetimibe, and PCSK9 inhibitors. However, overall odds reduction for MACE and odds reduction for MACE per 20 mg/dL LDL-C reduction were different across the 3 types of more-intensive LLT.

Registration:

URLs:
https://www.crd.york.ac.uk/PROSPERO/
and
http://www.umin.ac.jp/ctr
. Unique identifiers: PROSPERO: CRD42018081196, and UMIN-CTR: R000036229.
Fine-Tuning of PGC1α Expression Regulates Cardiac Function and Longevity
Authors: Zhu Xudong , Shen Weiyan , Yao Ke , Wang Hu , Liu Bo , Li Tangliang , Song Lijuan , Diao Daojun , Mao Genxiang , Huang Ping , Li Chengtao , Zhang Hongbo , Zou Yejun , Qiu Yugang , Zhao Yuzheng , Wang Wengong , Yang Yi , Hu Zeping , Auwerx Johan , Loscalzo Joseph , Zhou Yong , Ju Zhenyu 
Published: August 2019

Rationale:
PGC1α (peroxisome proliferator-activated receptor gamma coactivator 1α) represents an attractive target interfering bioenergetics and mitochondrial homeostasis, yet multiple attempts have failed to upregulate PGC1α expression as a therapy, for instance, causing cardiomyopathy.

Objective:
To determine whether a fine-tuning of PGC1α expression is essential for cardiac homeostasis in a context-dependent manner.

Methods and Results:

Moderate cardiac-specific PGC1α overexpression through a ROSA26 locus knock-in strategy was utilized in WT (wild type) mice and in G3Terc
−/−
(third generation of telomerase deficient; hereafter as G3) mouse model, respectively. Ultrastructure, mitochondrial stress, echocardiographic, and a variety of biological approaches were applied to assess mitochondrial physiology and cardiac function. While WT mice showed a relatively consistent PGC1α expression from 3 to 12 months old, age-matched G3 mice exhibited declined PGC1α expression and compromised mitochondrial function. Cardiac-specific overexpression of PGC1α (PGC1α
OE
) promoted mitochondrial and cardiac function in 3-month-old WT mice but accelerated cardiac aging and significantly shortened life span in 12-month-old WT mice because of increased mitochondrial damage and reactive oxygen species insult. In contrast, cardiac-specific PGC1α knock in in G3 (G3 PGC1α
OE
) mice restored mitochondrial homeostasis and attenuated senescence-associated secretory phenotypes, thereby preserving cardiac performance with age and extending health span. Mechanistically, age-dependent defect in mitophagy is associated with accumulation of damaged mitochondria that leads to cardiac impairment and premature death in 12-month-old WT PGC1α
OE
mice. In the context of telomere dysfunction, PGC1α induction replenished energy supply through restoring the compromised mitochondrial biogenesis and thus is beneficial to old G3 heart.

Conclusions:
Fine-tuning the expression of PGC1α is crucial for the cardiac homeostasis because the balance between mitochondrial biogenesis and clearance is vital for regulating mitochondrial function and homeostasis. These results reinforce the importance of carefully evaluating the PGC1α-boosting strategies in a context-dependent manner to facilitate clinical translation of novel cardioprotective therapies.
Relationship Between Brachial‐Ankle Pulse Wave Velocity and Incident Hypertension According to 2017 ACC/AHA High Blood Pressure Guidelines
Authors: Lee Seung Jae , Avolio Alberto , Seo Dae Chul , Kim Bum Soo , Kang Jin Ho , Lee Mi Yeon , Sung Ki‐Chul 
Published: August 2019

Background

Arterial stiffness predicts both cardiovascular events and incident hypertension. However, whether brachial‐ankle pulse wave velocity (ba
PWV
) is predictive of incident hypertension based on the 2017 American College of Cardiology/American Heart Association (ACC/AHA) High Blood Pressure Guidelines has not been established
.
We performed a large cohort study to investigate whether incident hypertension could be predicted from ba
PWV
measurements as a measure of arterial stiffness, even when applying updated hypertension criteria.

Methods and Results

A total of 10 360 Korean adults who underwent ba
PWV
examination during a health‐screening program between 2010 and 2016 were enrolled. Hypertension was defined according to the 2017
ACC
/
AHA
Guidelines as 130/80 mm Hg. Cox proportional hazard analysis was used to assess the risk of incident hypertension according to ba
PWV
quartiles. The mean age of the study subjects was 40.2 years and 75.6% were men. During the follow‐up period (median 2.17 years), 2000 subjects (19.3%) developed hypertension. The subjects in the highest ba
PWV
quartile group showed an increased risk of hypertension compared with the lowest ba
PWV
quartile group as confirmed by multivariate adjusted hazard ratios of 1.64 (95%
CI
1.41–1.89;
P
<0.001) in men and 12.36 (95%
CI
4.41–34.62;
P
=0.005) in women. The increased risk of developing hypertension was consistent after adjusting for several confounding factors.

Conclusions

Arterial stiffness measured by ba
PWV
is associated with incident hypertension according to the updated 2017
ACC
/
AHA
Guidelines and is a useful independent predictor of incident hypertension among relatively healthy people.
Associated Factors and Long-Term Prognosis of 24-Hour Worsening of Arterial Patency After Ischemic Stroke
Authors: Marto João Pedro , Lambrou Dimitris , Eskandari Ashraf , Nannoni Stefania , Strambo Davide , Saliou Guillaume , Maeder Philippe , Sirimarco Gaia , Michel Patrik 
Published: August 2019

Background and Purpose—
Early arterial recanalization in acute ischemic stroke is strongly associated with better outcomes. However, early worsening of arterial patency was seldom studied. We investigated potential predictors and long-term prognosis of worsening of arterial patency at 24 hours after stroke onset.

Methods—
Patients from the Acute Stroke Registry and Analysis of Lausanne registry including admission and 24-hour vascular imaging (computed tomography or magnetic resonance angiography) were included. Worsening of arterial patency was defined as a new occlusion and significant stenosis in any extracranial or intracranial artery, comparing 24 hours with admission imaging. Variables associated with worsening of arterial patency were assessed by stepwise multiple logistic regression. The impact of arterial worsening on 3-month outcome was investigated with an adjusted modified Rankin Scale shift analysis.

Results—
Among 2152 included patients, 1387 (64.5%) received intravenous thrombolysis and endovascular treatment, and 65 (3.0%) experienced 24-hour worsening of arterial patency. In multivariable analysis, history of hypertension seemed protective (adjusted odds ratio [aOR], 0.45; 95% CI, 0.27–0.75) while higher admission National Institutes of Health Stroke Scale (aOR, 1.06; 95% CI, 1.02–1.10), intracranial (aOR, 4.78; 95% CI, 2.03–11.25) and extracranial stenosis (aOR, 3.67; 95% CI, 1.95–6.93), and good collaterals (aOR, 3.71; 95% CI, 1.54–8.95) were independent predictors of worsening of arterial patency. Its occurrence was associated with a major unfavorable shift in the distribution of the modified Rankin Scale at 3 months (aOR, 5.97; 95% CI, 3.64–9.79).

Conclusions—
Stroke severity and admission vascular imaging findings may help to identify patients at a higher risk of developing worsening of arterial patency at 24 hours. The impact of worsening of arterial patency on long-term outcome warrants better methods to detect and prevent this early complication.
Validity and Reliability of Neurological Scores in Mice Exposed to Middle Cerebral Artery Occlusion
Authors: Bieber Michael , Gronewold Janine , Scharf Anne-Carina , Schuhmann Michael K. , Langhauser Friederike , Hopp Sarah , Mencl Stine , Geuss Eva , Leinweber Jonas , Guthmann Josua , Doeppner Thorsten R. , Kleinschnitz Christoph , Stoll Guido , Kraft Peter , Hermann Dirk M. 
Published: August 2019

Background and Purpose—
The selection of appropriate neurological scores and tests is crucial for the evaluation of stroke consequences. The validity and reliability of neurological deficit scores and tests has repeatedly been questioned in ischemic stroke models in the past.

Methods—
In 198 male mice exposed to transient intraluminal middle cerebral artery occlusion, we examined the validity and reliability of 11 neurological scores (Bederson score 0–3, Bederson score 0–4, Bederson score 0–5, modified neurological severity [0–14], subjective overall impression [0–10], or simple neurological tests: grip test, latency to move body length test, pole test, wire hanging test, negative geotaxis test, and elevated body swing test) in the acute stroke phase, that is, after 24 hours. Combinations of neurological scores or tests for predicting infarct volume were statistically analyzed.

Results—

Infarct volume was left skewed (median [Q1–Q3], 78.4 [54.8–101.3] mm
3
). Among all tests, the Bederson (0–5; r=0.63,
P
<0.001), modified neurological severity (r=0.80,
P
<0.001), and subjective overall impression (r=−0.63,
P
<0.001) scores had the highest test validities, using infarct volume as external reference. Subjective overall impression had the best agreement between 5 raters (Kendall W=0.11,
P
<0.001). The Bederson (0–5) score discriminated infarct volume in mice with small (≤50 mm
3
; r=0.33,
P
=0.027) and large (>50 mm
3
; r=0.48,
P
<0.001) brain infarcts, all other tests only in mice with large infarcts. Combining subjective overall impression with Bederson (0–5) score explained 47.6% of the variance of infarct volume.

Conclusions—
Despite their simplicity, the Bederson (0–5) score, modified neurological severity score, and subjective overall impression have reasonable validity and reliability in the acute stroke phase. The Bederson (0–5) score equally distinguishes infarct volume in small and large infarcts.

Visual Overview—

An online
visual overview
is available for this article.
In Your Best Interest
Authors: Strømland Monica , Andersen Anders J W. , Johansen Venke F. , Bahus Marianne K. 
Published: August 2019

We introduce the opportunity for Capability Approach, developed by Martha C. Nussbaum (1997, 2006, 2011), to be used as a guideline to balance the principle of the child’s best interests as formulated in the crc, art. 3 and respect for family life, echr, art. 8, in cases where these principles are drawn in different directions. To contextualize a dilemma, we refer to two stories from the Norwegian courts which illustrate how complex this can be. The stories are similar in the way that they both are related to an evaluation of children`s best interests. We argue conclusively that the list of capabilities could strengthen and supplement the content of the principle of child’s best interests. The list constitutes a basis for participation and insight into the child’s situation, which is valuable when in a position of making decisions critical to the child’s current and future abilities, opportunities and potentialities.
A Swarm of ‘Locusts’
Authors: Yasuhira Genji 
Published: August 2019

Abstract
In the Protestant Dutch Republic, Catholic priests were represented as one of the deadliest “enemies” in view of both their confessional doctrines and political inclination. Under pressure from the Reformed Church, numerous anti-Catholic edicts were issued for the prosecution of priests streaming like a swarm of “locusts” to the Utrecht city, the stronghold for Reformed and Catholic Churches alike in the Northern Netherlands. In theory, the policy of the political authorities barred priests from their pastoral duties to Catholics living in the city. In practice, however, the Utrecht magistracy publicly recognised, and non-publicly connived at, the presence of priests. Political practices of pro/persecution and toleration served to manage and regulate the precarious environment of confessional coexistence. In defying persecution and seeking toleration, Catholic priests tactically and discursively mobilised their civic status based on their and/or their families’ close relationship with, and contribution to, the civic community of Utrecht.
Games with names
Authors: Storch Anne 
Published: August 2019

Abstract
This paper discusses deliberate changes surrounding the practice of naming (people and objects). I first present a discussion of naming and healing, and then turn to the act of naming as an active agent for language change in the context of praise names and names that are used as comments on social change. There are particularly rich areas where the deliberate, creative change of language is strikingly visible, namely in tourism. The analysis of both the deliberate linguistic manipulations and the rationalization of these is informed by African philosophy and local metalinguistic discourse, as part of a project often referred to as the ‘Southern Theory’. I consider the philosophical and theoretical concepts of language and language change that stem from Kenyan and Tanzanian intellectuals and experts who are interested in emic approaches and local epistemologies, emphasizing cultural and social contexts of doing things with words. Intentional language change is seen in this contribution as complex and performative, and is analyzed as the result of individual agency as well as a community’s agreement over what might be done with words.
Biogeochemical Coupling between Ocean and Atmosphere—A Tribute to the Lifetime Contribution of Robert A. Duce
Authors: Brooks Sarah D. , Jickells Tim D. , Liss Peter S. , Thornton Daniel C. O. , Zhang Renyi 
Published: August 2019

AbstractTo mark the publication of the special collection in honor of Robert (Bob) A. Duce in the Journal of the Atmospheric Sciences, we have summarized his most important contributions to the subject of biogeochemical coupling between the atmosphere and ocean. Here we have divided these contributions into four themes—deposition from the atmosphere and its effects on the oceans, volatile elements emitted from the oceans, sea surface biology and aerosol formation, and marine aerosols and clouds. It is our intent that this summary along with the papers in this special collection provide an overview of the enormous contributions that Bob Duce has made to the subject during his distinguished scientific career.
An Observational Overview of Dusty Deep Convection in Martian Dust Storms
Authors: Heavens Nicholas G. , Kass David M. , Shirley James H. , Piqueux Sylvain , Cantor Bruce A. 
Published: August 2019

Abstract
Deep convection, as used in meteorology, refers to the rapid ascent of air parcels in Earth’s troposphere driven by the buoyancy generated by phase change in water. Deep convection undergirds some of Earth’s most important and violent weather phenomena and is responsible for many aspects of the observed distribution of energy, momentum, and constituents (particularly water) in Earth’s atmosphere. Deep convection driven by buoyancy generated by the radiative heating of atmospheric dust may be similarly important in the atmosphere of Mars but lacks a systematic description. Here we propose a comprehensive framework for this phenomenon of dusty deep convection (DDC) that is supported by energetic calculations and observations of the vertical dust distribution and exemplary dusty deep convective structures within local, regional, and global dust storm activity. In this framework, DDC is distinct from a spectrum of weaker dusty convective activity because DDC originates from preexisting or concurrently forming mesoscale circulations that generate high surface dust fluxes, oppose large-scale horizontal advective–diffusive processes, and are thus able to maintain higher dust concentrations than typically simulated. DDC takes two distinctive forms. Mesoscale circulations that form near Mars’s highest volcanoes in dust storms of all scales can transport dust to the base of the upper atmosphere in as little as 2 h. In the second distinctive form, mesoscale circulations at low elevations within regional and global dust storm activity generate freely convecting streamers of dust that are sheared into the middle atmosphere over the diurnal cycle.
Signals of Spring Thermal Contrast Related to the Interannual Variations in the Onset of the South China Sea Summer Monsoon
Authors: Li Yana , Yang Song , Deng Yi , Zheng Bin 
Published: August 2019

AbstractLand–sea thermal contrast is one of the key factors modulating the onset and strength of summer monsoons. This study investigates the precursory thermal-contrast signal of the onset of the South China Sea summer monsoon (SCSSM) and reveals that the land–sea thermal contrastDT(ToceanminusTlandat the surface) in March tracks the date of the monsoon onset very well. In an energy-balance framework, the monthly anomalies in this thermal contrast are decomposed into different components associated with the anomalies of various radiative and nonradiative dynamical processes over the South China Sea in early spring. It is found that the interannual variations ofDT, and thus the onset date of monsoon, are mainly tied to the anomalies in surface heat fluxes, ocean–land heat storage rate, and oceanic dynamical processes. The variation of ocean–land heat storage rate and ocean dynamics is the largest positive contributor to the change inDT. Specifically, an early SCSSM onset tends to be associated with an amplified “cold-land, warm-ocean” pattern that can be further attributed to increased soil moisture content in March, which enhances land surface cooling and weakens oceanic heat storage rate that benefits ocean surface warming. Furthermore, the variations ofDTand soil moisture content in March are positively related with the late-February precipitation over the Indochina Peninsula, which could therefore be regarded as a precursory signal for both the land–sea thermal contrast in March and the onset of the SCSSM.
Assessing External and Internal Sources of Atlantic Multidecadal Variability Using Models, Proxy Data, and Early Instrumental Indices
Authors: O’Reilly Christopher H. , Zanna Laure , Woollings Tim 
Published: August 2019

Abstract
Atlantic multidecadal variability (AMV) of sea surface temperature exhibits an important influence on the climate of surrounding continents. It remains unclear, however, the extent to which AMV is due to internal climate variability (e.g., ocean circulation variability) or changes in external forcing (e.g., volcanic/anthropogenic aerosols or greenhouse gases). Here, the sources of AMV are examined over a 340-yr period using proxy indices, instrumental data, and output from the Last Millennium Ensemble (LME) simulation. The proxy AMV closely follows the accumulated atmospheric forcing from the instrumental North Atlantic Oscillation (NAO) reconstruction (r = 0.65)—an “internal” source of AMV. This result provides strong observational evidence that much of the AMV is generated through the oceanic response to atmospheric circulation forcing, as previously demonstrated in targeted modeling studies. In the LME there is a substantial externally forced AMV component, which exhibits a modest but significant correlation with the proxy AMV (i.e., r = 0.37), implying that at least 13% of the AMV is externally forced. In the LME simulations, however, the AMV response to accumulated NAO forcing is weaker than in the proxy/observational datasets. This weak response is possibly related to the decadal NAO variability, which is substantially weaker in the LME than in observations. The externally forced component in the proxy AMV is also related to the accumulated NAO forcing, unlike in the LME. This indicates that the external forcing is likely influencing the AMV through different mechanistic pathways: via changes in radiative forcing in the LME and via changes in atmospheric circulation in the observational/proxy record.
Variational Assimilation of Radar Data and GLM Lightning-Derived Water Vapor for the Short-Term Forecasts of High-Impact Convective Events
Authors: Fierro Alexandre O. , Wang Yunheng , Gao Jidong , Mansell Edward R. 
Published: August 2019

Abstract
The assimilation of water vapor mass mixing ratio derived from total lightning data from the Geostationary Lightning Mapper (GLM) within a three-dimensional variational (3DVAR) system is evaluated for the analysis and short-term forecast (≤6 h) of a high-impact convective event over the northern Great Plains in the United States. Building on recent work, the lightning data assimilation (LDA) method adjusts water vapor mass mixing ratio within a fixed layer depth above the lifted condensation level by assuming nearly water-saturated conditions at observed lightning locations. In this algorithm, the total water vapor mass added by the LDA is balanced by an equal removal outside observed lightning locations. Additional refinements were also devised to partially alleviate the seasonal and geographical dependence of the original scheme. To gauge the added value of lightning, radar data (radial velocity and reflectivity) were also assimilated with or without lightning. Although the method was evaluated in quasi–real time for several high-impact weather events throughout 2018, this work will focus on one specific, illustrative severe weather case wherein the control simulation—which did not assimilate any data—was eventually able to initiate and forecast the majority of the observed storms. Given a relatively reasonable forecast in the control experiment, the GLM and radar assimilation experiments were still able to improve the short-term forecast of accumulated rainfall and composite radar reflectivity further, as measured by neighborhood-based metrics. These results held whether the simulations made use of one single 3DVAR analysis or high-frequency (10 min) successive cycling over a 1-h period.