bluuebunny/crossref_metadata_2025_split huggingface dataset:
How Do SGLT2 (Sodium-Glucose Cotransporter 2) Inhibitors and GLP-1 (Glucagon-Like Peptide-1) Receptor Agonists Reduce Cardiovascular Outcomes?
Authors: Lee Matthew M.Y. , Petrie Mark C. , McMurray John J.V. , Sattar Naveed 
Published: January 2020

Objective:
There is substantial interest in how GLP-1RA (glucagon-like peptide-1 receptor agonists) and SGLT2 (sodium-glucose cotransporter 2) inhibitors reduce cardiovascular and renal events; yet, robust mechanistic data in humans remain sparse. We conducted a narrative review of published and ongoing mechanistic clinical trials investigating the actions of SGLT2 inhibitors and GLP-1RAs to help the community appreciate the extent of ongoing work and the variety and design of such trials.

Approach and Results:
To date, trials investigating the mechanisms of action of SGLT2 inhibitors have focused on pathways linked to glucose metabolism and toxicity, hemodynamic/volume, vascular and renal actions, and cardiac effects, including those on myocardial energetics. The participants studied have included those with established cardiovascular disease (including coronary artery disease and heart failure), liver disease, renal impairment, obesity, and hypertension; some of these trials have enrolled patients both with and without type 2 diabetes mellitus. GLP-1RA mechanistic trials have focused on glucose-lowering, insulin-sparing, weight reduction, and blood pressure–lowering effects, as well as possible direct vascular, cardiac, and renal effects of these agents. Very few mechanisms of action of SGLT2 inhibitors or GLP-1RAs have so far been convincingly demonstrated. One small trial (n=97) of SGLT2 inhibitors has investigated the cardiac effects of these drugs, where a small reduction in left ventricular mass was found. Data on vascular effects are limited to one trial in type 1 diabetes mellitus, which suggests some beneficial actions. SGLT2 inhibitors have been shown to reduce liver fat. We highlight the near absence of mechanistic data to explain the beneficial effects of SGLT2 inhibitors in patients without diabetes mellitus. GLP-1RAs have not been found to have major cardiovascular mechanisms of action in the limited, completed trials. Conflicting data around the impact on infarct size have been reported. No effect on left ventricular ejection fraction has been demonstrated.

Conclusions:
We have tabulated the extensive ongoing mechanistic trials that will report over the coming years. We report 2 exemplar ongoing mechanistic trials in detail to give examples of the designs and techniques employed. The results of these many ongoing trials should help us understand how SGLT2 inhibitors and GLP-1RAs improve cardiovascular and renal outcomes and may also identify unexpected mechanisms suggesting novel therapeutic applications.
Hematopoietic Cell–Expressed Endothelial Nitric Oxide Protects the Liver From Insulin Resistance
Authors: Dick Brian P. , McMahan Ryan , Knowles Taft , Becker Lev , Gharib Sina A. , Vaisar Tomas , Wietecha Tomasz , O’Brien Kevin D. , Bornfeldt Karin E. , Chait Alan , Kim Francis 
Published: January 2020

Objective:

Mice genetically deficient in endothelial nitric oxide synthase (Nos3
−/−
) have fasting hyperinsulinemia and hepatic insulin resistance, indicating the importance of Nos3 (nitric oxide synthase) in maintaining metabolic homeostasis. Although the current paradigm holds that these metabolic effects are derived specifically from the expression of Nos3 in the endothelium, it has been established that bone marrow–derived cells also express Nos3. The aim of this study was to investigate whether bone marrow–derived cell Nos3 is important in maintaining metabolic homeostasis.

Approach and Results:
To test the hypothesis that bone marrow–derived cell Nos3 contributes to metabolic homeostasis, we generated chimeric male mice deficient or competent for Nos3 expression in circulating blood cells. These mice were placed on a low-fat diet for 5 weeks, a time period which is known to induce hepatic insulin resistance in global Nos3-deficient mice but not in wild-type C57Bl/6 mice. Surprisingly, we found that the absence of Nos3 in the bone marrow–derived component is associated with hepatic insulin resistance and that restoration of Nos3 in the bone marrow–derived component in global Nos3-deficient mice is sufficient to restore hepatic insulin sensitivity. Furthermore, we found that overexpression of Nos3 in bone marrow–derived component in wild-type mice attenuates the development of hepatic insulin resistance during high-fat feeding. Finally, compared with wild-type macrophages, the loss of macrophage Nos3 is associated with increased inflammatory responses to lipopolysaccharides and reduced anti-inflammatory responses to IL-4, a macrophage phenotype associated with the development of hepatic and systemic insulin resistance.

Conclusions:
These results would suggest that the metabolic and hepatic consequences of high-fat feeding are mediated by loss of Nos3/nitric oxide actions in bone marrow–derived cells, not in endothelial cells.
Epithelial and Endothelial Adhesion of Immune Cells Is Enhanced by Cardiotonic Steroid Signaling Through Na
+
/K
+
‐ATPase‐α‐1
Authors: Khalaf Fatimah K. , Tassavvor Iman , Mohamed Amal , Chen Yiliang , Malhotra Deepak , Xie Zijian , Tian Jiang , Haller Steven T. , Westfall Kristen , Tang W. H. Wilson , Kennedy David J. 
Published: January 2020

Background

Recent studies have highlighted a critical role for a group of natriuretic hormones, cardiotonic steroid (
CTS
), in mediating renal inflammation and fibrosis associated with volume expanded settings, such as chronic kidney disease. Immune cell adhesion is a critical step in the inflammatory response; however, little is currently understood about the potential regulatory role of
CTS
signaling in this setting. Herein, we tested the hypothesis that
CTS
signaling through Na
+
/K
+
‐
ATP
ase α‐1 (
NKA
α‐1) enhances immune cell recruitment and adhesion to renal epithelium that ultimately advance renal inflammation.

Methods and Results

We demonstrate that knockdown of the α‐1 isoform of Na/K‐
ATP
ase causes a reduction in
CTS
‐induced macrophage infiltration in renal tissue as well reduces the accumulation of immune cells in the peritoneal cavity in vivo. Next, using functional adhesion assay, we demonstrate that
CTS‐
induced increases in the adhesion of macrophages to renal epithelial cells were significantly diminished after reduction of
NKA
α‐1 in either macrophages or renal epithelial cells as well after inhibition of
NKA
α‐1‐Src signaling cascade with a specific peptide inhibitor,
pNaK
tide in vitro. Finally,
CTS‐
induced expression of adhesion markers in both endothelial and immune cells was significantly inhibited in an
NKA
α‐1‐Src signaling dependent manner in vitro.

Conclusions

These findings suggest that
CTS
potentiates immune cell migration and adhesion to renal epithelium through an
NKA
α‐1–dependent mechanism; our new findings suggest that pharmacological inhibition of this feed‐forward loop may be useful in the treatment of renal inflammation associated with renal disease.
Predicting Cardiovascular Outcomes by Baseline Lipoprotein(a) Concentrations: A Large Cohort and Long‐Term Follow‐up Study on Real‐World Patients Receiving Percutaneous Coronary Intervention
Authors: Liu Hui‐Hui , Cao Ye‐Xuan , Jin Jing‐Lu , Zhang Hui‐Wen , Hua Qi , Li Yan‐Fang , Guo Yuan‐Lin , Zhu Cheng‐Gang , Wu Na‐Qiong , Xu Rui‐Xia , Chen Xie‐Hui , Li Jian‐Jun 
Published: January 2020

Background

Although several studies have indicated that lipoprotein(a) is a useful prognostic predictor for patients following percutaneous coronary intervention (
PCI
), previous observations have somewhat been limited by either small sample size or short‐term follow‐up. Hence, this study aimed to evaluate the impact of lipoprotein(a) on long‐term outcomes in a large cohort of stable coronary artery disease patients after
PCI
.

Methods and Results

In this multicenter and prospective study, we consecutively enrolled 4078 stable coronary artery disease patients undergoing
PCI
from March 2011 to March 2016. They were categorized according to both the median of lipoprotein(a) levels and lipoprotein(a) values of <15 (low), 15 to 30 (medium), and ≥30 mg/
dL
(high). All patients were followed up for occurrence of cardiovascular events, including cardiovascular death, nonfatal myocardial infarction, and stroke. During an average of 4.9 years of follow‐up, 315 (7.7%) cardiovascular events occurred. The events group had significantly higher lipoprotein(a) levels than the nonevents group. Compared with the low lipoprotein(a) group, Kaplan–Meier analysis showed that the high lipoprotein(a) group had a significantly lower cumulative event‐free survival rate, and multivariate Cox regression analysis further revealed that the high lipoprotein(a) group had significantly increased cardiovascular events risk. Moreover, adding continuous or categorical lipoprotein(a) to the Cox model led to a significant improvement in C‐statistic, net reclassification, and integrated discrimination.

Conclusions

With a large sample size and long‐term follow‐up, our data confirmed that high lipoprotein(a) levels could be associated with a poor prognosis after
PCI
in stable coronary artery disease patients, suggesting that lipoprotein(a) measurements may be useful for patient risk stratification before selective
PCI
.
Role of Abnormally Enhanced MJO over the Western Pacific in the Formation and Subseasonal Predictability of the Record-Breaking Northeast Asian Heatwave in the Summer of 2018
Authors: Hsu Pang-Chi , Qian Yitian , Liu Yu , Murakami Hiroyuki , Gao Yingxia 
Published: January 2020

AbstractIn the summer of 2018, Northeast Asia experienced a heatwave event that broke the existing high-temperature records in several locations in Japan, the Korean Peninsula, and northeastern China. At the same time, an unusually strong Madden–Julian oscillation (MJO) was observed to stay over the western Pacific warm pool. Based on reanalysis diagnosis, numerical experiments, and assessments of real-time forecast data from two subseasonal-to-seasonal (S2S) models, we discovered the importance of the western Pacific MJO in the generation of this heatwave event, as well as its predictability at the subseasonal time scale. During the prolonged extreme heat period (11 July–14 August), a high pressure anomaly with variability at the intraseasonal (30–90 days) time scale appeared over Northeast Asia, causing persistent adiabatic heating and clear skies in this region. As shown in the composites of MJO-related convection and circulation anomalies, the occurrence of this 30–90-day high anomaly over Northeast Asia was linked with an anomalous wave train induced by tropical heating associated with the western tropical Pacific MJO. The impact of the MJO on the heatwave was further confirmed by sensitivity experiments with a coupled GCM. As the western Pacific MJO-related components were removed by nudging prognostic variables over the tropics toward their annual cycle and longer time scales (>90 days) in the coupled GCM, the anomalous wave train along the East Asian coast disappeared and the surface air temperature in Northeast Asia lowered. The MJO over the western Pacific warm pool also influenced the predictability of the extratropical heatwave. Our assessments of two S2S models’ real-time forecasts suggest that the extremity of this Northeast Asian heatwave can be better predicted 1–4 weeks in advance if the enhancement of MJO convection over the western Pacific warm pool is predicted well.
Aging Effects on Esophageal Transit Time in the Upright Position During Videofluoroscopy
Authors: Garand Kendrea L. (Focht) , Culp Lindsey , Wang Bin , Davidson Kate , Martin-Harris Bonnie 
Published: January 2020

Objectives: The purpose of this study was to examine age-related effects on esophageal transit times (ETT) among healthy adult participants. Methods: A total of 175 healthy, non-dysphagic participants underwent a modified barium swallow study (MBSS), and ETT was recorded for two standardized swallowing tasks. Differences across age groups were determined using Kruskal–Wallis test. Relationships between an Esophageal Clearance (Modified Barium Swallow Impairment Profile Component 17) score and ETT were also explored. Results: No significant differences were observed in ETT across age groups for nectar-thickened liquid ( P = .335) or pudding ( P = .231) consistencies. No significant differences were observed between males and females in ETT for either the nectar ( P = .112) or pudding trial ( P = .817). For nectar, the mean ETT for patients with Component 17 scores of 2 or greater were significantly higher than that of participants with a score of 0 ( P < .0001). For pudding, participants with a score >0 demonstrated significantly higher mean ETT compared to participants with a score of 0 (with P = .0008 and P < .0001, respectively). Conclusion: Study findings failed to support age-related or sex-related differences in ETT for two standardized swallowing tasks administered during a MBSS in healthy individuals. The normative values following a standardized protocol in this study provide guidance in clinical interpretation of esophageal function.
Olfactory Facilitation of Takeover Performance in Highly Automated Driving
Authors: Tang Qiuyang , Guo Gang , Zhang Zijian , Zhang Bingbing , Wu Yingzhang 
Published: January 2020

Objective This study aims to quantify the impact of olfactory stimulation and takeover modality on the performance of takeovers in conditionally automated driving. Background Takeover requests are important for the safety of automated vehicles. The reaction time and subsequent performance of drivers in the takeover process are crucial for safety. In this study, peppermint was adopted as an auxiliary modality to the tactile and auditory design of takeover requests. Methods Sixty participants took part in the experiment, which required participants to avoid a stalled vehicle after they were awoken from a state of light sleep by a takeover request. Takeover modality (tactile, auditory, and combined) was the within-subjects factor. In the between-subjects design, half of the participants received a peppermint odor stimulation when the takeover request occurred, and the other half received a placebo (air). Results The presence of peppermint odor did not influence the reaction time, but participants did show signs of being more alert afterwards. For the moment of takeover, use of the auditory modality had a significant positive effect on reaction time compared to the tactile conditions. Conclusion Peppermint odor had a positive impact on drivers’ takeover quality when engaged in nondriving-related activities such as light sleep, and the takeover request modalities were shown to be crucial for a safe and successful takeover. Application The results will be useful as a reference for developers of automated driving systems to design human–machine interfaces, shorten the driver’s reaction time, and improve takeover quality.
Outcomes of Endonasal Septoplasty and Extracorporeal Septal Reconstruction in Anterocaudal Septal Deviation
Authors: Tian Qiushi , Chu Teng , Sun Haimin , Pang Mingjie 
Published: January 2020

Objective: The aim of this study was to compare the functional and aesthetic outcomes of endonasal septoplasty (ES) and extracorporeal septal reconstruction (ESR) in anterocaudal septal deviation. Methods: In this study, patients (n = 46) who underwent nasal septoplasty surgery due to anterocaudal septal deviation during February 2015 to August 2017 were analyzed; 23 patients underwent ES and the others (n = 23) underwent ESR. The decision of whether to use the ES or ESR was randomized by random number table method. Nasal obstruction symptoms evaluation (NOSE) scores, total nasal resistance (TNR), aesthetic visual analog scale (VAS), nasal anatomical angles, and incidence of complications were used to assess the patients in 2 groups. Results: The NOSE scores, TNR, aesthetic VAS, tip deviation angle (TDA), nasolabial angle (NLA), nasofrontal angle (NFA) in the ESR group were significantly improved from preoperative to postoperative 1 year, whereas in the ES group, except aesthetic VAS, NLA, NFA, all other postoperative outcomes were improved from preoperative values. The objective and subjective postoperative results of ESR group were better than the ES group except TDA. The incidence of complications was not significantly different between the 2 groups. Conclusion: Our study have compared the nasal functional and aesthetic outcomes of 2 septoplasty techniques in a randomized controlled trial. The ESR technique is more effective than ES technique in correcting functional and aesthetic disorders caused by anterocaudal septal deviation.
The geographical network of international migration
Authors: Kincses Aron , Tóth Géza 
Published: January 2020

International migration offers a new field in which the results of network theory can be harvested. Through the migration countries’ networks (from where and to where migrants move), we have provided some of the most important tangible outcomes of network analysis in migration statistics.  The results of this research establish that there are hubs of international migration. Global migration destinations draw international migrants from greater distances. Migration connectivity between countries is constantly increasing. At the same time, most countries have few connections with other countries through migration, while a few have many connections. This network is interconnected by hubs with multiple connectivity capabilities.
Central Nervous System Systemic Lupus Erythematosus (CNS-SLE) Vasculitis Mimicking Lewy Body Dementia: A Case Report Emphasizing the Role of Imaging With an Analysis of 33 Comparable Cases From the Scientific Literature
Authors: Abraham Peter , Neel Ian , Bishay Steven , Sewell Daniel D. 
Published: January 2020

Introduction: Neuropsychiatric symptoms occur in 30% to 40% of patients living with systemic lupus erythematosus (SLE). Brain imaging may play a pivotal role in determining the etiology as it did for the case presented here. Methods: A new case of central nervous system (CNS) SLE is presented along with an analysis of 33 comparable cases from the scientific literature. Results: A 70-year-old female with subacute cutaneous lupus presented to a university-based geropsychiatry program after 1 year of benign visual hallucinations and several months of shuffling gait, recurrent falls, and forgetfulness. These symptoms were highly suggestive of Lewy body dementia; however, the patient’s history of basal ganglia infarct, cognitive testing demonstrating inattention and executive dysfunction, and follow-up brain imaging, which did not reveal acute findings, aligned with cerebral pathology previously attributed to vasculitis and supported the diagnosis of subcortical dementia due to SLE-CNS vasculitis. Oral prednisone 20 mg daily resolved her symptoms. Over the next 19 months, her prednisone was tapered completely and her symptoms did not return. A systematic literature search identified 33 comparable cases. Conclusion: An analysis of previously published cases suggests that extending the duration of the prednisone taper beyond 1 year may decrease the risk of later occurring neuropsychiatric symptoms in this patient population.
Prediction error and implicit learning in L1 and L2 syntactic priming
Authors: Jackson Carrie N. , Hopp Holger 
Published: January 2020

Aims and Objectives: This study examines the syntactic priming of adverb-first word order among 27 first language (L1) English, 33 L1 German, and 32 L1 German-second language (L2) English speakers to investigate the relationship between short-term priming and longer-term learning across different speaker groups. Design/Methodology: Participants completed a syntactic priming task in either English or German, in which they heard sentences containing fronted (i.e. adverb-first) or non-fronted adverbial phrases and described pictures containing similar adverbial phrases. Immediately before and after the priming task, participants completed picture description tasks containing similar sentence types to measure their baseline production of fronted adverbials, and whether subsequent production of fronted adverbials was modulated by the priming task. Data Analysis: We used mixed-effects logistic regression to compare participants’ production of fronted sentences during the priming task according to prime type (fronted vs. non-fronted) and their production of fronted sentences before versus after the priming task, including the additional factors of adverbial phrase (temporal phrase vs. locative phrase) and speaker group (L1 English vs. L1 German vs. L2 English). Findings/Conclusion: Participants exhibited greater short-term priming during the priming task for temporal versus locative phrases, with the L2 English speakers exhibiting the greatest short-term priming. There was a significant increase in the production of fronted sentences from baseline to post-test, with the L1 English speakers exhibiting the greatest gains. Originality: This study uses systematic between- and within-language comparisons to examine: (a) whether the extent of syntactic priming depends on the frequency of a construction in a speaker’s L1 or L2 (i.e. prediction error); and (b) whether prediction error and short-term priming lead to longer-term learning. Significance: Our findings show that the magnitude of prediction error influences both short-term adaptation and longer-term priming. However, the ability to harness prediction error for longer-term learning versus short-term adaptation may vary between L1 and L2 speakers.