bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systems Pharmacology Identifies an Arterial Wall Regulatory Gene Network Mediating Coronary Artery Disease Side Effects of Antiretroviral Therapy
Authors: Frades Itziar , Readhead Ben , Amadori Letizia , Koplev Simon , Talukdar Husain A. , Crane Heidi M. , Crane Paul K. , Kovacic Jason C. , Dudley Joel T. , Giannarelli Chiara , Björkegren Johan L.M. , Peter Inga 
Published: June 2019

Background:
Antiretroviral therapy (ART) for HIV infection increases risk for coronary artery disease (CAD), presumably by causing dyslipidemia and increased atherosclerosis. We applied systems pharmacology to identify and validate specific regulatory gene networks through which ART drugs may promote CAD.

Methods:
Transcriptional responses of human cell lines to 15 ART drugs retrieved from the Library of Integrated Cellular Signatures (overall 1127 experiments) were used to establish consensus ART gene/transcriptional signatures. Next, enrichments of differentially expressed genes and gene-gene connectivity within these ART-consensus signatures were sought in 30 regulatory gene networks associated with CAD and CAD-related phenotypes in the Stockholm Atherosclerosis Gene Expression study.

Results:

Ten of 15 ART signatures were significantly enriched both for differential expression and connectivity in a specific atherosclerotic arterial wall regulatory gene network (AR-RGN) causal for CAD involving RNA processing genes. An atherosclerosis in vitro model of cholestryl ester-loaded foam cells was then used for experimental validation. Treatments of these foam cells with ritonavir, nelfinavir, and saquinavir at least doubled cholestryl ester accumulation (
P
=0.02, 0.0009, and 0.02, respectively), whereas RNA silencing of the AR-RGN top key driver,
PQBP1
(polyglutamine binding protein 1), significantly curbed cholestryl ester accumulation following treatment with any of these ART drugs by >37% (
P
<0.05).

Conclusions:

By applying a novel systems pharmacology data analysis framework, 3 commonly used ARTs (ritonavir, nelfinavir, and saquinavir) were found altering the activity of AR-RGN, a regulatory gene network promoting foam cell formation and risk of CAD. Targeting AR-RGN or its top key driver
PQBP1
may help reduce CAD side effects of these ART drugs.
Novel Drug Targets for Ischemic Stroke Identified Through Mendelian Randomization Analysis of the Blood Proteome
Authors: Chong Michael , Sjaarda Jennifer , Pigeyre Marie , Mohammadi-Shemirani Pedrum , Lali Ricky , Shoamanesh Ashkan , Gerstein Hertzel Chaim , Paré Guillaume 
Published: June 2019

Background:
Novel, effective, and safe drugs are warranted for treatment of ischemic stroke. Circulating protein biomarkers with causal genetic evidence represent promising drug targets, but no systematic screen of the proteome has been performed.

Methods:
First, using Mendelian randomization (MR) analyses, we assessed 653 circulating proteins as possible causal mediators for 3 different subtypes of ischemic stroke: large artery atherosclerosis, cardioembolic stroke, and small artery occlusion. Second, we used MR to assess whether identified biomarkers also affect risk for intracranial bleeding, specifically intracerebral and subarachnoid hemorrhages. Third, we expanded this analysis to 679 diseases to test a broad spectrum of side effects associated with hypothetical therapeutic agents for ischemic stroke that target the identified biomarkers. For all MR analyses, summary-level data from genome-wide association studies (GWAS) were used to ascertain genetic effects on circulating biomarker levels versus disease risk. Biomarker effects were derived by meta-analysis of 5 GWAS (N≤20 509). Disease effects were derived from large GWAS analyses, including MEGASTROKE (N≤322 150) and UK Biobank (N≤408 961) studies.

Results:

Several biomarkers emerged as causal mediators for ischemic stroke. Causal mediators for cardioembolic stroke included histo-blood group ABO system transferase, coagulation factor XI, scavenger receptor class A5 (SCARA5), and tumor necrosis factor–like weak inducer of apoptosis (TNFSF12). Causal mediators for large artery atherosclerosis included ABO, cluster of differentiation 40, apolipoprotein(a), and matrix metalloproteinase-12. SCARA5 (odds ratio [OR]=0.78; 95% CI, 0.70–0.88;
P
=1.46×10
−5
) and TNFSF12 (OR=0.86; 95% CI, 0.81–0.91;
P
=7.69×10
−7
) represent novel protective mediators of cardioembolic stroke. TNFSF12 also increased the risk of subarachnoid (OR=1.53; 95% CI, 1.31–1.78;
P
=3.32×10
−8
) and intracerebral (OR=1.34; 95% CI, 1.14–1.58;
P
=4.05×10
−4
) hemorrhages, whereas SCARA5 decreased the risk of subarachnoid hemorrhage (OR=0.61; 95% CI, 0.47–0.81;
P
=5.20×10
−4
). Multiple side effects beyond stroke were identified for 6 of 7 biomarkers, most (75%) of which were beneficial. No adverse side effects were found for coagulation factor XI, apolipoprotein(a), and SCARA5.

Conclusions:
Through a systematic MR screen of the circulating proteome, causal roles for 5 established and 2 novel biomarkers for ischemic stroke were identified. Side-effect profiles were characterized to help inform drug target prioritization. In particular, SCARA5 represents a promising target for treatment of cardioembolic stroke, with no predicted adverse side effects.
Prevalence and Temporal Distribution of Fast and Slow Progressors of Infarct Growth in Large Vessel Occlusion Stroke
Authors: Rocha Marcelo , Desai Shashvat M. , Jadhav Ashutosh P. , Jovin Tudor G. 
Published: June 2019

Background and Purpose—
Fast and slow progressors of infarct growth due to anterior circulation large vessel occlusion are commonly observed in clinical practice. We aimed to estimate the prevalence and temporal distribution of fast and slow progressors among anterior circulation large vessel occlusion patients diagnosed within 24 hours of stroke onset.

Methods—
Single-center retrospective study of all patients with anterior circulation large vessel occlusion who underwent baseline computed tomographic perfusion or magnetic resonance imaging within 24 hours of stroke onset. Prevalence was determined for fast progressors (ischemic core >70 mL, <6 hours of stroke onset) and slow progressors (ischemic core ≤30 mL, >6–24 hours of stroke onset).

Results—
One hundred eighty-five patients were included. The median time interval from stroke onset to baseline core imaging was 7.6 hours (interquartile range, 3.9–13.2), and median core volume was 17 mL (range, 0–405). Patients had core volume ≤70 mL in 72% of cases in the overall cohort. The prevalence of fast progressors was 25% (95% CI, 17%–37%) and reached 40% (95% CI, 24%–59%) between 3 and 4.5 hours after stroke onset. The prevalence of slow progressors was 55% (95% CI, 46%–64%) and was similar across time intervals beyond 6 hours after stroke onset.

Conclusions—
Most anterior circulation large vessel occlusion patients had small-to-moderate ischemic core volume, irrespective of early or delayed presentation within 24 hours of stroke onset. Fast progressors were highly prevalent between 3 and 4.5 hours after stroke onset.
Recent Nationwide Impact of Mechanical Thrombectomy on Decompressive Hemicraniectomy for Acute Ischemic Stroke
Authors: Rumalla Kavelin , Ottenhausen Malte , Kan Peter , Burkhardt Jan-Karl 
Published: June 2019

Background and Purpose—
The treatment of patients with acute ischemic stroke has been revolutionized by endovascular mechanical thrombectomy (MT), leading to dramatically improved outcomes. Here, we analyzed the impact of recent changes in stroke management on nationwide trends in patient characteristics, treatment modalities, and outcomes.

Methods—

The National Inpatient Sample was analyzed using
International Classification of Diseases, Ninth and Tenth Editions
, Clinical Modification codes to identify adult stroke patients with anterior-circulation, large-vessel occlusion in the pre- (2012–2014) and the post-MT trial period (2015–2016). Univariate and multivariable predictors of decompressive hemicraniectomy (DHC) were ascertained in patients developing malignant cerebral edema.

Results—

The nationwide query identified 519 320 adult stroke patients with annually increasing volume (92 320 to 129 340), stroke severity, and treatment at urban teaching centers. DHC was performed in 9.5% of patients developing malignant cerebral edema (n=33 530) and was associated with a high rate of discharge to long-term nursing care (65%) and mortality (23%). Over time, the rate of MT (3.4% to 9.8%) increased whereas the rate of DHC for malignant cerebral edema declined from 11.4% to 4.8% (
P
<0.001). In a binary logistic regression model controlling for potential confounders (eg, age, severity of illness), MT patients were 43% less likely to require DHC (odds ratio, 0.7; 95% CI, 0.6–0.9).

Conclusions—
Nationwide trends indicated that successful reperfusion of penumbra with MT in stroke patients leads to a declining indication for DHC whereas stroke volume increases over time.
Synopsis of lobatifrons species-group (Hymenoptera: Bethylidae, Rhabdepyris) from Neotropical region, with redefinition of the group
Authors: STEIN P. R.W. , AZEVEDO C. O. 
Published: June 2019

The lobatifrons species-group of Neotropical region is redefined as to include the Rhabdepyris species with appendicular process at cuspis in the male genitalia. Rhabdepyris latissimus sp. nov., R. callosus sp. nov., R. concavus sp. nov. and R. demissus sp. nov. are described and illustrated. New geographical records and taxonomical data on R. septemlineatus Kieffer, 1906, R. quinquilineatus Kieffer, 1906, R. luteipennis, Evans, 1965, R. atlanticus Rosmann & Azevedo, 2005 are provided. R. lobatifrons Kieffer, 1910 is a junior synonym of R. septemlineatus. A key to males are given.
Terrestrial and Freshwater Invertebrate Fauna of the High Arctic Archipelago of Svalbard
Authors: COULSON STEPHEN JAMES 
Published: June 2019

An overview of the terrestrial and freshwater invertebrate fauna of the High Arctic archipelago of Svalbard is presented. Sixty seven additional species to the previous checklist are listed and the described terrestrial and freshwater invertebrate fauna of Svalbard now stands at 1,107 species. Species presented are cross referenced to the literature. A brief comparison with the invertebrate fauna of Greenland indicates that Svalbard may be under-represented in Hymenoptera, Hemiptera and Lepidoptera but over-represented in Collembola and Acari. However, since 82% of Svalbard primary source manuscripts originate from three locations along the west coast, there is a resulting likely bias in our knowledge of the invertebrate fauna. The west coast has a mild climate for the northerly latitude due to the influence of the West Spitsbergen Current, a northerly flowing branch of the North Atlantic Drift. The faunistically poorly known east coast is hypothesised to have a different invertebrate fauna due to the predominant winds and currents originating from the north east and hence this coast will have a different history of immigration and colonization from the west coast. The use of checklists is therefore cautioned due to possible sampling bias and omissions created by a concentration of work on popular groups and at a limited number of localities. However, this does not detract from their importance as baseline databases, especially during a period of rapid environmental change.
A review of the genus Bruchia Weise 1906 (Coleoptera: Chrysomelidae: Cassidinae)
Authors: STAINES C. L. 
Published: June 2019

The species of Bruchia are reviewed. Bruchia armata from Brazil, Colombia and Peru, and B. scapularis from Colombia are described as new. Each species is described and illustrated and a key to the species is provided.
Relationship between Tropical and Extratropical Diabatic Heating and Their Impact on Stationary–Transient Wave Interference
Authors: Park Mingyu , Lee Sukyoung 
Published: June 2019

Abstract
During boreal winter, the climatological stationary wave plays a key role in the poleward transport of heat in mid- and high latitudes. Latent heating is an important driver of boreal-winter stationary waves. In this study, the temporal relationship between tropical and extratropical heating and transient–stationary wave interference is investigated by performing observational data analyses and idealized model experiments. In line with stationary wave theory, the observed heating anomaly fields during constructive interference events have a spatial structure that reinforces the zonal asymmetry of the climatological heating field. The observational analysis shows that about 10 days prior to constructive interference events, tropical heating anomalies are established, and within 1 week North Pacific and then North Atlantic heating anomalies follow. This result suggests that constructive interference involves a heating–circulation relay: tropical latent heating drives circulation anomalies that transport moisture in such a manner as to increase latent heating in the North Pacific; circulation anomalies driven by this North Pacific heating similarly lead to enhanced latent heating in the North Atlantic. This heating–circulation relay picture is supported by initial-value model calculations in which the observed heating anomalies are used to drive model circulations. Our results also show that the constructive interference driven by both tropical and extratropical diabatic heating generates a relatively large-amplitude wave in high latitudes and leads to particularly prolonged Arctic warming episodes, whereas when both the tropical and extratropical diabatic heating are weak, constructive interference is confined to midlatitudes and does not lead to Arctic warming.
Estimating the Local Time of Emergence of Climatic Variables Using an Unbiased Mapping of GCMs: An Application in Semiarid and Mediterranean Chile
Authors: Chadwick Cristián , Gironás Jorge , Vicuña Sebastián , Meza Francisco 
Published: June 2019

Abstract
The time at which climate change signal can be clearly distinguished from noise is known as time of emergence (ToE) and is typically detected by a general circulation model (GCM) signal-to-noise ratio exceeding a certain threshold. ToE is commonly estimated at large scales from GCMs, although management decisions and adaptation strategies are implemented locally. This paper proposes a methodology to estimate ToE for both precipitation and temperature at local scales (i.e., river basin). The methodology considers local climatic conditions and unbiased GCM projections to estimate ToE by using the statistical power to find when the climate significantly differs from the historical one. The method suggests that ToE for temperature already occurred in three Chilean basins (Limarí, Maipo, and Maule). However, in terms of precipitation, an earlier ToE is clearly identified for the Maule basin, indicating that risk assessment and adaptation measures should be implemented first in this basin.
Measuring Real-Time Team Cognition During Team Training
Authors: Gorman Jamie C. , Grimm David A. , Stevens Ronald H. , Galloway Trysha , Willemsen-Dunlap Ann M. , Halpin Donald J. 
Published: June 2019

Objective A method for detecting real-time changes in team cognition in the form of significant communication reorganizations is described. We demonstrate the method in the context of scenario-based simulation training. Background We present the dynamical view that individual- and team-level aspects of team cognition are temporally intertwined in a team’s real-time response to challenging events. We suggest that this real-time response represents a fundamental team cognitive skill regarding the rapidity and appropriateness of the response, and methods and metrics are needed to track this skill. Method Communication data from medical teams (Study 1) and submarine crews (Study 2) were analyzed for significant communication reorganization in response to training events. Mutual information between team members informed post hoc filtering to identify which team members contributed to reorganization. Results Significant communication reorganizations corresponding to challenging training events were detected for all teams. Less experienced teams tended to show delayed and sometimes ineffective responses that more experienced teams did not. Mutual information and post hoc filtering identified the individual-level inputs driving reorganization and potential mechanisms (e.g., leadership emergence, role restructuring) underlying reorganization. Conclusion The ability of teams to rapidly and effectively reorganize coordination patterns as the situation demands is a team cognitive skill that can be measured and tracked. Application Potential applications include team monitoring and assessment that would allow for visualization of a team’s real-time response and provide individualized feedback based on team member’s contributions to the team response.
Long-term epigenetic changes in offspring mice exposed to alcohol during gestation and lactation
Authors: Cantacorps Lídia , Alfonso-Loeches Silvia , Guerri Consuelo , Valverde Olga 
Published: June 2019

Background: Alcohol exposure impairs brain development and leads to a range of behavioural and cognitive dysfunctions, termed as foetal alcohol spectrum disorders. Although different mechanisms have been proposed to participate in foetal alcohol spectrum disorders, the molecular insights of such effects are still uncertain. Using a mouse model of foetal alcohol spectrum disorder, we have previously shown that maternal binge-like alcohol drinking causes persistent effects on motor, cognitive and emotional-related behaviours associated with neuroimmune dysfunctions. Aims: In this study, we sought to evaluate whether the long-term behavioural alterations found in offspring with early exposure to alcohol are associated with epigenetic changes in the hippocampus and prefrontal cortex. Methods: Pregnant C57BL/6 female mice underwent a model procedure for binge alcohol drinking throughout both the gestation and lactation periods. Subsequently, adult offspring were assessed for their cognitive function in a reversal learning task and brain areas were extracted for epigenetic analyses. Results: The results demonstrated that early binge alcohol exposure induces long-term behavioural effects along with alterations in histone acetylation (histone H4 lysine 5 and histone H4 lysine 12) in the hippocampus and prefrontal cortex. The epigenetic effects were linked with an imbalance in histone acetyltransferase activity that was found to be increased in the prefrontal cortex of mice exposed to alcohol. Conclusions: In conclusion, our results reveal that maternal binge-like alcohol consumption induces persistent epigenetic modifications, effects that might be associated with the long-term cognitive and behavioural impairments observed in foetal alcohol spectrum disorder models.
Alternative splicing in serotonergic system: Implications in neuropsychiatric disorders
Authors: Latorre Eva , Mesonero Jose Emilio , Harries Lorna W 
Published: June 2019

Background: The serotonergic system is a key component of physiological brain function and is essential for proper neurological activity. Numerous neuropsychiatric disorders are associated with deregulation of the serotonergic system. Accordingly, many pharmacological treatments are focused on modulation of this system. While providing a promising line of therapeutic moderation, these approaches may be complicated due to the presence of alternative splicing events for key genes in this pathway. Alternative splicing is a co-transcriptional process by which different mRNA transcripts can be produced from the same gene. These different isoforms may have diverse activities and functions, and their relative balance is often critical for the maintenance of homeostasis. Alternative splicing greatly increases the production of proteins, augmenting cell plasticity, and provides an important control point for regulation of gene expression. Aim: The objective of this narrative review is to discuss the potential impact of alternative splicing of different components of the serotonergic system and speculate on their involvement in several neuropsychiatric disorders. Conclusions: The specific role of each isoform in disease and their relative activities in the signalling pathways involved are yet to be determined. We need to gain a better understanding of the basis of alternative isoforms of the serotonergic system in order to fully understand their impact and be able to develop new effective pharmacological isoform-specific targets.
Effects of a probiotic drink containing Lactobacillus casei strain Shirota on dental plaque microbiota
Authors: Hu Xiaoli , Huang Zhuwei , Zhang Yuejiao , Hong Yubing , Zheng Yuan 
Published: June 2019

Objective To investigate the effects of a probiotic drink containing Lactobacillus casei strain Shirota on dental plaque microbiota. Methods Caries-free young adults were administered a probiotic drink containing L. casei Shirota (Yakult) three times on day 1, then once daily for 28 days. Dental plaque samples were collected and analysed by 16S rRNA sequencing before (day 1), during (day 2), and one day following intervention (day 30). Results Out of samples from 10 included participants, 256 814 sequences passed through quality control, clustered into 170–234 different ‘species-level’ phylotypes. Actinobacteria, Bacteroidetes, Firmicutes, Fusobacteria and Proteobacteria were the most abundant phyla. Dental plaque microbiota composition significantly changed at different taxonomic levels following probiotic consumption. At genus level, the relative abundance of Veillonella and Kingella increased significantly following intervention, while that of Leptotrichia reduced significantly during intervention, but recovered to baseline level at day 30. Alpha diversity and overall structure of the dental plaque microbiota was not significantly impacted by the probiotic. Conclusion Yakult intake changed the abundance of some bacteria related to caries, suggesting that the change of composition may be beneficial to oral health, while the overall microbiota structure remained unaffected.