bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bivalirudin Versus Heparin Monotherapy in Elderly Patients With Myocardial Infarction
Authors: Wester Axel , Attar Rubina , Mohammad Moman A. , Isma Nazim , James Stefan , Omerovic Elmir , Erlinge David , Koul Sasha 
Published: March 2020

Background:
Elderly patients with acute myocardial infarction undergoing percutaneous coronary intervention are at increased risk of both ischemic and bleeding complications. The optimal anticoagulation strategy in these patients is uncertain. Therefore, we compared bivalirudin to heparin monotherapy in a contemporary cohort of such patients.

Methods:
A prespecified subgroup analysis of elderly patients with myocardial infarction (≥75 years) from the VALIDATE-SWEDEHEART trial (Bivalirudin Versus Heparin in ST-Segment and Non–ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies Registry Trial) was performed. In the trial, patients were randomized to either bivalirudin or heparin monotherapy during percutaneous coronary intervention, with mandatory potent P2Y12 inhibition, routine radial artery access, and only bail-out glycoprotein IIb/IIIa inhibition. Kaplan-Meier event rates were assessed for the primary end point, consisting of a composite of all-cause death, myocardial reinfarction, or major bleeding, within 180 days.

Results:
The elderly (n=1592) had more than twice the risk of all events compared with younger patients (n=4406). Baseline and periprocedural characteristics were equal between bivalirudin (n=799) and heparin (n=793) treated patients ≥75 years. No differences were found in the elderly between bivalirudin and heparin monotherapy regarding the primary end point (180-day all-cause death, myocardial reinfarction, or major bleeding), the individual components of the primary end point, definite stent thrombosis, or stroke.

Conclusions:
In this prespecified subgroup analysis of the VALIDATE-SWEDEHEART trial, elderly patients with myocardial infarction had a highly increased risk of all events. However, no difference in outcomes could be observed with an anticoagulation strategy with either bivalirudin or heparin as monotherapy in this patient group.
Between Apologetics, Emancipation and Imperial Paternalism
Authors: Urbaniak Jakub , Motsisi Mooketsi 
Published: March 2020

Abstract
Scholarship on the abolition of the slave trade and slavery has given little attention to specifically theological factors behind the movement. This article seeks to interrogate three themes that underpinned the activism of the British abolitionists, namely, deliverance/liberty, love of neighbor, and imago Dei. These are examined, first, within their own biblical-theological frame of reference and, second, in relation to other intellectual currents of the era as well as, anachronistically, in the light of some key features of liberation theology. The article considers whether the British abolitionists, whose rhetoric oscillated around apologetics and emancipation and was marked by imperial paternalism, developed a form of proto-liberation theology.
Detection of Human Influence on Precipitation Extremes in Asia
Authors: Dong Siyan , Sun Ying , Li Chao 
Published: March 2020

AbstractThis paper examines the possible influence of external forcings on observed changes in precipitation extremes in the mid-to-high latitudes of Asia during 1958–2012 and attempts to identify particular extreme precipitation indices on which there are better chances to detect the influence of external forcings. We compare a recently compiled dataset of observed extreme indices with those from phase 5 of the Coupled Model Intercomparison Project (CMIP5) simulations using an optimal fingerprinting method. We consider six indices that characterize different aspects of extreme precipitation, including annual maximum amount of precipitation falling in 1 day (Rx1day) or 5 days (Rx5day), the total amount of precipitation from the top 5% or top 1% daily amount on wet days, and the fraction of the annual total precipitation from these events. For single-signal analysis, the fingerprints of external forcings including anthropogenic agents are robustly detected in most studied extreme indices over all Asia and for midlatitude Asia but not for high-latitude Asia. For two-signal analysis, anthropogenic influence is detectable in these indices over Asia at 5% or slightly less than 5% significance level, whereas natural influence is not detectable. In high-latitude Asia, anthropogenic influence is detected only in a fractional index, representing a stark contrast to the midlatitude and full Asia results. We find relatively smaller internal variability and thus higher signal-to-noise ratio in the fractional indices when compared with the other ones. Our results point to the need for studying precipitation extreme indices that are less affected by internal variability while still representing the relevant nature of precipitation extremes to improve the possibility of detecting a forced signal if one is present in the data.
Long-term safety and efficacy of erenumab in patients with chronic migraine: Results from a 52-week, open-label extension study
Authors: Tepper Stewart J , Ashina Messoud , Reuter Uwe , Brandes Jan Lewis , Doležil David , Silberstein Stephen D , Winner Paul , Zhang Feng , Cheng Sunfa , Mikol Daniel D 
Published: March 2020

Background This study reports the long-term safety and efficacy of erenumab in chronic migraine patients. Methods This was a 52-week open-label extension study of a 12-week double-blind treatment phase study. During the double-blind treatment phase, patients received placebo or once-monthly erenumab 70 mg or 140 mg. During the open-label treatment phase, the initial monthly dose was erenumab 70 mg. Following protocol amendment, patients continued to receive erenumab 70 mg if they had already completed their Week 28 visit, otherwise, patients switched from 70 mg to 140 mg; if enrolled after the amendment, patients received 140 mg monthly throughout. Results In all, 451/609 (74.1%) enrolled patients completed the study. The exposure-adjusted patient incidence rate for any adverse event was 126.3/100 patient-years for the overall erenumab group. Overall, the adverse event profile was similar to that observed in the double-blind treatment phase. Adverse event incidence rates did not increase with long-term erenumab treatment compared with the double-blind treatment phase, and no new serious or treatment-emergent events were seen. Efficacy was sustained throughout the 52 weeks. Clinically significant reductions from double-blind treatment phase baseline (about half) were observed for monthly migraine days and migraine-specific medication days. Achievement of ≥50%, ≥75% and 100% reductions from the double-blind treatment phase baseline in monthly migraine days at Week 52 were reported by 59.0%, 33.2% and 8.9% of patients, respectively, for the combined dose group. A numerically greater benefit was observed with 140 mg compared with 70 mg at Weeks 40 and 52. Conclusions Sustained efficacy of long-term erenumab treatment in patients with chronic migraine is demonstrated, with safety results consistent with the known safety profile of erenumab and adverse event rates comparable to placebo adverse event rates in the double-blind treatment phase. Trial registration: This study is registered at ClinicalTrials.gov (NCT02174861)
WGCNA analysis of the subcutaneous fat transcriptome in a novel tree shrew model
Authors: Han Yuanyuan , Wang Wenguang , Jia Jie , Sun Xiaomei , Kuang Dexuan , Tong Pinfen , Li Na , Lu Caixia , Zhang Huatang , Dai Jiejie 
Published: March 2020

Obesity involves genetic and environmental factors. The co-expression gene network in relevant tissues in different obesity groups provides an entrance for profiling and identifying associated pathways and genes. We aim to identify the meaningful co-expressed gene network in mRNA extracted from adipose tissues representing different obesity phenotypes in a new tree shrew model. Furthermore, to find the potential drug target based on analyzing the possible pathways and hub genes responsible for obesity. Ten tree shrews were selected from F1 populations and divided into three groups based on their Lee’s index for mRNA sequencing. We identified clusters of highly correlated genes (modules) in differently expressed genes by weighted gene co-expression network analysis. Three modules were firmly correlated with not less than one obesity phenotype (associations ranging from −0.94 to 0.85, P < 0.01). The genes from the blue module (including 481 genes) are mostly enriched in the ribosome pathway. The genes from the brown module (including 389 genes) are mostly enriched in the lysosome pathway. The genes from the turquoise module (including 1781 genes) are mostly enriched in the ubiquitin-mediated proteolysis pathway. The hub gene in each module was determined, including UBA52 in the blue module, AKT1 in the brown module, and LRRK2 in the turquoise module. After profiling and analyzing the co-expression gene network of obese tree shrew, we identified differently expressed genes and pathways (ribosome, lysosome and ubiquitin-mediated proteolysis pathway) that might be involved in the development of obesity. Further study of the differently expressed genes and pathways might provide new targets for the prevention and therapy of obesity. Impact statement We constructed the transcriptomic network in adipose tissue in lean, moderate obesity and severe obesity groups of tree shrew for the first time. Compared to other laboratory animal models, the tree shrew is a prospective laboratory animal that has a closer genetic association with primates than with rodents. It is widely used in biomedical researches. Enrichment analyses revealed several molecular biological processes were involved in the ribosome, lysosome, and ubiquitin-mediated proteolysis process. These results provided insights into new targets for the prevention and therapy of obesity and a novel research model for obesity.
Exercise right heart catheterization before and after balloon pulmonary angioplasty in inoperable patients with chronic thromboembolic pulmonary hypertension
Authors: Wiedenroth Christoph B. , Rieth Andreas J. , Kriechbaum Steffen , Ghofrani H.‐Ardeschir , Breithecker Andreas , Haas Moritz , Roller Fritz , Richter Manuel J. , Lankeit Mareike , Mielzarek Lisa , Rolf Andreas , Hamm Christian W. , Mayer Eckhard , Guth Stefan , Liebetrau Christoph 
Published: March 2020

BackgroundBalloon pulmonary angioplasty is an evolving, interventional treatment option for inoperable patients with chronic thromboembolic pulmonary hypertension (CTEPH). Pulmonary hypertension at rest as well as exercise capacity is considered to be relevant outcome parameters. The aim of the present study was to determine whether measurement of pulmonary hemodynamics during exercise before and six months after balloon pulmonary angioplasty have an added value.MethodsFrom March 2014 to July 2018, 172 consecutive patients underwent balloon pulmonary angioplasty. Of these, 64 consecutive patients with inoperable CTEPH underwent a comprehensive diagnostic workup that included right heart catheterization at rest and during exercise before balloon pulmonary angioplasty treatments and six months after the last intervention.ResultsImprovements in pulmonary hemodynamics at rest and during exercise, in quality of life, and in exercise capacity were observed six months after balloon pulmonary angioplasty: WHO functional class improved in 78% of patients. The mean pulmonary arterial pressure (mPAP) at rest was reduced from 41 ± 9 to 31 ± 9 mmHg (p < 0.0001). The mPAP/cardiac output slope decreased after balloon pulmonary angioplasty (11.2 ± 25.6 WU to 7.7 ± 4.1 WU; p < 0.0001), and correlated with N‐terminal fragment of pro‐brain natriuretic peptide (p = 0.035) and 6‐minute walking distance (p = 0.01).ConclusionsExercise right heart catheterization provides valuable information on the changes of pulmonary hemodynamics after balloon pulmonary angioplasty in inoperable CTEPH patients that are not obtainable by measuring resting hemodynamics.
Nec-1 Attenuates Neurotoxicity Induced by Titanium Dioxide Nanomaterials on Sh-Sy5y Cells Through RIP1
Authors: Zhou Ting , Huang Wei-kun , Xu Qiu-yan , Zhou Xue , Wang Yue , Yue Zhao-hui , Song Bin 
Published: March 2020

AbstractTitanium dioxide nanomaterials are applied in numerous fields due to their splendid physicochemical characteristics, which in turn poses a potential threat to human health. Recently, numerous in vivo studies have revealed that titanium dioxide nanoparticles (TNPs) can be transported into animal brains after exposure through various routes. Absorbed TNPs can accumulate in the brain and may disturb neuronal cells, leading to brain dysfunction. In vitro studies verified the neurotoxicity of TNPs. The mechanisms underlying the neurotoxicity of TNPs remains unclear. Whether necroptosis is involved in the neurotoxicity of TNPs is unknown. Therefore, we performed an in vitro study and found that TNPs induced inflammatory injury in SH-SY5Y cells in a dose-dependent way, which was mitigated by necrostatin-1 (Nec-1) pretreatment. Since receptor-interacting protein kinase 1 (RIP1) is reported to be the target of Nec-1, we silenced it by siRNA. We exposed mutant and wild-type cells to TNPs and assessed inflammatory injury. Silencing RIP1 expression inhibited inflammatory injury induced by TNPs exposure. Taken together, Nec-1 ameliorates the neurotoxicity of TNPs through RIP1. However, more studies should be performed to comprehensively assess the correlation between the neurotoxicity of TNPs and RIP1.
RETRACTED ARTICLE: The PI3K/mTOR dual inhibitor BEZ235 nanoparticles improve radiosensitization of hepatoma cells through apoptosis and regulation DNA repair pathway
Authors: Tang Xiaolong , Li Amin , Xie Chunmei , Zhang Yinci , Liu Xueke , Xie Yinghai , Wu Binquan , Zhou Shuping , Huang Xudong , Ma Yongfang , Cao Weiya , Xu Ruyue , Shen Jing , Huo Zhen , Cai Shuyu , Liang Yong , Ma Dong 
Published: March 2020

Abstract
Polymer materials encapsulating drugs have broad prospects for drug delivery. We evaluated the effectiveness of polyethylene glycol-poly (lactic-co-glycolic acid) (PLGA-PEG) encapsulation and release characteristics of PI3K/mTOR inhibitor NVP-BEZ235 (BEZ235). We proposed a strategy for targeting radiosensitization of liver cancer cells. The biocompatibility, cell interaction, and internalization of Glypican-3 (GPC3) antibody-modified, BEZ235-loaded PLGA-PEG nanoparticles (NP-BEZ235-Ab) in hepatoma cells in vitro were studied. Also, the cell killing effect of NP-BEZ235-Ab combined with γ-ray cell was evaluated. We used confocal microscopy to monitor nanoparticle-cell interactions and cellular uptake, conducted focus-formation experiments to analyze the synergistic biological effects of NP-BEZ235-Ab and priming, and studied synergy in liver cancer cells using molecular biological methods such as western blotting. We found that PLGA-PEG has good loading efficiency for BEZ235 and high selectivity to GPC3-positive HepG2 liver cancer cells, thus documenting that NP-BEZ235-Ab acts as a small-molecule drug delivery nanocarrier. At the nominal concentration, the NP-BEZ235-Ab nanoformulation synergistically kills liver cancer cells with significantly higher efficiency than does the free drug. Thus, NP-BEZ235-Ab is a potential radiosensitizer.

Graphical Abstract
Construction of ZnTiO3/Bi4NbO8Cl heterojunction with enhanced photocatalytic performance
Authors: Gao Zhaoqun , Qu Xiaofei 
Published: March 2020

AbstractConstructing heterojunction is an effective strategy to enhance photocatalytic performance of photocatalysts. Herein, we fabricated ZnTiO3/Bi4NbO8Cl heterojunction with improved performance via a typical mechanical mixing method. The rhodamine (RhB) degradation rate over heterojunction is higher than that of individual ZnTiO3 or Bi4NbO8Cl under Xenon-arc lamp irradiation. Combining ZnTiO3 with Bi4NbO8Cl can inhibit the recombination of photo-excited carriers. The improved quantum efficiency was demonstrated by transient-photocurrent responses (PC), electrochemical impedance spectroscopy (EIS), photoluminescence (PL) spectra, and time-resolved PL (TRPL) spectra. This research may be valuable for photocatalysts in the industrial application.
Tanshinone IIA alleviates hypoxia/reoxygenation induced cardiomyocyte injury via lncRNA AK003290/miR-124-5p signaling
Authors: Chen Liye , Wei Lili , Yu Qiongyang , Shi Haozhe , Liu George 
Published: March 2020

Abstract
Background
Acute myocardial infarction (AMI) is the leading cause of death globally and has thus placed a heavy burden on healthcare. Tanshinone IIA (TSA) is a major active compound, extracted from Salvia miltiorrhiza Bunge, that possesses various pharmacological activities. The aim of the present study was to investigate the role of TSA in AMI and its underlying mechanism of action. Results: We have shown that TSA decreased the apoptosis rate, the amount of LDH, MDA as well as ROS of cardiomyocytes. Meantime, it elevated mitochondrial membrane potential (MMP) which was decreased by H/R treatment. It was also determined that miR-124-5p targets AK003290 directly. TSA up-regulated the expression of AK003290 and its function can be reversed by knock down of AK003290 as well as miR-124-5p overexpression.

Conclusion
TSA exerts the protective role against H/R induced apoptosis, oxidative and MMP loss of cardiomyocytes via regulating AK003290 and miR-124-5p signaling.
Novel approach in whole genome mining and transcriptome analysis reveal conserved RiPPs in Trichoderma spp
Authors: Vignolle Gabriel A. , Mach Robert L. , Mach-Aigner Astrid R. , Derntl Christian 
Published: March 2020

Abstract
Background
Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a highly diverse group of secondary metabolites (SM) of bacterial and fungal origin. While RiPPs have been intensively studied in bacteria, little is known about fungal RiPPs. In Fungi only six classes of RiPPs are described. Current strategies for genome mining are based on these six known classes. However, the genes involved in the biosynthesis of theses RiPPs are normally organized in biosynthetic gene clusters (BGC) in fungi.

Results
Here we describe a comprehensive strategy to mine fungal genomes for RiPPs by combining and adapting existing tools (e.g. antiSMASH and RiPPMiner) followed by extensive manual curation based on conserved domain identification, (comparative) phylogenetic analysis, and RNASeq data. Deploying this strategy, we could successfully rediscover already known fungal RiPPs. Further, we analysed four fungal genomes from the Trichoderma genus. We were able to find novel potential RiPP BGCs in Trichoderma using our unconventional mining approach.

Conclusion
We demonstrate that the unusual mining approach using tools developed for bacteria can be used in fungi, when carefully curated. Our study is the first report of the potential of Trichoderma to produce RiPPs, the detected clusters encode novel uncharacterized RiPPs. The method described in our study will lead to further mining efforts in all subdivisions of the fungal kingdom.
Cognitive, functional, physical, and nutritional status of the oldest old encountered in primary care: a systematic review
Authors: Escourrou Emile , Durrieu Florence , Chicoulaa Bruno , Dupouy Julie , Oustric Stéphane , Andrieu Sandrine , Gardette Virginie 
Published: March 2020

Abstract
Background
The oldest old (individuals over 90 years) are a fast-growing population. Characterizing their specificity would be helpful to adapt health care. This study aimed to characterize the cognitive, functional, nutritional, and physical status of individuals over 90.

Methods
We conducted a systematic review of cross-sectional or cohort studies of individuals aged 90 years old or more, living at home or in a nursing home, in April 2018. Two reviewers selected eligible articles, extracted data, and evaluated the risk of bias (assessed by the Newcastle-Ottawa Scale).

Results
The search strategy identified 3086 references; 35 articles were included referring to 8 cross-sectional and 27 longitudinal studies. Dementia was diagnosed in 30–42.9% of study participants, cognitive impairment in 12–50%, and 31–65% had no cognitive impairment. In terms of activities of daily living, 14–72.6% of individuals had no difficulty, 35.6–38% had difficulty, and 14.4–55.5% were dependent. For instrumental activities of daily living, 20–67.9% needed help. Regarding nutritional status, the Mini Nutritional Assessment Short Form mean score ranged from 10.3 (SD: 1.8) to 11.1 (SD: 2.4). Eight to 32% of individuals could not stand up from a chair, 19–47% could stand without the use of their arms; and 12.9–15% were not able to walk 4 m.

Conclusions
These results suggest a heterogeneous population with a certain proportion of oldest old with a low level of disability. These findings suggest that a specific approach in the care of the oldest old could help prevent disability.
Ten years risk assessment of atherosclerotic cardiovascular disease using Astro-CHARM and pooled cohort equation in a south Asian sub-population
Authors: Ashraf Tariq , Mengal Muhammad Naeem , Muhammad Atif Sher , Tareen Asal Khan , Khan Muhammad Nauman , Kazmi Khawar Abbas , Nadeem Asif , Sarwar Shakil , Bashir Zara , Qamar Nadeem , Karim Musa 
Published: March 2020

Abstract
Background
Atherosclerotic cardiovascular diseases (ASCVD) are on the rise in low and middle-income countries attributed to modern sedentary lifestyle and dietary habits. This has led to the need of assessment of the burden of at-risk population so that prevention measures can be developed. The objective of this study was to assess ten years risk assessment of ASCVD using Astro-CHARM and Pooled Cohort Equation (PCE) in a South Asian sub-population.

Methods
A total of 386 residents of all six districts of Karachi with no ASCVD were enrolled in the study through an exponential non-discriminative referral snowball sampling technique. The inclusion criteria consisted of age 40 years or above and either gender. Study participants were enrolled after obtaining informed written consent and those study participants who were found to have either congenital heart disease or valvular heart diseases or ischemic heart disease were excluded from the study based on initial screening. For the calculation of 10 years risk of ACVD based on Astro-CHARM and PCE, the variables were obtained including medical history and coronary artery calcium and C-reactive protein measurements.

Results
Mean estimated 10-year risk of fatal or non-fatal myocardial infarction or stroke as per the Astro-CHARM was 13.98 ± 8.01%, while mean estimated 10-year risk of fatal or non-fatal myocardial infarction or stroke as per the PCE was 22.26 ± 14.01%. Based on Astro-CHARM, 11.14% of the study participants were labeled as having high risk, while PCE estimated 20.73% of study participants as having high risk of ASCVD.

Conclusion
Despite the fact that our findings showed substantial differences in ten-year risk of ASCVD between Astro-CHARM and PCE, both calculators can be used to develop a new population and specific risk estimators for this South Asian sub-population. Our study provides the first step towards developing a risk assessment guided decision-making protocol for primary prevention of ASCVD in this population.