bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cycling reduces blood glucose excursions after an oral glucose tolerance test in pregnant women: a randomized crossover trial
Authors: Andersen Mette Bisgaard , Ovesen Per Glud , Daugaard Merete , Ostenfeld Eva Bjerre , Fuglsang Jens 
Published: May 2020

The aim of this study was to evaluate the effect of an acute bout of cycling immediately after oral glucose intake on glucose metabolism in pregnant women at risk for gestational diabetes mellitus (GDM). Fifteen pregnant women with BMI ≥ 27 kg/m2 were enrolled in a randomized crossover controlled study and underwent two oral glucose tolerance tests (OGTTs) ingesting 75 g of glucose followed by either 20 min of stationary cycling at moderate intensity (65%–75% maximal heart rate) or rest. Using continuous glucose monitors, glucose was measured up to 48 h after the OGTT. Glucose, insulin, and C-peptide were determined at baseline and after 1 and 2 h. One hour after glucose intake, mean blood glucose was significantly lower after cycling compared with rest (p = 0.002). Similarly, mean glucose peak level was significantly lower after cycling compared with after rest (p = 0.039). Lower levels of insulin and C-peptide were observed after 1 h (p < 0.01). Differences in glucose measurements after 2 h and up to 48 h were not statistically different. We found that 20 min of cycling at moderate intensity after glucose intake reduced blood glucose excursions in pregnant women at risk for GDM. ClinicalTrials.gov Identifier: NCT03644238. Novelty Bullets In pregnant women, we found that cycling after glucose intake resulted in significantly lower glucose levels compared with rest. The exercise intervention studied is feasible for pregnant women and could be readily used to reduce glucose excursions.
Optical properties of a Brane-World black hole as photons couple to the Weyl tensor
Authors: Zhang He-Xu , Li Cong , He Peng-Zhang , Fan Qi-Qi , Deng Jian-Bo 
Published: May 2020

AbstractIn this article, we have investigated the equations of motion of the photons coupled to Weyl tensor by the geometric optics approximation and the corresponding shadow in a Brane-World black hole spacetime. It is shown that there exists a double shadow for a black hole since the coupling photons with different polarization directions propagate along different paths in the spacetime. Furthermore, we discuss the effects of the metric parameter $$\alpha $$α related to the cosmological constant, X-cold dark matter parameter $$\beta $$β and the coupling parameter $$\lambda $$λ on the umbra (the overlap region of the double shadow) and the penumbra. We also obtain the finite-distance corrections to the deflection angle of light in the Brane-World black hole spacetime as the photons coupled to Weyl tensor by using a recent geometric method.
Emergent collective dynamics of bottom-heavy squirmers under gravity
Authors: Rühle Felix , Stark Holger 
Published: May 2020

Abstract.
We present the results of hydrodynamic simulations using the method of multi-particle collision dynamics for a system of squirmer microswimmers moving under the influence of gravity at low Reynolds numbers. In addition, the squirmers are bottom-heavy so that they experience a torque which aligns them along the vertical. The squirmers interact hydrodynamically by the flow fields of a stokeslet and rotlet, which are initiated by the acting gravitational force and torque, respectively, and by their own flow fields. By varying the ratio of swimming to bulk sedimentation velocity and the torque, we determine state diagrams for the emergent collective dynamics of neutral squirmers as well as strong pushers and pullers. For low swimming velocity and torque we observe conventional sedimentation, while the sedimentation profile becomes inverted when their values are increased. For neutral squirmers we discover convective rolls of circulating squirmers between both sedimentation states, which sit at the bottom of the system and are fed by plumes made of collectively sinking squirmers. At larger torques porous clusters occur that spawn single squirmers. The two latter states can also occur transiently starting from a uniform squirmer distribution and then disappear in the long-time limit. For strong pushers and pullers only weak plume formation is observed.

Graphical abstract
JGraphT—A Java Library for Graph Data Structures and Algorithms
Authors: Michail Dimitrios , Kinable Joris , Naveh Barak , Sichi John V. 
Published: May 2020

Mathematical software and graph-theoretical algorithmic packages to efficiently model, analyze, and query graphs are crucial in an era where large-scale spatial, societal, and economic network data are abundantly available. One such package is JGraphT, a programming library that contains very efficient and generic graph data structures along with a large collection of state-of-the-art algorithms. The library is written in Java with stability, interoperability, and performance in mind. A distinctive feature of this library is its ability to model vertices and edges as arbitrary objects, thereby permitting natural representations of many common networks, including transportation, social, and biological networks. Besides classic graph algorithms such as shortest-paths and spanning-tree algorithms, the library contains numerous advanced algorithms: graph and subgraph isomorphism, matching and flow problems, approximation algorithms for NP-hard problems such as independent set and the traveling salesman problem, and several more exotic algorithms such as Berge graph detection. Due to its versatility and generic design, JGraphT is currently used in large-scale commercial products, as well as noncommercial and academic research projects.
In this work, we describe in detail the design and underlying structure of the library, and discuss its most important features and algorithms. A computational study is conducted to evaluate the performance of JGraphT versus several similar libraries. Experiments on a large number of graphs over a variety of popular algorithms show that JGraphT is highly competitive with other established libraries such as NetworkX or the BGL.
Towards Question-based High-recall Information Retrieval
Authors: Zou Jie , Kanoulas Evangelos 
Published: May 2020

While continuous active learning algorithms have proven effective in finding most of the relevant documents in a collection, the cost for locating the last few remains high for applications such as Technology-assisted Reviews (TAR). To locate these last few but significant documents efficiently, Zou et al. [2018] have proposed a novel interactive algorithm. The algorithm is based on constructing questions about the presence or absence of entities in the missing relevant documents. The hypothesis made is that entities play a central role in documents carrying key information and that the users are able to answer questions about the presence or absence of an entity in the missing relevance documents. Based on this, a Sequential Bayesian Search-based approach that selects the optimal sequence of questions to ask was devised. In this work, we extend Zou et al. [2018] by (a) investigating the noise tolerance of the proposed algorithm; (b) proposing an alternative objective function to optimize, which accounts for user “erroneous” answers; (c) proposing a method that sequentially decides the best point to stop asking questions to the user; and (d) conducting a small user study to validate some of the assumptions made by Zou et al. [2018]. Furthermore, all experiments are extended to demonstrate the effectiveness of the proposed algorithms not only in the phase of abstract appraisal (i.e., finding the abstracts of potentially relevant documents in a collection) but also finding the documents to be included in the review (i.e., finding the subset of those relevant abstracts for which the article remains relevant). The experimental results demonstrate that the proposed algorithms can greatly improve performance, requiring reviewing fewer irrelevant documents to find the last relevant ones compared to state-of-the-art methods, even in the case of noisy answers. Further, they show that our algorithm learns to stop asking questions at the right time. Last, we conduct a small user study involving an expert reviewer. The user study validates some of the assumptions made in this work regarding the user’s willingness to answer the system questions and the extent of it, as well as the ability of the user to answer these questions.
Posttranslational Regulation of the Exon Skipping Machinery Controls Aberrant Splicing in Leukemia
Authors: Zhou Yalu , Han Cuijuan , Wang Eric , Lorch Adam H. , Serafin Valentina , Cho Byoung-Kyu , Gutierrez Diaz Blanca T. , Calvo Julien , Fang Celestia , Khodadadi-Jamayran Alireza , Tabaglio Tommaso , Marier Christian , Kuchmiy Anna , Sun Limin , Yacu George , Filip Szymon K. , Jin Qi , Takahashi Yoh-Hei , Amici David R. , Rendleman Emily J. , Rawat Radhika , Bresolin Silvia , Paganin Maddalena , Zhang Cheng , Li Hu , Kandela Irawati , Politanska Yuliya , Abdala-Valencia Hiam , Mendillo Marc L. , Zhu Ping , Palhais Bruno , Van Vlierberghe Pieter , Taghon Tom , Aifantis Iannis , Goo Young Ah , Guccione Ernesto , Heguy Adriana , Tsirigos Aristotelis , Wee Keng Boon , Mishra Rama K. , Pflumio Francoise , Accordi Benedetta , Basso Giuseppe , Ntziachristos Panagiotis 
Published: May 2020

Abstract

Splicing alterations are common in diseases such as cancer, where mutations in splicing factor genes are frequently responsible for aberrant splicing. Here we present an alternative mechanism for splicing regulation in T-cell acute lymphoblastic leukemia (T-ALL) that involves posttranslational stabilization of the splicing machinery via deubiquitination. We demonstrate there are extensive exon skipping changes in disease, affecting proteasomal subunits, cell-cycle regulators, and the RNA machinery. We present that the serine/arginine-rich splicing factors (SRSF), controlling exon skipping, are critical for leukemia cell survival. The ubiquitin-specific peptidase 7 (USP7) regulates SRSF6 protein levels via active deubiquitination, and USP7 inhibition alters the exon skipping pattern and blocks T-ALL growth. The splicing inhibitor H3B-8800 affects splicing of proteasomal transcripts and proteasome activity and acts synergistically with proteasome inhibitors in inhibiting T-ALL growth. Our study provides the proof-of-principle for regulation of splicing factors via deubiquitination and suggests new therapeutic modalities in T-ALL.

Significance:
Our study provides a new proof-of-principle for posttranslational regulation of splicing factors independently of mutations in aggressive T-cell leukemia. It further suggests a new drug combination of splicing and proteasomal inhibitors, a concept that might apply to other diseases with or without mutations affecting the splicing machinery.
This article is highlighted in the In This Issue feature, p. 1241
Bempegaldesleukin (NKTR-214) plus Nivolumab in Patients with Advanced Solid Tumors: Phase I Dose-Escalation Study of Safety, Efficacy, and Immune Activation (PIVOT-02)
Authors: Diab Adi , Tannir Nizar M. , Bentebibel Salah-Eddine , Hwu Patrick , Papadimitrakopoulou Vassiliki , Haymaker Cara , Kluger Harriet M. , Gettinger Scott N. , Sznol Mario , Tykodi Scott S. , Curti Brendan D. , Tagliaferri Mary A. , Zalevsky Jonathan , Hannah Alison L. , Hoch Ute , Aung Sandra , Fanton Christie , Rizwan Ahsan , Iacucci Ernesto , Liao Yijie , Bernatchez Chantale , Hurwitz Michael E. , Cho Daniel C. 
Published: May 2020

Abstract

This single-arm, phase I dose-escalation trial (NCT02983045) evaluated bempegaldesleukin (NKTR-214/BEMPEG), a CD122-preferential IL2 pathway agonist, plus nivolumab in 38 patients with selected immunotherapy-naïve advanced solid tumors (melanoma, renal cell carcinoma, and non–small cell lung cancer). Three dose-limiting toxicities were reported in 2 of 17 patients during dose escalation [hypotension (n = 1), hyperglycemia (n = 1), metabolic acidosis (n = 1)]. The most common treatment-related adverse events (TRAE) were flu-like symptoms (86.8%), rash (78.9%), fatigue (73.7%), and pruritus (52.6%). Eight patients (21.1%) experienced grade 3/4 TRAEs; there were no treatment-related deaths. Total objective response rate across tumor types and dose cohorts was 59.5% (22/37), with 7 complete responses (18.9%). Cellular and gene expression analysis of longitudinal tumor biopsies revealed increased infiltration, activation, and cytotoxicity of CD8+ T cells, without regulatory T-cell enhancement. At the recommended phase II dose, BEMPEG 0.006 mg/kg plus nivolumab 360 mg every 3 weeks, the combination was well tolerated and demonstrated encouraging clinical activity irrespective of baseline PD-L1 status.

Significance:
These data show that BEMPEG can be successfully combined with a checkpoint inhibitor as dual immunotherapy for a range of advanced solid tumors. Efficacy was observed regardless of baseline PD-L1 status and baseline levels of tumor-infiltrating lymphocytes, suggesting therapeutic potential for patients with poor prognostic risk factors for response to PD-1/PD-L1 blockade.
See related commentary by Rouanne et al., p. 1097.
This article is highlighted in the In This Issue feature, p. 1079
Extracellular Vesicle–Mediated Delivery of Circular RNA SCMH1 Promotes Functional Recovery in Rodent and Nonhuman Primate Ischemic Stroke Models
Authors: Yang Li , Han Bing , Zhang Zhiting , Wang Shuguo , Bai Ying , Zhang Yuan , Tang Ying , Du Lingli , Xu Ling , Wu Fangfang , Zuo Lei , Chen Xufeng , Lin Yu , Liu Kezhong , Ye Qingqing , Chen Biling , Li Bin , Tang Tianci , Wang Yu , Shen Ling , Wang Guangtian , Ju Minzi , Yuan Mengqin , Jiang Wei , Zhang John H. , Hu Gang , Wang Jianhong , Yao Honghong 
Published: May 2020

Background:
Stroke is a leading cause of adult disability that can severely compromise the quality of life of patients, yet no effective medication currently exists to accelerate rehabilitation. A variety of circular RNA (circRNA) molecules are known to function in ischemic brain injury. Lentivirus-based expression systems have been widely used in basic studies of circRNAs, but safety issues with such delivery systems have limited exploration of the potential therapeutic roles for circRNAs.

Methods:
Circular RNA SCMH1 (circSCMH1) was screened from the plasma of patients with acute ischemic stroke by using circRNA microarrays. Engineered rabies virus glycoprotein-circSCMH1-extracellular vesicles were generated to selectively deliver circSCMH1 to the brain. Nissl staining was used to examine infarct size. Behavioral tasks were performed to evaluate motor functions in both rodent and nonhuman primate ischemic stroke models. Golgi staining and immunostaining were used to examine neuroplasticity and glial activation. Proteomic assays and RNA-sequencing data combined with transcriptional profiling were used to identify downstream targets of circSCMH1.

Results:
CircSCMH1 levels were significantly decreased in the plasma of patients with acute ischemic stroke, offering significant power in predicting stroke outcomes. The decreased levels of circSCMH1 were further confirmed in the plasma and peri-infarct cortex of photothrombotic stroke mice. Beyond demonstrating proof-of-concept for an RNA drug delivery technology, we observed that circSCMH1 treatment improved functional recovery after stroke in both mice and monkeys, and we discovered that circSCMH1 enhanced the neuronal plasticity and inhibited glial activation and peripheral immune cell infiltration. CircSCMH1 binds mechanistically to the transcription factor MeCP2 (methyl-CpG binding protein 2), thereby releasing repression of MeCP2 target gene transcription.

Conclusions:
Rabies virus glycoprotein-circSCMH1-extracellular vesicles afford protection by promoting functional recovery in the rodent and the nonhuman primate ischemic stroke models. Our study presents a potentially widely applicable nucleotide drug delivery technology and demonstrates the basic mechanism of how circRNAs can be therapeutically exploited to improve poststroke outcomes.
Environment-Sensing Aryl Hydrocarbon Receptor Inhibits the Chondrogenic Fate of Modulated Smooth Muscle Cells in Atherosclerotic Lesions
Authors: Kim Juyong Brian , Zhao Quanyi , Nguyen Trieu , Pjanic Milos , Cheng Paul , Wirka Robert , Travisano Stanislao , Nagao Manabu , Kundu Ramendra , Quertermous Thomas 
Published: May 2020

Background:
Smooth muscle cells (SMC) play a critical role in atherosclerosis. The Aryl hydrocarbon receptor (AHR) is an environment-sensing transcription factor that contributes to vascular development, and has been implicated in coronary artery disease risk. We hypothesized that AHR can affect atherosclerosis by regulating phenotypic modulation of SMC.

Methods:

We combined RNA-sequencing, chromatin immunoprecipitation followed by sequencing, assay for transposase-accessible chromatin using sequencing, and in vitro assays in human coronary artery SMCs, with single-cell RNA-sequencing, histology, and RNAscope in an SMC-specific lineage-tracing
Ahr
knockout mouse model of atherosclerosis to better understand the role of
AHR
in vascular disease.

Results:

Genomic studies coupled with functional assays in cultured human coronary artery SMCs revealed that
AHR
modulates the human coronary artery SMC phenotype and suppresses ossification in these cells. Lineage-tracing and activity-tracing studies in the mouse aortic sinus showed that the
Ahr
pathway is active in modulated SMCs in the atherosclerotic lesion cap. Furthermore, single-cell RNA-sequencing studies of the SMC-specific
Ahr
knockout mice showed a significant increase in the proportion of modulated SMCs expressing chondrocyte markers such as
Col2a1
and
Alpl
, which localized to the lesion neointima. These cells, which we term “chondromyocytes,” were also identified in the neointima of human coronary arteries. In histological analyses, these changes manifested as larger lesion size, increased lineage-traced SMC participation in the lesion, decreased lineage-traced SMCs in the lesion cap, and increased alkaline phosphatase activity in lesions in the
Ahr
knockout in comparison with wild-type mice. We propose that
AHR
is likely protective based on these data and inference from human genetic analyses.

Conclusions:

Overall, we conclude that
AHR
promotes the maintenance of lesion cap integrity and diminishes the disease-related SMC-to-chondromyocyte transition in atherosclerotic tissues.
Comanagement of Risk Factors in Patients With Coronary Artery Disease: Insights From the APPEAR Study
Authors: Hejjaji Vittal , Gosch Kensey , Jones Philip G. , Breeding Tracie , Spertus John A. , Arnold Suzanne V. 
Published: May 2020

Background
Effective management of cardiovascular risk factors is the foundation of secondary prevention in coronary artery disease. The physician under whose sphere these are managed can vary, primary care physicians, cardiologists, or both, and the optimal management strategy for risk factor control is unknown.

Methods and Results

The APPEAR (Angina Prevalence and Provider Evaluation of Angina Relief) study was a cross‐sectional cohort study of outpatients with coronary artery disease (stable angina, percutaneous coronary intervention, coronary artery bypass grafting, or myocardial infarction) from 25
US
cardiology practices. After each patient visit, providers noted who managed each risk factor. Blood pressure and lipid levels were recorded from charts. We compared adherence to guideline‐directed risk factor control between management strategies (primary care physician alone, cardiologist alone, or comanaged). Among 1259 outpatients with coronary artery disease (mean [
SD
] age, 71 [11.1] years; 69% men), blood pressure and lipid management strategy varied. Mean blood pressure was 127.9/72.3 mm Hg, with 74% of patients at <140/90 mm Hg and 46% at <130/80 mm Hg. Mean low‐density lipoprotein was 83.5 mg/dL, with 75% of patients at <100 mg/dL and 91% on appropriate statin therapy. Patients managed by cardiologists alone tended to have higher rates of risk factor control for both blood pressure and lipids, even after adjusting for covariates.

Conclusions

Although comanagement has shown benefit in some clinical situations, we found that risk factor control in patients with coronary artery disease tended to be poorer when care was shared between cardiologists and primary care physicians. Further research is needed to better define which conditions are best comanaged and how to more effectively comanage patients in the fractured
US
healthcare system.
Coronavirus Disease 2019 (COVID‐19) Pandemic Implications in Pediatric and Adult Congenital Heart Disease
Authors: Alsaied Tarek , Aboulhosn Jamil A. , Cotts Timothy B. , Daniels Curt J. , Etheridge Susan P. , Feltes Timothy F. , Gurvitz Michelle Z. , Lewin Mark B. , Oster Matthew E. , Saidi Arwa 
Published: May 2020

Abstract
The corona virus disease ‐2019 (COVID‐19) is a recently described infectious disease caused by the severe acute respiratory syndrome corona virus 2 with significant cardiovascular implications. Given the increased risk for severe COVID‐19 observed in adults with underlying cardiac involvement, there is concern that patients with pediatric and congenital heart disease (CHD) may likewise be at increased risk for severe infection. The cardiac manifestations of COVID‐19 include myocarditis, arrhythmia and myocardial infarction. Importantly, the pandemic has stretched health care systems and many care team members are at risk for contracting and possibly transmitting the disease which may further impact the care of patients with cardiovascular disease. In this review, we describe the effects of COVID‐19 in the pediatric and young adult population and review the cardiovascular involvement in COVID‐19 focusing on implications for patients with congenital heart disease in particular.
Religion and Reconnecting with Nature
Authors: DiBona Christopher D. 
Published: May 2020

Abstract
Attention to the work of American pragmatist philosopher John Dewey and Native American novelist, poet, and essayist Leslie Silko reveals what are in many ways remarkably similar and complementary conceptualizations of religion, as both authors situate religion in the human’s experienced alienation from and reconnection with the natural world, draw heavily on Romantic motifs in literary art to convey the “religious” dynamics of these experiences, and suggest that readers who sincerely engage with certain literary works of art can come to share in these dynamics in a way that has the potential to help reorient their everyday relations with and attitudes toward the natural world. Reading Dewey alongside Silko thus offers us an interdisciplinary set of resources to articulate and promote an ecological conception of religion founded on a mutualistic-symbiotic mode of human dwelling on the earth.