bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimation of the impact of changing drug-use trend on HIV, hepatitis C and syphilis epidemics among people who use synthetic drug-only, polydrug and heroin-only during 2005–2035 in China: modelling study
Authors: Su Shu , Fairley Christopher K , Mao Limin , Medland Nicholas , Shen Mingwang , Li Yan , Zhuang Guihua , Zhang Lei 
Published: March 2020

ObjectiveThe rapid expansion of the recreational drug market becomes a global health concern. It is worrying that the bacterial and viral infection epidemics linking to drug use may worsen accordingly. This study aimed to estimate the impacts of changing trend and behaviours of using heroin only, synthetic drug (SD) only and polydrug (using SD and heroin concurrently) on HIV, hepatitis C virus (HCV) and syphilis epidemics among people who use drugs in China by 2035.MethodsWe constructed a compartmental model to estimate HIV, HCV and syphilis epidemics in the dynamic drug-use trend by three scenarios: SD-only use, heroin-only use and polydrug use based on Monte Carlo simulations. The parameters for the model were collected from a comprehensive literature search.ResultsOur model estimated that polydrug use led to the highest HIV and HCV prevalence among three drug-use patterns. The prevalences were projected to increase from 10.9% (95% CI 10.2% to 11.5%) and 61.7% (95% CI 59.4% to 62.5%) in 2005 to 19.0% (95% CI 17.3% to 20.7%) and 69.1% (95% CI 67.3% to 69.5%), respectively, in 2035 among people using polydrug. Similarly, HIV and HCV prevalence in the SD-only group were projected to increase from 0.4% (95% CI 0.3% to 0.4%) and 19.5% (95% CI 19.4% to 21.7%) to 1.8% (95% CI 1.4 to 2.1%) and 33.7% (95% CI 33.2% to 34.9%) in 2005–2035. Conversely, HIV prevalence in the heroin-only group was projected to decrease from 8.0% (95% CI 7.6% to 8.1%) to 2.2% (95% CI 2.0% to 2.3%) in 2005–2035. Syphilis prevalence was estimated to remain unchanged in all population groups within this time frame. It was projected that the proportion of HIV transmitted by sexual transmission will increase compared with unsafe injection transmission in all people who use drugs from 2005 to 2035.ConclusionOur modelling suggests that polydrug use is projected to lead to the highest HIV and HCV disease burden by 2035, and the proportion of HIV transmitted by sexual transmission will increase. Current HIV intervention among people using heroin seems effective according to our estimation.
Association of initial e-cigarette and other tobacco product use with subsequent cigarette smoking in adolescents: a cross-sectional, matched control study
Authors: Shahab Lion , Beard Emma , Brown Jamie 
Published: March 2020

IntroductionThis study assessed whether initiating e-cigarette use increases the uptake of cigarette smoking in US adolescents compared with behavioural and synthetic controls.MethodsData come from 78 265 adolescents in the National Youth Tobacco Survey (2014–2017) of whom 38 630 provided information about the first tobacco product they had used in 2014/15. Ever, past 30 day and established (30 day use and 100+ lifetime cigarettes) cigarette smoking was compared in adolescents who first used an e-cigarette (exposure group), a non-cigarette combustible (CT) or other non-combustible tobacco (NT) product (behavioural controls), and propensity score matched adolescents without initial e-cigarette use (synthetic controls).ResultsRelative to behavioural controls, adolescents who tried e-cigarettes first were less likely to have ever smoked cigarettes (26% vs CT (42.4%; OR 0.48, 95% CI 0.40 to 0.57), or NT initiators (52.7%; OR 0.32, 95% CI 0.26 to 0.39)), to be past 30 day (6% vs CT (11.9%; OR 0.48, 95% CI 0.36 to 0.62), or NT initiators (20.0%; OR 0.26, 95% CI 0.19 to 0.35)) or be established cigarette smokers (0.7% vs CT (3.9%; OR 0.17, 95% CI 0.10 to 0.30), or NT initiators (8.4%; OR 0.08, 95% CI 0.04 to 0.13)). E-cigarette initiators were also less likely than synthetic controls (without initial e-cigarette use) to have ever smoked cigarettes (OR 0.76, 95% CI 0.62 to 0.93), be past 30 day (OR 0.71, 95% CI 0.55 to 0.91) or be established cigarette smokers (OR 0.26, 95% CI 0.13 to 0.51).ConclusionLess than 1% of US adolescents who use e-cigarettes first were established cigarette smokers. They were less likely to be smokers than adolescents who tried other combustible or non-combustible tobacco products first and propensity score matched adolescents without initial e-cigarette use.
Daily energy balance and eating behaviour during a 14-day cold weather expedition in Greenland
Authors: Charlot Keyne , Chapelot Didier , Colin Philippe , Bourrilhon Cyprien 
Published: March 2020

We assessed energy compensation, appetite, and reward value of foods during a 14-day military expedition in Greenland realized by 12 male French soldiers, during which energy compensation was optimized by providing them with easy-to-eat palatable foods in excess. Although daily energy expenditure (estimated by accelerometry) stayed relatively constant throughout the expedition (15 ± 9 MJ·day−1), energy intake (EI; estimated by self-reported diaries) was 17% higher during the D8–D14 period compared with the D1–D7 period, leading to a neutral energy balance (EB). Body fat mass (BFM) significantly decreased (–1.0 ± 0.7 kg, p < 0.001) but not body mass (BM). Neither hunger scores (assessed by visual analog scales) nor components of the reward value of food (explicit liking (EL) and food preference) were significantly altered. However, changes in EL at D10 were positively correlated with changes in BM (r = 0.600, p < 0.05) and BFM (r = 0.680, p < 0.05) and changes in hunger in the EI of the relevant period (r = 0.743, p < 0.01 for D1–D7, r = 0.652, p < 0.05 for D8–14). This study shows that the negative EB and BM loss can be attenuated by an appropriate food supply and that subjective components of eating behaviour, such as hunger and EL, may be useful to predict the magnitude of energy compensation. Novelty Energy intake increases during of a 14-day expedition in the cold. Energy compensation was likely facilitated by providing participants with easy-to-eat palatable and familiar foods. Hunger scores and EL for energy-dense foods were associated with high EIs and low BM changes.
Bounds on ortho-positronium and J/ψ–Υ quarkonia invisible decays and constraints on hidden braneworlds in a SO(3,1)-broken 5D bulk
Authors: Sarrazin Michaël , Stasser Coraline 
Published: March 2020

While our visible Universe could be a 3-brane, some cosmological scenarios consider that other 3-branes could be hidden in the extra-dimensional bulk. Matter disappearance toward a hidden brane is mainly discussed for neutron — both theoretically and experimentally — but other particles are poorly studied. Recent experimental results offer new constraints on positronium or quarkonium invisible decays. In the present work, we show how a two-brane Universe allows for such invisible decays. We put this result in the context of the recent experimental data to constrain the brane energy scale [Formula: see text] (or effective brane thickness [Formula: see text]) and the interbrane distance [Formula: see text] for a relevant two-brane Universe in a [Formula: see text]-broken 5D bulk. Quarkonia present poor bounds compared to the results deduced from previous passing-through-walls-neutron experiments for which scenarios with [Formula: see text] GeV and [Formula: see text] fm are excluded. By contrast, positronium experiments can compete with neutron experiments depending on the matter content of each brane. To constrain scenarios up to the Planck scale, positronium experiments in vacuum cavity should be able to reach [Formula: see text].
International Symposium on Wen-Tsun Wu's Academic Thought and Mathematics Mechanization
Authors: Academy of Mathematics and Systems Science  
Published: March 2020

During May 12-17, 2019, shall we celebrate the late famous mathematician Wen-Tsun Wu's centenary birthday. Professor Wen-Tsun Wu is one of the most internationally influential mathematicians in China, who brought far-reaching influence on both mathematics and computer research by his great contributions to the field of topology and the opening of the new area of Mathematics Mechanization. His research includes algebraic topology, di.erential topology, mathematics mechanization, algebraic geometry, game theory as well as the history of mathematics. His work has been regarded as among the greatest classical influential results in topology. In late 1970s, he opened the area of mathematics mechanization by the so-called "Wu method" which automatically proves geometric theorems using computers and was taken as the pioneer work in automatic reasoning. The symposium focuses on his achievements in topology, mathematics mechanization as well as the history of mathematics, and casts light on their future prospects and potential applications.
Specific topics for the symposium include but are not limited to:
•Algebraic topology
•Automated reasoning
•Computational algebraic geometry and optimization
•Computational geometry and topology
•Computational number theory
•Coding theory and cryptology
•Di.erential and di.erence algebras
•History of mathematics
•Polynomial equation solving
•Symbolic or symbolic-numeric computation
•Applications of mathematical mechanization
IgA Nephropathy Recurrence after Kidney Transplantation: Role of Recipient Age and Human Leukocyte Antigen-B Mismatch
Authors: Rodas Lida M. , Ruiz-Ortiz Estibaliz , Garcia-Herrera Adriana , Pereira Arturo , Blasco Miquel , Ventura-Aguiar Pedro , Viñas Gomis Odette , Egri Natalia , De Sousa Erika , Palou Eduard , Diekmann Fritz , Poch Esteban , Campistol Josep M. , Quintana Luis Fernando 
Published: March 2020

<b><i>Background:</i></b> Recurrence of immunoglobulin (Ig)A nephropathy (rIgAN) is a growing cause of kidney allograft dysfunction. This study was aimed at investigating factors associated with rIgAN and the subsequent progression to end-stage renal disease (ESRD). <b><i>Methods:</i></b> Retrospective study including consecutive patients with IgA nephropathy (IgAN) who received a kidney transplant in our center between 1992 and 2016 and had a renal biopsy by clinical indication. The date of detection of chronic kidney disease (CKD) 5 was used as renal outcome. <b><i>Results:</i></b> Eighty-six kidney transplants were performed in patients with IgAN, 38 (44%) were from living donors (related <i>n</i> = 26). rIgAN was diagnosed in 23 allografts (27%). Renal function and proteinuria at the end of the follow-up period were worst in the rIgAN patients compared to those without rIgAN (2.2 vs. 1.4 mg/dL, <i>p</i> = 0.014, and 1.16 vs. 0.49 g/day, <i>p</i> = 0.005, respectively). Risk of rIgAN and progression to CKD 5 decreased with patient’s age (hazard ratio [HR] 0.95, 95% CI 0.92–0.98, <i>p</i> = 0.002, and HR 0.97, 95% CI 0.83–0.97, <i>p</i> = 0.008 per year, respectively). Patients with rIgAN had a higher risk of progression to CKD 5 (HR 6.7, 95% CI 1.3–35.7, <i>p</i> = 0.025). Full donor-recipient mismatch in the human leukocyte antigen (HLA)-B loci decreased the risk of rIgAN (HR 0.22, 95% CI 0.06–0.76, <i>p</i> = 0.017). <b><i>Conclusions:</i></b> rIgAN was an independent risk factor for ESRD after renal allograft. Younger age increased the risk of rIgAN and CKD 5. Conversely, HLA-B mismatching was a potential protective factor for rIgAN of this glomerular disease.
Nascent HDL (High-Density Lipoprotein) Discs Carry Cholesterol to HDL Spheres
Authors: Navdaev Alexei V. , Sborgi Lorenzo , Wright Samuel D. , Didichenko Svetlana A. 
Published: March 2020

Objective:
To characterize the fate of protein and lipid in nascent HDL (high-density lipoprotein) in plasma and explore the role of interaction between nascent HDL and mature HDL in promoting ABCA1 (ATP-binding cassette transporter 1)-dependent cholesterol efflux.

Approach and Results:
Two discoidal species, nascent HDL produced by RAW264.7 cells expressing ABCA1 (LpA-I [apo AI containing particles formed by incubating ABCA1-expressing cells with apo AI]), and CSL112, human apo AI (apolipoprotein AI) reconstituted with phospholipids, were used for in vitro incubations with human plasma or purified spherical plasma HDL. Fluorescent labeling and biotinylation of HDL were employed to follow the redistribution of cholesterol and apo AI, cholesterol efflux was measured using cholesterol-loaded cells. We show that both nascent LpA-I and CSL112 can rapidly fuse with spherical HDL. Redistribution of the apo AI molecules and cholesterol after particle fusion leads to the formation of (1) enlarged, remodeled, lipid-rich HDL particles carrying lipid and apo AI from LpA-I and (2) lipid-poor apo AI particles carrying apo AI from both discs and spheres. The interaction of discs and spheres led to a greater than additive elevation of ABCA1-dependent cholesterol efflux.

Conclusions:
These data demonstrate that although newly formed discs are relatively poor substrates for ABCA1, they can interact with spheres to produce lipid-poor apo AI, a much better substrate for ABCA1. Because the lipid-poor apo AI generated in this interaction can itself become discoid by the action of ABCA1, cycles of cholesterol efflux and disc-sphere fusion may result in net ABCA1-dependent transfer of cholesterol from cells to HDL spheres. This process may be of particular importance in atherosclerotic plaque where cholesterol acceptors may be limiting.
Cardiac Myosin Promotes Thrombin Generation and Coagulation In Vitro and In Vivo
Authors: Zilberman-Rudenko Jevgenia , Deguchi Hiroshi , Shukla Meenal , Oyama Yoshimasa , Orje Jennifer N. , Guo Zihan , Wyseure Tine , Mosnier Laurent O. , McCarty Owen J.T. , Ruggeri Zaverio M. , Eckle Tobias , Griffin John H. 
Published: March 2020

Objective:
Cardiac myosin (CM) is structurally similar to skeletal muscle myosin, which has procoagulant activity. Here, we evaluated CM’s ex vivo, in vivo, and in vitro activities related to hemostasis and thrombosis.

Approach and Results:
Perfusion of fresh human blood over CM-coated surfaces caused thrombus formation and fibrin deposition. Addition of CM to blood passing over collagen-coated surfaces enhanced fibrin formation. In a murine ischemia/reperfusion injury model, exogenous CM, when administered intravenously, augmented myocardial infarction and troponin I release. In hemophilia A mice, intravenously administered CM reduced tail-cut-initiated bleeding. These data provide proof of concept for CM’s in vivo procoagulant properties. In vitro studies clarified some mechanisms for CM’s procoagulant properties. Thrombin generation assays showed that CM, like skeletal muscle myosin, enhanced thrombin generation in human platelet-rich and platelet-poor plasmas and also in mixtures of purified factors Xa, Va, and prothrombin. Binding studies showed that CM, like skeletal muscle myosin, directly binds factor Xa, supporting the concept that the CM surface is a site for prothrombinase assembly. In tPA (tissue-type plasminogen activator)-induced plasma clot lysis assays, CM was antifibrinolytic due to robust CM-dependent thrombin generation that enhanced activation of TAFI (thrombin activatable fibrinolysis inhibitor).

Conclusions:
CM in vitro is procoagulant and prothrombotic. CM in vivo can augment myocardial damage and can be prohemostatic in the presence of bleeding. CM’s procoagulant and antifibrinolytic activities likely involve, at least in part, its ability to bind factor Xa and enhance thrombin generation. Future work is needed to clarify CM’s pathophysiology and its mechanistic influences on hemostasis or thrombosis.
Deep Phenotyping by Mass Cytometry and Single-Cell RNA-Sequencing Reveals LYN-Regulated Signaling Profiles Underlying Monocyte Subset Heterogeneity and Lifespan
Authors: Roberts Morgan E. , Barvalia Maunish , Silva Jessica A.F.D. , Cederberg Rachel A. , Chu William , Wong Amanda , Tai Daven C. , Chen Sam , Matos Israel , Priatel John J. , Cullis Pieter R. , Harder Kenneth W. 
Published: March 2020

Rationale:
Monocytes are key effectors of the mononuclear phagocyte system, playing critical roles in regulating tissue homeostasis and coordinating inflammatory reactions, including those involved in chronic inflammatory diseases such as atherosclerosis. Monocytes have traditionally been divided into 2 major subsets termed conventional monocytes and patrolling monocytes (pMo) but recent systems immunology approaches have identified marked heterogeneity within these cells, and much of what regulates monocyte population homeostasis remains unknown. We and others have previously identified LYN tyrosine kinase as a key negative regulator of myeloid cell biology; however, LYN’s role in regulating specific monocyte subset homeostasis has not been investigated.

Objective:

We sought to comprehensively profile monocytes to elucidate the underlying heterogeneity within monocytes and dissect how
Lyn
deficiency affects monocyte subset composition, signaling, and gene expression. We further tested the biological significance of these findings in a model of atherosclerosis.

Methods and Results:

Mass cytometric analysis of monocyte subsets and signaling pathway activation patterns in conventional monocytes and pMos revealed distinct baseline signaling profiles and far greater heterogeneity than previously described.
Lyn
deficiency led to a selective expansion of pMos and alterations in specific signaling pathways within these cells, revealing a critical role for LYN in pMo physiology. LYN’s role in regulating pMos was cell-intrinsic and correlated with an increased circulating half-life of
Lyn
-deficient pMos. Furthermore, single-cell RNA sequencing revealed marked perturbations in the gene expression profiles of
Lyn
−/−
monocytes with upregulation of genes involved in pMo development, survival, and function.
Lyn
deficiency also led to a significant increase in aorta-associated pMos and protected
Ldlr
−/−
mice from high-fat diet–induced atherosclerosis.

Conclusions:
Together our data identify LYN as a key regulator of pMo development and a potential therapeutic target in inflammatory diseases regulated by pMos.
Atherogenic Lipoprotein(a) Increases Vascular Glycolysis, Thereby Facilitating Inflammation and Leukocyte Extravasation
Authors: Schnitzler Johan G. , Hoogeveen Renate M. , Ali Lubna , Prange Koen H.M. , Waissi Farahnaz , van Weeghel Michel , Bachmann Julian C. , Versloot Miranda , Borrelli Matthew J. , Yeang Calvin , De Kleijn Dominique P.V. , Houtkooper Riekelt H. , Koschinsky Marlys L. , de Winther Menno P.J. , Groen Albert K. , Witztum Joseph L. , Tsimikas Sotirios , Stroes Erik S.G. , Kroon Jeffrey 
Published: March 2020

Rationale:
Patients with elevated levels of lipoprotein(a) [Lp(a)] are hallmarked by increased metabolic activity in the arterial wall on positron emission tomography/computed tomography, indicative of a proinflammatory state.

Objective:
We hypothesized that Lp(a) induces endothelial cell inflammation by rewiring endothelial metabolism.

Methods and Results:
We evaluated the impact of Lp(a) on the endothelium and describe that Lp(a), through its oxidized phospholipid content, activates arterial endothelial cells, facilitating increased transendothelial migration of monocytes. Transcriptome analysis of Lp(a)-stimulated human arterial endothelial cells revealed upregulation of inflammatory pathways comprising monocyte adhesion and migration, coinciding with increased 6-phophofructo-2-kinase/fructose-2,6-biphosphatase (PFKFB)-3–mediated glycolysis. ICAM (intercellular adhesion molecule)-1 and PFKFB3 were also found to be upregulated in carotid plaques of patients with elevated levels of Lp(a). Inhibition of PFKFB3 abolished the inflammatory signature with concomitant attenuation of transendothelial migration.

Conclusions:
Collectively, our findings show that Lp(a) activates the endothelium by enhancing PFKFB3-mediated glycolysis, leading to a proadhesive state, which can be reversed by inhibition of glycolysis. These findings pave the way for therapeutic agents targeting metabolism aimed at reducing inflammation in patients with cardiovascular disease.
A Computational Pipeline to Predict Cardiotoxicity
Authors: Yang Pei-Chi , DeMarco Kevin R. , Aghasafari Parya , Jeng Mao-Tsuen , Dawson John R.D. , Bekker Slava , Noskov Sergei Y. , Yarov-Yarovoy Vladimir , Vorobyov Igor , Clancy Colleen E. 
Published: March 2020

Rationale:
Drug-induced proarrhythmia is so tightly associated with prolongation of the QT interval that QT prolongation is an accepted surrogate marker for arrhythmia. But QT interval is too sensitive a marker and not selective, resulting in many useful drugs eliminated in drug discovery.

Objective:
To predict the impact of a drug from the drug chemistry on the cardiac rhythm.

Methods and Results:
In a new linkage, we connected atomistic scale information to protein, cell, and tissue scales by predicting drug-binding affinities and rates from simulation of ion channel and drug structure interactions and then used these values to model drug effects on the hERG channel. Model components were integrated into predictive models at the cell and tissue scales to expose fundamental arrhythmia vulnerability mechanisms and complex interactions underlying emergent behaviors. Human clinical data were used for model framework validation and showed excellent agreement, demonstrating feasibility of a new approach for cardiotoxicity prediction.

Conclusions:
We present a multiscale model framework to predict electrotoxicity in the heart from the atom to the rhythm. Novel mechanistic insights emerged at all scales of the system, from the specific nature of proarrhythmic drug interaction with the hERG channel, to the fundamental cellular and tissue-level arrhythmia mechanisms. Applications of machine learning indicate necessary and sufficient parameters that predict arrhythmia vulnerability. We expect that the model framework may be expanded to make an impact in drug discovery, drug safety screening for a variety of compounds and targets, and in a variety of regulatory processes.