bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing the lymphoid tissue bioavailability of antiretrovirals in human primary lymphoid endothelial cells and in mice
Authors: Dyavar Shetty Ravi , Gautam Nagsen , Podany Anthony T , Winchester Lee C , Weinhold Jonathan A , Mykris Timothy M , Campbell Kayla M , Alnouti Yazen , Fletcher Courtney V 
Published: June 2019

Abstract

Background
The secondary lymphoid tissues (LTs), lymph nodes (LNs) and gut-associated lymphoid tissue (GALT) are considered reservoirs for HIV. Antiretrovirals (ARVs) have lower penetration into LT. In vitro models predictive of ARV LT penetration have not been established.

Objectives
To develop an in vitro model of LT bioavailability using human lymphoid endothelial cells (HLECs) and investigate its predictability with in vivo pharmacokinetic (PK) studies in mice.

Methods
ARV bioavailability in HLECs was evaluated at the maximum plasma concentration (Cmax) observed in HIV-infected patients. ARVs were: abacavir, atazanavir, darunavir, dolutegravir, efavirenz, elvitegravir, emtricitabine, maraviroc, raltegravir, rilpivirine, ritonavir, tenofovir disoproxil fumarate and the PK booster cobicistat. The LT PK of representative drugs showing high (efavirenz), intermediate (dolutegravir) and low (emtricitabine) HLEC bioavailability was investigated in BALB/c mice given 50/10/30 mg/kg efavirenz/dolutegravir/emtricitabine orally, daily for 3 days. The concordance of in vitro and in vivo ARV bioavailability was examined.

Results
ARVs showed high (>67th percentile; rilpivirine, efavirenz, elvitegravir and cobicistat), intermediate (67th–33rd percentile; ritonavir, tenofovir disoproxil fumarate, dolutegravir and maraviroc) and low (<33rd percentile; atazanavir, darunavir, raltegravir, emtricitabine and abacavir) HLEC bioavailability. The hierarchy of efavirenz, dolutegravir and emtricitabine bioavailability in LN, gut and brain tissues of mice was: efavirenz>dolutegravir>emtricitabine.

Conclusions
ARVs displayed distinct HLEC penetration patterns. PK studies of representative ARVs in LT of mice were concordant with HLEC bioavailability. These findings support further development of this approach and its translational predictability in humans.
Jasmonate and auxin perception: how plants keep F-boxes in check
Authors: Williams Clara , Fernández-Calvo Patricia , Colinas Maite , Pauwels Laurens , Goossens Alain 
Published: June 2019

Abstract
Phytohormones regulate the plasticity of plant growth and development, and responses to biotic and abiotic stresses. Many hormone signal transduction cascades involve ubiquitination and subsequent degradation of proteins by the 26S proteasome. The conjugation of ubiquitin to a substrate is facilitated by the E1 activating, E2 conjugating, and the substrate-specifying E3 ligating enzymes. The most prevalent type of E3 ligase in plants is the Cullin–RING ligase (CRL)-type, with F-box proteins (FBPs) as the substrate recognition component. The activity of these SKP–Cullin–F-box (SCF) complexes needs to be tightly regulated in time and place. Here, we review the regulation of SCF function in plants on multiple levels, with a focus on the auxin and jasmonate SCF-type receptor complexes. We discuss in particular the relevance of protein–protein interactions and post-translational modifications as mechanisms to keep SCF functioning under control. Additionally, we highlight the unique property of SCFTIR1/AFB and SCFCOI1 to recognize substrates by forming co-receptor complexes. Finally, we explore how engineered selective agonists can be used to study and uncouple the outcomes of the complex auxin and jasmonate signaling networks that are governed by these FBPs.
Hyperfine excitation of SH+ in collisions with para- and ortho-H2
Authors: Dagdigian Paul J 
Published: June 2019

ABSTRACT
Time-independent close-coupling quantum scattering calculations are employed to compute hyperfine-resolved rate coefficients for (de-)excitation of SH+ in collisions with para- and ortho-H2. These calculations utilized a potential energy surface for the interaction of SH+(X3Σ−) with H2 recently computed by the explicitly correlated RCCSD(T)-F12a coupled-cluster method. Rate coefficients for temperatures ranging from 10 to 500 K were calculated for all transitions among the first 37 hyperfine energy levels of SH+, with rotational angular momenta n ≤ 6, in collisions with para- and ortho-H2. As a first application of these data, the rate coefficients were employed in simple radiative transfer calculations to simulate the excitation of SH+ in typical molecular clouds.
A nuclear ionized gas outflow in the Seyfert 2 galaxy UGC 2024
Authors: Muñoz-Vergara Dania , Nagar Neil M , Ramakrishnan Venkatessh , Finlez Carolina , Storchi-Bergmann Thaisa , Slater Roy , Firpo Veronica , Humire Pedro K , Soto-Pinto Pamela , Kraemer Steven B , Lena Davide , Robinson Andrew , Riffel Rogemar A , Crenshaw D Michael , Elvis Martin S , Fischer T C , Schnorr-Müller Allan , Schmitt Henrique R 
Published: June 2019

ABSTRACT
As part of a high-resolution observational study of feeding and feedback processes occurring in the vicinity of the active galactic nucleus in 40 galaxies, we observed the inner 3${^{\prime\prime}_{.}}$5 × 5 arcsec of the nearby spiral and Seyfert 2 galaxy UGC 2024 with the integral field unit of the Gemini-South Telescope. The observations enabled a study of the stellar and gas kinematics in this region at a spatial resolution of 0${^{\prime\prime}_{.}}$5 (218 pc), and a spectral resolution of 36  km s−1 over the wavelength range 4100–7300 Å. For the strongest emission-lines (H β, [$\rm{O\,{\small III}}$] λ5007 Å, H α, [$\rm{N\,{\small II}}$] λ6584 Å, and [$\rm{S\,{\small II}}$] λλ6717,6731 Å) we derived maps of the flux, radial velocity, and velocity dispersion. The flux distribution and kinematics of the [$\rm{O\,{\small III}}$] emission line are roughly symmetric around the nucleus: the radial velocity is close to systemic over the full field of view. The kinematics of the other strong emission lines trace both this systemic velocity component, and ordered rotation (with kinematic centre 0${^{\prime\prime}_{.}}$2 north-west of the nucleus). The stellar continuum morphology and kinematics are, however, asymmetrical around the nucleus. We interpret these unusual kinematics as the superposition of a component of gas rotating in the galaxy disc plus a ‘halo’ component of highly ionized gas. This halo either traces a quasi-spherical fountain with average radial velocity 200 km s−1, in which case the total nuclear outflow mass and momentum are 2 × 105 M⊙ and 4 × 107 M⊙ km s−1, respectively, or a dispersion supported halo created by a past nuclear starburst.
A Fanci knockout mouse model reveals common and distinct functions for FANCI and FANCD2
Authors: Dubois Emilie L , Guitton-Sert Laure , Béliveau Mariline , Parmar Kalindi , Chagraoui Jalila , Vignard Julien , Pauty Joris , Caron Marie-Christine , Coulombe Yan , Buisson Rémi , Jacquet Karine , Gamblin Clémence , Gao Yuandi , Laprise Patrick , Lebel Michel , Sauvageau Guy , D. d’Andrea Alan , Masson Jean-Yves 
Published: June 2019

AbstractFanconi Anemia (FA) clinical phenotypes are heterogenous and rely on a mutation in one of the 22 FANC genes (FANCA-W) involved in a common interstrand DNA crosslink-repair pathway. A critical step in the activation of FA pathway is the monoubiquitination of FANCD2 and its binding partner FANCI. To better address the clinical phenotype associated with FANCI and the epistatic relationship with FANCD2, we created the first conditional inactivation model for FANCI in mouse. Fanci −/− mice displayed typical FA features such as delayed development in utero, microphtalmia, cellular sensitivity to mitomycin C, occasional limb abnormalities and hematological deficiencies. Interestingly, the deletion of Fanci leads to a strong meiotic phenotype and severe hypogonadism. FANCI was localized in spermatocytes and spermatids and in the nucleus of oocytes. Both FANCI and FANCD2 proteins co-localized with RPA along meiotic chromosomes, albeit at different levels. Consistent with a role in meiotic recombination, FANCI interacted with RAD51 and stimulated D-loop formation, unlike FANCD2. The double knockout Fanci−/− Fancd2−/− also showed epistatic relationship for hematological defects while being not epistatic with respect to generating viable mice in crosses of double heterozygotes. Collectively, this study highlights common and distinct functions of FANCI and FANCD2 during mouse development, meiotic recombination and hematopoiesis.
New therapeutic options for Alport syndrome
Authors: Torra Roser , Furlano Mónica 
Published: June 2019

Abstract
Alport syndrome (AS) is the most frequent inherited kidney disease after autosomal dominant polycystic kidney disease. It has three different patterns of inheritance—autosomal dominant, autosomal recessive and X-linked—which in part explains the wide spectrum of disease, ranging from isolated microhaematuria to end-stage renal disease early in life. The search for a treatment for AS is being pursued vigorously, not only because of the obvious unmet need but also because AS is a rare disease and any drug approved will have an orphan drug designation with its various benefits. Moreover, AS patients are quite young with very few comorbidities, which facilitates clinical trials. This review identifies the particularities of each pattern of inheritance but focuses mainly on new drugs or therapeutic targets for the disease. Most treatment-related investigations are directed not at the main abnormality in AS, namely collagen IV composition, but rather at the associated inflammation and fibrosis. Thus, AS may serve as a proof of concept for numerous drugs of potential value in many diseases that cause chronic kidney disease.
A direct method for Bloch wave excitation by scattering at the edge of a lattice. Part II: Finite size effects
Authors: Brougham R I , Thompson I 
Published: June 2019

Summary
A method for determining the reflection and transmission properties of a periodic structure occupying a half-space, previously developed for lattices formed from point scatterers, is generalized to allow for finite size effects. This facilitates the consideration of much higher frequencies (or more precisely, much higher scatterer size to wavelength ratios), and also a wider range of boundary conditions. The method is presented in a general context of linear wave theory, and physical interpretations are given for acoustics, elasticity, electromagnetism and water waves.
Dynamic Asset Sales with a Feedback Effect
Authors: Frenkel Sivan 
Published: June 2019

Abstract
I analyze a dynamic model of over-the-counter asset sales in which the seller receives stock-sensitive compensation, and the transaction conveys information about the firm’s value. I examine how the market’s response to an asset sale feeds back to the seller’s decision on the timing and the sale price and analyze the unique pattern of stock prices before and after the sale. The implications of bargaining power, inventories, gains from synergy, and the introduction of a vesting period are discussed. The model sheds light on observed properties of corporate sell-offs and explains market dry-ups during downturn periods.
Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Monosodium urate crystal interleukin-1β release is dependent on Toll-like receptor 4 and transient receptor potential V1 activation
Authors: Rossato Mateus F. , Hoffmeister Carin , Trevisan Gabriela , Bezerra Fabio , Cunha Thiago M. , Ferreira Juliano , Silva Cassia R. 
Published: June 2019

AbstractObjectiveThe present study aimed to elucidate the mechanisms involved in MSU-induced IL-1β release in a rodent animal model of acute gout arthritis.MethodsPainful (mechanical and thermal hypersensitivity, ongoing pain and arthritis score) and inflammatory (oedema, plasma extravasation, cell infiltration and IL-1β release) parameters were assessed several hours after intra-articular injection of MSU (100 µg/articulation) in wild-type or knockout mice for Toll-like receptor 4 (TLR4), inducible nitric oxide synthase (iNOS), transient receptor potential (TRP) V1 and the IL-1 receptor (IL-1R). Also, wild-type animals were treated with clodronate, lipopolysaccharide from Rhodobacter sphaeroides (LPS-RS) (TLR4 antagonist), spleen tyrosine kinase (SYK) inhibitor (iSYK), aminoguanidine (AMG, an iNOS inhibitor) or SB366791 (TRPV1 antagonist). Nitrite/nitrate and IL-1β levels were measured on the synovial fluid of wild-type mice, 2 h after intra-articular MSU injections, or medium from macrophages stimulated for MSU (1000 μg) for 2 h.ResultsIntra-articular MSU injection caused robust nociception and severe inflammation from 2 up to 6 h after injection, which were prevented by the pre-treatment with clodronate, LPS-RS, iSYK, AMG and SB366791, or the genetic ablation of TLR4, iNOS, TRPV1 or IL-1R. MSU also increased nitrite/nitrate and IL-1β levels in the synovial fluid, which was prevented by clodronate, LPS-RS, iSYK and AMG, but not by SB366791. Similarly, MSU-stimulated peritoneal macrophages released nitric oxide, which was prevented by LPS-RS, iSYK and AMG, but not by SB366791, and released IL-1β, which was prevented by LPS-RS, iSYK, AMG and SB366791.ConclusionOur data indicate that MSU may activate TLR4, SYK, iNOS and TRPV1 to induce the release of IL-1β by macrophages, triggering nociception and inflammation during acute gout attack.
What matters the adherence with BP 24-hr self-monitoring wearable device among hypertensive patients? A population-based survey
Authors: Zhang Yuting , Yang Ningxi , Si Guanglin , Zhang Yupeng , Dong Zhuangzhuang , Huang Yuwei , Tan Xiaodong 
Published: June 2019

Abstract
Wearable mobile health (mHealth) technologies are a convenient and cost-effective community-based intervention to improve management of hypertension in resource-limited populations. This study was designed to evaluate user characteristics of blood pressure (BP) wearable technology among a community-based population in a rural area of China. During the period of April through July 2018, a self-monitoring intervention program for hypertension control was implemented in a remote area of central China. Participants completed a cross-sectional survey which included demographic characteristics, Technology Fluency, the Compliance of Hypertensive Patients’ Scale, and the Health-related Quality of Life Survey. Participants were given a wearable BP-monitoring device which wirelessly uploaded data and monitored for 1 month. Participants (n = 317) were 64.57 years (SD = 11.68), 53.94% were male. During the 30-day monitoring, 52.68% of the sample uploaded BP wristband data daily were identified as “BP device users.” No differences existed between device users and nonusers related to cardiovascular health measurements, technology fluency, and health-related quality of life. Device users were more likely to report a higher level of hypertension compliance. Individuals reporting a higher level of compliance in hypertension management are more likely to interact with a wearable BP-monitoring device than persons with lower levels of compliance. Further evaluation of mobile health systems involving a wearable device as part of a hypertension management program is needed in a resource-limited community-based setting.
Mediation and arbitration: the process of enforcement
Authors: Zeller Bruno , Trakman Leon 
Published: June 2019

Abstract
Mediation is an important means of resolving international commercial disputes. The mediators whom the parties appoint can help to avoid contentious, dilatory and costly conflicts, including by resort to arbitration and/or litigation. The problem is the recognition and enforcement of mediated agreements often diverges from one state to the next. This makes it difficult to predict whether a mediated agreement will be enforced in a particular jurisdiction. The draft 2018 Singapore Mediation Convention [SMC] seeks to address this problem by providing uniform rules to govern the recognition and enforcement of mediated agreements. The obstacle faced by the SMC is that leading commercial states, notably in the EU, have resisted signing onto the SMC. They argue that mediation is, and ought to be, regulated domestically; and that the SMC is likely to marginalize domestic conceptions of mediation.
This article evaluates the significance of mediation in resolving international commercial disputes. It stresses the growing importance of mediation in international commercial dealings, how the SMC can assist to fill a void in regulating such mediation, and how it can prevent commercial disputes from regressing into protracted arbitration with ensuing enforcement complications. Focusing on the SMC's rules governing the enforcement of mediation agreements, it examines how those rules are likely to operate in law, and their perceived strengths and limitations in practice.
Simulation for Continuing Pharmacy Education: Development and Implementation of a Simulation-Based Workshop on Medicines Reconciliation for Pharmacists
Authors: Katoue Maram G. , Ker Jean 
Published: June 2019

Introduction:Simulation has been increasingly used to train health care professionals on clinical skills. Little is published on simulation-based education in the context of continuing pharmacy education (CPE) of pharmacists. This article describes the development implementation and evaluation of simulation-based workshop to train hospital pharmacists on medicines reconciliation in Kuwait. The study aimed to explore pharmacists' perceptions about simulation use in CPE. It also assessed the impact of the workshops on pharmacists' attitudes toward, knowledge, and comfort level to apply medicines reconciliation.Methods:One hundred ten pharmacists attended 11 simulation-based workshops. Data were collected using focus groups and self-administered surveys in a mixed-method research design. Focus groups were audio-recorded, transcribed verbatim, and analyzed for content. Descriptive statistics were used to report surveys' findings.Results:The workshops were well-received by pharmacists. Few pharmacists recalled previous exposure to simulation in CPE activities. Pharmacists' perceived challenges to simulation integration into their professional training were the need for good preparation/setting, qualified faculty, well-trained simulated patients, and time constrains. Participants felt that simulation enhanced their attitudes toward, knowledge, and comfort level to apply medicines reconciliation. They rated their knowledge level as having increased by 62.3% and comfort level as having increased by 37.0%. They overwhelmingly welcomed more integration of simulation in CPE activities.Discussion:A simulation-based continuing education workshop was well-received by pharmacists and enhanced their self-reported knowledge, comfort level, and preparedness to apply medicines reconciliation. Efforts are needed to expand simulation use in the development, refinement, and maintenance of clinical skills of pharmacists throughout their educational continuum including CPE.
Microsatellite Instability and Adjuvant Chemotherapy in Stage II Colon Cancer
Authors: Koenig Julie L. , Toesca Diego A.S. , Harris Jeremy P. , Tsai Chiaojung Jillian , Haraldsdottir Sigurdis , Lin Albert Y. , Pollom Erqi L. , Chang Daniel T. 
Published: June 2019

Background:
Randomized control trials and population-based studies do not demonstrate a definitive benefit for adjuvant chemotherapy (ACT) in stage II colon cancer (CC). Tumor sidedness and microsatellite instability (MSI) status may predict response to ACT, but previous studies have limited microsatellite data. We assessed the efficacy of ACT and possible interaction with MSI status and tumor sidedness in patients with resected stage II CC diagnosed between 2010 and 2013 using the National Cancer Database.

Materials and Methods:
Overall survival was evaluated with the Kaplan-Meier method and multivariate and propensity score matched Cox proportional hazards models. The interaction between receipt of ACT, MSI status, and tumor sidedness was evaluated. The efficacy of ACT was assessed in patient subgroups by MSI status and tumor sidedness.

Results:
Among 6964 stage II CC patients with known MSI status, 1497 (21.5%) received ACT, 843 had MSI tumors, and 6121 had microsatellite stable (MSS) tumors. In multivariate and propensity score matched analyses, ACT was associated with improved survival after adjusting for factors including high-risk features, MSI status, and tumor sidedness (multivariate hazard ratio, 0.52; P<0.001). There was no interaction between receipt of ACT and MSI status (P=0.25). Patients with MSS tumors benefitted from ACT (multivariate hazard ratio, 0.47; P<0.001), even without other high-risk features. Patients with MSI tumors did not (P=0.671). ACT was associated with improved survival regardless of tumor sidedness.

Conclusions:
MSS alone may warrant ACT in stage II CC while patients with MSI tumors may not derive significant benefit from ACT.
Survival Trends of Patients With Surgically Resected Gastric Cardia Cancer From 1988 to 2015
Authors: Ze-Long Yang , Guo-Hui Mei , Lin Zhu , Wei-Hong Yang , Ke-Cheng Zhang , Yan-Wen Jin 
Published: June 2019

Background:
The incidence of gastric cardia cancer (GCC) patients has been increasing, while the survival trends of GCC patients over time remains unclear. Thus, the aim of our study was to determine the survival trends of GCC patients over time using a population-based data in the United States.

Methods:
A total of 9044 surgically resected GCC patients during 1988 to 2015 from the Surveillance, Epidemiology, and End Results (SEER) database were identified. The survival probabilities were calculated by Kaplan-Meier method and the different survival probabilities between groups were examined by log-rank test.

Results:
The median overall survival time was 27 (interquartile range, 12 to 99) months, and the median disease-specific survival time was 32 (interquartile range, 13 to 320) months for GCC patients. There was a statistically significant increase in median overall survival time (17 to 46 mo; P<0.001) and disease-specific survival time (19 to 67 mo; P<0.001) from 1988 to 1997 to 2008 to 2015. More GCC patients were diagnosed at an early stage in recent years. Meanwhile, adequate lymph nodes examined (eLNs) were obtained in more GCC patients during surgery. Also, the proportion of GCC patients who received chemoradiotherapy increased significantly. Moreover, early diagnosis, adequate eLNs, and chemoradiotherapy were associated with mortality.

Conclusions:
The survival rates of surgically resected GCC patients had a significant improvement from 1988 to 1997 to 2008 to 2015 in the United States, which might relate to the early discovery of GCC, greater utilization of adequate eLNs, and chemoradiotherapy.