bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Delta-Opioid Receptor Gene Polymorphism Moderates the Therapeutic Response to Extended-Release Buprenorphine in Opioid Use Disorder
Authors: Kranzler Henry R , Lynch Kevin G , Crist Richard C , Hartwell Emily , Le Moigne Anne , Laffont Celine M , Andorn Anne C 
Published: September 2020

Abstract

Background
Buprenorphine treatment is not equally effective in all patients with opioid use disorder (OUD). Two retrospective studies showed that, among African Americans (AAs), rs678849, a polymorphism in the delta-opioid receptor gene, moderated the therapeutic effect of sublingual buprenorphine.

Methods
We examined rs678849 as a moderator of the response to an extended-release subcutaneous buprenorphine formulation (BUP-XR) in a 24-week OUD treatment study of 127 AAs and 327 European Americans (EAs). Participants were randomly assigned to receive: (1) BUP-XR as 2 monthly injections of 300 mg followed by either 300 mg monthly or 100 mg monthly for 4 months, or (2) monthly volume-matched placebo injections. Generalized estimating equations logistic regression analyses tested, per population group, the main and interaction effects of treatment (BUP-XR vs placebo) and genotype group (rs678849*CC vs CT/TT) on weekly urine drug screens (UDS).

Results
Among AAs, the placebo group had higher rates of opioid-positive UDS than the BUP-XR group (log odds ratio = 1.67, 95% CI = 0.36, 2.98), but no genotype by treatment effect (P = .80). Among EAs, the placebo group also showed higher rates of opioid-positive UDS than the BUP-XR group (log odds ratio = 1.97, 95% CI = 1.14, 2.79) but a significant genotype by treatment interaction (χ 2(1) = 4.33, P = .04).

Conclusion
We found a moderating effect of rs678849 on the response to buprenorphine treatment of OUD in EAs, but not AAs. These findings require replication in well-powered, prospective studies of both AA and EA OUD patients treated with BUP-XR and stratified on rs678849 genotype.
On Ultraproduct Embeddings and Amenability for Tracial von Neumann Algebras
Authors: Atkinson Scott , Kunnawalkam Elayavalli Srivatsav 
Published: September 2020

Abstract
We define the notion of self-tracial stability for tracial von Neumann algebras and show that a tracial von Neumann algebra satisfying the Connes embedding problem (CEP) is self-tracially stable if and only if it is amenable. We then generalize a result of Jung by showing that a separable tracial von Neumann algebra that satisfies the CEP is amenable if and only if any two embeddings into $R^{\mathcal{U}}$ are ucp-conjugate. Moreover, we show that for a II$_1$ factor $N$ satisfying CEP, the space $\mathbb{H}$om$(N, \prod _{k\to \mathcal{U}}M_k)$ of unitary equivalence classes of embeddings is separable if and only $N$ is hyperfinite. This resolves a question of Popa for Connes embeddable factors. These results hold when we further ask that the pairs of embeddings commute, admitting a nontrivial action of $\textrm{Out}(N\otimes N)$ on ${\mathbb{H}}\textrm{om}(N\otimes N, \prod _{k\to \mathcal{U}}M_k)$ whenever $N$ is non-amenable. We also obtain an analogous result for commuting sofic representations of countable sofic groups.
Limit Polygons of Convex Domains in the Projective Plane
Authors: Nie Xin 
Published: September 2020

Abstract
For any sequence of properly convex domains in the real projective plane such that the zeros of Pick differentials have bounded multiplicity and get further and further apart, we determine all Hausdorff limit domains that one can obtain after normalizing each member of the sequence by a projective transformation. We then show that the result can be applied to convex domains generated by projective triangular reflection groups.
High Seroprevalence of Anti-SARS-CoV-2 Antibodies in Chelsea, Massachusetts
Authors: Naranbhai Vivek , Chang Christina C , Beltran Wilfredo F Garcia , Miller Tyler E , Astudillo Michael G , Villalba Julian A , Yang Diane , Gelfand Jeffrey , Bernstein Bradley E , Feldman Jared , Hauser Blake M , Caradonna Timothy M , Alter Galit , Murali Mandakolathur R , Jasrasaria Rashmi , Quinlan Joan , Xerras Dean C , Betancourt Joseph R , Louis David N , Schmidt Aaron G , Lennerz Jochen , Poznansky Mark C , Iafrate A John 
Published: September 2020

Abstract
SARS-CoV-2 antibody testing allows quantitative determination of disease prevalence, which is especially important in high-risk communities. We performed anonymized convenience sampling of 200 currently asymptomatic residents of Chelsea, the epicenter of COVID-19 illness in Massachusetts, by BioMedomics SARS-CoV-2 combined IgM-IgG point-of-care lateral flow immunoassay. The seroprevalence was 31.5% (17.5% IgM+IgG+, 9.0% IgM+IgG−, and 5.0% IgM−IgG+). Of the 200 participants, 50.5% reported no symptoms in the preceding 4 weeks, of which 24.8% (25/101) were seropositive, and 60% of these were IgM+IgG−. These data are the highest seroprevalence rates observed to date and highlight the significant burden of asymptomatic infection.
Abnormal Levels of Some Biomarkers of Immune Activation Despite Very Early Treatment of Human Immunodeficiency Virus
Authors: Schnittman Samuel R , Deitchman Amelia N , Beck-Engeser Gabriele , Ahn HaeLee , York Vanessa A , Hartig Heather , Hecht Frederick M , Martin Jeffrey N , Deeks Steven G , Aweeka Francesca T , Hunt Peter W 
Published: September 2020

AbstractBackgroundDespite early antiretroviral therapy (ART), ART-suppressed people with human immunodeficiency virus (HIV) (PWH) remain at higher risk for infections and infection-related cancers than the general population. The immunologic pathways that remain abnormal in this setting, potentially contributing to these complications, are unclear.MethodsART-suppressed PWH and HIV-negative controls, all cytomegalovirus seropositive and enriched for HIV risk factors, were sampled from an influenza vaccine responsiveness study. PWH were stratified by timing of ART initiation (within 6 months of infection [early ART] vs later) and nadir CD4+ T-cell count among later initiators. Between-group differences in kynurenine-tryptophan (KT) ratio, interferon-inducible protein 10, soluble CD14 and CD163, soluble tumor necrosis factor receptor 2, interleukin 6, and soluble urokinase plasminogen activator receptor were assessed after confounder adjustment.ResultsMost participants (92%) were male, reflecting the demographics of early-ART initiators in San Francisco. Most biomarkers were higher among later-ART initiators. Participants in the early-ART group achieved near-normal soluble tumor necrosis factor receptor 2, interleukin 6, and soluble urokinase plasminogen activator receptor levels, but substantially higher KT ratio than those without HIV after confounder adjustment (P = .008). Soluble CD14, soluble CD163, and interferon-inducible protein 10 trended similarly.ConclusionsWhile early-ART initiators restore near-normal levels of many inflammatory markers, the kynurenine pathway of tryptophan catabolism remains abnormally high. Because this pathway confers adaptive immune defects and predicts tuberculosis and cancer progression, this it may contribute to persistent risks of these complications in this setting.
Characterization of carbapenemase-producingSerratia marcescensand whole-genome sequencing for plasmid typing in a hospital in Madrid, Spain (2016–18)
Authors: Pérez-Viso Blanca , Hernández-García Marta , Ponce-Alonso Manuel , Morosini María Isabel , Ruiz-Garbajosa Patricia , del Campo Rosa , Cantón Rafael 
Published: September 2020

AbstractObjectivesCarbapenemase-producing Enterobacterales (CPE) are increasingly recognized in nosocomial infections, also affecting ICU patients. We aimed to characterize the carbapenemase-producing Serratia marcescens (CPSm) isolates recovered in our hospital in Madrid (Spain) between March 2016 and December 2018.MethodsOverall, 50 isolates from clinical and epidemiological surveillance samples were recovered from 24 patients admitted to the medical ICU and 10 non-ICU-related patients based on their phenotypic resistance. Carbapenemase characterization, antibiotic susceptibility, PFGE clonal relatedness, plasmid characterization, WGS (Illumina-NovaSeq 6000) and phylogenetic analysis were performed.ResultsA single isolate was finally considered for each patient, except for Patient 8 that was colonized by two different isolates (n = 35). Isolates were characterized as VIM-1 (n = 29) or OXA-48 producers (n = 6). Up to seven genetic lineages were found by PFGE, with dominance of two clones. Plasmid characterization confirmed that almost all CPSm carried the same ∼60 kb IncL OXA-48- or VIM-1-encoding plasmid, which was related to the globally disseminated IncL-pOXA-48a. WGS allowed plasmid reconstruction with two variants: IncL-pVIM-1 (∼65 kb) and IncL-pOXA-48 (∼62 kb). blaOXA-48–Tn1999 (∼5 kb) was the unique antibiotic resistance gene in pOXA-48, whereas pVIM-1 plasmids (∼8 kb) harboured a class 1 integron containing 5′-blaVIM-1+aacA4+dfrB1+aadA1+catB2+qacEDelta1+sul1-3′.ConclusionsOur results confirm the dissemination of CPSm within our institution in both ICU and non-ICU environments, representing two prevalent CPSm clones, and the same IncL-pOXA-48 plasmid previously described in other Enterobacterales, but containing the blaVIM-1 gene. This also reinforces the relevance of species different from Klebsiella pneumoniae or Escherichia coli in the CPE landscape and circulating lineages and plasmids in local CPE epidemiology.
Evaluating artificial intelligence in medicine: phases of clinical research
Authors: Park Yoonyoung , Jackson Gretchen Purcell , Foreman Morgan A , Gruen Daniel , Hu Jianying , Das Amar K 
Published: September 2020

Abstract
Increased scrutiny of artificial intelligence (AI) applications in healthcare highlights the need for real-world evaluations for effectiveness and unintended consequences. The complexity of healthcare, compounded by the user- and context-dependent nature of AI applications, calls for a multifaceted approach beyond traditional in silico evaluation of AI. We propose an interdisciplinary, phased research framework for evaluation of AI implementations in healthcare. We draw analogies to and highlight differences from the clinical trial phases for drugs and medical devices, and we present study design and methodological guidance for each stage.
The Impact of COVID-19 on Clinical Trial Execution at the Dana-Farber Cancer Institute
Authors: Tolaney Sara M , Lydon Christine A , Li Tianyu , Dai Jiale , Standring Andrea , Legor Kristen A , Caparrotta Caryn M , Schenker Matthew P , Glazer Daniel I , Tayob Nabihah , DuBois Steven G , Meyerhardt Jeffrey A , Taplin Mary-Ellen , Johnson Bruce E 
Published: September 2020

Abstract
Interventions designed to limit the spread of coronavirus disease 2019 (COVID-19) are having profound effects on the delivery of health care, but data showing the impact on oncology clinical trial enrollment, treatment, and monitoring are limited. We prospectively tracked relevant data from oncology clinical trials at Dana-Farber Cancer Institute from January 1, 2018, to June 30, 2020, including the number of open trials, new patient enrollments, in-person and virtual patient visits, dispensed investigational infusions, dispensed or shipped oral investigational agents, research biopsies, and blood samples. We ascertained why patients came off trials and determined on-site clinical research staffing levels. We used 2-sided Wilcoxon rank sum tests to assess the statistical significance of the reported changes. Nearly all patients on interventional treatment trials were maintained, and new enrollments continued at just under one-half the prepandemic rate. The median number of investigational prescriptions shipped to patients increased from 0 to 74 (range = 22-107) per week from March to June 2020. The median number of telemedicine appointments increased from 0 to 107 (range = 33-267) per week from March to June 2020. Research biopsies and blood collections decreased dramatically after Dana-Farber Cancer Institute implemented COVID-19–related policies in March 2020. The number of research nurses and clinical research coordinators on site also decreased after March 2020. Substantial changes were required to safely continue clinical research during the pandemic, yet we observed no increases in serious adverse events or major violations related to drug dosing. Lessons learned from adapting research practices during COVID-19 can inform industry sponsors and governmental agencies to consider altering practices to increase operational efficiency and convenience for patients.
Stereotactic body radiotherapy using the forward-planned static-port tomotherapy for lung cancer: a novel planning technique with the newly-developed mode
Authors: Manabe Yoshihiko , Miyakawa Akifumi , Kondo Takuhito , Yamada Yuki , Hashimoto Seiji , Ishikura Satoshi , Shibamoto Yuta 
Published: September 2020

Abstract
With the newly-developed static-port forward-planning (FP) mode of tomotherapy, the ratio of the dose of the planning target volume (PTV) periphery to the maximum dose can be easily adjusted by modifying leaf margins when planning stereotactic body radiotherapy (SBRT). The purpose of this study was to evaluate the characteristics of FP plans compared to helical intensity-modulated radiotherapy (IMRT) and helical 3D conformal radiotherapy (3DCRT) plans of SBRT for lung tumors. The three plans were created for 14 tumors in 11 patients. For 13 tumors, 60 Gy in 7.5-Gy fractions was prescribed for a minimum coverage dose of 95% of the PTV (D95). The prescribed isodose line (PIL) was intended to be 60–80% of the maximum dose. Nine angles were used for the FP plans. The median D98 and D50 of the internal target volume for FP, helical-IMRT and helical-3DCRT plans were 70.4, 71.4 and 60.5 Gy, respectively (P &lt; 0.001), and 77.7, 75.7 and 62.3 Gy, respectively (P &lt; 0.0001). The median PIL and the lung volume receiving ≥20 Gy (V20) were 73.4, 73.4 and 94.3%, respectively (P &lt; 0.0001), and 4.7, 4.0 and 5.7%, respectively (P &lt; 0.0001). These parameters were not significantly different between the FP and helical-IMRT plans. The median beam-on times were 238.6, 418.9 and 197.1 s, respectively (P &lt; 0.0001). The FP plans reduced the beam-on time by 43% compared to the helical-IMRT plans. The dose distribution of the FP plans was comparable to that of the helical-IMRT plans. The helical-3DCRT plans could not adjust PIL to be 60–80%.
Stomatal response to isothiocyanates inArabidopsis thaliana
Authors: Afrin Sonya , Okuma Eiji , Tahjib-Ul-Arif Md , Jahan Md Sarwar , Nakamura Toshiyuki , Nakamura Yoshimasa , Munemasa Shintaro , Murata Yoshiyuki 
Published: September 2020

AbstractAllyl isothiocyanate (AITC) induces stomatal closure accompanied by reactive oxygen species (ROS) production and glutathione (GSH) depletion in Arabidopsis thaliana. In this study, stomatal responses to three other isothiocyanates (ITCs), benzyl isothiocyanate (BITC), sulforaphane (SFN), and phenethyl isothiocyanate (PEITC), were investigated in A. thaliana. All these ITCs significantly induced stomatal closure, where PEITC and BITC were most effective. The selected ITCs also induced ROS accumulation, cytosolic alkalization, and GSH depletion in guard cells. Moreover, all ITCs increased the frequency of cytosolic free calcium ([Ca2+]cyt) spikes (transient elevation), while PEITC and BITC showed the highest frequency. There was a strong positive correlation between the number of [Ca2+]cyt spikes per guard cell and the decrease in stomatal aperture. Both cytosolic alkalization and GSH content have a positive correlation with the decrease in stomatal aperture, but ROS production did not have a significant correlation with the decrease in stomatal apertures. These results indicate that the molecules with a functional ITC group induce stomatal closure that is accompanied by GSH depletion, cytosolic alkalization, [Ca2+]cyt spikes, and ROS production, and that the former three cellular events, rather than ROS production, are highly correlated with the decrease in stomatal aperture.
High rate of gravitational waves mergers from flyby perturbations of wide black hole triples in the field
Authors: Michaely Erez , Perets Hagai B 
Published: September 2020

ABSTRACT
Ultrawide triple black holes (TBHs; with an outer orbit &gt;103 au) in the field can be considerably perturbed by flyby encounters with field stars through the excitation of their outer orbit eccentricities. We study the cumulative effect of such flybys, and show them to be conductive for the production of gravitational-wave (GW) sources. Flyby encounters with TBHs can destabilize them, leading to binary–single resonant encounters between the outer black hole (BH) and the inner binary. These encounters can result in either a prompt GW merger of two of the TBH components during the resonant phase, or the disruption of the TBH. In the latter case, a more compact binary is left behind, while the third BH is ejected. Such compact remnant binaries may still inspiral through GW emission, producing delayed GW mergers, with a significant fraction of these merging in less than a Hubble time. We find a volumetric merger rate of ∼3–10 Gpc−3 yr−1 contributed by the (former) prompt-merger TBH channel and ${\sim} 100\!-\!250\,{\rm {\rm Gpc^{-3}\,yr^{-1}}}$ contributed by the (latter) delayed-merger TBH channel. The prompt channel gives rise to eccentric mergers in the aLIGO band, while the majority of the delayed GW mergers are circularized when enter the aLIGO band. We find the total eccentric volumetric merger rate to be ∼1–10 Gpc−3 yr−1 from both channels. We expect these mergers to show no significant spin–orbit alignment, and uniform delay-time distribution.
Gaia DR2 giants in the Galactic dust – II. Application of the reddening maps and models
Authors: Gontcharov George A , Mosenkov Aleksandr V 
Published: September 2020

ABSTRACT
We exploit a complete sample of 101  810 Gaia DR2 giants, selected in Paper I in the space cylinder with a radius of 700 pc around the Sun and a height of |Z| = 1800 pc, using the Gaia DR2 parallaxes, GBP and GRP photometry, and WISE W3 photometry. We explain the spatial variations of the modes of the observables GBP − GRP and GRP − W3 by the spatial variations of the corresponding reddenings described in the GM20 3D dust distribution model. Presented in this paper, GM20 is an advanced version of the model introduced by Gontcharov in 2009. GM20 proposes two intersecting dust layers, along the Galactic mid-plane and in the Gould Belt, with exponential vertical and sinusoidal longitudinal variations of the dust spatial density in each layer. The Belt layer is an ellipse, oriented nearly between the centre and anticentre of the Galaxy, and with semi-major and semi-minor axes of 600 and 146 pc, respectively. GBP − GRP and GRP − W3 give similar solutions, but different equatorial layer scale heights of 150 ± 15 and 180 ± 15 pc, respectively, and $(G_\mathrm{BP}-G_\mathrm{RP})_0=(1.14\pm 0.01)-(0.022\pm 0.010)\, |Z|$, $(G_\mathrm{RP}-W3)_0=(1.44\pm 0.01)-(0.015\pm 0.010)\, |Z|$, where Z is in kpc. We compare GM20 with several 3D reddening models and maps in their ability to predict the observed colour modes. GM20 and the 3D map by Gontcharov appear to be the best among the models and maps, respectively. However, the most reliable models and maps mainly disagree only in their estimates of low reddening, including the reddening across the whole dust layer.
A search for H2O masers in 100 active dwarf galaxies
Authors: Rosenthal M J , Zaw I 
Published: September 2020

ABSTRACT
We present the results of the first dedicated survey for 22 GHz H2O maser emission in dwarf galaxies outside of the Local Group, with the aim of discovering disc masers. Studies of disc masers yield accurate and precise measurements of black hole (BH) mass, and such measurements in dwarf galaxies would be key to understanding the low-mass end of BH–galaxy coevolution. We used the Green Bank Telescope to survey 100 nearby (z ≲ 0.055) dwarf galaxies (M* ≲ 109.5 M⊙) with optical emission line ratios indicative of accretion on to a massive black hole. We detected no new masers down to a limit of ∼12 mJy (5σ). We compared the properties of our sample with those of ∼1850 known detections and non-detections in massive galaxies. We find, in agreement with previous studies, that masers are preferentially hosted by Seyferts and highly obscured, [O iii]-bright active galactic nuclei (AGNs). Our sample has fewer Seyferts, is less obscured, and is [O iii]-faint. Though the overall maser detection rate is ∼3 per cent in massive galaxies, the predicted rate for our sample, weighted by its optical properties, is ∼0.6–1.7 per cent, corresponding to a probability of making no detections of ∼20–50 per cent. We also found a slight increase in the detection rate with increased stellar mass in previously surveyed galaxies. However, further observations are required to discern whether there is an intrinsic difference between the maser fraction in active dwarf galaxies and in their massive counterparts for the same AGN properties.
The CO universe: modelling CO emission and H2 abundance in cosmological galaxy formation simulations
Authors: Inoue Shigeki , Yoshida Naoki , Yajima Hidenobu 
Published: September 2020

ABSTRACT
We devise a physical model of formation and distribution of molecular gas clouds (MGCs) in galaxies. We use the model to predict the intensities of rotational transition lines of carbon monoxide (CO) and the molecular hydrogen (H2) abundance. Using the outputs of IllustrisTNG cosmological simulations, we populate MGCs of unresolved sizes in individual simulated galaxies, where the effect of the interstellar radiation field with dust attenuation is also taken into account. We then use the publicly available code despotic (Derive the Energetics and SPectra of Optically Thick Interstellar Clouds) to compute the CO line luminosities and H2 densities without assuming the CO-to-H2 conversion factor (αCO). Our method allows us to study the spatial and kinematic structures traced by CO(1–0) and higher transition lines. We compare the CO luminosities and H2 masses with recent observations of galaxies at low and high redshifts. Our model reproduces well the observed CO–luminosity function and the estimated H2 mass in the local UniverseAbout 10 per cent of molecules in the Universe reside in dwarf galaxies with stellar masses lower than 109 M⊙, but the galaxies are generally ‘CO-dark’ and have typically high αCO. Our model predicts generally lower CO line luminosities than observations at redshifts z ≳ 1–2. We argue that the difference can be explained by the highly turbulent structure suggested for the high-redshift star-forming galaxies.