bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gaia white dwarfs within 40 pc II: the volume-limited Northern hemisphere sample
Authors: McCleery Jack , Tremblay Pier-Emmanuel , Gentile Fusillo Nicola Pietro , Hollands Mark A , Gänsicke Boris T , Izquierdo Paula , Toonen Silvia , Cunningham Tim , Rebassa-Mansergas Alberto 
Published: July 2020

ABSTRACT
We present an overview of the sample of Northern hemisphere white dwarfs within 40 pc of the Sun detected from Gaia Data Release 2 (DR2). We find that 521 sources are spectroscopically confirmed degenerate stars, 111 of which were first identified as white dwarf candidates from Gaia DR2 and followed up recently with the William Herschel Telescope and Gran Telescopio Canarias. Three additional white dwarf candidates remain spectroscopically unobserved and six unresolved binaries are known to include a white dwarf but were not in our initial selection in the Gaia DR2 Hertzsprung–Russell diagram. Atmospheric parameters are calculated from Gaia and Pan-STARRS photometry for all objects in the sample, confirming most of the trends previously observed in the much smaller 20 pc sample. Local white dwarfs are overwhelmingly consistent with Galactic disc kinematics, with only four halo candidates. We find that DAZ white dwarfs are significantly less massive than the overall DA population ($\overline{M}_\mathrm{DAZ}$ = 0.59 M⊙, $\overline{M}_\mathrm{DA}$ = 0.66 M⊙). It may suggest that planet formation is less efficient at higher mass stars, producing more massive white dwarfs. We detect a sequence of crystallized white dwarfs in the mass range from 0.6 $\lesssim M/\mbox{$\mathrm{M}_\odot $}\ \lesssim$ 1.0 and find that the vast majority of objects on the sequence have standard kinematic properties that correspond to the average of the sample, suggesting that their nature can be explained by crystallization alone. We also detect 26 double degenerates and white dwarf components in 56 wide binary systems.
Thermal inertias of pebble-pile comet 67P/Churyumov–Gerasimenko
Authors: Arakawa Sota , Ohno Kazumasa 
Published: July 2020

ABSTRACT
The Rosetta mission to comet 67P/Churyumov–Gerasimenko has provided new data to better understand what comets are made of. The weak tensile strength of the cometary surface materials suggests that the comet is a hierarchical dust aggregate formed through gravitational collapse of a bound clump of small dust aggregates so-called ‘pebbles’ in the gaseous solar nebula. Since pebbles are the building blocks of comets, which are the survivors of planetesimals in the solar nebula, estimating the size of pebbles using a combination of thermal observations and numerical calculations is of great importance to understand the planet formation in the outer Solar system. In this study, we calculated the thermal inertias and thermal skin depths of the hierarchical aggregates of pebbles, for both diurnal and orbital variations of the temperature. We found that the thermal inertias of the comet 67P/Churyumov–Gerasimenko are consistent with the hierarchical aggregate of cm- to dm-sized pebbles. Our findings indicate that the icy planetesimals may have formed via accretion of cm- to dm-sized pebbles in the solar nebula.
Augmented base pairing networks encode RNA-small molecule binding preferences
Authors: Oliver Carlos , Mallet Vincent , Gendron Roman Sarrazin , Reinharz Vladimir , Hamilton William L , Moitessier Nicolas , Waldispühl Jérôme 
Published: July 2020

Abstract
RNA-small molecule binding is a key regulatory mechanism which can stabilize 3D structures and activate molecular functions. The discovery of RNA-targeting compounds is thus a current topic of interest for novel therapies. Our work is a first attempt at bringing the scalability and generalization abilities of machine learning methods to the problem of RNA drug discovery, as well as a step towards understanding the interactions which drive binding specificity. Our tool, RNAmigos, builds and encodes a network representation of RNA structures to predict likely ligands for novel binding sites. We subject ligand predictions to virtual screening and show that we are able to place the true ligand in the 71st–73rd percentile in two decoy libraries, showing a significant improvement over several baselines, and a state of the art method. Furthermore, we observe that augmenting structural networks with non-canonical base pairing data is the only representation able to uncover a significant signal, suggesting that such interactions are a necessary source of binding specificity. We also find that pre-training with an auxiliary graph representation learning task significantly boosts performance of ligand prediction. This finding can serve as a general principle for RNA structure-function prediction when data is scarce. RNAmigos shows that RNA binding data contains structural patterns with potential for drug discovery, and provides methodological insights for possible applications to other structure-function learning tasks. The source code, data and a Web server are freely available at http://rnamigos.cs.mcgill.ca.
The duties of a resulting trustee
Authors: Collings Matthew 
Published: July 2020

Abstract
The precise duties surrounding express trusts have caused issues enough (as we explore in this journal)—but what of the duties of resulting trustees? They have been considered in the authorities, and have been the subject of academic commentary, but have nevertheless remained somewhat opaque. A recent judgment in the Court of Appeal in Singapore (its highest court) has thoroughly traversed the principal English and Commonwealth authorities and collated the academic articles. It provides a comprehensive and valuable insight into the duties of resulting trustees.
Granger Causality of the Electroencephalogram Reveals Abrupt Global Loss of Cortical Information Flow during Propofol-induced Loss of Responsiveness
Authors: Pullon Rebecca M. , Yan Lucy , Sleigh Jamie W. , Warnaby Catherine E. 
Published: July 2020

Background
It is a commonly held view that information flow between widely separated regions of the cerebral cortex is a necessary component in the generation of wakefulness (also termed “connected” consciousness). This study therefore hypothesized that loss of wakefulness caused by propofol anesthesia should be associated with loss of information flow, as estimated by the effective connectivity in the scalp electroencephalogram (EEG) signal.

Methods
Effective connectivity during anesthesia was quantified by applying bivariate Granger to multichannel EEG data recorded from 16 adult subjects undergoing a slow induction of, and emergence from, anesthesia with intravenous propofol. During wakefulness they were conducting various auditory and motor tasks. Functional connectivity using EEG coherence was also estimated.

Results
There was an abrupt, substantial, and global decrease in effective connectivity around the point of loss of responsiveness. Recovery of behavioral responsiveness was associated with a comparable recovery in information flow pattern (expressed as normalized values). The median (interquartile range) change was greatest in the delta frequency band: decreasing from 0.15 (0.21) 2 min before loss of behavioral response, to 0.06 (0.04) 2 min after loss of behavioral response (P < 0.001). Regional decreases in information flow were maximal in a posteromedial direction from lateral frontal and prefrontal regions (0.82 [0.24] 2 min before loss of responsiveness, decreasing to 0.17 [0.05] 2 min after), and least for information flow from posterior channels. The widespread decrease in bivariate Granger causality reflects loss of cortical coordination. The relationship between functional connectivity (coherence) and effective connectivity (Granger causality) was inconsistent.

Conclusions
Propofol-induced unresponsiveness is marked by a global decrease in information flow, greatest from the lateral frontal and prefrontal brain regions in a posterior and medial direction. Loss of information flow may be a useful measure of connected consciousness.

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Perioperative Use of Gabapentinoids for the Management of Postoperative Acute Pain
Authors: Verret Michael , Lauzier François , Zarychanski Ryan , Perron Caroline , Savard Xavier , Pinard Anne-Marie , Leblanc Guillaume , Cossi Marie-Joëlle , Neveu Xavier , Turgeon Alexis F. ,   the Canadian Perioperative Anesthesia Clinical Trials (PACT) Group
Published: July 2020

Background
Widely used for acute pain management, the clinical benefit from perioperative use of gabapentinoids is uncertain. The aim of this systematic review was to assess the analgesic effect and adverse events with the perioperative use of gabapentinoids in adult patients.

Methods
Randomized controlled trials studying the use of gabapentinoids in adult patients undergoing surgery were included. The primary outcome was the intensity of postoperative acute pain. Secondary outcomes included the intensity of postoperative subacute pain, incidence of postoperative chronic pain, cumulative opioid use, persistent opioid use, lengths of stay, and adverse events. The clinical significance of the summary estimates was assessed based on established thresholds for minimally important differences.

Results
In total, 281 trials (N = 24,682 participants) were included in this meta-analysis. Compared with controls, gabapentinoids were associated with a lower postoperative pain intensity (100-point scale) at 6 h (mean difference, −10; 95% CI, −12 to −9), 12 h (mean difference, −9; 95% CI, −10 to −7), 24 h (mean difference, −7; 95% CI, −8 to −6), and 48 h (mean difference, −3; 95% CI, −5 to −1). This effect was not clinically significant ranging below the minimally important difference (10 points out of 100) for each time point. These results were consistent regardless of the type of drug (gabapentin or pregabalin). No effect was observed on pain intensity at 72 h, subacute and chronic pain. The use of gabapentinoids was associated with a lower risk of postoperative nausea and vomiting but with more dizziness and visual disturbance.

Conclusions
No clinically significant analgesic effect for the perioperative use of gabapentinoids was observed. There was also no effect on the prevention of postoperative chronic pain and a greater risk of adverse events. These results do not support the routine use of pregabalin or gabapentin for the management of postoperative pain in adult patients.

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Androgenic Modulation of the Chloride Transporter NKCC1 Contributes to Age-dependent Isoflurane Neurotoxicity in Male Rats
Authors: Chinn Gregory A. , Sasaki Russell Jennifer M. , Yabut Nicole A. , Maharjan Deenu , Sall Jeffrey W. 
Published: July 2020

Background
Cognitive deficits after perinatal anesthetic exposure are well established outcomes in animal models. This vulnerability is sex-dependent and associated with expression levels of the chloride transporters NKCC1 and KCC2. The hypothesis was that androgen signaling, NKCC1 function, and the age of isoflurane exposure are critical for the manifestation of anesthetic neurotoxicity in male rats.

Methods
Flutamide, an androgen receptor antagonist, was administered to male rats on postnatal days 2, 4, and 6 before 6 h of isoflurane on postnatal day 7 (ntotal = 26). Spatial and recognition memory were subsequently tested in adulthood. NKCC1 and KCC2 protein levels were measured from cortical lysates by Western blot on postnatal day 7 (ntotal = 20). Bumetanide, an NKCC1 antagonist, was injected immediately before isoflurane exposure (postnatal day 7) to study the effect of NKCC1 inhibition (ntotal = 48). To determine whether male rats remain vulnerable to anesthetic neurotoxicity as juveniles, postnatal day 14 animals were exposed to isoflurane and assessed as adults (ntotal = 30).

Results
Flutamide-treated male rats exposed to isoflurane successfully navigated the spatial (Barnes maze probe trial F[1, 151] = 78; P < 0.001; mean goal exploration ± SD, 6.4 ± 3.9 s) and recognition memory tasks (mean discrimination index ± SD, 0.09 ± 0.14; P = 0.003), unlike isoflurane-exposed controls. Flutamide changed expression patterns of NKCC1 (mean density ± SD: control, 1.49 ± 0.69; flutamide, 0.47 ± 0.11; P < 0.001) and KCC2 (median density [25th percentile, 75th percentile]: control, 0.23 [0.13, 0.49]; flutamide, 1.47 [1.18,1.62]; P < 0.001). Inhibiting NKCC1 with bumetanide was protective for spatial memory (probe trial F[1, 162] = 6.6; P = 0.011; mean goal time, 4.6 [7.4] s). Delaying isoflurane exposure until postnatal day 14 in males preserved spatial memory (probe trial F[1, 140] = 28; P < 0.001; mean goal time, 6.1 [7.0] s).

Conclusions
Vulnerability to isoflurane neurotoxicity is abolished by blocking the androgen receptor, disrupting the function of NKCC1, or delaying the time of exposure to at least 2 weeks of age in male rats. These results support a dynamic role for androgens and chloride transporter proteins in perinatal anesthetic neurotoxicity.

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Volatile versus Total Intravenous Anesthesia for Cancer Prognosis in Patients Having Digestive Cancer Surgery
Authors: Makito Kanako , Matsui Hiroki , Fushimi Kiyohide , Yasunaga Hideo 
Published: July 2020

Background
Previous experimental and clinical studies have shown that anesthetic agents have varying effects on cancer prognosis; however, the results were inconsistent among these studies. The authors compared overall and recurrence-free survival in patients given volatile or intravenous anesthesia for digestive tract cancer surgery.

Methods
The authors selected patients who had elective esophagectomy, gastrectomy, hepatectomy, cholecystectomy, pancreatectomy, colectomy, and rectal cancer surgery from July 2010 to March 2018 using the Japanese Diagnosis Procedure Combination database. Patients were divided into a volatile anesthesia group (desflurane, sevoflurane, or isoflurane with/without nitrous oxide) and a propofol-based total intravenous anesthesia group. The authors hypothesized that total intravenous anesthesia is associated with greater overall and recurrence-free survival than volatile anesthesia. Subgroup analyses were performed for each type of surgery.

Results
The authors identified 196,303 eligible patients (166,966 patients in the volatile anesthesia group and 29,337 patients in the propofol-based total intravenous anesthesia group). The numbers (proportions) of death in the volatile anesthesia and total intravenous anesthesia groups were 17,319 (10.4%) and 3,339 (11.4%), respectively. There were no significant differences between the two groups in overall survival (hazard ratio, 1.02; 95% CI, 0.98 to 1.07; P = 0.28) or recurrence-free survival (hazard ratio, 0.99; 95% CI, 0.96 to 1.03; P = 0.59), whereas instrumental variable analyses showed a slight difference in recurrence-free survival (hazard ratio, 0.92; 95% CI, 0.87 to 0.98; P = 0.01). Subgroup analyses showed no significant difference in overall or recurrence-free survival between the groups in any type of surgery.

Conclusions
Overall and recurrence-free survival were similar between volatile and intravenous anesthesia in patients having digestive tract surgery. Selection of the anesthetic approach for these patients should be based on other factors.

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Psychological Attachment Orientations of Surrogate Decision-Makers and Goals-of-Care Decisions for Brain Injury Patients in ICUs
Authors: Knies Andrea K. , Zhang Qiang , Juthani Prerak , Tu Stephanie , Pach Jolanta , Martinez Aida , Monin Joan K. , Hwang David Y. 
Published: July 2020

Objectives:
To determine whether ICU surrogates with “insecure” psychologic attachment orientations are more prone to requesting tracheostomy and gastrostomy (i.e., life-sustaining therapy) for severe acute brain injury patients with poor prognosis compared to surrogates with “secure” orientations.

Design:
Cross-sectional survey from November 2017 to August 2018.

Setting:
Single neuroscience ICU at an academic medical center.

Subjects:
Consecutive sample of surrogates of patients admitted to the ICU with a minimum length of stay of 24 hours.

Interventions:
None.

Measurements and Main Results:
We identified surrogates’ psychologic attachment orientation via a standard tool, the Relationship Questionnaire, and collected other surrogate and patient demographics. We also presented surrogates with a hypothetical scenario of an intubated severe acute brain injury patient with poor prognosis and asked each surrogate whether he or she would request life-sustaining therapy or comfort measures only. Fisher exact test was used to compare frequency of life-sustaining therapy selection between secure and insecure surrogates. Additionally, we conducted univariate and multivariate analyses to determine other independent predictors of life-sustaining therapy selection. Two-hundred seventy-five of 713 (38.6%) eligible respondents participated; 153 (55.6%) surrogates were secure, and 122 (44.4%) insecure. There was no significant difference in the proportion of secure respondents selecting life-sustaining therapy compared to insecure (18.3% vs 20.5%; p = 0.38). Although still nonsignificant, the observed difference was slightly greater for those with a specific “anxious” insecure subtype versus “nonanxious” (18.2% vs 23.0%; p = 0.41). Overall, a higher proportion of respondents selecting life-sustaining therapy (vs comfort measures only) reported feeling uncertain or very uncertain about the hypothetical decision (45.3% vs 9.5%; p < 0.001). In a multivariate model, nonwhite race and high religiosity were significant predictors of life-sustaining therapy selection.

Conclusions:
Although surrogate attachment orientation is not predictive of life-sustaining therapy selection, nonwhite race and high religiosity are. Future interventions designed to support severe acute brain injury surrogates could focus on surrogates prone to selecting life-sustaining therapy with high degrees of uncertainty.
Coronavirus Disease 2019 Pandemic Measures: Reports From a National Survey of 9,120 ICU Clinicians
Authors: Kleinpell Ruth , Ferraro David M. , Maves Ryan C. , Kane Gill Sandra L. , Branson Richard , Greenberg Steven , Doersam Jennifer K. , Raman Rameela , Kaplan Lewis J. 
Published: July 2020

Importance:
Recent reports identify that among hospitalized coronavirus disease 2019 patients, 30% require ICU care. Understanding ICU resource needs remains an essential component of meeting current and projected needs of critically ill coronavirus disease 2019 patients.

Objectives:
This study queried U.S. ICU clinician perspectives on challenging aspects of care in managing coronavirus disease 2019 patients, current and anticipated resource demands, and personal stress.

Design, Setting, and Participants:
Using a descriptive survey methodology, an anonymous web-based survey was administered from April 7, 2020, to April 22, 2020 (email and newsletter) to query members of U.S. national critical care organizations.

Measurements and Main Results:
Through a 16-item descriptive questionnaire, ICU clinician perceptions were assessed regarding current and emerging critical ICU needs in managing the severe acute respiratory syndrome coronavirus 2 infected patients, resource levels, concerns about being exposed to severe acute respiratory syndrome coronavirus 2, and perceived level of personal stress. A total of 9,120 ICU clinicians responded to the survey, representing all 50 U.S. states, with 4,106 (56.9%) working in states with 20,000 or more coronavirus disease 2019 cases. The 7,317 respondents who indicated their profession included ICU nurses (n = 6,731, 91.3%), advanced practice providers (nurse practitioners and physician assistants; n = 334, 4.5%), physicians (n = 212, 2.9%), respiratory therapists (n = 31, 0.4%), and pharmacists (n = 30, 0.4%). A majority (n = 6,510, 88%) reported having cared for a patient with presumed or confirmed coronavirus disease 2019. The most critical ICU needs identified were personal protective equipment, specifically N95 respirator availability, and ICU staffing. Minimizing healthcare worker virus exposure during care was believed to be the most challenging aspect of coronavirus disease 2019 patient care (n = 2,323, 30.9%). Nurses report a high level of concern about exposing family members to severe acute respiratory syndrome coronavirus 2 (median score of 10 on 0–10 scale). Similarly, the level of concern reached the maximum score of 10 in ICU clinicians who had provided care to coronavirus disease 2019 patients.

Conclusions:
This national ICU clinician survey identifies continued concerns regarding personal protective equipment supplies with the chief issue being N95 respirator availability. As the pandemic continues, ICU clinicians anticipate a number of limited resources that may impact ICU care including personnel, capacity, and surge potential, as well as staff and subsequent family members exposure to severe acute respiratory syndrome coronavirus 2. These persistent concerns greatly magnify personal stress, offering a therapeutic target for professional organization and facility intervention efforts.
Response and Survival Outcomes to Ibrutinib Monotherapy for Patients With Waldenström Macroglobulinemia on and off Clinical Trials
Authors: Castillo Jorge J. , Gustine Joshua N. , Meid Kirsten , Flynn Catherine A. , Demos Maria G. , Guerrera Maria L. , Jimenez Cristina , Kofides Amanda , Liu Xia , Munshi Manit , Tsakmaklis Nicholas , Patterson Christopher J. , Xu Lian , Yang Guang , Hunter Zachary R. , Treon Steven P. 
Published: July 2020

AbstractIbrutinib is the first approved therapy for symptomatic patients with Waldenström macroglobulinemia (WM). The approval was based on a single, multicenter, phase II trial in previously treated WM patients. We sought to evaluate whether there were differences in clinical characteristics, response, and survival outcomes to ibrutinib monotherapy between WM patients treated on and off clinical trials. Treatment naïve and previously treated patients who received ibrutinib monotherapy at our institution and participated in two prospective studies (ON trial; n = 72) or a prospective database (OFF trial; n = 157) were included. The median times from WM diagnosis to ibrutinib initiation were 3.1 and 3.5 years for ON and OFF trial patients, respectively (p = 0.38). Similar rates of categorical response at 6, 12, and 24 months and at best response were also observed between ON trial and OFF trial patients. The 4‐year PFS and OS rates for ON trial and OFF trial patients were 72% and 63%, respectively (log‐rank p = 0.14) and 83% and 81%, respectively (log‐rank p = 0.14). CXCR4 mutations impacted response and survival outcomes to ibrutinib monotherapy. The 4‐year rates of ibrutinib discontinuation in ON and OFF trial patients were 36% and 44%, respectively (p = 0.11). Ibrutinib is effective in the routine clinical care of both treatment‐naïve and previously treated WM patients. The findings of our study validate the efficacy of ibrutinib monotherapy reported in multiple phase II clinical trials.