bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oxygen isotope (δ18O) trends measured from Ordovician conodont apatite using secondary ion mass spectrometry (SIMS): Implications for paleo-thermometry studies
Authors: Edwards Cole T. , Jones Clive M. , Quinton Page C. , Fike David A. 
Published: May 2021

Abstract
The oxygen isotopic compositions (δ18O) of minimally altered phosphate minerals and fossils, such as conodont elements, are used as a proxy for past ocean temperature. Phosphate is thermally stable under low to moderate burial conditions and is ideal for reconstructing seawater temperatures because the P-O bonds are highly resistant to isotopic exchange during diagenesis. Traditional bulk methods used to measure conodont δ18O include multiple conodont elements, which can reflect different environments and potentially yield an aggregate δ18O value derived from a mixture of different water masses. In situ spot analyses of individual elements using micro-analytical techniques, such as secondary ion mass spectrometry (SIMS), can address these issues.
Here we present 108 new δ18O values using SIMS from conodont apatite collected from four Lower to Upper Ordovician stratigraphic successions from North America (Nevada, Oklahoma, and the Cincinnati Arch region of Kentucky and Indiana, USA). The available elements measured had a range of thermal alteration regimes that are categorized based on their conodont alteration index (CAI) as either low (CAI = 1–2) or high (CAI = 3–4). Though individual spot analyses of the same element yield δ18O values that vary by several per mil (‰), most form a normal distribution around a mean value. Isotopic variability of individual spots can be minimized by avoiding surficial heterogeneities like cracks, pits, or near the edge of the element and the precision can be improved with multiple (≥4) spot analyses of the same element. Mean δ18O values from multiple conodonts from the same bed range between 0.0 and 4.3‰ (median 1.0‰), regardless of low or high CAI values. Oxygen isotopic values measured using SIMS in this study reproduce values similar to published trends, namely, δ18O values increase during the Early–Middle Ordovician and plateau by the mid Darriwilian (late Middle Ordovician). Twenty-two of the measured conodonts were from ten sampled beds that had been previously measured using bulk analysis. SIMS-based δ18O values from these samples are more positive by an average of 1.7‰ compared to bulk values, consistent with observations by others who attribute the shift to carbonate- and hydroxyl-related SIMS matrix effects. This offset has implications for paleo-temperature model estimates, which indicate that a 4 °C temperature change corresponds to a 1‰ shift in δ18O (‰). Although this uncertainty precludes precise paleo-temperature reconstructions by SIMS, it is valuable for identifying spatial and stratigraphic trends in temperature that might not have been previously possible with bulk approaches.
Cost-effectiveness of empagliflozin versus canagliflozin, dapagliflozin, or standard of care in patients with type 2 diabetes and established cardiovascular disease
Authors: Reifsnider Odette S , Kansal Anuraag R , Gandhi Pranav K , Cragin Lael , Brand Sarah B , Pfarr Egon , Fahrbach Kyle , Ustyugova Anastasia 
Published: May 2021

IntroductionEmpagliflozin, a sodium-glucose co-transporter-2 (SGLT-2) inhibitor, is approved in the USA to reduce risk of cardiovascular (CV) death in adults with type 2 diabetes mellitus (T2DM) and established CV disease, based on EMPA-REG OUTCOME (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) trial results. Empagliflozin reduced major adverse CV event (MACE) by 14%, CV death by 38%, and hospitalization for heart failure (HHF) by 35% vs placebo, each on top of standard of care (SoC). SGLT-2 inhibitors canagliflozin and dapagliflozin have also been compared with placebo, all on top of SoC, in CV outcome trials. In the CANVAS (Canagliflozin Cardiovascular Assessment Study) Program, canagliflozin reduced MACE by 14% and HHF by 33%. Dapagliflozin reduced HHF by 27% in the DECLARE-TIMI 58 trial (Multicenter Trial to Evaluate the Effect of Dapagliflozin on the Incidence of Cardiovascular Events). This analysis estimated the cost-effectiveness of empagliflozin versus canagliflozin, dapagliflozin, or SoC, in US adults with T2DM and established CV disease.Research design and methodsIndividual patient-level discrete-event simulation was conducted to predict time-to-event for CV and renal outcomes, and specific adverse events over patients’ lifetimes. Occurrence of events in EMPA-REG OUTCOME was estimated based on event-free survival curves with time-dependent covariates. An HR for canagliflozin or dapagliflozin versus empagliflozin on each clinical event was estimated from published CANVAS, DECLARE-TIMI 58, and EMPA-REG OUTCOME data using indirect treatment comparison. Public sources provided US costs and utilities.ResultsThe model predicted longer survival for empagliflozin versus canagliflozin, dapagliflozin, and SoC mainly due to direct reduction in CV death. Empagliflozin dominated canagliflozin, yielding more quality-adjusted life years (QALYs; 0.38) at a lower cost (−US$306). Compared with dapagliflozin and SoC, empagliflozin yielded 0.50 and 0.84 incremental QALYs at US$1517 and US$27 539 incremental costs, yielding incremental cost-effectiveness ratios of US$3054/QALY and US$32 848/QALY, respectively.ConclusionsEmpagliflozin was projected to dominate canagliflozin and be highly cost-effective compared with dapagliflozin and SoC using US healthcare costs.
Systematic depression and anxiety screening for patients and caregivers: implementation and process improvement in a cystic fibrosis clinic
Authors: Goetz Danielle Marie , Frederick Carla , Savant Adrienne , Cogswell Alex , Fries Lynne , Roach Christine , Shea Nicole , Borowitz Drucy , Smith Beth 
Published: May 2021

IntroductionDepression and anxiety are common. Rates are significantly higher in cystic fibrosis (CF), and impact health outcomes. Screening is recommended, but is difficult to implement/sustain annually in a busy CF centre. The aim was to develop an acceptable model for depression and anxiety screening in adolescents/adults with CF and their caregivers that could be sustained and shared.MethodsQuality improvement methodology with plan-do-study-act cycles, flow diagrams, review of data monthly with our designated ‘Mental Health Team’ and caregiver satisfaction surveys, were used to begin screening in clinics and to improve the process. We then piloted our process at a larger paediatric CF centre.ResultsPrior to 2013, screening was not performed at our CF centre. After the first quarter of depression screening, 88% of adolescents and 69% of adults with CF were screened. The process was refined. By the second year, 99% of patients were screened. Anxiety screening began in year three; 97%–99% of patients were screened for both anxiety and depression in years 3–5. Annual caregiver screening rates were >95%. Screening was changed from Patient Health Questionnaire-2 (PHQ-2) to PHQ-9 due to better sensitivity in caregivers, and expanded to patients. Anxiety screening began in year 3 with the Generalised Anxiety Disorder-7 questionnaire. Patients and caregivers reported acceptance of screening. At the larger paediatric centre used as a pilot, 89.6% of patients were screened in year 1. Feedback included recommendations to improve tracking/follow-up of positive screens.ConclusionsDevelopment and implementation of a stepwise process for depression and anxiety screening was successful in a paediatric/adult CF clinic, due to constant re-evaluation by an engaged team with feedback from patients via survey. A systematic approach at a busy CF centre can serve as a model to implement screening in a clinic.
mHOMR: a prospective observational study of an automated mortality prediction model to identify patients with unmet palliative needs
Authors: Wegier Pete , Kurahashi Allison , Saunders Stephanie , Lokuge Bhadra , Steinberg Leah , Myers Jeff , Koo Ellen , van Walraven Carl , Downar James 
Published: May 2021

ObjectiveIdentification of patients with shortened life expectancy is a major obstacle to delivering palliative/end-of-life care. We previously developed the modified Hospitalised-patient One-year Mortality Risk (mHOMR) model for the automated identification of patients with an elevated 1-year mortality risk. Our goal was to investigate whether patients identified by mHOMR at high risk for mortality in the next year also have unmet palliative needs.MethodWe conducted a prospective observational study at two quaternary healthcare facilities in Toronto, Canada, with patients admitted to general internal medicine service and identified by mHOMR to have an expected 1-year mortality risk of 10% or more. We measured patients’ unmet palliative needs—a severe uncontrolled symptom on the Edmonton Symptom Assessment Scale or readiness to engage in advance care planning (ACP) based on Sudore’s ACP Engagement Survey.ResultsOf 518 patients identified by mHOMR, 403 (78%) patients consented to participate; 87% of those had either a severe uncontrolled symptom or readiness to engage in ACP, and 44% had both. Patients represented frailty (38%), cancer (28%) and organ failure (28%) trajectories were admitted for a median of 6 days, and 94% survived to discharge.ConclusionsA large majority of hospitalised patients identified by mHOMR have unmet palliative needs, regardless of disease, and are identified early enough in their disease course that they may benefit from a palliative approach to their care. Adoption of such a model could improve the timely introduction of a palliative approach for patients, especially those with non-cancer illness.
Palliative care for homeless and vulnerably housed people: scoping review and thematic synthesis
Authors: James Richard , Flemming Kate , Hodson Melanie , Oxley Tammy 
Published: May 2021

IntroductionPeople who are homeless or vulnerably housed are subject to disproportionately high risks of physical and mental illness and are further disadvantaged by difficulties in access to services. Research has been conducted examining a wide range of issues in relation to end-of-life care for homeless and vulnerably housed people, however, a contemporary scoping review of this literature is lacking.ObjectivesTo understand the provision of palliative care for people who are homeless or vulnerably housed from the perspective of, and for the benefit of, all those who should be involved in its provision.DesignScoping review with thematic synthesis of qualitative and quantitative literature.Data sourcesMEDLINE, Embase, PsycINFO, Social Policy and Practice and CINAHL databases were searched, from inception to May 2020. Citation chasing and manual searching of grey literature were also employed.ResultsSixty-four studies, involving 2117 homeless and vulnerably housed people were included, with wide variation in methodology, population and perspective. The thematic synthesis identified three themes around: experiences, beliefs and wishes; relationships; and end-of-life care.ConclusionDiscussion highlighted gaps in the evidence base, especially around people experiencing different types of homelessness. Existing evidence advocates for service providers to offer needs-based and non-judgemental care, for organisations to use existing assets in co-producing services, and for researchers to address gaps in the evidence base, and to work with providers in transforming existing knowledge into evaluable action.
Accessing tens-to-hundreds femtoseconds nuclear state lifetimes with low-energy binary heavy-ion reactions
Authors: Ciemała M. , Ziliani S. , Crespi F. C. L. , Leoni S. , Fornal B. , Maj A. , Bednarczyk P. , Benzoni G. , Bracco A. , Boiano C. , Bottoni S. , Brambilla S. , Bast M. , Beckers M. , Braunroth T. , Camera F. , Cieplicka-Oryńczak N. , Clément E. , Coelli S. , Dorvaux O. , Erturk S. , De France G. , Fransen C. , Goldkuhle A. , Grębosz J. , Harakeh M. N. , Iskra Ł. W. , Jacquot B. , Karpov A. , Kicińska-Habior M. , Kim Y.-H. , Kmiecik M. , Lemasson A. , Lenzi S. M. , Lewitowicz M. , Li H. , Matea I. , Mazurek K. , Michelagnoli C. , Matejska-Minda M. , Million B. , Müller-Gatermann C. , Nanal V. , Napiorkowski P. , Napoli D. R. , Palit R. , Rejmund M. , Schmitt Ch. , Stanoiu M. , Stefan I. , Vardaci E. , Wasilewska B. , Wieland O. , Ziębliński M. , Zielińska M. 
Published: May 2021

AbstractA novel Monte Carlo technique has been developed to determine lifetimes of excited states in the tens-to-hundreds femtoseconds range in products of low-energy heavy-ion binary reactions, with complex velocity distributions. The method is based on a detailed study of Doppler-broadened $$\gamma $$
γ
-ray lineshapes. Its relevance is demonstrated in connection with the $$^{18}\text {O}(7.0\, \text {MeV/u})+\,^{181}\text {Ta}$$

18

O

(
7.0

MeV/u
)

+

181

Ta

experiment, performed at GANIL with the AGATA+VAMOS+PARIS setup, to study neutron-rich O, C, N, ... nuclei. Excited states in $$^{17}\text {O}$$

17

O

and $$^{19}\text {O}$$

19

O

, with known lifetimes, are used to validate the method over the $$\sim 20{-}400\,\text {fs}$$

∼
20
-
400

fs

lifetime-sensitivity range. Emphasis is given to the unprecedented position resolution provided by $$\gamma $$
γ
-tracking arrays, which turns out to be essential for reaching the required accuracy in Doppler-shift correction. The technique is anticipated to be an important tool for lifetime investigations in exotic neutron-rich nuclei, produced with intense ISOL-type beams.
Fragmentation of charmed quark to double-charmed hadrons
Authors: Baranov S. P. , Kopeliovich B. Z. 
Published: May 2021

AbstractWe consider the production of hadrons containing two charmed quarks in pp and ee collisions. We perform a numerical comparison of the fragmentation approach with the full calculation at $${{{\mathcal {O}}}}(\alpha _s^4)$$

O
(

α
s
4

)

. We conclude that the non-fragmentation contributions remain important up to transverse momenta as large as about 40 GeV, thus making questionable the applicability of the fragmentation approximation at smaller transverse momenta.
Reversing Imatinib's Immunosuppressive Effects by Modulating Type I IFN Signaling
Authors: Largaespada David A. 
Published: May 2021

Abstract
Signal pathway inhibition is a well-validated approach for treating cancers driven by activated kinases such as KIT. However, kinase inhibitors may make tumor cells less responsive to tumor immune surveillance and less sensitive to immunotherapies. In this issue, Liu and colleagues report that, in a mouse model, inhibition of oncogenic KIT in gastrointestinal stromal tumors reduces type I interferon (IFN) production and signaling, and the effectiveness of the immune system in controlling tumor growth. They were able to partially overcome the immunosuppressive effects of KIT inhibition using agonists of the type I IFN response, pointing the way toward intelligently combining kinase inhibitors and immune modulators for therapy.
See article by Liu et al., p. 542
Galectin-1 Supports a Dangerous Liaison between Monocytes and Multiple Myeloma
Authors: Ugel Stefano , Bronte Vincenzo 
Published: May 2021

Abstract

In multiple myeloma, the accumulation of cells with negative immunoregulatory properties, such as monocytic myeloid-derived suppressor cells (M-MDSC), has a protumoral effect. Lim and colleagues unveil a novel circuit regulating the cross-talk between M-MDSCs and cancerous plasma cells centered on the interaction between myeloma-derived galactin-1 and CD304 (neuropilin-1) on the surface of circulating M-MDSCs.
See article by Lim et al., p. 503
Interação na internet e ideologia: excesso e atenuação
Authors: Gomes Regina Souza 
Published: May 2021

Este trabalho tem como objetivo contribuir para a compreensão, sob a perspectiva da Semiótica de linha francesa, dos discursos que circulam nas redes sociais e em sites de internet, caracterizados, principalmente, pelas altercações políticas, pelas polarizações e pelos excessos nas relações enunciativas, pelas posições ideológicas arraigadas e apaixonadas (Barros, 2014; 2015; 2016). Em contrapartida, circulam também sites e textos que caminham em direção inversa – para uma busca, pelo menos aparente, de desaceleração, a exemplo do Movimento Slow. Analisaremos, para tanto, as postagens do ex-Ministro da Educação em sua conta pessoal do Twitter, colhidas entre setembro e outubro de 2019, e sites que preconizam a atonia e os valores da contemplação, do equilíbrio e da harmonia, alinhados com o Movimento Slow (tais como Ciclo Vivo), além de reportagens sobre o tema, em jornais portugueses e brasileiros. Levaremos em conta, para a análise, principalmente, a sintaxe intensiva e as categorias tensivas da triagem e da mistura para a apreensão dos valores ideológicos, sem deixar de observar os recursos discursivos de aspectualização e de argumentação. A análise aponta para convergências, com diferentes gradações, tanto temáticas quanto de andamento e intensidade.
Aerobic Exercise Restores Aging‐Associated Reductions in Arterial Adropin Levels and Improves Adropin‐Induced Nitric Oxide‐Dependent Vasorelaxation
Authors: Fujie Shumpei , Hasegawa Natsuki , Horii Naoki , Uchida Masataka , Sanada Kiyoshi , Hamaoka Takafumi , Padilla Jaume , Martinez‐Lemus Luis A. , Maeda Seiji , Iemitsu Motoyuki 
Published: May 2021

Background
Adropin is a peptide hormone that promotes nitric oxide (NO) production via activation of endothelial NO synthase (eNOS) in endothelial cells. Its circulating levels are reduced with aging and increased with aerobic exercise training (AT). Using a mouse model, we hypothesized that AT restores aging‐associated reductions in arterial and circulating adropin and improves adropin‐induced NO‐dependent vasorelaxation. Further, we hypothesized these findings would be consistent with data obtained in elderly humans.

Methods and Results
In the animal study, 50‐week‐old SAMP1 male mice that underwent 12 weeks of voluntary wheel running, or kept sedentary, were studied. A separate cohort of 25‐week‐old SAMP1 male mice were used as a mature adult sedentary group. In the human study, 14 healthy elderly subjects completed an 8‐week AT program consisting of 45 minutes of cycling 3 days/week. In mice, we show that advanced age is associated with a decline in arterial and circulating levels of adropin along with deterioration of endothelial function, arterial NO production, and adropin‐induced vasodilation. All these defects were restored by AT. Moreover, AT‐induced increases in arterial adropin were correlated with increases in arterial eNOS phosphorylation and NO production. Consistently with these findings in mice, AT in elderly subjects enhanced circulating adropin levels and these effects were correlated with increases in circulating nitrite/nitrate (NOx) and endothelial function.

Conclusions
Changes in arterial adropin that occur with age or AT relate to alterations in endothelial function and NO production, supporting the notion that adropin should be considered a therapeutic target for vascular aging.

Registration

URL:
https://www.umin.ac.jp
; Unique identifier: UMIN000035520.
Challenging the Rule of Political Liberalism
Authors: Harbo Tor-Inge 
Published: May 2021

Abstract
The origin of the ongoing conflict between the EU and Poland may, according to the author, partly be subscribed to the EU-institutions conceptualization of the rule of law. This conceptualization, which in the article is referred to as “the rule of political liberalism”, establishes a particular set of legal institutional and substantial frames and limits for national democratic politics. Granted that the rule of law is an inherently contested concept, the author deconstructs the rule of political liberalism, reveals its weaknesses and ideological bias and proposes an alternative understanding of the rule of law. “The rule of pragmatism” is based on a pragmatic conceptualization of the law, and proscribes a regard for social context and consequences rather than abstract constructions and (good) intention. If applied by the EU institutions, the rule of pragmatism will secure greater legal and political pluralism in Europe and thus contributes to the mending of EU’s legitimacy deficit.
Changing trends in quality of media reporting of suicide in the community following a celebrity suicide in India
Authors: Menon Vikas , Kar Sujita Kumar , Ransing Ramdas , Sharma Ginni , Pattnaik Jigyansa Ipsita , Kaliamoorthy Charanya , Varadharajan Natarajan , Mukherjee Srijeeta , Agrawal Aditya , Padhy Susanta Kumar , Arafat SM Yasir 
Published: May 2021

Objective: Little is known about changes in quality of media reporting of suicide in the community following a celebrity suicide. Our objective was to compare trends in quality of media reporting of suicide, before and after the suicide of an Indian entertainment celebrity, against the World Health Organization suicide reporting guidelines. Method: Online news portals of English and local language newspapers, as well as television channels, were searched to identify relevant suicide-related news articles. Comparison of reporting characteristics before and after the celebrity suicide was performed using chi-square test or Fisher’s exact test. Results: A total of 3867 eligible news reports were retrieved. There was a significant increase in harmful reporting characteristics, such as reporting the name, age and gender of the deceased ( p < 0.001 for all comparisons), mentioning the location ( p < 0.001) and reason for suicide ( p = 0.04) and including photos of the deceased ( p = 0.002) following the celebrity suicide. Helpful reporting practices were less affected; there was a significant rise in inclusion of expert opinion ( p = 0.04) and mention of suicide-related warning signs ( p = 0.02). Conclusion: Following a celebrity suicide, significant changes in the quality of media reporting of suicide were noted with an increase in several potentially harmful reporting characteristics.
A prospective study to determine the clinical utility of pharmacogenetic testing of veterans with treatment-resistant depression
Authors: McCarthy Michael J , Chen Yucui , Demodena Anna , Leckband Susan G , Fischer Eileen , Golshan Shahrokh , Suppes Trisha , Kelsoe John R 
Published: May 2021

Background: Pharmacotherapies for depression are often ineffective and treatment-resistant depression (TRD) is common across bipolar disorder (BD), major depressive disorder (MDD), and post-traumatic stress disorder (PTSD). Patient genetic information can be used to predict treatment outcomes. Prospective studies indicate that pharmacogenetic (PGX) tests have utility in the treatment of depression. However, few studies have examined the utility of PGX in other diagnoses typified by depression, or in veterans, a cohort with high rates of medical comorbidity, social stress, and suicide. Aim: To determine the efficacy of genetically guided pharmacological treatment of TRD. Methods: We conducted an 8-week, prospective, multisite, single-blind study in 182 veterans with TRD including patients with BD, MDD, and PTSD. Subjects were randomly assigned to PGX-guided treatment in which the clinician incorporated PGX information into decision-making, or treatment as usual (TAU). Results: Overall, the PGX group improved marginally faster compared to TAU, but the difference was not statistically significant. Secondary analyses revealed that only PTSD patients showed a potential benefit from PGX testing. Patients predicted by PGX testing to have moderate levels of genetic risk showed a significant benefit from the PGX-guided treatment, whereas other risk groups demonstrated no benefit. Clinicians generally found the PGX test was useful, particularly in more depressed patients and/or those with more warnings for significant or serious adverse outcomes. Clinicians more often used the results to select a drug, but only rarely to adjust dosing. Conclusions: The data reveal possible group differences in the utility of PGX testing in veterans with TRD. ClinicalTrials.gov Identifier: NCT04469322.