bluuebunny/crossref_metadata_2025_split huggingface dataset:
Feasibility and acceptability of personalised breast cancer screening (DECIDO study): protocol of a single-arm proof-of-concept trial
Authors: Pons-Rodriguez Anna , Forné Izquierdo Carles , Vilaplana-Mayoral Jordi , Cruz-Esteve Inés , Sánchez-López Isabel , Reñé-Reñé Mercè , Cazorla Cristina , Hernández-Andreu Marta , Galindo-Ortego Gisela , Llorens Gabandé Montserrat , Laza-Vásquez Celmira , Balaguer-Llaquet Pau , Martínez-Alonso Montserrat , Rué Montserrat 
Published: December 2020

IntroductionPersonalised cancer screening aims to improve benefits, reduce harms and being more cost-effective than age-based screening. The objective of the DECIDO study is to assess the acceptability and feasibility of offering risk-based personalised breast cancer screening and its integration in regular clinical practice in a National Health System setting.Methods and analysisThe study is designed as a single-arm proof-of-concept trial. The study sample will include 385 women aged 40–50 years resident in a primary care health area in Spain. The study intervention consists of (1) a baseline visit; (2) breast cancer risk estimation; (3) a second visit for risk communication and screening recommendations based on breast cancer risk and (4) a follow-up to obtain the study outcomes.A polygenic risk score (PRS) will be constructed as a composite likelihood ratio of 83 single nucleotide polymorphisms. The Breast Cancer Surveillance Consortium risk model, including age, race/ethnicity, family history of breast cancer, benign breast disease and breast density will be used to estimate a preliminary 5-year absolute risk of breast cancer. A Bayesian approach will be used to update this risk with the PRS value.The primary outcome measures will be attitude towards, intention to participate in and satisfaction with personalised breast cancer screening. Secondary outcomes will include the proportions of women who accept to participate and who complete the different phases of the study. The exact binomial and the Student’s t-test will be used to obtain 95% CIs.Ethics and disseminationThe study protocol was approved by the Drug Research Ethics Committee of the University Hospital Arnau de Vilanova. The trial will be conducted in compliance with this study protocol, the Declaration of Helsinki and Good Clinical Practice.The results will be published in peer-reviewed scientific journals and disseminated in scientific conferences and media.Trial registration numberNCT03791008.
Safety of immune checkpoint inhibitor rechallenge after discontinuation for grade ≥2 immune-related adverse events in patients with cancer
Authors: Allouchery Marion , Lombard Thomas , Martin Mickael , Rouby Franck , Sassier Marion , Bertin Celia , Atzenhoffer Marina , Miremont-Salame Ghada , Perault-Pochat Marie-Christine , Puyade Mathieu 
Published: December 2020

BackgroundSafety of rechallenge of immune checkpoint inhibitor (ICI) after grade ≥2 immune-related adverse events (irAEs) leading to ICI discontinuation remains unclear.MethodsAll adverse drug reactions involving at least one ICI reported up to December 31, 2019 were extracted from the French pharmacovigilance database. Patients were included if they experienced at least one grade ≥2 irAE resulting in ICI discontinuation, with subsequent ICI rechallenge. The primary outcome was the recurrence of at least one grade ≥2 irAE in these patients after ICI rechallenge.ResultsWe included 180 patients: 61.1% were men (median age of 66 years), 43.9% had melanoma and 78.9% were receiving anti-programmed cell death 1. First ICI discontinuation was related to 191 irAEs. After ICI rechallenge, 38.9% of the patients experienced at least one grade ≥2 irAE. Among them, 70.0% experienced the same irAE, 25.7% a distinct irAE, and 4.3% both the same and a distinct irAE. Lower recurrence rates of irAEs were associated with rechallenge with the same ICI treatment (p=0.02) or first endocrine irAEs (p=0.003). Gastrointestinal irAEs were more likely to recur (p=0.007). The median duration from ICI discontinuation to rechallenge and the severity of the initial irAE did not predict recurrent irAEs after ICI rechallenge (p=0.53 and p=0.40, respectively).ConclusionsIn this study, 61.1% of the patients who discontinued ICI treatment for grade ≥2 irAEs experienced no recurrent grade ≥2 irAEs after ICI rechallenge. Although ICI rechallenge appears to be safe under close monitoring, it should always be discussed balancing usefulness of rechallenge, patient comorbidities and risk of recurrence of first irAE(s). Due to inherent bias associated with pharmacovigilance studies, further prospective studies are needed to assess risk factors that may influence patient outcomes after ICI rechallenge.
Serum CD73 is a prognostic factor in patients with metastatic melanoma and is associated with response to anti-PD-1 therapy
Authors: Turiello Roberta , Capone Mariaelena , Giannarelli Diana , Morretta Elva , Monti Maria Chiara , Madonna Gabriele , Mallardo Domenico , Festino Lucia , Azzaro Rosa , Levesque Mitchell P , Imhof Laurence , Weide Benjamin , Amaral Teresa , Chevrier Marc , Sucker Antje , Rutkowski Piotr , Schadendorf Dirk , Lebbe Celeste , Luke Jason John , Wistuba-Hamprecht Kilian , Dummer Reinhard , Pinto Aldo , Morello Silvana , Ascierto Paolo A 
Published: December 2020

BackgroundInhibitors of immune checkpoint programmed cell death protein 1 (PD-1) receptor on T cells have shown remarkable clinical outcomes in metastatic melanoma. However, most patients are resistant to therapy. Production of extracellular adenosine, via CD73-mediated catabolism of AMP, contributes to suppress T-cell-mediated responses against cancer. In this study, we analyzed the expression and activity of soluble CD73 in sera of patients with melanoma undergoing anti-PD-1± cytotoxic T-lymphocyte-associated antigen 4 therapy.MethodsSoluble CD73 expression and activity were retrospectively analyzed in serum of a total of 546 patients with melanoma from different centers before starting treatment (baseline) with anti-PD-1 agents, nivolumab or pembrolizumab, and compared with those of 96 healthy subjects. The CD73 activity was correlated with therapy response and survival of patients.ResultsPatients with melanoma show significantly higher CD73 activity and expression than those observed in healthy donors (p<0.0001). Elevated pretreatment levels of CD73 activity were associated with non-response to therapy with nivolumab or pembrolizumab. During treatment, levels of soluble CD73 activity remain unchanged from baseline and still stratify clinical responders from non-responders. High levels of serum CD73 enzymatic activity associate with reduced overall survival (OS; HR=1.36, 95% CI 1.03 to 1.78; p=0.03) as well as progression-free survival (PFS; HR=1.42, 95% CI 1.13 to 1.79, p=0.003). Further, the multivariate Cox regression analysis indicates that serum CD73 activity is an independent prognostic factor besides serum lactate dehydrogenase levels and the presence of brain metastases for both OS (p=0.009) and PFS (p=0.001).ConclusionOur data indicate the relevance of serum CD73 in patients with advanced melanoma receiving anti-PD-1 therapy and support further investigation on targeting CD73 in combination with anti-PD-1 antibodies.
Corticosteroid dosing and opioid use are high in patients with SLE and remain elevated after belimumab initiation: a retrospective claims database analysis
Authors: Birt Julie A , Wu Jianmin , Griffing Kirstin , Bello Natalia , Princic Nicole , Winer Isabelle , Lew Carolyn R , Costenbader Karen H 
Published: December 2020

ObjectivesTo investigate corticosteroid and opioid use among patients with SLE and to examine the impact of belimumab initiation on the use of other SLE therapies.MethodsWe identified adult patients with SLE (International Classification of Diseases, 9th Revision/10th Revision 710.0 and M32) between 1 January 2012 and 31 May 2018 (earliest SLE diagnosis=index date) within MarketScan administrative claims data. Patients were followed from index date for a minimum of 12 months and until the earlier of disenrolment in their health plan or study end (31 May 2018). Corticosteroid utilisation, corticosteroid dose (in prednisone equivalents) and opioid utilisation (overall, by strength (weak, strong) and by duration (chronic use defined as >90 days of cumulative drug supply)) were measured during follow-up. Oral corticosteroid and opioid use were compared in the 6 months before and after initiation of belimumab.ResultsThere were 49 413 patients with SLE eligible for analysis (mean (SD) age: 50.1 (14.0) years, 90.2% female). Of these, 68.5% received corticosteroids, and the average number of prescriptions was 4.59 (4.11) over the first 12 months of follow-up. Among patients with oral corticosteroids, average daily dose was 19.4 (14.2) mg and 59.6% had an average daily dose of ≥15 mg. Half (52.6%) had at least one opioid prescription and of these, 34.6% had chronic use over the first 12 months of follow-up. Among patients initiating belimumab during follow-up (n=1710), oral corticosteroid use decreased by 9.1% (p=0.001), and average daily dose decreased from 14.5 (18.4) mg to 11.9 (18.0) mg (p<0.001) in the 6 months after initiation compared with the 6 months prior. Initiation of belimumab had no impact on prevalence of opioid use.ConclusionsA high proportion of patients with SLE are treated with corticosteroids to control SLE and opioid therapy to manage chronic pain. While there was no change in opioid use, oral corticosteroid use and dose intensity decreased following initiation of belimumab.
Impact of a single non-sex-related stroke risk factor on atrial fibrillation and oral anticoagulant outcomes: a systematic review and meta-analysis
Authors: Grymonprez Maxim , Steurbaut Stephane , De Sutter An , Lahousse Lies 
Published: December 2020

AimsOral anticoagulants (OACs) are crucial for treating atrial fibrillation (AF) patients at high thromboembolic risk. However, in AF patients at intermediate thromboembolic risk with a single non-sex-related stroke risk factor (CHA2DS2-VASc score 1 in men, 2 in women), guidelines advise to consider starting anticoagulation, which may result in OAC non-initiation due to underestimation of the thromboembolic risk of a single stroke risk factor and overestimation of the OAC-related bleeding risk. A critical appraisal of the role of OACs and the benefit–risk profile of non-vitamin K antagonist oral anticoagulants (NOACs) compared with vitamin K antagonists (VKAs) in this patient subgroup are needed.Methods and resultsThis systematic review provides an overview of literature on the effectiveness and safety of OACs in AF patients with a single non-sex-related stroke risk factor after searching Medline and Embase. Differences between individual stroke risk factors regarding the ischaemic stroke risk in non-anticoagulated AF patients are identified in a meta-analysis, demonstrating the highest increased risk in patients aged 65–74 years old or with diabetes mellitus, followed by heart failure, hypertension and vascular disease. Furthermore, meta-analysis results favour NOACs over VKAs, given their equal effectiveness and superior safety in AF patients at intermediate thromboembolic risk (HR 0.93, 95% CI 0.65 to 1.34 for stroke or systemic embolism; HR 0.60, 95% CI 0.45 to 0.80 for major bleeding; HR 0.48, 95% CI 0.14 to 1.59 for intracranial bleeding; HR 0.58, 95% CI 0.47 to 0.71 for mortality).ConclusionOur systematic review with meta-analysis favours the use of anticoagulation in AF patients with a single non-sex-related stroke risk factor, especially when age ≥65 years or diabetes mellitus is present, with a preference for NOACs over VKAs.
Long-term evolution of composition and structure after repeated group selection over eight decades
Authors: Rogers Nicole S. , D’Amato Anthony W. , Leak William B. 
Published: December 2020

In northeastern North America, group selection is frequently used in northern hardwood forests to maintain uneven-aged stand structure and promote regeneration of tree species spanning a range of shade tolerances. For this study, long-term application of group selection at the Bartlett Experimental Forest, New Hampshire, USA, provided a unique opportunity to address cohort- and stand-level progression after 80 years of treatment. Cohort-level evolution reflected successional and developmental dynamics associated with even-aged forest systems, whereas aggregate stand-level conditions were consistent with expectations for uneven-aged systems. As cohorts aged, diameter distributions progressed towards descending monotonic forms and species composition transitioned from shade-intolerant species to shade-tolerant species. Standing deadwood and downed woody material in cohorts followed trajectories of aging even-aged stands through time. Although American beech (Fagus grandifolia Ehrh.) was a primary species across cohorts and at the stand level, stand-level regeneration included a mixture of ecologically and commercially valuable species. These long-term results offer important insights into emergent cohort- and stand-level conditions and processes that may affect continued recruitment of desirable compositional and structural conditions in stands managed using group selection over numerous cutting cycles.
Ectopic Humanized Mesenchymal Niche in Mice Enables Robust Engraftment of Myelodysplastic Stem Cells
Authors: Mian Syed A. , Abarrategi Ander , Kong Kar Lok , Rouault-Pierre Kevin , Wood Henry , Oedekoven Caroline A. , Smith Alexander E. , Batsivari Antoniana , Ariza-McNaughton Linda , Johnson Peter , Snoeks Thomas , Mufti Ghulam J. , Bonnet Dominique 
Published: December 2020

Abstract

Myelodysplastic syndromes (MDS) are clonal stem cell diseases characterized mainly by ineffective hematopoiesis. Here, we present an approach that enables robust long-term engraftment of primary MDS stem cells (MDS-SC) in mice by implantation of human mesenchymal cell–seeded scaffolds. Critically for modeling MDS, where patient sample material is limiting, mononuclear bone marrow cells containing as few as 104 CD34+ cells can be engrafted and expanded by this approach with the maintenance of the genetic make-up seen in the patients. Noninvasive high-resolution ultrasound imaging shows that these scaffolds are fully perfused. Our data show that the human microenvironment but not mouse is essential to MDS-SC homing and engraftment. Notably, the alternative niche provided by healthy donor mesenchymal stromal cells enhances engraftment of MDS-SCs. This study characterizes a new tool to model MDS human disease with the level of engraftment previously unattainable in mice and offers insights into human-specific determinants of the MDS-SC microenvironment.

Significance:
These findings are significant for understanding the niche dependence of MDS. This report provides the evidence of the migratory behavior of hematopoietic stem cells in myeloid cancers. Our model offers a unique opportunity to study the clonal behavior of the myeloid/lymphoid cancers and delineate how cancer cells interact with different niches.
The ‘Revolving Door’ of Direct Participation in Hostilities
Authors: Silvestri Alessandro 
Published: December 2020

Abstract
Contemporary trends of warfare have witnessed a so-called ‘civilian footprint’ in support of military operations while battlefields have increasingly shifted towards urban areas. International humanitarian law established a framework through which civilians are protected from direct attack ‘unless and for such time as they take a direct part in hostilities’. Three key areas have traditionally been associated with the analysis of direct participation in hostilities (‘dph’): civilian legal status, what behaviour amounts to dph, and what modalities govern this loss of protection. This article will focus on the latter and attempt to create a feasible and practical framework capable of harnessing the temporal scope of dph and limit the so-called ‘revolving door phenomenon’. The framework developed in this article will account for criteria that could and should aid decision-making on the battlefield, most notably causal associations between individuals and dph acts and the physical or non-physical nature of dph acts’ deployments.
The Actualisation of the L'viv Dialect in the Works of Yurii Vynnychuk
Authors: Pidkuĭmukha Liudmyla 
Published: December 2020

The Actualisation of the L'viv Dialect in the Works of Yurii VynnychukThe article offers an analysis of the actualisation of Ukrainian vocabulary, primarily in the Galician dialect. Yurii Vynnychuk's novels Tsenzor sniv (Eng. Dream Censor) and Tango smerti (Eng. The Tango of Death) have been chosen as sources for this research. Particular attention is paid to vocabulary for naming abstract notions, some polite words, and vocabulary relating to L'viv domestic life. Furthermore, the semantic structure and stylistic features of the actualised L'viv dialect are identified. The results indicate that the vocabulary in Yurii Vynnychuk's novels was used to describe life in L'viv during the interwar period. In addition, an analysis of modern dictionaries demonstrates that Galician vocabulary, and the L'viv dialect in particular, are returning to the core of the lexical system. Aktualizacja lwowskiego koine w powieściach Jurija VynnychukaArtykuł poświęcony jest aktualizacji słownictwa galicyjskiego. Materiałem badawczym są powieści Jurija Vynnychuka Cenzor sniv (2013) i Tango smerti (2016), na których podstawie autor charakteryzuje główne grupy lwowskiego koine, wyróżniając słownictwo abstrakcyjne, domowe, indywidualne wzory etykiety i wiele innych. Określa funkcje zaktualizowanego słownictwa w tekstach literackich oraz analizuje reprezentację jednostek leksykalnych we współczesnych słownikach języka ukraińskiego. Ponadto w artykule dokonana została analiza osobliwości opisu używanych skrótów słownikowych badanych leksemów.
Terrestrial Evaporation and Global Climate: Lessons from Northland, a Planet with a Hemispheric Continent
Authors: Laguë Marysa M. , Pietschnig Marianne , Ragen Sarah , Smith Timothy A. , Battisti David S. 
Published: December 2020

AbstractMotivated by the hemispheric asymmetry of land distribution on Earth, we explore the climate of Northland, a highly idealized planet with a Northern Hemisphere continent and a Southern Hemisphere ocean. The climate of Northland can be separated into four distinct regions: the Southern Hemisphere ocean, the seasonally wet tropics, the midlatitude desert, and the Great Northern Swamp. We evaluate how modifying land surface properties on Northland drives changes in temperatures, precipitation patterns, the global energy budget, and atmospheric dynamics. We observe a surprising response to changes in land surface evaporation, where suppressing terrestrial evaporation in Northland cools both land and ocean. In previous studies, suppressing terrestrial evaporation has been found to lead to local warming by reducing latent cooling of the land surface. However, reduced evaporation can also decrease atmospheric water vapor, reducing the strength of the greenhouse effect and leading to large-scale cooling. We use a set of idealized climate model simulations to show that suppressing terrestrial evaporation over Northern Hemisphere continents of varying size can lead to either warming or cooling of the land surface, depending on which of these competing effects dominates. We find that a combination of total land area and contiguous continent size controls the balance between local warming from reduced latent heat flux and large-scale cooling from reduced atmospheric water vapor. Finally, we demonstrate how terrestrial heat capacity, albedo, and evaporation all modulate the location of the ITCZ both over the continent and over the ocean.
Gambling and Problem Gambling in Canada in 2018: Prevalence and Changes Since 2002
Authors: Williams Robert J. , Leonard Carrie A. , Belanger Yale D. , Christensen Darren R. , el-Guebaly Nady , Hodgins David C. , McGrath Daniel S. , Nicoll Fiona , Stevens Rhys M.G. 
Published: December 2020

Objective: The purpose of this study was to provide an updated profile of gambling and problem gambling in Canada and to examine how the rates and pattern of participation compare to 2002. Method: An assessment of gambling and problem gambling was included in the 2018 Canadian Community Health Survey and administered to 24,982 individuals aged 15 and older. The present analyses selected for adults (18+). Results: A total of 66.2% of people reported engaging in some type of gambling in 2018, primarily lottery and/or raffle tickets, the only type in which the majority of Canadians participate. There are some significant interprovincial differences, with perhaps the most important one being the higher rate of electronic gambling machine (EGM) participation in Manitoba and Saskatchewan. The overall pattern of gambling in 2018 is very similar to 2002, although participation is generally much lower in 2018, particularly for EGMs and bingo. Only 0.6% of the population were identified as problem gamblers in 2018, with an additional 2.7% being at-risk gamblers. There is no significant interprovincial variation in problem gambling rates. The interprovincial pattern of problem gambling in 2018 is also very similar to what was found in 2002 with the main difference being a 45% decrease in the overall prevalence of problem gambling. Conclusions: Gambling and problem gambling have both decreased in Canada from 2002 to 2018 although the provincial patterns are quite similar between the 2 time periods. Several mechanisms have likely collectively contributed to these declines. Decreases have also been reported in several other Western countries in recent years and have occurred despite the expansion of legal gambling opportunities, suggesting a degree of inoculation or adaptation in large parts of the population.
The effect of ocular dominance on macular function: A pattern electroretinogram study
Authors: Kılınç Hekimsoy Hilal , Sekeroglu Mehmet Ali 
Published: December 2020

Purpose: To investigate the effect of ocular dominance on pattern electroretinogram (PERG) recordings in the participants who have no ophthalmic diseases. Methods: One hundred and twelve eyes of 56 participants (mean age 32.96 ± 10.82 years) were included in this prospective, cross-sectional study. After detailed ophthalmological examination and determination of the ocular dominance with hole-in-a-card test, the PERG was performed to determine implicit time and amplitudes of P50 and N95. Results: There were no significant interocular differences in visual acuity, refractive error, or intraocular pressure ( p > 0.05 for all). Thirty-six (64.3%) of the participants had ocular dominance in the right eye. The dominant eyes had significantly higher P50 amplitude than in the fellow nondominant eyes (6.90 µV in dominant vs 5.87 µV in nondominant; p = 0.015; 95% confidence interval). There was no significant difference in N95 amplitude, N95/P50 ratio, and implicit times of P50 and N95 between the dominant and nondominant eyes of the participants ( p = 0.090, p = 0.124 p = 0.817, p = 0.668; respectively). Conclusion: The analysis revealed a significantly increased P50 amplitude of the PERG, which is known to be highly associated with macular function, in dominant eyes of the patients when compared to fellow nondominant eyes.