bluuebunny/crossref_metadata_2025 huggingface dataset:
InDeep: 3D fully convolutional neural networks to assistin silicodrug design on protein–protein interactions
Authors: Mallet Vincent , Checa Ruano Luis , Moine Franel Alexandra , Nilges Michael , Druart Karen , Bouvier Guillaume , Sperandio Olivier
Published: December 2021

Motivation

Protein–protein interactions (PPIs) are key elements in numerous biological pathways and the subject of a growing number of drug discovery projects including against infectious diseases. Designing drugs on PPI targets remains a difficult task and requires extensive efforts to qualify a given interaction as an eligible target. To this end, besides the evident need to determine the role of PPIs in disease-associated pathways and their experimental characterization as therapeutics targets, prediction of their capacity to be bound by other protein partners or modulated by future drugs is of primary importance.

Results

We present InDeep, a tool for predicting functional binding sites within proteins that could either host protein epitopes or future drugs. Leveraging deep learning on a curated dataset of PPIs, this tool can proceed to enhanced functional binding site predictions either on experimental structures or along molecular dynamics trajectories. The benchmark of InDeep demonstrates that our tool outperforms state-of-the-art ligandable binding sites predictors when assessing PPI targets but also conventional targets. This offers new opportunities to assist drug design projects on PPIs by identifying pertinent binding pockets at or in the vicinity of PPI interfaces.

Availability and implementation

The tool is available on GitLab at https://gitlab.pasteur.fr/InDeep/InDeep.

Supplementary information

Supplementary data are available at Bioinformatics online.
Exercise against cocaine sensitization in mice: a [18F]fallypride micro-PET study
Authors: Becker Guillaume , Lespine Louis-Ferdinand , Bahri Mohamed Ali , Serrano Maria Elisa , Lemaire Christian , Luxen André , Tirelli Ezio , Plenevaux Alain
Published: December 2021

Wheel-running exercise in laboratory rodents (animal model useful to study the neurobiology of aerobic exercise) decreases behavioural markers of vulnerability to addictive properties of various drugs of abuse including cocaine. However, neurobiological mechanisms underpinning this protective effect are far from fully characterized. Here, 28-day-old female C57BL/6J mice were housed with (n = 48) or without (n = 48) a running wheel for 6 weeks before being tested for acute locomotor responsiveness and initiation of locomotor sensitization to intraperitoneal injections of 8 mg/kg cocaine. The long-term expression of sensitization took place 3 weeks after the last session. On the day after, all mice underwent a micro-PET imaging session with [18F]fallypride radiotracer (dopamine 2/3 receptors antagonist). Exercised mice were less sensitive to acute and sensitized cocaine hyperlocomotor effects, such attenuation being particularly well marked for long-term expression of sensitization (η2P = 0.262). Chronic administration of cocaine was associated with a clear-cut increase of [18F]fallypride binding potential in mouse striatum (η2P = 0.170) while wheel-running exercise was associated with a moderate decrease in dopamine 2/3 receptors density in striatum (η2P = 0.075), a mechanism that might contribute to protective properties of exercise against drugs of abuse vulnerability.
The ERA Registry Annual Report 2019: summary and age comparisons
Authors: Boenink Rianne , Astley Megan E , Huijben Jilske A , Stel Vianda S , Kerschbaum Julia , Ots-Rosenberg Mai , Åsberg Anders A , Lopot Frantisek , Golan Eliezer , Castro de la Nuez Pablo , Rodríguez Camblor Marta , Trujillo-Alemán Sara , Ruiz San Millan Juan Carlos , Ucio Mingo Pablo , Díaz Juan Manuel , Bouzas-Caamaño M Encarnación , Artamendi Marta , Aparicio Madre Manuel I , Santiuste de Pablos Carmen , Slon Roblero María Fernanda , Zurriaga Oscar , Stendahl Maria E , Bell Samira , Idrizi Alma , Ioannou Kyriakos , Debska-Slizien Alicja , Galvão Ana A , De Meester Johan M , Resić Halima , Hommel Kristine , Radunovic Danilo , Pálsson Runolfur , Lassalle Mathilde , Finne Patrik , De los Ángeles-Garcia Bazaga María , Gjorgjievski Nikola , Seyahi Nurhan , Bonthuis Marjolein , Ortiz Alberto , Jager Kitty J , Kramer Anneke
Published: December 2021

Background

Data on renal replacement therapy (RRT) for end-stage renal disease were collected by the European Renal Association (ERA) Registry via national and regional renal registries in Europe and countries bordering the Mediterranean Sea. This article provides a summary of the 2019 ERA Registry Annual Report, including data from 34 countries and additional age comparisons.

Methods

Individual patient data for 2019 were provided by 35 registries and aggregated data by 17 registries. Using these data, the incidence and prevalence of RRT, the kidney transplantation activity and the survival probabilities were calculated.

Results

In 2019, a general population of 680.8 million people was covered by the ERA Registry. Overall, the incidence of RRT was 132 per million population (p.m.p.). Of these patients, 62% were men, 54% were ≥65 years of age and 21% had diabetes mellitus as primary renal disease (PRD), and 84% had haemodialysis (HD), 11% had peritoneal dialysis (PD) and 5% had pre-emptive kidney transplantation as an initial treatment modality. The overall prevalence of RRT on 31 December 2019 was 893 p.m.p., with 58% of patients on HD, 5% on PD and 37% living with a kidney transplant. The overall kidney transplant rate was 35 p.m.p. and 29% of the kidney grafts were from a living donor. The unadjusted 5-year survival probability was 42.3% for patients commencing dialysis, 86.6% for recipients of deceased donor grafts and 94.4% for recipients of living donor grafts in the period 2010–14. When comparing age categories, there were substantial differences in the distribution of PRD, treatment modality and kidney donor type, and in the survival probabilities.
Simultaneous [18F]fluoride and gadobutrol enhanced coronary positron emission tomography/magnetic resonance imaging for in vivo plaque characterization
Authors: Wurster Thomas H , Landmesser Ulf , Abdelwahed Youssef S , Skurk Carsten , Morguet Andreas , Leistner David M , Fröhlich Georg , Haghikia Arash , Engel Leif Christopher , Schuster Andreas , Noutsias Michel , Schulze Daniel , Hamm Bernd , Furth Christian , Brenner Winfried , Botnar Rene M , Bigalke Boris , Makowski Marcus R
Published: December 2021

Aims

18F-sodium fluoride ([18F]fluoride) and gadobutrol are promising probes for positron emission tomography (PET) and magnetic resonance imaging (MRI) characterizing coronary artery disease (CAD) activity. Unlike [18F]fluoride-PET/computed tomography (CT), the potential of PET/MR using [18F]fluoride and gadobutrol simultaneously, has so far not been evaluated. This study assessed feasibility and diagnostic potential of [18F]fluoride and gadobutrol enhanced dual-probe PET/MR in patients with CAD.

Methods and results

Twenty-one patients (age, 66.7 ± 6.7 years) with CAD scheduled for invasive coronary angiography (XCA) underwent simultaneous [18F]fluoride (mean activity/effective dose: 157.2 ± 29.7 MBq/3.77 ± 0.72 mSv) and gadobutrol enhanced PET/MR on an integrated PET/MRI (3 T) scanner. Optical coherence tomography (OCT) was used as reference. Target-to-background ratio (TBR, [18F]fluoride-PET) and contrast-to-noise ratio (CNR) values (MRI, gadobutrol) were calculated for each coronary segment. Previously suggested PET/CT-TBR thresholds for adverse coronary events were evaluated. High-risk plaques, i.e. calcified and non-calcified thin-cap fibroatheromas (TCFAs) were predominantly located in segments with a TBR >1.28 (P = 0.012). Plaques containing a lipid core on OCT, were more frequently detected in segments with a TBR >1.25 (P < 0.001). TBR values significantly correlated with maximum calcification thickness (P = 0.009), while fibrous cap thickness was significantly less in segments with a TBR >1.28 (P = 0.044). Above a TBR threshold of >1.28, CNR values significantly correlated with the presence of calcified TCFAs (P = 0.032).

Conclusion

Simultaneous [18F]fluoride and gadobutrol dual-probe PET/MRI is feasible in clinical practice and may facilitate the identification of high-risk patients. The combination of coronary MR-derived CNR values post gadobutrol and [18F]fluoride based TBR values may improve identification of high-risk plaque features.
The valve uptake index: improving assessment of prosthetic valve endocarditis and updating [18F]FDG PET/CT(A) imaging criteria
Authors: Roque Albert , Pizzi María N , Fernández-Hidalgo Nuria , Romero-Farina Guillermo , Burcet Gemma , Reyes-Juarez José Luis , Espinet Carina , Castell-Conesa Joan , Escobar Manuel , Ferreira-González Ignacio , Aguadé-Bruix Santiago , Cuellar-Calabria Hug
Published: December 2021

Aims

Diagnosis of prosthetic valve endocarditis (PVE) by positron emission computed tomography angiography (PET/CTA) is based on visual and quantitative morpho-metabolic features. However, the fluorodeoxyglucose (FDG) uptake pattern can be sometimes visually unclear and susceptible to subjectivity. This study aimed to validate a new parameter, the valve uptake index [VUI, maximum standardized uptake value (SUVmax)−mean standardized uptake value (SUVmean)/SUVmax], designed to provide a more objective indication of the distribution of metabolic activity. Secondly, to re-evaluate the utility of traditionally used PVE imaging criteria and determine the potential value of adding the VUI in the diagnostic algorithm of PVE.

Methods and results

Retrospective analysis of 122 patients (135 prosthetic valves) admitted for suspicion of endocarditis, with a conclusive diagnosis of definite (N = 57) or rejected (N = 65) PVE, and who had undergone a cardiac PET/CTA scan as part of the diagnostic evaluation. We measured the VUI and recorded the SUVmax, SUVratio, uptake pattern, and the presence of endocarditis-related anatomic lesions. The VUI, SUVmax, and SUVratio values were 0.54 ± 0.1 vs. 0.36 ± 0.08, 7.68 ± 3.07 vs. 3.72 ± 1.11, and 4.28 ± 1.93 vs. 2.16 ± 0.95 in the ‘definite’ PVE group vs. the ‘rejected’ group, respectively (mean ± SD; P < 0.001). A cut-off value of VUI > 0.45 showed a sensitivity, specificity, and diagnostic accuracy for PVE of 85%, 88%, and 86.7% and increased diagnostic ability for confirming endocarditis when combined with the standard diagnostic criteria.

Conclusions

The VUI demonstrated good diagnostic accuracy for PVE, even increasing the diagnostic power of the traditionally used morphometabolic parameters, which also confirmed their own diagnostic performance. More research is needed to assess whether the integration of the VUI into the PVE diagnostic algorithm may clarify doubtful cases and thus improve the diagnostic yield of PET/CTA.
Trend, population structure, and trait mapping from 15 years of national varietal trials of UK winter wheat
Authors: Shorinola Oluwaseyi , Simmonds James , Wingen Luzie U , Uauy Cristobal
Published: December 2021

There are now a rich variety of genomic and genotypic resources available to wheat researchers and breeders. However, the generation of high-quality and field-relevant phenotyping data which is required to capture the complexities of gene × environment interactions remains a major bottleneck. Historical datasets from national variety performance trials (NVPT) provide sufficient dimensions, in terms of numbers of years and locations, to examine phenotypic trends and study gene × environment interactions. Using NVPT for winter wheat varieties grown in the United Kingdom between 2002 and 2017, we examined temporal trends for eight traits related to yield, adaptation, and grain quality performance. We show a non-stationary linear trend for yield, grain protein content, Hagberg Falling Number (HFN), and days to ripening. Our data also show high environmental stability for yield, grain protein content, and specific weight in UK winter wheat varieties and high environmental sensitivity for HFN. We also show that UK varieties released within this period cluster into four main population groups. Using the historical NVPT data in a genome-wide association analysis, we uncovered a significant marker-trait association peak on wheat chromosome 6A spanning the NAM-A1 gene that have been previously associated with early senescence. Together, our results show the value of utilizing the data routinely collected during national variety evaluation process for examining breeding progress and the genetic architecture of important traits.
NLR diversity and candidate fusiform rust resistance genes in loblolly pine
Authors: Ence Daniel , Smith Katherine E , Fan Shenghua , Gomide Neves Leandro , Paul Robin , Wegrzyn Jill , Peter Gary F , Kirst Matias , Brawner Jeremy , Nelson C Dana , Davis John M
Published: December 2021

Resistance to fusiform rust disease in loblolly pine (Pinus taeda) is a classic gene-for-gene system. Early resistance gene mapping in the P. taeda family 10-5 identified RAPD markers for a major fusiform rust resistance gene, Fr1. More recently, single nucleotide polymorphism (SNP) markers associated with resistance were mapped to a full-length gene model in the loblolly pine genome encoding for a nucleotide-binding site leucine-rich repeat (NLR) protein. NLR genes are one of the most abundant gene families in plant genomes and are involved in effector-triggered immunity. Inter- and intraspecies studies of NLR gene diversity and expression have resulted in improved disease resistance. To characterize NLR gene diversity and discover potential resistance genes, we assembled de novo transcriptomes from 92 loblolly genotypes from across the natural range of the species. In these transcriptomes, we identified novel NLR transcripts that are not present in the loblolly pine reference genome and found significant geographic diversity of NLR genes providing evidence of gene family evolution. We designed capture probes for these NLRs to identify and map SNPs that stably cosegregate with resistance to the SC20-21 isolate of Cronartium quercuum f.sp. fusiforme (Cqf) in half-sib progeny of the 10-5 family. We identified 10 SNPs and 2 quantitative trait loci associated with resistance to SC20-21 Cqf. The geographic diversity of NLR genes provides evidence of NLR gene family evolution in loblolly pine. The SNPs associated with rust resistance provide a resource to enhance breeding and deployment of resistant pine seedlings.
New data and collaborations at theSaccharomycesGenome Database: updated reference genome, alleles, and the Alliance of Genome Resources
Authors: Engel Stacia R , Wong Edith D , Nash Robert S , Aleksander Suzi , Alexander Micheal , Douglass Eric , Karra Kalpana , Miyasato Stuart R , Simison Matt , Skrzypek Marek S , Weng Shuai , Cherry J Michael
Published: December 2021

Saccharomyces cerevisiae is used to provide fundamental understanding of eukaryotic genetics, gene product function, and cellular biological processes. Saccharomyces Genome Database (SGD) has been supporting the yeast research community since 1993, serving as its de facto hub. Over the years, SGD has maintained the genetic nomenclature, chromosome maps, and functional annotation, and developed various tools and methods for analysis and curation of a variety of emerging data types. More recently, SGD and six other model organism focused knowledgebases have come together to create the Alliance of Genome Resources to develop sustainable genome information resources that promote and support the use of various model organisms to understand the genetic and genomic bases of human biology and disease. Here we describe recent activities at SGD, including the latest reference genome annotation update, the development of a curation system for mutant alleles, and new pages addressing homology across model organisms as well as the use of yeast to study human disease.
The genomic basis of high-elevation adaptation in wild house mice (Mus musculus domesticus) from South America
Authors: Beckman Elizabeth J , Martins Felipe , Suzuki Taichi A , Bi Ke , Keeble Sara , Good Jeffrey M , Chavez Andreas S , Ballinger Mallory A , Agwamba Kennedy , Nachman Michael W
Published: December 2021

Understanding the genetic basis of environmental adaptation in natural populations is a central goal in evolutionary biology. The conditions at high elevation, particularly the low oxygen available in the ambient air, impose a significant and chronic environmental challenge to metabolically active animals with lowland ancestry. To understand the process of adaptation to these novel conditions and to assess the repeatability of evolution over short timescales, we examined the signature of selection from complete exome sequences of house mice (Mus musculus domesticus) sampled across two elevational transects in the Andes of South America. Using phylogenetic analysis, we show that house mice colonized high elevations independently in Ecuador and Bolivia. Overall, we found distinct responses to selection in each transect and largely nonoverlapping sets of candidate genes, consistent with the complex nature of traits that underlie adaptation to low oxygen availability (hypoxia) in other species. Nonetheless, we also identified a small subset of the genome that appears to be under parallel selection at the gene and SNP levels. In particular, three genes (Col22a1, Fgf14, and srGAP1) bore strong signatures of selection in both transects. Finally, we observed several patterns that were common to both transects, including an excess of derived alleles at high elevation, and a number of hypoxia-associated genes exhibiting a threshold effect, with a large allele frequency change only at the highest elevations. This threshold effect suggests that selection pressures may increase disproportionately at high elevations in mammals, consistent with observations of some high-elevation diseases in humans.
Loneliness Progression Among Older Adults During the Early Phase of the COVID-19 Pandemic in the United States and Canada
Authors: Lin Tian , Horta Marilyn , Heald Kristen , Heemskerk Amber , Darboh Bri , Levi Adina , Spreng R Nathan , Turner Gary R , Ebner Natalie C
Published: December 2021

Objectives

Older adults are at high risk for complications from coronavirus disease 2019 (COVID-19). Health guidelines recommend limiting physical contact during the pandemic, drastically reducing opportunities for in-person social exchange. Older adults are also susceptible to negative consequences from loneliness, and the COVID-19 pandemic has likely exacerbated this age-related vulnerability.

Methods

In 107 community-dwelling older individuals (65–90 years, 70.5% female) from Florida, the United States, and Ontario, Canada, we examined change in loneliness over the course of the pandemic after implementation of COVID-19-related physical distancing guidelines (March–September 2020; T1–T5; biweekly concurrent self-report) using multilevel modeling. We also explored gender differences in loneliness during the early phase of the COVID-19 pandemic at both data collection sites.

Results

Consistent across the 2 sites, levels of loneliness remained stable over time for the full sample (T1–T5). However, our exploratory moderation analysis suggested gender differences in the trajectory of loneliness between the United States and Canada, in that older men in Florida and older women in Ontario reported an increase in loneliness over time.

Discussion

Leveraging a longitudinal, binational data set collected during the early phase of the COVID-19 pandemic, this study advances understanding of stability and change in loneliness among a North American sample of individuals aged 65 and older faced with the unique challenges of social isolation. These results can inform public health policy in anticipation of future pandemics and highlight the need for targeted intervention to address acute loneliness among older populations.
Lifetime Adversity in the Context of Monthly Adversity and Psychological Well-Being in Midlife: Evidence of Cumulative Disadvantage, But Not Steeling Effects of Lifetime Adversity
Authors: Infurna Frank J , Luthar Suniya S , Grimm Kevin J
Published: December 2021

Objectives

Our objective is to examine whether lifetime adversity has either a “steeling effect” or “cumulative disadvantage effect” on the consequences of monthly adversity on psychological well-being in middle-aged adults. An exploratory step was to examine whether such associations differed based on the domain of adversity (personal, family/friend, bereavement, social–environmental, and relationship).

Method

Multilevel modeling was applied to data from a sample of participants in midlife (n = 358, ages 50–65, 54% women) who were assessed monthly for 2 years.

Results

Lifetime adversity did not show steeling effects, but instead appeared to exacerbate the impact of monthly adversity on psychological well-being, indicating cumulative disadvantage. On months where an adversity was reported, on average, individuals who reported more lifetime adversity showed stronger increases in depressive symptoms, anxiety, and negative affect and decreases in positive affect. There was limited evidence to suggest for steeling effects for life satisfaction. Reporting adversity in the personal, bereavement, social–environmental, and relationship domains showed the strongest associations with psychological well-being.

Discussion

Our discussion focuses on how lifetime adversity showed a cumulative disadvantage effect on the consequences of monthly adversity on psychological well-being. We also elaborate on future directions for research that include other conceptualizations of adversity and research to examine mechanisms underlying this relationship.
The Prevalence of Dissemination and Implementation Research and Training Grants at National Cancer Institute–Designated Cancer Centers
Authors: Mueller Nora M , Hsieh Ada , Ramanadhan Shoba , Lee Rebekka M , Emmons Karen M
Published: December 2021

Background

Dissemination and implementation (D&I) research is a key factor in the uptake and use of evidence-based cancer control interventions. National Cancer Institute (NCI)–designated cancer centers are ideal settings in which to further D&I knowledge. The purpose of this study was to summarize the characteristics of NCI-funded D&I science grants in the nation’s cancer centers to understand the nature, extent, and opportunity for this key type of translational work.

Methods

We used the National Institutes of Health Research Portfolio Online Reporting Tool to identify active NCI-funded grants in D&I science at NCI clinical cancer centers (n = 13) and comprehensive cancer centers (n = 51) as well as their academic affiliates. Active projects were eligible for inclusion if they 1) were awarded directly to an NCI cancer center or an academic or research affiliate, and 2) identified D&I content in the abstract. Portfolio data were collected in February 2021.

Results

We identified 104 active NCI-funded D&I research or training grants across the 64 cancer centers; 57.8% of cancer centers had at least 1 NCI-funded D&I grant. Most awards (71.1%) were for research grants. Training grants constituted 29.1% of D&I-focused grants. Overall, 50.0% of grants (n = 52) concentrated on specific cancers. Almost two-thirds of grants (n = 68, 65.4%) had a stated health equity focus.

Conclusions

More than one-half of NCI-designated cancer centers have active funding in D&I science, reflecting a substantial investment by NCI. There remains considerable room for further development, which would further support NCI’s translational mission.
Growth of Managed Older Douglas-fir Stands: Implications of the Black Rock Thinning Trial in the Coast Range of Western Oregon
Authors: Tappeiner John , Adams Darius , Montgomery Claire , Maguire Douglas
Published: December 2021

The most recent remeasurement of growth (at approximate total stand age 100 years) from the Black Rock Thinning Trial in western Oregon provides useful information for forest owners interested in accelerating restoration of older forest characteristics in Douglas-fir stands of the Pacific Northwest. Thinnings at several intensities at total stand age of roughly 50 years effectively reset stand growth patterns. With quadratic mean diameters in thinned plots up to 40% higher than those of unthinned controls, thinned plot mean annual increments (MAIs) and periodic annual increments continue to rise 55 years after thinning, with the peak in board foot and cubic foot MAI apparently still decades in the future. Assuming repeatable future thinning responses similar to the Black Rock Trial, financial analysis of the opportunity costs of extending rotations to 100 years indicates that some thinning treatments can reduce opportunity costs by up to half at a 6% discount rate.
The Mereological Structure of Distributivity: A Case Study of BinominalEach
Authors: Law Jess H-K
Published: December 2021

Binominal each is known to exhibit selectional requirements on the noun phrase that immediately precedes it. The goal of this paper is to reduce these selectional requirements to a single requirement of monotonic growth of measurement in relation to the ‘size’ of distributivity. More concretely, it is argued that binominal each imposes a constraint on the functional dependencies arising from distributive quantification, requiring that the measurement of its host grows monotonically with the number of values being distributively quantified. To make constraints on dependencies formally explicit, I devise a version of dynamic plural logic with features from van den Berg (1996) and Brasoveanu (2008, 2013) to semantically represent dependencies arising from evaluating distributive quantification. The use of a dynamic logic, coupled with a delayed evaluation mechanism in terms of higher order meaning (Cresti, 1995; Swart, 2000; Charlow, 2021, allows the constraint to act as an output context constraint on distributive quantification, which mirrors the use of output constraints pioneered by Farkas (1997, 2002b) and and further developed in Brasoveanu (2013), Henderson (2014) and Kuhn (2017).
The use of radiolucent pedicle fixation in degenerative lumbar spine surgery
Authors: Xie Nathan , Kim Sihyong J , Mobbs Ralph J , Reddy Rajesh
Published: December 2021

Radiolucent pedicle screw fixation has become popularized in the field of oncological spine surgery owing to its ability to provide superior post-operative planning for adjuvant radiotherapy and radiological monitoring of tumour progression. We present the case of a 45-year-old female with degenerative spine pathology who underwent L4/5 and L5/S1 posterior lumbar interbody fusion with carbon fibre reinforced-polyetheretherketone pedicle screw fixation. The authors highlight the potential advantages of radiolucent pedicle fixation, which may translate into the degenerative spine surgery domain.
Arthropod exposure accounts for about half of skin disorders in returning travellers
Authors: Faucon Caroline , Godefroy Nagisa , Itani Oula , Nouchi Agathe , Tebano Gianpiero , Ouedraogo Elise , Monsel Gentiane , Caumes Eric
Published: December 2021

We report the spectrum of skin diseases in returning international travellers seen in our department, with the participation of a dermatologist for each consultation. Of 135 dermatoses (60% appearing abroad), 33.3% were considered as tropical, and 44–52% were related to arthropod exposure, highlighting the need and importance of anti-mosquito measures.
Four genomic clades of Candida auris identified in Canada, 2012–2019
Authors: De Luca Domenica G , Alexander David C , Dingle Tanis C , Dufresne Philippe J , Hoang Linda M , Kus Julianne V , Schwartz Ilan S , Mulvey Michael R , Bharat Amrita
Published: December 2021

Candida auris is an emerging yeast that is associated with antifungal resistance and healthcare-associated outbreaks. From 2012 to 2019, there were 24 known cases of C. auris colonization or infection in Canada. Isolates were from axilla/groin (n = 6), ear (n = 5), blood (n = 4), toe (n = 2), and a variety of other sites (n = 7). Canadian isolates belonged to the four main genomic clades: Clade I (formerly called South Asian clade, n = 12), Clade II (East Asian, n = 3), Clade III (African, n = 4), and Clade IV (South American, n = 5). Isolates within each clade were clonal; however, whole genome sequencing may be helpful in identifying clusters within healthcare facilities.

Lay summary

The fungal pathogen Candida auris has caused many hospital outbreaks and is often multidrug resistant. All four major strains of C. auris were identified in Canada from 2012 to 2019. Genomic epidemiology may be useful for identifying and reducing transmission of C. auris within hospitals.
Transients from ONe white dwarf – neutron star/black hole mergers
Authors: Bobrick Alexey , Zenati Yossef , Perets Hagai B , Davies Melvyn B , Church Ross
Published: December 2021

We conduct the first 3D hydrodynamic simulations of oxygen–neon white dwarf–neutron star/black hole mergers (ONe WD–NS/BH mergers). Such mergers constitute a significant fraction, and may even dominate, the inspiral rates of all WD–NS binaries. We post-process our simulations to obtain the nuclear evolution of these systems and couple the results to a supernova spectral synthesis code to obtain the first light curves and spectra for these transients. We find that the amount of 56Ni synthesized in these mergers grows as a strong function of the WD mass, reaching typically 0.05 and up to $0.1\, {\rm M}_\odot$ per merger. Photodisintegration leads to similar amounts of 4He and about a ten times smaller amount of 1H. The nuclear yields from these mergers, in particular those of 55Mn, may contribute significantly to Galactic chemical evolution. The transients expected from ONe WD–NS mergers are dominantly red/infrared, evolve on month-long time-scales and reach bolometric magnitudes of up to −16.5. The current surveys must have already detected these transients or are, alternatively, putting strong constraints on merger scenarios. The properties of the expected transients from WD–NS mergers best agree with faint type Iax supernovae. The Vera Rubin Observatory (LSST) will be detecting up to thousands of merging ONe WD–NS systems per year. We simulate a subset of our models with 2D axisymmetric flash code to investigate why they have been challenging for previous studies. We find that the likely main challenge has been effectively modelling the nuclear statistical equilibrium regime in such mergers.
On the stability of additional moons orbiting Kepler-1625 b
Authors: Moraes R A , Borderes-Motta G , Winter O C , Monteiro J
Published: December 2021

Since it was proposed, the exomoon candidate Kepler-1625 b-I has changed the way we see satellite systems. Because of its unusual physical characteristics, many questions about the stability and origin of this candidate have been raised. Currently, we have enough theoretical studies to show that if Kepler-1625 b-I is indeed confirmed, it will be stable. Regarding its origin, previous works indicated that the most likely scenario is capture, although conditions for in situ formation have also been investigated. In this work, we assume that Kepler-1625 b-I is an exomoon and study the possibility of an additional, massive exomoon being stable in the same system. To model this scenario, we perform N-body simulations of a system including the planet, Kepler-1625 b-I, and one extra Earth-like satellite. Based on previous results, the satellites in our system will be exposed to tidal interactions with the planet and to gravitational effects owing to the rotation of the planet. We find that the satellite system around Kepler-1625 b is capable of harbouring two massive satellites. The extra Earth-like satellite can be stable in various locations between the planet and Kepler-1625 b-I, with a preference for regions inside $25\, R_{\rm p}$. Our results suggest that the strong tidal interaction between the planet and the satellites is an important mechanism to ensure the stability of satellites in circular orbits closer to the planet, while the 2:1 mean motion resonance between the Earth-like satellite and Kepler-1625 b-I would provide stability for satellites in wider orbits.
A detailed study of stellar populations of three star clusters with extended main-sequence turnoffs
Authors: Chen Jing , Li Zhongmu , Zhang Su , Deng Yangyang , Zhao Wenchang
Published: December 2021

This paper investigates the extended main-sequence turnoffs (eMSTOs) and stellar populations of three clusters with different ages using Gaia Data Release 2 (DR2) data in detail. The colour–magnitude diagrams (CMDs) of three Galactic clusters show broad main sequences, eMSTOs, blue stragglers, and red giant clumps. We explore the effects of age spread, binaries, and rotating stars on the morphology of the entire CMD, paying particular attention to the effects of binary stars and rotating stars on eMSTOs. Some synthetic CMDs are built on the basis of the advanced stellar population synthesis (ASPS) model to study the observed CMDs and search for the best-fitting stellar population models. The age of the youngest stars, age spread, metallicity, colour excess, distance modulus, binary fraction, and rotating star fraction of clusters are determined. The results show that both binaries and rotating stars are responsible for the eMSTO of intermediate-age cluster LP 585, but binary stars affect more than rotating stars on the eMSTO morphologies of the youngest (M11) and oldest (NGC 6819) clusters in our samples. It suggests that M11 (∼0.3 Gyr) is possibly a composite stellar population of rotating and binary stars, while clusters LP 585 (∼1.1 Gyr) and NGC 6819 (∼2.0 Gyr) are simple stellar populations of rotating and binary stars.
Application of genetic algorithm to estimate the large angular scale features of cosmic microwave background
Authors: Nayak Parth , Saha Rajib
Published: December 2021

Genetic Algorithm (GA) – motivated by natural evolution – is a robust method to estimate the global optimal solutions of problems involving multiple objective functions. In this article, for the first time, we apply GA to reconstruct the CMB temperature anisotropy map over large angular scales of the sky using (internal) linear combination (ILC) of the final-year WMAP and Planck satellite observations. To avoid getting trapped into a local minimum, we implement the GA with generous diversity in the populations by selecting pairs with diverse fitness coefficients and by introducing a small but significant amount of mutation of genes. We find that the new GA-ILC method produces a clean map which agrees very well with that obtained using the exact analytical expression of weights in ILC. By performing extensive Monte Carlo simulations of the CMB reconstruction using the GA-ILC algorithm, we find that residual foregrounds in the cleaned map are minimal and tend to occupy localized regions along the galactic plane. The CMB angular power spectrum shows no indication of any bias in the entire multipole range 2 ≤ ℓ ≤ 32 studied in this work. The error in the CMB angular power spectrum is also minimal and given entirely by the cosmic-variance-induced error. Our results agree well with those obtained by various other reconstruction methods by different research groups. This problem-independent robust GA-ILC method provides a flexible way towards the complex and challenging task of CMB component reconstruction in cosmology.
Long-term dynamical evolution of Pallene (Saturn XXXIII) and its diffuse, dusty ring
Authors: Muñoz-Gutiérrez Marco A , Granados Contreras A P , Madeira Gustavo , A’Hearn Joseph A , Giuliatti Winter Silvia
Published: December 2021

The distinctive set of Saturnian small satellites, Aegaeon, Methone, Anthe, and Pallene, constitutes an excellent laboratory to understand the evolution of systems immersed in co-orbital dusty rings/arcs, subjected to perturbations from larger satellites and non-gravitational forces. In this work, we carried out a comprehensive numerical exploration of the long-term evolution of Pallene and its ring. Through frequency map analysis, we characterized the current dynamical state around Pallene. A simple tidal evolution model serves to set a time frame for the current orbital configuration of the system. With detailed short- and long-term N-body simulations we determine whether Pallene is currently in resonance with one or more of six of Saturn’s major moons. We analysed a myriad of resonant arguments extracted from the direct and indirect parts of the disturbing function, finding that Pallene is not in mean motion resonance from the present up to 5 Myr into the future; none the less, some resonant arguments exhibit intervals of libration and circulation at different time-scales and moon pairings. We studied the dynamical evolution of micrometric particles forming the ring, considering gravitational and non-gravitational forces. Non-gravitational forces are responsible for particles vertical excursions and outward migration. By estimating the satellite’s mass production rate, we find that Pallene could be responsible for keeping its ring in steady-state only if it is mainly composed of large micrometre-sized particles. If mainly composed of particles with a few micrometres for which Pallene is the only source, the ring will spread out, both radially and vertically, until it finally disappears.
Risk of herpes zoster in patients with rheumatoid arthritis in the biologics era from 2011 to 2015 and its association with methotrexate, biologics, and corticosteroids
Authors: Yamaguchi Rei , Tanaka Eiichi , Nakajima Ayako , Inoue Eisuke , Abe Mai , Sugano Eri , Sugitani Naohiro , Saka Kumiko , Ochiai Moeko , Higuchi Yoko , Sugimoto Naoki , Ikari Katsunori , Yamanaka Hisashi , Harigai Masayoshi
Published: December 2021

Objectives

To elucidate the incidence and risk factors of herpes zoster (HZ) in patients with rheumatoid arthritis (RA) in the biologics era.

Methods

We determined the rate of HZ occurrence among the RA patients that participated in the Institute of Rheumatology, Rheumatoid Arthritis surveys from 2011 to 2015, by assessing medical records. The standardised incidence rate per 1000 patient-years with a 95% confidence interval (CI) was calculated, and risk factors for HZ were analysed using a time-dependent Cox regression analysis.

Results

Among 7815 patients (female, 84.7%) contributing to 25,863 patient-years of observation, 340 HZ events in 309 patients were confirmed. The standardised incidence rate (95% CI) per 1000 patient-years was 8.5 (6.9–10.5) in total, 6.0 (3.7–9.2) in men, and 11.0 (8.7–13.7) in women. Risk factors for HZ were age per 10 years (hazard ratio 1.14, 95% CI 1.03–1.26, p < .05), Japanese version of the Health Assessment Questionnaire (J-HAQ) score of 0.5–1.5 (versus J-HAQ = 0; 1.51, 1.09–2.10, p < .05), methotrexate use (1.58, 1.06–2.36, p < .05), and biologic use (1.88, 1.44–2.47, p < .01).

Conclusions

In the era when biologics were frequently used and corticosteroid use and doses were decreasing, methotrexate and biologics increased the risk for HZ.
Efficacy and safety of abatacept in biologic-naïve patients with active rheumatoid arthritis by background methotrexate dose:post hocanalysis of a randomized, placebo-controlled, phase 4 study
Authors: Tanaka Yoshiya , Matsubara Tsukasa , Hashizume Koichi , Amano Norihito , Takeuchi Tsutomu
Published: December 2021

Objectives

The objective of this study is to evaluate efficacy and safety of abatacept in biologic-naïve, anti-citrullinated protein antibody (ACPA)-positive Japanese patients with active rheumatoid arthritis (RA) by background methotrexate (MTX) dose.

Methods

In this post hoc analysis of a randomized, double-blind, placebo-controlled phase 4 study (NCT01758198), patients received intravenous abatacept (∼10 mg/kg) or placebo both with MTX (≥6 mg/week). Efficacy (Disease Activity Score 28 using C-reactive protein [DAS28 (CRP)] and Health Assessment Questionnaire-Disability Index [HAQ-DI]) was assessed by baseline MTX dosage (≤8 and >8 mg/week) to week 16; safety was assessed by MTX dosage ≤8 and >8 mg/week. Change from baseline in DAS28 (CRP) and HAQ-DI was assessed using longitudinal repeated measures analysis.

Results

Overall, 101 and 102 patients received abatacept + MTX ≤8 and >8 mg/week, while 96 and 106 patients received placebo + MTX ≤8 and >8 mg/week, respectively. Regardless of baseline MTX dose received, mean changes from baseline in DAS28 (CRP) and HAQ-DI in abatacept groups were similar; repeated measures analysis showed similar trends in changes from baseline in DAS28 (CRP) and HAQ-DI. Abatacept safety profile was consistent with previous observations.

Conclusions

Post hoc analysis demonstrated similar efficacy and safety of abatacept in biologic-naïve ACPA-positive Japanese patients with RA regardless of baseline MTX dose.
Procollagen I N-terminal peptide correlates with inflammation on sacroiliac joint magnetic resonance imaging in ankylosing spondylitis but not in non-radiographic axial spondyloarthritis: A cross-sectional study
Authors: Li Xuegang , Liang Anqi , Chen Yufeng , Lam Nelson SiuKei , Long Xinxin , Xu Xianghe , Zhong Shuping
Published: December 2021

Objectives

To identify disease activity scores and biomarkers that reflect magnetic resonance imaging (MRI)-determined sacroiliac joint (SIJ) inflammation in ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA).

Methods

Patients who had AS and nr-axSpA were enrolled. All the patients underwent SIJ MRI. SpondyloArthritis Research Consortium of Canada (SPARCC) method was used to score bone marrow edema in the inflammatory lesions on MRI. Radiographic assessment of the spine was performed using modified Stoke Ankylosing Spondylitis Spine Score. Clinical variables, inflammatory markers, serum alkaline phosphatase, osteocalcin (OC), C-terminal telopeptide of type I collagen (CTX-I), and procollagen I N-terminal peptide (PINP) were measured. Correlation analysis between MRI-determined SIJ inflammation scores and disease activity scores and laboratory variables was performed.

Results

Thirty-five patients had AS and 36had nr-axSpA. Significant differences were noted between the AS group and the nr-axSpA group in terms of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Ankylosing Spondylitis Disease Activity Score (ASDAS)-ESR, ASDAS-CRP, PINP, and SPARCC (p < .001, p = .004, p < .001, p < .001, p = .030, p < .001, respectively). MRI-determined SIJ inflammatory scores correlated with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), OC, CTX-I, and PINP in AS (p = .036, p = .023, p = .002, p = .041, p = .004, respectively) and correlated with ESR, CRP, ASDAS-ESR, ASDAS-CRP, BASDAI, and BASFI in nr-axSpA (p = .003, p = .002, p < .001, p < .001, p = .010, p = .007, respectively). Multivariate analysis showed that PINP exhibited a positive correlation independent of the MRI inflammatory score and that age exhibited a negative correlation independent of the MRI inflammatory score.

Conclusions

In AS, PINP and age independently correlated with active inflammation on SIJ MRI. PINP may be useful as a marker of objective inflammation in AS.
Efficacy and safety of canakinumab for colchicine-resistant or colchicine-intolerant familial Mediterranean fever: A single-centre observational study
Authors: Tomokawa Takuya , Koga Tomohiro , Endo Yushiro , Michitsuji Toru , Kawakami Atsushi
Published: December 2021

Objectives

To evaluate the efficacy and safety of canakinumab in Japanese patients with colchicine-resistant or colchicine-intolerant familial Mediterranean fever (FMF) in a real-world clinical setting.

Methods

We reviewed 13 Japanese FMF patients to whom canakinumab was introduced during the period of October 2017 to December 2020. All patients were diagnosed as FMF according to Tel-Hashomer criteria. We performed genetic analyses for Mediterranean fever or MEFV by targeted next-generation sequencing. Efficacy was assessed by attack frequency and the percentage of patients who achieved attack improvement at 24 weeks. Safety was assessed by adverse events observed during canakinumab treatment.

Results

The median duration and follow-up of canakinumab treatment were 13 and 16 months, respectively. The median attack frequency was 0.50 [0.30–1.00] at 24 weeks, which was a significant decrease from 2.00 [0.85–2.88] at the time of induction (p = .019). There were three patients (23%) with complete resolution of attacks at 24 weeks. No serious adverse events were observed. However, one patient had small intestinal ulceration which led to the discontinuation of canakinumab.

Conclusions

Although the number of cases is small, this study suggests that canakinumab is efficacious and safe for use in Japanese patients with colchicine-resistant or colchicine-intolerant FMF in a real-world clinical setting in Japan.
The association between rest-activity rhythms and glycemic markers: the US National Health and Nutrition Examination Survey, 2011–2014
Authors: Xiao Qian , Matthews Charles E , Playdon Mary , Bauer Cici
Published: December 2021

Objectives

Previous studies conducted in mostly homogeneous sociodemographic samples have reported a relationship between weakened and/or disrupted rest-activity patterns and metabolic dysfunction. This study aims to examine rest-activity rhythm characteristics in relation to glycemic markers in a large nationally representative and diverse sample of American adults.

Methods

This study used data from the National Health and Nutrition Examination Survey 2011–2014. Rest-activity characteristics were derived from extended cosine models using 24-hour actigraphy. We used multinomial logistic regression and multiple linear regression models to assess the associations with multiple glycemic markers (i.e., glycated hemoglobin, fasting glucose and insulin, homeostatic model assessment of insulin resistance, and results from the oral glucose tolerance test), and compared the results across different categories of age, gender, race/ethnicity, and body mass index.

Results

We found that compared to those in the highest quintile of F statistic, a model-fitness measure with higher values indicating a stronger cosine-like pattern of daily activity, participants in the lowest quintile (i.e, those with the weakest rhythmicity) were 2.37 times more likely to be diabetic (OR Q1 vs. Q5 2.37 (95% CI 1.72, 3.26), p-trend < .0001). Similar patterns were observed for other rest-activity characteristics, including lower amplitude (2.44 (1.60, 3.72)), mesor (1.39 (1.01, 1.91)), and amplitude:mesor ratio (2.09 (1.46, 2.99)), and delayed acrophase (1.46 (1.07, 2.00)). Results were consistent for multiple glycemic biomarkers, and across different sociodemographic and BMI groups.

Conclusions

Our findings support an association between weakened and/or disrupted rest-activity rhythms and impaired glycemic control among a diverse US population.