bluuebunny/crossref_metadata_2025 huggingface dataset:
The orbit and stellar masses of the archetype colliding-wind binary WR 140
Authors: Thomas Joshua D , Richardson Noel D , Eldridge J J , Schaefer Gail H , Monnier John D , Sana Hugues , Moffat Anthony F J , Williams Peredur , Corcoran Michael F , Stevens Ian R , Weigelt Gerd , Zainol Farrah D , Anugu Narsireddy , Le Bouquin Jean-Baptiste , ten Brummelaar Theo , Campos Fran , Couperus Andrew , Davies Claire L , Ennis Jacob , Eversberg Thomas , Garde Oliver , Gardner Tyler , Fló Joan Guarro , Kraus Stefan , Labdon Aaron , Lanthermann Cyprien , Leadbeater Robin , Lester T , Maki Courtney , McBride Brendan , Ozuyar Dogus , Ribeiro J , Setterholm Benjamin , Stober Berthold , Wood Mackenna , Zurmühl Uwe
Published: April 2021

We present updated orbital elements for the Wolf–Rayet (WR) binary WR 140 (HD 193793; WC7pd  + O5.5fc). The new orbital elements were derived using previously published measurements along with 160 new radial velocity measurements across the 2016 periastron passage of WR 140. Additionally, four new measurements of the orbital astrometry were collected with the CHARA Array. With these measurements, we derive stellar masses of $M_{\rm WR} = 10.31\pm 0.45 \, \mathrm{M}_\odot$ and $M_{\rm O} = 29.27\pm 1.14 \, \mathrm{M}_{\odot }$. We also include a discussion of the evolutionary history of this system from the Binary Population and Spectral Synthesis model grid to show that this WR star likely formed primarily through mass-loss in the stellar winds, with only a moderate amount of mass lost or transferred through binary interactions.
Explaining cosmological anisotropy: evidence for causal horizons from CMB data
Authors: Fosalba Pablo , Gaztañaga Enrique
Published: April 2021

The origin of power asymmetry and other measures of statistical anisotropy on the largest scales of the universe, as manifested in cosmic microwave background (CMB) and large-scale structure data, is a long-standing open question in cosmology. In this paper, we analyse the Planck Legacy temperature anisotropy data and find strong evidence for a violation of the Cosmological principle of isotropy, with a probability of being a statistical fluctuation of the order of ∼10−9. The detected anisotropy is related to large-scale directional ΛCDM cosmological parameter variations across the CMB sky, which are sourced by three distinct patches in the maps with circularly averaged sizes between 40° and 70° in radius. We discuss the robustness of our findings to different foreground separation methods and analysis choices, and find consistent results from WMAP data when limiting the analysis to the same scales. We argue that these well-defined regions within the cosmological parameter maps may reflect finite and casually disjoint horizons across the observable universe. In particular, we show that the observed relation between horizon size and mean dark energy density within a given horizon is in good agreement with expectations from a recently proposed model of the universe that explains cosmic acceleration and cosmological parameter tensions between the high- and low-redshift universe from the existence of casual horizons within our universe.
Information content of higher order galaxy correlation functions
Authors: Samushia Lado , Slepian Zachary , Villaescusa-Navarro Francisco
Published: April 2021

The shapes of galaxy N-point correlation functions can be used as standard rulers to constrain the distance–redshift relationship. The cosmological density fields traced by late-time galaxy formation are initially nearly Gaussian, and hence, all the cosmological information can be extracted from their two-point correlation function. Subsequent non-linear evolution under gravity, as well as halo and then galaxy formation, generates higher order correlation functions. Since the mapping of the initial to the final density field is, on large scales, invertible, it is often claimed that the information content of the initial field’s power spectrum is equal to that of all the higher order functions of the final, non-linear field. This claim implies that reconstruction of the initial density field from the non-linear field renders analysis of higher order correlation functions of the latter superfluous. We show that this claim is false when the N-point functions are used as standard rulers. Constraints available from joint analysis of the two and three-point correlation functions can, in some cases, exceed those offered by the initial power spectrum. We provide a mathematical justification for this claim and demonstrate it using a large suite of N-body simulations. In particular, we show that for the z = 0 real-space matter field in the limit of vanishing shot-noise, taking modes up to kmax = 0.2 h Mpc−1, using the bispectrum alone offers a factor of 2 reduction in the variance on the cosmic distance scale relative to that available from the linear power spectrum.
The evolution of the UV luminosity and stellar mass functions of Lyman-α emitters from z ∼ 2 to z ∼ 6
Authors: Santos S , Sobral D , Butterworth J , Paulino-Afonso A , Ribeiro B , da Cunha E , Calhau J , Khostovan A A , Matthee J , Arrabal Haro P
Published: April 2021

We measure the evolution of the rest-frame UV luminosity function (LF) and the stellar mass function (SMF) of Lyman-α (Ly α) emitters (LAEs) from z ∼ 2 to z ∼ 6 by exploring ∼4000 LAEs from the SC4K sample. We find a correlation between Ly α luminosity (LLy α) and rest-frame UV (MUV), with best fit M$_{\rm UV}=-1.6_{-0.3}^{+0.2}\log _{10} (\rm L_{Ly\,\alpha }/erg\, s^{-1})+47_{-11}^{+12}$ and a shallower relation between LLy α and stellar mass (M⋆), with best fit $\log _{10} (\rm M_\star /{\rm M}_\odot)=0.9_{-0.1}^{+0.1}\log _{10} (\rm L_{Ly\,\alpha }/erg\, s^{-1})-28_{-3.8}^{+4.0}$. An increasing LLy α cut predominantly lowers the number density of faint MUV and low M⋆ LAEs. We estimate a proxy for the full UV LFs and SMFs of LAEs with simple assumptions of the faint end slope. For the UV LF, we find a brightening of the characteristic UV luminosity (M$_{\rm UV}^*$) with increasing redshift and a decrease of the characteristic number density (Φ*). For the SMF, we measure a characteristic stellar mass (${\rm M_\star ^*/{\rm M}_\odot }$) increase with increasing redshift, and a Φ* decline. However, if we apply a uniform luminosity cut of $\log _{10} (\rm L_{Ly\,\alpha }/erg\, s^{-1}) \ge 43.0$, we find much milder to no evolution in the UV and SMF of LAEs. The UV luminosity density (ρUV) of the full sample of LAEs shows moderate evolution and the stellar mass density (ρM) decreases, with both being always lower than the total ρUV and ρM of more typical galaxies but slowly approaching them with increasing redshift. Overall, our results indicate that both ρUV and ρM of LAEs slowly approach the measurements of continuum-selected galaxies at z > 6, which suggests a key role of LAEs in the epoch of reionization.
Tangled magnetic field model of QPOs
Authors: Bretz Joseph , van Eysden C A , Link Bennett
Published: April 2021

The highly tangled magnetic field of a magnetar supports shear waves similar to Alfvén waves in an ordered magnetic field. Here, we explore if torsional modes excited in the stellar interior and magnetosphere can explain the quasi-periodic oscillations (QPOs) observed in the tail of the giant flare of SGR 1900+14. We solve the initial value problem for a tangled magnetic field that couples interior shear waves to relativistic Alfvén shear waves in the magnetosphere. Assuming stellar oscillations arise from the sudden release of magnetic energy, we obtain constraints on the energetics and geometry of the process. If the flare energy is deposited initially inside the star, the wave energy propagates relatively slowly to the magnetosphere which is at odds with the observed rise time of the radiative event of ≲ 10 ms. Nor can the flare energy be deposited entirely outside the star, as most of the energy reflects off the stellar surface, giving surface oscillations of insufficient magnitude to produce detectable modulations of magnetospheric currents. Energy deposition in a volume that straddles the stellar surface gives agreement with the observed rise time and excites a range of modes with substantial amplitude at observed QPO frequencies. In general, localized energy deposition excites a broad range of modes that encompasses the observed QPOs, though many more modes are excited than the number of observed QPOs. If the flare energy is deposited axisymmetrically, as is possible for a certain class of MHD instabilities, the number of modes that is excited is considerably reduced.
Dengue virus 2 capsid protein chaperones the strand displacement of 5′-3′ cyclization sequences
Authors: Yong Xin Ee , Palur V Raghuvamsi , Anand Ganesh S , Wohland Thorsten , Sharma Kamal K
Published: April 2021

By virtue of its chaperone activity, the capsid protein of dengue virus strain 2 (DENV2C) promotes nucleic acid structural rearrangements. However, the role of DENV2C during the interaction of RNA elements involved in stabilizing the 5′-3′ panhandle structure of DENV RNA is still unclear. Therefore, we determined how DENV2C affects structural functionality of the capsid-coding region hairpin element (cHP) during annealing and strand displacement of the 9-nt cyclization sequence (5CS) and its complementary 3CS. cHP has two distinct functions: a role in translation start codon selection and a role in RNA synthesis. Our results showed that cHP impedes annealing between 5CS and 3CS. Although DENV2C does not modulate structural functionality of cHP, it accelerates annealing and specifically promotes strand displacement of 3CS during 5′-3′ panhandle formation. Furthermore, DENV2C exerts its chaperone activity by favouring one of the active conformations of cHP. Based on our results, we propose mechanisms for annealing and strand displacement involving cHP. Thus, our results provide mechanistic insights into how DENV2C regulates RNA synthesis by modulating essential RNA elements in the capsid-coding region, that in turn allow for DENV replication.
TIMEOR: a web-based tool to uncover temporal regulatory mechanisms from multi-omics data
Authors: Conard Ashley Mae , Goodman Nathaniel , Hu Yanhui , Perrimon Norbert , Singh Ritambhara , Lawrence Charles , Larschan Erica
Published: April 2021

Uncovering how transcription factors regulate their targets at DNA, RNA and protein levels over time is critical to define gene regulatory networks (GRNs) and assign mechanisms in normal and diseased states. RNA-seq is a standard method measuring gene regulation using an established set of analysis stages. However, none of the currently available pipeline methods for interpreting ordered genomic data (in time or space) use time-series models to assign cause and effect relationships within GRNs, are adaptive to diverse experimental designs, or enable user interpretation through a web-based platform. Furthermore, methods integrating ordered RNA-seq data with protein–DNA binding data to distinguish direct from indirect interactions are urgently needed. We present TIMEOR (Trajectory Inference and Mechanism Exploration with Omics data in R), the first web-based and adaptive time-series multi-omics pipeline method which infers the relationship between gene regulatory events across time. TIMEOR addresses the critical need for methods to determine causal regulatory mechanism networks by leveraging time-series RNA-seq, motif analysis, protein–DNA binding data, and protein-protein interaction networks. TIMEOR’s user-catered approach helps non-coders generate new hypotheses and validate known mechanisms. We used TIMEOR to identify a novel link between insulin stimulation and the circadian rhythm cycle. TIMEOR is available at https://github.com/ashleymaeconard/TIMEOR.git and http://timeor.brown.edu.
Aviator: a web service for monitoring the availability of web services
Authors: Fehlmann Tobias , Kern Fabian , Hirsch Pascal , Steinhaus Robin , Seelow Dominik , Keller Andreas
Published: April 2021

With Aviator, we present a web service and repository that facilitates surveillance of online tools. Aviator consists of a user-friendly website and two modules, a literature-mining based general and a manually curated module. The general module currently checks 9417 websites twice a day with respect to their availability and stores many features (frontend and backend response time, required RAM and size of the web page, security certificates, analytic tools and trackers embedded in the webpage and others) in a data warehouse. Aviator is also equipped with an analysis functionality, for example authors can check and evaluate the availability of their own tools or those of their peers. Likewise, users can check the availability of a certain tool they intend to use in research or teaching to avoid including unstable tools. The curated section of Aviator offers additional services. We provide API snippets for common programming languages (Perl, PHP, Python, JavaScript) as well as an OpenAPI documentation for embedding in the backend of own web services for an automatic test of their function. We query the respective APIs twice a day and send automated notifications in case of an unexpected result. Naturally, the same analysis functionality as for the literature-based module is available for the curated section. Aviator can freely be used at https://www.ccb.uni-saarland.de/aviator.
Sensory Effects of Nicotine and Tobacco
Authors: Carstens Earl , Carstens M Iodi
Published: April 2021

Introduction

Ingestion of nicotine by smoking, vaping, or other means elicits various effects including reward, antinociception, and aversion due to irritation, bitter taste, and unpleasant side effects such as nausea and dizziness.

Aims and Methods

Here we review the sensory effects of nicotine and the underlying neurobiological processes.

Results and Conclusions

Nicotine elicits oral irritation and pain via the activation of neuronal nicotinic acetylcholine receptors (nAChRs) expressed by trigeminal nociceptors. These nociceptors excite neurons in the trigeminal subnucleus caudalis (Vc) and other brainstem regions in a manner that is significantly reduced by the nAChR antagonist mecamylamine. Vc neurons are excited by lingual application of nicotine and exhibit a progressive decline in firing to subsequent applications, consistent with desensitization of peripheral sensory neurons and progressively declining ratings of oral irritation in human psychophysical experiments. Nicotine also elicits a nAChR-mediated bitter taste via excitation of gustatory afferents. Nicotine solutions are avoided even when sweeteners are added. Studies employing oral self-administration have yielded mixed results: Some studies show avoidance of nicotine while others report increased nicotine intake over time, particularly in adolescents and females. Nicotine is consistently reported to increase human pain threshold and tolerance levels. In animal studies, nicotine is antinociceptive when delivered by inhalation of tobacco smoke or systemic infusion, intrathecally, and by intracranial microinjection in the pedunculopontine tegmentum, ventrolateral periaqueductal gray, and rostral ventromedial medulla. The antinociception is thought to be mediated by descending inhibition of spinal nociceptive transmission. Menthol cross-desensitizes nicotine-evoked oral irritation, reducing harshness that may account for its popularity as a flavor additive to tobacco products.

Implications

Nicotine activates brain systems underlying reward and antinociception, but at the same time elicits aversive sensory effects including oral irritation and pain, bitter taste, and other unpleasant side effects mediated largely by nicotinic acetylcholine receptors (nAChRs). This review discusses the competing aversive and antinociceptive effects of nicotine and exposure to tobacco smoke, and the underlying neurobiology. An improved understanding of the interacting effects of nicotine will hopefully inform novel approaches to mitigate nicotine and tobacco use.
DOTFL1 affects the floral transition in orchid Dendrobium Chao Praya Smile
Authors: Li Yan , Zhang Bin , Wang Yanwen , Gong Ximing , Yu Hao
Published: April 2021

A major obstacle for orchid (Orchidaceae) breeding and production is a long juvenile phase before orchid reproductive development. The molecular basis for prolonged vegetative growth in orchids remains largely unclear despite many efforts to clarify the relevant mechanisms. In this study, we report functional characterization of Dendrobium Orchid TERMINAL FLOWER1 (DOTFL1), an ortholog of TFL1 in Arabidopsis (Arabidopsis thaliana), from the orchid Dendrobium Chao Praya Smile. DOTFL1 is highly expressed in pseudobulbs and the shoot apical meristem (SAM) before and during the floral transition, but is downregulated in inflorescence apices and open flowers. Ectopic expression of DOTFL1 rescues the early-flowering and terminal-flower phenotypes of tfl1-20 in Arabidopsis. Overexpression of DOTFL1 in Dendrobium orchids delays flowering and produces defective inflorescence meristems and flowers with vegetative traits, whereas knockdown of DOTFL1 accelerates flowering and perturbs the maintenance of the inflorescence meristem. Notably, DOTFL1 suppresses orchid flowering and associated pseudobulb formation during the floral transition. We further reveal that two orchid MADS-box transcription factors, Dendrobium Orchid SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (DOSOC1) and AGAMOUS-LIKE 24 (DOAGL24), could interact with each other and bind to the CArG-box motif at DOTFL1, implying a regulatory hierarchy similar to their counterparts in Arabidopsis. Taken together, our findings suggest that DOTFL1 promotes vegetative growth, modulates successive developmental events required for reproductive success in Dendrobium orchids, and may have evolved with a previously unknown role in controlling pseudobulb formation in the Orchidaceae family.
Entiers Ultrafriables En Progressions Arithmétiques
Authors: Dartyge Cécile , Feutrie David , Tenenbaum Gérald
Published: April 2021

A natural integer is called y-ultrafriable if none of the prime powers occurring in its canonical decomposition exceed y. We investigate the distribution of y-ultrafriable integers not exceeding x among arithmetic progressions to the modulus q. Given a sufficiently small, positive constant ɛ, we obtain uniform estimates valid for $q\leqslant y^{c/\log_2y}$ whenever $\log y\leqslant (\log x)^\varepsilon$, and for $q\leqslant \sqrt{y}$ if $(\log x)^{2+\varepsilon}\leqslant y\leqslant x$.
The role of PD-1/PD-Ls in the pathogenesis of IgG4-related disease
Authors: Zhang Xia , Lu Hui , Peng Linyi , Zhou Jiaxin , Wang Mu , Li Jieqiong , Liu Zheng , Zhang Wen , Zhao Yan , Zeng Xiaofeng , Lu Liwei
Published: April 2021

Objective

To investigate the role of programmed cell death protein 1 (PD-1) and its two ligands, PD-L1 and PD-L2, in the pathogenesis of IgG4-related disease (IgG4-RD).

Methods

Patients with IgG4-RD (n = 43) and healthy controls (n = 34) were recruited. Expression levels of PD-1, PD-L1 and PD-L2 in plasma, submandibular gland and T cell subsets were determined by ELISA, immunohistochemistry and flow cytometry. Naïve T cells were stimulated with or without PD-L1/PD-L2 or anti-PD-L1/anti-PD-L2 for 7 days and the proportion of CD4+CD25+ Treg cells was detected by flow cytometry.

Results

The expression of PD-1, PD-L1 and PD-L2 in the plasma, submandibular gland and on the surface of Treg cells was increased in IgG4-RD patients. Plasma soluble (s)PD-1 was positively correlated with serum IgG, IgG1, IgG3, IgG4, IgG4-RD responder index and numbers of organs involved, and negatively correlated with serum IgM, IgA, C3 and C4. Plasma sPD-L2 was positively correlated with serum IgG1, and plasma sPD-L1 was positively correlated with sPD-L2 and negatively correlated with C3. Stimulation of PD-L1 but not PD-L2 promoted the differentiation of naïve T cells from IgG4-RD patients into CD4+CD25+ Treg cells.

Conclusion

Plasma concentrations of sPD-1, sPD-L1 and sPD-L2 were significantly increased in patients with IgG4-RD, and the expression of PD-1 and PD-L2 on Treg cells was upregulated. PD-1–PD-L1 can promote the differentiation of naïve T cells into Treg cells and thus participate in the pathogenesis of IgG4-RD.
Relationship Between White Matter Microstructure and Hallucination Severity in the Early Stages of Psychosis: A Diffusion Tensor Imaging Study
Authors: Sato Yutaro , Sakuma Atsushi , Ohmuro Noriyuki , Katsura Masahiro , Abe Koichi , Tomimoto Kazuho , Iizuka Kunio , Ito Fumiaki , Tomita Hiroaki , Matsumoto Kazunori
Published: April 2021

Background

Diffusion tensor imaging (DTI) studies have investigated the relationship between hallucinations in schizophrenia and white matter (WM) microstructure. However, only a few studies have focused on hallucination severity in the early stages of psychosis, and the involvement of the WM microstructure in the development of hallucinations remains unclear. This study aimed to examine the WM microstructure related to hallucination severity in the early stages of psychosis.

Methods

DTI analysis using tract-based spatial statistics (TBSS) was applied to 138 participants, consisting of 105 individuals with early stages of psychosis (56 individuals with clinical high risk for psychosis [CHR] and 49 individuals with first-episode psychosis [FEP]) and 33 healthy controls (HCs). Group comparisons of fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) were performed. We examined the association of FA, MD, RD, and AD with hallucination severity in the early stages of psychosis.

Results

Lower FA and higher MD and RD in multiple WM tracts were observed in the early stages of psychosis compared to HCs. We found an association between hallucination severity and increased MD in the WM tract, consisting mainly of the left superior longitudinal fasciculus (SLF) and inferior fronto-occipital fasciculus (IFOF).

Conclusions

Our findings indicate that dysconnectivity in brain networks associated with language processing is related to the development of hallucinations. Further studies of the early stages of psychosis are needed to elucidate the mechanism of hallucinations.
Worksite Temperature Screening for COVID-19
Authors: Stave Gregg M. , Smith Sharon E. , Hymel Pamela A. , Heron Richard J.L.
Published: April 2021

Objective:

To determine whether temperature screening is useful in detecting and reducing workplace transmission of SARS-CoV-2.

Methods:

A survey was conducted to determine whether temperature screening successfully identified workers with coronavirus disease 2019 (COVID-19) among a convenience sample of medical directors of multinational corporations in a wide range of industries.

Results:

More than 15 million screenings were performed by 14 companies. Fewer than 700 episodes of fever were identified. Of these, only about 53 cases of COVID-19 were detected. By contrast about 2000 workers with diagnosed COVID-19 were in the workplace and not detected by screening.

Conclusions:

One case of COVID-19 was identified by screening for approximately every 40 cases that were missed. Worksite temperature screening was ineffective for detecting workers with COVID-19 and is not recommended.
Environmental DNA metabarcoding reveals and unpacks a biodiversity conservation paradox in Mediterranean marine reserves
Authors: Boulanger Emilie , Loiseau Nicolas , Valentini Alice , Arnal Véronique , Boissery Pierre , Dejean Tony , Deter Julie , Guellati Nacim , Holon Florian , Juhel Jean-Baptiste , Lenfant Philippe , Manel Stéphanie , Mouillot David
Published: April 2021

Although we are currently experiencing worldwide biodiversity loss, local species richness does not always decline under anthropogenic pressure. This conservation paradox may also apply in protected areas but has not yet received conclusive evidence in marine ecosystems. Here, we survey fish assemblages in six Mediterranean no-take reserves and their adjacent fishing grounds using environmental DNA (eDNA) while controlling for environmental conditions. We detect less fish species in marine reserves than in nearby fished areas. The paradoxical gradient in species richness is accompanied by a marked change in fish species composition under different managements. This dissimilarity is mainly driven by species that are often overlooked by classical visual surveys but detected with eDNA: cryptobenthic, pelagic, and rare fishes. These results do not negate the importance of reserves in protecting biodiversity but shed new light on how under-represented species groups can positively react to fishing pressure and how conservation efforts can shape regional biodiversity patterns.
Litoribacterium kuwaitense gen. nov., sp. nov., isolated from a Kuwait tidal flat
Authors: Mahmoud Huda , Eapen Susan , Al-Bajjali Fatimah , Al-Qattan Anwar , Jose Liny
Published: April 2021

A Gram-stain-positive, strictly aerobic, spore-forming, rod-shaped and non-motile bacterium designated strain SIJ1T was obtained from tidal flat sediment collected from the northern shore of Kuwait Bay, northwest of the Arabian Gulf. Strain SIJ1T grew optimally at 30 °C and pH 7–8 in the presence of 6 % (w/v) NaCl. The cell-wall peptidoglycan was based on meso-diaminopimelic acid and an unsaturated menaquinone with seven isoprene units (MK-7) was the predominant respiratory quinone. It contained anteiso-C15 : 0, iso-C16 : 0 and iso-C15 : 0 as the major fatty acids and ribose as the major whole-cell sugar. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, unidentified phospholipid, an unidentified glycolipid, phosphoglycolipid and an unidentified lipid. Phylogenetic analysis based on 16S rRNA genes revealed that SIJ1T showed a distinct evolutionary lineage within the Firmicutes. The DNA G+C content was 43.1 mol% and the full genome analysis for strain SIJ1T showed that it had a genome size of 3 989 945 bp and contained 4085 predicted protein-encoding genes. The SIJ1T annotated genome showed more stress resistance encoding genes in comparison to its closely related strains. The amino acid identity and average nucleotide identity data for the whole genome proved that strain SIJ1T does indeed represent a novel genus. The strain was distinguishable from the phylogenetically related genera through differences in several phenotypic properties. On the basis of the phenotypic, phylogenetic and genetic data, strain SIJ1T represents a novel genus and species in the family Bacillaceae, for which the name Litoribacterium kuwaitense gen. nov., sp. nov. is proposed. The type strain is SIJ1T (=DSM 28862T=LMG 28316T).
High proportion of post-acute sequelae of SARS-CoV-2 infection in individuals 1-6 months after illness and association with disease severity in an outpatient telemedicine population
Authors: O’Keefe James B. , Minton H. Caroline , Johnson Colin , Moore Miranda A. , O’Keefe Ghazala A. D. , Benameur Karima , Higdon Jason , Fairley Jessica K.
Published: April 2021

Background

Individuals with coronavirus disease 2019 (COVID-19) may have persistent symptoms following their acute illness. The prevalence and predictors of these symptoms, termed post-acute sequelae of SARS-CoV-2 (PASC), are not fully described.

Methods

Participants discharged from an outpatient telemedicine program for COVID-19 were emailed a survey (1-6 months after discharge) about ongoing symptoms, acute illness severity, and quality of life. Standardized telemedicine notes from acute illness were used for covariates (comorbidities and provider-assessed symptom severity). Bivariate and multivariable analyses were performed to assess predictors of persistent symptoms.

Results

Two hundred and ninety patients completed the survey, of whom 115 (39.7%) reported persistent symptoms including fatigue (n= 59, 20.3%), dyspnea on exertion (n=41, 14.1%), and mental fog (n=39, 13.5%) among others. Proportion of persistent symptoms did not differ based on duration since illness (<90 days: n=32, 37.2% versus>90 days: n=80, 40.4%, p = 0.61). Predictors of persistent symptoms included provider-assessed moderate-severe illness (aOR 3.24, 95% CI 1.75, 6.02), female sex (aOR 1.99 95% 0.98, 4.04; >90 days out: aOR 2.24 95% CI 1.01, 4.95), and middle age (aOR 2.08 95% CI 1.07, 4.03). Common symptoms associated with reports of worse physical health included weakness, fatigue, myalgias, and mental fog.

Conclusions

Symptoms following acute COVID-19 are common and may be predicted by factors during the acute phase of illness. Fatigue and neuropsychiatric symptoms figured prominently. Select symptoms seem to be particularly associated with perceptions of physical health following COVID-19 and warrant specific attention on future studies of PASC.
Association of single nucleotide polymorphisms in XRCC1 and ATM with recurrence in patients with cervical cancer
Authors: Cho Soo Youn , Kim Kidong , Ryu Sang Young , Kim Moon-Hong , Kim Beob-Jong
Published: April 2021

Objective

The primary objective of this study was to determine the association of the genotype of X-ray repair complementing defective repair in Chinese hamster cell 1 (XRCC1) 580C>T with recurrence-free survival (RFS) in patients with cervical cancer who underwent radical surgery followed by adjuvant concurrent chemoradiation (CRT). Secondary objectives were to assess 1) the association of single nucleotide polymorphisms (SNPs) in XRCC1 and ataxia telangiectasia mutated (ATM) gene with RFS, overall survival (OS) and completion of CRT, 2) the association of haplotypes of XRCC1 and ATM with RFS, OS and completion of CRT, 3) concordance rate between genotypes from cancer tissue and that from normal tissue and 4) the association of clinicopathologic variables with RFS and OS.

Materials and Methods

Clinicopathologic variables were extracted from medical records of 159 patients who underwent radical hysterectomy followed by adjuvant CRT in a cancer center between 1999 and 2004. After exclusion of six patients without paraffin blocks, 153 patients were included in this study. DNA was extracted from a formalin-fixed, paraffin embedded tissue block containing tumor tissue and another block containing uninvolved lymph node. Genotyping for XRCC1 580C>T (rs 1799782), XRCC1 1196A>G (rs 25487), ATM 3078-77C>T (rs 664677), ATM 5557G>A (rs 1801516) and ATM 6807+238G>C (rs609429) was performed using pyrosequencing. Haplotype estimation was performed using haplo.stats in R version 2.15.0. The association of genotype or haplotype of SNPs with RFS, OS and completion of CRT was evaluated via Cox regression analysis, chi-square or Fisher’s exact test. The concordance rate between genotype from cancer tissue and that from normal tissue was examined according to SNP. The association of clinicopathologic variables with RFS and OS was estimated via Cox regression analysis.

Results

None of SNPs was associated with RFS, OS and completion of CRT. Concordance rate between genotype from cancer tissue and that from normal tissue for XRCC1 580C>T, XRCC1 1196A>G, ATM 3078-77C>T, ATM 5557G>A and ATM 6807+238G>C were 72%, 88%, 73%, 100% and 54%, respectively. Age, stage, histologic type, LVSI and parametrial invasion were associated with RFS, and clinical tumor size, resection margin, lymph node involvement and completion of CRT were associated with OS.

Conclusion

Genotype of XRCC1 580C>T was not associated with RFS in patients with cervical cancer who underwent radical surgery followed by adjuvant CRT. Low concordance rate between cancer and germline genotype was identified in cervical cancer.
Professionals’ views on the mental health problems and vulnerability of children and young people during the early phase of the COVID-19 pandemic
Authors: Edbrooke-Childs Julian , Labno Angelika , Cortina Melissa A. , Gilleard Anna , Hayes Daniel , Yoon Yeosun , Dalton-Locke Christian , Johnson Sonia , Simpson Alan , Vera San Juan Norha , Brooks-Hall Ellie ,   Mental Health Policy Research Unit
Published: April 2021

The COVID-19 pandemic caused major disruptions to everyday life for children and young people. The aim of this study was to examine professionals’ views on the mental health problems and vulnerabilities of children and young people during the early phase of the COVID-19 pandemic. We conducted a secondary analysis of an online survey completed by mental health professionals in the UK between 22 April 2020 and 12 May 2020. The final sample was N = 601 professionals who at least partly worked with children and young people. Quantitative and qualitative survey data showed that professionals were concerned about young people experiencing economic disadvantage and young people from minority ethnic groups, as pre-existing social inequalities resulted in increased risk of infection and reduced access to physical and mental health care. Professionals were concerned about young people with little family support and young people at risk of relapse or deterioration in mental health, reporting the exacerbation of pre-existing mental health difficulties and challenging behaviours. Further research, involving young people as researchers, is needed to explore the continued impact for children and young people, and their families, including in comparison to their experiences before the pandemic.
Reopening California : Seeking Robust, Non-Dominated COVID-19 Exit Strategies
Authors: de Lima Pedro Nascimento , Lempert Robert , Vardavas Raffaele , Baker Lawrence , Ringel Jeanne , Rutter Carolyn M. , Ozik Jonathan , Collier Nicholson
Published: April 2021

Amid global scarcity of COVID-19 vaccines and the threat of new variant strains, California and other jurisdictions face the question of when and how to implement and relax COVID-19 Nonpharmaceutical Interventions (NPIs). While policymakers have attempted to balance the health and economic impacts of the pandemic, decentralized decision-making, deep uncertainty, and the lack of widespread use of comprehensive decision support methods can lead to the choice of fragile or inefficient strategies. This paper uses simulation models and the Robust Decision Making (RDM) approach to stress-test California’s reopening strategy and other alternatives over a wide range of futures. We find that plans which respond aggressively to initial outbreaks are required to robustly control the pandemic. Further, the best plans adapt to changing circumstances, lowering their stringent requirements to reopen over time or as more constituents are vaccinated. While we use California as an example, our results are particularly relevant for jurisdictions where vaccination roll-out has been slower.
COVID-19 vaccine willingness and cannabis use histories
Authors: Spechler Philip A. , Stewart Jennifer L. , Kuplicki Rayus ,   the Tulsa 1000 Investigators, Paulus Martin P.
Published: April 2021

Background

Cannabis use is associated with problematic health-behaviors such as excessive alcohol and tobacco use, and sedentary behavior. Here, we examined the association between cannabis use history and an especially topical health-behavior, willingness to receive a COVID-19 vaccine.

Methods

COVID-19 vaccine willingness was surveyed in a subset of participants from the Tulsa 1000 Study, which is a longitudinal study of psychiatric treatment-seeking and healthy control participants. We identified 45 participants who completed a COVID-19 vaccine questionnaire and reported more than 10 lifetime cannabis uses. Those participants were compared to a group of 45 individuals with very light (<10) cannabis use histories who were propensity score-matched on age, sex, income, and race. Two-group t-tests and Bayes factor analysis on vaccine willingness were conducted between groups. Exploratory correlation analyses were conducted on vaccine willingness and lifetime cannabis use levels within the cannabis group only.

Results

Vaccine willingness did not differ between the two groups (t88=0.33, p=.74; BF01=4.3). However, a negative correlation was identified within the cannabis group, such that higher lifetime cannabis use histories correlated with less willingness to receive a vaccine (rho43= -.33, p=.03).

Conclusions

Although vaccine willingness did not differ between the two matched groups, preliminary evidence suggests that heavy lifetime cannabis use might indicate a reluctance to engage in health-promoting behaviors like receiving a COVID-19 vaccine.
Local density determines nuclear movements during syncytial blastoderm formation in a cricket
Authors: Donoughe Seth , Hoffmann Jordan , Nakamura Taro , Rycroft Chris H. , Extavour Cassandra G.
Published: April 2021

Animal embryos pass through an early stage called the blastoderm, in which cells are arranged in a continuous layer at the periphery of the embryo. Despite the broad evolutionary conservation of this embryonic stage, the cellular behaviours that lead to blastoderm formation vary across animals, and the mechanisms that regulate these behaviours are poorly understood. In most insects, pre-blastoderm development begins as a syncytium: that is, many nuclei divide and move throughout the single shared cytoplasm of the embryo. Then these syncytial nuclei must move from their scattered positions within the cytoplasm to form a single layer at the cortex. Recent work showed that in the fruit flyDrosophila melanogaster, some of these early nuclear movements are caused by pulses of cytoplasmic flows that are coupled to synchronous divisions. Here, we show that the cricketGryllus bimaculatushas an altogether different solution to the problem. We quantified nuclear dynamics during the period of syncytial cleavages and movements that lead to blastoderm formation inG. bimaculatusembryos with transgenically labeled nuclei. We found that: (1) cytoplasmic flows were unimportant for nuclear movement, and (2) division cycles, nuclear speeds, and the directions of nuclear movement were not synchronized across the embryo as inD. melanogaster, but instead were heterogeneous in space and time. Moreover, several aspects of nuclear divisions and movements were correlated with local nuclear density. We show that previously proposed models for the movement ofD. melanogastersyncytial nuclei cannot explain the behaviours ofG. bimaculatussyncytial nuclei. We introduce a novel geometric model based on asymmetric local pulling forces on nuclei, which recapitulates the density-dependent nuclear speeds and orientations of unperturbedG. bimaculatusembryos, without invoking the common paradigms of localized polarity cues or cell lineage as determinants of nuclear activity. Our model also accurately predicts nuclear behavior in embryos physically manipulated to contain regions of atypical nuclear densities. We show that this model can be used to generate falsifiable predictions about the dynamics of blastoderm formation in other insect species.
CellDART: Cell type inference by domain adaptation of single-cell and spatial transcriptomic data
Authors: Bae Sungwoo , Na Kwon Joong , Koh Jaemoon , Lee Dong Soo , Choi Hongyoon , Kim Young Tae
Published: April 2021

Deciphering the cellular composition in genome-wide spatially resolved transcriptomic data is a critical task to clarify the spatial context of cells in a tissue. In this study, we developed a method, CellDART, which estimates the spatial distribution of cells defined by single-cell level data using domain adaptation of neural networks and applied it to the spatial mapping of human lung tissue. The neural network that predicts the cell proportion in a pseudospot, a virtual mixture of cells from single-cell data, is translated to decompose the cell types in each spatial barcoded region. First, CellDART was applied to mouse brain and human dorsolateral prefrontal cortex tissue to identify cell types with a layer-specific spatial distribution. Overall, the suggested approach was competent to the other computational methods in predicting the spatial localization of excitatory neurons. Besides, CellDART was capable of decomposing cellular proportion in mouse hippocampus Slide-seq data. Furthermore, CellDART elucidated the cell type predominance defined by the human lung cell atlas across the lung tissue compartments and it corresponded to the known prevalent cell types. CellDART is expected to help to elucidate the spatial heterogeneity of cells and their close interactions in various tissues.
The RNA m6A reader YTHDF2 controls NK cell anti-tumor and anti-viral immunity
Authors: Ma Shoubao , Yan Jiazhuo , Barr Tasha , Zhang Jianying , Chen Zhenhua , Wang Li-Shu , Sun Joseph C. , Chen Jianjun , Caligiuri Michael A , Yu Jianhua
Published: April 2021

N6-methyladenosine (m6A) is the most prevalent post-transcriptional modification on RNA. NK cells are the predominant innate lymphoid cells that mediate anti-viral and anti-tumor immunity. However, whether and how m6A modifications affect NK cell immunity remains unknown. Here, we discover that YTHDF2, a well-known m6A reader, is upregulated in NK cells upon activation by cytokines, tumors, and cytomegalovirus infection.Ythdf2deficiency in NK cells impairs NK cell anti-tumor and anti-viral activityin vivo. YTHDF2 maintains NK cell homeostasis and terminal maturation, correlating with modulating NK cell trafficking and regulating Eomes, respectively. YTHDF2 promotes NK cell effector function and is required for IL-15-mediated NK cell survival and proliferation by forming a STAT5-YTHDF2 positive feedback loop. Transcriptome-wide screening identifiesTardbpto be involved in cell proliferation or survival as a YTHDF2-binding target in NK cells. Collectively, we elucidate the biological roles of m6A modifications in NK cells and highlight a new direction to harness NK cell anti-tumor immunity.
An Ohio State Scenic River Shows Elevated Antibiotic Resistance Genes, IncludingAcinetobacterTetracycline and Macrolide Resistance, Downstream of Wastewater Treatment Plant Effluent
Authors: Murphy April , Barich Daniel , Fennessy Siobhan , Slonczewski Joan L.
Published: April 2021

The entry of antibiotic resistance genes (ARGs) into aquatic systems has been documented for large municipal wastewater treatment plants, but there is less study of the impact of smaller plants that are situated on small rural rivers. We sampled water metagenomes for ARG and taxa composition from the Kokosing River, a small rural river in Knox County, Ohio, which has been designated an Ohio State Scenic River for retention of natural character. Samples were obtained 1.0 km upstream, 120 m downstream, and 6.4 km downstream from the effluent release of the Mount Vernon wastewater treatment plant (WWTP). ARGS were identified in metagenomes using ShortBRED markers from the CARD database screened against UniPROT. Through all seasons, the metagenome just downstream of the WWTP effluent showed a substantial elevation of at least 15 different ARGs, including 6 ARGs commonly associated withAcinetobacter baumanniisuch asmsrE, mphE(macrolide resistance) andtet(39) (tetracycline resistance). The ARGs most prevalent near the effluent pipe persisted 6.4 km downriver. Using MetaPhlAn2 clade-specific marker genes, the taxa distribution near the effluent showed elevation of reads annotated asAcinetobacterspecies as well as gut-associated taxa, Bacteroides and Firmicutes. The ARG levels and taxa prevalence showed little dependence on seasonal chlorination of the effluent. Nitrogen and phosphorus were elevated near the effluent pipe but had no consistent correlation with ARG levels. We show that in a rural river microbiome, year-round wastewater effluent substantially elevates ARGs including those associated with multidrug-resistantA. baumanii.

IMPORTANCE

Antibiotic resistance is a growing problem worldwide, with frequent transmission between pathogens and environmental organisms. Rural rivers can support high levels of recreational use by people unaware of inputs from treated wastewater, while WWTPs can generate a small but significant portion of flow volume into a river surrounded by forest and agriculture. There is little information on the rural impacts of WWTP effluent on the delivery and transport of antibiotic resistance genes. In our study, the river water proximal to wastewater effluent shows evidence for the influx of multidrug-resistantAcinetobacter baumanii, an opportunistic pathogen of concern for hospitals but also widespread in natural environments. Our work highlights the importance of wastewater effluent in management of environmental antibiotic resistance, even in high quality, rural river systems.
Rapid and simultaneous identification of three mutations by the Novaplex™ SARS-CoV-2 Variants I Assay kit
Authors: Kami Wakaki , Kinjo Takeshi , Arakaki Wakako , Oki Hiroya , Motooka Daisuke , Nakamura Shota , Fujita Jiro
Published: April 2021

Background

The emergence of SARS-CoV-2 variants has caused an unexpected rebound globally. The World Health Organization has listed three variants (B.1.1.7, B.1.351, and P.1) as variants of concern. To understand the epidemiology and thereby plan appropriate safety measures, differential identification of the variants is indeed critical.

Objectives

Although whole-genome sequencing is the gold standard for variant identification, it is time-consuming and relatively expensive. Therefore, a rapid, easy, and cost-effective platform targeting multiple regions of the genome is required. Here, we assessed the usefulness of the Novaplex™ SARS-CoV-2 Variants I Assay kit in identifying mutations in the variants.

Study design

We retrospectively examined 30 stored nasal swabs from COVID-19-positive patients tested between November 2020 and March 2021. RNA extracted from these swabs was subjected to the commercial kit and real-time reverse transcription-PCR was performed. To determine the genome sequences of SARS-CoV-2 in the collected samples and deduce the consensus sequences among the identified variants, genome sequencing libraries were prepared and mapped to the reference genome.

Results

Four of the tested samples were determined as variants. Of them, two harbored both H69/V70 deletion and N501Y substitution, whereas two harbored E484K substitution alone.

Conclusions

The variant with E484K substitution alone (“R.1”) has been now categorized as a variant of interest in Japan. Additionally, the kit-based assay was found to be feasible, convenient, and user-friendly in identifying the abovementioned mutations with a turnaround time of only 2 hours.
Optimism and pessimism in optimised replay
Authors: Antonov Georgy , Gagne Christopher , Eldar Eran , Dayan Peter
Published: April 2021

The replay of task-relevant trajectories is known to contribute to memory consolidation and improved task performance. A wide variety of experimental data show that the content of replayed sequences is highly specific and can be modulated by reward as well as other prominent task variables. However, the rules governing the choice of sequences to be replayed still remain poorly understood. One recent theoretical suggestion is that the prioritization of replay experiences in decision-making problems is based on their effect on the choice of action. We show that this implies that subjects should replay sub-optimal actions that they dysfunctionally choose rather than optimal ones, when, by being forgetful, they experience large amounts of uncertainty in their internal models of the world. We use this to account for recent experimental data demonstrating exactly pessimal replay, fitting model parameters to the individual subjects’ choices.