bluuebunny/crossref_metadata_2025 huggingface dataset:
The thermalization of massive galaxy clusters
Authors: Sereno Mauro , Lovisari Lorenzo , Cui Weiguang , Schellenberger Gerrit
Published: August 2021

In the hierarchical scenario of structure formation, galaxy clusters are the ultimate virialized products in mass and time. Hot baryons in the intracluster medium (ICM) and cold baryons in galaxies inhabit a dark matter dominated halo. Internal processes, accretion, and mergers can perturb the equilibrium, which is established only at later times. However, the cosmic time when thermalization is effective is still to be assessed. Here, we show that massive clusters in the observed universe attained an advanced thermal equilibrium ∼1.8 Gyr ago, at redshift z = 0.14 ± 0.06, when the universe was 11.7 ± 0.7 Gyr old. Hot gas is mostly thermalized after the time when cosmic densities of matter and dark energy match. We find in a statistically nearly complete and homogeneous sample of 120 clusters from the Planck Early Sunyaev-Zel’dovich (ESZ) sample that the kinetic energy traced by the galaxy velocity dispersion is a faithful probe of the gravitational energy since a look back time of at least ∼5.4 Gyr, whereas the efficiency of hot gas in converting kinetic to thermal energy, as measured through X-ray observations in the core-excised area within r500, steadily increases with time. The evolution is detected at the ∼98 per cent probability level. Our results demonstrate that halo mass accretion history plays a larger role for cluster thermal equilibrium than radiative physics. The evolution of hot gas is strictly connected to the cosmic structure formation.
The abundance of satellites around Milky Way- and M31-like galaxies with the TNG50 simulation: a matter of diversity
Authors: Engler Christoph , Pillepich Annalisa , Pasquali Anna , Nelson Dylan , Rodriguez-Gomez Vicente , Chua Kun Ting Eddie , Grebel Eva K , Springel Volker , Marinacci Federico , Weinberger Rainer , Vogelsberger Mark , Hernquist Lars
Published: August 2021

We study the abundance of satellite galaxies around 198 Milky Way- (MW) and M31-like hosts in TNG50, the final installment in the IllustrisTNG suite of cosmological magnetohydrodynamical simulations. MW/M31-like analogues are defined as discy galaxies with stellar masses of $M_* = 10^{10.5 - 11.2}~\rm {M}_\odot$ in relative isolation at z = 0. By defining satellites as galaxies with $M_* \ge 5\times 10^{6}~\rm {M}_\odot$ within $300~\rm {kpc}$ (3D) of their host, we find a remarkable level of diversity and host-to-host scatter across individual host galaxies. The median TNG50 MW/M31-like galaxy hosts a total of $5^{+6}_{-3}$ satellites with $M_* \ge 8 \times 10^6~\rm {M}_\odot$, reaching up to $M_* \sim 10^{8.5^{+0.9}_{-1.1}}~\rm {M}_\odot$. Even at a fixed host halo mass of $10^{12}~\rm {M}_\odot$, the total number of satellites ranges between 0 and 11. The abundance of subhaloes with $M_\rm {dyn} \ge 5 \times 10^7~\rm {M}_\odot$ is larger by a factor of more than 10. The number of all satellites (subhaloes) ever accreted is larger by a factor of 4–5 (3–5) than those surviving to z = 0. Hosts with larger galaxy stellar mass, brighter K-band luminosity, more recent halo assembly, and – most significantly – larger total halo mass typically have a larger number of surviving satellites. The satellite abundances around TNG50 MW/M31-like galaxies are consistent with those of mass-matched hosts from observational surveys (e.g. SAGA) and previous simulations (e.g. Latte). While the observed MW satellite system falls within the TNG50 scatter across all stellar masses considered, M31 is slightly more satellite-rich than our 1σ scatter but well consistent with the high-mass end of the TNG50 sample. We find a handful of systems with both a Large and a Small Magellanic Cloud-like satellite. There is no missing satellites problem according to TNG50.
Central kinematics of the Galactic globular cluster M80
Authors: Göttgens Fabian , Kamann Sebastian , Baumgardt Holger , Dreizler Stefan , Giesers Benjamin , Husser Tim-Oliver , den Brok Mark , Fétick Romain , Krajnovic Davor , Weilbacher Peter M
Published: August 2021

We use spectra observed with the integral-field spectrograph Multi Unit Spectroscopic Explorer (MUSE) to reveal the central kinematics of the Galactic globular cluster Messier 80 (M80, NGC 6093). Using observations obtained with the recently commissioned narrow-field mode of MUSE, we are able to analyse 932 stars in the central 7.5 arcsec by 7.5 arcsec of the cluster for which no useful spectra previously existed. Mean radial velocities of individual stars derived from the spectra are compared to predictions from axisymmetric Jeans models, resulting in radial profiles of the velocity dispersion, the rotation amplitude, and the mass-to-light ratio. The new data allow us to search for an intermediate-mass black hole (IMBH) in the centre of the cluster. Our Jeans model finds two similarly probable solutions around different dynamical cluster centres. The first solution has a centre close to the photometric estimates available in the literature and does not need an IMBH to fit the observed kinematics. The second solution contains a location of the cluster centre that is offset by about 2.4 arcsec from the first one and it needs an IMBH mass of $4600^{+1700}_{-1400}~\text{M}_\odot {}$. N-body models support the existence of an IMBH in this cluster with a mass of up to 6000 M⊙ in this cluster, although models without an IMBH provide a better fit to the observed surface brightness profile. They further indicate that the cluster has lost nearly all stellar-mass black holes. We further discuss the detection of two potential high-velocity stars with radial velocities of 80–90 $\text{km}\, \text{s}^{-1}$ relative to the cluster mean.
Press–Schechter primordial black hole mass functions and their observational constraints
Authors: Sureda Joaquín , Magaña Juan , Araya Ignacio J , Padilla Nelson D
Published: August 2021

We present a modification of the Press–Schechter (PS) formalism to derive general mass functions for primordial black holes (PBHs), considering their formation as being associated with the amplitude of linear energy density fluctuations. To accommodate a wide range of physical relations between the linear and non-linear conditions for collapse, we introduce an additional parameter to the PS mechanism, and that the collapse occurs at either a given cosmic time, or as fluctuations enter the horizon. We study the case where fluctuations obey Gaussian statistics and follow a primordial power spectrum of broken power-law form with a blue spectral index for small scales. We use the observed abundance of supermassive black holes (SMBH) to constrain the extended mass functions taking into account dynamical friction. We further constrain the modified PS by developing a method for converting existing constraints on the PBH mass fraction, derived assuming monochromatic mass distributions for PBHs, into constraints applicable for extended PBH mass functions. We find that when considering well-established monochromatic constraints, there are regions in parameter space where all the dark matter can be made of PBHs. Of special interest is the region for the characteristic mass of the distribution ${\sim}10^2\, \mathrm{M}_\odot$, for a wide range of blue spectral indices in the scenario where PBHs form as they enter the horizon, where the linear threshold for collapse is of the order of the typical overdensities, as this is close to the black hole masses detected by LIGO, which are difficult to explain by stellar collapse.
The spatial distribution of Milky Way satellites, gaps in streams, and the nature of dark matter
Authors: Lovell Mark R , Cautun Marius , Frenk Carlos S , Hellwing Wojciech A , Newton Oliver
Published: August 2021

The spatial distribution of Milky Way (MW) subhaloes provides an important set of observables for testing cosmological models. These include the radial distribution of luminous satellites, planar configurations, and the abundance of dark subhaloes whose existence or absence is key to distinguishing among dark matter models. We use the cocoN-body simulations of cold dark matter (CDM) and 3.3 keV thermal relic warm dark matter (WDM) to predict the satellite spatial distribution in the limit that the impact of baryonic physics is minimal. We demonstrate that the radial distributions of CDM and 3.3 keV-WDM luminous satellites are identical if the minimum pre-infall halo mass to form a galaxy is >108.5 ${\, \rm M_\odot }$. The distribution of dark subhaloes is significantly more concentrated in WDM due to the absence of low mass, recently accreted substructures that typically inhabit the outer parts of a MW halo in CDM. We show that subhaloes of mass [107, 108] ${\, \rm M_\odot }$ and within 30 kpc of the centre are the stripped remnants of larger haloes in both models. Therefore, their abundance in WDM is 3× higher than one would anticipate from the overall WDM subhalo population. We estimate that differences between CDM and WDM concentration–mass relations can be probed for subhalo–stream impact parameters <2 kpc. Finally, we find that the impact of WDM on planes of satellites is likely negligible. Comprehensive comparisons with observations will require further work with high resolution, self-consistent hydrodynamical simulations.
How well is angular momentum accretion modelled in semi-analytic galaxy formation models?
Authors: Hou Jun , Lacey Cedric G , Frenk Carlos S
Published: August 2021

Gas cooling and accretion in haloes delivers mass and angular momentum on to galaxies. In this work, we investigate the accuracy of the modelling of this important process in several different semi-analytic (SA) galaxy formation models (galform, l-galaxies, and morgana) through comparisons with a hydrodynamical simulation performed with the moving-mesh code arepo. Both SA models and the simulation were run without any feedback or metal enrichment, in order to focus on the cooling and accretion process. All of the SA models considered here assume that gas cools from a spherical halo. We found that the assumption that the gas conserves its angular momentum when moving from the virial radius, rvir, to the central region of the halo, r ∼ 0.1rvir, is approximately consistent with the results from our simulation. We also found that, compared to the simulation, the morgana model tends to overestimate the mean specific angular momentum of cooled-down gas, the l-galaxies model also tends to overestimate this in low-redshift massive haloes, while the two older galform models tend to underestimate the angular momentum. In general, the predictions of the new galform cooling model developed by Hou et al. agree the best with the simulation.
Expanded access use of rezafungin for salvage therapy of invasive Candida glabrata infection: A case report
Authors: Adeel Alina , Qu Ming D , Siddiqui Efaza , Levitz Stuart M , Ellison Richard T
Published: August 2021

Rezafungin is a semi-synthetic, long acting echinocandin with broad spectrum activity against many Candida species (spp)., and Aspergillus spp., including subset of drug-resistant strains. It is currently in phase III trials and was found to be safe and effective for treatment of candidemia and/or invasive Candida infections in a phase II trial. However, there are no long-term safety or efficacy data. We report on the successful ongoing compassionate use of rezafungin obtained through expanded access for over one year in a patient with a multidrug-resistant Candida glabrata mediastinal infection from a vascular graft infection and retained foreign material.
Repurposable drugs for SARS-CoV-2 and influenza sepsis with scRNA-seq data targeting post-transcription modifications
Authors: Wang Zhihan , Guo Kai , Gao Pan , Pu Qinqin , Li Changlong , Hur Junguk , Wu Min
Published: August 2021

Coronavirus disease 2019 (COVID-19) has impacted almost every part of human life worldwide, posing a massive threat to human health. The lack of time for new drug discovery and the urgent need for rapid disease control to reduce mortality have led to a search for quick and effective alternatives to novel therapeutics, for example drug repurposing. To identify potentially repurposable drugs, we employed a systematic approach to mine candidates from U.S. FDA-approved drugs and preclinical small-molecule compounds by integrating gene expression perturbation data for chemicals from the Library of Integrated Network-Based Cellular Signatures project with a publicly available single-cell RNA sequencing dataset from patients with mild and severe COVID-19 (GEO: GSE145926, public data available and accessed on 22 April 2020). We identified 281 FDA-approved drugs that have the potential to be effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, 16 of which are currently undergoing clinical trials to evaluate their efficacy against COVID-19. We experimentally tested and demonstrated the inhibitory effects of tyrphostin-AG-1478 and brefeldin-a, two chemical inhibitors of glycosylation (a post-translational modification) on the replication of the single-stranded ribonucleic acid (ssRNA) virus influenza A virus as well as on the transcription and translation of host cell cytokines and their regulators (IFNs and ISGs). In conclusion, we have identified and experimentally validated repurposable anti-SARS-CoV-2 and IAV drugs using a systems biology approach, which may have the potential for treating these viral infections and their complications (sepsis).
Inhibitory activity of medicinal mushroom Ganoderma lucidum on colorectal cancer by attenuating inflammation
Authors: Liu Mandy M , Liu Tiantian , Yeung Steven , Wang Zhijun , Andresen Bradley , Parsa Cyrus , Orlando Robert , Zhou Bingsen , Wu Wei , Li Xia , Zhang Yilong , Wang Charles , Huang Ying
Published: August 2021

The medicinal mushroom Ganoderma lucidum (GL, Reishi or Lingzhi) exhibits an inhibitory effect on cancers. However, the underlying mechanism of the antitumor activity of GL is not fully understood. In this study, we characterized the gene networks regulated by a commercial product of GL containing a mixture of spores and fruiting bodies namely “GLSF”, in colorectal carcinoma. We found that in vitro co-administration of GLSF extract at non-toxic concentrations significantly potentiated growth inhibition and apoptosis induced by paclitaxel in CT26 and HCT-15 cells. GLSF inhibited NF-κB promoter activity in HEK-293 cells but did not affect the function of P-glycoprotein in K562/DOX cells. Furthermore, we found that when mice were fed a modified diet containing GLSF for 1 month prior to the CT26 tumor cell inoculation, GLSF alone or combined with Nab-paclitaxel markedly suppressed tumor growth and induced apoptosis. RNA-seq analysis of tumor tissues derived from GLSF-treated mice identified 53 differentially expressed genes compared to normal tissues. Many of the GLSF-down-regulated genes were involved in NF-κB-regulated inflammation pathways, such as IL-1β, IL-11 and Cox-2. Pathway enrichment analysis suggested that several inflammatory pathways involving leukocyte migration and adhesion were most affected by the treatment. Upstream analysis predicted activation of multiple tumor suppressors such as α-catenin and TP53 and inhibition of critical inflammatory mediators. “Cancer” was the major significantly inhibited biological effect of GLSF treatment. These results demonstrate that GLSF can improve the therapeutic outcome for colorectal cancer through a mechanism involving suppression of NF-κB-regulated inflammation and carcinogenesis.
Metabolic Pathways forS-Metolachlor Detoxification Differ Between Tolerant Corn and Multiple-Resistant Waterhemp
Authors: Strom Seth A , Hager Aaron G , Concepcion Jeanaflor Crystal T , Seiter Nicholas J , Davis Adam S , Morris James A , Kaundun Shiv S , Riechers Dean E
Published: August 2021

Herbicide resistance in weeds can be conferred by target-site and/or non-target-site mechanisms, such as rapid metabolic detoxification. Resistance to the very-long-chain fatty acid–inhibiting herbicide, S-metolachlor, in multiple herbicide-resistant populations (CHR and SIR) of waterhemp (Amaranthus tuberculatus) is conferred by rapid metabolism compared with sensitive populations. However, enzymatic pathways for S-metolachlor metabolism in waterhemp are unknown. Enzyme assays using S-metolachlor were developed to determine the specific activities of glutathione S-transferases (GSTs) and cytochrome P450 monooxygenases (P450s) from CHR and SIR seedlings to compare with tolerant corn and sensitive waterhemp (WUS). GST activities were greater (∼2-fold) in CHR and SIR compared to WUS but much less than corn. In contrast, P450s in microsomal extracts from CHR and SIR formed O-demethylated S-metolachlor, and their NADPH-dependent specific activities were greater (>20-fold) than corn or WUS. Metabolite profiles of S-metolachlor generated via untargeted and targeted liquid chromatography–mass spectrometry from CHR and SIR differed from WUS, with greater relative abundances of O-demethylated S-metolachlor and O-demethylated S-metolachlor-glutathione conjugates formed by CHR and SIR. In summary, our results demonstrate that S-metolachlor metabolism in resistant waterhemp involves Phase I and Phase II metabolic activities acting in concert, but the initial O-demethylation reaction confers resistance.
The Impact of Parental Presence on Their Children During Painful Medical Procedures: A Systematic Review
Authors: Rheel Emma , Malfliet Anneleen , Van Ryckeghem Dimitri M L , Pas Roselien , Vervoort Tine , Ickmans Kelly
Published: August 2021

Objective

Whether parental presence during their children’s painful medical procedures is advantageous with regard to children’s pain-related outcomes is questionable. Research on this topic is equivocal, and additional questions, such as whether levels of parental involvement may play a role as well, remain to be addressed. The purpose of this systematic review is to summarize and critically appraise the literature on the impact of parental presence vs absence during their children’s painful medical procedures on the child’s pain-related outcomes.

Methods

The review protocol was registered on Prospero (ID CRD42018116614). A systematic search in PubMed, Web of Science, and PsycArticles resulted in 22 eligible studies incorporating 2,157 participants. Studies were considered eligible if they included children (≤18 years old) undergoing a painful medical procedure and compared parental presence and/or involvement with parental absence during the procedure.

Results

The children’s pain-related outcomes included self-reported pain intensity, self-reported fear, anxiety and distress, observed pain-related behavior, and physiological parameters. Overall, evidence points in the direction of beneficial effects of parental presence vs absence with regard to children’s self-reported pain intensity and physiological parameters, whereas mixed findings were recorded for children’s self-reported fears, anxiety and distress, and observed pain-related behaviors.

Conclusions

To provide clear recommendations on how to involve the parent during the procedure, as well as for which type of children and parents parental presence has the best effects, further research is needed, as indicated in this review.
A Network Analysis of Selected Psychosocial Factors in Vulvodynia and Its Subtypes
Authors: Chisari Claudia , Begleris Ioannis , Monajemi Mani B , Lewis Fiona , Moss-Morris Rona , Scott Whitney , McCracken Lance M
Published: August 2021

Objective

Psychosocial factors are related to pain and sex-related outcomes in provoked vulvodynia and possibly in mixed and spontaneous vulvodynia. However, a broader behavioral framework, such as the psychological flexibility model, has received limited attention in this context. Recently, additional psychosocial variables have also emerged that appear relevant to vulvodynia, including perceived injustice, body-exposure anxiety during intercourse, and unmitigated sexual communion. The present study applied network analysis to explore relations between psychological flexibility, newly emerging psychosocial variables relevant to vulvodynia, and their associations with vulvodynia outcomes. The study also explored potential differences across vulvodynia subtypes.

Design

An online cross-sectional study of 349 participants with vulvodynia (112 provoked, 237 spontaneous/mixed) was carried out.

Methods

Participants completed self-report questionnaires, including questions on pain and sexual outcomes, depression, facets of psychological flexibility, body-exposure anxiety during intercourse, unmitigated sexual communion, and perceived injustice. Networks were computed for the total sample and for provoked and mixed/spontaneous vulvodynia subsamples.

Results

Perceived injustice, pain acceptance, and depression were “central” factors among the included variables, in all models. Psychological flexibility processes were relevant for all networks. Depression was more central in the network for mixed/spontaneous vulvodynia; body-exposure anxiety during intercourse was most central for the provoked subtype.

Conclusions

Among the included variables, perceived injustice, pain acceptance, depression, and psychological flexibility appear to be important in vulvodynia. As different factors are significant across subtypes, tailored treatment approaches are suggested.
A Structural Connectivity Disruption One Decade before the Typical Age for Dementia: A Study in Healthy Subjects with Family History of Alzheimer’s Disease
Authors: Ramírez-Toraño F , Abbas Kausar , Bruña Ricardo , Marcos de Pedro Silvia , Gómez-Ruiz Natividad , Barabash Ana , Pereda Ernesto , Marcos Alberto , López-Higes Ramón , Maestu Fernando , Goñi Joaquín
Published: August 2021

The concept of the brain has shifted to a complex system where different subnetworks support the human cognitive functions. Neurodegenerative diseases would affect the interactions among these subnetworks and, the evolution of impairment and the subnetworks involved would be unique for each neurodegenerative disease. In this study, we seek for structural connectivity traits associated with the family history of Alzheimer’s disease, that is, early signs of subnetworks impairment due to Alzheimer’s disease.

The sample in this study consisted of 123 first-degree Alzheimer’s disease relatives and 61 nonrelatives. For each subject, structural connectomes were obtained using classical diffusion tensor imaging measures and different resolutions of cortical parcellation. For the whole sample, independent structural-connectome-traits were obtained under the framework of connICA. Finally, we tested the association of the structural-connectome-traits with different factors of relevance for Alzheimer’s disease by means of a multiple linear regression.

The analysis revealed a structural-connectome-trait obtained from fractional anisotropy associated with the family history of Alzheimer’s disease. The structural-connectome-trait presents a reduced fractional anisotropy pattern in first-degree relatives in the tracts connecting posterior areas and temporal areas.

The family history of Alzheimer’s disease structural-connectome-trait presents a posterior–posterior and posterior–temporal pattern, supplying new evidences to the cascading network failure model.
The Role of Idiothetic Signals, Landmarks, and Conjunctive Representations in the Development of Place and Head-Direction Cells: A Self-Organizing Neural Network Model
Authors: St. Clere Smithe Toby , Stringer Simon M
Published: August 2021

Place and head-direction (HD) cells are fundamental to maintaining accurate representations of location and heading in the mammalian brain across sensory conditions, and are thought to underlie path integration—the ability to maintain an accurate representation of location and heading during motion in the dark. Substantial evidence suggests that both populations of spatial cells function as attractor networks, but their developmental mechanisms are poorly understood. We present simulations of a fully self-organizing attractor network model of this process using well-established neural mechanisms. We show that the differential development of the two cell types can be explained by their different idiothetic inputs, even given identical visual signals: HD cells develop when the population receives angular head velocity input, whereas place cells develop when the idiothetic input encodes planar velocity. Our model explains the functional importance of conjunctive “state-action” cells, implying that signal propagation delays and a competitive learning mechanism are crucial for successful development. Consequently, we explain how insufficiently rich environments result in pathology: place cell development requires proximal landmarks; conversely, HD cells require distal landmarks. Finally, our results suggest that both networks are instantiations of general mechanisms, and we describe their implications for the neurobiology of spatial processing.
The Impact of Di-Isononyl Phthalate Exposure on Specialized Epithelial Cells in the Colon
Authors: Chiu Karen , Bashir Shah Tauseef , Chiu Justin , Nowak Romana A , Flaws Jodi A
Published: August 2021

Di-isononyl phthalate (DiNP) is a high-molecular-weight phthalate commonly used as a plasticizer for polyvinyl chloride and other end products, such as medical devices and construction materials. Most of our initial exposure to DiNP occurs by ingestion of DiNP-contaminated foods. However, little is known about the effects of DiNP on the colon. Therefore, the goal of this study was to test the hypothesis that DiNP exposure alters immune responses and impacts specialized epithelial cells in the colon. To test this hypothesis, adult female mice were orally dosed with corn-oil vehicle control or doses of DiNP ranging from 20 µg/kg/d to 200 mg/kg/d for 10–14 days. After the dosing period, mice were euthanized in diestrus, and colon tissues and sera were collected for histological, genomic, and proteomic analysis of various immune factors and specialized epithelial cells. Subacute exposure to DiNP significantly increased protein levels of Ki67 and MUC2, expression of a Paneth cell marker (Lyz1), and estradiol levels in sera compared with control. Gene expression of mucins (Muc1, Muc2, Muc3a, and Muc4), Toll-like receptors (Tlr4 and Tlr5), and specialized epithelial cells (ChgA, Lgr5, Cd24a, and Vil1) were not significantly different between treatment groups and control. Cytokine levels of IL-1RA and CXCL12 were also not significantly different between DiNP treatment groups and control. These data reveal that DiNP exposure increases circulating estradiol levels and gene expression in specialized epithelial cells with immune response capabilities (eg, goblet and Paneth cells) in the mouse colon, which may initiate immune responses to prevent further damage in the colon.
Integrated optimization of multiproduct multiperiod transportation and inventory under a carbon cap constraint for online retailers
Authors: Cheng Yaorong , Li Yijun
Published: August 2021

This study aims to solve the problem of multiproduct multiperiod integrated transportation and inventory optimization for online retailers. A carbon cap constraint and multitype of capacitated trucks are simultaneously incorporated into the proposed mixed-integer program. A simulated annealing (SA) algorithm is designed. CPLEX 12.9.0 is used to solve the submodel obtained from the neighbourhood search and is also used to get the optimal solutions for instances. Experimental results show that the simulated annealing algorithm can find satisfactory solutions within a reasonable time. When the problem size increases, the growth of the computational time of the SA algorithm is significantly smaller than that of the CPLEX. A sensitivity analysis for the carbon cap is also conducted. The results indicate that if the carbon cap is gradually tightened, the total cost increases first with a gentle slope, and then with a remarkable slope, same as for the total number of trucks used; the total carbon emissions first decrease with a gentle slope, and then decline with a significant slope. When the carbon cap is strict, only a few different types of trucks will be considered. The percentage changes of the total cost increase and the total carbon emission reduction are also compared. When the allowed carbon emissions are gradually reduced, situation of a higher amount of carbon emission reduction and a lower amount of cost increase can be achieved. Additionally, using multiple types of trucks in the integrated optimization of transportation and inventory decisions can achieve greater cost savings with lower increments of carbon emission.
Diversity and transmission of Aleutian mink disease virus in feral and farmed American mink and native mustelids
Authors: Virtanen Jenni , Zalewski Andrzej , Kołodziej-Sobocińska Marta , Brzeziński Marcin , Smura Teemu , Sironen Tarja
Published: August 2021

Aleutian mink disease virus (AMDV), which causes Aleutian disease, is widely spread both in farmed mink and wild mustelids. However, only limited data are available on the role of wild animals in AMDV transmission and spread. Our aim was to shed light on AMDV transmission among wild mustelids and estimate the effect of intense farming practices on the virus circulation by studying AMDV prevalence and genetic diversity among wild mustelids in Poland. We compared AMDV seroprevalence and proportion of PCR-positive individuals in American mink, polecats, otters, stone martens, and pine martens and used the phylogenetic analysis of the NS1 region to study transmission. In addition, we used a metagenomic approach to sequence complete AMDV genomes from tissue samples. In eastern Poland, AMDV seroprevalence in wild mustelids varied from 22 per cent in otters to 62 per cent and 64 per cent in stone martens and feral mink, respectively. All studied antibody-positive mink were also PCR positive, whereas only 10, 15, and 18 per cent of antibody-positive polecats, pine martens, and stone martens, respectively, were PCR positive, suggesting lower virus persistence among these animal species as compared to feral mink. In phylogenetic analysis, most sequences from feral mink formed region-specific clusters that have most likely emerged through multiple introductions of AMDV to feral mink population over decades. However, virus spread between regions was also observed. Virus sequences derived from farmed and wild animals formed separate subclusters in the phylogenetic tree, and no signs of recent virus transmission between farmed and wild animals were observed despite the frequent inflow of farmed mink escapees to wild populations. These results provide new information about the role of different mustelid species in AMDV transmission and about virus circulation among the wild mustelids. In addition, we pinpoint gaps of knowledge, where more studies are needed to achieve a comprehensive picture of AMDV transmission.
Effectiveness of the WHO-authorized Covid-19 Vaccines: a Rapid Review of Global Reports till June 30, 2021
Authors: Cheng Chang-Jie , Lu Chun-Yi , Chang Ya-Hui , Sun Yu , Chu Hai-Jui , Lee Chun-Yu , Liu Chang-Hsiu , Lin Cheng-Huai , Lu Chien-Jung , Li Chung-Yi
Published: August 2021

Objective

Large clinical trials have proved the efficacy of Covid-19 vaccine, and the number of literature about the effectiveness is rapidly growing in the first half of year after mass vaccination was administrated globally. This rapid review aims to provide evidence syntheses as a means to complement the current evidence on the vaccine effectiveness (VE) against various outcomes in real-world settings.

Methods

This review is conducted based on the updated guideline of PRISMA 2020. Databases (PubMed, EMBASE, and MedRxiv) were searched up to 30 June 2021, (PROSPERO ID: 266866). The studies that assessed the VE of the 6 WHO-authorized vaccines (BNT162b2, ChAdOx1, Ad26.COV2.S, mRNA-1273, BBIBP-CorV, and CoronaVac) were eligible to be included. Quality assessment was performed based on ROBINS-I by 2 independent reviewers.

Findings

A total of 39 studies were included, covering over 15 million of participants from 11 nations. Among the general population after 2 doses of vaccination, the VE against symptomatic SARS-CoV-2 infection was estimated at 89%–97%, 92% (95% CI, 78%–97%) and 94% (95% CI, 86%–97%) for BNT162b2, ChAdOx1 and mRNA-1273, respectively. As for the protective effects against B.1.617.2 related symptomatic infection, the VE was 88% (95% CI, 85.3%–90.1%) by BNT162b2 and 67.0% (95% CI, 61.3%–71.8%) by ChAdOx1 after fully vaccination.

Conclusion

This review revealed a consistently high effectiveness of vaccines among the general population in real-world settings. Further studies are needed to provide the information on different races/ethnicity, the effects against SARS-CoV-2 variants, and the duration of protection with longer study time.
What medical students think about measurement of their wellbeing and the implications for pastoral support: cross sectional survey and qualitative interviews
Authors: Simons G , Effah R , Baldwin DS
Published: August 2021

Objectives

To find out how, why and when medical students think wellbeing should be measured.

Design

A mixed methods study comprising a cross-sectional online survey (November 2020-March 2021) and semi-structured on-line interviews. Views on the frequency of availability for measurement, the format, type and purpose of measurement, and with whom wellbeing should be discussed were measured. When an outcome was scored 7-9 on a 9-point Likert scale of agreement by ≥75% of participants it was considered critical, in line with COMET and GRADE processes for rating recommendations. Inductive thematic analysis was undertaken on the interview transcripts by two independent researchers.

Setting

All Medicine programmes at University of Southampton.

Participants

Medical students from all years took part in the survey (n=118) and interviews (n=16).

Results

Participant demographics were similar to national medical student demographics. Most participants (94%) felt able to give 5 minutes to measure their wellbeing at least once a month. No single format of measurement was rated critical. Research, governance and individual feedback all reached the 75% threshold for the purpose being considered critically important. Only subjective assessments undertaken by the individual in real-time were rated as critically important (78.1%) measurement tools. Students selected that they would discuss their wellbeing with other medical students (n=87) nearly as often as they selected a member of the Faculty (n=104). Top determinants of wellbeing picked by medical students were energy, ability to do activities of daily living, and negative feelings. Five interview themes further explained these findings.

Conclusions

Five recommendations about self-care teaching, quality-assured pastoral and peer support, proactive wellbeing check-ins and demographic data are discussed in light of these findings. Methods to achieve them are suggested, which are medical student-centred, and which make use of existing resources.

Strengths and limitations of this study

This study provides new information on how, why and when medical students think their wellbeing should be measured.

A mixed methods approach allowed the reasons behind the survey answers to be captured in ensuing interviews.

Using the ≥75% a prior cut off for critical importance from COMET and GRADE allowed evidence-based recommendations for wellbeing measurement for medical students.

It was not possible to recruit the number of students needed to make national inferences, although participant demographics were similar to national medical student demographics.

A national cross-sectional survey would provide further evidence for medical schools in devising wellbeing provisions.
JAK2V617F mutant megakaryocytes contribute to hematopoietic aging in a murine model of myeloproliferative neoplasm
Authors: Lee Sandy , Wong Helen , Castiglione Melissa , Murphy Malea , Kaushansky Kenneth , Zhan Huichun
Published: August 2021

Megakaryocytes (MKs) is an important component of the hematopoietic niche. Abnormal MK hyperplasia is a hallmark feature of myeloproliferative neoplasms (MPNs). The JAK2V617F mutation is present in hematopoietic cells in a majority of patients with MPNs. Using a murine model of MPN in which the human JAK2V617F gene is expressed specifically in the MK lineage, we show that the JAK2V617F-bearing MKs promote hematopoietic stem cell (HSC) aging, manifesting as myeloid-skewed hematopoiesis with an expansion of CD41+HSCs, a reduced engraftment and self-renewal capacity, and a reduced differentiation capacity. HSCs from 2yr old mice with JAK2V617F-bearing MKs were more proliferative and less quiescent than HSCs from age-matched control mice. Examination of the marrow hematopoietic niche reveals that the JAK2V617F-bearing MKs not only have decreased direct interactions with hematopoietic stem/progenitor cells during aging, but also suppress the vascular niche function during aging. Unbiased RNA expression profiling reveals that HSC aging has a profound effect on MK transcriptomic profiles, while targeted cytokine array shows that the JAK2V617F-bearing MKs can alter the hematopoietic niche through increased levels of pro-inflammatory and anti-angiogenic factors. Therefore, as a hematopoietic niche cell, MKs represent an important connection between the extrinsic and intrinsic mechanisms for HSC aging.

Significance Statement

The relative contribution of intrinsic and extrinsic mechanisms to HSC aging remains debated. We find that JAK2V617F mutant MKs can accelerate hematopoietic aging both directly (via decreased MK-HSC interaction) and indirectly (via suppressing vascular niche function). We also show that HSC aging has a profound effect on MK function. Our data suggest that, as a hematopoietic niche cell, MKs represent an important connection between HSC-intrinsic and HSC-extrinsic aging mechanisms.
A murine model with JAK2V617F expression in both hematopoietic cells and vascular endothelial cells recapitulates the key features of human myeloproliferative neoplasm
Authors: Zhang Haotian , Yeware Amar , Lee Sandy , Zhan Huichun
Published: August 2021

The myeloproliferative neoplasms (MPNs) are characterized by an expansion of the neoplastic hematopoietic stem/progenitor cells (HSPC) and an increased risk of cardiovascular complications. The acquired kinase mutation JAK2V617F is present in hematopoietic cells in a majority of patients with MPNs. Vascular endothelial cells (ECs) carrying the JAK2V617F mutation can also be detected in patients with MPNs. In this study, we show that a murine model with both JAK2V617F-bearing hematopoietic cells and JAK2V617F-bearing vascular ECs recapitulated all the key features of the human MPN disease, which include disease transformation from essential thrombocythemia to myelofibrosis, extramedullary splenic hematopoiesis, and spontaneous cardiovascular complications. During aging and MPN disease progression, there was a loss of both HSPC number and HSPC function in the marrow while the neoplastic hematopoiesis was relatively maintained in the spleen, mimicking the advanced phases of human MPN disease. Different vascular niche of the marrow and spleen could contribute to the different JAK2V617F mutant stem cell functions we have observed in this JAK2V617F-positive murine model. Compared to other MPN murine models reported so far, our studies demonstrate that endothelial dysfunction plays an important role in both the hematologic and cardiovascular abnormalities of MPN.

Key Points

A murine model in which JAK2V617F is expressed in both hematopoietic cells and ECs recapitulated the key features of the human MPN disease

Different vascular niche of the marrow and spleen could contribute to different JAK2V617F HSC functions during MPN disease progression
Host-associated microbial diversity in New Zealand cicadas uncovers elevational structure and replacement of obligate bacterial endosymbionts byOphiocordycepsfungal pathogens
Authors: Haji Diler , Vailionis Jason , Stukel Mark , Gordon Eric , Lemmon Emily Moriarty , Lemmon Alan R. , McCutcheon John P. , Simon Chris
Published: August 2021

Host-microbe interactions influence eukaryotic evolution, particularly in the sap-sucking insects that often rely on obligate microbial symbionts to provision deficient nutrients in their diets. Cicadas (Hemiptera: Auchenorrhyncha: Cicadidae) specialize on xylem fluid and derive many essential amino acids and vitamins from intracellular bacteria or fungi (Hodgkinia,Sulcia, andOphiocordyceps) that are propagated via transmission from mothers to offspring. Despite the beneficial role of these symbionts in nutrient provisioning, they are generally not considered to function within the gut where microbiota may play an important dietary role during insect diversification. Here, we investigate the relative impact of host phylogeny and ecology on gut microbial diversity in cicadas by sequencing 16S ribosomal RNA gene amplicons from 197 wild-collected cicadas and new mitochondrial genomes across 38 New Zealand cicada species, including natural hybrids between one species pair. We find a lack of phylogenetic structure and hybrid effects but a significant role of elevation in explaining variation in gut microbiota. Additionally, we provide evidence ofHodgkinialoss with gains ofOphiocordycepsfungal pathogens in all New Zealand cicadas examined that suggests convergent domestications of fungal pathogens. This highlights the macroevolutionary instability of obligate symbiosis and the relative importance of ecology rather than phylogeny for structuring gut microbial diversity in cicadas.

Importance

An unresolved question in evolutionary biology is how beneficial associations between eukaryotes and microbes impact macroevolutionary patterns. We report substantial data from natural populations that suggest the absence of macroevolutionary impacts from gut microbiota in cicadas. Instead, gut microbial diversity is better explained by elevational variation across an island landscape. Cicadas, like many insects, have obligate nutritional associations with bacteria housed in organs outside of the gut, but we show that these associations seem also to be unstable at macroevolutionary scales. We report evidence for unexpected and widespread replacement of obligate bacteria by a domesticated and formerly pathogenicOphiocordycepsfungus representing an evolutionarily convergent pattern across the cicada phylogeny.
Loss-of-function mutation in IKZF2 leads to immunodeficiency with dysregulated germinal center reactions and reduction of MAIT cells
Authors: Hetemäki Iivo , Kaustio Meri , Kinnunen Matias , Heikkilä Nelli , Keskitalo Salla , Miettinen Simo , Sarkkinen Joona , Glumoff Virpi , Andersson Noora , Kettunen Kaisa , Vanhanen Reetta , Nurmi Katariina , Eklund Kari K , Dunkel Johannes , Mäyränpää Mikko , Schlums Heinrich , Arstila T. Petteri , Kisand Kai , Bryceson Yenan T. , Peterson Pärt , Otava Ulla , Syrjänen Jaana , Saarela Janna , Varjosalo Markku , Kekäläinen Eliisa
Published: August 2021

The IKAROS family transcription factors regulate lymphocyte development. Loss-of-function variants in IKZF1 cause primary immunodeficiency, but IKAROS family members IKZF2 and IKZF3 have not yet been associated with immunodeficiency yet. Here, we describe a pedigree with a heterozygous truncating variant in IKZF2, encoding the translational activator and repressor HELIOS which is highly expressed in regulatory T cells and effector T cells, particularly of the CD8+ T cell lineage. Protein-protein interaction analysis revealed that the variant abolished HELIOS dimerizations as well as binding to members of the Mi-2/NuRD chromatin remodeling complex. Patients carrying the IKZF2 variant presented with a combined immunodeficiency phenotype characterized by recurrent upper respiratory infections, thrush and mucosal ulcers, as well as chronic lymphadenopathy. With extensive immunophenotyping, functional assays, and transcriptional analysis we show that reduced HELIOS expression was associated with chronic T cell activation and increased production of pro-inflammatory cytokines both in effector and regulatory T cells. Lymph node histology from patients indicated dysregulated germinal center reactions. Moreover, affected individuals displayed profoundly reduced circulating MAIT cell numbers. In summary, we show that this novel loss-of-function variant in HELIOS leads to an immunodeficiency with signs of immune overactivation.

One sentence summary

Truncating variant of HELIOS causes immunodeficiency with signs of immune overactivation.
Automation improves repeatability of retinal oximetry measurements
Authors: Karlsson Robert Arnar , Olafsdottir Olof Birna , Belhadj Soumaya , Helgadottir Vedis , Eliasdottir Thorunn Scheving , Stefansson Einar , Hardarson Sveinn Hakon
Published: August 2021

Purpose

Retinal oximetry is a technique based on spectrophotometry where images are analyzed with software capable of calculating vessel oxygen saturation and vessel diameter. In this study, the effect of automation of measurements of retinal vessel oxygen saturation and vessel diameter is explored.

Methods

Until now, operators have had to choose each vessel segment to be measured explicitly. A new, automatic version of the software automatically selects the vessels once the operator defines a measurement area.

Five operators analyzed image pairs from the right eye of 23 healthy subjects with semiautomated retinal oximetry analysis software, Oxymap Analyzer (v2.5.1), and an automated version (v3.0). Inter- and intra-operator variability was investigated using the intraclass correlation coefficient (ICC) between oxygen saturation measurements of vessel segments in the same area of the retina.

Results

For manual saturation measurements, the inter-rater ICC was 0.80 for arterioles and venules. For automated saturation measurements, the inter-rater ICC was 0.97 for arterioles and 0.96 for venules. For manual diameter measurements, the inter-rater ICC was 0.71 for arterioles and venules. For automated diameter measurements the inter-rater ICC was 0.97 for arterioles and 0.95 for venules. The inter-rater ICCs were different (p < 0.01) between the semiautomated and automated version in all instances.

Conclusion

Automated measurements of retinal oximetry values are more repeatable compared to measurements where vessels are selected manually.