bluuebunny/crossref_metadata_2025 huggingface dataset:
Pembrolizumab-associated expansion of radiation-induced morphoea responsive to dupilumab: a case report
Authors: Said Jordan T , Iriarte Christopher , Talia Jordan , Leung Bonnie , Virgen Cesar A , Robertson Matthew , Rabin Michael S , Larocca Cecilia , LeBoeuf Nicole R
Published: April 2023

Immune checkpoint inhibition (ICI) can induce progression of pre-existing radiation-induced morphoea beyond the irradiated field and into deeper structures including the muscle and fascia. Dupilumab, an interleukin-4 receptor antagonist, should be considered in patients with refractory radiation or ICI-induced morphoea and may allow for continued anticancer treatment.
Protective and pathogenic functions of innate lymphoid cells in transplantation
Authors: Mak Martin L , Reid Kyle T , Crome Sarah Q
Published: April 2023

Innate lymphoid cells (ILCs) are a family of lymphocytes with essential roles in tissue homeostasis and immunity. Along with other tissue-resident immune populations, distinct subsets of ILCs have important roles in either promoting or inhibiting immune tolerance in a variety of contexts, including cancer and autoimmunity. In solid organ and hematopoietic stem cell transplantation, both donor and recipient-derived ILCs could contribute to immune tolerance or rejection, yet understanding of protective or pathogenic functions are only beginning to emerge. In addition to roles in directing or regulating immune responses, ILCs interface with parenchymal cells to support tissue homeostasis and even regeneration. Whether specific ILCs are tissue-protective or enhance ischemia reperfusion injury or fibrosis is of particular interest to the field of transplantation, beyond any roles in limiting or promoting allograft rejection or graft-versus host disease. Within this review, we discuss the current understanding of ILCs functions in promoting immune tolerance and tissue repair at homeostasis and in the context of transplantation and highlight where targeting or harnessing ILCs could have applications in novel transplant therapies.
Stability of maxillary anterior teeth during retention and 1 year after removal of retention—an RCT on adolescents retained with two different bonded retainers and a vacuum-formed retainer
Authors: Naraghi Sasan , Ganzer Niels , Bondemark Lars , Sonesson Mikael
Published: April 2023

Background

Maxillary bonded and removable retainers maintain teeth in correct positions following orthodontic treatment. There is insufficient evidence regarding the capacity of the retention methods to stabilize the maxillary teeth both during and after retention.

Objective

To evaluate retention capacity and 1-year post-retention changes in the irregularity of maxillary anterior teeth and single anterior tooth contact point discrepancy (CPD) of two bonded and one removable retention method.

Trial design

Three-arm parallel group single-centre randomized controlled trial.

Methods

Ninety adolescent patients treated with fixed orthodontic appliances were enrolled. After gaining informed consent, the patients were randomized in blocks of 30 by an independent person into one of three groups: A) bonded retainer 13–23; B) bonded retainer 12–22; and C) removable vacuum-formed retainer. The primary outcomes were changes in Little’s irregularity index (LII) and single CPD measured on digitalized casts before retention (T1), after 2 years of retention (T2), and 1-year post-retention (T3).

Blinding

The digital casts were blinded for the outcome assessor.

Results

Data on all 90 patients were analysed according to intention-to-treat principles. Changes in LII during retention were 0.3 mm in group A, 0.6 mm in group B, and 1.0 mm in group C. No significant differences between the groups were seen (P > 0.05). Changes during post-retention were 1.1 mm in group A, 0.5 mm in group B, and 0.4 mm in group C. Group A showed more significant changes than groups B and C (P = 0.003). During the whole post-treatment period, no significant differences were shown between the groups (P > 0.05). CPD did not differ significantly between the groups at any point.

Harms

Three patients showed changes of LII over 3 mm or CPD over 2 mm during the post-retention period, and two accepted to be realigned.

Limitations

The trial was a single-centre study evaluating 1-year post-retention changes.

Conclusions

The changes were clinically insignificant during and after the retention period. Thus, all three methods showed equal retention capacity.

Trial registration

www.clinicaltrials.com (NCT04616755).
Dissociation Between Neuronal and Astrocytic Calcium Activity in Response to Locomotion in Mice
Authors: Fedotova Anna , Brazhe Alexey , Doronin Maxim , Toptunov Dmytro , Pryazhnikov Evgeny , Khiroug Leonard , Verkhratsky Alexei , Semyanov Alexey
Published: April 2023

Locomotion triggers a coordinated response of both neurons and astrocytes in the brain. Here we performed calcium (Ca2+) imaging of these two cell types in the somatosensory cortex in head-fixed mice moving on the airlifted platform. Ca2+ activity in astrocytes significantly increased during locomotion from a low quiescence level. Ca2+ signals first appeared in the distal processes and then propagated to astrocytic somata, where it became significantly larger and exhibited oscillatory behaviour. Thus, astrocytic soma operates as both integrator and amplifier of Ca2+ signal. In neurons, Ca2+ activity was pronounced in quiescent periods and further increased during locomotion. Neuronal Ca2+ concentration ([Ca2+]i) rose almost immediately following the onset of locomotion, whereas astrocytic Ca2+ signals lagged by several seconds. Such a long lag suggests that astrocytic [Ca2+]i elevations are unlikely to be triggered by the activity of synapses among local neurons. Ca2+ responses to pairs of consecutive episodes of locomotion did not significantly differ in neurons, while were significantly diminished in response to the second locomotion in astrocytes. Such astrocytic refractoriness may arise from distinct mechanisms underlying Ca2+ signal generation. In neurons, the bulk of Ca2+ enters through the Ca2+ channels in the plasma membrane allowing for steady-level Ca2+ elevations in repetitive runs. Astrocytic Ca2+ responses originate from the intracellular stores, the depletion of which affects subsequent Ca2+ signals. Functionally, neuronal Ca2+ response reflects sensory input processed by neurons. Astrocytic Ca2+ dynamics is likely to provide metabolic and homeostatic support within the brain active milieu.
Skeletal Muscle Consequences of Phosphatidylethanolamine Synthesis Deficiency
Authors: Grapentine Sophie , Singh Rathnesh K , Bakovic Marica
Published: April 2023

The maintenance of phospholipid homeostasis is increasingly being implicated in metabolic health. Phosphatidylethanolamine (PE) is the most abundant phospholipid on the inner leaflet of cellular membranes, and we have previously shown that mice with a heterozygous ablation of the PE synthesizing enzyme, Pcyt2 (Pcyt2+/−), develop obesity, insulin resistance, and NASH. Skeletal muscle is a major determinant of systemic energy metabolism, making it a key player in metabolic disease development. Both the total PE levels and the ratio of PE to other membrane lipids in skeletal muscle are implicated in insulin resistance; however, the underlying mechanisms and the role of Pcyt2 regulation in this association remain unclear. Here, we show how reduced phospholipid synthesis due to Pcyt2 deficiency causes Pcyt2+/- skeletal muscle dysfunction and metabolic abnormalities. Pcyt2+/- skeletal muscle exhibits damage and degeneration, with skeletal muscle cell vacuolization, disordered sarcomeres, mitochondria ultrastructure irregularities and paucity, inflammation, and fibrosis. There is intramuscular adipose tissue accumulation, and major disturbances in lipid metabolism with impaired FA mobilization and oxidation, elevated lipogenesis, and long-chain fatty acyl-CoA, diacylglycerol, and triacylglycerol accumulation. Pcyt2+/− skeletal muscle exhibits perturbed glucose metabolism with elevated glycogen content, impaired insulin signaling, and reduced glucose uptake. Together, this study lends insight into the critical role of PE homeostasis in skeletal muscle metabolism and health with broad implications on metabolic disease development.
Personalized embryo transfer reduces success rates because endometrial receptivity analysis fails to accurately identify the window of implantation
Authors: Richter Kevin S , Richter Martin L
Published: April 2023

After more than a decade of increasingly widespread clinical use, personalized embryo transfer guided by endometrial receptivity analysis (ERA) remains controversial and unproven. One key element missing from the historical literature is the recognition that potential benefits from personalized embryo transfer are entirely dependent on the accuracy and predictive value of the ERA test. Results from the first comprehensive clinical trial, designed in a way that allowed independent evaluation of both potential benefits of personalized embryo transfer and the predictive value of the ERA test upon which it is based, were recently published. However, the authors failed to conduct an appropriate analysis or recognize the significance of their results. Here, we present a simple reanalysis of data from this otherwise excellent randomized controlled trial, demonstrating for the first time that the ERA was unable to identify the window of implantation as purported and that, as a result, personalized embryo transfer based on the ERA actually reduced rather than increased the birth rates. Based on these results and the lack of any contradictory evidence, it is our opinion that all clinical use of ERA-guided personalized embryo transfer should be discontinued immediately, outside of a controlled experimental setting with appropriate informed consent of all participating patients.
Identification of tipping years and shifts in mesozooplankton community structure using multivariate analyses: a long-term study in southern North Sea
Authors: Di Pane J , Boersma M , Marques R , Deschamps M , Ecker U , Meunier C L
Published: April 2023

Many previous studies on the changes in zooplankton communities considered only subsets of the total community. In this study, we investigated the temporal dynamics of the mesozooplankton community structure, considering all taxa (holo- and meroplankton) sampled over the last five decades at Helgoland Roads. We identified two tipping years. The first one occurred in 1983, which is consistent with previous studies conducted on copepods. The second shift, even more pronounced, took place in the mid-2000s. During the first shift, most taxa significantly increased in abundance and kept high densities until the end of the 1990s. Then, we observed in the mid-2000s a sharp decrease in community diversity and abundances of almost all taxa. One of the aims of the study was to test the robustness depending on the choice of taxa. To test this, we selected different subsets of the total zooplankton community, both randomly as well as based on functionality. We observed very similar trends over time for all groups, showing the complete community experienced the same changes. However, the timing of the tipping years depended on the organisms considered. These results highlight that the observed changes in the planktonic community are surprisingly robust and visible in most planktonic organisms.
Factors contributing to pharmacists leaving employment in general practice in Australia: an exploratory study
Authors: Deeks Louise S , Kosari Sam , Peterson Gregory M , Sudeshika Thilini , Naunton Mark
Published: April 2023

Objective

To identify perceived factors contributing to pharmacists leaving employment in general practice.

Methods

Qualitative semi-structured interviews were conducted with pharmacists who had left employment in general practice within 12 months of commencing (5 pharmacists out of 14 recruited into these roles) in Canberra, Australia. Thematic analysis was undertaken.

Key findings

The main specific reasons cited for leaving were lack of utilisation and part-time hours, while the over-arching themes identified were: challenges of the new role, poor role definition, professional relationships and job satisfaction.

Conclusions

In this cohort of newly appointed general practice pharmacists, employment turnover was relatively high. The interview findings indicated a need for strategies, including having clear role descriptions that are understood by all members of the practice team, so that pharmacists with appropriate skillsets can be supported and retained in the general practice setting.
Structural and Energetic Basis for Differential Binding of Ebola and Marburg Virus Glycoproteins to a Bat-Derived Niemann-Pick C1 Protein
Authors: Igarashi Manabu , Hirokawa Takatsugu , Takada Ayato
Published: April 2023

Background

Our previous study demonstrated that the fruit bat (Yaeyama flying fox)-derived cell line FBKT1 showed preferential susceptibility to Ebola virus (EBOV), whereas the human cell line HEK293T was similarly susceptible to EBOV and Marburg virus (MARV). This was due to 3 amino acid differences of the endosomal receptor Niemann-Pick C1 (NPC1) between FBKT1 and HEK293T (ie, TET and SGA, respectively, at positions 425–427), as well as 2 amino acid differences at positions 87 and 142 of the viral glycoprotein (GP) between EBOV and MARV.

Methods/Results

To understand the contribution of these amino acid differences to interactions between NPC1 and GP, we performed molecular dynamics simulations and binding free energy calculations. The average binding free energies of human NPC1 (hNPC1) and its mutant having TET at positions 425–427 (hNPC1/TET) were similar for the interaction with EBOV GP. In contrast, hNPC1/TET had a weaker interaction with MARV GP than wild-type hNPC1. As expected, substitutions of amino acid residues at 87 or 142 in EBOV and MARV GPs converted the binding affinity to hNPC1/TET.

Conclusions

Our data provide structural and energetic insights for understanding potential differences in the GP-NPC1 interaction, which could influence the host tropism of EBOV and MARV.
Amplicon Sequencing Reveals Complex Infection in Infants Congenitally Infected With Trypanosoma Cruzi and Informs the Dynamics of Parasite Transmission
Authors: Hakim Jill M C , Waltmann Andreea , Tinajeros Freddy , Kharabora Oksana , Machaca Edith Málaga , Calderon Maritza , del Carmen Menduiña María , Wang Jeremy , Rueda Daniel , Zimic Mirko , Verástegui Manuela , Juliano Jonathan J , Gilman Robert H , Mugnier Monica R , Bowman Natalie M ,   Chagas Working Group
Published: April 2023

Congenital transmission of Trypanosoma cruzi is an important source of new Chagas infections worldwide. The mechanisms of congenital transmission remain poorly understood, but there is evidence that parasite factors are involved. Investigating changes in parasite strain diversity during transmission could provide insight into the parasite factors that influence the process. Here we use amplicon sequencing of a single copy T. cruzi gene to evaluate the diversity of infection in clinical samples from Chagas positive mothers and their infected infants. Several infants and mothers were infected with multiple parasite strains, mostly of the same TcV lineage, and parasite strain diversity was higher in infants than mothers. Two parasite haplotypes were detected exclusively in infant samples, while one haplotype was never found in infants. Together, these data suggest multiple parasites initiate a congenital infection and that parasite factors influence the probability of vertical transmission.
Transect-based trapping for area-wide delimitation of insects
Authors: Caton Barney P , Fang Hui , Pallipparambil Godshen R , Manoukis Nicholas C
Published: April 2023

Typical delimitation trapping survey designs for area-wide (nonlocalized) insect populations are regularly spaced grids, and alternative shapes have not been evaluated. We hypothesized that transect-based designs could give similar detection rates with significantly shorter servicing distances. We used the TrapGrid model to investigate novel “trap-sect” designs incorporating crossed, spoked, and parallel lines of traps, comparing them to a regular grid, in single survey and multiple-site scenarios. We calculated minimum servicing distances and simulated mean probabilities of detecting a pest population, judging overall performance of trap network designs using both metrics. For single sites, trap-sect designs reduced service distances by 65–89%, and most had similar detection probabilities as the regular grid. Kernel-smoothed intensity plots indicated that the best performing trap-sect designs distributed traps more fully across the area. With multiple sites (3 side by side), results depended on insect dispersal ability. All designs performed similarly in terms of detection for highly mobile insects, suggesting that designs minimizing service distances would be best for such pests. For less mobile pests the best trap-sect designs had 4–6 parallel lines, or 8 spokes, which reduced servicing distances by 33–50%. Comparisons of hypothetical trap-sect arrays to real program trap locations for 2 pests demonstrated that the novel designs reduced both trap numbers and service distances, with little differences in mean nearest trap distance to random pest locations. Trap-sect designs in delimitation surveys could reduce costs and increase program flexibility without harming the ability to detect populations.
Identification of Spodoptera frugiperda (Lepidoptera: Noctuidae) and its two host strains in China by PCR-RFLP
Authors: Jiang Jian-Zhao , Huang Bo-Yu , Wu Qian , Li Shi-Yu , Gu Jun , Huang Li-Hua
Published: April 2023

The fall armyworm (FAW) Spodoptera frugiperda was first found in China in 2018. In other countries, FAW has evolved corn and rice strain biotypes. It is not possible to identify these strains based on morphology. In addition, FAW is very similar in appearance to several other common pests. These situations bring great challenges to the population management of FAW. In this study, we developed a rapid identification method based on PCR-RFLP to distinguish the two FAW strains and the FAW from other lepidopteran pests. A 697 bp mitochondrial cytochrome c oxidase I (COI) was cloned and sequenced from FAW, Spodoptera litura, Spodoptera exigua, and Mythimna separata. The COI fragments of these species revealed unique digestion patterns created by three enzymes (Tail, AlWN I, and BstY II). Thus, these four species can be distinguished from each other. The enzyme Ban I recognized a unique SNP site on a 638 bp triosephosphate isomerase (Tpi) fragment of the corn strain FAW. The Tpi fragment of the corn strain was cut into two bands. However, the rice strain could not be digested. Using this method, all 28 FAW samples collected from different host plants and locations in China were identified as the corn strain. This suggests that the rice strain has not yet invaded China. This method allows discrimination of FAW from other Lepidopteran pests and distinguishes the two FAW host strains.
Approximate Expected Utility Rationalization
Authors: Echenique Federico , Imai Taisuke , Saito Kota
Published: April 2023

We propose a new measure of deviations from expected utility theory. For any positive number e, we give a characterization of the datasets with a rationalization that is within e (in beliefs, utility, or perceived prices) of expected utility (EU) theory, under the assumption of risk aversion. The number e can then be used as a measure of how far the data is to EU theory. We apply our methodology to data from three large-scale experiments. Many subjects in these experiments are consistent with utility maximization, but not with EU maximization. Our measure of distance to expected utility is correlated with the subjects’ demographic characteristics.
A simple method for fast simulation of total reflection waves of single-well imaging with eccentric tools
Authors: Xu Jiaqi , Hu Hengshan , Han Bo
Published: April 2023

In the exploration of unconventional oil and gas reservoirs, single-well acoustic imaging has become an important technique to detect geophysical structures around the borehole. In this study, we propose a simple method to calculate the total reflection wavefields of pressure and displacement for single-well imaging (SWI) with eccentric monopole or dipoles. To calculate the pressure at the eccentric site for incident waves with different angles of incidence and azimuth, reciprocity is applied to the radiation from the eccentric monopole source and the far-field forces generating the waves corresponding to the incident waves. Displacement solutions are derived by calculating the gradient of the pressure fields. When considering eccentric monopole or dipole sources for an inclined reflector outside the borehole, reciprocity is again used to derive the total reflection waves, including the same type of waves (P-P/SV-SV/SH- SH) and the converted waves (P- SV/SV-P). The analytical results agree well with the reference solutions of the 3D finite-difference time-domain method, illustrating the validation of the method. The analysis shows that the pressure amplitude in the eccentric position is greater than that in the borehole axis, proving that the eccentric monopole can increase the weak amplitude of reflection waves. We also simulate the wavefields for the acoustic imaging model for eccentric monopole and dipoles. The results show that the pressure and displacement wavefields in the eccentric position are sensitive to the azimuth angle of the reflector, proving that SWI with eccentric logging tools is capable of identifying the azimuth angle.
Breakthrough invasive fungal infection in patients with myeloid malignancy receiving posaconazole tablet prophylaxis: Clinical features, risk factors, and posaconazole profiles
Authors: Hong Jin Yeong , Kang Cheol-In , Yang Jinyoung , Ko Jae-Hoon , Huh Kyungmin , Cho Sun Young , Chung Doo Ryeon , Jung Chul Won , Peck Kyong Ran
Published: April 2023

Posaconazole (PSC) delayed-release tablet prophylaxis is the standard of care for preventing invasive fungal infection (IFI) in patients with acute myeloid leukemia undergoing myelosuppressive chemotherapy. The clinical features, risk factors, and PSC profiles of breakthrough IFI (bIFI) in patients receiving PSC tablet prophylaxis were investigated. A single-center retrospective cohort study was conducted, including adult patients with myeloid malignancy who received prophylactic PSC tablets while undergoing chemotherapy from June 2016 to June 2021. Logistic regression analysis was used to identify risk factors for bIFI. A receiver operating characteristic curve was used to predict the relationship between PSC trough level at steady state and bIFI. A total of 434 patients with myeloid malignancy who received PSC tablets were screened. A total of 10 patients with bIFI were compared with 208 non-IFI patients. There were four proven and six probable IFI cases, nine due to Aspergillus, and one due to Fusarium species. The bIFI patients had higher in-hospital mortality (30.0%) than the non-IFI patients (1.9%; P < 0.001). History of allogeneic hematopoietic stem cell transplantation (odds ratio [OR] 6.27; 95% confidence interval [CI] 1.63–24.09), prolonged neutropenia ≥28 days (OR 4.33; 95% CI 1.20–15.70), and low plasma PSC concentration <0.7 µg/ml (OR 16.33; 95% CI 4.15–64.26) were risk factors for bIFI. The optimal cutoff value of plasma PSC concentration predicting bIFI was 0.765 µg/ml (sensitivity, 60.0%; specificity, 91.3%; area under the curve, 0.746). bIFI was not uncommon in patients with myeloid malignancy receiving PSC tablet prophylaxis and associated with poor outcomes. Therapeutic drug monitoring may still be necessary, even in patients receiving PSC tablets.
The progenitor galaxies of stellar haloes as ‘failed’ Milky Ways
Authors: Bose Sownak , Deason Alis J
Published: April 2023

The stellar halo of the Milky Way records the history of its interactions with dwarf galaxies, whose subsequent destruction results in the formation of an extended stellar component. Recent works have suggested that galaxies with masses comparable to the Large Magellanic Cloud (LMC, $M_\star \sim 10^9$ M☉) may be the primary building blocks of the stellar halo of our Galaxy. We use cosmological simulations of the Lambda cold dark matter model to investigate LMC-mass galaxies at $z$ = 1–2 using a semi-analytical model of galaxy formation. We find that LMC analogues at $z$ = 2 evolve until the present day along three distinct pathways: (i) those that are destroyed in Milky Way-mass hosts; (ii) those that are themselves the main progenitors of Milky Way-mass galaxies; and (iii) those that survive until $z$ = 0, with stellar mass ∼1.0 dex lower than typical Milky Ways. We predict that the properties of these galaxies at $z$ = 2 (stellar metallicities, sizes, gas content, etc.) are largely indistinguishable, irrespective of which of these pathways is eventually taken; a survey targeting such galaxies in this redshift range would struggle to tell apart a ‘destroyed’ stellar halo progenitor from a ‘surviving’ LMC analogue. The only factor that determines the eventual fate of these galaxies is their proximity to a neighbouring Milky Way main progenitor at $z$ = 2: while the mean separation to a ‘surviving’ galaxy is around 7 Mpc, it is only 670 kpc to a ‘destroyed’ galaxy. This suggests that old stellar populations in the Milky Way may share intrinsic (i.e. non-dynamical) properties that are essentially indistinguishable from progenitors of its stellar halo.
Interstellar formation of functionalized cyclopropenes
Authors: Flint Athena R , Rogers Blake N , Fortenberry Ryan C
Published: April 2023

Nearly two decades since the detection of cyclopropenone (c-C3H2O) in the interstellar medium (ISM), the understanding of how this molecule comes to be remains incomplete. Many hypotheses place the ubiquitous hydrocarbon c-C3H2 at the centre of such discussions. However, insights into c-C3H2 chemistry are further complicated by the recent detection of ethynyl cyclopropenylidene (c-C3HC2H) and the observation of a radio line possibly belonging to methylenecyclopropene (c-C3H2CH2). In a necessary reconciliation of past and current work on the chemical capabilities of c-C3H2 in interstellar environments, the formation pathways of several functionalized cyclopropenes from c-C3H2 and a hydrogenated radical are explored. Chemically accurate CCSD(T)-F12/cc-pVTZ-F12 calculations are used to evaluate the energies of reaction and generate structures along the reaction pathway for formation products deemed chemically plausible. Potential energy scans are used to include or rule out certain paths to product formation based on conformation to the necessary requirements of cold interstellar chemistry. Four functionalized cyclopropenes in addition to c-C3H2O have net exothermic reactions when forming from c-C3H2 (c-C3H2CC, c-C3H2S, c-C3H2NH, and c-C3H2CH2). The former three are found to have reaction profiles favourable for formation in the cold ISM, while c-C3H2CH2 can only form by passage through an association barrier that must be mitigated by an energy source of some kind. c-C3H2S and c-C3H2NH are the best candidates for new spectroscopic searches. A complete detection of c-C3H2CH2 is necessary to fully understand cyclopropenylidene chemistry in the ISM.
Massive pre-stellar cores in radiation-magneto-turbulent simulations of molecular clouds
Authors: He Chong-Chong , Ricotti Massimo
Published: April 2023

We simulate the formation and collapse of pre-stellar cores at few-au resolution in a set of radiation-magnetohydrodynamic simulations of giant molecular clouds (GMCs) using the grid-based code RAMSES-RT. We adopt, for the first time to our best knowledge, realistic initial/boundary conditions by zooming in on to individual massive pre-stellar cores within the GMC. We identify two distinct modes of fragmentation: ‘quasi-spherical’ and ‘filamentary’. In both modes, the fragments eventually become embedded in a quasi-steady accretion disc or toroid with radii ∼500–5000 au and opening angles H/R ∼ 0.5 − 1. The discs/toroids are Toomre stable but the accreted pre-existing fragments are found orbiting the outer disc, appearing as disc fragmentation. Each core converts nearly 100 per cent of the gas mass into a few massive stars forming near the disc centre. Large and massive discs around high-mass stars are supported by magnetic pressure in the outer disc, at radii >200–1000 au, and turbulent pressure in the inner disc. The most massive core accretes several times more mass than its initial mass, forming a cluster of 8 massive (proto)stars enshrouded by a toroid, suggesting a competitive accretion scenario for the formation of stars above ∼30 M⊙. We also find that the H ii regions produced by a single massive star remain trapped in the dense circumstellar discs for a few hundred kiloyears, while the dynamic motions of massive stars in wide binaries or multiple systems displace the stars from the densest parts of the disc, allowing UV radiation to escape producing steady or pulsating bipolar H ii regions.
Survival and dynamics of rings of co-orbital planets under perturbations
Authors: Raymond Sean N , Veras Dimitri , Clement Matthew S , Izidoro Andre , Kipping David , Meadows Victoria
Published: April 2023

In co-orbital planetary systems, two or more planets share the same orbit around their star. Here we test the dynamical stability of co-orbital rings of planets perturbed by outside forces. We test two setups: (i) ‘stationary’ rings of planets that, when unperturbed, remain equally spaced along their orbit and (ii) horseshoe constellation systems, in which planets are continually undergoing horseshoe librations with their immediate neighbours. We show that a single rogue planet crossing the planets’ orbit more massive than a few lunar masses ($0.01\!-\!0.04 {\rm \, M_\oplus }\!\!$ ) systematically disrupts a co-orbital ring of 6, 9, 18, or 42 Earth-mass planets located at 1 au. Stationary rings are more resistant to perturbations than horseshoe constellations, yet when perturbed they can transform into stable horseshoe constellation systems. Given sufficient time, any co-orbital ring system will be perturbed into either becoming a horseshoe constellation or complete destabilization.
The C/N ratio from FUV spectroscopy as a constraint on evolution of the dwarf nova HS 0218 + 3229
Authors: Toloza Odette , Gänsicke Boris T , Guzmán-Rincón Laura M , Marsh Tom R , Szkody Paula , Schreiber Matthias R , de Martino Domitilla , Zorotovic Monica , El-Badry Kareem , Koester Detlev , Lagos Felipe
Published: April 2023

White dwarfs that accrete from non-degenerate companions show anomalous carbon and nitrogen abundances in the photospheres of their stellar components have been postulated to be descendants of supersoft X-ray binaries. Measuring the carbon-to-nitrogen abundance ratio may provide constraints on their past evolution. We fit far-ultraviolet spectroscopy of the cataclysmic variable HS 0218 + 3229 taken with the Cosmic Origins Spectrograph using Markov chain Monte Carlo methods, and found the carbon-to-nitrogen ratio is about one tenth of the Solar value $(\rm{\log \mathrm{[C/N]}}=-0.56\pm 0.15)$. We also provide estimates of the silicon and aluminium abundances, and upper limits for iron and oxygen. Using the parameters we derived for HS 0218 + 3229 we reconstruct its past. We calculated a grid of mesa models and implemented Gaussian process fits in order to determine its most likely initial binary configuration. We found that an initial mass of the donor of $M_{\rm donor;i}=0.90-0.98,\rm{\mathrm{M}_{\odot }}$ and an initial orbital period of Porb; i = 2.88 d (Porb; i = 3.12–3.16 d) for an assumed initial white dwarf mass of $\rm{M_{\mathrm{WD}}}_\mathrm{;i}=0.83\, \rm{\mathrm{M}_{\odot }}$$(\rm{M_{\mathrm{WD}}}_{\rm ;i}=0.60\, \rm{\mathrm{M}_{\odot }})$ can replicate the measured parameters. The low mass ratio, $M_{\rm donor;i} / \rm{M_{\mathrm{WD}}}_{\rm ;i} =1.08-1.18\, (1.5-1.63)$, suggests that the system did not go through a phase of hydrogen-burning on the white dwarf’s surface. However, we can not exclude a phase of thermal time-scale mass transfer in the past. We predict that HS 0218 + 3229 will evolve below the ≃ 76.2 ± 1 min period minimum for normal cataclysmic variables.
Mildly relativistic motion in the radio-quiet quasar PG 1351+640
Authors: Wang Ailing , An Tao , Guo Shaoguang , Ho Luis C , Baan Willem A , Braun Robert , Chen Sina , Cheng Xiaopeng , Hartley Philippa , Yang Jun , Zhang Yingkang
Published: April 2023

Measuring the proper motion of the emission component in radio-quiet quasars (RQQs) could help to distinguish between the origins of the radio emission and to understand whether the jet production mechanism is the same in radio-loud quasars and RQQs. PG 1351+640 is one of the few RQQs suitable for proper motion studies: it has two compact components on milli-arcsec scales, a flat-spectrum core and a steep-spectrum jet; both components are ≳2 mJy at 5 GHz and are well suited for Very Long Baseline Array (VLBA) observations. We compare recent VLBA observations with that made seventeen years ago and find no significant change in the core-jet separation between 2005 and 2015 (a proper motion of 0.003 mas yr−1). However, the core-jet separation increased significantly between 2015 and 2022, inferring a jet proper motion velocity of 0.063 mas yr−1, which corresponds to an apparent transverse velocity of $0.37\, c$ . The result suggests that the jet of the RQQ PG 1351+640 is mildly relativistic and oriented at a relatively small viewing angle.
Work experience, information revelation, and study effort
Authors: Mergoupis Thanos , Zubrickas Robertas
Published: April 2023

Firms screen graduates using grade thresholds, which can turn into students’ targeted learning outcomes or reference points in the model of study effort choice. Variability in the usage of grade thresholds implies students’ uncertainty about the value of grades. Work experience from internships can reduce this uncertainty and, in turn, affect the choice of study effort. We theoretically show that a reduction in uncertainty induces more effort from less able students but, in contrast, less effort from more able students. Consistent with the theory, we empirically find that students returning from year-long internships have a flatter grade-ability profile.
Magnetic field of solar dark filaments obtained from He i10830 Å spectropolarimetric observation
Authors: Yamasaki Daiki , Huang Yu Wei , Hashimoto Yuki , Cabezas Denis P , Kawate Tomoko , UeNo Satoru , Ichimoto Kiyoshi
Published: April 2023

Solar filaments are dense, cool plasma clouds in the solar corona. They are supposed to be supported in a dip of the coronal magnetic field. However, the models still disagree between two types of field configuration; one is the normal polarity model proposed by Kippenhahn and Schlueter (1957, Z. Astrophys., 43, 36), and the other is the reverse polarity model proposed by Kuperus and Raadu (1974, A&A, 31, 189). To understand the mechanism that makes the filaments become unstable before eruption, it is critical to know the magnetic structure of solar filaments. We performed spectropolarimetric observation in the He i (10830 Å) line to investigate the magnetic field configuration of dark filaments. The observation was carried out with the Domeless Solar Telescope at Hida Observatory with a polarization sensitivity of 3.0 × 10−4. We obtained eight samples of filaments in a quiet region. As a result of the analysis of full Stokes profiles of filaments, we found that the field strengths were estimated as 8–35 G. By comparing the direction of the magnetic field in filaments and the global distribution of the photospheric magnetic field, we determined the magnetic field configuration of the filaments, and we concluded that one out of the eight samples has normal polarity configuration, and seven out of the eight have reverse polarity configuration.
Lessons learned and new strategies for success: Evaluating the Implementation of Competency-Based Medical Education in Queen’s Pediatrics
Authors: Acker Amy , Leifso Kirk , Crawford Lindsay , Braund Heather , Hawksby Emily , Hall Andrew K , McEwen Laura , Dalgarno Nancy , Dagnone Jeffrey Damon
Published: April 2023

Objectives

In 2017, Queen’s University launched Competency-Based Medical Education (CBME) across 29 programs simultaneously. Two years post-implementation, we asked key stakeholders (faculty, residents, and program leaders) within the Pediatrics program for their perspectives on and experiences with CBME so far.

Methods

Program leadership explicitly described the intended outcomes of implementing CBME. Focus groups and interviews were conducted with all stakeholders to describe the enacted implementation. The intended versus enacted implementations were compared to provide insight into needed adaptations for program improvement.

Results

Overall, stakeholders saw value in the concept of CBME. Residents felt they received more specific feedback and monthly Competence Committee (CC) meetings and Academic Advisors were helpful. Conversely, all stakeholders noted the increased expectations had led to a feeling of assessment fatigue. Faculty noted that direct observation and not knowing a resident’s previous performance information was challenging. Residents wanted to see faculty initiate assessments and improved transparency around progress and promotion decisions.

Discussion

The results provided insight into how well the intended outcomes had been achieved as well as areas for improvement. Proposed adaptations included a need for increased direct observation and exploration of faculty accessing residents’ previous performance information. Education was provided on the performance expectations of residents and how progress and promotion decisions are made. As well, “flex blocks” were created to help residents customize their training experience to meet their learning needs. The results of this study can be used to inform and guide implementation and adaptations in other programs and institutions.
Integration of multiple stress signals in plants using synthetic Boolean logic gates
Authors: Anderson Charles E , Ferreira Savio S , Antunes Mauricio S
Published: April 2023

As photosynthetic organisms, plants have a potential role in the sustainable production of high-value products such as medicines, biofuels, and chemical feedstocks. With effective engineering using synthetic biology approaches, plant-based platforms could conceivably be designed to minimize the costs and waste of production for materials that would otherwise be uneconomical. Additionally, modern agricultural crops could be engineered to be more productive, resilient, or restorative in different or rapidly changing environments and climates. Information-processing genetic devices and circuits containing multiple interacting parts that behave predictably must be developed to achieve these complex goals. A genetic Boolean AND logic gate is a device that computes the presence or absence of 2 inputs (signals and stimuli) and produces an output (response) only when both inputs are present. We optimized individual genetic components and used synthetic protein heterodimerizing domains to rationally assemble genetic AND logic gates that integrate 2 hormonal inputs in transgenic Arabidopsis thaliana plants. These AND gates produce an output only in the presence of both abscisic acid and auxin but not when either or neither hormone is present. The AND logic gate can also integrate signals resulting from 2 plant stresses, cold temperature and bacterial infection, to produce a response. The design principles used here are generalizable, and, therefore, multiple orthogonal AND gates could be assembled and rationally layered to process complex genetic information in plants. These layered logic gates may be used in genetic circuits to probe fundamental questions in plant biology, such as hormonal crosstalk, in addition to plant engineering for bioproduction.
The Impact of Racial Descriptive Norms on Vaccination against COVID-19
Authors: Oceno Marzia , Yen Wei-Ting
Published: April 2023

Racial disparities have persisted in COVID-19 infection, hospitalization, and death rates in the United States. Differences in vaccination hesitancy have also emerged by race: communities of color and, particularly, African Americans have been more reluctant to get a vaccine to prevent COVID-19. Can racial descriptive norms provide a tool to increase confidence and reduce hesitancy within the US public? We conducted a survey experiment at the end of January 2021 on a sample of non-Hispanic white and Black American adults. The experiment varied whether information about uptake intent by race was provided, and what racial group was reported to be more likely to get a vaccine if one were available to them today. Our results show that the tendency to conform to one’s racial ingroup can play a key role in improving vaccination attitudes across race. Indeed, whites become significantly more willing to get vaccinated now or in the near future after they learn that a majority of whites intend to do so. Furthermore, both Blacks with high science trust and whites with low science trust are more likely to accept multiple vaccine doses and yearly boosters if their racial ingroup plans on getting vaccinated. Finally, the desire for ingroup conformity leads Blacks with low science trust to be more willing to receive a vaccine when they are provided a choice among vaccine brands.
Synovial macrophage activation mediates pain experiences in experimental knee osteoarthritis
Authors: Blackler Garth , Lai-Zhao Yue , Klapak Joseph , Philpott Holly T. , Pitchers Kyle K. , Maher Andrew R. , Fiset Benoit , Walsh Logan A. , Gillies Elizabeth R. , Appleton C. Thomas
Published: April 2023

It has been suggested that synovial macrophages mediate nociceptive signals in knee osteoarthritis (OA) but the underlying mechanisms are unknown. Our objectives were to investigate the role of synovial macrophages and their activation via signal transducer and activator of transcription (STAT) signaling in mediating OA pain experiences.

We induced experimental OA in rats via knee destabilization surgery and then performed RNA sequencing analysis in sorted synovial macrophages to identify signaling pathways associated with macrophage activation. Next, we repeated intra-articular injections of liposomal clodronate to deplete macrophages, or liposomal inhibitors of STAT1 or STAT6 to block macrophage activation, and tested the effects on local and distal mechanical pain sensitivity. We also assessed synovitis, cartilage damage, and synovial macrophage infiltration with histopathology and immunofluorescence, and crosstalk between liposomal drug-treated synovium and articular chondrocytes in co-culture.

Most enriched signaling pathways in activated OA macrophages involved STAT signalling. Macrophage depletion and STAT6 inhibition led to marked, sustained improvements in mechanical pain sensitivity and synovial inflammation compared to controls, but macrophage depletion caused increased synovial fibrosis and vascularization. In contrast, STAT1 and STAT6 inhibition in macrophages did not worsen synovial or cartilage pathology. In crosstalk assays, macrophage STAT1-inhibited synovium caused the greatest increases in the expression of anabolic and catabolic chondrocyte genes and sulphated glycosaminoglycan secretion in chondrocytes.

Our results suggest that synovial macrophages play a key role in mediating pain experiences in experimental knee OA, and that selectively blocking STAT6 in synovial macrophages may reduce OA-related pain without accelerating joint tissue damage. (248/250)

One Sentence Summary

Selective drug targeting to synovial macrophages improves pain experiences in surgical joint destabilization-induced experimental rodent knee OA. (145/150)
TISSUE: uncertainty-calibrated prediction of single-cell spatial transcriptomics improves downstream analyses
Authors: Sun Eric D. , Ma Rong , Negredo Paloma Navarro , Brunet Anne , Zou James
Published: April 2023

Whole-transcriptome spatial profiling of genes at single-cell resolution remains a challenge. To address this limitation, spatial gene expression prediction methods have been developed to infer the spatial expression of unmeasured transcripts, but the quality of these predictions can vary greatly. Here we present TISSUE (Transcript Imputation with Spatial Single-cell Uncertainty Estimation) as a general framework for estimating uncertainty for spatial gene expression predictions and providing uncertainty-aware methods for downstream inference. Across eleven benchmark datasets, TISSUE provides well-calibrated prediction intervals for predicted expression values. Moreover it consistently reduces false discovery rates for differential gene expression analysis, improves clustering and visualization of predicted spatial transcriptomics, and improves the performance of supervised learning models trained on predicted gene expression profiles. Applying TISSUE to a MERFISH spatial transcriptomics dataset of the adult mouse subventricular zone, we identified subtypes within the neural stem cell lineage and developed subtype-specific regional classifiers. TISSUE is publicly available as a flexible wrapper method for existing spatial gene expression prediction methods to assist researchers with implementing uncertainty-aware analyses of spatial transcriptomics data.