bluuebunny/crossref_metadata_2025 huggingface dataset:
Anisotropic tomography of the East Japan subduction zone: influence of inversion algorithms
Authors: Jia Ruo , Zhao Dapeng
Published: May 2023

An important element of seismic tomography is the inversion process. In this work, we use P-wave arrival times of local earthquakes recorded at onshore and offshore seismic stations in East Japan to investigate the influence of two well-known inversion algorithms (LSQR and L-BFGS-B) on anisotropic tomography. Our synthetic tests show that a large damping parameter in the LSQR algorithm can lead to a stable and fast convergence, but it can result in many small value disturbances. The L-BFGS-B algorithm, which has second-order convergence, could converge fast to the optimal solution without damping regularization, but an inappropriate bound on the unknown parameters makes them hard to be recovered fully and causes strong trade-off between isotropic velocity and azimuthal anisotropy. If appropriate control parameters are adopted, the two inversion algorithms lead to almost the same results, though the L-BFGS-B provides a more efficient convergence and leads to a slightly better fit to the data than LSQR does. The two algorithms are applied to investigate the 3-D P-wave velocity (Vp) structure and azimuthal anisotropy of the East Japan subduction zone. Our results show that high-Vp anomalies and trench-normal fast-velocity directions (FVDs) exist in the forearc crust beneath the Pacific Ocean off South Hokkaido, which may reflect a cold and hydrated forearc crust with aligned microcracks or fractures. Significant low-Vp anomalies and trench-parallel FVDs exist at 40–80 km depths beneath Hokkaido, reflecting a water-rich mantle wedge with aligned B-type olivine. In the subducting Pacific slab, strong anisotropy with trench-parallel FVDs is revealed, reflecting localized horizontal bending of the slab.
The estimated effect of season and vitamin D in the first trimester on pubertal timing in girls and boys: a cohort study and an instrumental variable analysis
Authors: Gaml-Sørensen Anne , Brix Nis , Ernst Andreas , Lunddorf Lea Lykke Harrits , Lindh Christian , Toft Gunnar , Henriksen Tine Brink , Arah Onyebuchi A , Ramlau-Hansen Cecilia Høst
Published: May 2023

Background

Season of birth has been associated with age at menarche. Maternal vitamin D levels in pregnancy may explain this effect. We investigated whether the season of first trimester or maternal 25-hydroxyvitamin D3 [25(OH)D3] levels were associated with pubertal timing in children.

Methods

We conducted a follow-up study of 15 819 children born in 2000–03 from the Puberty Cohort, nested in the Danish National Birth Cohort (DNBC). Mean differences in attaining numerous pubertal markers, including a combined estimate for the average age at attaining all pubertal markers, were estimated for low (November–April) relative to high (May–October) sunshine exposure season in the first trimester using multivariable interval-censored regression models. Moreover, we conducted a two-sample instrumental variable analysis using season as an instrument for maternal first-trimester 25(OH)D3 plasma levels obtained from a non-overlapping subset (n = 827) in the DNBC.

Results

For the combined estimate, girls and boys of mothers who had their first trimester during November–April had earlier pubertal timing than girls and boys of mothers whose first trimester occurred during May–October: –1.0 months (95% CI: –1.7 to –0.3) and –0.7 months (95% CI: –1.4 to –0.1), respectively. In the instrumental variable analysis, girls and boys also had earlier pubertal timing: respectively, –1.3 months (95% CI: –2.1 to –0.4) and –1.0 months (95% CI: –1.8 to –0.2) per SD (22 nmol/L) decrease in 25(OH)D3.

Conclusions

Both first pregnancy trimester during November–April and lower 25(OH)D3 were associated with earlier pubertal timing in girls and boys.
Clinical pharmacists’ participation in ward rounds in hospitals: responses from a national survey
Authors: Babu Dona , Rowett Debra , Lim Renly , Marotti Sally , Wisdom Alice , Ellett Lisa Kalisch
Published: May 2023

Objectives

The inclusion of clinical pharmacists in ward rounds (WRs) can reduce adverse drug events, improve communication and enable collaborative decision-making. The aim of this study is to investigate the level of and factors that influence WR participation by clinical pharmacists in Australia.

Methods

An online administered, anonymous survey of clinical pharmacists in Australia was conducted. The survey was open to pharmacists aged ≥18 years, who had worked in an Australian hospital in a clinical role in the previous two weeks. It was distributed via The Society of Hospital Pharmacists of Australia and on pharmacist-specific social media threads. Survey questions related to the extent of WR participation and factors that influence WR participation. Cross-tabulation analysis was conducted to determine whether there was an association between WR participation and factors that influence WR participation.

Key findings

Ninety-nine responses were included. The level of WR participation by clinical pharmacists in Australian hospitals was low, with only 26/67 (39%) pharmacists who had a WR in their clinical unit actually attending the WR in the previous 2 weeks. Factors that influenced WR participation included having recognition of the role of the clinical pharmacist within the WR team, support from pharmacy management and the broader interprofessional team, and having adequate time and expectation from pharmacy management and colleagues to participate in WRs.

Conclusions

This study highlights the need for ongoing interventions such as restructuring workflows and increasing the awareness of the role of a clinical pharmacist in WR to increase participation of pharmacists in this interprofessional activity.
Leveraging the lymphohematopoietic graft-versus-host reaction (LGVHR) to achieve allograft tolerance and restore self tolerance with minimal toxicity
Authors: Sykes Megan
Published: May 2023

Mixed allogeneic chimerism has considerable potential to advance the achievement of immune tolerance to alloantigens for transplantation and the restoration of self-tolerance in patients with autoimmune disease. In this article, I review evidence that graft-versus-host (GVH) alloreactivity without graft-vs-host disease (GVHD), termed a lymphohematopoietic graft-vs-host reaction (LGVHR), can promote the induction of mixed chimerism with minimal toxicity. LGVHR was originally shown to occur in an animal model when non-tolerant donor lymphocytes were administered to mixed chimeras in the absence of inflammatory stimuli and was found to mediate powerful graft-vs-leukemia/lymphoma effects without GVHD. Recent large animal studies suggest a role for LGVHR in promoting durable mixed chimerism and the demonstration that LGVHR promotes chimerism in human intestinal allograft recipients has led to a pilot study aiming to achieve durable mixed chimerism.
Clinical, contextual and hospital-level factors associated with escalation and de-escalation of empiric Gram-negative antibiotics among US inpatients
Authors: Baghdadi Jonathan D , Goodman Katherine E , Magder Laurence S , Heil Emily L , Claeys Kimberly , Bork Jacqueline , Harris Anthony D
Published: May 2023

Background

Empiric Gram-negative antibiotics are frequently changed in response to new information. To inform antibiotic stewardship, we sought to identify predictors of antibiotic changes using information knowable before microbiological test results.

Methods

We performed a retrospective cohort study. Survival-time models were used to evaluate clinical factors associated with antibiotic escalation and de-escalation (defined as an increase or decrease, respectively, in the spectrum or number of Gram-negative antibiotics within 5 days of initiation). Spectrum was categorized as narrow, broad, extended or protected. Tjur’s D statistic was used to estimate the discriminatory power of groups of variables.

Results

In 2019, 2 751 969 patients received empiric Gram-negative antibiotics at 920 study hospitals. Antibiotic escalation occurred in 6.5%, and 49.2% underwent de-escalation; 8.8% were changed to an equivalent regimen. Escalation was more likely when empiric antibiotics were narrow-spectrum (HR 19.0 relative to protected; 95% CI: 17.9–20.1), broad-spectrum (HR 10.3; 95% CI: 9.78–10.9) or extended-spectrum (HR 3.49; 95% CI: 3.30–3.69). Patients with sepsis present on admission (HR 1.94; 95% CI: 1.91–1.96) and urinary tract infection present on admission (HR 1.36; 95% CI: 1.35–1.38) were more likely to undergo antibiotic escalation than patients without these syndromes. De-escalation was more likely with combination therapy (HR 2.62 per additional agent; 95% CI: 2.61–2.63) or narrow-spectrum empiric antibiotics (HR 1.67 relative to protected; 95% CI: 1.65–1.69). Choice of empiric regimen accounted for 51% and 74% of the explained variation in antibiotic escalation and de-escalation, respectively.

Conclusions

Empiric Gram-negative antibiotics are frequently de-escalated early in hospitalization, whereas escalation is infrequent. Changes are primarily driven by choice of empiric therapy and presence of infectious syndromes.
DSPE-PEG polymer enhanced berberine absorption specifically in the small intestine of rats through paracellular passway
Authors: Gao Yang , Sun Jianmei , Wang Shucong , Huxiao Lisong , Xu Yali , Zhang Hailong
Published: May 2023

Objectives

This study focuses on investigating the potential impact of DSPE-PEG polymers on intestinal absorption and related mechanism of berberine in rats.

Methods

Effect of DSPE-PEG polymer on intestinal absorption of berberine was investigated with an in situ closed-loop method in rats. To confirm the safety of DSPE-PEG polymer, morphological observation of rat intestine and measurement of biological markers in the intestinal perfusion of rats was performed. Underling mechanism behind promoting action of DSPE-PEG polymer was explored from its impact on the P-gp function and tight junction using in vitro diffusion chamber system, Caco-2 monolayer cells and western blot.

Key findings

DSPE-PEG polymer demonstrated significant enhancement action on the berberine absorption in rats without any obvious membrane toxicity. DSPE-PEG polymer (1.0%, w/v) induced the most significant promoting effect on berberine absorption specifically in the small intestine of rats. Results of mechanistic studies revealed that DSPE-PEG polymer might not regulate intestinal P-gp function, but significantly down-regulated the expression of tight junction-related proteins, which accordingly led to loosening the tight junctions of intestinal epithelium cells, and consequently increased paracellular absorption of berberine in rats.

Conclusions

DSPE-PEG polymer, as an excellent absorption enhancer, seems very promising in increasing oral bioavailability of berberine.
Evaluation of in vivo and ex vivo pre-treated bone marrow-derived mesenchymal stem cells with resveratrol in streptozotocin-induced type 1 diabetic rats
Authors: Khalil S G , Younis N N , Shaheen M A , Hammad S K , Elswefy S E
Published: May 2023

Objectives

To compare the therapeutic potential of rat bone marrow-derived mesenchymal stem cells (BM-MSCs) preconditioned ex-vivo with resveratrol (MCR) and BM-MSCs isolated from resveratrol-pre-treated rats (MTR) in type-1 diabetic rats.

Methods

Type-1 diabetes was induced by a single streptozotocin injection (50 mg/kg; ip) in 24 rats. Following the confirmation of T1DM, diabetic rats were randomly divided into four groups: diabetic control (DC), diabetic rats treated with insulin subcutaneous (7.5 IU/kg/day), diabetic rats treated with MCR cells (3 × 106cells/rat, intravenous) and diabetic rats treated with MTR cells (3 × 106cells/rat, intravenous). Rats were sacrificed 4 weeks following cellular transplantation.

Key findings

Untreated diabetic rats suffered from pancreatic cell damage, had high blood glucose levels, increased apoptotic, fibrosis, and oxidative stress markers and decreased survival and pancreatic regeneration parameters. Both MSCs preconditioned ex-vivo with RES and MSCs isolated from rats pre-treated with RES homed successfully in injured pancreas and showed therapeutic potential in the treatment of STZ-induced T1DM. MCR cells showed better efficiency than MTR cells.

Conclusions

The pre-conditioning of BM-MSCs with resveratrol may be a promising therapeutic possibility in T1DM. Resveratrol-preconditioned BM-MSCs encouraged effects almost comparable to that of exogenous insulin with the advantages of cured pancreas and restored islets not attained by insulin.
Development of a deep learning-based error detection system without error dose maps in the patient-specific quality assurance of volumetric modulated arc therapy
Authors: Kimura Yuto , Kadoya Noriyuki , Oku Yohei , Jingu Keiichi
Published: May 2023

To detect errors in patient-specific quality assurance (QA) for volumetric modulated arc therapy (VMAT), we proposed an error detection method based on dose distribution analysis using unsupervised deep learning approach and analyzed 161 prostate VMAT beams measured with a cylindrical detector. For performing error simulation, in addition to error-free dose distribution, dose distributions containing nine types of error, including multileaf collimator (MLC) positional errors, gantry rotation errors, radiation output errors and phantom setup errors, were generated. Only error-free data were employed for the model training, and error-free and error data were employed for the tests. As a deep learning model, the variational autoencoder (VAE) was adopted. The anomaly of test data was quantified by calculating Mahalanobis distance based on the feature vectors acquired from a trained encoder. Based on this anomaly, test data were classified as ‘error-free’ or ‘any-error.’ For comparison with conventional approaches, gamma (γ)-analysis was performed, and supervised learning convolutional neural network (S-CNN) was constructed. Receiver operating characteristic curves were obtained to evaluate their performance with the area under the curve (AUC). For all error types, except systematic MLC positional and radiation output errors, the performance of the methods was in the order of S-CNN ˃ VAE-based ˃ γ-analysis (only S-CNN required error data for model training). For example, in random MLC positional error simulation, the AUC of our method, S-CNN and γ-analysis were 0.699, 0.921 and 0.669, respectively. Our results showed that the VAE-based method has the potential to detect errors in patient-specific VMAT QA.
Solitary infantile myofibromatosis of the petrous bone: a diagnostic pitfall in uncommon location illustrated by a case report
Authors: El Ouazzani Hafsa , Azzam Imane , Benyahya Zainab , Chehrastane Rachida , Oujilal Abdelilah , Zouaidia Fouad , Cherradi Nadia
Published: May 2023

Infantile myofibromatosis (IM) is the most common fibrous disorder of infancy and early childhood. Solitary intracranial involvement is rare and often unrecognized. This makes its early diagnosis and adequate management difficult. The majority of lesions are localized to the skull or dura with variable intracranial extension. Herein, we report a misdiagnosed and aggressive presentation of a solitary IM of the petrous bone. Our aim is to discuss histopathological differential diagnoses and management difficulties.
Breast hibernoma in a male patient: a rare case report and review of the literature
Authors: Hanna Sam , Davis Arie , Diab Jason , Clement Zackariah
Published: May 2023

Hibernomas are uncommon, benign, lipomatous tumours of brown fat. Although hibernomas may arise from any region where brown fat exists, common locations include thigh, shoulder, back and neck. We report a rare finding of a breast hibernoma in a 43-year-old male. The patient was managed surgically with an excision of the breast mass. This report will outline the pathology and clinical findings of breast hibernomas and review of the literature.
Solitary mesenteric fibromatosis in a male patient: clinical case report
Authors: David Aulestia José , Piedra Jorge , Guachilema Ribadeneira Alex , Remache Veronica , Vasconez Carla , Arias Grace
Published: May 2023

Mesenteric fibromatosis is a rare tumor that grows slowly and asymptomatically and is more frequent among men. The risk factors described in the literature may not be present in all cases. The clinical presentation is variable and depends on the localization of the tumor and the involvement of surrounding structures. Imaging studies such as abdominal computed tomography and magnetic resonance imaging are the preferred methods for the diagnosis of this tumor. However, a definitive diagnosis is made based on histopathology and immunohistochemistry results. Surgical resection remains the preferred option for the treatment of mesenteric fibromatosis. This report presents a clinical case of mesenteric fibromatosis in a male patient who presented with partial abdominal obstruction and the absence of risk factors for mesenteric fibromatosis.
Complete median nerve axonotmesis as a late postoperative complication in distal radius fracture
Authors: Barrera-Ochoa Sergi , Prieto Meré Jose Antonio
Published: May 2023

Locked volar plate fixation is currently the gold-standard treatment for distal radius fractures. Although volar plating is considered as a reasonably safe treatment option for distal radial fractures, several complications can be observed, such as median nerve injury. We present an 84-year-old male with an intra-articular comminuted fracture of the left distal radius that presented as a late postoperative complication a complete axonotmesis of the median nerve due to screw migration of a locked volar plate. An electromyography was performed confirming complete median nerve axonotmesis, and with proximal stimulation, a Martin–Gruber anastomosis in the proximal forearm was discovered.
Network analysis of a northern long-eared bat (Myotis septentrionalis) maternity colony in a suburban forest patch
Authors: Gorman Katherine M , Barr Elaine L , Nocera Tomás , Ford W Mark
Published: May 2023

Many bat species are highly social, forming groups of conspecifics, particularly during the maternity season. In temperate North America, these social groups are typically comprised of closely related individuals or individuals that share some common trait (i.e. reproductive state or shared hibernacula from the previous winter). In the summer, when bats use forests for day-roosts, these social groups often demonstrate nonrandom patterns of periodically associating in common roosts and disassociating using different roosts as a ‘fission–fusion society’. As cave hibernating bat species in North America continue to decline due to the impacts of White-nose Syndrome, opportunities to describe these dynamics are becoming rare. Unfortunately, these patterns often are still poorly documented, yet understanding these behaviors is critical for species-specific habitat conservation and management. In our study, we tracked female northern long-eared bats (Myotis septentrionalis) to their day-roosts in a small, suburban forest fragment in coastal New York, USA, in the summers of 2018 and 2019. We confirmed that the bats shared roost sites and, using network analyses, analyzed social dynamics and space use. In contrast to previous research on this imperiled species in large, unfragmented core forests, we found a more dense, connected roost network that concentrated around forest patch edges. Unusual for this species, primary roosts were anthropogenic structures. Our findings suggest that northern long-eared bats can utilize small forest patches and that incorporation of specific types of anthropogenic roosts might be an effective strategy for long-term conservation in more urbanized landscapes where forest management actions to enhance day-roosting conditions are impractical and the risk of stochastic loss of roosts is high.
Healthcare Decision Making for Children in Singapore: The Missing Chapter in Comparison with English Law
Authors: Chua Hillary
Published: May 2023

In medical practice, Singaporean paediatricians regularly encounter ethical dilemmas concerning the medical treatment of children and adolescents. While such disputes tend to be resolved out of court, it is useful to understand the legal framework for decision making in hard cases. Unlike in England and Wales where there is an abundance of litigation in this area and the law is well established, Singapore has a dearth of case law and a few discrete statutes regarding consent to medical treatment by children. Local legal resources on this subject are limited, and the differences between Singaporean and English law are not always made clear in medical guidance. Therefore, this article provides a comparative roadmap and seeks to answer key questions in Singaporean law on healthcare decision making for children, such as: Who can make decisions on their behalf? When can children give or refuse consent to treatment on their own? What is the threshold for judicial intervention in disputes concerning children’s medical care? How should ‘best interests’ be determined? This article identifies gaps and proposes ways that Singaporean law can develop by drawing inspiration from English judgments while making adaptations to the local context. It outlines situations when it is appropriate for the courts to decide cases concerning children’s medical treatment, notwithstanding the preference for alternative dispute resolution in Singapore.
Extreme evaporation of planets in hot thermally unstable protoplanetary discs: the case of FU Ori
Authors: Nayakshin Sergei , Owen James E , Elbakyan Vardan
Published: May 2023

Disc accretion rate onto low mass protostar FU Ori suddenly increased hundreds of times 85 yr ago and remains elevated to this day. We show that the sum of historic and recent observations challenges existing FU Ori models. We build a theory of a new process, Extreme Evaporation (EE) of young gas giant planets in discs with midplane temperatures of ≳ 30 000 K. Such temperatures are reached in the inner 0.1 AU during thermal instability bursts. In our 1D time-dependent code the disc and an embedded planet interact through gravity, heat, and mass exchange. We use disc viscosity constrained by simulations and observations of dwarf novae instabilities, and we constrain planet properties with a stellar evolution code. We show that dusty gas giants born in the outer self-gravitating disc reach the innermost disc in a ∼O(104) yr with radius of ∼10RJ. We show that their EE rates are $\gtrsim 10^{-5} {\rm {\rm M}_{\odot }}$ yr−1; if this exceeds the background disc accretion activity then the system enters a planet-sourced mode. Like a stellar secondary in mass-transferring binaries, the planet becomes the dominant source of matter for the star, albeit for ∼O(100) yr. We find that a ∼6 Jupiter mass planet evaporating in a disc fed at a time-averaged rate of $\sim 10^{-6} {\rm {\rm M}_{\odot }}$ yr−1 appears to explain all that we currently know about FU Ori accretion outburst. More massive planets and/or planets in older less massive discs do not experience EE process. Future FUOR modelling may constrain planet internal structure and evolution of the earliest discs.
A renewed search for radio emission from the variable γ-ray pulsar PSR J2021+4026
Authors: Shaw B , Stappers B W , Weltevrede P , Jordan C A , Mickaliger M B , Lyne A G
Published: May 2023

We undertake the first targeted search at 1.5 GHz for radio emission from the variable γ-ray pulsar PSR J2021+4026. This radio-quiet pulsar assumes one of two stable γ-ray emission states, between which it transitions on a time-scale of years. These transitions, in both γ-ray flux and pulse profile shape, are accompanied by contemporaneous changes to the pulsar’s spin-down rate. A number of radio pulsars are known to exhibit similar correlated variability, which in some cases involves an emission state in which the radio emission ceases to be detectable. In this paper, we perform a search for radio emission from PSR J2021+4026, using archival radio observations recorded when the pulsar was in each of its emission/spin-down states. Using improved techniques, we search for periodic radio emission as well as single pulse phenomena such as giant radio pulses and RRAT-like emission. Our search reveals no evidence of radio emission from PSR J2021+4026. We estimate that the flux density for periodic emission from PSR J2021+4026 does not exceed 0.2 mJy at this frequency. We also estimate single-pulse flux limits for RRAT-like bursts and giant radio pulses to be 0.3 and 100 Jy, respectively. We discuss the transitioning behaviour of PSR J2021+4026 in the context of pulsar glitches, intermittent pulsars and the increasingly common emission-rotation correlation observed in radio pulsars.
Clusters, clouds, and correlations: relating young clusters to giant molecular clouds in M33 and M31
Authors: Peltonen Joshua , Rosolowsky Erik , Johnson L Clifton , Seth Anil C , Dalcanton Julianne , Bell Eric F , Braine Jonathan , Koch Eric W , Lazzarini Margaret , Leroy Adam K , Skillman Evan D , Smercina Adam , Wainer Tobin , Williams Benjamin F
Published: May 2023

We use young clusters and giant molecular clouds (GMCs) in the galaxies M33 and M31 to constrain temporal and spatial scales in the star formation process. In M33, we compare the Panchromatic Hubble Andromeda Treasury: Triangulum Extended Region (PHATTER) catalogue of 1214 clusters with ages measured via colour–magnitude diagram (CMD) fitting to 444 GMCs identified from a new 35 pc resolution Atacama Large Millimeter/submillimeter Array (ALMA) 12CO(2–1) survey. In M31, we compare the Panchromatic Hubble Andromeda Treasury (PHAT) catalogue of 1249 clusters to 251 GMCs measured from a Combined Array for Research in Millimeter-wave Astronomy (CARMA) 12CO(1–0) survey with 20 pc resolution. Through two-point correlation analysis, we find that young clusters have a high probability of being near other young clusters, but correlation between GMCs is suppressed by the cloud identification algorithm. By comparing the positions, we find that younger clusters are closer to GMCs than older clusters. Through cross-correlation analysis of the M33 cluster data, we find that clusters are statistically associated when they are ≤10 Myr old. Utilizing the high precision ages of the clusters, we find that clusters older than ≈18 Myr are uncorrelated with the molecular interstellar medium (ISM). Using the spatial coincidence of the youngest clusters and GMCs in M33, we estimate that clusters spend ≈4–6 Myr inside their parent GMC. Through similar analysis, we find that the GMCs in M33 have a total lifetime of ≈11–15 Myr. We also develop a drift model and show that the above correlations can be explained if the clusters in M33 have a 5–10 km s−1 velocity dispersion relative to the molecular ISM.
Collisional excitation of N+(3P) in interstellar clouds
Authors: Gueguen Marie , Lique François
Published: May 2023

The detection of the N+ ion in ionized interstellar regions, as well as its use as a tracer for atomic nitrogen (N) in interstellar media, makes it an interesting ion from the astrophysical point of view. Accurate determination of the N+ abundance in the interstellar clouds requires detailed modelling of its excitation conditions. Hence, collisional excitation induced by the dominant interstellar species has to be studied. In this paper, we study the collisional excitation of N+ by He and H2. We provide new potential energy surfaces describing the interactions between N+ and He and between N+ and H2 considered as a structureless collider. Quantum calculations of the excitation cross-sections for collisions of N+ with He and H2 are provided, as well as the first excitation rate coefficients for N+ induced by these two species. The results are compared to collisional data for the excitation induced by electrons. It is shown that the excitation of N+ by a neutral collider can play a significant role in weakly ionized regions as well as in warm molecular clouds.
MeerKAT caught a Mini Mouse: serendipitous detection of a young radio pulsar escaping its birth site
Authors: Motta S E , Turner J D , Stappers B , Fender R P , Heywood I , Kramer M , Barr E D
Published: May 2023

In MeerKAT observations pointed at a Galactic X-ray binary located on the Galactic plane, we serendipitously discovered a radio nebula with cometary-like morphology. The feature, which we named ‘the Mini Mouse’ based on its similarity with the previously discovered ‘Mouse’ nebula, points back towards the previously unidentified candidate supernova remnant G45.24+0.18. We observed the location of the Mini Mouse with MeerKAT in two different observations, and we localized with arcsecond precision the 138-ms radio pulsar PSR J1914+1054g, recently discovered by the FAST telescope, to a position consistent with the head of the nebula. We confirm a dispersion measure of about 418 pc cm−3 corresponding to a distance between 7.8 and 8.8 kpc based on models of the electron distribution. Using our accurate localization and two period measurements spaced 90 d apart, we calculate a period derivative of (2.7 ± 0.3) × 10 −14 s s−1. We derive a characteristic age of approximately 82 kyr and a spin-down luminosity of 4 × 1035 erg s−1. For a pulsar age comparable with the characteristic age, we find that the projected velocity of the neutron star is between 320 and 360 km s−1 if it was born at the location of the supernova remnant. The size of the proposed remnant appears small if compared with the pulsar characteristic age; however, the relatively high density of the environment near the Galactic plane could explain a suppressed expansion rate and thus a smaller remnant.
Evolution of radioactive elements in the LMC: predictions for future γ-ray surveys
Authors: Vasini Arianna , Matteucci F , Spitoni E , Siegert Thomas
Published: May 2023

Short-lived radionuclides, such as 26Al and 60Fe, are tracers of star formation. Therefore, their abundances can unravel the recent star formation history of the host galaxy. In view of future γ-ray surveys, we predict the masses and fluxes of these two elements in the Large Magellanic Cloud (LMC) using new chemical evolution models. Our best model reproduces the abundance patterns of [α/Fe] ratios, the gas mass, the average metallicity, the present time supernova and nova rates observed in LMC. We show three main results: (i) the best model for the LMC suggests a star formation rate very mild at the beginning with a recent burst, and a Salpeter-like initial mass function. (ii) The predicted mass of 26Al is 0.33 M⊙, 2/3 produced by massive stars and 1/3 by novae. (iii) The predicted mass of 60Fe is 0.44 M⊙, entirely produced by massive stars. This result suggests a larger fraction of 60Fe, at variance with the Milky Way. The explanation for this lies in the adopted initial mass function, that for the LMC contains more massive stars than for the Milky Way. These predictions can be useful for the COSI-SMEX mission planned for launch in 2027. The expected γ-ray line fluxes for the 1.809 MeV line of 26Al and the 1.173 and 1.332 MeV lines of 60Fe are in the range of (0.2–$2.7)\times 10^{-6}\, \mathrm{ph\, cm^{-2}\, s^{-1}}$ and (0.7–$2.8)\times 10^{-7}\, \mathrm{ph\, cm^{-2}\, s^{-1}}$, respectively. This new instrument could have the sensitivity to detect the upper end of the predicted 1.8 MeV flux within its nominal two-yr mission.
The properties of wind and jet from a super-Eddington accretion flow around a supermassive black hole
Authors: Yang Hai , Yuan Feng , Kwan Tom , Dai Lixin
Published: May 2023

Wind and jet are important medium of active galactic nucleus (AGN) feedback thus it is crucial to obtain their properties for the feedback study. In this paper we investigate the properties of wind and jet launched from a magnetized super-Eddington accretion flow around a supermassive black hole. For this aim, we have performed radiation magnetohydrodynamical simulation of a magnetically arrested super-Eddington accretion flows. We then have analysed the simulation data by the ‘virtual particle trajectory’ approach and obtained the mass flux, poloidal, and toroidal velocities, and mass-flux-weighted momentum and energy fluxes of wind and jet. The mass flux is found to be two to six times higher than that obtained based on the time-averaged streamline method widely used in literature. The momentum flux of wind is found to be larger than that of jet, while the total energy flux of jet is at most three times larger than that of wind. These results are similar to the case of hot accretion flows and imply that winds likely play a more important role than jet in AGN feedback. The acceleration mechanism of wind and jet is analysed and found to be dominated by Lorentz force rather than radiation force.
Skew spectrum and smoothed skewness of 21-cm signals from epoch of reionization
Authors: Ma Qing-Bo , Peng Ling
Published: May 2023

Due to the non-linear ionizing and heating processes, the 21-cm signals from epoch of reionization (EoR) are expected to have strong non-Gaussian fluctuations. In this paper, we use the seminumerical simulations to study the non-Gaussian statistics, i.e. skew spectrum and smoothed skewness of the 21-cm signals from EoR. We find the 21-cm skew spectrum and smoothed skewness have similar evolution features with the 21-cm bispectrum. All of them are sensitive to the EoR models, while not too much to the cosmic volume applied. With the SKA1-low telescope as reference, we find both the skew spectrum and smoothed skewness have much higher signal-to-noise ratios than the 21-cm bispectrum.
Spontaneous resolution of inflammatory myopathy involving the masseter muscle following COVID-19 mRNA vaccination
Authors: Tada Tomomi , Murao Haruka , Shiratani Reo , Park JeongHoon , Hideshima Makoto , Kanki Hideaki , Ishikawa Nachi , Shibahara Takayuki , Fujimoto Jun , Higa Shinji
Published: May 2023

According to previous reports, most cases of inflammatory myopathy following messenger RNA (mRNA) vaccination can be classified as idiopathic inflammatory myopathy, particularly dermatomyositis, owing to their similar clinical features and courses. However, some patients have different clinical features and courses. We report a rare case of transient inflammatory myopathy involving the masseter muscle following the third dose of coronavirus disease 2019 (COVID-19) mRNA vaccination. An 80-year-old woman presented with a history of fever and fatigue for 3 months soon after receiving the third COVID-19 mRNA vaccination. Her symptoms progressed to jaw pain and inability to open her mouth. She also experienced mild proximal muscle weakness in the lower limbs but no skin manifestations or daily difficulties. Fat-saturated T2-weighted magnetic resonance imaging showed bilateral high-intensity signals for the masseter and quadriceps muscles. The patient experienced spontaneous resolution of fever and improvement of symptoms 5 months after onset. The timing of the onset of symptoms, the lack of detectable autoantibodies, and the atypical presentation of myopathy in the masseter muscles, in addition to the spontaneous mild course of the disease, all indicate the substantial role of mRNA vaccination in this myopathy. Since then, the patient has been followed up for 4 months without any recurrence of symptoms or any additional treatment. It is important to recognise that the course of myopathy after COVID-19 mRNA vaccination could be different from that of typical idiopathic inflammatory myopathies.
MULocDeep web service for protein localization prediction and visualization at subcellular and suborganellar levels
Authors: Jiang Yuexu , Jiang Lei , Akhil Chopparapu Sai , Wang Duolin , Zhang Ziyang , Zhang Weinan , Xu Dong
Published: May 2023

Predicting protein localization and understanding its mechanisms are critical in biology and pathology. In this context, we propose a new web application of MULocDeep with improved performance, result interpretation, and visualization. By transferring the original model into species-specific models, MULocDeep achieved competitive prediction performance at the subcellular level against other state-of-the-art methods. It uniquely provides a comprehensive localization prediction at the suborganellar level. Besides prediction, our web service quantifies the contribution of single amino acids to localization for individual proteins; for a group of proteins, common motifs or potential targeting-related regions can be derived. Furthermore, the visualizations of targeting mechanism analyses can be downloaded for publication-ready figures. The MULocDeep web service is available at https://www.mu-loc.org/.
DNA modifications impact natural transformation of Acinetobacter baumannii
Authors: Vesel Nina , Iseli Christian , Guex Nicolas , Lemopoulos Alexandre , Blokesch Melanie
Published: May 2023

Acinetobacter baumannii is a dangerous nosocomial pathogen, especially due to its ability to rapidly acquire new genetic traits, including antibiotic resistance genes (ARG). In A. baumannii, natural competence for transformation, one of the primary modes of horizontal gene transfer (HGT), is thought to contribute to ARG acquisition and has therefore been intensively studied. However, knowledge regarding the potential role of epigenetic DNA modification(s) on this process remains lacking. Here, we demonstrate that the methylome pattern of diverse A. baumannii strains differs substantially and that these epigenetic marks influence the fate of transforming DNA. Specifically, we describe a methylome-dependent phenomenon that impacts intra- and inter-species DNA exchange by the competent A. baumannii strain A118. We go on to identify and characterize an A118-specific restriction-modification (RM) system that impairs transformation when the incoming DNA lacks a specific methylation signature. Collectively, our work contributes towards a more holistic understanding of HGT in this organism and may also aid future endeavors towards tackling the spread of novel ARGs. In particular, our results suggest that DNA exchanges between bacteria that share similar epigenomes are favored and could therefore guide future research into identifying the reservoir(s) of dangerous genetic traits for this multi-drug resistant pathogen.
Epigenetic plasticity safeguards heterochromatin configuration in mammals
Authors: Fukuda Kei , Shimi Takeshi , Shimura Chikako , Ono Takao , Suzuki Takehiro , Onoue Kenta , Okayama Satoko , Miura Hisashi , Hiratani Ichiro , Ikeda Kazuho , Okada Yasushi , Dohmae Naoshi , Yonemura Shigenobu , Inoue Azusa , Kimura Hiroshi , Shinkai Yoichi
Published: May 2023

Heterochromatin is a key architectural feature of eukaryotic chromosomes critical for cell type-specific gene expression and genome stability. In the mammalian nucleus, heterochromatin segregates from transcriptionally active genomic regions and exists in large, condensed, and inactive nuclear compartments. However, the mechanisms underlying the spatial organization of heterochromatin need to be better understood. Histone H3 lysine 9 trimethylation (H3K9me3) and lysine 27 trimethylation (H3K27me3) are two major epigenetic modifications that enrich constitutive and facultative heterochromatin, respectively. Mammals have at least five H3K9 methyltransferases (SUV39H1, SUV39H2, SETDB1, G9a and GLP) and two H3K27 methyltransferases (EZH1 and EZH2). In this study, we addressed the role of H3K9 and H3K27 methylation in heterochromatin organization using a combination of mutant cells for five H3K9 methyltransferases and an EZH1/2 dual inhibitor, DS3201. We showed that H3K27me3, which is normally segregated from H3K9me3, was redistributed to regions targeted by H3K9me3 after the loss of H3K9 methylation and that the loss of both H3K9 and H3K27 methylation resulted in impaired condensation and spatial organization of heterochromatin. Our data demonstrate that the H3K27me3 pathway safeguards heterochromatin organization after the loss of H3K9 methylation in mammalian cells.
Single-stranded DNA recruitment mechanism in replication origin unwinding by DnaA initiator protein and HU, an evolutionary ubiquitous nucleoid protein
Authors: Yoshida Ryusei , Ozaki Shogo , Kawakami Hironori , Katayama Tsutomu
Published: May 2023

The Escherichia coli replication origin oriC contains the initiator ATP-DnaA-Oligomerization Region (DOR) and its flanking duplex unwinding element (DUE). In the Left-DOR subregion, ATP-DnaA forms a pentamer by binding to R1, R5M and three other DnaA boxes. The DNA-bending protein IHF binds sequence-specifically to the interspace between R1 and R5M boxes, promoting DUE unwinding, which is sustained predominantly by binding of R1/R5M-bound DnaAs to the single-stranded DUE (ssDUE). The present study describes DUE unwinding mechanisms promoted by DnaA and IHF-structural homolog HU, a ubiquitous protein in eubacterial species that binds DNA sequence-non-specifically, preferring bent DNA. Similar to IHF, HU promoted DUE unwinding dependent on ssDUE binding of R1/R5M-bound DnaAs. Unlike IHF, HU strictly required R1/R5M-bound DnaAs and interactions between the two DnaAs. Notably, HU site-specifically bound the R1-R5M interspace in a manner stimulated by ATP-DnaA and ssDUE. These findings suggest a model that interactions between the two DnaAs trigger DNA bending within the R1/R5M-interspace and initial DUE unwinding, which promotes site-specific HU binding that stabilizes the overall complex and DUE unwinding. Moreover, HU site-specifically bound the replication origin of the ancestral bacterium Thermotoga maritima depending on the cognate ATP-DnaA. The ssDUE recruitment mechanism could be evolutionarily conserved in eubacteria.
GenomeFLTR: filtering reads made easy
Authors: Dotan Edo , Alburquerque Michael , Wygoda Elya , Huchon Dorothée , Pupko Tal
Published: May 2023

In the last decade, advances in sequencing technology have led to an exponential increase in genomic data. These new data have dramatically changed our understanding of the evolution and function of genes and genomes. Despite improvements in sequencing technologies, identifying contaminated reads remains a complex task for many research groups. Here, we introduce GenomeFLTR, a new web server to filter contaminated reads. Reads are compared against existing sequence databases from various representative organisms to detect potential contaminants. The main features implemented in GenomeFLTR are: (i) automated updating of the relevant databases; (ii) fast comparison of each read against the database; (iii) the ability to create user-specified databases; (iv) a user-friendly interactive dashboard to investigate the origin and frequency of the contaminations; (v) the generation of a contamination-free file. Availability: https://genomefltr.tau.ac.il/.
An evaluation of biobanking and therapeutic clinical trial representation among adult glioma patients from rural and urban Utah
Authors: Earl Emma R , Colman Howard , Mendez Joe , Jensen Randy L , Karsy Michael
Published: May 2023

Background

Social determinants of health (SDOHs)—specifically those related to rurality, health care accessibility, and income—may play as-yet-unidentified roles in prognosis for glioma patients, and their impact on access to clinical trials is important to understand. We examined SDOHs of patients enrolled in glioma clinical trials and evaluate disparities in trial participation and outcomes between rural and urban patients.

Methods

We retrospectively identified patients enrolled in glioma clinical trials at Huntsman Cancer Institute (HCI) from May 2012 to May 2022 to evaluate clinical trial participation. We used multivariable models to evaluate SDOHs and geographic information system mapping to assess representation across Utah’s counties. We utilized the most recent 10-year datasets of patients treated for glioma at HCI and from the Utah Cancer Registry to analyze survival and incidence, respectively.

Results

A total of 570 participants (68 trials) resided in Utah, 84.4% from urban counties, 13.5% from rural counties, and 2.1% from frontier (least-populous) counties. Nineteen counties (65.5%) were underrepresented in trials (enrolled participants vs. eligible), 1 (3.5%) was represented in a near-1:1 ratio, and 9 (31.0%) were overrepresented. Counties with greater enrollment had greater population densities, highest per-capita income, and proximity to HCI. Among patients treated at HCI, patients from rural/frontier counties had equivalent survival with urban patients across nearly all glioma types, including glioblastomas, despite underrepresentation in clinical trials.

Conclusions

By highlighting disparities in clinical trial enrollment, our results can support efforts to improve recruitment in underrepresented regions, which can assist providers in delivering equitable care for all patients.
Long-Term Risk of Subsequent Malignant Neoplasms Among Childhood and Adolescent Lymphoma Survivors (1975-2013): A Population-Based Predictive Nomogram
Authors: Liu Junqi , Zheng Qingzhu , Beeraka Narasimha M , Zhang Xiao , Li Tingxuan , Song Ruixia , Zhao Di , Fan Ruitai
Published: May 2023

Background

Studies are needed to assess risk factors pertinent to the incidence of secondary malignancies among childhood and adolescent lymphoma survivors. We aimed to identify risk factors pertinent to the incidence of secondary malignancies and subsequently establish a clinically practical predictive nomogram.

Methods

A total of 5561 patients who were diagnosed with primary lymphoma below the age of 20 years between 1975 and 2013 and survived for at least 5 years were identified. Standardized incidence ratio (SIR) and excess risk (ER) analysis were performed by sex, age, and year when primary lymphoma was diagnosed, sites and types of primary lymphoma, and therapy strategies. Univariable and multivariable logistic regression were used to identify independent risk factors for adolescent and childhood lymphoma-related secondary malignancies. Based on 5 factors (age, time from lymphoma diagnosis, gender, lymphoma type, and therapy), a nomogram for predicting the risk of a secondary malignancy for patients with childhood and adolescent primary lymphoma was established.

Results

Among 5561 lymphoma survivors, 424 developed a secondary malignancy. Females (SIR = 5.34, 95% CI, 4.73-5.99; ER = 50.58) exhibited a higher SIR and ER than males (SIR = 3.28, 95% CI, 2.76-3.87; ER = 15.53). Blacks were at a higher risk than Caucasians or others. Nodular lymphocyte-predominant Hodgkin lymphoma survivors exhibited typically high SIR (13.13, 95% CI, 6-24.92) and ER (54.79) among all lymphoma classifications. Lymphoma survivors who underwent radiotherapy, whether they received chemotherapy or not, had typically higher SIR and ER. Among all types of secondary malignancies, “bone and joint neoplasms” (SIR = 11.07, 95% CI, 5.52-19.81) and “soft tissue neoplasms” (SIR = 12.27, 95% CI, 7.59-18.76) presented significantly high SIR whereas “breast cancer” and “endocrine cancer” associated with higher ER. The median diagnosis age of secondary malignancies was 36 years old, and the median time interval between the diagnosis of two malignancies was 23 years. A nomogram was constructed to predict the risk of secondary malignancies in patients diagnosed with primary lymphoma before 20 years of age. After internal validation, the AUC and C-index of the nomogram are 0.804 and 0.804, respectively.

Conclusion and Relevance

The established nomogram provides a convenient and reliable tool for predicting the risk of a secondary malignancy among childhood and adolescent lymphoma survivors, concluding significant concern for lymphoma survivors with high-risk estimates.