bluuebunny/crossref_metadata_2025 huggingface dataset:
Higher risk of adverse cardiovascular outcomes in females with type 2 diabetes Mellitus: an Umbrella review of systematic reviews
Authors: Yaow Clyve Yu Leon , Chong Bryan , Chin Yip Han , Kueh Martin Tze Wah , Ng Cheng Han , Chan Kai En , Tang Ansel Shao Pin , Chung Charlotte , Goh Rachel , Kong Gwyneth , Muthiah Mark , Sukmawati Indah , Lukito Antonia Anna , Chan Mark Y , Khoo Chin Meng , Mehta Anurag , Mamas Mamas A , Dimitriadis Georgios K , Chew Nicholas W S
Published: April 2023

Background

Previous studies have shown that females with type 2 diabetes mellitus (T2DM) may have excess mortality risk compared to their male counterparts. An important next step to address the high global burden of T2DM and cardiovascular disease (CVD) is an umbrella review to summarize data on sex differences in cardiovascular outcomes for patients with T2DM and assess the strength of the evidence observed.

Methods and results

Medline and Embase were searched from inception till 7 August 2022 for systematic reviews and meta-analyses studying the effects of sex on cardiovascular outcomes in T2DM patients. Results from reviews were synthesized with a narrative synthesis, with a tabular presentation of findings and forest plots for reviews that performed a meta-analysis. 27 review articles evaluating sex differences in cardiovascular outcomes were included. Females with T2DM had a higher risk of developing coronary heart disease (CHD; RRR: 1.52, 95%CI: 1.32–1.76, P < 0.001), acute coronary syndrome (ACS; RRR: 1.38, 95%CI: 1.25–1.52, P < 0.001), heart failure (RRR: 1.09, 95%CI: 1.05–1.13, P < 0.001) than males. Females had a higher risk of all-cause mortality (RRR: 1.13, 95%CI: 1.07–1.19, P < 0.001), cardiac mortality (RRR: 1.49, 95%CI: 1.11–2.00, P = 0.009) and CHD mortality (RRR: 1.44, 95%CI: 1.20–1.73, P < 0.001) as compared to males.

Conclusions

This umbrella review demonstrates that females with T2DM have a higher risk of cardiovascular outcomes than their male counterparts. Future research should address the basis of this heterogeneity and epidemiological factors for better quality of evidence, and identify actionable interventions that will narrow these sex disparities.
Clinical, electrocardiographic, and echocardiographic parameters associated with the development of pacing and implantable cardioverter-defibrillator indication in patients with transthyretin amyloid cardiomyopathy
Authors: Kawahara Yusei , Kanazawa Hisanori , Takashio Seiji , Tsuruta Yuichiro , Sumi Hitoshi , Kiyama Takuya , Kaneko Shozo , Ito Miwa , Hoshiyama Tadashi , Hirakawa Kyoko , Ishii Masanobu , Tabata Noriaki , Yamanaga Kenshi , Fujisue Koichiro , Hanatani Shinsuke , Sueta Daisuke , Arima Yuichiro , Araki Satoshi , Usuku Hiroki , Nakamura Taishi , Yamamoto Eiichiro , Soejima Hirofumi , Matsushita Kenichi , Kawano Hiroaki , Tsujita Kenichi
Published: April 2023

Aims

This study aimed to identify factors for attention leading to future pacing device implantation (PDI) and reveal the necessity of prophylactic PDI or implantable cardioverter-defibrillator (ICD) implantation in transthyretin amyloid cardiomyopathy (ATTR-CM) patients.

Methods and results

This retrospective single-center observational study included consecutive 114 wild-type ATTR-CM (ATTRwt-CM) and 50 hereditary ATTR-CM (ATTRv-CM) patients, neither implanted with a pacing device nor fulfilling indications for PDI at diagnosis. As a study outcome, patient backgrounds were compared with and without future PDI, and the incidence of PDI in each conduction disturbance was examined. Furthermore, appropriate ICD therapies were investigated in all 19 patients with ICD implantation. PR-interval ≥220 msec, interventricular septum (IVS) thickness ≥16.9 mm, and bifascicular block were significantly associated with future PDI in ATTRwt-CM patients, and brain natriuretic peptide ≥35.7 pg/mL, IVS thickness ≥11.3 mm, and bifascicular block in ATTRv-CM patients. The incidence of subsequent PDI in patients with bifascicular block at diagnosis was significantly higher than that of normal atrioventricular (AV) conduction in both ATTRwt-CM [hazard ratio (HR): 13.70, P = 0.019] and ATTRv-CM (HR: 12.94, P = 0.002), whereas that of patients with first-degree AV block was neither (ATTRwt-CM: HR: 2.14, P = 0.511, ATTRv-CM: HR: 1.57, P = 0.701). Regarding ICD, only 2 of 16 ATTRwt-CM and 1 of 3 ATTRv-CM patients received appropriate anti-tachycardia pacing or shock therapy, under the number of intervals to detect for ventricular tachycardia of 16–32.

Conclusions

According to our retrospective single-center observational study, prophylactic PDI did not require first-degree AV block in both ATTRwt-CM and ATTRv-CM patients, and prophylactic ICD implantation was also controversial in both ATTR-CM. Larger prospective, multi-center studies are necessary to confirm these results.
Late recurrence of atrial fibrillation 5 years after catheter ablation: predictors and outcome
Authors: Choi Sung Hwa , Yu Hee Tae , Kim Daehoon , Park Je-Wook , Kim Tae-Hoon , Uhm Jae-Sun , Joung Boyoung , Lee Moon-Hyoung , Hwang Chun , Pak Hui-Nam
Published: April 2023

Aims

Atrial fibrillation (AF) is a chronic progressive disease that continuously recurs even after successful AF catheter ablation (AFCA). We explored the mechanism of long-term recurrence by comparing patient characteristics and redo-ablation findings.

Methods and results

Among the 4248 patients who underwent a de novo AFCA and protocol-based rhythm follow-up at a single centre, we enrolled 1417 patients [71.7% male, aged 60.0 (52.0–67.0) years, 57.9% paroxysmal AF] who experienced clinical recurrences (CRs), and divided them according to the period of recurrence: within one year (n = 645), 1–2 years (n = 339), 2–5 years (n = 308), and after 5 years (CR>5 yr, n = 125). We also compared the redo-mapping and ablation outcomes of 198 patients. In patients with CR>5 yr, the proportion of paroxysmal AF was higher (P = 0.031); however, the left atrial (LA) volume (quantified by computed tomography, P = 0.003), LA voltage (P = 0.003), frequency of early recurrence (P < 0.001), and use of post-procedure anti-arrhythmic drugs (P < 0.001) were lower. A CR>5 yr was independently associated with a low LA volume [odds ratio (OR) 0.99 (0.98–1.00), P = 0.035], low LA voltage [OR 0.61 (0.38–0.94), P = 0.032], and lower early recurrence [OR 0.40 (0.23–0.67), P < 0.001]. Extra-pulmonary vein triggers during repeat procedures were significantly greater in patients with a CR>5 yr, despite no difference in the de novo protocol (P for trend 0.003). The rhythm outcomes of repeat ablation procedures did not differ according to the timing of the CR (log-rank P = 0.330).

Conclusions

Patients with a later CR exhibited a smaller LA volume, lower LA voltage, and higher extra-pulmonary vein triggers during the repeat procedure, suggesting AF progression.
Differential Control of Small-conductance Calcium-activated Potassium Channel Diffusion by Actin in Different Neuronal Subcompartments
Authors: Gu Shiju , Tzingounis Anastasios V , Lykotrafitis George
Published: April 2023

Small-conductance calcium-activated potassium (SK) channels show a ubiquitous distribution on neurons, in both somatodendritic and axonal regions. SK channels are associated with neuronal activity regulating action potential frequency, dendritic excitability, and synaptic plasticity. Although the physiology of SK channels and the mechanisms that control their surface expression levels have been investigated extensively, little is known about what controls SK channel diffusion in the neuronal plasma membrane. This aspect is important, as the diffusion of SK channels at the surface may control their localization and proximity to calcium channels, hence increasing the likelihood of SK channel activation by calcium. In this study, we successfully investigated the diffusion of SK channels labeled with quantum dots on human embryonic kidney cells and dissociated hippocampal neurons by combining a single-particle tracking method with total internal reflection fluorescence microscopy. We observed that actin filaments interfere with SK mobility, decreasing their diffusion coefficient. We also found that during neuronal maturation, SK channel diffusion was gradually inhibited in somatodendritic compartments. Importantly, we observed that axon barriers formed at approximately days in vitro 6 and restricted the diffusion of SK channels on the axon initial segment (AIS). However, after neuron maturation, SK channels on the AIS were strongly immobilized, even after disruption of the actin network, suggesting that crowding may cause this effect. Altogether, our work provides insight into how SK channels diffuse on the neuronal plasma membrane and how actin and membrane crowding impacts SK channel diffusion.
Horizontal Transposon Transfer and Their Ecological Drivers: The Case of Flower-breeding Drosophila
Authors: Carvalho Tuane L , Cordeiro Juliana , Vizentin-Bugoni Jeferson , Fonseca Pedro M , Loreto Elgion L S , Robe Lizandra J
Published: April 2023

Understanding the mechanisms that shape the architecture, diversity, and adaptations of genomes and their ecological and genetic interfaces is of utmost importance to understand biological evolution. Transposable elements (TEs) play an important role in genome evolution, due to their ability to transpose within and between genomes, providing sites of nonallelic recombination. Here we investigate patterns and processes of TE-driven genome evolution associated with niche diversification. Specifically, we compared TE content, TE landscapes, and frequency of horizontal transposon transfers (HTTs) across genomes of flower-breeding Drosophila (FBD) with different levels of specialization on flowers. Further, we investigated whether niche breadth and ecological and geographical overlaps are associated with a potential for HTT rates. Landscape analysis evidenced a general phylogenetic pattern, in which species of the D. bromeliae group presented L-shaped curves, indicating recent transposition bursts, whereas D. lutzii showed a bimodal pattern. The great frequency of highly similar sequences recovered for all FBD suggests that these species probably experienced similar ecological pressures and evolutionary histories that contributed to the diversification of their mobilomes. Likewise, the richness of TEs superfamilies also appears to be associated with ecological traits. Furthermore, the two more widespread species, the specialist D. incompta and the generalist D. lutzii, presented the highest frequency of HTT events. Our analyses also revealed that HTT opportunities are positively influenced by abiotic niche overlap but are not associated with phylogenetic relationships or niche breadth. This suggests the existence of intermediate vectors promoting HTTs between species that do not necessarily present overlapping biotic niches.
3-D geometry of the Lonar impact crater, India, imaged from cultural seismic noise
Authors: Kumar Vivek , Rai Shyam S
Published: April 2023

The Lonar impact crater in the Deccan Volcanic Province of India is an excellent analogue for impact-induced structures on the Moon and other terrestrial planets. We present a detailed architecture of the crater using a high-resolution 3-D seismic velocity image to a depth of 1.5 km through the inversion of high-frequency ambient noise data recorded over 20 broad-band seismographs operating around the crater. The ambient noise waveform is dominated by cultural noise in the 1–10 Hz band. The shear wave velocity (Vs) model is created from Rayleigh wave group velocity data with a horizontal resolution of 0.5–1 km in the period range of 0.1–1.2 s. A key feature of the model is a velocity reduction of 10–15 per cent below the crater compared to outside the ejecta zone. The low-velocity zone below the crater is nearly circular and extends to a depth of ∼500 m. This estimated crater's depth is consistent with global depth–diameter scaling relations for simple craters. The basement, with a Vs of more than 2.5 km s−1, lies beneath the Deccan basalt, which has a Vs of ∼2.4 km s−1. These results are consistent with laboratory-measured data from the Lonar crater and borehole data in the western Deccan trap. This study opens a new window for exploring impact craters and sub-basalt structures using high-frequency ambient noise tomography.
First-time testers in the GetaKit study: conceptualizing new paths to care for gbMSM
Authors: O’Byrne Patrick , McCready Lance , Tigert Jason , Musten Alexandra , Orser Lauren
Published: April 2023

When analyzing the data for Ontario, Canada, HIV rates continue to be highest among gay, bisexual and other men who have sex with men (gbMSM). Since HIV diagnosis is a key component of HIV care, self-testing has provided options for allowing this population to access care, resulting in a significant number of first-time testers. Between 1 April 2021 and 31 January 2022, 882 gbMSM participants ordered an HIV self-test through GetaKit. Of these, 270 participants reported that they had never undergone HIV testing previously. Our data showed that first-time testers were generally younger, members of BIPOC (Black, Indigenous and people of color) communities and they reported more invalid test results than those who had tested previously. This suggests that HIV self-testing may be a more successful and appealing component of the HIV prevention armamentarium for this population, but one that is not without its shortcomings as an entry to care.
Context matters in smoking prevention: evaluating smoke-free school hours in Danish vocational schools
Authors: Danielsen Dina , Jensen Tina S , Kjeld Simone G , Bast Lotus S , Andersen Susan
Published: April 2023

Youth is a crucial period for smoking preventive interventions. School-based interventions targeting the policy level and the sociocultural processes of smoking show promising effects in reducing smoking uptake and prevalence. This study presents findings from the qualitative process evaluation of a smoking preventive intervention, Focus, in the vocational school (VET) setting. Specifically, the study focused on contextual factors affecting the implementation of smoke-free school hours (SFSH). Participant observations and focus groups were conducted in four VETs during the implementation period October–December 2018. The data encompass participant observation field notes (n = 21 school days), student focus groups (n = 8) (aged 16–20), teacher focus groups (n = 5) and semi-structured individual interviews with VET leaders (n = 3). The study found that SFSH was not clearly communicated to students due to the educational structure and chaotic rhythm of the school days, ambivalent attitudes among teachers toward enforcement of smoking rules and lack of clear managerial support. The interplay of these factors counteracted the implementation of SFSH in the VET context. The presented contextual factors are important when interpreting the effectiveness of the Focus intervention and for informing future preventive efforts aiming to reduce smoking among youth in high risk of smoking cigarettes.
Building knowledge in opioid prescribing in post-operative treatment
Authors: Morgan Kirsty , Solomon Lisa Mays , Jones Nicholas , Picco Louisa , Nielsen Suzanne
Published: April 2023

Introduction

Opioids prescribed in hospital are a key risk factor for harm in the community. This study aimed to gain an in-depth understanding of factors affecting post-operative opioid prescribing amongst clinicians using the capability, opportunity, motivation generate behaviour framework, more commonly known as COM-B.

Methods

Focus groups and semi-structured interviews were used to gain an in-depth understanding of factors affecting optimal practice when prescribing opioids for post-operative patients at discharge. A topic guide was written using the COM-B behaviour change model to ensure the full range of possible factors influencing prescribing behaviours were explored.

Results

We found barriers and facilitators of optimal opioid prescribing practice across all three domains of capability, opportunity and motivation. Capability among junior doctors could be increased in the areas of risk assessment and prescribing appropriate discharge analgesia, though education and training were not key barriers to improving practice. Findings indicated that opportunity to practice optimal prescribing was hindered by a lack of time at discharge and technology. Beliefs about one’s own and others’ responsibilities also impacted motivation to practice optimal prescribing behaviours. Pharmacists were identified as key supports for patient education and appropriate prescribing.

Conclusions

Educating prescribers about opioid risks and clinical practice guidelines are necessary interventions, however, our findings indicate that if implemented in isolation, they may not have the desired impact. Interventions also need to address discharge time pressures and presumptions that GPs are aware of whether opioids should be ceased or continued after surgical discharge.
BK Polyomavirus Diversity After Hematopoietic Stem Cell Transplantation
Authors: Odegard Elizabeth A , Meeds Heidi L , Kleiboeker Steven B , Ziady Assem , Sabulski Anthony , Jodele Sonata , Seif Alix E , Davies Stella M , Laskin Benjamin L , Blackard Jason T
Published: April 2023

BK polyomavirus (BKPyV) infection is common after hematopoietic stem cell transplantation (HSCT) and is associated with the development of hemorrhagic cystitis (HC). The role that BKPyV plays in the pathogenesis of HC is not well characterized. We investigated the impact of BKPyV diversity on the development of HC using a previously established cohort of pediatric HSCT patients. There were 147 urine samples with quantifiable BKPyV at month 1 after HSCT; 137 (93.2%) were amplified using our in-house polymerase chain reaction approach and sent for next-generation sequencing. Subtype Ia was most frequent (61.3%), followed by subtype Ib1 (31.4%). The median viral load of subtype Ia samples was higher than for subtype Ib1 at month 1. Across the protein coding regions, APOBEC-induced mutations and signature patterns associated with HC were identified. This is the largest sequencing study of a single cohort of HSCT patients, providing a vast resource of sequence data for future analyses.
Full-length prion protein incorporated into prion aggregates is a marker for prion strain-specific destabilization of aggregate structure following cellular uptake
Authors: Shoup Daniel , Priola Suzette A
Published: April 2023

Accumulation of insoluble aggregates of infectious, partially protease-resistant prion protein (PrPD) generated via the misfolding of protease sensitive prion protein (PrPC) into the same infectious conformer, is a hallmark of prion diseases. Aggregated PrPD is taken up and degraded by cells, a process likely involving changes in aggregate structure that can be monitored by accessibility of the N-terminus of full-length PrPD to cellular proteases. We therefore tracked the protease sensitivity of full-length PrPD before and after cellular uptake for two murine prion strains, 22L and 87V. For both strains, PrPD aggregates were less stable following cellular uptake with increased accessibility of the N-terminus to cellular proteases across most aggregate sizes. However, a limited size range of aggregates was able to better protect the N-termini of full-length PrPD, with the N-terminus of 22L-derived PrPD more protected than that of 87V. Interestingly, changes in aggregate structure were associated with minimal changes to the protease-resistant core of PrPD. Our data show that cells destabilize the aggregate quaternary structure protecting PrPD from proteases in a strain-dependent manner, with structural changes exposing protease sensitive PrPD having little effect on the protease-resistant core, and thus conformation, of aggregated PrPD.
A new era of the Asian clinical research network: a report from the ATLAS international symposium
Authors: Terada Mitsumi , Nakamura Kenichi , Matsuda Tomohiro , Okuma Hitomi Sumiyoshi , Sudo Kazuki , Yusof Akhmal , Imasa Marcelo , Sirachainan Ekaphop , Anh Pham Tuan , Fujiwara Yasuhiro , Yamamoto Noboru , Voon Pei Jye , Chokephaibulkit Kulkanya , Shibata Tatsuhiro , Inoue Manami , Mano Hiroyuki , Shimoi Tatsunori , Sriuranpong Virote , Yonemori Kan , Shimada Kazuaki
Published: April 2023

This report summarizes the presentations and discussions in the first Asian Clinical Trials Network for Cancers (ATLAS) international symposium that was held on 24 April 2022, in Bangkok, Thailand, and hosted by the National Cancer Center Hospital (NCCH), co-hosted by the Pharmaceuticals and Medical Devices Agency (PMDA), Clinical Research Malaysia (CRM) and the Thai Society of Clinical Oncology (TSCO), and supported by Embassy of Japan in Thailand. Since 2020, the NCCH has conducted the ATLAS project to enhance research environments and infrastructures to facilitate international clinical research and cancer genomic medicine in the Asian region. The purpose of the symposium was to discuss what we can achieve under the ATLAS project, to share the latest topics and common issues in cancer research and to facilitate mutual understanding. Invitees included stakeholders from academic institutions, mainly at ATLAS collaborative sites, as well as Asian regulatory authorities. The invited speakers discussed ongoing collaborative research, regulatory perspectives to improve new drug access in Asia, the status of phase I trials in Asia, the introduction of research activities at the National Cancer Center (NCC) and the implementation of genomic medicine. As the next steps after this symposium, the ATLAS project will foster increased cooperation between investigators, regulatory authorities and other stakeholders relevant to cancer research, and establish a sustainable pan-Asian cancer research group to increase the number of clinical trials and deliver novel drugs to patients with cancer in Asia.
Cloning, expression, and bioinformatics analysis of heavy metal resistance-related genes fd-I and fd-II from Acidithiobacillus ferrooxidans
Authors: Leng Feifan , Wu Yamiao , Hu Shu , Jing Yanjun , Ding Miao , Wei Qingwei , Zhang Qingchun , Wang Yonggang
Published: April 2023

Five heavy metals were introduced into the bacterial heavy metal resistance tests. The results showed that apparent inhibition effects of Cd2+ and Cu2+ on the growth of Acidithiobacillus ferrooxidans BYSW1 occurred at high concentrations (>0.04 mol l−1). Significant differences (P < 0.001) were both noticed in the expression of two ferredoxin-encoding genes (fd-I and fd-II) related to heavy metal resistance in the presence of Cd2+ and Cu2+ . When exposed to 0.06 mol l−1 Cd2+, the relative expression levels of fd-I and fd-II were about 11 and 13 times as much as those of the control, respectively. Similarly, exposure to 0.04 mol l−1 Cu2+ caused approximate 8 and 4 times higher than those of the control, respectively. These two genes were cloned and expressed in Escherichia coli, and the structures, functions of two corresponding target proteins, i.e. Ferredoxin-I (Fd-I) and Ferredoxin-II (Fd-II), were predicted. The recombinant cells inserted by fd-I or fd-II were more resistant to Cd2+ and Cu2+ compared with wild-type cells. This study was the first investigation regarding the contribution of fd-I and fd-II to enhancing heavy metal resistance of this bioleaching bacterium, and laid a foundation for further elucidation of heavy metal resistance mechanisms caused by Fd.
Morphological and molecular characterization of Lasiodiplodia theobromae associated with leaf spot and blight disease of Coscinium fenestratum (Gaertn.) Colebr.—a new host record from India
Authors: Jose Jain Mary , Kumar Shambhu , Johnson Merin , Mufeeda K T , Kripa T S , Mahadevakumar S , Singh Raghvendra
Published: April 2023

Coscinium fenestratum is a medicinally significant critically endangered plant found in Western Ghats of India. The leaf spot and blight was observed in Kerala during 2021 with disease incidence of 40% in 20 assessed plants in 0.6 hectare. The associated fungus was isolated on potato dextrose agar medium. A total of six morpho-culturally identical isolates were isolated and morphologically identified. Based on morpho-cultural features, the fungus was identified at genus level as Lasiodiplodia sp., which was further authentically confirmed as Lasiodiplodia theobromae by molecular identification with a representative isolate (KFRIMCC 089) using multigene (ITS, LSU, SSU, TEF1-α, and TUB2) sequence analysis and concatenated phylogenetic analysis (ITS-TEF1-α-TUB2). Pathogenicity tests were also assessed in vitro and in vivo using mycelial disc and spore suspension of L. theobromae, and the isolated fungus’s pathogenic behaviour was confirmed after re-isolation and morpho-cultural features. Literature survey reveals that there are no reports of L. theobromae on C. fenestratum from all over the world. Hence, C. fenestratum is being firstly reported as a new host record for L. theobromae from India.
Far-infrared polarization of the supernova remnant Cassiopeia A with SOFIA HAWC +
Authors: Rho Jeonghee , Ravi Aravind P , Tram Le Ngoc , Hoang Thiem , Chastenet Jérémy , Millard Matthew , Barlow Michael J , De Looze Ilse , Gomez Haley L , Kirchschlager Florian , Dunne Loretta
Published: April 2023

We present polarization observations of the young supernova remnant (SNR) Cas A using the High-resolution Airborne Wideband Camera-Plus (HAWC +) instrument onboard the Stratospheric Observatory for Infrared Astronomy (SOFIA). The polarization map at 154 $\mu$m reveals dust grains with strong polarization fractions (5–30 per cent), supporting previous measurements made over a smaller region of the remnant at 850 $\mu$m. The 154-$\mu$m emission and the polarization signal is coincident with a region of cold dust observed in the southeastern shell and in the unshocked central ejecta. The highly polarized far-IR emission implies the grains are large (>0.14 $\mu$m) and silicate-dominated. The polarization level varies across the SNR, with an inverse correlation between the polarization degree and the intensity and smaller polarization angle dispersion for brighter SNR emission. Stronger polarization is detected between the bright structures. This may result from a higher collision rate between the gas and dust producing a lower grain alignment efficiency where the gas density is higher. We use the dust emission to provide an estimate of the magnetic field strength in Cas A using the Davis–Chandrasekhar–Fermi method. The high polarization level is direct evidence that grains are highly elongated and strongly aligned with the magnetic field of the SNR. The dust mass from the polarized region is 0.14 ± 0.04 M⊙, a lower limit of the amount of dust present within the ejecta of Cas A. This result strengthens the hypothesis that core-collapse SNe are an important contributor to the dust mass in high redshift galaxies.
Tree-based solvers for adaptive mesh refinement code flash – IV. An X-ray radiation scheme to couple discrete and diffuse X-ray emission sources to the thermochemistry of the interstellar medium
Authors: Gaches Brandt A L , Walch Stefanie , Wünsch Richard , Mackey Jonathan
Published: April 2023

X-ray radiation, in particular radiation between 0.1 and 10 keV, is evident from both point-like sources, such as compact objects and T-Tauri young stellar objects, and extended emission from hot, cooling gas, such as in supernova remnants. The X-ray radiation is absorbed by nearby gas, providing a source of both heating and ionization. While protoplanetary chemistry models now often include X-ray emission from the central young stellar object, simulations of star-forming regions have yet to include X-ray emission coupled to the chemo-dynamical evolution of the gas. We present an extension of the treeray reverse ray trace algorithm implemented in the flash magnetohydrodynamic code which enables the inclusion of X-ray radiation from 0.1 keV < Eγ < 100 keV, dubbed xraythespot. xraythespot allows for the use of an arbitrary number of bins, minimum and maximum energies, and both temperature-independent and temperature-dependent user-defined cross-sections, along with the ability to include both point and extended diffuse emission and is coupled to the thermochemical evolution. We demonstrate the method with several multibin benchmarks testing the radiation transfer solution and coupling to the thermochemistry. Finally, we show two example star formation science cases for this module: X-ray emission from protostellar accretion irradiating an accretion disc and simulations of molecular clouds with active chemistry, radiation pressure, and protostellar radiation feedback from infrared to X-ray radiation.
Galaxy clustering from the bottom up: a streaming model emulator I
Authors: Cuesta-Lazaro Carolina , Nishimichi Takahiro , Kobayashi Yosuke , Ruan Cheng-Zong , Eggemeier Alexander , Miyatake Hironao , Takada Masahiro , Yoshida Naoki , Zarrouk Pauline , Baugh Carlton M , Bose Sownak , Li Baojiu
Published: April 2023

In this series of papers, we present a simulation-based model for the non-linear clustering of galaxies based on separate modelling of clustering in real space and velocity statistics. In the first paper, we present an emulator for the real-space correlation function of galaxies, whereas the emulator of the real-to-redshift space mapping based on velocity statistics is presented in the second paper. Here, we show that a neural network emulator for real-space galaxy clustering trained on data extracted from the dark quest suite of N-body simulations achieves sub-per cent accuracies on scales 1 < r < 30 $h^{-1} \, \mathrm{Mpc}$, and better than 3 per cent on scales r < 1 $h^{-1}\, \mathrm{Mpc}$ in predicting the clustering of dark-matter haloes with number density 10−3.5$(h^{-1}\, \mathrm{Mpc})^{-3}$, close to that of SDSS LOWZ-like galaxies. The halo emulator can be combined with a galaxy–halo connection model to predict the galaxy correlation function through the halo model. We demonstrate that we accurately recover the cosmological and galaxy–halo connection parameters when galaxy clustering depends only on the mass of the galaxies’ host halos. Furthermore, the constraining power in σ8 increases by about a factor of 2 when including scales smaller than 5 $h^{-1} \, \mathrm{Mpc}$. However, when mass is not the only property responsible for galaxy clustering, as observed in hydrodynamical or semi-analytic models of galaxy formation, our emulator gives biased constraints on σ8. This bias disappears when small scales (r < 10 $h^{-1}\, \mathrm{Mpc}$) are excluded from the analysis. This shows that a vanilla halo model could introduce biases into the analysis of future data sets.
Multi-epoch hard X-ray view of Compton-thick AGN Circinus Galaxy
Authors: Kayal Abhijit , Singh Veeresh , Ricci Claudio , Mithun N P S , Vadawale Santosh , Dewangan Gulab , Gandhi Poshak
Published: April 2023

The circumnuclear material around active galactic nuclei (AGNs) is one of the essential components of the obscuration-based unification model. However, our understanding of the circumnuclear material in terms of its geometrical shape, structure, and its dependence on accretion rate is still debated. In this paper, we present the multi-epoch broad-band X-ray spectral modelling of a nearby Compton-thick AGN in Circinus galaxy. We utilize all the available hard X-ray (>10 keV) observations taken from different telescopes, i.e. BeppoSAX, Suzaku, NuSTAR, and AstroSat, at 10 different epochs across 22 yr from 1998 to 2020. The 3.0–79 keV broad-band X-ray spectral modelling using physically motivated models, namely MYTorus, borus02, and uxclumpy, infers the presence of a torus with a low covering factor of 0.28, an inclination angle of 77°–81° and Compton-thick line-of-sight column densities (NH,LOS = 4.13–9.26 × 1024 cm−2) in all the epochs. The joint multi-epoch spectral modelling suggests that the overall structure of the torus is likely to remain unchanged. However, we find tentative evidence for the variable line-of-sight column density on time-scales ranging from 1 d to 1 week to a few years, suggesting a clumpy circumnuclear material located at subparsec to tens of parsec scales.
Young but fading radio sources: searching for remnants among compact steep-spectrum radio sources
Authors: Orienti M , Murgia M , Dallacasa D , Migliori G , D’Ammando F
Published: April 2023

The incidence of young but fading radio sources provides important information on the life cycle of radio emission in radio-loud active galactic nuclei. Despite its importance for constraining the models of radio source evolution, there are no systematic studies of remnants in complete samples of young radio sources. We report results of the study of 18 compact steep-spectrum (CSS) radio sources, selected from the statistically complete B3-VLA (Very Large Array) CSS sample, characterized by a steep optically thin spectrum (α ≥ 1.0) and no core detection in earlier studies. Our deep multifrequency VLA, pc-scale Very Long Baseline Array, and enhanced Multi Element Remotely Linked Interferometer Network (e-MERLIN) observations allowed us to locate the core component in 10 objects. In three CSS sources, there is no clear evidence of present-time active regions, suggesting that they are likely in a remnant phase. Among sources with core detection, we find three objects that have no clear active regions (hotspots) at the edges of the radio structure, suggesting that the radio emission may have just restarted. Our results support a power-law distribution of the source ages, although the poor statistics prevents us from setting solid constraints on the percentage of remnants and restarted sources in subpopulations of radio sources.
Integral Field Spectroscopy of the cometary starburst galaxy NGC 4861
Authors: Roche Nathan , Vílchez José M , Iglesias-Páramo Jorge , Papaderos Polychronis , Sánchez Sebastian F , Kehrig Carolina , Duarte Puertas Salvador
Published: April 2023

Using the PMAS Integral Field Unit on the Calar Alto 3.5 m telescope, we observed the southern component (Markarian 59) of the ‘cometary’ starburst galaxy NGC 4861. Mrk 59 is centred on a giant nebula and concentration of stars 1 kpc in diameter. Strong $\rm H\,\alpha$ emission points to a star-formation rate (SFR) at least 0.47 $\rm M_{\odot }\, yr^{-1}$. Mrk 59 has a very high [O iii] $\rm \lambda 5007/H\,\beta$ ratio, reaching 7.35 in the central nebula, with a second peak at a star-forming hotspot further north. Fast outflows are not detected but nebular motion and galaxy rotation produce relative velocities up to 40 km $\rm s^{-1}$. Spectral analysis of different regions with ‘Fitting Analysis using Differential evolution Optimization’ (FADO) finds that the stars in the central and ‘spur’ nebulae are very young, $\rm \le 125~Myr$ with a large $\rm \lt 10~Myr$ contribution. Older stars ($\rm \sim 1~Gyr$) make up the northern disk component, while the other regions show mixtures of 1 Gyr age with very young stars. This and the high specific SFR $\rm \sim 3.5~Gyr^{-1}$ imply a bimodal star formation history, with Mrk 59 formed in ongoing starbursts fuelled by a huge gas inflow, turning the galaxy into an asymmetric ‘green pea’ or blue compact dwarf. We map the He ii λ4686 emission, and identify a broad component from the central nebula, consistent with the emission of ∼300 Wolf–Rayet stars. About a third of the He ii λ4686 flux is a narrow line emitted from a more extended area covering the central and spur nebulae, and may have a different origin.
Inner edges of planetesimal belts: collisionally eroded or truncated?
Authors: Imaz Blanco Amaia , Marino Sebastian , Matrà Luca , Booth Mark , Carpenter John , Faramaz Virginie , Henning Thomas , Hughes A Meredith , Kennedy Grant M , Pérez Sebastián , Ricci Luca , Wyatt Mark C
Published: April 2023

The radial structure of debris discs can encode important information about their dynamical and collisional history. In this paper, we present a three-phase analytical model to analyse the collisional evolution of solids in debris discs, focusing on their joint radial and temporal dependence. Consistent with previous models, we find that as the largest planetesimals reach collisional equilibrium in the inner regions, the surface density of dust and solids becomes proportional to ∼r2 within a certain critical radius. We present simple equations to estimate the critical radius and surface density of dust as a function of the maximum planetesimal size and initial surface density in solids (and vice versa). We apply this model to Atacama Large Millimeter/submillimeter Array observations of seven wide debris discs. We use both parametric and non-parametric modelling to test if their inner edges are shallow and consistent with collisional evolution. We find that four out of seven have inner edges consistent with collisional evolution. Three of these would require small maximum planetesimal sizes below 10 km, with HR 8799’s disc potentially lacking solids larger than a few centimetres. The remaining systems have inner edges that are much sharper, which requires maximum planetesimal sizes ≳ 10 km. Their sharp inner edges suggest they could have been truncated by planets, which JWST could detect. In the context of our model, we find that the seven discs require surface densities below a Minimum Mass Solar Nebula, avoiding the so-called disc mass problem. Finally, during the modelling of HD 107146 we discover that its wide gap is split into two narrower ones, which could be due to two low-mass planets formed within the disc.
Three-body recombination of hydrogen in the early Universe
Authors: Flower D R
Published: April 2023

It has been suggested recently that three-body recombination of two protons and an electron might be significant in the formation of atomic hydrogen in the early Universe. We demonstrate that this process is completely negligible in the primordial plasma and that the value of the redshift, at which the transition from ionized to atomic hydrogen occurs, is determined by an equilibrium between the rates of two-body radiative recombination of a proton and an electron and its inverse, namely photoionization of atomic hydrogen.
The monomeric archaeal primase from Nanoarchaeum equitans harbours the features of heterodimeric archaeoeukaryotic primases and primes sequence-specifically
Authors: Schneider Andy , Bergsch Jan , Lipps Georg
Published: April 2023

The marine thermophilic archaeon Nanoarchaeum equitans possesses a monomeric primase encompassing the conserved domains of the small catalytic and the large regulatory subunits of archaeoeukaryotic heterodimeric primases in one protein chain. The recombinant protein primes on templates containing a triplet with a central thymidine, thus displaying a pronounced sequence specificity typically observed with bacterial type primases only. The N. equitans primase (NEQ395) is a highly active primase enzyme synthesizing short RNA primers. Termination occurs preferentially at about nine nucleotides, as determined by HPLC analysis and confirmed with mass spectrometry. Possibly, the compact monomeric primase NEQ395 represents the minimal archaeoeukaryotic primase and could serve as a functional and structural model of the heterodimeric archaeoeukaryotic primases, whose study is hindered by engagement in protein assemblies and rather low activity.
Progesterone receptor mediates ovulatory transcription through RUNX transcription factor interactions and chromatin remodelling
Authors: Dinh Doan T , Breen James , Nicol Barbara , Foot Natalie J , Bersten David C , Emery Alaknanda , Smith Kirsten M , Wong Ying Y , Barry Simon C , Yao Humphrey H C , Robker Rebecca L , Russell Darryl L
Published: April 2023

Progesterone receptor (PGR) plays diverse roles in reproductive tissues and thus coordinates mammalian fertility. In the ovary, rapid acute induction of PGR is the key determinant of ovulation through transcriptional control of a unique set of genes that culminates in follicle rupture. However, the molecular mechanisms for this specialized PGR function in ovulation is poorly understood. We have assembled a detailed genomic profile of PGR action through combined ATAC-seq, RNA-seq and ChIP-seq analysis in wildtype and isoform-specific PGR null mice. We demonstrate that stimulating ovulation rapidly reprograms chromatin accessibility in two-thirds of sites, correlating with altered gene expression. An ovary-specific PGR action involving interaction with RUNX transcription factors was observed with 70% of PGR-bound regions also bound by RUNX1. These transcriptional complexes direct PGR binding to proximal promoter regions. Additionally, direct PGR binding to the canonical NR3C motif enable chromatin accessibility. Together these PGR actions mediate induction of essential ovulatory genes. Our findings highlight a novel PGR transcriptional mechanism specific to ovulation, providing new targets for infertility treatments or new contraceptives that block ovulation.
Controlled sulfur-based engineering confers mouldability to phosphorothioate antisense oligonucleotides
Authors: Genna Vito , Iglesias-Fernández Javier , Reyes-Fraile Laura , Villegas Nuria , Guckian Kevin , Seth Punit , Wan Brad , Cabrero Cristina , Terrazas Montserrat , Brun-Heath Isabelle , González Carlos , Sciabola Simone , Villalobos Anabella , Orozco Modesto
Published: April 2023

Phosphorothioates (PS) have proven their effectiveness in the area of therapeutic oligonucleotides with applications spanning from cancer treatment to neurodegenerative disorders. Initially, PS substitution was introduced for the antisense oligonucleotides (PS ASOs) because it confers an increased nuclease resistance meanwhile ameliorates cellular uptake and in-vivo bioavailability. Thus, PS oligonucleotides have been elevated to a fundamental asset in the realm of gene silencing therapeutic methodologies. But, despite their wide use, little is known on the possibly different structural changes PS-substitutions may provoke in DNA·RNA hybrids. Additionally, scarce information and significant controversy exists on the role of phosphorothioate chirality in modulating PS properties. Here, through comprehensive computational investigations and experimental measurements, we shed light on the impact of PS chirality in DNA-based antisense oligonucleotides; how the different phosphorothioate diastereomers impact DNA topology, stability and flexibility to ultimately disclose pro-Sp S and pro-Rp S roles at the catalytic core of DNA Exonuclease and Human Ribonuclease H; two major obstacles in ASOs-based therapies. Altogether, our results provide full-atom and mechanistic insights on the structural aberrations PS-substitutions provoke and explain the origin of nuclease resistance PS-linkages confer to DNA·RNA hybrids; crucial information to improve current ASOs-based therapies.
Epidemiology, biology, and management of venous thromboembolism in gliomas: An interdisciplinary review
Authors: Jo Jasmin , Diaz Maria , Horbinski Craig , Mackman Nigel , Bagley Stephen , Broekman Marika , Rak Janusz , Perry James , Pabinger Ingrid , Key Nigel S , Schiff David
Published: April 2023

Patients with diffuse glioma are at high risk of developing venous thromboembolism (VTE) over the course of the disease, with up to 30% incidence in patients with glioblastoma (GBM) and a lower but nonnegligible risk in lower-grade gliomas. Recent and ongoing efforts to identify clinical and laboratory biomarkers of patients at increased risk offer promise, but to date, there is no proven role for prophylaxis outside of the perioperative period. Emerging data suggest a higher risk of VTE in patients with isocitrate dehydrogenase (IDH) wild-type glioma and the potential mechanistic role of IDH mutation in the suppression of production of the procoagulants tissue factor and podoplanin. According to published guidelines, therapeutic anticoagulation with low molecular weight heparin (LMWH) or alternatively, direct oral anticoagulants (DOACs) in patients without increased risk of gastrointestinal or genitourinary bleeding is recommended for VTE treatment. Due to the elevated risk of intracranial hemorrhage (ICH) in GBM, anticoagulation treatment remains challenging and at times fraught. There are conflicting data on the risk of ICH with LMWH in patients with glioma; small retrospective studies suggest DOACs may convey lower ICH risk than LMWH. Investigational anticoagulants that prevent thrombosis without impairing hemostasis, such as factor XI inhibitors, may carry a better therapeutic index and are expected to enter clinical trials for cancer-associated thrombosis.
Regulating the properties of XQ-2d for targeted delivery of therapeutic agents to pancreatic cancers
Authors: Yang Qiuxia , Peng Yongbo , Deng Zhengyu , Zhang Dailiang , Long Cheng-Yu , Zhang Guo-Rong , Li Juan , Wang Xue-Qiang , Tan Weihong
Published: April 2023

Enhanced recognition ability, cell uptake capacity, and biostability are characteristics attributed to aptamer-based targeted anticancer agents, and are possibly associated with increased accumulation at the tumor site, improved therapeutic efficacy and reduced negative side effects. Herein, a phosphorothioate backbone modification strategy was applied to regulate the biomedical properties of pancreatic cancer cell–targeting aptamer for efficient in vivo drug delivery. Specifically, the CD71- targeting aptamer XQ-2d was modified into a fully thio-substituted aptamer S-XQ-2d, improving the plasma stability of S-XQ-2d and mitomycin C (MMC)-functionalized S-XQ-2d (MFSX), thus considerably prolonging their half-life in mice. Moreover, the binding and uptake capacities of S-XQ-2d were significantly enhanced. MFSX showed the same level of cytotoxicity as that of MMC against targeted cancer cells, but lower toxicity to non-targeted cells, highlighting its specificity and biosafety. Brief mechanistic studies demonstrated that XQ-2d and S-XQ-2d had different interaction modes and internalization pathways with the targeted cells.
A versatile model with three-dimensional triangular lattice for unconventional transport and various topological effects
Authors: You Jing-Yang , Su Gang , Feng Yuan Ping
Published: April 2023

The finite Berry curvature in topological materials can induce many subtle phenomena, such as the anomalous Hall effect (AHE), spin Hall effect (SHE), anomalous Nernst effect (ANE), non-linear Hall effect (NLHE) and bulk photovoltaic effects. To explore these novel physics as well as their connection and coupling, a precise and effective model should be developed. Here, we propose such a versatile model—a 3D triangular lattice with alternating hopping parameters, which can yield various topological phases, including kagome bands, triply degenerate fermions, double Weyl semimetals and so on. We reveal that this special lattice can present unconventional transport due to its unique topological surface states and the aforementioned topological phenomena, such as AHE, ANE, NLHE and the topological photocurrent effect. In addition, we also provide a number of material candidates that have been synthesized experimentally with this lattice, and discuss two materials, including a non-magnetic triangular system for SHE, NLHE and the shift current, and a ferromagnetic triangular lattice for AHE and ANE. Our work provides an excellent platform, including both the model and materials, for the study of Berry-curvature-related physics.