bluuebunny/crossref_metadata_2025 huggingface dataset:
Floquet engineering of magnetism in topological insulator thin films
Authors: Liu Xiaoyu , Fan Benshu , Hübener Hannes , De Giovannini Umberto , Duan Wenhui , Rubio Angel , Tang Peizhe
Published: April 2023

Dynamic manipulation of magnetism in topological materials is demonstrated here via a Floquet engineering approach using circularly polarized light. Increasing the strength of the laser field, besides the expected topological phase transition (PT), the magnetically doped topological insulator thin film also undergoes a magnetic PT from ferromagnetism to paramagnetism, whose critical behavior strongly depends on the quantum quenching. In sharp contrast to the equilibrium case, the non-equilibrium Curie temperatures vary for different time scale and experimental setup, not all relying on change of topology. Our discoveries deepen the understanding of the relationship between topology and magnetism in the non-equilibrium regime and extend optoelectronic device applications to topological materials.
Randomised controlled trials of antihypertensive therapy: does exclusion of orthostatic hypotension alter treatment effect? A systematic review and meta-analysis
Authors: Reddin Catriona , Murphy Robert , Hanrahan Caoimhe , Loughlin Elaine , Ferguson John , Judge Conor , Waters Ruairi , Canavan Michelle , Kenny Rose Anne , O’Donnell Martin
Published: April 2023

Background and purpose

Management of antihypertensive therapy is challenging in patients with symptomatic orthostatic hypotension, a population often excluded from randomised controlled trials of antihypertensive therapy. In this systematic review and meta-analysis, we sought to determine whether the association of antihypertensive therapy and adverse events (e.g. falls, syncope), differed among trials that included or excluded patients with orthostatic hypotension.

Methods

We performed a systematic review and meta-analysis of randomised controlled trials comparing blood pressure lowering medications to placebo, or different blood pressure targets on falls or syncope outcomes and cardiovascular events. A random-effects meta-analysis was used to estimate a pooled treatment-effect overall in subgroups of trials that excluded patients with orthostatic hypotension and trials that did not exclude patients with orthostatic hypotension, and tested P for interaction. The primary outcome was fall events.

Results

46 trials were included, of which 18 trials excluded orthostatic hypotension and 28 trials did not. The incidence of hypotension was significantly lower in trials that excluded participants with orthostatic hypotension (1.3% versus 6.2%, P < 0.001) but not incidences of falls (4.8% versus 8.8%; P = 0.40) or syncope (1.5% versus 1.8%; P = 0.67). Antihypertensive therapy was not associated with an increased risk of falls in trials that excluded (OR 1.00, 95% CI; 0.89–1.13) or included (OR 1.02, 95% CI; 0.88–1.18) participants with orthostatic hypotension (P for interaction = 0.90).

Conclusions

The exclusion of patients with orthostatic hypotension does not appear to affect the relative risk estimates for falls and syncope in antihypertensive trials.
Predicting future falls in older people using natural language processing of general practitioners’ clinical notes
Authors: Dormosh Noman , Schut Martijn C , Heymans Martijn W , Maarsingh Otto , Bouman Jonathan , van der Velde Nathalie , Abu-Hanna Ameen
Published: April 2023

Background

Falls in older people are common and morbid. Prediction models can help identifying individuals at higher fall risk. Electronic health records (EHR) offer an opportunity to develop automated prediction tools that may help to identify fall-prone individuals and lower clinical workload. However, existing models primarily utilise structured EHR data and neglect information in unstructured data. Using machine learning and natural language processing (NLP), we aimed to examine the predictive performance provided by unstructured clinical notes, and their incremental performance over structured data to predict falls.

Methods

We used primary care EHR data of people aged 65 or over. We developed three logistic regression models using the least absolute shrinkage and selection operator: one using structured clinical variables (Baseline), one with topics extracted from unstructured clinical notes (Topic-based) and one by adding clinical variables to the extracted topics (Combi). Model performance was assessed in terms of discrimination using the area under the receiver operating characteristic curve (AUC), and calibration by calibration plots. We used 10-fold cross-validation to validate the approach.

Results

Data of 35,357 individuals were analysed, of which 4,734 experienced falls. Our NLP topic modelling technique discovered 151 topics from the unstructured clinical notes. AUCs and 95% confidence intervals of the Baseline, Topic-based and Combi models were 0.709 (0.700–0.719), 0.685 (0.676–0.694) and 0.718 (0.708–0.727), respectively. All the models showed good calibration.

Conclusions

Unstructured clinical notes are an additional viable data source to develop and improve prediction models for falls compared to traditional prediction models, but the clinical relevance remains limited.
Using Renin Activity to Guide Mineralocorticoid Receptor Antagonist Therapy in Patients with Low Renin and Hypertension
Authors: Mansur Arian , Vaidya Anand , Turchin Alexander
Published: April 2023

BACKGROUND

Mineralocorticoid receptor antagonists (MRAs) are often empirically used for patients with low-renin hypertension (LRH) or probable primary aldosteronism (PA) who decline surgery. However, the optimal approach to MRA therapy is unknown. Studies have shown that a rise in renin is an effective biomarker of prevention of cardiovascular complications of PA. This study aimed to determine whether empiric MRA therapy in patients with LRH or probable PA targeting unsuppressed renin is associated with a decrease in blood pressure and/or proteinuria.

METHODS

Retrospective single-center cohort study from 2005 to 2021 included adults with LRH or probable PA (renin activity <1.0 ng/ml/h and detectable aldosterone levels). All patients were empirically treated with an MRA, targeting renin ≥1.0 ng/ml/h.

RESULTS

Out of 39 patients studied, 32 (82.1%) achieved unsuppressed renin. Systolic and diastolic blood pressure decreased from 148.0 and 81.2 to 125.8 and 71.6 mm Hg, respectively (P < 0.001 for both). Similar blood pressure reductions were seen whether patients had high (>10 ng/dl) or low (<10 ng/dl) aldosterone levels. The majority (24/39; 61.5%) of patients had at least one baseline anti-hypertensive medication stopped. Among the six patients who had detectable proteinuria and albumin-to-creatinine (ACR) measurements post-treatment, the mean ACR decreased from 179.0 to 36.1 mg/g (P = 0.03). None of the patients studied had to completely stop treatment due to adverse reactions.

CONCLUSIONS

Empiric MRA therapy in patients with LRH or probable PA targeting unsuppressed renin can safely and effectively improve blood pressure control and reduce proteinuria.
Comparison of Adipocyte Viability After Short-Term Cryopreservation of Adipose Aspirates Through 3 Different Techniques
Authors: Koçak Polen , Ünsal Naz , Canikyan Serli , Kul Yaren , Cohen Steven R , Tiryaki Tunç
Published: April 2023

Background

Effective cryopreservation allows for the long-term storage of living cells or tissues with the possibility of later clinical applications. Unfortunately, no successful investigations on the long-term preservation of adipose aspirates for prospective autologous fat grafting have been conducted.

Objectives

In this study, we aimed to compare 3 different freezing methods to preserve adipose aspirates obtained from conventional lipoplasty to determine the optimal cryopreservation technique.

Methods

To determine the optimal cryopreservation technique, hematoxylin and eosin staining, MTS assay, and Annexin assay were performed on each of the 3 groups plus a fourth control group. Group 1 served as the control, and fat tissue was analyzed immediately after adipose harvesting with no cryopreservation. For experimental Group 2, 15 mL of adipose aspirates were directly frozen at −80°C for up to 2 weeks. For experimental Group 3, 15 mL of adipose aspirates were frozen inside the adi-frosty containing 100% isopropanol and stored at −80°C for up to 2 weeks. For experimental Group 4, 15 mL of adipose aspirates were frozen with freezing solution containing 90% fetal bovine serum (v/v) and 10% dimethyl sulfoxide (v/v).

Results

The results demonstrated that the experimental Group 3 had significantly more live adipocytes and greater cellular function of adipose aspirates than the experimental Groups 2 and 4.

Conclusion

Cryopreservation with adi-frosty containing 100% isopropanol appears to be the best means of cryopreservation of fat.

Level of Evidence: 3
Recognition of conspecific immunological status in a neotropical paper wasp
Authors: de Souza André Rodrigues , França Wilson , Prato Amanda , Rantala Markus J , do Nascimento Fábio Santos
Published: April 2023

Host immune activation is common under a pathogen invasion. This physiological response can promote changes in the body surface compounds, thus providing chemical cues related to health that might be useful to conspecifics. By recognizing the current immunological status of social partners, individuals can modulate their behavior to minimize the risk of infection. Tegument wounding, an immune elicitor, is a required step for many parasites to become established in a host. By using the neotropical eusocial paper wasp Mischocyttarus metathoracicus as a model organism, we first performed a lure presentation experiment in the field to test if wasps discriminate conspecific immunological status (experimentally manipulated by wounding) during on nest social interactions. Then, we performed gas chromatography–mass spectrometry analyses to test if immunostimulation by wounding alters the wasps’ cuticular hydrocarbon profile. We found that wasps reduce the duration of aggressive physical contact when interacting with wounded lures, despite displaying a similar frequency of inspective and aggressive behaviors toward both the wounded and the control lures. Besides, we found a subtle increase in a single cuticular hydrocarbon in the wounded wasps. Thus, wasps recognize conspecific immunological status, likely by chemical cues, and modulate their behavior in order to defend the colony against intruders while minimizing the personal risk of infection.
Antibodies against the flotillin-1/2 complex in patients with multiple sclerosis
Authors: Lleixà Cinta , Caballero-Ávila Marta , Pascual-Goñi Elba , Martín-Aguilar Lorena , Vidal Nuria , Tejada Clara , Valdés-Hevia Eduardo , Zárate Elisa , Vesperinas Ana , Collet Roger , Franco-Leyva Teresa , Martínez-Martínez Laura , Moga Esther , Cortés-Vicente Elena , Rojas-García Ricard , Gómez-Anson Beatriz , Gil Anna , González-Mingot Cristina , Brieva Luis , Martínez-Yélamos Sergio , Querol Luis
Published: April 2023

Multiple sclerosis is a tissue-specific autoimmune disease of the central nervous system in which the antigen(s) remains elusive. Antibodies targeting the flotillin-1/2 complex have been described in 1–2% of the patients in a recent study. Other candidate antigens as anoctamin-2 or neurofascin-155 have been previously described in multiple sclerosis patients, although their clinical relevance remains uncertain. Our study aims to analyse the frequency and clinical relevance of antibodies against neurofascin-155, anoctamin-2 and flotillin-1/2 complex in multiple sclerosis. Serum (n = 252) and CSF (n = 50) samples from 282 multiple sclerosis patients were included in the study. The control group was composed of 260 serum samples (71 healthy donors and 189 with other neuroinflammatory disorders). Anti-flotillin-1/2, anti-anoctamin-2 and anti-neurofascin-155 antibodies were tested by cell-based assays using transfected cells. We identified six multiple sclerosis patients with antibodies against the flotillin-1/2 complex (2.1%) and one multiple sclerosis patient with antibodies against anoctamin-2 (0.35%). All multiple sclerosis patients were negative for anti-neurofascin-155 antibodies. Three of the anti-flotillin-1/2 positive patients showed anti-flotillin-1/2 positivity in other serum samples extracted at different moments of their disease. Immunoglobulin G subclasses of anti-flotillin-1/2 antibodies were predominantly one and three. We confirm that antibodies targeting the flotillin-1/2 complex are present in a subgroup of patients with multiple sclerosis. Further studies are needed to understand the clinical and pathological relevance of anti-flotillin-1/2 autoantibodies in multiple sclerosis.
Benedicamus Domino tropes in the Birgittine Order: embellishing everyday liturgy
Authors: Lagergren Karin
Published: April 2023

A remarkable feature of the Birgittine monastic Order is its daily use of tropes for the embellishment of an exclusively monophonic liturgy. Ferial tropes were sung in both Mass and Office and their purpose was to highlight the Marian devotion that was central to the Order’s spirituality. In the Birgittine sisters’ ferial Office liturgy, the so-called Cantus sororum, the Benedicamus Domino was a notable location for the provision of tropes, which were performed daily at Lauds and Vespers. These Benedicamus tropes are a complex mix of unica, as well as musical and textual patchworks of pre-existing and new and/or remodelled musical and textual material. This article explains the place and importance of Benedicamus Domino tropes in Birgittine liturgy and spirituality, illustrated by new transcriptions of the Benedicamus tropes that were consistently assigned to embellish each particular day of the week.
Ancestral reconstruction of the MotA stator subunit reveals that conserved residues far from the pore are required to drive flagellar motility
Authors: Islam Md Imtiazul , Ridone Pietro , Lin Angela , Michie Katharine A , Matzke Nicholas J , Hochberg Georg , Baker Matthew A B
Published: April 2023

The bacterial flagellar motor (BFM) is a rotary nanomachine powered by the translocation of ions across the inner membrane through the stator complex. The stator complex consists of two membrane proteins: MotA and MotB (in H+-powered motors), or PomA and PomB (in Na+-powered motors). In this study, we used ancestral sequence reconstruction (ASR) to probe which residues of MotA correlate with function and may have been conserved to preserve motor function. We reconstructed 10 ancestral sequences of MotA and found four of them were motile in combination with contemporary Escherichia coli MotB and in combination with our previously published functional ancestral MotBs. Sequence comparison between wild-type (WT) E. coli MotA and MotA-ASRs revealed 30 critical residues across multiple domains of MotA that were conserved among all motile stator units. These conserved residues included pore-facing, cytoplasm-facing, and MotA–MotA intermolecular facing sites. Overall, this work demonstrates the role of ASR in assessing conserved variable residues in a subunit of a molecular complex.
Permeability of artificial sandstones identified by their dual-pore structure
Authors: Lu Minghui , Han Tongcheng , Wang Pan , Fu Li-Yun
Published: April 2023

Geophysical exploration technologies are developed not only to detect and quantify the geofluid in a reservoir but also with the expectation to identify the reservoir's permeability that determines its exploitability. However, the knowledge about whether there is a geophysically invertible pore parameter that determines the permeability of a rock, the key to the geophysical identification of permeability, remains poorly understood. We address this knowledge gap by establishing, through dedicated laboratory measurements and theoretical modelling, the correlations between permeability and the porosity and aspect ratios of the dual-pore structure in artificial sandstones with approximately the same porosity but with different permeability. Permeability is found to increase with increasing compliant porosity but show no apparent relations with the dual-pore aspect ratios, indicating compliant porosity is the key parameter determining the permeability of rocks with the same porosity. The results reveal the key factor that influences permeability in sandstones with the same porosity, and provide a potential way to simply identify the permeability to indicate the exploitability of a geofluid reservoir.
Climate change scenarios in fisheries and aquatic conservation research
Authors: Burgess M G , Becker S L , Langendorf R E , Fredston A , Brooks C M
Published: April 2023

Scenarios are central to fisheries and aquatic conservation research on climate change. Scenarios project future greenhouse-gas emissions, which climate models translate into warming projections. Recent climate research and global development trends have significantly changed our understanding of plausible emissions pathways to 2100 and climate sensitivities to emissions. Here, we review these developments and make recommendations for scenario use in fisheries and aquatic conservation research. Although emissions pathways are uncertain, recent research suggests that scenarios producing ∼3.4–4.5 W/m2 radiative forcing by 2100 (e.g. scenarios SSP2-3.4 and SSP2-4.5/RCP4.5) might be most plausible. This corresponds to ∼2–3 degrees C global warming by 2100 with median climate sensitivities, or 1.5–4 degrees C considering climate-system uncertainties. Higher- and lower-emissions scenarios (e.g. RCP2.6 and RCP6.0) might be plausible and should be explored in research. However, high-emission scenarios (RCP8.5/SSP5-8.5, SSP3-7.0) seem implausible and should be used with clear rationales and caveats to ensure results are not misinterpreted by scholars, policymakers, and media. We analyse fisheries and aquatic conservation papers published from 2015 to 2022 in major journals, and find that RCP8.5/SSP5-8.5 are the most commonly used scenarios, though RCP4.5/SSP2-4.5 use has increased since 2020. Studies predominantly project quantitative rather than qualitative differences between these scenarios’ impacts.
No effects of plasticized microplastics on the body condition and reproduction of a marine fish
Authors: McCormick M I , Fakan E P , Vamvounis G , Bosshard S , Moad C , Smyth E , Gatenby P , Edmiston J , Patel K , Allan B J M
Published: April 2023

This study experimentally explored the influence of periodic consumption of polystyrene (PS) microplastic fragments on the body condition and fitness of a tropical marine fish. Adult damselfish, Acanthochromis polyacanthus, were pulse fed microplastic fragments bound with one of two different common plasticizers [di-2-ethylhexyl phthalate (DEHP), di-2-ethylhexyl terephthalate (DEHT)] together with virgin-plastic and no-plastic controls. Ingestion of plastic over a 150d period had no detectable effect on growth, indices of body condition, or gonadosomatic indices. Histology of the liver showed no detrimental effects of ingesting any of the plastic treatments on hepatocyte density or vacuolation. Plastic consumption had no effect on the number of clutches produced over the breeding period, the number of eggs, or the survival of embryos. It is believed that the relatively inert nature of PS, the low amount of plasticizers leached from the fragments and fast gut through-put times meant fish were exposed to low levels of toxic compounds.
Dynamics of an age-structured HIV model with general nonlinear infection rate
Authors: Yuan Yuan , Fu Xianlong
Published: April 2023

In this paper, the asymptotical behaviour of an age-structured Human Immunodeficiency Virus infection model with general non-linear infection function and logistic proliferation term is studied. Based on the existence of the equilibria and theory of operator semigroups, linearized stability/instability of the disease-free and endemic equilibria is investigated through the distribution of eigenvalues of the linear operator. Then persistence of the solution semi-flow of the considered system is studied by showing the existence of a global attractor and the obtained result shows that the solution semi-flow is persistent as long as the basic reproduction number $R_{0}>1$. Moreover, the Hopf bifurcations problem around the endemic equilibrium is also considered for the situation with a specific infection function. Since the system has two different delays, four cases are discussed to investigate the influence of the time delays on the dynamics of system around the endemic equilibrium including stability and Hopf bifurcations. At last, some numerical examples with concrete parameters are provided to illustrate the obtained results.
On a hierarchy of effective models for the biomechanics of human compact bone tissue
Authors: Nika Grigor
Published: April 2023

We derive a hierarchy of effective models that can be used to model the biomechanics of human compact bone taking into account scale-size effects observed experimentally. The classification of the effective models depends on the hierarchy of four characteristic lengths: the size of the heterogeneities, two intrinsic lengths of the constituents and the overall characteristic length of the domain. Depending on the different scale interactions between the size of the heterogeneities, the two intrinsic lengths of the constituents, and the characteristic length of the domain we obtain either an effective Cauchy continuum or an effective Cosserat continuum. The passage to the limit relies on suitable use of the periodic unfolding operator. Moreover, we perform numerical simulations to validate our results.
On global in time self-similar solutions of Smoluchowski equation with multiplicative kernel
Authors: Breschi G , Fontelos M A
Published: April 2023

We study the similarity solutions (SS) of Smoluchowski coagulation equation with multiplicative kernel $K(x,y)=(xy)^{s}$ for $s<\frac{1}{2}$. When $s<0$ , the SS consists of three regions with distinct asymptotic behaviours. The appropriate matching yields a global description of the solution consisting of a Gamma distribution tail, an intermediate region described by a lognormal distribution and a region of very fast decay of the solutions to zero near the origin. When $s\in \left ( 0,\frac{1}{2}\right ) $, the SS is unbounded at the origin. It also presents three regions: a Gamma distribution tail, an intermediate region of power-like (or Pareto distribution) decay and the region close to the origin where a singularity occurs. Finally, full numerical simulations of Smoluchowski equation serve to verify our theoretical results and show the convergence of solutions to the selfsimilar regime.
Identifying a response parameter in a model of brain tumour evolution under therapy
Authors: Baravdish G , Johansson B T , Svensson O , Ssebunjo W
Published: April 2023

A nonlinear conjugate gradient method is derived for the inverse problem of identifying a treatment parameter in a nonlinear model of reaction–diffusion type corresponding to the evolution of brain tumours under therapy. The treatment parameter is reconstructed from additional information about the tumour taken at a fixed instance of time. Well-posedness of the direct problems used in the iterative method is outlined as well as uniqueness of a solution to the inverse problem. Moreover, the parameter identification is recasted as the minimization of a Tikhonov type functional and the existence of a minimizer to this functional is shown. Finite-difference discretization of the space and time derivatives are employed for the numerical implementation. Numerical simulations on full 3D brain data are included showing that information about a spacewise-dependent treatment parameter can be recovered in a stable way.
Stability and convergence analysis of high-order numerical schemes with DtN-type absorbing boundary conditions for nonlocal wave equations
Authors: Wang Jihong , Yang Jerry Zhijian , Zhang Jiwei
Published: April 2023

The stability and convergence analysis of high-order numerical approximations for the one- and two-dimensional nonlocal wave equations on unbounded spatial domains are considered. We first use the quadrature-based finite difference schemes to discretize the spatially nonlocal operator, and apply the explicit difference scheme to approximate the temporal derivative to achieve a fully discrete infinity system. After that, we construct the Dirichlet-to-Neumann (DtN)-type absorbing boundary conditions (ABCs), to reduce the infinite discrete system into a finite discrete system. To do so, we first adopt the idea in Du et al. (2018, Commun. Comput. Phys., 24, 1049–1072) and Du et al. (2018, SIAM J. Sci. Comp., 40, A1430–A1445) to derive the Dirichlet-to-Dirichlet (DtD)-type mappings for one- and two-dimensional cases, respectively. We then use the discrete nonlocal Green’s first identity to achieve the discrete DtN-type mappings from the DtD-type mappings. The resulting DtN-type mappings make it possible to perform the stability and convergence analysis of the reduced problem. Numerical experiments are provided to demonstrate the accuracy and effectiveness of the proposed approach.
Interference Between Enteric Viruses and Live-Attenuated Rotavirus Vaccine Virus in a Healthy Australian Birth Cohort
Authors: El-Heneidy Asmaa , Grimwood Keith , Lambert Stephen B , Ware Robert S
Published: April 2023

Background

Rotavirus vaccines have reduced effectiveness in high-mortality settings. Interference between enteric viruses and live-attenuated oral vaccine strains may be a factor.

Methods

In a birth cohort of healthy Australian infants, parents collected weekly stool samples. Three hundred eighty-one paired swabs collected within 10-days of RotaTeq vaccination from 140 infants were tested for 10 enteric viruses and RotaTeq strains.

Results

Collectively, both ribonucleic acid and deoxyribonucleic acid viruses were negatively associated with RotaTeq shedding (adjusted odds ratio = 0.29, 95% confidence interval = 0.14–0.58 and adjusted odds ratio = 0.30, 95% confidence interval = 0.11–0.78, respectively).

Conclusions

Enteric viruses may interfere with RotaTeq replication in the gut and thus RotaTeq stool shedding.
Red clover root-associated microbiota is shaped by geographic location and choice of farming system
Authors: Jambagi Shridhar , Hodén Kristian Persson , Öhlund Linda , Dixelius Christina
Published: April 2023

Aims

This study evaluated the red clover (Trifolium pratense) root-associated microbiota to clarify the presence of pathogenic and beneficial microorganisms in 89 Swedish field sites.

Methods and results

16S rRNA and ITS amplicon sequencing analysis were performed on DNA extracted from the red clover root samples collected to determine the composition of the prokaryotic and eukaryotic root-associated microbe communities. Alpha and beta diversities were calculated and relative abundance of various microbial taxa and their co-occurrence were analyzed. Rhizobium was the most prevalent bacterial genus, followed by Sphingomonas, Mucilaginibacter, Flavobacterium, and the unclassified Chloroflexi group KD4-96. The Leptodontidium, Cladosporium, Clonostachys, and Tetracladium fungal genera known for endophytic, saprotrophic, and mycoparasitic lifestyles were also frequently observed in all samples. Sixty-two potential pathogenic fungi were identified with a bias toward grass pathogens and a higher abundance in samples from conventional farms.

Conclusions

We showed that the microbial community was mainly shaped by geographic location and management procedures. Co-occurrence networks revealed that the Rhizobiumleguminosarum bv. trifolii was negatively associated with all fungal pathogenic taxa recognized in this study.
Enhanced Valsa canker resistance conferred by expression of MdLecRK-S.4.3 in Pyrus betulifolia is largely suppressed by PbePUB36
Authors: Sun E , Yu Hongqiang , Chen Zhongjian , Cai Minrui , Mao Xia , Li Yanyan , Zuo Cunwu
Published: April 2023

L-type lectin receptor-like kinases (L-LecRKs) act as sensors of extracellular signals and as initiators for plant immune responses; however, the function of LecRK-S.4 in plant immunity has not yet been extensively investigated. In the present study we found that MdLecRK-S.4.3 in apple (Malus domestica), a homologous gene of LecRK-S.4, was differentially expressed during infection by Valsa mali and Valsa pyri. Overexpression of MdLecRK-S.4.3 facilitated the induction of immune responses and enhanced the resistance to Valsa canker of fruits of apple and pear (Pyrus betulifolia), and of suspension cells of pear ‘Duli-G03’. The expression of PbePUB36, a RLCK XI sub-family member, was significantly repressed in the MdLecRK-S.4.3-overexpressing cell lines. Overexpression of PbePUB36 interfered with the resistance to Valsa canker and the immune response caused by up-regulation of MdLecRK-S.4.3. In addition, we found that MdLecRK-S.4.3 interacted with BAK1 and/or PbePUB36 in vivo. Thus, whilst MdLecRK-S.4.3 activated various immune responses and positively regulated Valsa canker resistance, this could be largely compromised by PbePUB36. MdLecRK-S.4.3 interacted with PbePUB36 and/or MdBAK1 to mediate the immune responses. Our finding provides a basis for further examination of the molecular mechanisms underlying resistance to Valsa canker, and can contribute to resistance breeding.
The first X-ray look at SMSS J114447.77-430859.3: the most luminous quasar in the last 9 Gyr
Authors: Kammoun E S , Igo Z , Miller J M , Fabian A C , Reynolds M T , Merloni A , Barret D , Nardini E , Petrucci P O , Piconcelli E , Barnier S , Buchner J , Dwelly T , Grotova I , Krumpe M , Liu T , Nandra K , Rau A , Salvato M , Urrutia T , Wolf J
Published: April 2023

SMSS J114447.77-430859.3 (z  = 0.83) has been identified in the SkyMapper Southern Survey as the most luminous quasar in the last $\sim 9\, \rm Gyr$ . In this paper, we report on the eROSITA/Spectrum–Roentgen–Gamma (SRG) observations of the source from the eROSITA All Sky Survey, along with presenting results from recent monitoring performed using Swift, XMM-Newton, and NuSTAR. The source shows a clear variability by factors of ∼10 and ∼2.7 over time-scales of a year and of a few days, respectively. When fit with an absorbed power law plus high-energy cutoff, the X-ray spectra reveal a Γ = 2.2 ± 0.2 and $E_{\rm cut}=23^{+26}_{-5}\, \rm keV$ . Assuming Comptonization, we estimate a coronal optical depth and electron temperature of $\tau =2.5-5.3\, (5.2-8)$ and $kT=8-18\, (7.5-14)\, \rm keV$ , respectively, for a slab (spherical) geometry. The broadband SED is successfully modelled by assuming either a standard accretion disc illuminated by a central X-ray source, or a thin disc with a slim disc emissivity profile. The former model results in a black hole mass estimate of the order of $10^{10}\, \mathrm{ M}_\odot$ , slightly higher than prior optical estimates; meanwhile, the latter model suggests a lower mass. Both models suggest sub-Eddington accretion when assuming a spinning black hole, and a compact ($\sim 10\, r_{\rm g}$ ) X-ray corona. The measured intrinsic column density and the Eddington ratio strongly suggest the presence of an outflow driven by radiation pressure. This is also supported by variation of absorption by an order of magnitude over the period of $\sim 900 \ \rm d$ .
Swing amplification and theGaiaphase spirals
Authors: Widrow Lawrence M
Published: April 2023

We explore the interplay between in-plane and vertical dynamics in stellar discs within the framework of the shearing box approximation. Julian and Toomre used the shearing sheet to show that leading density waves are amplified as they swing into trailing ones. We extend their formalism into the dimension perpendicular to the disc to obtain explicit solutions for the disc’s response to an impulsive, external excitation. An excitation that is symmetric about the mid-plane produces a density/breathing wave as well as two-armed phase spirals in the vertical phase space plane. On the other hand, an excitation that is antisymmetric about the mid-plane leads to a bending wave and single-armed phase spirals. In either case, self-gravity plays a crucial role in driving the evolution of the disturbance and determining the amplitude and pitch angle of the ensuing spirals. We also show that when the disc is excited by a co-rotating cloud, it develops stationary phase spirals in the wake of the cloud. The results call into question simple kinematic arguments that have been used to determine the age of the phase spirals seen in the Gaia survey.
A large bubble around the AGB star R Dor detected in the UV
Authors: Ortiz R , Guerrero M A
Published: April 2023

Many asymptotic giant branch (AGB) and supergiant stars exhibit extended detached shells in the far-infrared, resembling rings or arcs. These structures have long been interpreted as the bow shock formed in the interface between the stellar wind and the interstellar medium (ISM), the astrosphere. To date, only a few AGB stars have been observed showing an extended shell in the ultraviolet (UV): the cometary tail drifting away from o Ceti, and a bubble around IRC+10216, CIT6, and U Hya. This paper describes a search of UV extended shells around AGB stars using archival Galaxy Evolution Explorer (GALEX) far-UV images. After inspecting visually 282 GALEX images, we identified the fourth discovery of a UV bubble around the AGB star R Dor. The bubble is seen as a 26 arcmin × 29 arcmin ring, corresponding to an actual diameter of 0.41 × 0.46 parsec2. The mass of the thin UV bubble is estimated to be ≃0.003 M⊙. The morphological asymmetry (less than ∼20 per cent) and brightness variations of this shell are uncorrelated with the stellar proper motion and thus they can rather be ascribed to inhomogeneities in the ISM. Archival Infrared Astronomical Satellite 60 and 100 μm images reveal that the bubble is filled with cold (i.e. ${\lesssim} 32$ K) dust. All UV bubbles known to date are limited to be within a distance ${\lesssim} 350$ pc and at high Galactic latitudes ($|b| \gtrsim 35^{\circ }$), which suggests that their detection is hampered in most cases by the strong UV interstellar extinction.
An investigation of the circumgalactic medium around
z ∼ 2.2 AGN with ACA and ALMA
Authors: Jones G C , Maiolino R , Carniani S , Circosta C , Fudamoto Y , Scholtz J
Published: April 2023

While observations of molecular gas at cosmic noon and beyond have focused on the gas within galaxies (i.e. the interstellar medium, ISM), it is also crucial to study the molecular gas reservoirs surrounding each galaxy (i.e. in the circumgalactic medium, CGM). Recent observations of galaxies and quasars hosts at high redshift (z > 2) have revealed evidence for cold gaseous haloes of scale rCGM ∼ 10 kpc, with one discovery of a molecular halo with rCGM ∼ 200 kpc, and a molecular gas mass one order of magnitude larger than the ISM of the central galaxy. As a follow up, we present deep ACA and ALMA observations of CO(3–2) from this source and two other quasar host galaxies at z ∼ 2.2. While we find evidence for CO emission on scales of r ∼ 10 kpc, we do not find evidence for molecular gas on scales larger than r > 20 kpc. Therefore, our deep data do not confirm the existence of massive molecular haloes on scales of ∼100 kpc for these X-ray selected quasars. As an interesting byproduct of our deep observations, we obtain the tentative detection of a negative continuum signal on scales larger than r > 200 kpc, which might be tracing the Sunyaev–Zeldovich effect associated with the halo heated by the active galactic nucleus (AGN). If confirmed with deeper data, this could be direct evidence of the preventive AGN feedback process expected by cosmological simulations.
Upper limits on transmitter rate of extragalactic civilizations placed by Breakthrough Listen observations
Authors: Uno Yuri , Hashimoto Tetsuya , Goto Tomotsugu , Ho Simon C-C , Hsu Tzu-Yin , Burns Ross
Published: April 2023

The Search for Extra-Terrestrial Intelligence (SETI) has been conducted for over 60 yr, yet no technosignatures have been identified. Previous studies have focused on stars in our Galaxy, with few searches in the extragalactic Universe despite a larger volume being available. Civilizations capable of harvesting energy from a star or a galaxy are classified as KII or KIII on the Kardashev scale, respectively. Technosignatures from such advanced civilizations would be extremely luminous and detectable by current radio telescopes, even from distant galaxies. To explore the frontier of extragalactic SETI, we investigate the likely prevalence of extragalactic civilizations possessing a radio transmitter, known as the transmitter rate, based on observational results from the Breakthrough Listen (BL) observations. We calculated the transmitter rate by considering the background galaxies in the field of view of target stars in BL observations. We used a statistical method to derive the total mass of stars in those background galaxies from a galaxy stellar mass function. Our statistical method suggests that less than one in hundreds of trillions of extragalactic civilizations within 969 Mpc possess a radio transmitter above 7.7 × 1026 W of power, assuming one civilization per one-solar-mass stellar system. Additionally, we cross-matched the BL survey fields with the WISE × SuperCOSMOS Photometric Redshift Catalogue and compared with the statistical method. Our result sets the strictest limits to date on the transmitter rate at such high-power levels, emphasizing the high efficiency of searching for radio transmitters in galaxies and the rarity of technologically advanced civilizations in our Universe.
Base excision repair of the N-(2-deoxy-d-erythro-pentofuranosyl)-urea lesion by the hNEIL1 glycosylase
Authors: Tomar Rachana , Minko Irina G , Sharma Pankaj , Kellum Andrew H , Lei Li , Harp Joel M , Iverson T M , Lloyd R Stephen , Egli Martin , Stone Michael P
Published: April 2023

The N-(2-deoxy-d-erythro-pentofuranosyl)-urea DNA lesion forms following hydrolytic fragmentation of cis-5R,6S- and trans-5R,6R-dihydroxy-5,6-dihydrothymidine (thymine glycol, Tg) or from oxidation of 7,8-dihydro-8-oxo-deoxyguanosine (8-oxodG) and subsequent hydrolysis. It interconverts between α and β deoxyribose anomers. Synthetic oligodeoxynucleotides containing this adduct are efficiently incised by unedited (K242) and edited (R242) forms of the hNEIL1 glycosylase. The structure of a complex between the active site unedited mutant CΔ100 P2G hNEIL1 (K242) glycosylase and double-stranded (ds) DNA containing a urea lesion reveals a pre-cleavage intermediate, in which the Gly2 N-terminal amine forms a conjugate with the deoxyribose C1′ of the lesion, with the urea moiety remaining intact. This structure supports a proposed catalytic mechanism in which Glu3-mediated protonation of O4′ facilitates attack at deoxyribose C1′. The deoxyribose is in the ring-opened configuration with the O4′ oxygen protonated. The electron density of Lys242 suggests the ‘residue 242-in conformation’ associated with catalysis. This complex likely arises because the proton transfer steps involving Glu6 and Lys242 are hindered due to Glu6-mediated H-bonding with the Gly2 and the urea lesion. Consistent with crystallographic data, biochemical analyses show that the CΔ100 P2G hNEIL1 (K242) glycosylase exhibits a residual activity against urea-containing dsDNA.
Probabilistic establishment of speckle-associated inter-chromosomal interactions
Authors: Joo Jaegeon , Cho Sunghyun , Hong Sukbum , Min Sunwoo , Kim Kyukwang , Kumar Rajeev , Choi Jeong-Mo , Shin Yongdae , Jung Inkyung
Published: April 2023

Inter-chromosomal interactions play a crucial role in genome organization, yet the organizational principles remain elusive. Here, we introduce a novel computational method to systematically characterize inter-chromosomal interactions using in situ Hi-C results from various cell types. Our method successfully identifies two apparently hub-like inter-chromosomal contacts associated with nuclear speckles and nucleoli, respectively. Interestingly, we discover that nuclear speckle-associated inter-chromosomal interactions are highly cell-type invariant with a marked enrichment of cell-type common super-enhancers (CSEs). Validation using DNA Oligopaint fluorescence in situ hybridization (FISH) shows a strong but probabilistic interaction behavior between nuclear speckles and CSE-harboring genomic regions. Strikingly, we find that the likelihood of speckle-CSE associations can accurately predict two experimentally measured inter-chromosomal contacts from Hi-C and Oligopaint DNA FISH. Our probabilistic establishment model well describes the hub-like structure observed at the population level as a cumulative effect of summing individual stochastic chromatin-speckle interactions. Lastly, we observe that CSEs are highly co-occupied by MAZ binding and MAZ depletion leads to significant disorganization of speckle-associated inter-chromosomal contacts. Taken together, our results propose a simple organizational principle of inter-chromosomal interactions mediated by MAZ-occupied CSEs.
DNA rehybridization drives product release from Cas9 ribonucleoprotein to enable multiple-turnover cleavage
Authors: Pan Juan , Mabuchi Megumu , Robb Gregory Brett
Published: April 2023

The RNA-guided Cas9 endonuclease from Staphylococcus aureus (SauCas9) can catalyze multiple-turnover reactions whereas Cas9 from Streptococcus pyogenes (SpyCas9) is a single-turnover enzyme. Here we dissect the mechanism of multiple-turnover catalysis by SauCas9 and elucidate its molecular basis. We show that the multiple-turnover catalysis does not require more than stoichiometric RNA guides to Cas9 nuclease. Rather, the RNA-guide loaded ribonucleoprotein (RNP) is the reactive unity that is slowly released from product and recycled in the subsequent reaction. The mechanism that RNP is recycled for multiple-turnover reaction entails the unwinding of the RNA:DNA duplex in the R-loop. We argue that DNA rehybridization is required for RNP release by supplementing the energy cost in the process. Indeed, turnover is arrested when DNA rehybridization is suppressed. Further, under higher salt conditions, both SauCas9 and SpyCas9 showed increased turnover, and engineered SpyCas9 nucleases that form fewer direct or hydrogen bonding interactions with target DNA became multiple-turnover enzymes. Thus, these results indicate that for both SpyCas9 and SauCas9, turnover is determined by the energetic balance of the post-chemistry RNP-DNA interaction. Due to the conserved protein core folds, the mechanism underpinning turnover we establish here is likely operant in all Cas9 nucleases.
Consumer attitudes and behaviors toward more sustainable diets: a scoping review
Authors: Kenny Tara A , Woodside Jayne V , Perry Ivan J , Harrington Janas M
Published: April 2023

There is an urgent need to move toward more sustainable diets. Although this will require radical and systemic changes across food systems, altering consumer ideologies and practices is essential to garner support for such actions. In this scoping review, the evidence on consumers’ attitudes and behaviors toward more sustainable diets is synthesized and a range of factors, considerations, and proposed strategies are presented that can contribute to building the societal-level support for urgent and systems-level changes. The findings suggest that consumers, insofar as they are interested in sustainability and have the capacity to engage with the concept, primarily approach the concept of sustainable diet from a human health perspective. However, the interconnectedness of human health and well-being with environmental health is poorly understood and under-researched in the context of consumer behaviors and attitudes toward sustainable diets. This highlights the need for (1) sustained efforts from public health professionals to encourage a realignment of the term sustainable diet with its multidimensional meaning by championing an ecological public health approach in all efforts aimed at promoting more sustainable consumption, from awareness raising to policy development; (2) a broader research lens focused on the multidimensional concept of sustainability in the literature exploring consumer attitudes and behaviors; and (3) the development of multidisciplinary, clear, and evidence-based sustainable-eating messages, including holistic sustainable dietary guidance, to address knowledge gaps, minimize conflicting narratives, and build consumer agency. The findings contribute to understanding how support can be generated for the necessary structural and system-level changes required to support behavior change.
Real-World Treatment Trends Among Patients with Metastatic Castration-Sensitive Prostate Cancer: Results from an International Study
Authors: Barata Pedro C , Leith Andrea , Ribbands Amanda , Montgomery Rachel , Last Matthew , Arondekar Bhakti , Ivanova Jasmina , Niyazov Alexander
Published: April 2023

Background

Continuous androgen deprivation therapy ± first-generation non-steroidal antiandrogen was previously the standard-of-care for patients with metastatic castration-sensitive prostate cancer (mCSPC). Treatment intensification with novel hormonal therapy (NHT) or taxane chemotherapy is now approved and guideline-recommended for these patients.

Methods

Physician-reported data on adult patients with mCSPC from the Adelphi Prostate Cancer Disease Specific Programme were analyzed descriptively. We evaluated real-world treatment trends for patients with mCSPC in 5 European countries (United Kingdom, France, Germany, Spain, and Italy) and the United States (US), looking at differences between patients initiating treatment in 2016-2018 and in 2019-2020. We also investigated treatment trends by ethnicity and insurance status in the US.

Results

This study found that most patients with mCSPC do not receive treatment intensification. However, greater use of treatment intensification with NHT and taxane chemotherapy was observed in 2019-2020 than in 2016-2018 across 5 European countries. In the US, greater use of treatment intensification with NHT in 2019-2020 than in 2016-2018 was observed for all ethnicity groups and those with Medicare and commercial insurance status.

Conclusions

As the number of patients with mCSPC who receive treatment intensification increases, more patients who progress to metastatic castration-resistant prostate cancer (mCRPC) will have been exposed to intensified treatments. Treatment options for patients with mCSPC and mCRPC overlap, suggesting that an unmet need will emerge for new therapies. Further studies are needed to understand optimal treatment sequencing in mCSPC and mCRPC.
The Management of Metastatic Castrate-Sensitive Prostate Cancer: From Guidelines to Real-World Practice
Authors: Gebrael Georges , Thomas Vinay Mathew , Swami Umang , Agarwal Neeraj
Published: April 2023

This commentary highlights 2 international studies on real-world treatment trends and patterns among patients with metastatic castration-sensitive and resistant prostate cancer and how interventions targeting physicians and patients can bridge the gap between evidence-based medicine and real-world practice.