bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimizing Best Practice Advisory alerts in electronic medical records with a multi-pronged strategy at a tertiary care hospital in Singapore
Authors: Ng Hannah Jia Hui , Kansal Amit , Abdul Naseer Jishana Farhad , Hing Wee Chuan , Goh Carmen Jia Man , Poh Hermione , D’souza Jared Louis Andre , Lim Er Luen , Tan Gamaliel
Published: August 2023

Objective

Clinical decision support (CDS) alerts can aid in improving patient care. One CDS functionality is the Best Practice Advisory (BPA) alert notification system, wherein BPA alerts are automated alerts embedded in the hospital’s electronic medical records (EMR). However, excessive alerts can change clinician behavior; redundant and repetitive alerts can contribute to alert fatigue. Alerts can be optimized through a multipronged strategy. Our study aims to describe these strategies adopted and evaluate the resultant BPA alert optimization outcomes.

Materials and Methods

This retrospective single-center study was done at Jurong Health Campus. Aggregated, anonymized data on patient demographics and alert statistics were collected from January 1, 2018 to December 31, 2021. “Preintervention” period was January 1–December 31, 2018, and “postintervention” period was January 1–December 31, 2021. The intervention period was the intervening period. Categorical variables were reported as frequencies and proportions and compared using the chi-square test. Continuous data were reported as median (interquartile range, IQR) and compared using the Wilcoxon rank-sum test. Statistical significance was defined at P < .05.

Results

There was a significant reduction of 59.6% in the total number of interruptive BPA alerts, despite an increase in the number of unique BPAs from 54 to 360 from pre- to postintervention. There was a 74% reduction in the number of alerts from the 7 BPAs that were optimized from the pre- to postintervention period. There was a significant increase in percentage of overall interruptive BPA alerts with action taken (8 [IQR 7.7–8.4] to 54.7 [IQR 52.5–58.9], P-value < .05) and optimized BPAs with action taken (32.6 [IQR 32.3–32.9] to 72.6 [IQR 64.3–73.4], P-value < .05). We estimate that the reduction in alerts saved 3600 h of providers’ time per year.

Conclusions

A significant reduction in interruptive alert volume, and a significant increase in action taken rates despite manifold increase in the number of unique BPAs could be achieved through concentrated efforts focusing on governance, data review, and visualization using a system-embedded tool, combined with the CDS Five Rights framework, to optimize alerts. Improved alert compliance was likely multifactorial—due to decreased repeated alert firing for the same patient; better awareness due to stakeholders’ involvement; and less fatigue since unnecessary alerts were removed. Future studies should prospectively focus on patients’ clinical chart reviews to assess downstream effects of various actions taken, identify any possibility of harm, and collect end-user feedback regarding the utility of alerts.
Melatonin supplementation promotes muscle fiber hypertrophy and regulates lipid metabolism of skeletal muscle in weaned piglets
Authors: Chen Wentao , Tu Yuang , Cai Peiran , Wang Liyi , Zhou Yanbing , Liu Shiqi , Huang Yuqin , Zhang Shu , Gu Xin , Yi Wuzhou , Shan Tizhong
Published: August 2023

Melatonin has been reported to play crucial roles in regulating meat quality, improving reproductive properties, and maintaining intestinal health in animal production, but whether it regulates skeletal muscle development in weaned piglet is rarely studied. This study was conducted to investigate the effects of melatonin on growth performance, skeletal muscle development, and lipid metabolism in animals by intragastric administration of melatonin solution. Twelve 28-d-old DLY (Duroc × Landrace × Yorkshire) weaned piglets with similar body weight were randomly divided into two groups: control group and melatonin group. The results showed that melatonin supplementation for 23 d had no effect on growth performance, but significantly reduced serum glucose content (P < 0.05). Remarkably, melatonin increased longissimus dorsi muscle (LDM) weight, eye muscle area and decreased the liver weight in weaned piglets (P < 0.05). In addition, the cross-sectional area of muscle fibers was increased (P < 0.05), while triglyceride levels were decreased in LDM and psoas major muscle by melatonin treatment (P < 0.05). Transcriptome sequencing showed melatonin induced the expression of genes related to skeletal muscle hypertrophy and fatty acid oxidation. Enrichment analysis indicated that melatonin regulated cholesterol metabolism, protein digestion and absorption, and mitophagy signaling pathways in muscle. Gene set enrichment analysis also confirmed the effects of melatonin on skeletal muscle development and mitochondrial structure and function. Moreover, quantitative real-time polymerase chain reaction analysis revealed that melatonin supplementation elevated the gene expression of cell differentiation and muscle fiber development, including paired box 7 (PAX7), myogenin (MYOG), myosin heavy chain (MYHC) IIA and MYHC IIB (P < 0.05), which was accompanied by increased insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 5 (IGFBP5) expression in LDM (P < 0.05). Additionally, melatonin regulated lipid metabolism and activated mitochondrial function in muscle by increasing the mRNA abundance of cytochrome c oxidase subunit 6A (COX6A), COX5B, and carnitine palmitoyltransferase 2 (CPT2) and decreasing the mRNA expression of peroxisome proliferator-activated receptor gamma (PPARG), acetyl-CoA carboxylase (ACC) and fatty acid-binding protein 4 (FABP4) (P < 0.05). Together, our results suggest that melatonin could promote skeletal muscle growth and muscle fiber hypertrophy, improve mitochondrial function and decrease fat deposition in muscle.
Direct binding of calmodulin to the cytosolic C-terminal regions of sweet/umami taste receptors
Authors: Yoshida Atsuki , Ito Ayumi , Yasui Norihisa , Yamashita Atsuko
Published: August 2023

Sweet and umami taste receptors recognize chemicals such as sugars and amino acids on their extracellular side and transmit signals into the cytosol of the taste cell. In contrast to ligands that act on the extracellular side of these receptors, little is known regarding the molecules that regulate receptor functions within the cytosol. In this study, we analysed the interaction between sweet and umami taste receptors and calmodulin, a representative Ca2+-dependent cytosolic regulatory protein. High prediction scores for calmodulin binding were observed on the C-terminal cytosolic side of mouse taste receptor type 1 subunit 3 (T1r3), a subunit that is common to both sweet and umami taste receptors. Pull-down assay and surface plasmon resonance analyses showed different affinities of calmodulin to the C-terminal tails of distinct T1r subtypes. Furthermore, we found that T1r3 and T1r2 showed the highest and considerable binding to calmodulin, whereas T1r1 showed weaker binding affinity. Finally, the binding of calmodulin to T1rs was consistently higher in the presence of Ca2+ than in its absence. The results suggested a possibility of the Ca2+-dependent feedback regulation process of sweet and umami taste receptor signaling by calmodulin.
Binding profile of quinonoid-dihydrobiopterin to quinonoid-dihydropteridine reductase examined by in silico and in vitro analyses
Authors: Kono Haruka , Hara Satoshi , Furuta Tadaomi , Ichinose Hiroshi
Published: August 2023

Quinonoid dihydropteridine reductase (QDPR) catalyses the reduction of quinonoid-form dihydrobiopterin (qBH2) to tetrahydrobiopterin (BH4). BH4 metabolism is a drug target for neglected tropical disorders because trypanosomatid protozoans, including Leishmania and Trypanosoma, require exogenous sources of biopterin for growth. Although QDPR is a key enzyme for maintaining intracellular BH4 levels, the precise catalytic properties and reaction mechanisms of QDPR are poorly understood due to the instability of quinonoid-form substrates. In this study, we analysed the binding profile of qBH2 to human QDPR in combination with in silico and in vitro methods. First, we performed docking simulation of qBH2 to QDPR to obtain possible binding modes of qBH2 at the active site of QDPR. Then, among them, we determined the most plausible binding mode using molecular dynamics simulations revealing its atomic-level interactions and confirmed it with the in vitro assay of mutant enzymes. Moreover, it was found that not only qBH2 but also quinonoid-form dihydrofolate (qDHF) could be potential physiological substrates for QDPR, suggesting that QDPR may be a bifunctional enzyme. These findings in this study provide important insights into biopterin and folate metabolism and would be useful for developing drugs for neglected tropical diseases.
Continuity and change in the British diplomatic service in the Levant
Authors: Patrizio Gunning Lucia , Vlami Despina
Published: August 2023

In this article, we examine the organization of the British diplomatic service in the Ottoman Empire and analyse its transition from a prestigious, privately financed, highly individualized public office to a state-funded, but fragmented and poorly paid body. We survey the idiosyncratic character of the diplomatic apparatus set up by the Levant Company to serve its business pursuits, infiltrate local society and obtain political favours. In 1825 the Foreign Office replaced the Levant Company officers with public servants who had no ties or affinities with Levantine society. However, to obtain antiquities for the British Museum, the Foreign Office had to turn once again to British Levantines. Based on our earlier published work,1 as well as recent unpublished archival research, this paper explains how the collecting of antiquities in the Ottoman Empire relied entirely on the British diplomatic service and its Levantine connection.
A common inducer molecule enhances sugar utilization by Shewanella oneidensis MR-1
Authors: Gruenberg Megan C , TerAvest Michaela A
Published: August 2023

Shewanella oneidensis MR-1 is an electroactive bacterium that is a promising host for bioelectrochemical technologies, which makes it a common target for genetic engineering, including gene deletions and expression of heterologous pathways. Expression of heterologous genes and gene knockdown via CRISPRi in S. oneidensis are both frequently induced by β-D-1-thiogalactopyranoside (IPTG), a commonly used inducer molecule across many model organisms. Here, we report and characterize an unexpected phenotype; IPTG enhances the growth of wild-type S. oneidensis MR-1 on the sugar substrate N-acetylglucosamine (NAG). IPTG improves the carrying capacity of S. oneidensis growing on NAG while the growth rate remains similar to cultures without the inducer. Extracellular acetate accumulates faster and to a higher concentration in cultures without IPTG than those with it. IPTG appears to improve acetate metabolism, which combats the negative effect that acetate accumulation has on the growth of S. oneidensis with NAG. We recommend using extensive experimental controls and careful data interpretation when using both NAG and IPTG in S. oneidensis cultures.
NCI Rectal-Anal Task Force consensus recommendations for design of clinical trials in rectal cancer
Authors: Kennecke Hagen F , Auer Rebecca , Cho May , Dasari N Arvind , Davies-Venn Cynthia , Eng Cathy , Dorth Jennifer , Garcia-Aguilar Julio , George Manju , Goodman Karyn A , Kreppel Lillian , Meyer Joshua E , Monzon Jose , Saltz Leonard , Schrag Deborah , Smith J Joshua , Zell Jason A , Das Prajnan ,   the National Cancer Institute Rectal-Anal Task Force, Allegra Carmen , Kennecke Hagen , Auer Rebecca , Kreppel Lillian , Benson Al , Mamon Harvey , Chang George , Meyer Josh , Cho May , Meyerhardt Jeff , Das Prajnan , Monzon Jose , Dasari Arvind , Ou Fang-Shu , Deming Dusty , Rajdev Lakshmi , Dorth Jennifer , Rogers Jane , Eng Cathy , Romak Lindsay , Fisher George , Romesser Paul , Garcia-Aguilar Julio , Saltz Leonard , George Manju , Schrag Deborah , George Thomas , Sheybani Arshin , Goodman Karyn , Shi Qian , Gordon Vallerie , Smith J Joshua , Hall William , VanderWalde Noam , Iqbal Atif , Yothers Greg , Kachnic Lisa , Zell Jason
Published: August 2023

The optimal management of locally advanced rectal cancer is rapidly evolving. The National Cancer Institute Rectal-Anal Task Force convened an expert panel to develop consensus on the design of future clinical trials of patients with rectal cancer. A series of 82 questions and subquestions, which addressed radiation and neoadjuvant therapy, patient perceptions, rectal cancer populations of special interest, and unique design elements, were subject to iterative review using a Delphi analytical approach to define areas of consensus and those in which consensus is not established. The task force achieved consensus on several areas, including the following: 1) the use of total neoadjuvant therapy with long-course radiation therapy either before or after chemotherapy, as well as short-course radiation therapy followed by chemotherapy, as the control arm of clinical trials; 2) the need for greater emphasis on patient involvement in treatment choices within the context of trial design; 3) efforts to identify those patients likely, or unlikely, to benefit from nonoperative management or minimally invasive surgery; 4) investigation of the utility of circulating tumor DNA measurements for tailoring treatment and surveillance; and 5) the need for identification of appropriate end points and recognition of challenges of data management for patients who enter nonoperative management trial arms. Substantial agreement was reached on priorities affecting the design of future clinical trials in patients with locally advanced rectal cancer.
Florence Nightingale and the Provincial Response to the Crimean War
Authors: Memel Jonathan Godshaw
Published: August 2023

Florence Nightingale rose to fame early in 1855 at a time when provincialism was assuming unprecedented importance in Victorian culture. The London papers The Times and the Illustrated London News linked Nightingale to the typically provincial domain of the parish and the home: her public image reflecting the wish to extend domestic comfort to soldiers, adrift on foreign land and neglected by uncaring military authorities. Nightingale’s campaigns to improve soldiers’ conditions then galvanized the charitable enthusiasms of households across Britain and its colonies, as the public sent contributions ranging from knitted slippers to bedsheets repurposed as wound dressings on ships to the Crimea. Nightingale subsequently introduced army reading rooms stocked with works of regional and provincial fiction, either as actual volumes or as instalments in periodicals such as Household Words, to bring the imaginative connections between the parish and the Scutari hospitals closer still. While recent work by Stefanie Markovits and Holly Furneaux has shown how the cultural lives of ‘home’ and ‘the East’ were closer than previously thought, I contend that two distinctively provincial features of Nightingale’s place within the conflict have not been sufficiently recognized. First, Nightingale drew on gendered notions of the home and domesticity that were crucial to the provincial as it gained appeal and meaning during the middle of the century. Second, in facilitating imaginative connections between soldiers and the reading public many thousands of miles away, Nightingale showed that the provincial operated most effectively at distance, where its effects were felt most strongly among an increasingly dispersed and fragmented nation.
A meta-analysis of the accuracy of Xpert MTB/RIF in diagnosing intestinal tuberculosis
Authors: Ding Yuan-Lin , Yan Rui-Chao , Chen Hao-Kai , Guo Xu-Guang
Published: August 2023

Objective

A detection method with high efficiency and accuracy is urgently needed in clinical work. The purpose of our study was to determine the diagnostic accuracy of the Xpert MTB/RIF assay for intestinal tuberculosis (ITB).

Methods

We searched PubMed and 4 other databases from their establishment to July 19, 2022, for published essays of diagnostic performance in which Xpert MTB/RIF was used to test patients with clinically suspected ITB. An assessment of the quality of the selected literature was conducted using QUADAS-2. We built forest plots by MetaDiSc software.

Results

The pooled Xpert MTB/RIF sensitivity was 48%, and the specificity was 99%. Moreover, the positive likelihood ratio for ITB diagnosis was 21.61. The negative likelihood ratio was 0.54. There were substantial variations between the study estimates of sensitivity (I2 = 87.6%) and specificity (I2 = 82.4%).

Conclusion

Intestinal TB is detected with limited diagnostic sensitivity by Xpert MTB/RIF but with high specificity. An Xpert-positive result may facilitate the rapid identification of ITB cases. Nevertheless, a negative result has less certainty in excluding the disease.
Temperature influence on the compression and breakage behaviour of yeast cells
Authors: Overbeck Achim , Michel Stephanie , Kampen Ingo , Kwade Arno
Published: August 2023

Industrial biotechnology uses microbial cells to produce a wide range of products. While the genetic and molecular properties of these organisms are well understood, less is known about their mechanical properties. Previous work has established a test procedure for single yeast cells using a nanoindentation instrument equipped with a flat-punch probe, which allows single cells (Saccharomyces cerevisiae) to be compressed between two parallel surfaces. The resulting force–displacement curves clearly showed the bursting of the cells and were used to determine characteristics such as burst force and burst energy. Other studies have investigated the influence of growth conditions and measurement conditions on the mechanical characteristics. The recent study examined the mechanical characteristics according to the temperature during compression. Temperature from 0°C to 25°C has no significant effect on the micromechanical properties. Increasing the temperature up to 35°C causes a reduction in the strength of the cells. At even higher temperatures, up to 50°C, the burst force and burst energy increase significantly. A deformation geometry model was used to calculate the cell wall tensile strength as a function of temperature. The results of these studies may facilitate the identification of efficient conditions for cell disruption and product recovery in downstream biotechnological processes.
Mycobacterial contamination in tap and shower waters in Thailand
Authors: Song Jack Jia Xin , Oguma Kumiko
Published: August 2023

Waterborne disease is increasingly becoming associated with opportunistic premise plumbing pathogens (OPPPs), which can resist residual chlorination, regrow throughout drinking water distribution systems, and colonize premise plumbing. Nontuberculous mycobacteria (NTM) include clinically important species and exert a high burden on healthcare systems. We briefly report a qPCR-based survey of Mycobacterium spp. numbers in tap, POU-treated, and shower waters from Bangkok, Thailand. Non-stagnant tap waters and non-stagnant shower waters had mean numbers of 1.3 × 103 and 2.4 × 103 copies/mL, respectively. Water stagnation resulted in mean numbers higher by up to 1.0 log. The lowest number, 25 copies/mL, was obtained from a POU-treated sample, while the highest number, 2.0 × 104 copies/mL, came from a stagnant tap. Comparing with international data, mean numbers in this study were greater than those in nine out of 11 (82%) comparable studies, and the maximum numbers in this study were also high. Our samples of Bangkok waters exhibited relatively high Mycobacterium spp. numbers, suggesting the need for appropriate POU treatment systems where NTM infection is a health concern. This survey data can be used to set inactivation performance targets in POU water disinfection system design and may also lead to quantitative microbial risk assessment (QMRA) studies.
JWST UNCOVER: discovery of z > 9 galaxy candidates behind the lensing cluster Abell 2744
Authors: Atek Hakim , Chemerynska Iryna , Wang Bingjie , Furtak Lukas J , Weibel Andrea , Oesch Pascal , Weaver John R , Labbé Ivo , Bezanson Rachel , van Dokkum Pieter , Zitrin Adi , Dayal Pratika , Williams Christina C , Nannayakkara Themiya , Price Sedona H , Brammer Gabriel , Goulding Andy D , Leja Joel , Marchesini Danilo , Nelson Erica J , Pan Richard , Whitaker Katherine E
Published: August 2023

We present the results of a search for high-redshift (z > 9) galaxy candidates in the JWST UNCOVER survey, using deep NIRCam and NIRISS imaging in seven bands over ∼45 arcmin2 and ancillary Hubble Space Telescope (HST) observations. The NIRCam observations reach a 5σ limiting magnitude of ∼29.2 AB. The identification of high-z candidates relies on a combination of a dropout selection and photometric redshifts. We find 16 candidates at 9 < z < 12 and three candidates at 12 < z < 13, eight candidates are deemed very robust. Their lensing amplification ranges from μ = 1.2 to 11.5. Candidates have a wide range of (lensing corrected) luminosities and young ages, with low stellar masses [6.8 < log(M⋆/M⊙) < 9.5] and low star formation rates (SFR = 0.2–7 M⊙ yr−1), confirming previous findings in early JWST observations of z > 9. A few galaxies at z ∼ 9−10 appear to show a clear Balmer break between the F356W and F444W/F410M bands, which helps constrain their stellar mass. We estimate blue UV continuum slopes between β = −1.8 and −2.3, typical for early galaxies at z > 9 but not as extreme as the bluest recently discovered sources. We also find evidence for a rapid redshift-evolution of the mass-luminosity relation and a redshift evolution of the UV continuum slope for a given range of intrinsic magnitude, in line with theoretical predictions. These findings suggest that deeper JWST observations are needed to reach the fainter galaxy population at those early epochs, and follow-up spectroscopy will help better constrain the physical properties and star formation histories of a larger sample of galaxies.
A simulation-based inference pipeline for cosmic shear with the Kilo-Degree Survey
Authors: Lin Kiyam , von wietersheim-Kramsta Maximilian , Joachimi Benjamin , Feeney Stephen
Published: August 2023

The standard approach to inference from cosmic large-scale structure data employs summary statistics that are compared to analytic models in a Gaussian likelihood with pre-computed covariance. To overcome the idealizing assumptions about the form of the likelihood and the complexity of the data inherent to the standard approach, we investigate simulation-based inference (SBI), which learns the likelihood as a probability density parameterized by a neural network. We construct suites of simulated summary statistics, exactly Gaussian distributed for validation purposes, for the most recent Kilo-Degree Survey (KiDS) weak gravitational lensing analysis and demonstrate that SBI recovers the full 12-dimensional KiDS posterior distribution with just under 104 simulations. We optimize the simulation strategy by initially covering the parameter space by a hypercube, followed by batches of actively learnt additional points. The data compression in our SBI implementation is robust to suboptimal choices of fiducial parameter values and of data covariance. Together with a fast simulator, SBI is therefore a competitive and more versatile alternative to standard inference.
Energy balance SED modelling can be effective at high redshifts regardless of UV-FIR offsets
Authors: Haskell P , Smith D J B , Cochrane R K , Hayward C C , Anglés-Alcázar D
Published: August 2023

Recent works have suggested that energy balance spectral energy distribution (SED) fitting codes may be of limited use for studying high-redshift galaxies for which the observed ultraviolet and far-infrared emission are offset (spatially ‘decoupled’). It has been proposed that such offsets could lead energy balance codes to miscalculate the overall energetics, preventing them from recovering such galaxies’ true properties. In this work, we test how well the SED fitting code magphys can recover the stellar mass, star formation rate (SFR), specific SFR, dust mass, and luminosity by fitting 6706 synthetic SEDs generated from four zoom-in simulations of dusty, high-redshift galaxies from the FIRE project via dust continuum radiative transfer. Comparing our panchromatic results (using wavelengths 0.4–500 μm, and spanning 1 < z < 8) with fits based on either the starlight ($\lambda _\mathrm{eff} \le 2.2\, \mu$m) or dust ($\ge 100\, \mu$m) alone, we highlight the power of considering the full range of multiwavelength data alongside an energy balance criterion. Overall, we obtain acceptable fits for 83 per cent of the synthetic SEDs, though the success rate falls rapidly beyond z ≈ 4, in part due to the sparser sampling of the priors at earlier times since SFHs must be physically plausible (i.e. shorter than the age of the universe). We use the ground truth from the simulations to show that when the quality of fit is acceptable, the fidelity of magphys estimates is independent of the degree of UV/FIR offset, with performance very similar to that previously reported for local galaxies.
Self-consistent dynamical models with a finite extent – III. Truncated power-law spheres
Authors: Baes Maarten , Vander Meulen Bert
Published: August 2023

Fully analytical dynamical models usually have an infinite extent, while real star clusters, galaxies, and dark matter haloes have a finite extent. The standard method for generating dynamical models with a finite extent consists of taking a model with an infinite extent and applying a truncation in binding energy. This method, however, cannot be used to generate models with a preset analytical mass density profile. We investigate the self-consistency and dynamical properties of a family of power-law spheres with a general tangential Cuddeford (TC) orbital structure. By varying the density power-law slope γ and the central anisotropy β0, these models cover a wide parameter space in density and anisotropy profiles. We explicitly calculate the phase–space distribution function for various parameter combinations, and interpret our results in terms of the energy distribution of bound orbits. We find that truncated power-law spheres can be supported by a TC orbital structure if, and only if, γ ≥ 2β0, which means that the central density slope–anisotropy inequality is both a sufficient and a necessary condition for this family. We provide closed expressions for structural and dynamical properties such as the radial and tangential velocity dispersion profiles, which can be compared against more complex numerical modelling results. This work significantly adds to the available suite of self-consistent dynamical models with a finite extent and an analytical description.
Detecting deviations from Gaussianity in high-redshift CMB lensing maps
Authors: Zhang Zhuoqi (Jackie) , Omori Yuuki , Chang Chihway
Published: August 2023

While the probability density function of the cosmic microwave background (CMB) convergence field approximately follows a Gaussian distribution, primordial non-Gaussianities, and small contributions from structures at low redshifts make the overall distribution slightly non-Gaussian. Some of the late-time component can be modelled using the distribution of galaxies and subtracted off from the original CMB lensing map to produce a map of matter distribution at high redshifts. Using this high-redshift mass map, we are able to directly study the early phases of structure formation. In this work, we forecast the detectability of signatures of non-Gaussianity due to non-linear structure formation at z > 1.2. Assuming the optimal case of no systematics, we find that it is challenging to detect such signatures in current surveys, but future experiments such as the deep field of CMB-S4 will be able to make detections of ∼7σ.
Investigating the porosity of Enceladus
Authors: Kisvárdai Imre , Pál Bernadett D , Kereszturi Ákos
Published: August 2023

The interior of Enceladus, a medium-sized icy moon of Saturn hosts hydrothermal activity and exhibits tidal heating and related geyser-like activity. There are major disagreements in the existing literature on the porosity of the interior due to the different theoretical assumptions on which porosity related calculations are based. We present an application of experimental equations – derived for the Earth – for icy planetary objects and Enceladus in particular. We chose a set of boundary values for our initial parameters from measured porosity values of chondrite samples as references and calculated the porosity related values of Enceladus using various approaches. We present a comprehensive investigation of the effects of using these different porosity calculation methods on icy moons. With our most realistic approach, we also calculated the same values for the Earth and Mars for comparison. Our result for Enceladus is a minimum porosity of about 5 per cent at the centre of the body. For the total pore volume, we estimated 1.51 · 107 km3 for Enceladus, 2.11 · 108 km3 for the Earth and 1.62 · 108 km3 for Mars. Using the same method, we estimated the total pore surface area. From this, we derived that the pore surface under a given 1 km2 area of the surface on Enceladus is about 1.37 · 109 km2, while for the Earth this value is only 5.07 · 107 km2.
Modelling stellar evolution in mass-transferring binaries and gravitational-wave progenitors with metisse
Authors: Agrawal Poojan , Hurley Jarrod , Stevenson Simon , Rodriguez Carl L , Szécsi Dorottya , Kemp Alex
Published: August 2023

Massive binaries are vital sources of various transient processes, including gravitational-wave mergers. However, large uncertainties in the evolution of massive stars, both physical and numerical, present a major challenge to the understanding of their binary evolution. In this paper, we upgrade our interpolation-based stellar evolution code metisse to include the effects of mass changes, such as binary mass transfer or wind-driven mass loss, not already included within the input stellar tracks. metisse’s implementation of mass loss (applied to tracks without mass loss) shows excellent agreement with the sse fitting formulae and with detailed mesa tracks, except in cases where the mass transfer is too rapid for the star to maintain equilibrium. We use this updated version of metisse within the binary population synthesis code bse to demonstrate the impact of varying stellar evolution parameters, particularly core overshooting, on the evolution of a massive (25 and 15 M⊙) binary system with an orbital period of 1800 d. Depending on the input tracks, we find that the binary system can form a binary black hole or a black hole–neutron star system, with primary (secondary) remnant masses ranging between 4.47 (1.36) and 12.30 (10.89) M⊙, and orbital periods ranging from 6 d to the binary becoming unbound. Extending this analysis to a population of isolated binaries uniformly distributed in mass and orbital period, we show that the input stellar models play an important role in determining which regions of the binary parameter space can produce compact binary mergers, paving the way for predictions for current and future gravitational-wave observatories.
Universal relations to measure neutron star properties from targeted r-mode searches
Authors: Ghosh Suprovo
Published: August 2023

R-mode oscillations of rotating neutron stars (NS) are promising candidates for continuous gravitational wave (GW) observations. In our recent work, we derived universal relations between the NS parameters compactness and dimensionless tidal deformability with the r-mode frequency. In this work, we investigate how these universal relations can be used to infer various NS intrinsic parameters following a successful detection of the r-modes. In particular, we show that for targeted r-mode searches, these universal relations along with the ‘I–Love–Q’ relation can be used to estimate both the moment of inertia and the distance of the NS, thus breaking the degeneracy of distance measurement for continuous gravitational wave (CGW) observations. We also discuss that, with a prior knowledge of the distance of the NS from electromagnetic observations, these universal relations can also be used to constrain the dense matter equation of state (EOS) inside the NS. We quantify the accuracy to which such measurements can be done using the Fisher information matrix for a broad range of possible, unknown parameters for both the a-LIGO and Einstein Telescope (ET) sensitivities.
Variation of temperature and non-thermal velocity with height in fan loops
Authors: Sharma Aishawnnya , Tripathi Durgesh
Published: August 2023

We study the variation of temperature and non-thermal velocity with height in fan loops. For this purpose, we have used the observations recorded by the Extreme Ultraviolet Imaging Spectrometer onboard Hinode. We have employed the emission measure (EM)-loci method to estimate the temperatures of different coronal fan loops and then compute the non-thermal velocities using the obtained temperatures in Si vii 275.35 Å and Fe viii 185.21 Å lines. The EM-loci analysis provides nearly iso-thermal temperature along the fan loops. We obtain the peak temperatures in the range $\log \, T(K)$  = 5.85–5.95 for fan loops, and the subtraction of thermal broadening gives the non-thermal velocities in the range ≈5–15 and 11–29 km s−1 for Si vii 275.35 Å and Fe viii 185.21 Å, respectively. Our method provides quantitative accuracy in the measurement of non-thermal velocity, which is an important parameter in understanding the dynamics of heating of the solar atmosphere.
Digging a little deeper: characterizing three new extreme ULX candidates
Authors: Roberts T P , Walton D J , Mackenzie A D A , Heida M , Scaringi S
Published: August 2023

A prime motivation for compiling catalogues of any celestial X-ray source is to increase our numbers of rare subclasses. In this work, we take a recent multimission catalogue of ultraluminous X-ray sources (ULXs) and look for hitherto poorly-studied ULX candidates that are luminous ($L_{\rm X} \ge 10^{40}\,{\rm erg\,s}^{-1}$), bright ($f_{\rm X} \ge 5 \times 10^{-13}\,{\rm erg\,cm}^{-2}\,{\rm s}^{-1}$), and have archival XMM–Newton data. We speculate that this luminosity regime may be ideal for identifying new pulsating ULXs (PULXs), given that the majority of known PULXs reach similar high luminosities. We find three sources that match our criteria and study them using archival data. We find 4XMM J165251.5−591503 to possess a bright and variable Galactic optical/IR counterpart, and so conclude it is very likely to be a foreground interloper. 4XMM J091948.8−121429 does appear to be an excellent ULX candidate associated with the dwarf irregular galaxy PGC 26378, but has only one detection to date with low data quality. The best data set belongs to 4XMM J112054.3+531040 which we find to be a moderately variable, spectrally hard (Γ ≈ 1.4) X-ray source located in a spiral arm of NGC 3631. Its spectral hardness is similar to known PULXs, but no pulsations are detected by accelerated pulsation searches in the available data. We discuss whether other missions provide objects for similar studies and compare this method to others suggested for identifying good PULX candidates.
Empirically Driven multiwavelength K-corrections at low redshift
Authors: Fielder Catherine E , Andrews Brett H , Newman Jeffrey , Salim Samir
Published: August 2023

K-corrections – a necessary ingredient for converting between flux in observed bands to flux in rest-frame bands – are critical for comparing galaxies at differing redshifts. These corrections often rely on fits to empirical or theoretical spectral energy distribution (SED) templates of galaxies. However, templates can only produce reliable K-corrections in regimes where SED models are robust. For instance, the templates utilized in some popular software packages are not well-constrained in some bands (e.g. WISE W4 in Kcorrect), which results in ill-behaved K-corrections. We address this shortcoming by developing an empirically driven approach to K-corrections that limits the dependence on SED templates. We perform a polynomial fit for the K-correction as a function of a galaxy’s rest-frame colour determined in a pair of well-constrained bands (e.g. 0(g − r)) and redshift, exploiting the fact that galaxy SEDs can be approximated as a one-parameter family at low redshift. For bands well-constrained by SED templates, our empirically driven K-corrections yield results comparable to the SED fitting methods used by Kcorrect and the GSWLC-M2 catalogue (the updated medium-deep GALEX–SDSS–WISE Legacy Catalogue). However, our method dramatically outperforms Kcorrect derived K-corrections for WISE W4. Our method is also robust to incorrect template assumptions outside of the optical bands and enforces that the K-correction must be zero at z = 0. Our K-corrected photometry and code are publicly available.
The Gating Domain of MEF28 Is Essential for Editing Two Contiguous Cytidines in nad2 mRNA in Arabidopsis thaliana
Authors: Bayer-Császár Eszter , Jörg Anja , Härtel Barbara , Brennicke Axel , Takenaka Mizuki
Published: August 2023

In plant organelles, each C-to-U RNA-editing site is specifically recognized by pentatricopeptide repeat (PPR) proteins with E1-E2, E1-E2-E+ or E1-E2-DYW domain extensions at the C-terminus. The distance between the PPR domain–binding site and the RNA-editing site is usually fixed at four bases, increasing the specificity of target-site recognition in this system. We here report, in contrast to the general case, on MEF28, which edits two adjacent mitochondrial sites, nad2-89 and nad2-90. When the sDYW domain of MEF28 was replaced with one derived from MEF11 or CRR22, the ability to edit downstream sites was lost, suggesting that the DYW domain of MEF28 provides unique target flexibility for two continuous cytidines. By contrast, substitutions of the entire E1-E2-DYW domains by MEF19E1-E2, SLO2E1-E2-E+ or CRR22E1-E2-E+ target both nad2 sites. In these cases, access to the contiguous sites in the chimeric PPR proteins is likely to be provided by the trans-associated DYW1-like proteins via the replaced E1-E2 or E1-E2-E+ domains. Furthermore, we demonstrated that the gating domain of MEF28 plays an important role in specific target-site recognition of the DYW domain. This finding suggests that the DYW domain and its internal gating domain fine-tune the specificity of the target site, which is valuable information for designing specific synthetic RNA-editing tools based on plant RNA-editing factors.
Comprehensive dissection of meiotic DNA double-strand breaks and crossovers in cucumber
Authors: Wang Yanling , Dong Zhaonian , Ma Yalin , Zheng Yi , Huang Sanwen , Yang Xueyong
Published: August 2023

Meiotic recombination drives genetic diversity and crop genome optimization. In plant breeding, parents with favorable traits are crossed to create elite varieties. Different hybridizations produce diverse types of segment reshuffling between homologous chromosomes. However, little is known about the factors that cause hybrid-specific changes in crossovers (COs). Here, we constructed 2 F2 populations from crosses between a semiwild and 2 domesticated cucumber (Cucumis sativus) accessions and examined CO events. COs mainly occurred around genes and differed unevenly along chromosomes between the 2 hybrids. Fine-scale CO distributions were suppressed in regions of heterozygous structural variations (SVs) and were accelerated by high sequence polymorphism. C. sativus RADiation sensitive 51A (CsRAD51A) binding, histone H3 lysine 4 trimethylation (H3K4me3) modification, chromatin accessibility, and hypomethylation were positively associated with global CO landscapes and in local DNA double-strand break (DSB) hotspots and genes. The frequency and suppression of COs could be roughly predicted based on multiomic information. Differences in CO events between hybrids could be partially traced to distinct genetic and epigenetic features and were significantly associated with specific DSB hotspots and heterozygous SVs. Our findings identify the genomic and epigenetic features that contribute to CO formation and hybrid-specific divergence in cucumber and provide theoretical support for selecting parental combinations and manipulating recombination events at target genomic regions during plant breeding.
Deterrence Without Mutual Destruction
Authors: Issacharoff Samuel
Published: August 2023

With openness comes vulnerability. David Sloss's new work, Tyrants on Twitter, elevates the abuse of social media by autocrats to a new war front, reminiscent of the concerns for foreign penetration during the Cold War. His response to this new round of “information warfare” is the mobilization of a transnational alliance of the 40 or so leading democratic countries to register citizens for use of social media and filter out tyrants and their fronts, be they real people or bots. The book begins by chronicling the extent of democratic decline, a well-defended starting point. More complicated is the argument that the correlation between democratic decline and foreign interference establishes the causal role of the latter. Even more difficult is the conclusion that there is need for war-like footing to mobilize against foreign threats. The review ends with a note of caution on the costs associated with democratic societies closing up in the face of foreign challenge.
Youth, Generations, and Generational Research
Authors: Andolina Molly W
Published: August 2023

Kevin Munger’s Generation Gap: Why the Baby Boomers Still Dominate American Politics and Culture is the latest addition in a growing collection of analyses that attempt to evaluate the impact of millennials and Generation Z on the body politic. Combining a review of cultural trends, election statistics, news consumption patterns, and unique survey data, Munger argues that baby boomer political dominance is perched to run headlong into younger, tech-savvy cohorts who have the potential—but not yet the power—to replace them. Munger calls attention to the ways in which the political system has favored boomer issues and concerns, highlighting how the ensuing public policies reward the older generation and undermine the collective economic fortune of today’s youth. This review discusses the history of generational research as well as recent work about today’s younger cohorts to provide context for understanding both the strengths and shortcomings of Generation Gap. The field is richer with Munger’s contribution, but many critical questions remain.
Liberal Pragmatism and Liberal Fantasy in the Era of Backlash Politics
Authors: Goodhart Michael
Published: August 2023

Jack Snyder's book Human Rights for Pragmatists: Social Power in Modern Times is less a theory of human rights than a political sociology of liberal modernization. Focusing on that account, this article argues that the story of liberal modernization Snyder’s book presents is a distortional fable and, as such, undermines its own claims to pragmatism. This review further contends that this fable of liberal modernization creates a fantasy in which the solution to the problems of contemporary liberal states and the liberal international order is more liberalism. The review concludes by suggesting that any pragmatic account must at least take seriously the possibility that liberalism is part of the problem and, therefore, that it might not be the solution.
Predictors of inflammatory arthritis among new rheumatology referrals: a cross-sectional study
Authors: Thoms Brendan L , Bonnell Levi N , Tompkins Bradley , Nevares Alana , Lau ChiChi
Published: August 2023

Objectives

Early diagnosis and treatment of inflammatory arthritis (IA) is essential to optimize disease control. We aimed to identify variables that distinguish IA from non-inflammatory arthropathy by performing a cross-sectional study of rheumatology referral letters and visit records. Further work describes time to assessment and documentation of variables within referral letters.

Methods

We reviewed rheumatology referral letters and new patient visits over a 6-month period. The diagnosis of IA was based on the clinical judgement of the assessing rheumatologist. IA diagnoses included RA, SpAs, unspecified IA, PMR, crystalline arthropathies and remitting seronegative symmetrical synovitis with pitting oedema. Univariate analysis was performed for each variable. Multivariable logistic regression was performed on statistically significant variables.

Results

Of 697 patients referred for arthralgia, 25.7% were diagnosed with IA. Variables predictive of IA included tenderness and swelling on examination and ≥1 h of morning stiffness. Increasing arthralgia duration, fatigue and brain fog were negative predictors. The median time from referral to IA diagnosis was 55 days and 20.7% of these patients were seen within 6 weeks. Among referral letters, documentation of arthralgia duration, morning stiffness or joint examination findings was uncommon (31%, 20.5% and 56.7%, respectively).

Conclusion

We identified positive and negative predictors of IA. Referral letters often missed key information required for the triaging process. Future efforts will be directed towards build a triaging tool to improve the referral quality and capture of those patients with IA who need earlier access to rheumatology care.
Tixagevimab/cilgavimab for the prevention of COVID-19 in vaccine-refractory patients with autoimmune diseases: a prospective cohort study
Authors: Minopoulou Ioanna , Tascilar Koray , Corte Giulia , Mutlu Melek Yalcin , Schmidt Katja , Bohr Daniela , Hartmann Fabian , Manger Karin , Manger Bernhard , Korn Klaus , Kleyer Arnd , Simon David , Harrer Thomas , Schett Georg , Fagni Filippo
Published: August 2023

Objectives

To investigate the effects of passive immunization with the anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibodies tixagevimab/cilgavimab on humoral responses and on coronavirus disease 2019 (COVID-19) outcomes in vaccine-refractory patients with immune-mediated inflammatory diseases (IMIDs) at high risk of severe COVID-19.

Methods

A prospective cohort study was performed on a cohort of high-risk vaccine-refractory IMID patients treated with a single dose of tixagevimab/cilgavimab (150 mg/150 mg). COVID-19 outcomes as well as serum and salivary anti-SARS-CoV-2 IgG were assessed at baseline and for at least 6 months. Results were compared with an untreated high-risk vaccine-refractory IMID population. Standardized incidence ratios (SIRs) of COVID-19 compared with the general population were calculated for both groups.

Results

A total of 38 high-risk IMID patients received tixagevimab/cilgavimab and were compared with 114 untreated high-risk IMID controls. Serum anti-spike IgG increased to 6.6 OD (s.d. 0.8) at day 1 and remained positive up to month 6 [6.3 OD (s.d. 1.4)]. Salivary anti-spike IgG peaked at month 2 [1.6 OD (s.d. 1.1)] and decreased from month 3 [0.8 OD (s.d. 0.3)]. No severe or extended infection was observed in the tixagevimab/cilgavimab group. Compared with the general population, the SIR of COVID-19 in treated patients was 0.76 (95% CI 0.24, 1.58) despite the increased risk profile. The SIR of the control group was 1.51 (95% CI 1.07, 2.02), corresponding to a significantly increased incidence.

Conclusions

Passive immunization with tixagevimab/cilgavimab is safe and effective in inducing anti-SARS-CoV-2 immunity and potentially in preventing COVID-19 in high-risk vaccine-refractory IMID patients. These data provide a proof of concept for the use of monoclonal antibodies as a preventative strategy against SARS-CoV-2 in vulnerable populations.