bluuebunny/crossref_metadata_2025 huggingface dataset:
Reliability of the palaeomagnetic signal recorded in a lava flow erupted on 4 December 2021 in La Palma (Canary Islands, Spain)
Authors: Calvo-Rathert Manuel , Vernet Eva , Parés Josep M , Soler Vicente , Sánchez-Moreno Elisa-María , Bógalo María-Felicidad , Carrancho Ángel , Yamamoto Yuhji , Rodríguez-Méndez Lidia
Published: August 2024

A basaltic lava flow erupted from the Tajogaite volcano on 4 December 2021, in La Palma (Canary Islands, Spain) was sampled to find out to what extent reliable and correct information on both intensity and direction of the Earth's magnetic field can be obtained from the palaeomagnetic signal recorded in a lava flow which erupted under known conditions. Samples were taken every few centimetres across a flow up to a total of 27 oriented cores. Palaeomagnetic experiments showed a strong viscous overprint in many samples. Nevertheless, the mean palaeomagnetic direction obtained agrees well with the actual value from IGRF-13. Rock magnetic experiments were performed to obtain additional information about the quality and reliability of the results and the reasons for unsuccessful determinations. Analysis of mostly irreversible thermomagnetic curves showed that the carriers of remanence were magnetite and titanomagnetite of low and/or intermediate Curie-temperature. Hysteresis parameter ratios showed a pronounced variability across the flow. Analyses of frequency dependent susceptibility, IRM acquisition coercivity spectra and FORCs showed a noticeably presence of very low coercivity grains (multidomain and superparamagnetic-single domain boundary). Multimethod palaeointensity experiments were performed with the Thellier-Coe, multispecimen and Tsunakawa-Shaw methods. Only three of 25 cores from the flow yielded successful Thellier-Coe determinations, in agreement with the expected field value of 38.7 μT (IGRF-13). However, palaeointensities of 60 per cent of the specimens agree with the expected value performing an informal analysis without considering criteria thresholds. Four of six Tsunakawa-Shaw determinations performed on samples from the flow yielded correct results, but three multispecimen determinations providing apparently successful determinations largely underestimate the expected field intensity. Combination of three Thellier-Coe and four Tsunakawa-Shaw successful determinations yields a multimethod palaeointensity result B = (36.9 ± 2.0) μT in good agreement with the expected field intensity.
Estimating spatio-temporal variable parameters of Epidemic Type Aftershock Sequence model in a region with limited seismic network coverage: a case study of the East African Rift System
Authors: Bantidi Thystere Matondo , Ishibe Takeo , Tuluka Georges Mavonga , Enescu Bogdan
Published: August 2024

The Epidemic-Type Aftershock Sequence (ETAS) model is currently the most powerful statistical seismicity model that reproduces the general characteristics of earthquake clustering in space and time. However, its application can be hampered by biased parameter estimations related to earthquake catalogue deficiencies, particularly in regions where the spatial coverage of local recording networks is relatively poor. Here, we systematically investigate the possible influences of the effect introduced by data truncation through the choice of the cut-off magnitude (${{m}_{\rm cut}})$ and missing events due to heterogeneity of the seismic network on ETAS parameter estimates along the East African Rift System (EARS). After dividing the region into six source zones based on rheological and mechanical behaviours, the ETAS model is fitted to the earthquakes within each zone using the Davidon–Fletcher–Powell optimization algorithm. The fits and variations in parameter estimates are compared for each zone to the others and the seismological implications are discussed. We found that some parameters vary as a function of ${{m}_{\rm cut}}$ primarily driven by changes in catalogue size. Additionally, a systematic regional dependency of ETAS parameters is found across source zones. Furthermore, a median heat flow value for each analysed source zone in the EARS is calculated. In contrast to previous findings in other tectonic settings, the results reveal no significant correlations between the crustal heat flows and the ETAS parameters describing earthquake productivity (${{K}_0}$) and the relative efficiency of an earthquake with magnitude M to produce aftershocks ($\alpha $). Our findings have significant implications for understanding the mechanisms of earthquake interaction and, therefore, provide tight constraints on the model's parameters that may serve as a testbed for existing earthquake forecasting models in this region where the vulnerability of local buildings and structures exacerbate seismic risk.
2’ Life-changing minutes: impact evaluation of a novel health promotion format on cancer prevention
Authors: Ribeiro Nuno , Carvalho Luís , Oliveira Pedro , Marcos Nuno T
Published: August 2024

Cancer is one of the most important societal challenges in the world, with over 23 million new cases/year and 10 million deaths/year, that will only be properly tackled with a stronger focus on prevention. This calls for an informed population, aware of risk factors and willing to adopt preventive behaviors and early cancer screenings. For that purpose, 2’ Life-changing minutes was created, the first ever televised Entertainment-Education series on cancer prevention. This study aims to evaluate the impact of 2’ Life-changing minutes, a novel E-E format for cancer prevention, on knowledge gains and behavior changes. Two complementary studies were performed involving a total of 1314 participants: a test-screening (TS) study targeting potential viewers of the series, and a natural-screening (NS) study targeting those that spontaneously watched the series on television. We found (i) very high levels of appreciation and narrative engagement, and also willingness to see more episodes; (ii) statistically significant knowledge gains, ranging from 17% to 44%, on all four topics tested; (iii) evidence of effective behavior change. Regression analysis showed that narrative engagement was the best predictor of behavior change [NS: odds ratio (OR) = 3.38, 95% confidence interval (CI) = 1.70–6.74, p = 0.001; TS: OR = 2.05, 95% CI = 1.13–0.371, p = 0.018]. This study demonstrates the series’ real impact and serves as a proof-of-concept for a novel strategy of cancer prevention that is based around compelling health narratives, rather than information or data, to engage viewers, increase knowledge and induce behavior change.
Finite element analysis of a generalized Robin boundary value problem in curved domains based on the extension approach
Authors: Kashiwabara Takahito
Published: August 2024

A theoretical analysis of the finite element method for a generalized Robin boundary value problem, which involves a second-order differential operator on the boundary, is presented. If $\varOmega $ is a general smooth domain with a curved boundary, we need to introduce an approximate domain $\varOmega _{h}$ and to address issues owing to the domain perturbation $\varOmega \neq \varOmega _{h}$. In contrast to the lift approach used in existing studies, we employ the extension approach, which need not assume that boundary nodes of $\partial \varOmega _{h}$ lie exactly on $\partial \varOmega $. Assuming that approximate domains and function spaces are given by isoparametric finite elements of order $k$, we prove the optimal rate of convergence in the $H^{1}$- and $L^{2}$-norms. A numerical example is given for the piecewise linear case $k = 1$.
P03 An evaluation of Antibiotic Champions events in GP practices in Cambridgeshire and Peterborough Integrated Care System
Authors: Patel J , Ransom S , Bennet C , Culloty S , Micallef C
Published: August 2024

Background

In 2022, all GP practices in the area were asked to nominate an Antibiotic Champion for each practice. These Antibiotic Champions were then asked to write actions plans for their antimicrobial stewardship (AMS) initiatives and invited to quarterly virtual educational meetings: Antibiotic Champion events. The first event was launched on 2 November 2022.

Objectives

We sought to understand whether Antibiotic Champions attending the Antibiotic Champions events were finding these events useful to their practice and whether they wanted additional support to deliver their antibiotic prescribing targets.

Methods

Following the 8 November 2023 Antibiotic Champion event, we disseminated electronic evaluation forms, using MS Forms to all attendees via the Training Hub which arranges the logistics for the virtual meetings. This e-survey was available from 8 February to 3 December 2023 and regular reminders were sent by the Training Hub.

Results

From 68 participants, 21 responded (30.1% response rate). A total of 66.7% (14/21) identified as medical doctors with 28.6% (6/21) declaring that they were pharmacists and 5% (1/21) advanced clinical practitioners. There was no representation from the nursing or pharmacy technician professions. In all, 90.5% (19/21) declared that they were prescribers and 76% (16/21) prescribed antimicrobials in their roles. The majority of respondents—71.4% (15/21)—had been in the NHS for >10 years. Figure 1 portrays the feedback from respondents on further support needed to deliver AMS metrics whilst Figure 2 delineates respondent satisfaction for the Antibiotic Champion event meetings. Finally, Figure 3 outlines AMS activities in GP practices. In November 2022, the national primary care metrics for total antibiotic prescribing (0.871) and broad-spectrum antibiotic (10%) were not being achieved locally but national ePACT data issued in November 2023 highlighted that the broad-spectrum metric was now being achieved (9.92%).

Conclusions

This study presents an easy, cost-effective way of engaging with healthcare professionals in GP practices, over a large and varied geographical area, on antimicrobial stewardship initiatives. We suggest that these events may have helped support GP practices to deliver their AMS targets.
P12 Clinical perceptions of the need for anaerobic coverage in patients treated for aspiration pneumonia (AP)
Authors: Dewar Simon , Lee Natalie , Antonenka Uladzimir , Botsani Tamanna , Brown Maya , Khoja Omar , Lam Angel Sin Yu , Lawson Harry , Shetty Chirag , Vijendren Natasha , Yung Lok Yiu (Charlotte) , Zilles Lucia
Published: August 2024

Background

In 2023, the British Thoracic Society (BTS) published a clinical statement on management of patients with aspiration pneumonia (AP). As part of the recommendations, it was highlighted that routine anti-anaerobic coverage is not required for patients treated for AP, except in specific clinical circumstances. However, hospital inpatients treated for AP are frequently antimicrobial regimens that include metronidazole.

Objectives

This small study aimed to garner the perceptions of prescribing clinicians regarding antimicrobial prescribing for AP.

Methods

A questionnaire was devised, consisting of seven questions based on a Likert scale (1=strongly agree, 5=strongly disagree), and the option to provide additional qualitative comments. This was distributed to healthcare professionals at the Western General Hospital, Edinburgh in February 2024. Specialties targeted were Medicine of the Elderly, General Medicine and Respiratory Medicine. Eighteen responses were returned, with 50% of responders being Foundation grade doctors.

Results

Monotherapies for AP were generally disfavoured by respondents, although there was more confidence in using co-trimoxazole monotherapy over either amoxicillin or doxycycline. However, there was no clear consensus about the need for metronidazole as part of treatment regimens. This was supported by the qualitative statements made by respondents. Only 38% of respondents felt that AP did not require initiation of antimicrobials in all circumstances. Additional comments from respondents also offered insights into specialty-specific decision-making. There was a particular preference amongst doctors working in Medicine of the Elderly for using metronidazole co-therapy in treatment of AP, in part due to perceived severity of infection in their patient population. 87% of respondents reported that they use NHS Lothian’s antimicrobial companion app to support their prescribing decisions. This app has the potential to be utilized as an educational tool for junior doctors with regards to antimicrobial prescribing.

Conclusions

This small study highlights that there is still the perception that metronidazole is required in treatment of AP, and that monotherapy is generally disfavoured by prescribing clinicians. Further work in this area could include targeted quality improvement projects and education in the areas most likely to treat patients with AP.
P36 Improving AMS programmes for paediatric services via a shared post working collaboratively across five hospital trusts within South Yorkshire
Authors: Fuller Charlotte , Leavesley Neil , Joslin Fran , Shackley Fiona , Hinds Lucy , Kerrison Caroline
Published: August 2024

Methods

This project is run by a paediatric AMS leadership fellow, funded 50% by NHS England and 50% by South Yorkshire ICS, as an out of training programme experience (OOPE) through the Future Leaders Programme. This 12 month post allocates 0.3 FTE to embedding AMS principles and practices into the routine care of children accessing Barnsley, Chesterfield, Doncaster, Sheffield and Rotherham hospital trusts. A service evaluation was first undertaken to identify compliance of hospital AMS programmes with national and international guidance, followed by network formation of 32 healthcare professionals across the South Yorkshire region, including paediatricians, microbiologists and pharmacists. A regional antimicrobial prescribing monitoring and feedback system was launched, providing bi-monthly central analysis and reporting of individual trust and regional data, enabling trusts to meet monitoring requirements with only data collection as local time spent. A standardized regional education programme has been designed, with the curriculum agreed across the network. Focusing on attitudes towards responsibility, AMS principles and human factors in prescribing, this has been delivered face-to-face to paediatric prescribers in each hospital, with pre- and post-session confidence scoring in four domains.

Results

Baseline service evaluation revealed inconsistencies in AMS programmes between trusts, with only 53% of quality indicators fully met in paediatric services, compared with 73% in adults. The predominant reason reported for suboptimal compliance was staff shortages within hospital AMS teams. Since project inception (8 months), quality indicator compliance within paediatric services across South Yorkshire has increased from 53% to 65%, closing the gap between adult and paediatric AMS support. Three rounds of antimicrobial prescribing data have been collected. For prescriber confidence, the challenging prescriptions domain scored lowest. The regional education programme has increased overall prescriber confidence scores from 71.3% to 89%. Further regional AMS interventions, facilitated by the collaborative network, are in progress including regional audits and a regional antibiotic guideline.

Conclusions

Forming an AMS-focused regional collaborative network has increased awareness of services and barriers across the region, allowed for coordinated interventions familiar to rotating trainees, and facilitated the sharing of resources and learning. This approach has reduced the workload of local AMS teams by addressing the barrier of staff shortages, alongside increasing coverage of AMS programmes to paediatric services. ICBs across the UK could choose to fund similar posts dedicated to the co-ordination of AMS programmes across regions, maximizing efficiency in a climate of ongoing workforce challenges.
The reimplantation of anomalous aortic origin of the right coronary artery under lower mini-sternotomy
Authors: Maekawa Koki , Yamanaka Shota , Onga Yohe , Takahashi Shu , Kanamori Taro
Published: August 2024

The patient was 28-year-old male. He was suffered from chest pain at rest. He was diagnosed with AAORCA (anomalous aortic origin of the right coronary artery) by emergency catheter. Myocardial scintigraphy indicated ischemic changes in the right coronary artery region, so surgery was the plan. Reimplantation was selected because the coronary artery computed tomography showed little intramural travel and mild coronary artery stenosis. The surgery was performed under lower mini-sternotomy to facilitate early return to work. The patient had a good postoperative course, and was discharged from the hospital postoperative Day 11 after rehabilitation. We report a case of the right coronary artery reimplantation with lower mini-sternotomy for AAORCA.
Photosynthesis and photoprotection in top leaves respond faster to irradiance fluctuations than bottom leaves in a tomato canopy
Authors: Shao Bingjie , Zhang Yuqi , Vincenzi Elena , Berman Sarah , Vialet-Chabrand Silvere , Marcelis Leo F M , Li Tao , Kaiser Elias
Published: August 2024

Accounting for the dynamic responses of photosynthesis and photoprotection to naturally fluctuating irradiance can improve predictions of plant performance in the field, but the variation of these dynamics within crop canopies is poorly understood. We conducted a detailed study of dynamic and steady-state photosynthesis, photoprotection, leaf pigmentation, and stomatal anatomy in four leaf layers (100, 150, 200, and 250 cm from the floor) of a fully grown tomato (Solanum lycopersicum cv. Foundation) canopy in a greenhouse. We found that leaves at the top of the canopy exhibited higher photosynthetic capacity and slightly faster photosynthetic induction compared with lower-canopy leaves, accompanied by higher stomatal conductance and a faster activation of carboxylation and linear electron transport capacities. In upper-canopy leaves, non-photochemical quenching showed faster induction and relaxation after increases and decreases in irradiance, allowing for more effective photoprotection in these leaves. Despite these observed differences in transient responses between leaf layers, steady-state rather than dynamic photosynthesis traits were more influential for predicting photosynthesis under fluctuating irradiance. Also, a model analysis revealed that time-averaged photosynthesis under fluctuating irradiance could be accurately predicted by one set of Rubisco activation/deactivation parameters across all four leaf layers, thereby greatly simplifying future modelling efforts of whole-canopy photosynthesis.
Anticipatory declarations in obstetric care: a relational and spatial examination of patient empowerment, institutional impacts and temporal challenges
Authors: Hulme Aimee V
Published: August 2024

Seeking an anticipatory declaration from the Court of Protection (CoP) to manage a risk of future loss of capacity in pregnant people during labour and delivery appears to be occurring more frequently. This article examines a growing case sample of recent CoP judgments in which anticipatory declarations have been sought and adopts a combined relational and spatial approach to question whether these types of anticipatory declarations empower patient autonomous choice, and to illuminate the complex web of relational, spatial, and temporal factors that hold influence over the way in which mental capacity law operates. Viewing such processes from both a patient and institutional perspective offers useful insights into the law’s normative workings, boundaries, and constraints, and ultimately points to conclusions on the (in)effectiveness of anticipatory declarations as a legal mechanism for dealing with the risk of a patient losing capacity in the future. Moreover, however, taking a broader, spatial view signals the challenges posed by these cases to mental capacity legislation itself. The justifiability of the binary construct of capacity/incapacity has been challenged by some writers in this field, and this article offers further reflection on the integrity of this binary through its discussion of anticipatory orders for pregnant people.
Molecular epidemiology and antifungal susceptibility of dermatophytes and Candida isolates in superficial fungal infections at a grade A tertiary hospital in Northern China
Authors: Zhang Ruijun , Song Ziping , Su Xiaorui , Li Ting , Xu Juan , He Xiao , Yang Yuanwen , Chang Bingmei , Kang Yuying
Published: August 2024

This study analyzed the prevalence and antifungal susceptibility of superficial fungal infections in 295 cases from 2019 to 2020 at a dermatology clinic. Dermatophytes were the predominant pathogens (69.5%), including Trichophytonrubrum, T. interdigitale, Microsporum canis, et al., followed by Candida spp. (29.5%), including Candidaalbicans, Ca. parapsilosis, and Ca. glabrata. The most common infections were onychomycosis (36.3%), tinea cruris (30.5%), and tinea corporis (18.6%). The distribution of SFI types showed variations based on gender, age, and season. Common antifungal agents, including terbinafine, voriconazole, ciclopiroxamine, amphotericin B, itraconazole, and ketoconazole have exhibited low minimum inhibitory concentrations against dermatophytes, especially terbinafine, which has been potent against superficial fungal infections caused by dermatophytes in the local area. Candida spp. strains were generally susceptible or classified as wild-type to 5-flucytosine and amphotericin B, with 92.0% being wild-type for itraconazole. However, resistance to fluconazole and voriconazole was observed in a small percentage of Ca. albicans and Ca. parapsilosis strains. The emergence of drug-resistant Candida underscores the importance of prudent antifungal use and continuous surveillance.
Pulse profile variability associated with the glitch of PSR J1048-5832
Authors: Liu P , Yuan J -P , Ge M -Y , Ye W -T , Zhou S -Q , Dang S -J , Zhou Z -R , Gügercinoğlu E , Wang W -H , Wang P , Li A , Li D , Wang N
Published: August 2024

PSR J1048$-$5832 (B1046$-$58) is a Vela-like pulsar that has exhibited multiple glitch events. In this study, we analyse the timing data spanning nearly 16 yr, acquired from both the Fermi Gamma-ray Space Telescope and the Parkes 64 m radio telescope. As a result, a total of five glitches are detected within this data set. Among them, a previously unknown small glitch is newly found at MJD 56985(9) (November 24, 2014), making it the smallest glitch recorded from this source so far. The increments of the spin frequency and its first derivative are $\Delta \nu \approx 2.2(3) \times 10^ {-8}$ Hz, and $\Delta \dot{\nu } \approx 3(2) \times 10^ {-15}$ s$^{-2}$, respectively. Significant changes in the integrated normalized mean pulse profile are detected following three of the five glitch events, notably in the radio band. Although no evidence of a correlation is found between the spin-down rate and profile evolution, the jump phenomenon of $W_{55}$ (pulse width at the 55% peak amplitude) after the glitch in the narrow mode suggests that the glitch may influence the profile change. We discuss the influence of glitches on the pulsar’s emission properties in terms of platelet motion by a crustquake and also put constraints on the equation of state from the moment of inertia and response time-scales of involved superfluid layers inside the neutron star.
Haunted haloes: tracking the ghosts of subhaloes lost by halo finders
Authors: Diemer Benedikt , Behroozi Peter , Mansfield Philip
Published: August 2024

Dark matter subhaloes are key for the predictions of simulations of structure formation, but their existence frequently ends prematurely due to two technical issues, namely numerical disruption in N-body simulations and halo finders failing to identify them. Here, we focus on the second issue, using the phase-space friends-of-friends halo finder Rockstar as a benchmark (though we expect our results to translate to comparable codes). We confirm that the most prominent cause for losing track of subhaloes is tidal distortion rather than a low number of particles. As a solution, we present a flexible post-processing algorithm that tracks all subhalo particles over time, computes subhalo positions and masses based on those particles, and progressively removes stripped matter. If a subhalo is lost by the halo finder, this algorithm keeps tracking its so-called ghost until it has almost no particles left or has truly merged with its host. We apply this technique to a large suite of N-body simulations and restore lost subhaloes to the halo catalogues, which has a substantial effect on key summary statistics of large-scale structure. Specifically, the subhalo mass function increases by about 20 per cent to 30 per cent and the halo correlation function by about 50 per cent at small scales. While these quantitative results are somewhat specific to our algorithm, they demonstrate that particle tracking is a promising way to reliably follow haloes and to reduce the need for orphan models. Our algorithm and augmented halo catalogues are publicly available.
Discovery of double stars by Giovanni Battista Hodierna in 1654
Authors: González-Payo J , Caballero J A
Published: August 2024

It has been generally accepted that the originators of the double star astronomy were Christian Mayer and William Herschel. We recovered the memory of the poorly known Italian astronomer Giovanni Battista Hodierna, who published the first catalogue of stellar binaries over a century before Mayer and Herschel. We analysed the fourth section of 1654 G. B. Hodierna’s book ‘De systemate orbis cometici deque admirandis coeli characteribus’. There, Hodierna listed a dozen pairs of stars whose identification with modern star names had been lost for centuries. To identify the pairs, we used Hodierna’s Latin descriptions of location in constellations for all primary stars, ecliptic coordinates and angular separations to companions for some, and the Washington Double Star, Hipparcos, and Gaia catalogues. We were able to identify the twelve primaries and eleven multiple systems with companions, of which nine were double and two were triple. Besides, with up-to-date data, we confirmed that four systems are physically bound: Atlas and Pleione, $\alpha ^{1,2}$ Lib, $\nu ^{1,2}$ Dra, and $\theta ^{1}$ Ori A, C, and D. The other seven pairs are alignments of very bright stars at different distances.
Effects of the photospheric cut-off on the p-mode frequency stability
Authors: Kolotkov Dmitrii Y , Broomhall Anne-Marie , Hasanzadeh Amir
Published: August 2024

Sub-photospheric acoustic resonators allow for the formation of standing p-mode oscillations by reflecting acoustic waves with frequencies below the acoustic cut-off frequency. We employ the Klein–Gordon equation with a piecewise acoustic potential to study the characteristic frequencies of intermediate-degree p modes, modified by the cut-off effect. For a perfectly reflective photosphere, provided by the infinite value of the acoustic cut-off frequency, characteristic discrete frequencies of the trapped p modes are fully prescribed by the width of the acoustic potential barrier. Finite values of the acoustic cut-off frequency result in the reduction of p-mode frequencies, associated with the decrease in the sound speed by the cut-off effect. For example, for a spherical degree of $\ell = 100$, characteristic p-mode frequencies are found to decrease by up to 200 µHz and the effect is more pronounced for higher radial harmonics. The frequency separation between two consecutive radial harmonics is shown to behave non-asymptotically with non-uniform spacing in the radial harmonic number due to the cut-off effect. We also show how the 11-yr variability of the Sun’s photospheric magnetic field can result in the p-mode frequency shifts through the link between the acoustic cut-off frequency and the plasma parameter $\beta$. Using this model, we readily reproduce the observed typical amplitudes of the p-mode frequency shift and its phase behaviour relative to other 11-yr solar cycle proxies. The use of the developed model for comparison with observations requires its generalization for 2D effects, more realistic profiles of the acoustic potential, and broad-band stochastic drivers.
Kinematics and dynamics of the Galactic bar revealed by Gaia long-period variables
Authors: Zhang Hanyuan , Belokurov Vasily , Evans N Wyn , Kane Sarah G , Sanders Jason L
Published: August 2024

We use low-amplitude long period variable (LA-LPV) candidates in Gaia DR3 to trace the kinematics and dynamics of the Milky Way bar. LA-LPVs, like other LPVs, are intrinsically bright and follow a tight period–luminosity relation, but unlike e.g. Mira variables, their radial velocity measurements are reliable due to their smaller pulsation amplitudes. We supplement the Gaia astrometric and radial velocity measurements with distance moduli assigned using a period–luminosity relation to acquire full 6D phase space information. The assigned distances are validated by comparing to geometric distances and StarHorse distances, which shows biases less than $\sim 5~{{\rm per\ cent}}$. Our sample provides an unprecedented panoramic picture of the inner Galaxy with minimal selection effects. We map the kinematics of the inner Milky Way and find a significant kinematic signature corresponding to the Galactic bar. We measure the pattern speed of the Galactic bar using the continuity equation and find $\Omega _{\rm b}=34.1\pm 2.4$ km s$^{-1}$ kpc$^{-1}$. We develop a simple robust and potential-independent method to measure the dynamical length of the bar using only kinematics and find $R_{\rm b}\sim 4.0$ kpc. We validate both measurements using N-body simulations. Assuming knowledge of the gravitational potential of the inner Milky Way, we analyse the orbital structure of the Galactic bar using orbital frequency ratios. The $x_1$ orbits are the dominant bar-supporting orbital family in our sample. Amongst the selected bar stars, the $x_1 v_1$ or ‘banana’ orbits constitute a larger fraction ($\sim 15~{{\rm per\ cent}}$) than other orbital families in the bar, implying that they are the dominant family contributing to the Galactic X-shape, although contributions from other orbital families are also present.
X-rays from a newly discovered superbubble in M31
Authors: Liu Jiejia , Huang Rui , Li Chengzhe , Mao Junjie , Li Hui , Cui Wei
Published: August 2024

A superbubble is a hot, dilute, and X-ray-emitting gas cavity produced by stellar winds and supernova explosions. It is an intriguing feature for the study of stellar feedback processes. We report a study of possible superbubbles in the Andromeda Galaxy (M31). We identify one out of 83 extended sources as a strong superbubble candidate, SB1, from the M31 X-ray source catalogue. SB1 is located in the northern disc of M31 and exhibits soft, extended X-ray emission surrounded by an Hα shell. The XMM–Newton spectral analysis reveals that SB1 has a temperature of ∼0.14 keV and an X-ray luminosity of $L_{\rm X}\sim 3.5\times 10^{37}\,{\rm erg\, s}^{-1}$ in the 0.3–10.0 keV band. Two stellar clusters are found at the west rim of SB1. The estimated age of SB1 is similar to that of an overlapping young stellar cluster, and the colour-magnitude diagram reveals the presence of young stellar objects with an age of less than 10 Myr. We propose that SB1 is a superbubble, likely having triggered star formation in this cluster by compressing the accumulated gas, thereby leading to the formation of gas-dense regions.
Variants in NLRP2 and ZFP36L2, non-core components of the human subcortical maternal complex, cause female infertility with embryonic development arrest
Authors: Rui Ximan , Zhang Xiaolan , Jia Xinru , Han Jian , Wang Congjing , Cao Qiqi , Zhong Ou , Ding Jie , Zhao Chun , Zhang Junqiang , Ling Xiufeng , Li Hong , Ma Xiang , Meng Qingxia , Huo Ran
Published: August 2024

The subcortical maternal complex (SCMC), which is vital in oocyte maturation and embryogenesis, consists of core proteins (NLRP5, TLE6, OOEP), non-core proteins (PADI6, KHDC3L, NLRP2, NLRP7), and other unknown proteins that are encoded by maternal effect genes. Some variants of SCMC genes have been linked to female infertility characterized by embryonic development arrest. However, so far, the candidate non-core SCMC components associated with embryonic development need further exploration and the pathogenic variants that have been identified are still limited. In this study, we discovered two novel variants [p.(Ala131Val) and p.(Met326Val)] of NLRP2 in patients with primary infertility displaying embryonic development arrest from large families. In vitro studies using 293T cells and mouse oocytes, respectively, showed that these variants significantly decreased protein expression and caused the phenotype of embryonic development arrest. Additionally, we combined the ‘DevOmics’ database with the whole exome sequence data of our cohort and screened out a new candidate non-core SCMC gene ZFP36L2. Its variants [p.(Ala241Pro) and p.(Pro291dup)] were found to be responsible for embryonic development arrest. Co-immunoprecipitation experiments in 293T cells, used to demonstrate the interaction between proteins, verified that ZFP36L2 is one of the human SCMC components, and microinjection of ZFP36L2 complementary RNA variants into mouse oocytes affected embryonic development. Furthermore, the ZFP36L2 variants were associated with disrupted stability of its target mRNAs, which resulted in aberrant H3K4me3 and H3K9me3 levels. These disruptions decreased oocyte quality and further developmental potential. Overall, this is the first report of ZFP36L2 as a non-core component of the human SCMC and we found four novel pathogenic variants in the NLRP2 and ZFP36L2 genes in 4 of 161 patients that caused human embryonic development arrest. These findings contribute to the genetic diagnosis of female infertility and provide new insights into the physiological function of SCMC in female reproduction.
Network medicine-based epistasis detection in complex diseases: ready for quantum computing
Authors: Hoffmann Markus , Poschenrieder Julian M , Incudini Massimiliano , Baier Sylvie , Fritz Amelie , Maier Andreas , Hartung Michael , Hoffmann Christian , Trummer Nico , Adamowicz Klaudia , Picciani Mario , Scheibling Evelyn , Harl Maximilian V , Lesch Ingmar , Frey Hunor , Kayser Simon , Wissenberg Paul , Schwartz Leon , Hafner Leon , Acharya Aakriti , Hackl Lena , Grabert Gordon , Lee Sung-Gwon , Cho Gyuhyeok , Cloward Matthew E , Jankowski Jakub , Lee Hye Kyung , Tsoy Olga , Wenke Nina , Pedersen Anders Gorm , Bønnelykke Klaus , Mandarino Antonio , Melograna Federico , Schulz Laura , Climente-González Héctor , Wilhelm Mathias , Iapichino Luigi , Wienbrandt Lars , Ellinghaus David , Van Steen Kristel , Grossi Michele , Furth Priscilla A , Hennighausen Lothar , Di Pierro Alessandra , Baumbach Jan , Kacprowski Tim , List Markus , Blumenthal David B
Published: August 2024

Most heritable diseases are polygenic. To comprehend the underlying genetic architecture, it is crucial to discover the clinically relevant epistatic interactions (EIs) between genomic single nucleotide polymorphisms (SNPs) (1–3). Existing statistical computational methods for EI detection are mostly limited to pairs of SNPs due to the combinatorial explosion of higher-order EIs. With NeEDL (network-based epistasis detection via local search), we leverage network medicine to inform the selection of EIs that are an order of magnitude more statistically significant compared to existing tools and consist, on average, of five SNPs. We further show that this computationally demanding task can be substantially accelerated once quantum computing hardware becomes available. We apply NeEDL to eight different diseases and discover genes (affected by EIs of SNPs) that are partly known to affect the disease, additionally, these results are reproducible across independent cohorts. EIs for these eight diseases can be interactively explored in the Epistasis Disease Atlas (https://epistasis-disease-atlas.com). In summary, NeEDL demonstrates the potential of seamlessly integrated quantum computing techniques to accelerate biomedical research. Our network medicine approach detects higher-order EIs with unprecedented statistical and biological evidence, yielding unique insights into polygenic diseases and providing a basis for the development of improved risk scores and combination therapies.
The impact of the embryonic DNA methylation program on CTCF-mediated genome regulation
Authors: Monteagudo-Sánchez Ana , Richard Albert Julien , Scarpa Margherita , Noordermeer Daan , Greenberg Maxim V C
Published: August 2024

During mammalian embryogenesis, both the 5-cytosine DNA methylation (5meC) landscape and three dimensional (3D) chromatin architecture are profoundly remodeled during a process known as ‘epigenetic reprogramming.’ An understudied aspect of epigenetic reprogramming is how the 5meC flux, per se, affects the 3D genome. This is pertinent given the 5meC-sensitivity of DNA binding for a key regulator of chromosome folding: CTCF. We profiled the CTCF binding landscape using a mouse embryonic stem cell (ESC) differentiation protocol that models embryonic 5meC dynamics. Mouse ESCs lacking DNA methylation machinery are able to exit naive pluripotency, thus allowing for dissection of subtle effects of CTCF on gene expression. We performed CTCF HiChIP in both wild-type and mutant conditions to assess gained CTCF–CTCF contacts in the absence of 5meC. We performed H3K27ac HiChIP to determine the impact that ectopic CTCF binding has on cis-regulatory contacts. Using 5meC epigenome editing, we demonstrated that the methyl-mark is able to impair CTCF binding at select loci. Finally, a detailed dissection of the imprinted Zdbf2 locus showed how 5meC-antagonism of CTCF allows for proper gene regulation during differentiation. This work provides a comprehensive overview of how 5meC impacts the 3D genome in a relevant model for early embryonic events.
Perspectives of Sexual and Gender Minority Youth on Anti-Vaping Messages in Social Media
Authors: Theis Ryan P , Pilla Jenine , Okker-Edging Kate , Pluta Kathryn , LeLaurin Jennifer H , Hanby Elaine , Zulkiewicz Brittany A , Clark Danielle , Bteddini Dima , Wright Stacy E , Fahnlander Alexandra M , Katz-Wise Sabra L , Lydon-Staley David M , Maziak Wasim , Charlton Brittany M , Scout N F N , Machado Ana M , Gordon Bob , Applegate Julia M , Potter Jennifer E , Strasser Andrew A , Liu Sixiao , Salloum Ramzi G , Tan Andy S L
Published: August 2024

Introduction

Sexual and gender minority (SGM) youth have higher rates of nicotine vaping than other youth in the United States. While social media can be effective in reaching youth and discouraging vaping, informed cultural tailoring is necessary to ensure effective messaging to SGM youth. This study aimed to understand SGM youth perspectives on anti-vaping social media messages and tailoring approaches.

Aims and Methods

In-depth, qualitative videoconference interviews were conducted from February to July 2022 with 34 SGM youth recruited in the United States via social media ads. The interview guide addressed participants’ beliefs about vaping, the context of vaping, perspectives on tailoring messages, and responses to examples of social media anti-vaping messages. Coding and thematic analysis followed a team-based approach.

Results

SGM youth perspectives fell into four categories—representation and diversity, facts and evidence, empowering messages, and source credibility. Participants stressed the importance of accurate, genuine representation of SGM youth in messages, but also noted that more overt representation may be seen as tokenizing. Participants recommended partnering with known LGBTQ + influencers who can promote or share anti-vaping messages on social media platforms. They also recommended using culturally tailored language, including statistics specific to SGM youth, and invoking themes of empowerment to improve the relevance, reach, and effectiveness of anti-vaping campaigns.

Conclusions

Findings can inform future efforts to develop anti-vaping messages for SGM youth with effective reach through social media. Nuanced perspectives on SGM representation in messages suggest a careful approach to tailoring. Concerns around inauthenticity may be minimized by ensuring SGM youth are included in message development and dissemination.

Implications

This study describes the importance of being attentive to the tailoring preferences among the current generation of SGM youth. Findings will inform social media-based messaging strategies that discourage nicotine vaping tailored for SGM youth in health campaign material design and evaluation, ensuring that tailored messages are designed in ways that avoid unintended consequences. The study also describes methods for effectively engaging SGM youth in research to improve the relevance of health education materials for this population and increase reach, which in turn can lead to a reduction in vaping practices among SGM youth.
Balanced crystalloid (Sterofundin) vs. normal saline for diabetic ketoacidosis: a prospective intervention trial with historical controls
Authors: Bharti D , Selvam S , Sharma N , Dutta P , Pannu A K
Published: August 2024

Background

Fluid therapy with normal saline (NS) in diabetic ketoacidosis (DKA) can cause hyperchloremic acidosis and delay DKA resolution. Balanced crystalloids may address this concern, though results with Ringer lactate and Plasma-Lyte have been mixed.

Aim

This study aimed to compare the effectiveness of Sterofundin (SF) vs. NS in the management of DKA.

Methods

A prospective, intervention trial with historical controls was conducted at the Postgraduate Institute of Medical Education and Research, Chandigarh, India. Patients aged 13 years or older with DKA were enrolled. The primary outcome was the time taken to DKA resolution, with a predefined superiority margin of a one-fourth reduction in resolution time. Secondary outcomes included total intravenous fluid and short-acting regular insulin requirements, the need for 0.45% saline, hospital stay duration and in-hospital mortality.

Results

A total of 150 patients (mean age 36.8 years, 56.7% males) were included, with 75 receiving SF (intervention group) and 75 receiving NS (historical control group). The SF group showed a significantly shorter mean time to DKA resolution (13.8 ± 6.0 h) compared to the NS group (18.1 ± 5.5 h; P < 0.001). SF patients required less total intravenous fluid (4500 vs. 6000 ml; P = 0.004), less insulin (98 units vs. 112 units; P = 0.017) and had a lower need for 0.45% saline (8% vs. 74.3%; P < 0.001). Patients receiving SF had shorter hospital stays (4 [interquartile range, IQR 3–5] days vs. 4 [IQR 4–6] days; P = 0.020). Mortality rates were similar between the groups (SF: 9.3%, NS: 8.1%; P = 0.791).

Conclusion

SF may be a superior alternative to NS for fluid therapy in DKA.
Acute kidney injury, an underrecognized feature of VEXAS syndrome
Authors: Kalantari Kambiz , Sullivan Megan M , Herrera Hernandez Loren P , Bu Lihong , Cornell Lynn D , Nasr Samih H , Fervenza Fernando C , Montes Daniel , Mangaonkar Abhishek A , Go Ronald S , Kusne Yael N , Patnaik Mrinal M , Lasho Terra L , Olteanu Horatiu , Reichard Kaaren K , Warrington Kenneth J , Koster Matthew J
Published: August 2024

Objectives

Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic (VEXAS) syndrome is an autoinflammatory disease caused by somatic mutation of UBA1 and affects multiple organ systems. Involvement of the kidneys is not well characterized. We aimed to investigate the incidence, risk factors and histopathologic features of acute kidney injury (AKI) in VEXAS syndrome.

Methods

Patients with genetically confirmed UBA1 mutation consistent with VEXAS were included. Charts were manually reviewed. Cox regression analysis was used to identify variables associated with time-to-first AKI event. For patients with a kidney biopsy, histopathologic findings were reviewed.

Results

Eighty-one patients were included, all white men, with a mean age of 66.3 ± 8.6 years. Median (IQR) follow up was 3.5 (2.1–5.2) years during which 20 (25%) developed AKI and 22% died. AKI relapsed in 90% of cases for a median of 6 times during the follow up period. Cumulative incidence estimates (95% CI) for AKI at 1, 3 and 5 years were 6.2% (0.80–11.3%), 16.7% (7.5–25.0%) and 27.9% (14.9–38.9%), respectively. Age and baseline C-reactive protein (CRP) were significantly associated with time-to-first AKI event. Six patients underwent a kidney biopsy. Findings included, plasma cell-rich interstitial nephritis (n = 3), neutrophilic-rich interstitial inflammation (n = 1), leukocytoclastic peritubular capillaritis (n = 1) and acute tubular injury (n = 1). AKI responded well to treatment with glucocorticoids but had relapse upon tapering.

Conclusion

AKI is an underrecognized feature of VEXAS occurring in 25% of patients in this cohort. Age at diagnosis and CRP were associated with time to first AKI event during follow up. Plasma cell-rich interstitial nephritis was the most common histopathologic finding.
Signature analysis of high-throughput transcriptomics screening data for mechanistic inference and chemical grouping
Authors: Harrill Joshua A , Everett Logan J , Haggard Derik E , Word Laura J , Bundy Joseph L , Chambers Bryant , Harris Felix , Willis Clinton , Thomas Russell S , Shah Imran , Judson Richard
Published: August 2024

High-throughput transcriptomics (HTTr) uses gene expression profiling to characterize the biological activity of chemicals in in vitro cell-based test systems. As an extension of a previous study testing 44 chemicals, HTTr was used to screen an additional 1,751 unique chemicals from the EPA’s ToxCast collection in MCF7 cells using 8 concentrations and an exposure duration of 6 h. We hypothesized that concentration-response modeling of signature scores could be used to identify putative molecular targets and cluster chemicals with similar bioactivity. Clustering and enrichment analyses were conducted based on signature catalog annotations and ToxPrint chemotypes to facilitate molecular target prediction and grouping of chemicals with similar bioactivity profiles. Enrichment analysis based on signature catalog annotation identified known mechanisms of action (MeOAs) associated with well-studied chemicals and generated putative MeOAs for other active chemicals. Chemicals with predicted MeOAs included those targeting estrogen receptor (ER), glucocorticoid receptor (GR), retinoic acid receptor (RAR), the NRF2/KEAP/ARE pathway, AP-1 activation, and others. Using reference chemicals for ER modulation, the study demonstrated that HTTr in MCF7 cells was able to stratify chemicals in terms of agonist potency, distinguish ER agonists from antagonists, and cluster chemicals with similar activities as predicted by the ToxCast ER Pathway model. Uniform manifold approximation and projection (UMAP) embedding of signature-level results identified novel ER modulators with no ToxCast ER Pathway model predictions. Finally, UMAP combined with ToxPrint chemotype enrichment was used to explore the biological activity of structurally related chemicals. The study demonstrates that HTTr can be used to inform chemical risk assessment by determining in vitro points of departure, predicting chemicals’ MeOA and grouping chemicals with similar bioactivity profiles.