bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural and Functional Glycosylation of the Abdala COVID-19 Vaccine
Authors: Burnap Sean A , Calvaresi Valeria , Cabrera Gleysin , Pousa Satomy , Limonta Miladys , Ramos Yassel , González Luis Javier , Harvey David J , Struwe Weston B
Published: January 2025

Abdala is a COVID-19 vaccine produced in Pichia pastoris and is based on the receptor-binding domain (RBD) of the SARS-CoV-2 spike. Abdala is currently approved for use in multiple countries with clinical trials confirming its safety and efficacy in preventing severe illness and death. Although P. pastoris is used as an expression system for protein-based vaccines, yeast glycosylation remains largely uncharacterised across immunogens. Here, we characterise N-glycan structures and their site of attachment on Abdala and show how yeast-specific glycosylation decreases binding to the ACE2 receptor and a receptor-binding motif (RBM) targeting antibody compared to the equivalent mammalian-derived RBD. Reduced receptor and antibody binding is attributed to changes in conformational dynamics resulting from N-glycosylation. These data highlight the critical importance of glycosylation in vaccine design and demonstrate how individual glycans can influence host interactions and immune recognition via protein structural dynamics.
Endometriosis and risk of depression among oral contraceptive users: a pooled analysis of cohort studies from 13 countries
Authors: De Corte P , Milhoranca I , Oberg A S , Kurth T , Mechsner S , Heinemann K
Published: January 2025

STUDY QUESTION

Does endometriosis affect the mental health of women using oral contraceptives?

SUMMARY ANSWER

Among oral contraceptive users, women with endometriosis have a higher risk of depression compared to those without endometriosis, although the absolute risk increase is small.

WHAT IS KNOWN ALREADY

Previous studies have suggested a potential link between endometriosis and mental health issues, but the impact of endometriosis on depression among oral contraceptive users remains unclear.

STUDY DESIGN, SIZE, DURATION

A secondary pooled cohort study utilizing data from two longitudinal patient-centric studies (INAS-VIPOS and PRO-E2) was conducted across 11 European countries, Colombia and Australia. The study included 93 541 women newly prescribed oral contraceptives, with or without endometriosis, and without a self-reported history of depression.

PARTICIPANTS/MATERIALS, SETTING, METHODS

Participant’s mental health was captured using self-administered questionnaires at baseline and every 6–12 months thereafter, asking about any newly occurred episodes of depression. Incidence rates (IRs) of self-reported depression were calculated per 10 000 woman-years. Absolute risk difference (ARD) and number needed to harm (NNH) were calculated with 95% CIs. The association between endometriosis and self-reported depression was estimated through crude and adjusted hazard ratios (HRs) with 95% CI, using stabilized inverse probability of treatment weighting (IPTW).

MAIN RESULTS AND THE ROLE OF CHANCE

Of the included 93 541 women, 21 090 had endometriosis (49 541 woman-years) and 72 451 had no endometriosis (137 137 woman-years.) Of those with endometriosis, 308 (1.5%) reported an episode of depression (IR: 62.2/10 000, 95% CI: 55.4–69.5) compared to 535 (0.7%) of women without endometriosis (IR 39.0/10 000, 95% CI: 35.8–42.5). The ARD and NNH were 23.2 per 10 000 (95% CI: 15.2–30.9) and 431 (95% CI: 323.7–657.0) respectively. The HR of depression in women with endometriosis was 1.85 (95% CI: 1.60–2.13) using stabilized IPTW to control for age, BMI, smoking, education, and age at menarche. Subgroup and sensitivity analyses showed similar results.

LIMITATIONS, REASONS FOR CAUTION

While efforts were made to control for confounding factors, residual confounding may still exist. Additionally, the results can only be generalized to users of oral contraceptives.

WIDER IMPLICATIONS OF THE FINDINGS

These results highlight the importance of considering the mental health implications of endometriosis among women using oral contraceptives. Further research is needed to explore additional contributing factors and potential interventions.

STUDY FUNDING/COMPETING INTEREST(S)

No funding was received for this study. No competing interests apply for this research.

TRIAL REGISTRATION NUMBER

N/A.
Impact of microwave processing and high pressure processing on omega-3 fatty acid enriched snack of microalgae (Nannochloropsis sp)-cocoa balls
Authors: Luo Tong , Ninan Neethu , Truong Vi Khanh , He Shan , Alhaji Jwaher Haji , Binobead Manal Abdulaziz
Published: January 2025

This study investigates the development of a functional snack, NSP (Nannochloropsis sp.)-cocoa balls, enriched with omega-3 fatty acids, utilizing two advanced processing methods: microwave processing and high-pressure processing (HPP). The primary objective was to assess the efficiency of these techniques in preserving nutritional value, particularly omega-3 content, while maintaining desirable sensory qualities over a 12-day storage period. Microwave processing was found to partially retain omega-3 fatty acids but resulted in increased firmness and faster oxidation due to moisture loss during heating. In contrast, HPP effectively preserved omega-3 content and maintained the original texture and sensory appeal of the NSP-cocoa balls. The even distribution of omega-3 fatty acids in HPP-treated samples enhanced their resistance to oxidation, contributing to greater stability. Sensory evaluations identified the HPP-treated cocoa balls, specifically those prepared using Recipe 4, as the most preferred for their texture and superior nutritional profile. Furthermore, food safety analyses confirmed the safety of these snacks for consumption throughout the storage period. This comprehensive study highlights HPP as a superior processing method for developing functional foods that balance nutrient preservation with sensory quality, offering a promising approach for creating health-focused, shelf-stable snacks.
Preclinical evaluation of the efficacy and safety of adeno-associated virus 8-tissue-nonspecific alkaline phosphatase-D10 in Alpl-/- and AlplPrx1/Prx1 mouse models for the treatment of early and late-onset hypophosphatasia
Authors: de Oliveira Flavia Amadeu , Tokuhara Cintia Kazuko , Mohamed Fatma F , Narisawa Sonoko , Lira dos Santos Elis J , Andras Natalie L , Shadid Mohammad , Miyake Koichi , Foster Brian L , Millán José Luis
Published: January 2025

We previously documented successful resolution of skeletal and dental disease in the infantile and late-onset murine models of hypophosphatasia (HPP) with a single injection of an adeno-associated serotype 8 vector encoding mineral-targeted TNAP (AAV8-TNAP-D10). Here, we conducted dosing studies in both HPP mouse models. A single escalating dose from 4 × 108 up to 4 × 1010 (vg/b) was intramuscularly injected into 4-day-old Alpl-/- mice (an infantile HPP model) and a single dose from 4 × 106 up to 4 × 109 (vg/b) was administered to 8-wk-old AlplPrx1/Prx1 mice (a late-onset HPP model). Wild-type littermates were used as controls. Serum alkaline phosphatase activity was increased, and PPi levels were decreased in a dose-dependent manner in both the Alpl-/- and AlplPrx1/Prx1 models. Radiographic and μCT analysis of long bones of female and male Alpl-/- mice showed full correction of skeletal phenotype at 4 × 1010 vg/b. We observed full correction of the bone phenotype at 4 × 108 and 4 × 109 in female AlplPrx1/Prx1 mice, but bones remained hypomineralized with the 4 × 106 and 4 × 107 (vg/b) doses after 70 d of treatment. We observed skeletal improvements using the 4 × 109 (vg/b) dose, but the phenotype was not fully corrected in male AlplPrx1/Prx1. Immunohistochemistry using anti-TNAP and anti-D10 antibodies showed high immunolocalization in the femurs of female AlplPrx1/Prx1 mice, while D10 immunolocalization was high in the liver of male AlplPrx1/Prx1 mice at a dose of 4 × 109 (vg/b). This sex-dependent difference was not seen in the infantile HPP model. A serum proteome analysis showed enhanced inflammatory pathways in treated AlplPrx1/Prx1 males compared to treated female mice. We also found a few areas of ectopic calcification in soft organs at the highest tested dose of 4 × 1010 (vg/b) in Alpl-/- or 4 × 109 (vg/b) in the AlplPrx1/Prx1 model. This pre-clinical study will inform the design of clinical trials to develop gene therapy in early-onset and late-onset HPP patients.
Functional performance and symptomatology of adults with skeletal dysplasia across self-care, mobility, and cognition—a cross-sectional study
Authors: Nguyen Daphne , Ireland Penelope , Pacey Verity
Published: January 2025

Individuals with skeletal dysplasia (SD) experience physical challenges in performing everyday activities as a result of their altered biomechanics and systemic comorbidities. The purpose of this study was to objectively assess functional performance and identify symptomatology across self-care, mobility, and cognitive tasks among adults with SD. The secondary aim was to describe any differences in performance between individuals with proportionate forms of SD compared with those with disproportionate forms. A cross-sectional online survey and functional assessment, the Functional Independence Measure (FIM), was administered to adults diagnosed with SD. Summary statistics were computed and analyzed. Survey open-ended text responses were examined. Data were collected on 40 adults (median age 41.2 yr) presenting with 10 types of SD (14 with proportionate SD, 26 disproportionate SD). A total of 39 (97.5%) participants required assistance or modification when completing functional activities. Increased reliance on assistance was observed across self-care and mobility tasks (median FIM scores 51/56 and 31.5/35 respectively), compared with cognitive items (median FIM score 34.5/35). Up to 50% of participants reported experiencing pain, fatigue, and/or other symptoms during self-care and mobility tasks. These symptoms were more prevalent when completing self-care activities at home and when mobilizing in the community. Participants with proportionate forms of SD demonstrated higher levels of independence in upper body dressing, toileting, and bed/chair/wheelchair transfers, whereas participants with disproportionate forms had higher scores in eating and grooming tasks. Adults with SD demonstrated functional challenges and symptomatology associated with activities of daily living. Overall, there are minimal differences in FIM scores between individuals with proportionate forms of SD and those with disproportionate forms. Use of assistive equipment, modifications, and allowing extra time with tasks may improve independence among this population group.
Chemical compounds associated with Schistocerca piceifrons piceifrons (Orthoptera: Acrididae), by Gas Chromatography–Mass Spectrometry analysis
Authors: García-García Luis Daniel , Barrientos-Lozano Ludivina , Torres-Castillo Jorge Ariel , Rocha-Sánchez Aurora Y , Almaguer-Sierra Pedro , González-Gaona Othón Javier , Rodríguez-Rodríguez José
Published: January 2025

Semiochemicals are chemicals that mediate inter- and intraspecific interactions between insects. Recently, these chemicals have begun to be investigated as an alternative for the management of the Central American locust, Schistocerca piceifrons piceifrons (Walker, 1870), a pest that can cause substantial damage to crops, pastures, and native vegetation. A suitable method for investigating the range of semiochemicals present in Central American locust is surface washing in organic solvents. In the work described here, the extraction of chemical compounds was carried out with hexane in a 1:10 (w/v) ratio, in 2 resting periods (1 and 24 h) and 2 stages of Central American locust development (young adult and adult in reproductive stage). By Gas Chromatography–Mass Spectrometry, 17 chemical compounds previously identified with semiochemical potential in other insects were detected. The study of semiochemicals in Central American locust offers the opportunity to identify specific chemical compounds that may have the potential to implement management alternatives for this pest. Specific studies of each compound detected in this work are needed to elucidate whether they have semiochemical activity and potential to combat the pest and reduce the environmental damage caused by the application of synthetic chemical products.
Making the case for an International Childhood Cancer Data Partnership
Authors: Forjaz Gonçalo , Kohler Betsy , Coleman Michel P , Steliarova-Foucher Eva , Negoita Serban , Guidry Auvil Jaime M , Michels Fernanda Silva , Goderre Johanna , Wiggins Charles , Durbin Eric B , Geleijnse Gijs , Henrion Marie-Charlotte , Altmayer Candice , Dubois Thomas , Penberthy Lynne
Published: January 2025

Childhood cancers are a heterogeneous group of rare diseases, accounting for less than 2% of all cancers diagnosed worldwide. Most countries, therefore, do not have enough cases to provide robust information on epidemiology, treatment, and late effects, especially for rarer types of cancer. Thus, only through a concerted effort to share data internationally will we be able to answer research questions that could not otherwise be answered. With this goal in mind, the US National Cancer Institute and the French National Cancer Institute co-sponsored the Paris Conference for an International Childhood Cancer Data Partnership in November 2023. This meeting convened more than 200 participants from 17 countries to address complex challenges in pediatric cancer research and data sharing. This Commentary delves into some key topics discussed during the Paris Conference and describes pilots that will help move this international effort forward. Main topics presented include: (1) the wide variation in interpreting the European Union’s General Data Protection Regulation among Member States; (2) obstacles with transferring personal health data outside of the European Union; (3) standardization and harmonization, including common data models; and (4) novel approaches to data sharing such as federated querying and federated learning. We finally provide a brief description of 3 ongoing pilot projects. The International Childhood Cancer Data Partnership is the first step in developing a process to better support pediatric cancer research internationally through combining data from multiple countries.
Sex differences in melanoma survival—a GEM study
Authors: Murali Tharani , Schwartz Matthew , Reynolds Adam Z , Luo Li , Ridgeway Grace , Busam Klaus J , Cust Anne E , Anton-Culver Hoda , Gallagher Richard P , Zanetti Roberto , Rosso Stefano , Sacchetto Lidia , Begg Colin B , Orlow Irene , Thomas Nancy E , Berwick Marianne ,   for the GEM Study Team, Berwick Marianne , Begg Colin , Orlow Irene , Busam Klaus J , Berwick Marianne , Luo Li , Boyce Tawny W , Cust Anne E , Armstrong Bruce K , Kricker Anne , Venn Alison , Dwyer Terence , Tucker Paul , Gallagher Richard P , Marrett Loraine D , Zanetti Roberto , Rosso Stefano , Sacchetto Lidia , Anton-Culver Hoda , Gruber Stephen B , Huang Shu-Chen , Thomas Nancy E , Conway Kathleen , Ollila David W , Googe Paul B , Edmiston Sharon N , Hao Honglin , Parrish Eloise , Gibbs David C , Rebbeck Timothy R , Kanetsky Peter A , Taylor Julia Lee , Madronich Sasha , Roy Pampa , Canchola Rebecca , LaPilla Emily , Yoo Sarah , Sharma Ajay , Cotignola Javier , Eaton Alison , Groben Pamela , White Kirsten , Walker Amy , Panossian Saarene
Published: January 2025

Sex differences in melanoma are prominent, with female having a significant survival advantage. However, it is unclear why we see this survival advantage. Here, we investigate the relationship between sex, clinicopathologic variables, and melanoma specific survival in 1753 single primary melanomas from patients in the GEM (Genes, Environment, and Melanoma) study. Using Cox proportional hazard models and formal mediation analysis, the effect of sex on survival is explained largely by differences in the clinicopathologic features of tumors at diagnosis. Specifically, we find evidence that 86.5% of the effect of sex on melanoma survival is mediated by differences in age at diagnosis, Breslow thickness, ulceration, mitoses, and site (hazard ratio [HR] = 1.85, P < .001). This analysis indicates that the female survival advantage in melanoma is not primarily due to a direct effect of sex (HR = 1.19, P = .42) but is largely a result of an indirect effect of sex mediated by clinicopathologic features.
Overcoming prejudices and stigmatization towards refugees: A novel approach through deliberative citizen dialogues in Turkey
Authors: Yabanci Bilge
Published: January 2025

Can changing how refugees and asylum seekers are narrated in public debates help citizens reassess their prejudices? Which narratives would garner support from ordinary citizens and promise to generate an attitude shift? While hate speech and far-right narratives targeting forcibly displaced people, refugees and asylum seekers are reported extensively, little is known about how citizens would respond to alternative narratives that portray them as rights-bearing agents. This study uses an interdisciplinary theoretical framework that brings migration scholarship in dialogue with cognitive fields and social psychology and offers a novel participatory approach to generate data. In eight cities across Turkey, citizens were invited to deliberate three sets of ‘de-stigmatizing narratives’ based on (1) social solidarity, (2) collective memory of welcoming and settling refugees in the past, and (3) the injustices of exploitation that refugees encounter while earning a living. Participants were steered to discuss each narrative through (a) progressive framing (fairness, egalitarianism, and social cohesion) and (b) conservative-nationalist framing (maintenance of law, order, and identity). The findings reveal that engaging with de-stigmatizing narratives evokes affective empathy, leading to moderate, refugee-supportive attitudes among participants even in a context where anti-refugee attitudes have escalated to communal attacks targeting refugees. However, positive attitudes towards refugees display a local turn, varying by city and often after progressive frames are supported by conservative-nationalist ones. The study highlights the importance of participatory community mobilization and sub-national/local approaches to shift, counter, or replace prevailing narratives to help reduce misinformation and prejudices about refugees.
Revisiting the cosmological time dilation of distant quasars: influence of source properties and evolution
Authors: Brewer Brendon J , Lewis Geraint F , Li Yuan (Cher)
Published: January 2025

After decades of searching, cosmological time dilation was recently identified in the time-scale of variability seen in distant quasars. Here, we expand on the previous analysis to disentangle this cosmological signal from the influence of the properties of the source population, specifically the quasar bolometric luminosity and the rest-frame emission wavelength at which the variability was observed. Furthermore, we consider the potential influence of the evolution of the quasar population over cosmic time. We find that a significant intrinsic scatter of $0.288 \pm 0.021$ dex in the variability time-scales, which was not considered in the previous analysis, is favoured by the data. This slightly increases the uncertainty in the results. However, the expected cosmological dependence of the variability time-scales is confirmed to be robust to changes in the underlying assumptions. We find that the variability time-scales increase smoothly with both wavelength and bolometric luminosity, and that black hole mass has no effect on the variability time-scale once rest wavelength and bolometric luminosity are accounted for. Moreover, if the standard cosmological model is correct, governed by relativistic expansion, we also find very little cosmological evolution in the intrinsic variability time-scales of distant quasars.
Searching for short-timescale radio anomalies using nonlinear dimensionality reduction techniques
Authors: Yang X , Hobbs G , Zhang S-B , Zic A , Toomey L , Li Y , Wang J-S , Dai S , Wu X-F
Published: January 2025

We have searched for anomalous events using 2,520 hours of archival observations from Murriyang, CSIRO’s Parkes radio telescope. These observations were originally undertaken to search for pulsars. We used a machine-learning algorithm based on ResNet and Uniform Manifold Approximation and Projection (UMAP) in order to identify parts of the data stream that potentially contain anomalous signals. Many of these anomalous events are radio frequency interference, which were subsequently filtered using multibeam information. We detected 202 anomalous events and provide their positions and event times. Our results show that the UMAP unsupervised machine learning pipeline effectively identifies anomalous signals in high-time-resolution datasets, highlighting its potential for use in future surveys. However, the pipeline is not applicable for standard searches for dispersed single pulses. We classify the detected events and, in particular, we are currently unable to determine the possible origin of events that last multiple seconds. For these we encourage follow-up observations.
Investigation of oscillations above the acoustic cut-off frequency for a sample of Kepler stars. II. Identifying temporal frequency shifts
Authors: Millson L J , Broomhall A-M , Santos A R G , Kiefer R , Jones M
Published: January 2025

Stellar oscillations with frequencies greater than the acoustic cut-off frequency are not trapped within the star’s interior. Geometric interference between these high-frequency waves produces a peak-like structure in the power spectrum of the star, known as the pseudo-modes. In this study, we aim to analyse 51 stars previously identified (from a sample of 91 Kepler stars) to contain statistically significant evidence for pseudo-modes, to determine if the pseudo-mode frequencies vary in time. We obtained these frequency variations and the uncertainty by the resampled periodogram approach, where periodogram realisations were created from successive, overlapping 90-d time segments, and a cross-correlation function was generated between them. The computed shifts were compared against temporal p-mode frequency shifts and a stellar magnetic activity proxy, $S_{\mathrm{ph}}$. We found that for 16 per cent of the stars pseudo-mode frequency shifts were significantly anticorrelated with p-mode shifts, as is the case for the Sun. However, we also found pseudo-mode and p-mode shifts to be significantly correlated in-phase in 8 per cent of our sample. The remainder showed no significant correlation. We also searched for trends between the maximum variation of pseudo-mode frequency shifts and stellar parameters. Whilst we found no correlation between the maximum variation and stellar photospheric and chromospheric proxies, we found frequency variations to have a greater amplitude for cooler and slower rotating stars, which is in opposition to p-mode frequency shift variation. Temporal changes to pseudo-mode frequencies may be attributable to variations in stellar magnetic activity, and therefore can contribute to our understanding of stellar activity cycles.
Resonant capture of stars by black hole binaries: extreme eccentricity excitation
Authors: Reved Omri , Friedland Lazar , Stone Nicholas C
Published: January 2025

Massive black hole (MBH) binaries in galactic nuclei are one of the leading sources of ${\sim}$mHz gravitational waves (GWs) for future missions such as Laser Interferometer Space Antenna (LISA). However, the poor sky localization of GW interferometers will make it challenging to identify the host galaxy of MBH mergers absent an electromagnetic counterpart. One such counterpart is the tidal disruption of a star that has been captured into mean motion resonance with the inspiralling binary. Here we investigate the production of tidal disruption events (TDEs) through capture into, and subsequent evolution in, orbital resonance. We examine the full non-linear evolution of planar autoresonance for stars that lock into autoresonance with a shrinking MBH binary. Capture into the 2:1 resonance is guaranteed for any realistic astrophysical parameters (given a relatively small MBH binary mass ratio), and the captured star eventually attains an eccentricity $e\approx 1$, leading to a TDE. Stellar discs can be produced around MBHs following an active galactic nucleus episode, and we estimate the TDE rates from resonant capture produced when a secondary MBH begins inspiralling through such a disc. In some cases, the last resonant TDE can occur within a decade of the eventual LISA signal, helping to localize the GW event.
Conditions for super-Eddington accretion onto the first black holes
Authors: Gordon Simone T , Smith Britton D , Khochfar Sadegh , Beckmann Ricarda S
Published: January 2025

Observations of supermassive black holes (BHs) at high redshift challenge our understanding of the evolution of the first generation of BHs in proto-galactic environments. One possibility is that they grow much more rapidly than current estimates of feedback and accretion efficiency permit. Following our previous analysis of super-Eddington accretion on to stellar-mass BHs in mini-haloes under no-feedback conditions, we now investigate whether this can be sustained when thermal feedback is included. We use four sets of cosmological simulations at sub-pc resolution with initial BH masses varying from $1 \times 10^{3} \ \mathrm{ to} \ 6 \times 10^{4} \ {\rm M_\odot }$, exploring a range of feedback efficiencies. We also vary the feedback injection radius to probe the threshold of numerical overcooling. We find that super-Eddington growth sustained of the order of $\sim$$100 \ \rm kyr$ is possible with weak thermal feedback efficiency in all environments and moderate efficiency for two of the BHs. Trans-Eddington growth is possible for a $3 \times 10^{3}\!\! - \!\! 6 \times 10^{3}\ {\rm M_\odot }$ BH at moderate feedback efficiencies. We discuss the effectiveness of thermal feedback in heating the gas, suppressing accretion, and driving outflows at these parameter configurations. Our results suggest that super-Eddington growth may be possible in the presence of thermal feedback for BHs formed from the first stars.
WISDOM Project – XXII. A 5 per cent precision CO-dynamical supermassive black hole mass measurement in the galaxy NGC 383
Authors: Zhang Hengyue , Bureau Martin , Ruffa Ilaria , Cappellari Michele , Davis Timothy A , Dominiak Pandora , Elford Jacob S , Iguchi Satoru , Lelli Federico , Sarzi Marc , Williams Thomas G
Published: January 2025

We present a measurement of the supermassive black hole (SMBH) mass of the nearby lenticular galaxy NGC 383, based on Atacama Large Millimeter/sub-millimeter Array (ALMA) observations of the $^{12}$CO(2-1) emission line with an angular resolution of $0.050{\,\rm arcsec}\times 0.024{\,\rm arcsec}$ ($\approx 16\times 8$ pc$^2$). These observations spatially resolve the nuclear molecular gas disc down to $\approx 41\,300$ Schwarzschild radii and the SMBH sphere of influence by a factor of $\approx 24$ radially, better than any other SMBH mass measurement using molecular gas to date. The high resolution enables us to probe material with a maximum circular velocity of $\approx 1040$ km s$^{-1}$, even higher than those of the highest resolution SMBH mass measurements using megamasers. We detect a clear Keplerian increase (from the outside in) of the line-of-sight rotation velocities, a slight offset between the gas disc kinematic (i.e. the position of the SMBH) and morphological (i.e. the centre of the molecular gas emission) centres, an asymmetry of the innermost rotation velocity peaks and evidence for a mild position angle warp and/or non-circular motions within the central $\approx 0.3\,{\rm arcsec}$. By forward modelling the mass distribution and ALMA data cube, we infer an SMBH mass of $(3.58\pm 0.19)\times 10^9$ M$_\odot$ ($1\sigma$ confidence interval), more precise (5 per cent) but consistent within $\approx 1.4\sigma$ with the previous measurement using lower resolution molecular gas data. Our measurement emphasizes the importance of high spatial resolution observations for precise SMBH mass determinations.
Black hole-disc coevolution in the presence of magnetic fields: refining the Thorne limit with emission from within the plunging region
Authors: Mummery Andrew
Published: January 2025

The accretion of material on to a black hole modifies the properties of that hole owing to the capture of both matter and radiation. Adding matter to the hole through an accretion disc generally acts to increase the hole’s spin parameter, while the capture of radiation generally provides a retarding torque. The balance between the torques provided by adding matter and radiation leads to a maximum spin parameter that can be obtained by a black hole which grows by accretion, known as the Thorne limit. In the simplest theory of thin disc accretion this Thorne limit has the value $a_{\bullet , {\rm lim}} \simeq 0.998$. The purpose of this paper is to highlight that any modification to theories of accretion flows also modify this limiting value, and to compute precisely the modification arising from a particular extension of accretion theory: the inclusion of bright emission from within the plunging region which is sourced from the magnetohydrodynamic stresses ubiquitously observed in simulations. This extra emission further suppresses black hole spin-up and results in new, lower, limits on the final black hole spin. These limits depend on the details of the magnetic stresses acting within the plunging region, but typical values seen in simulations and observations would lower the limit to $a_{\bullet , {\rm lim}} \simeq 0.99$, a subtle but not negligible deviation.
Tissue fibrosis in cardiorenal syndrome: crosstalk between heart and kidneys
Authors: Dutta Abhi , Chakraborty Sanchari , Roy Antara , Mittal Anupam , Basak Trayambak
Published: January 2025

Cardiorenal syndrome (CRS) is represented as an intricate dysfunctional interplay between the heart and kidneys, marked by cardiorenal inflammation and fibrosis. Unlike other organs, the repair process in cardiorenal injury involves a regenerative phase characterized by proliferation and polyploidization, followed by a subsequent pathogenic phase of fibrosis. In CRS, acute or chronic cardiorenal injury leads to hyperactive inflammation and fibrotic remodeling, associated with injury-mediated immune cell (Macrophages, Monocytes, and T-cells) infiltration and myofibroblast activation. An inflammatory to fibrotic transition corresponds with macrophage transition (M1-M2) associated with increased TGF-β response. Chronic inflammation disrupts hemodynamic pathways, leading to imbalanced oxidative stress and the production of cytokines and growth factors that promote fibrotic stimulation, contributing to pathological cardiorenal remodeling. The inflammatory response paves the pre-fibrotic cardiorenal niche and drives subsequent fibrotic remodeling by activated myofibroblasts. A fibrotic cardiorenal response in CRS is characterized by increased and degradation-resistant deposition of extracellular proteins especially fibrillar Collagen -I, -III, -V, and non-fibrillar Collagen-IV by active myofibroblasts. Recent advances in basic research animal models of CRS have advanced the knowledge of cardiorenal fibrosis. However, a significant need for clinical applications, trials, and evaluation is still needed. Circulating biomarkers like procollagen peptides and TGF-β have clinically been associated with cardiorenal fibrosis diagnosis in CRS. Treatments targeting the fibrotic pathways have also shown efficacy in amelioration of cardiorenal fibrosis in preclinical models. Recent combination therapies targeting multiple fibrotic pathways have been shown to offer promising results. Understanding the heterogenic pathological progression and fibrogenesis could identify novel therapeutic approaches for clinical CRS diagnosis and treatment.
Rethinking chronic care: how blended patient-centered care delivery and innovative financing models can contribute to achieving universal health coverage—a case study of an integrated approach in Kenya
Authors: van Andel Judith , Gómez-Pérez Gloria P , Otieno Peter , Siteyi Angela , Teerling Julia , Rinke de Wit Tobias , Asiki Gershim
Published: January 2025

Universal Health Coverage (UHC) aims to ensure all individuals have access to essential health services without financial hardship. Chronic diseases, like hypertension and diabetes, play a critical role in achieving UHC due to their lifelong management needs. This paper examines the implementation of a digital and mobile-based, patient-centered care model aimed at improving care for hypertensive and diabetic patients in Kenya. Between 2018 and 2019, 1626 patients from nine clinics in Nairobi, Kiambu, Nyeri and Vihiga counties were enrolled in an integrated non-communicable disease (NCD) care model including self-management devices for home monitoring, a digital health wallet (M-TIBA) for co-payment and facility-based peer support groups. Follow-up data was collected November–December 2020. Results indicated significantly improved patient outcomes, with 50% of hypertensive and 74% of diabetic patients achieving disease control, compared to 42% and 52% at baseline. Additionally, peer group participation increased adherence to self-monitoring and lifestyle modifications, contributing to better health outcomes. Despite these successes, challenges such as accessing medications and technical issues with digital tools were identified. Financial sustainability and scalability remain critical concerns, particularly in under-resourced settings. The case study highlights the potential of digital health solutions to enhance chronic care and support UHC by improving accessibility and reducing costs. A multifaceted approach, combining digital tools with face-to-face support and addressing structural barriers in healthcare systems, is essential for long-term success. The findings contribute to the broader discourse on integrated care models for NCDs in low-resource settings, underscoring the importance of sustainable financing and innovative care delivery mechanisms.
Digital interventions for alcohol use and alcohol use disorders in low- and-middle-income countries: a systematic review
Authors: Khatore Payal , Yolanda Hizkia , Joyner Jaeden , Nadkarni Abhijit
Published: January 2025

Background

Despite the high burden of alcohol use and alcohol use disorders (AUDs) in low-and-middle-income countries (LMICs), access to health care is poor. Digital interventions (DIs) have recently emerged as promising avenues for addressing substance use. Such interventions could potentially address barriers to help-seeking in LMICs, such as travel costs, shortage of professionals, stigma, etc.

Aim

To synthesize evidence on the effectiveness and implementation of DIs for AUDs in LMICs.

Methods

The systematic review had a comprehensive search strategy that combined search terms for DIs (e.g. SMS, eHealth), alcohol use (e.g. hazardous drinking) and LMICs (e.g. India). Studies presenting primary data that reported effectiveness (e.g. relapse) and/or implementation or intervention-related outcomes (e.g. feasibility) of DIs for AUDs in LMICs were eligible. Three databases (EMBASE, MEDLINE and PsycINFO) were searched from their inception till June 2023. Data was extracted in relevant categories and analysed.

Results

Twenty-one reports from 19 studies were included. Types of DIs ranged from standalone mobile applications and web portals to human-delivered interventions via digital platforms. 12 studies reported positive or partially positive alcohol use outcomes (e.g. number of drinking days, abstinence). DIs with human involvement were found to be more effective than standalone DIs. Additionally, high levels of acceptability, feasibility and satisfaction were reported across interventions.

Conclusion

DIs are acceptable and feasible in LMICs and broadly effective in improving alcohol use outcomes. Firm conclusions could not be drawn because of methodological issues such as small sample sizes, short follow-up periods and limited generalisability. Adequate investment, improved research methodology and increased focus on implementation outcomes are required for determining the role that DIs can play in addressing AUDs in LMICs.
Effectiveness of cognitive functional therapy for chronic spinal pain: a systematic review with meta-analysis
Authors: Marelli Michele , Cioeta Matteo , Pellicciari Leonardo , Rossi Fabio , Guida Stefania , Bargeri Silvia
Published: January 2025

Objective

To assess the effectiveness of cognitive functional therapy (CFT) in reducing disability and pain compared to other interventions in chronic spinal pain patients.

Methods

Five databases were queried to October 2023 for retrieving randomized controlled trials (RCTs), including patients with chronic spinal pain and administering CFT. Primary outcomes were disability and pain. Secondary outcomes included psychological factors, quality of life, patient satisfaction, and adverse events. Two independent reviewers performed study selection, data extraction, risk of bias assessment (Cochrane RoB 2.0), and evidence certainty (GRADE approach). Random-effect models were used for meta-analyses. Clinical relevance was assessed with the smallest worthwhile effect.

Results

Eight RCTs (N = 1228) for chronic low back pain (CLBP), one (N = 72) for chronic neck pain (CNP) were included. Compared to other conservative interventions, CFT may reduce disability (MD: −9.41; 95%CI: −12.56, −6.27) and pain (MD: −1.59; 95%CI: −2.33, −0.85 for CLBP) at short-term follow-up with probable to possible clinical relevance in CLBP and with low and very low evidence certainty, respectively. Similar results, with larger effect sizes, were observed for CFT compared to any unstructured or unsupervised minimal care treatments. Efficacy persisted in longer-term follow-ups, except for comparison with other conservative interventions. The CNP study showed positive results for CFT. Evidence certainty was low to very low. Sparse evidence was found for secondary outcomes.

Conclusion

CFT may offer clinically relevant benefits for CLBP, although the evidence remains mainly of low to very low certainty. Well-conducted studies, particularly in CNP and other spinal pain conditions are needed to strengthen these findings.

Registration

PROSPERO CRD42023482667.
Quantifying the portrayal of alcohol-related A&E attendances and prevention in the British medical documentary series ‘24 hours in A&E’
Authors: Webster Karielle , Knight Holly , Morling Joanne R
Published: January 2025

Background

Alcohol misuse is linked to numerous health and socioeconomic harms. Edutainment and docutainment television programmes can act as health promotion tools, influencing health perceptions and behaviours. Inaccurate portrayals can engender misinformation. Limited research has assessed alcohol-related illnesses and prevention in edutainment/docutainment, with none examining British medical documentaries.

Methods

A quantitative content analysis assessed the portrayal of alcohol-related attendances (ARAs), behaviours, and prevention in the series 24 hours in A&E. Main series episodes broadcast 2011–2022, depicting ARAs, were coded. Descriptive statistics and a Fisher’s exact were then undertaken.

Results

ARAs featured 38 patients in 23 episodes (8.3% episodes total). Significantly more ARA episodes were broadcast from 2011 to 2016 than 2017–2022 (P = 0.002). ARAs were mainly portrayed in males (63.2%), young adults (73.7%) and White ethnic groups (78.9%). Binge drinking and pubs/bar/nightclubs/‘nights out’ were the main behaviours and settings depicted. ARAs encompassed predominantly accidents/injuries (72.7%). Prevention featured infrequently (15.8% patients) and involved secondary (50.0%) or tertiary prevention (50.0%) for alcohol-use disorders (AUDs).

Conclusion

ARAs were under-portrayed. While prevention portrayals and demographics were largely consistent with reality, ethnic minority groups, AUDs and chronic alcohol-related illnesses were underrepresented. Binge drinking and night-time economy settings were over-portrayed. Inaccurate depictions could lead to misperceptions of alcohol-related health harms.
A review of falls and injuries of nursing home residents presenting to the emergency department
Authors: O’Connor Aoife , Noonan Claire , Fallon Aoife , Kennelly Sean
Published: January 2025

Background

Falls are frequently reported within the HSE. The Irish Longitudinal Study on Ageing (TILDA) found that 40% of over 50 s experience a fall in a two-year period, with 20% requiring hospital attendance. It has been estimated that the cost of injuries related to falls in older people will increase exponentially over the coming years. There is no national database in Ireland with statistics for nursing home (NH) residents presenting with falls to our Emergency Departments (EDs).

Aim

To review the prevalence and risk factors for nursing home patients presenting to the ED with falls.

Design

Retrospective chart review.

Method

Retrospective review of all NH presentations to the ED of a university hospital over one year.

Results

There were 519 ED presentations by NH residents over one year. 48.17% (n = 250) presented with a fall. One-third of ED visits presented during conventional working hours. Falls patients were more likely to be admitted when not reviewed by a GP prior to presentation. The average length of stay for falls admissions was 10.77 days (n = 132), versus 9.56 (n = 153) for admissions with no documented fall. There was no statistical difference in the falls risk medications between the groups. Patients presenting with falls were more likely to have bone protection reviewed during their stay (P = 0.011). Patients with falls were also more likely to use mobility aids (P < 0.001).

Conclusion

Rapid referral to falls prevention programmes and the use of standardized care pathways for high falls risk patients are essential for future prevention and management.
A complete framework for cosmological emulation and inference with CosmoPower
Authors: Jense H T , Harrison I , Calabrese E , Spurio Mancini A , Bolliet B , Dunkley J , Hill J C
Published: January 2025

We present a coherent, re-usable python framework building on the CosmoPower emulator code for high-accuracy calculations of cosmological observables with Einstein–Boltzmann codes. For detailed statistical analyses, such codes require high computing power, making parameter space exploration costly, especially for beyond-$\Lambda$CDM analyses. Machine learning-enabled emulators of Einstein–Boltzmann codes are becoming an increasingly popular solution to this problem. To enable generation, sharing, and use of emulators for inference, we define standards for robustly describing, packaging, and distributing them. We present software for easily performing these tasks in an automated and replicable manner and provide examples and guidelines for generating emulators and wrappers for using them in popular cosmological inference codes. We demonstrate our framework with a suite of high-accuracy emulators for the CAMB code’s calculations of CMB $C_\ell$, $P(k)$, background evolution, and derived parameter quantities. We show these emulators are accurate enough for analysing both $\Lambda$CDM and a set of extension models ($N_{\rm eff}$, $\sum m_\nu$, $w_0 w_a$) with stage-IV observatories, recovering the original high-accuracy spectra to tolerances well within the cosmic variance uncertainties. We show our emulators also recover cosmological parameters in a simulated cosmic-variance limited experiment, finding results well within $0.1 \sigma$ of the input cosmology, while requiring $\lesssim 1/50$ of the evaluation time.
Bank regulation, investment, and capital requirements under adverse selection
Authors: Rivera Thomas J
Published: January 2025

This article studies the optimal design of bank capital regulations when capital markets are subject to adverse selection. I show how the implementation of capital requirements can eliminate the information frictions that make raising capital costly by screening banks to reveal their private information to the market. The optimal regulations induce information revelation via recapitalization programs when the banking sector is weak and pool the banks’ private information via uniform capital requirements otherwise. Optimal capital requirements are linked to the securities issued to meet them, demonstrating potential welfare gains from incorporating more and less informationally sensitive securities into the design of capital regulations. Finally, the analysis generates insights into the joint design of equity capital requirements and additional tier 1 capital securities.
A processual framework for understanding the rise of the populist right: the case of Brazil (2013–2018)
Authors: Bradlow Benjamin H , Gold Tomás
Published: January 2025

How and in what sequence do social structures, contingent events, and agents’ decisions combine over time to bring about a new populist right? To answer this question, we propose a framework to analyze social processes spanning three levels of analysis: global political economy, national political articulation, and subnational political geography. We challenge static theories that focus solely on the “supply and demand” for populism, as well as purely contingent accounts of a “perfect storm.” Instead, we argue that processes across these three levels link together in causal chains to produce an “ecosystem” of right-wing populist support. To specify this framework, we analyze the ascendance of Jair Bolsonaro to the presidency of Brazil between 2013 and 2018, drawing upon quantitative macroeconomic and protest event data, qualitative interview and archival data collected from private sector actors and social movements, and geo-spatial electoral data. Finally, we probe the generalizability of this analytical framework through a discussion of secondary work on recent cases of right-wing populism in the Global South. By focusing on the dynamic connection of inter-scalar processes over time, we illustrate how our framework paves the way for further conjunctural analyses of the current right-wing populist upsurge.
Influence of macrophages and neutrophilic granulocyte-like cells on crystalline silica-induced toxicity in human lung epithelial cells
Authors: Gaté Laurent , Sébillaud Sylvie , Lorcin Mylène , Seidel Carole , Darne Christian
Published: January 2025

In many industrial activities, workers may be exposed by inhalation to particles that are aerosolized, To predict the human health hazard of these materials, we propose to develop a co-culture model (macrophages, granulocytes, and alveolar epithelial cells) designed to be more representative of the inflammatory pulmonary response occurring in vivo. Phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 cells were used as macrophages, All-trans retinoic acid (ATRA)-differentiated HL60 were used as granulocytes and A549 were used as epithelial alveolar type II cells. A crystalline silica sample DQ12 was used as a prototypical particle for its capabilities to induce DNA damage, inflammatory response, and oxidative stress in epithelial cells; its polyvinylpyridine-N-oxide (PVNO)-surface modified counterpart was also used as a negative particulate control. Cells in mono-, bi- or tri-culture were exposed to DQ12 or DQ12-PVNO for 24 h. DQ12 but not DQ12-PVNO induced a significant increase in DNA damage in A549 cells. The presence of differentiated THP-1 reduced the genotoxic effects of this crystalline silica sample. The exposure of A549 to DQ12 but not DQ12-PVNO induced a significant change in interleukin-8 (IL-8) protein levels which was exacerbated when differentiated THP-1, and HL-60, were added. In addition, while no production of TNFα was detected in the A549 monoculture, elevated levels of this cytokine were observed in the co-culture systems. This work shows that a cell culture model that takes into consideration the complexity of the pulmonary inflammatory response might be more dependable to study the toxicological properties of particles than “simple” monoculture models.