bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fusion imaging for guidance of pulmonary arteriovenous malformation embolisation with minimal radiation and contrast exposure
Authors: Vargas-Acevedo Catalina , Mejia Ernesto , Zablah Jenny E. , Morgan Gareth J. 
Published: March 2024

AbstractHereditary haemorrhagic telangiectasia is an inherited disorder characterised by vascular dysplasia that leads to the development of arteriovenous malformations. Pulmonary arteriovenous malformations occur in approximately 30% of patients with haemorrhagic telangiectasia. Given the complex characteristics of haemorrhagic telangiectasia lesions, the application of three-dimensional fusion imaging holds significant promise for procedural guidance and decrease in contrast and radiation dosing. We reviewed all patients who underwent transcatheter approach for pulmonary arteriovenous malformation occlusion with fusion image guidance from June 2018 to September 2023 from a single centre. A total of nine cases with haemorrhagic telangiectasia and transcatheter occlusion of pulmonary arteriovenous malformations using fusion imaging were identified. Five (56%) were male, mean age at procedure was 15.7 years (10–28 years) and mean number of pulmonary arteriovenous malformations intervened was three per patient (1–7). Two of the cases were complex repeat embolisations. The mean fluoroscopy time was 40.6 min (10.7–68.8 min), with mean contrast dose of 28.8 mL (11–60 mL; mean of 0.51 mL/kg) and mean radiation dose of 66.3 mGy (25.6–140 mGy; mean of 40.5 mGy/m2). There were no complications reported during the procedures, with no additional interventions necessary. Fusion imaging in pulmonary arteriovenous malformations embolisation for patients with haemorrhagic telangiectasia is feasible and has the potential to reduce contrast and radiation doses. To our knowledge, we describe the lowest radiation and contrast doses per patient using fusion imaging technology reported in the literature to date.
Extended surface brightness modeling of three sources strongly lensed by an ultra-massive elliptical galaxy
Authors: Bolamperti Andrea 
Published: March 2024

AbstractRare systems with multiple sources strongly lensed by a single galaxy provide the most robust way to explore the geometry of the Universe and to study the inner mass structure of lens galaxies. We present here a study of the SDSS J0100+1818 deflector, analyzing its total and baryonic mass distributions. The system comprises an ultra-massive early-type galaxy, surrounded by ten multiple images of three background sources. Exploiting high-resolution HST photometry and VLT/X-shooter spectroscopy we conduct a strong lensing analysis with the software GLEE to reconstruct the complex surface brightness distributions of the background sources over approximately 7200 HST pixels. These results are presented in our recent paper, Bolamperti et al. (2023). Finally, we present some preliminary results from new VLT/MUSE observations, that will allow us to build a new strong lensing+dynamics joint model and measure the values of the total matter density and of the cosmological constant parameters, Ωm and ΩΛ.
Lens Discovery in the Era of Wide-area Surveys
Authors: Holloway Philip , Marshall Philip J , Verma Aprajita 
Published: March 2024

AbstractForthcoming data from the Vera Rubin Observatory, Euclid and Roman telescopes are expected to increase the number of strong lenses by two orders of magnitude. With current discovery methods these would be accompanied by an even greater number of false positives. In that context we find that using an ensemble of classifiers would provide a more complete sample of high-purity lenses and present methods to post-process the outputs of such classifiers to give reliable probabilities that a given image contains a lens.
Lensed radio arcs at milli-arcsecond resolution: Methods, science results, and current status
Authors: Powell Devon M. 
Published: March 2024

AbstractStrong gravitational lensing by galaxies provides us with a powerful laboratory for testing dark matter models. Various particle models for dark matter give rise to different small-scale distributions of mass in the lens galaxy, which can be differentiated with sensitive observations. Th. The sensitivity of a gravitational lens observation to the presence (or absence) of low-mass dark structures in the lens galaxy is determined mainly by the angular resolution of the instrument and the spatial structure of the source. Here, I discuss results from the analysis of a global VLBI observation of a gravitationally lensed radio jet. With an angular resolution better than 5 milli-arcseconds and a highly extended, spatially resolved source, we are able to place competitive constraints on the particle mass in fuzzy dark matter models using this single observation. I also discuss preliminary results from our analysis of warm dark matter models using this lens system.
Angular structure and gravitational imaging
Authors: O’Riordan Conor M. 
Published: March 2024

AbstractIn gravitational imaging, the mass model for the main lensing galaxy is one of the main sources of systematic uncertainty. We use subhalo detection models with increasing levels of angular complexity in the lens mass model to analyse 100 HST mock observations. We find that perturbations of just 1% are enough to cause a 20% false positive subhalo detection rate, with order 3 multipoles having the strongest effect. The area in an observation where a substructure can be detected drops by a factor of 10 if multipoles up to 3 per cent amplitude are included in the lens model. The mass of the smallest detectable substructure however is not affected. We find a detection limit of M>108.2M⊙ at 5σ in all models. In order for strong lensing searches for dark matter objects to remain reliable in the future, angular structure beyond the elliptical power-law must be included.
Time Delay Cosmograpy of SDSSJ1433 with the 2.1m Wendelstein Telescope
Authors: Queirolo G. 
Published: March 2024

AbstractTime delay cosmography is based on the study of multiply gravitationally lensed images of a variable source. Their time delay differences are linearly dependent on the Fermat potential differences at the images’ positions and the Hubble parameter, whose exact value is to this date strongly debated in the framework of the Hubble tension. In this paper we present the study of SDSSJ1433, a quadruply lensed QSO, the time delays of which have been obtained after a 3-year observational campaign from the 2.1m Wendelstein telescope in the optical ǵ filter, and the corresponding mass model was constrained from multi-band archival HST observations. The resulting H0 value is $$77.4\frac{{km}}{{s\,Mpc}}$$ with a precision of∼ 6 %.
Frequency reconfigurable circular microstrip G-slotted antenna with DGS for various wireless applications
Authors: Mamta  , Nath Vandana 
Published: March 2024

AbstractA novel reconfigurable circular microstrip G-slotted antenna having a circularly defected ground structure (DGS) capable of switching its resonance frequency for several microwave applications is presented in this paper. Reconfigurability of the proposed G-slot antenna is obtained by incorporating three PIN diodes. One diode is embedded in the patch and two diodes are integrated into the DGS structure at appropriate places in the slot to achieve four different wireless applications such as aeronautical radio navigation (4.3 GHz with gain 3.6 dB), satellite communication (3.78 GHz with gain 3.7 dB), mobile communication (4.55 GHz with gain 4.0 dB), and WiMAX (3.35 GHz with gain 3.3 dB). These four bands are achieved depending on the different biasing conditions of the three PIN switches used. Antenna performance has been analyzed in ANSYS Electronics Desktop 2018.2 software. The equivalent circuit component of the switching element (PIN diode) has been considered and designed during the simulation. The creative structure lies in the way that it exhibits higher gain with compact size than the previously reported similar antenna. A prototype of the proposed patch antenna has been fabricated on a Roger substrate and its testing and measurement have been performed to demonstrate its desirable characteristics and features.
I think learning ancient Greek via video game is…’: An online survey to understand perceptions of Digital Game-Based Learning for ancient Greek
Authors: Di Gioia Irene 
Published: March 2024

AbstractPlaying is connected at a deep level to how we learn, participate in and create culture, as it is dynamic, complex and even unpredictable just as learning is (Reinhardt, 2019). Even Plato in his Theaetetus recognises the importance of such a component in experiencing culture and knowledge. Could playing (or gaming) therefore be a useful didactical approach in promoting the study of ancient Greek around the world? From 10th May 2023 at 1 pm. until 1st June 2023 at 1 pm., an internet survey was conducted online by the researcher Irene Di Gioia through the use of Google Forms questionnaires. This questionnaire was distributed via different social networks and communication tools. The survey aimed to understand if people around the world are interested in the idea of learning ancient Greek via a video game and if so, which video gaming activities learners prefer. The goal of the survey was therefore to understand if a ludic pedagogical approach using Digital Game-Based Learning could theoretically represent an interest experience for learners or potential learners, and furthermore to investigate their feelings, prejudices, and motivations regarding the study of ancient Greek. From the analysed data the researcher will therefore develop a video game to teach ancient Greek language and culture, which comprises the focus of her ongoing PhD dissertation at Georg-August University of Göttingen (Germany) and Alma Mater Studiorum University of Bologna (Italy).
Frictional Strength, Stability, and Potential Shear Heating on Icy Satellite Faults
Authors: Zaman Maheenuz , McCarthy Christine , Skarbek Rob M. , Savage Heather M. 
Published: March 2024

AbstractWe determined the frictional strength and stability of polycrystalline ice and ice‐ammonia to constrain fault behavior on icy satellites such as Enceladus and Europa. Friction experiments including velocity steps and slide‐hold‐slide tests were conducted to measure the steady‐state coefficient of friction, velocity dependence and healing between temperatures of 98 and 248 K at a normal stress of 100 kPa. Rate‐state friction parameters determined from velocity steps provide stability values. The friction results are used to infer fault strength and frictional heating of an icy crust with depth for both a pure ice crust and one containing ammonia. We find a reduced coefficient of friction for an ammonia‐bearing crust and stronger velocity dependence in the presence of partial melt. The temperature dependence of fault stability maps a seismogenic zone with depth analogous to the synoptic model for terrestrial fault stability, where we find instability between 0.7 and 3.9 km with a return to stability from 4.6 km if we assume a 6 km ice shell. We consider the role of sliding velocity and fault thickness on localized frictional heating in both systems and estimate the depth of melt generation in an ammonia‐bearing crust. Our results imply that faults at conditions similar to icy satellites can be seismogenic.
Earth System Model Analysis of How Astronomical Forcing Is Imprinted Onto the Marine Geological Record: The Role of the Inorganic (Carbonate) Carbon Cycle and Feedbacks
Authors: Vervoort P. , Kirtland Turner S. , Rochholz F. , Ridgwell A. 
Published: March 2024

AbstractAstronomical cycles are strongly expressed in marine geological records, providing important insights into Earth system dynamics and an invaluable means of constructing age models. However, how various astronomical periods are filtered by the Earth system and the mechanisms by which carbon reservoirs and climate components respond, particularly in absence of dynamic ice sheets, is unclear. Using an Earth system model that includes feedbacks between climate, ocean circulation, and inorganic (carbonate) carbon cycling relevant to geological timescales, we systematically explore the impact of astronomically‐modulated insolation forcing and its expression in model variables most comparable to key paleoceanographic proxies (temperature, the δ13C of inorganic carbon, and sedimentary carbonate content). Temperature predominately responds to obliquity and is little influenced by the modeled carbon cycle feedbacks. In contrast, the cycling of nutrients and carbon in the ocean generates significant precession power in atmospheric CO2, benthic ocean δ13C, and sedimentary wt% CaCO3, while inclusion of marine sedimentary and weathering processes shifts power to the long eccentricity period. Our simulations produce reduced pCO2 and dissolved inorganic carbon δ13C at long eccentricity maxima and, contrary to early Cenozoic marine records, CaCO3 preservation in the model is enhanced during eccentricity modulated warmth. Additionally, the magnitude of δ13C variability simulated in our model underestimates marine proxy records. These model‐data discrepancies hint at the possibility that the Paleogene silicate weathering feedback was weaker than modeled here and that additional organic carbon cycle feedbacks are necessary to explain the full response of the Earth system to astronomical forcing.
A Multi‐Model Ensemble of Baseline and Process‐Based Models Improves the Predictive Skill of Near‐Term Lake Forecasts
Authors: Olsson Freya , Moore Tadhg N. , Carey Cayelan C. , Breef‐Pilz Adrienne , Thomas R. Quinn 
Published: March 2024

AbstractWater temperature forecasting in lakes and reservoirs is a valuable tool to manage crucial freshwater resources in a changing and more variable climate, but previous efforts have yet to identify an optimal modeling approach. Here, we demonstrate the first multi‐model ensemble (MME) reservoir water temperature forecast, a forecasting method that combines individual model strengths in a single forecasting framework. We developed two MMEs: a three‐model process‐based MME and a five‐model MME that includes process‐based and empirical models to forecast water temperature profiles at a temperate drinking water reservoir. We found that the five‐model MME improved forecast performance by 8%–30% relative to individual models and the process‐based MME, as quantified using an aggregated probabilistic skill score. This increase in performance was due to large improvements in forecast bias in the five‐model MME, despite increases in forecast uncertainty. High correlation among the process‐based models resulted in little improvement in forecast performance in the process‐based MME relative to the individual process‐based models. The utility of MMEs is highlighted by two results: (a) no individual model performed best at every depth and horizon (days in the future), and (b) MMEs avoided poor performances by rarely producing the worst forecast for any single forecasted period (<6% of the worst ranked forecasts over time). This work presents an example of how existing models can be combined to improve water temperature forecasting in lakes and reservoirs and discusses the value of utilizing MMEs, rather than individual models, in operational forecasts.
BCL-XL inhibitors enhance the apoptotic efficacy of BRAF inhibitors in BRAFV600E colorectal cancer
Authors: Jenkins Laura J. , Luk Ian Y. , Chionh Fiona , Tan Tao , Needham Kristen , Ayton Jamieson , Reehorst Camilla M. , Vukelic Natalia , Sieber Oliver M. , Mouradov Dmitri , Gibbs Peter , Williams David S. , Tebbutt Niall C. , Desai Jayesh , Hollande Frédéric , Dhillon Amardeep S. , Lee Erinna F. , Merino Delphine , Fairlie W. Douglas , Mariadason John M. 
Published: March 2024

AbstractMetastatic BRAFV600E colorectal cancer (CRC) carries an extremely poor prognosis and is in urgent need of effective new treatments. While the BRAFV600E inhibitor encorafenib in combination with the EGFR inhibitor cetuximab (Enc+Cet) was recently approved for this indication, overall survival is only increased by 3.6 months and objective responses are observed in only 20% of patients. We have found that a limitation of Enc+Cet treatment is the failure to efficiently induce apoptosis in BRAFV600E CRCs, despite inducing expression of the pro-apoptotic protein BIM and repressing expression of the pro-survival protein MCL-1. Here, we show that BRAFV600E CRCs express high basal levels of the pro-survival proteins MCL-1 and BCL-XL, and that combining encorafenib with a BCL-XL inhibitor significantly enhances apoptosis in BRAFV600E CRC cell lines. This effect was partially dependent on the induction of BIM, as BIM deletion markedly attenuated BRAF plus BCL-XL inhibitor-induced apoptosis. As thrombocytopenia is an established on-target toxicity of BCL-XL inhibition, we also examined the effect of combining encorafenib with the BCL-XL -targeting PROTAC DT2216, and the novel BCL-2/BCL-XL inhibitor dendrimer conjugate AZD0466. Combining encorafenib with DT2216 significantly increased apoptosis induction in vitro, while combining encorafenib with AZD0466 was well tolerated in mice and further reduced growth of BRAFV600E CRC xenografts compared to either agent alone. Collectively, these findings demonstrate that combined BRAF and BCL-XL inhibition significantly enhances apoptosis in pre-clinical models of BRAFV600E CRC and is a combination regimen worthy of clinical investigation to improve outcomes for these patients.
Gasdermin E promotes translocation of p65 and c-jun into nucleus in keratinocytes for progression of psoriatic skin inflammation
Authors: Long Fangyuan , Wei Xuecui , Chen Yujie , Li Min , Lian Ni , Yu Shanshan , Chen Sihan , Yang Yong , Li Min , Gu Heng , Chen Xu 
Published: March 2024

AbstractGasdermin E (GSDME) has recently been identified as a critical executioner to mediate pyroptosis. While epidermal keratinocytes can initiate GSDME-mediated pyroptosis, the role of keratinocyte GSDME in psoriatic dermatitis remains poorly characterized. Through analysis of GEO datasets, we found elevated GSDME levels in psoriatic lesional skin. Additionally, GSDME levels correlated with both psoriasis severity and response to biologics treatments. Single-cell RNA sequencing (scRNA-seq) from a GEO dataset revealed GSDME upregulation in keratinocytes of psoriasis patients. In the imiquimod (IMQ)-induced psoriasis-like dermatitis mouse model, both full-length and cleaved forms of caspase-3 and GSDME were elevated in the epidermis. Abnormal proliferation and differentiation of keratinocytes and dermatitis were attenuated in Gsdme-/- mice and keratinocyte-specific Gsdme conditional knockout mice after IMQ stimulation. Exposure of keratinocytes to mixed cytokines (M5), mimicking psoriatic conditions, led to GSDME cleavage. Moreover, the interaction between GSDME-FL and p65 or c-jun was significantly increased after M5 stimulation. GSDME knockdown inhibited nuclear translocation of p65 and c-jun and decreased upregulation of psoriatic inflammatory mediators such as IL1β, CCL20, CXCL1, CXCL8, S100A8, and S100A9 in M5-challenged keratinocytes. In conclusion, GSDME in keratinocytes contributes to the pathogenesis and progression of psoriasis, potentially in a pyroptosis-independent manner by interacting and promoting translocation of p65 and c-jun. These findings suggest that keratinocyte GSDME could serve as a potential therapeutic target for psoriasis treatment.
Heterozygous THBS2 pathogenic variant causes Ehlers–Danlos syndrome with prominent vascular features in humans and mice
Authors: Hadar Noam , Porgador Omri , Cohen Idan , Levi Hilla , Dolgin Vadim , Yogev Yuval , Sued-Hendrickson Sufa , Shelef Ilan , Didkovsky Elena , Eskin-Schwartz Marina , Birk Ohad S. 
Published: March 2024

AbstractEhlers–Danlos syndromes (EDS) are a group of connective tissue disorders caused by mutations in collagen and collagen-interacting genes. We delineate a novel form of EDS with vascular features through clinical and histopathological phenotyping and genetic studies of a three-generation pedigree, displaying an apparently autosomal dominant phenotype of joint hypermobility and frequent joint dislocations, atrophic scarring, prolonged bleeding time and age-related aortic dilatation and rupture. Coagulation tests as well as platelet counts and function were normal. Reticular dermis displayed highly disorganized collagen fibers and transmission electron microscopy (TEM) revealed abnormally shaped fibroblasts and endothelial cells, with high amount and irregular shape of extracellular matrix (ECM) substance, especially near blood vessels. Genetic analysis unraveled a heterozygous mutation in THBS2 (NM_003247.5:c.2686T>C, p.Cys896Arg). We generated CRISPR/Cas9 knock-in (KI) mice, bearing the heterozygous human mutation in the mouse ortholog. The KI mice demonstrated phenotypic traits correlating with those observed in the human subjects, as evidenced by morphologic, histologic, and TEM analyses, in conjunction with bleeding time assays. Our findings delineate a novel form of human EDS with classical-like elements combined with vascular features, caused by a heterozygous THBS2 missense mutation. We further demonstrate a similar phenotype in heterozygous THBS2Cys896Arg KI mice, in line with previous studies in Thbs2 homozygous null-mutant mice. Notably, THBS2 encodes Thrombospondin-2, a secreted homotrimeric matricellular protein that directly binds the ECM-shaping Matrix Metalloproteinase 2 (MMP2), mediating its clearance. THBS2 loss-of-function attenuates MMP2 clearance, enhancing MMP2-mediated proteoglycan cleavage, causing ECM abnormalities similar to those seen in the human and mouse disease we describe.
A phase I/IIa safety and efficacy trial of intratympanic gamma-secretase inhibitor as a regenerative drug treatment for sensorineural hearing loss
Authors: Schilder Anne G. M. , Wolpert Stephan , Saeed Shakeel , Middelink Leonie M. , Edge Albert S. B. , Blackshaw Helen ,   REGAIN Consortium, Schilder Anne , Middelink Leonie , Edge Albert , Bibas Athanasios , Arram Elizabeth , Bilhet Asger , Cooper Hannah , Dalhoff Ernst , van Diggelen Femke , Rutten Rolf Jan , van Es Helmuth , Hojgaard Karin , Iliadou Eleftheria , Yildirim Omursen , Khalil Sherif , Kikidis Dimitris , Lowenheim Hubert , Markatos Nikos , Mueller Marcus , Schade-Mann Thore , Schneider Fritz , Vardonikolaki Katerina , Wilke August , Pastiadis Kostas , Bibas Athanasios G. 
Published: March 2024

AbstractInhibition of Notch signalling with a gamma-secretase inhibitor (GSI) induces mammalian hair cell regeneration and partial hearing restoration. In this proof-of-concept Phase I/IIa multiple-ascending dose open-label trial (ISRCTN59733689), adults with mild-moderate sensorineural hearing loss received 3 intratympanic injections of GSI LY3056480, in 1 ear over 2 weeks. Phase I primary outcome was safety and tolerability. Phase lla primary outcome was change from baseline to 12 weeks in average pure-tone air conduction threshold across 2,4,8 kHz. Secondary outcomes included this outcome at 6 weeks and change from baseline to 6 and 12 weeks in pure-tone thresholds at individual frequencies, speech reception thresholds (SRTs), Distortion Product Otoacoustic Emissions (DPOAE) amplitudes, Signal to Noise Ratios (SNRs) and distribution of categories normal, present-abnormal, absent and Hearing Handicap Inventory for Adults/Elderly (HHIA/E). In Phase I (N = 15, 1 site) there were no severe nor serious adverse events. In Phase IIa (N = 44, 3 sites) the average pure-tone threshold across 2,4,8 kHz did not change from baseline to 6 and 12 weeks (estimated change −0.87 dB; 95% CI −2.37 to 0.63; P = 0.252 and −0.46 dB; 95% CI −1.94 to 1.03; P = 0.545, respectively), nor did the means of secondary measures. DPOAE amplitudes, SNRs and distribution of categories did not change from baseline to 6 and 12 weeks, nor did SRTs and HHIA/E scores. Intratympanic delivery of LY3056480 is safe and well-tolerated; the trial’s primary endpoint was not met.