bluuebunny/crossref_metadata_2025 huggingface dataset:
Predicting Viscosity of Multi-Walled Carbon Nanotube/Water Nanofluids Using Gaussian Process Regression and Emperor Penguin Optimizer Algorithm
Authors: Shekhar Shekhar , Sambyo Koj
Published: February 2025

Thermal management is essential in many industries like energy, transportation, and HVAC systems. Since thermal management is so important, there is a need for improved heat transfer fluids, such as nanofluids. The current study uses machine learning (ML) approaches to predict the viscosity of multi-walled carbon nanotube (MWCNT)-water nanofluids. The dataset comprised 446 experimental data points with characteristics such as weight concentration, temperature, shear time, shear stress, and viscosity were used in current research. The dataset was evaluated with a Gaussian Process Regression (GPR) model and the hyperparameters were further optimized via Emperor Penguin Optimizer (EPO).With the achieved values of R2 of 0.9995, RMSE of 0.0016, and MAPE of 1.89%, the proposed model GPR-EPO, yielded better predictive performance than other machine learning models such as Gradient Boosting Regressor, XGBoost, and Extra Trees Regressor. Additionally, for validation the GPR-EPO model was compared with conventional model like Batchelor and Einstein, it was found more precise and yielded better predictive performance. This study highlights the significant role of AI-driven technique in predicting nanofluid viscosity with accuracy as well as reducing the experimental efforts. The GPR method was found to have the best performance by using radial basis function (RBF) kernel and optimized the hyperparameters with EPO algorithm. Such models can serve as a valuable tool for engineers and researchers to investigate nanofluids and develop efficient thermal management systems.
Margaret Cavendish on Matter and Metaphysical Structure
Authors: Peterman Alison
Published: February 2025

This essay provides an interpretation of Margaret Cavendish’s claim that everything that exists in nature is matter. Cavendish’s materialism is not, as it is usually interpreted, the thesis that most often goes under the label ‘materialism’: that there are only certain kinds of substances, where those kinds are best understood in terms of the properties they have. The essay argues that Cavendish’s materialism involves a rejection of traditional substance–property ontology and similar ontologies, which are structured by dependence and inherence relations. It is instead an affirmation of a non-hierarchical ontology of matter, which is structured by parthood and composition relations.
Hume’s Gambit
Authors: Watts Gabriel
Published: February 2025

This essay develops an irreligious reading of Hume’s decision to return to philosophy after his skeptical crisis at the end of Book One of A Treatise of Human Nature. Any irreligious reading of Hume’s epistemology must articulate Hume’s epistemic grounds for preferring his experimental science of human nature to sophisticated superstitious anthropologies. The essay argues that Hume believes his use of animal analogies to confirm his hypotheses offers him the best possible ‘security’ against positing false causal claims about the nature of our ‘mental operations’, and that the superior security of this experimental method of reasoning provides him with epistemic grounds for preferring his science of human nature to superstitious metaphysics, even though both have title to our assent. The essay concludes by suggesting that in continuing to philosophize after his skeptical crisis, Hume risks his intellectual reputation on a bet that ‘the latest posterity’ will find his science of human nature a surer path to useful truths than superstition, because his experimental philosophy of human nature is the most epistemically secure form of anthropology there is. This irreligious gambit is the origin of Hume’s philosophy.
Mary Shepherd on Space and Minds
Authors: Fasko Manuel , West Peter
Published: February 2025

In her last known work, ‘Lady Mary Shepherd’s Metaphysics’ (1832), Mary Shepherd writes that ‘mind, may inhere in definite portions of matter . . . or of infinite space’. Shepherd thus suggests that a mind—a ‘capacity for sensation in general’—may have a spatial location. This is prima facie surprising given that she is committed to the view that the mind is unextended. This essay argues that Shepherd can consistently honor both of these commitments. First, even though finite minds due to their unextendedness cannot occupy space as material bodies do, such minds can nonetheless be said to have a spatial location in virtue of their ‘presence’, or what Shepherd calls ‘inherence’, in a material body. Second, in a similar way, the divine mind is present throughout the whole of space and is thus omnipresent. In contrast to finite minds, the divine mind does not require a body to be present in space. Rather, God’s omnipresence is best understood in a ‘holenmerist’ sense, where the divine mind is wholly present in every part of creation.
(A little) quantified modal logic for normativists
Authors: Povich Mark
Published: February 2025

Burgess (‘Quinus ab omni nævo vindicatus’), building on Quine (‘Reference and modality’), convincingly argued that claims in quantified modal logic cannot be understood as synonymous with or logically equivalent to claims about the analyticity of certain sentences. According to modal normativism, metaphysically necessary claims instead express or convey our actual semantic rules. In this paper, I show how the normativist can use Sidelle’s neglected work on rigidity to account for two important phenomena in quantified modal logic: the necessity of identity and the substitutivity of identicals into modal contexts.
Frege pipes up
Authors: Felappi Giulia
Published: February 2025

Martone has recently built a case aimed at showing that any attempt to exploit the ingredients of the semantic machinery of demonstratives to solve Frege’s Puzzle seems hopeless. In this reply, I show that Martone’s case seems unable to shatter our hopes.
A large language model framework for literature-based disease–gene association prediction
Authors: Li Peng-Hsuan , Sun Yih-Yun , Juan Hsueh-Fen , Chen Chien-Yu , Tsai Huai-Kuang , Huang Jia-Hsin
Published: February 2025

With the exponential growth of biomedical literature, leveraging Large Language Models (LLMs) for automated medical knowledge understanding has become increasingly critical for advancing precision medicine. However, current approaches face significant challenges in reliability, verifiability, and scalability when extracting complex biological relationships from scientific literature using LLMs. To overcome the obstacles of LLM development in biomedical literature understating, we propose LORE, a novel unsupervised two-stage reading methodology with LLM that models literature as a knowledge graph of verifiable factual statements and, in turn, as semantic embeddings in Euclidean space. LORE captured essential gene pathogenicity information when applied to PubMed abstracts for large-scale understanding of disease–gene relationships. We demonstrated that modeling a latent pathogenic flow in the semantic embedding with supervision from the ClinVar database led to a 90% mean average precision in identifying relevant genes across 2097 diseases. This work provides a scalable and reproducible approach for leveraging LLMs in biomedical literature analysis, offering new opportunities for researchers to identify therapeutic targets efficiently.
Harnessing the full potential of drones for fieldwork
Authors: Surasinghe Thilina D , Singh Kunwar K , Frazier Amy E
Published: February 2025

Field-based research in the biological sciences encounters several challenges, including cost, accessibility, safety, and spatial coverage. Drones have emerged as a transformative technology to address these challenges while providing a less intrusive alternative to field surveys. Although drones have mainly been used for high-resolution image collection, their capabilities extend beyond mapping and image production. They can be tailored to track wildlife, measure environmental parameters, and collect physical samples, and their versatility enables researchers to tackle a variety of biodiversity and conservation challenges. In this article, we advocate for drones to be integrated more comprehensively into field-based research, from site reconnaissance to sampling, interventions, and monitoring. We discuss the future innovations needed to harness their full potential, including customized instrumentation, fit-for-purpose software and apps, and better integration with existing online databases. We also support leveraging community scientists and empowering citizens to contribute to scientific endeavors while promoting environmental stewardship via drones.
Impact of morbilliform drug eruptions on health-related quality of life: a qualitative analysis
Authors: Yan Allison , Gallardo Matthew , Veliky Cole , McFeeters Jacob , Nusbaum Kelsey , Johnson Kirsten , Fisher Kristopher , Korman Abraham , Kaffenberger Benjamin
Published: February 2025

Quality of life has not been well-explored in patients hospitalized with morbilliform drug eruptions. We found that morbilliform drug eruptions impacted patients across six major domains: impact on other medical conditions, self-image, medical distrust, impact on diet, mental health, and physical symptoms. Dermatologists and other healthcare providers should remain cognizant of the impacted domains in the counseling and management of this patient population.
Environmental triggers of psoriasis: insights from a UK patient-reported cohort (mySkin)
Authors: Kroah-Hartman Madeline , Lee John Y W , Dooley Niamh , Tan Wei Ren , Mineur Maaike F M , Paolino Alexandra , Pizzato Jade , Jackson-Duffy Freya , Powell Kingsley , Sagoo Manpreet K , Sewell Georgia , Lancelot Camille , Moorhead Lucy , McAteer Helen , Coker Bolaji , Weinman John , Barker Jonathan N , Chapman Sarah , Norton Sam , Smith Catherine H , Mahil Satveer K
Published: February 2025

We developed mySkin, an online platform that captures self-report information from people with psoriasis across the UK, to improve our knowledge on the environmental determinants of psoriasis. In this cross-sectional analysis of the first 529 participants, stress was the most commonly reported trigger for both the onset and worsening of disease. Within individuals, triggers for psoriasis onset also often triggered disease worsening. We did not observe a clear association between different triggers to psoriasis onset and subsequent disease severity. These findings highlight the value of patient self-report data to deliver valuable insights into the role of environmental triggers and may inform early intervention strategies to mitigate against triggers of disease progression.
The role of microglia in the prion-like transmission of protein aggregates in neurodegeneration
Authors: Öztürk Muhammet M , Emgård Jakob , García-Revilla Juan , Fernández-Calle Rosalía , Yang Yiyi , Deierborg Tomas , Roos Tomas T
Published: February 2025

Numerous neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and ALS (amyotrophic lateral sclerosis) share a neuropathological hallmark: aberrant protein aggregation in the CNS (central nervous system). Microglia, the brain’s innate immune cells, also play a pivotal role in the pathogenesis of these disorders. Multiple studies indicate that these pathological aggregates can propagate throughout the brain in a prion-like manner. A protein/peptide that adopts a prion-like conformation can induce homologous proteins to misfold into a prion-like conformation through templated seeding, enabling cell-to-cell spread and accelerating protein aggregation throughout the brain. Two important questions in the prion-like paradigm are where the prion-like misfolding occurs and how the prion-like aggregates are spread throughout the CNS. Here, we review the role of microglia and associated inflammation in the prion-like spread of pathologically aggregated proteins/peptides in Alzheimer’s disease, Parkinson’s disease, and ALS. A growing body of evidence suggests that microglia can internalize prion-like proteins and transport them to neighboring neurons and other glial cells. Microglia may also influence the potential seeding of proteins in neurons and induce inflammatory pathways in their microenvironment. This review aims to broaden the understanding of the role of microglia in the prion-like spread of protein aggregation.
Global, regional, and national burden of pulmonary arterial hypertension and related heart failure from 1990 to 2021, with predictions to 2050: insights from the global burden of disease study 2021
Authors: Liu Ke , Zeng Yi , Wang Hualing , Yang Huiping , Liu Lida , Chen Xingyu , Yang Xiuli , Liu Yufei , Zhu Yi , Zhang Chuantao
Published: February 2025

Background

Pulmonary arterial hypertension (PAH) and PAH-related heart failure (PAH-HF) have undergone significant epidemiological changes since 1990. However, large-scale studies are scarce. This study evaluates global epidemiologic trends from 1990 to 2021 and projects them to 2050 to inform public health policies.

Methods

Data on the incidence, prevalence, deaths, and disability-adjusted life years (DALYs) of PAH and PAH-HF were analyzed using models like joinpoint regression, bayesian age-period-cohort and decomposition analysis. Trends were reported by sex, age group, and geographic region, with projections extending to 2050.

Results

In 2021, the global age-standardized incidence rate (ASIR), prevalence rate (ASPR), mortality rate (ASMR), and DALY rate (ASDR) for PAH were 0.52, 2.28, 0.27, and 8.24 per 100 000 population, respectively. Compared to 1990, ASIR and ASPR increased, while ASDR and ASMR declined. Females showed higher burdens in nearly all outcomes. In 2021, Zambia and Switzerland had the highest ASIR and ASPR of PAH, while Mongolia recorded the highest ASMR and ASDR. For PAH-HF, the number of prevalent cases and years lived with disability from 1990 to 2021, though most heart failure subtypes showed declines in ASPR. Decomposition analysis attributed increases in PAH incidence, prevalence, and DALYs primarily to population growth, while aging primarily drove increases in deaths. Future projections suggest continued growth in ASIR but declines in other burden indicators after 2021.

Conclusions

From 1990 to 2021, the global burden of PAH and PAH-HF increased, with significant gender disparities. These results provide valuable guidance for healthcare strategies and resource allocation.
The Patient Journey in Chronic Coronary Syndromes with/without Obstructive Coronary Arteries
Authors: La Sarena , Tavella Rosanna , Wu Jing , Spertus John A , Pasupathy Sivabaskari , Girolamo Olivia , Zeitz Christopher , Worthley Matthew , Arstall Margaret , Sinhal Ajay , Beltrame John
Published: February 2025

Background

In patients undergoing invasive coronary angiography for the investigation of angina, the management pathways for obstructive coronary artery disease (CAD) are well described, whereas the clinical and diagnostic journey of patients with ANOCA has largely been inferred, as there is limited quantitative data.

Objectives

To compare the journey of patients with ANOCA versus Obstructive CAD, particularly in relation to (i) clinical presentation and (ii) diagnostic assessment, (iii) 12 month patient-reported outcome measures (PROMs) and (iv) three year composite MACE

Methods

A total of 2,285 ANOCA and 4,087 Obstructive CAD consecutive patients were included from the CADOSA (Coronary Angiogram Database of South Australia) registry between 2012-2018.

Results

At presentation for elective invasive angiography, the chest pain features and non-invasive ischemic markers were indistinguishable between patients with Obstructive CAD and ANOCA, although the latter were younger (67±11 vs. 61 ± 11 years, p<0.001), more likely to be female (27% vs. 58%, p<0.001) and have fewer traditional cardiac risk factors. However, following angiography (compared to those with Obstructive CAD) patients with ANOCA were less likely to attain a cardiac discharge diagnosis (100% vs. 22%) or receive anti-anginal therapy (76% vs. 57%), despite the same prevalence of persistent angina (weekly angina: 10% vs 11% over 12 months).

Conclusions

Although the pre-angiography journey (symptoms & non-invasive ischemic investigations) of patients with Obstructive CAD and ANOCA is indistinguishable, the post-angiography journey is portrayed by a vast diagnostic and treatment gap in those with ANOCA, which needs to be addressed.
Multiple domestication centres of the Indian pig population
Authors: Desai Shailesh , Singh Prajjval Pratap , Pandey Rudra Kumar , Mishra Rahul Kumar , Chaubey Akhilesh Kumar , Kumar Ajit , Tiwary Sachin Kr , Gupta Sandeep , Achilli Alessandro , Rambaldi Migliore Nicola , Chaubey Gyaneshwer
Published: February 2025

The domestication of animals is a major milestone in human history and has been studied in various fields. Pig domestication, in particular, has been widely studied, and it is believed that India is one of at least six domestication centers. However, there is a lack of systematic studies using high-resolution genetic markers, including complete mitogenomes, to investigate the domestication and genetic roots of pigs in India. In the present study, we investigated the origin and evolution of Indian pigs using mitochondrial genetic data to complement archaeological datasets. The phylogenetic status of Indian pig breeds was determined by analyzing all available mitochondrial data, incorporating a global dataset of 239 mitogenomes. The Bayesian and maximum likelihood tree analyses unveiled at least eight haplogroups diverging from three main branches, two of which are geographically restricted to India. We propose that the North Indian domestic haplogroup might represent an independent in-situ domestication event in North India, probably dating before ∼5,000 YBP. An additional North East Indian domestic haplogroup is nested within a widespread Asian clade that also includes Indian mitogenomes from the Andaman and Nicobar Islands that diverged more recently from distinct East and Southeast Asian roots. In conclusion, we propose that North Indian farmers could have been responsible for the independent domestication of local wild boars giving rise to the current domestic lineage identified in North India. At least one additional domestic lineage arrived in India more recently and remained mainly localized in the northeast. Domestic mitogenomes from the Indian islands show a notable connection with pig populations from Vietnam, and their arrival might be related to Austroasiatic-speaking human populations. Overall, this study provides valuable insights into the complex dynamics of pig domestication in India.
Ethylene positively regulates anthocyanin synthesis in 'Viviana' lily via the LvMYB5-LvERF113-LvMYB1 module
Authors: Zhang Yibing , Sun Yibo , Du Weifeng , Sun Shaokun , Zhang Shimiao , Nie Mengyao , Liu Yudong , Irfan Muhammad , Zhang Li , Chen Lijing
Published: February 2025

Ethylene (ET) influences the synthesis of anthocyanins, although its regulatory effects can differ significantly across various plant species. In apples (Malus domestica), ET promotes anthocyanin synthesis, whereas in Arabidopsis thaliana, it inhibits its accumulation. Our research showed that ethephon (Eth), an ET derivative, promotes anthocyanin synthesis in 'Viviana' lilies, which has great potential in the cut flower industry. The regulatory mechanism whereby ethylene influences anthocyanin synthesis in lilies remains unclear. In this study, we screened and characterized an ET-induced ET response factors (ERFs), LvERF113, with inhibitory function. Our analyses suggested that LvERF113 could inhibit the negative regulatory function of LvMYB1 at transcriptional and posttranslational levels, promoting anthocyanin synthesis in 'Viviana' lily tepals. In addition, LvERF113 is positively regulated by LvMYB5, forming the LvMYB5-LvERF113-LvMYB1 module controlling anthocyanin synthesis by ET in 'Viviana' lily. These findings offer new insights into the ET regulatory network of anthocyanin synthesis and provide a theoretical basis for the application of ET derivatives in the cut flower industry.
Building Reparations: Key Factors for Success in Transitional Justice Efforts
Authors: Southey Safia K
Published: February 2025

Amidst the focus on traditional postconflict justice mechanisms, the significance of financial compensation warrants reevaluation. This research investigates the dearth of literature on reparations, seeking to unravel the circumstances that led to successful administrative reparation programs for intrastate human rights violations. Through an analysis of 32 historical cases across 20 countries, this study highlights political motivations and financial stability as key factors shaping reparations’ success, using Argentina and Nepal to illustrate how reparations can be implemented across different contexts. Recognizing that political calculations underpin the birth of nearly all implemented programs, a novel categorization system emerges, encompassing three overlapping motivators: legal obligation, protection of power and personal/political gain. Within this framework, understanding these motivators becomes imperative for the establishment of effective policies.
Molecular Evolution of Nucleoside Deoxyribosyl Transferase (NDT) to Enhance the Activity towards 2’-Fluoro-2’-Deoxynucleoside
Authors: Yang Su-Been , Yoo Yeon-Jin , Choi Kanghyun , Kim Byungkyun , Choi Si-Sun , Kang Seung-Hoon , Kim Eung-Soo
Published: February 2025

Nucleoside deoxyribosyl transferase (NDT) is an enzyme that catalyzes the transfer of purine and pyrimidine bases between 2'-deoxyribonucleosides and is widely used for synthesizing nucleoside analogs in various biotechnological applications. While NDT exhibits high activity toward natural nucleosides, its activity toward unnatural nucleoside analogs is significantly lower. Previously, the NDT mutant named fNDT(L59Q) was identified displaying 4.4-fold higher activity toward 2'-fluoro-2'-deoxyuridine (2FDU). In this study, molecular evolution strategies using error-prone PCR were employed to further generate mutant enzymes with enhanced activity toward 2FDU. After two rounds of mutational screening, two mutant clones that exhibited high activity against 2FDU were identified as fNDT-i1 (V52A) and fNDT-i2 (L28I), respectively. A double mutant fNDT-i4, was subsequently constructed by combining the V52A and L28I mutations. Whole-cell-based activity measurements showed that fNDT-i4 exhibited 4.0-fold and 20.6-fold higher activity at 40°C and 50°C, respectively, compared to the wild-type NDT. The detailed characterization of the purified enzymes conducted under various conditions, including temperature, pH, thermal stability, and enzyme kinetics experiments, showed that fNDT-i1 and fNDT-i4 exhibited 3.1- and 3.7-fold higher catalytic efficiency, respectively than wild-type NDT. The L59Q mutation was identified as a key factor in improving the thermal stability, whereas the V52A and L28I mutations were critical for improving substrate affinity and reaction efficiency. These findings provide the potential of fNDT-i1 and fNDT-i4 as highly efficient biocatalysts for developing industrially relevant nucleoside analog synthesis.
Obinutuzumab maintenance versus observation for patients with newly diagnosed high tumor burden follicular lymphoma who achieved complete metabolic response after obinutuzumab plus bendamustine induction therapy: a multicenter, randomized, phase III study (JCOG2008, MAIN study)
Authors: Kobayashi Tsutomu , Ishizawa Kenichi , Machida Ryunosuke , Sadachi Ryo , Sasaki Keita , Kim Haryoon , Kataoka Keisuke , Munakata Wataru , Fukuhara Noriko , Nagai Hirokazu ,   Lymphoma Study Group of the Japan Clinical Oncology Group
Published: February 2025

Maintenance therapy with monoclonal anti-CD20 antibody is the standard approach in patients with follicular lymphoma who initially treated and achieved response to immunochemotherapy. Maintenance therapy reduces the risk of lymphoma progression, but the risk of late or delayed fatal treatment-emergent adverse events is a clinically important issue. The aim of this randomized phase III study is to confirm the non-inferiority of observation compared to obinutuzumab maintenance therapy in patients with untreated high tumor burden follicular lymphoma who achieved complete metabolic response after obinutuzumab plus bendamustine induction therapy (JCOG2008, MAIN study). The first registration is performed before obinutuzumab plus bendamustine administration. Those who achieved complete metabolic response at the end of induction are included in the second registration and randomized to an obinutuzumab maintenance arm or observation only. This study has been registered in the Japan Registry for Clinical Trials as jRCT1031210379.
Proportion of patients in phase 2 oncology trials receiving treatments that are ultimately approved
Authors: Ouimet Charlotte , Fodor Bianca , Del Paggio Joseph C , Kimmelman Jonathan
Published: February 2025

Background

Many patients enroll in phase 1 dose expansion cohorts or phase 2 clinical trials (together referred to below as “phase 2”) seeking access to novel treatments. Little is known about the extent to which they benefit by enrolling. Herein, we use a novel metric of benefit—therapeutic proportion—to assess the probability that patients in phase 2 trials receive treatment that eventually advances to FDA (Food and Drug Administration) approval for their condition.

Methods

We randomly sampled 400 trials identified in a search of Clinicaltrials.gov for cancer phase 2 trials initiated between November 1, 2012 and November 1, 2015. We determined whether the drug/dose/indication tested in each trial advanced to FDA approval within 7.5 years. We determined whether the drug/dose/indication presented substantial clinical benefit using the ESMO-MCBS (European Society for Medical Oncology - Magnitude of Clinical Benefit Scale), or whether it received off-label recommendation in NCCN (National Comprehensive Cancer Network) guidelines.

Results

Collectively, trials in our sample enrolled 25 002 patient-participants in 608 specific treatment cohorts. A total of 4045 patients received a treatment that advanced to FDA approval (16.2%; 95% CI = 10.3 to 22.7). The therapeutic proportion increased to 19.4% (95% CI = 14.1 to 25.8) when considering NCCN off-label recommendations and decreased to 9.3% (95% CI = 4.7 to 14.6) for FDA-approved regimens considered being of substantial clinical benefit by ESMO-MCBS. Bootstrap test of mean difference showed no statistical difference in proportions based on drug class, trial phase, or sponsorship.

Conclusion

One in 6 patients in phase 2 clinical trials receives treatments that are eventually approved. This represents a higher therapeutic value than phase 1 trials.
Assessment of TB Infection-Related Outpatient Clinical Outcomes Across Neighborhood-Level Deprivation Quartiles
Authors: Day Melissa E , Duan Qing , Burkhardt Mary Carol , Klein Melissa , Schlaudecker Elizabeth P , Beck Andrew F
Published: February 2025

Background

Pediatric tuberculosis infection (TBI) disproportionately affects those in complex social situations. Neighborhood characteristics may influence access to care and TBI-related outcomes. We sought to examine links between neighborhood-level socioeconomic deprivation and clinical outcomes.

Methods

In this retrospective cohort study, we identified children with TBI treated at our pediatric infectious diseases clinics between 2012-2023. We geocoded each child’s address to identify neighborhood-level material community deprivation index (MCDI) scores. Outcomes included missed clinic visits, missed antibiotic doses, and changes in antibiotic therapy due to adherence concerns. We assessed time between referral and first visit, first and second visits, and first and last visits. Kruskal-Wallis rank sum test and chi-squared tests examined relationships between DI quartile and clinical outcomes. Log-rank testing and Cox proportional hazard regression models evaluated time-to-event analyses.

Results

We identified 150 children with TBI. There were no differences across MCDI quartiles in rates of missed clinic visits, missed antibiotic doses, changed therapy, or therapy completion. Higher deprivation was associated with longer time between referral and first visit (median 12 days for low/moderate-low deprivation quartiles vs. 24 days for high/moderate-high deprivation quartiles, p=0.004). The high/moderate-high deprivation category had a 39% lower hazard of getting to the first clinic visit after referral compared to the low/moderate-low deprivation category (HR 0.61; 95%CI 0.43, 0.85) after adjustment for race, insurance, and language.

Conclusions

Children with TBI from socioeconomically deprived neighborhoods have longer times from referral to first clinical evaluation. Exploring drivers of differences could promote more equitable TBI care.
Resettlement vs. spontaneous applications. Canadians’ attitudes to asylum policy in a comparative perspective
Authors: Van Wolleghem Pierre Georges
Published: February 2025

Increasing irregular crossings into Canada have put the asylum issue at the forefront of the political debate. This article explores Canadian citizens’ attitudes toward two distinct asylum policies: the long-established resettlement policy endorsed by the federal government, and spontaneous applications, which have sparked public debate over the past seven years. Analyzing original survey data from 2021, I show that a majority of Canadians support asylum policies, irrespective of type. Delving into opposition to these policies, I identify welfare chauvinism as the primary factor, although attitudes to international collaboration on refugee matters and to the United Nations also correlate with policy preferences. A comparative analysis of attitudes in Canada, the USA, the UK, and the Netherlands reveals similar influences on asylum policy preferences. By shifting the focus from attitudes to refugees to attitudes to asylum policy, this study provides novel evidence of an important dimension of Canadians’ attitudes toward refugee-related matters.
High-resolution urban air quality monitoring from citizen science data with echo-state transformer networks
Authors: Bonas Matthew , Castruccio Stefano
Published: February 2025

Citizen science data for monitoring air pollution have recently emerged as a powerful yet under-explored resource to complement expensive and sparse national air quality monitors. In urban environments, these new data have the potential to allow for high-resolution and high-frequency forecasts, and thereby to provide an assessment of population exposure at neighbourhood level. The complex spatio-temporal structure of these data, however, requires new flexible methods that are also able to provide timely forecasts. In this work, we propose a novel method that first provides forecasts with a reservoir computing approach, an echo-state network, adjusts the forecast with a transformer network with attention mechanism and then merges the echo-state and transformer forecast into a combined network. The stochastic nature of the method allows for a fast and more accurate forecast then individual predictors as well as standard statistical methods. Simulation and application to San Francisco air pollution show how the proposed method is able to produce high-resolution urban maps of air quality. Additionally, we show how these forecasts can be used to provide neighbour-level exposure assessment using population data, a task that would not be achievable with sparse government-sponsored air quality networks.
Identifying regions of concomitant compound precipitation and wind speed extremes over Europe
Authors: Boulin Alexis , Di Bernardino Elena , Laloë Thomas , Toulemonde Gwladys
Published: February 2025

The task of simplifying the complex spatio-temporal variables associated with climate modelling is of utmost importance and comes with significant challenges. In this research, our primary objective is to develop a clustering framework to handle compound extreme events within gridded climate data across Europe. Specifically, we intend to identify subregions that display asymptotic independence between precipitation and wind speed extremes, meaning that occurrences of extreme rain and wind speed in one subregion do not affect those in the other. To achieve this, we utilize daily precipitation sums and daily maximum wind speed data derived from the ERA5 reanalysis dataset spanning from 1979 to 2022. Our approach hinges on a tuning parameter and the application of a divergence measure to spotlight disparities in extremal dependence structures without relying on specific parametric assumptions. We propose a data-driven approach to determine the tuning parameter. This enables us to generate clusters that are spatially concentrated, which can provide more insightful information about the regional distribution of compound precipitation and wind speed extremes. The proposed method is able to extract valuable information about extreme compound events while also significantly reducing the size of the dataset within reasonable computational timeframes.
Structural Analysis of Cerebral Organoids Using Confocal Microscopy and Transmission/Scanning Electron Microscopy
Authors: Noh Seulgi , Park Yurim , Kim Beomsue , Mun Ji Young
Published: February 2025

Cerebral organoid cultures from human-induced pluripotent stem cells are widely used to study complex human brain development; however, there is still limited ultrastructural information regarding the development. In this study, we examined the structural details of cerebral organoids using various microscopy techniques. Two protocols were chosen as representative methods for the development of brain organoids: the classic whole-cerebral organoid (Whole-CO) culture technique, and the air–liquid interface-cerebral organoid (ALI-CO) culture technique. Immunostained confocal laser scanning microscopy (CLSM) revealed the formation of the CTIP2- and TBR1-positive cortical deep layer on days 90 and 150, depending on the developmental progress of both methods. Furthermore, the presence of astrocytes and oligodendrocytes was verified through immunostained CLSM utilizing two-dimensional and three-dimensional reconstruction images after a 150-day period. Transmission electron microscopy analysis revealed nanometer-resolution details of the cellular organelles and neuron-specific structures including synapses and myelin. Large-area scanning electron microscopy confirmed the well-developed neuronal connectivity from each culture method on day 150. Using those microscopy techniques, we clearly showed significant details within two representative culture protocols, the Whole-CO and ALI-CO culture methods. These multi-level images provide ultrastructural insight into the features of cerebral organoids depending on the developmental stage.
Characterization of interstellar carbon dust analogues synthesized by dielectric barrier discharge and evolution after irradiation with 3 MeV H+
Authors: Gerber Ioana Cristina , Mihaila Ilarion , Pohoata Valentin , Sandu Andrei , Agheorghiesei Catalin , Soroaga Laurentiu Valentin , Iancu Decebal , Andrei Radu Florin , Burducea Ion , Straticiuc Mihai , Duca Dumitru , Egorov Dmitrii , Carpentier Yvain , Chazallon Bertrand , Faccinetto Alessandro , Nuns Nicolas , Focsa Cristian , Pirim Claire , Topala Ionut
Published: February 2025

‘Fluffy’ hydrogenated amorphous carbon (a-C:H) was synthesized using a dielectric barrier discharge plasma, driven by nanosecond high voltage pulses at 1 kHz frequency in a helium-butane mixture. The a-C:H samples were characterized by scanning and transmission electron microscopy, laser-assisted and secondary ion mass spectrometry, and Raman and Fourier-transform infrared spectroscopy. We find that a-C:H samples exhibit infrared absorption features in good agreement with those observed for carbonaceous dust in IRAS 08572+3915 galaxy. We discuss their nano to microscale structure and derive their hydrogen to carbon (H/C) ratios from the results obtained by three distinct experimental characterization techniques. Relying on the average H/C value determined by mass spectrometry and Raman spectroscopy, we can then constrain the absorption strengths values to those best corresponding to our dust analogue, and calculate the H/C ratio from the infrared spectra. Altogether, we find that our dust analogue consists of a dominant hydrogen-rich aliphatic network, with small, isolated, aromatic regions. The a-C:H dust analogue was then irradiated with 3 MeV H+ and subsequently analyzed ex situ. Morphological and chemical changes, including the evolution of H/C, CH2/CH3, and sp2/sp3 ratios, were observed with increasing proton fluence, indicating dehydrogenation and graphitization. Proton bombardment shifted the initial location of a-C:H in the hydrocarbon ternary phase diagram toward the central region defined by IRAS 08572+3915 observations. The decay of the 3.4 μm band with proton fluence was used to calculate CH destruction cross-sections, results consistent with a direct effect of cosmic rays on the disappearance of the 3.4 μm band.
Long-Time 2D Simulations of Fallback Supernovae: A Systematic Investigation of Explosions Dynamics and Mass Ejection
Authors: Sykes Bailey , Müller Bernhard
Published: February 2025

We present a set of eight fallback simulations of zero-metallicity progenitors with masses between 60 M⊙ and 95 M⊙. The simulations are computed in 2D with the general relativistic CoCoNuT-FMT code for the first few seconds after black hole formation, and then mapped to the Newtonian code Prometheus for long-duration simulations to shock breakout. All simulations produce successful explosions with final energies ranging from 0.41 × 1051 erg to 2.5 × 1051 erg and black hole masses from 20.7 M⊙ to 34.4 M⊙. Explosion energies and remnant masses do not vary monotonically with progenitor mass, but the mass cuts cluster near the outer edge of the helium core. A supplementary model with decreased neutrino heating provides a tentative indication that successful explosions require the shock to reach the sonic point in the infall profile by the time of black hole formation. The propagation of the shock to the surface is only approximately captured by proposed shock invariants, but these may still be sufficient to extrapolate the final black hole mass from the first seconds of evolution. We also discuss potential multi-messenger signatures of the predicted fallback explosions. The enrichment of the ejecta in intermediate mass and iron-group elements varies considerably and is non-negligible for the more powerful explosions. Low-level neutrino emission after black hole formation from these very massive progenitors may be detectable in the case of a Galactic event.
On the progenitor of the Crab pulsar
Authors: Cruz-Cruz Elvira , Kochanek C S
Published: February 2025

We investigate the progenitor of the Crab supernova by examining the remnant’s surrounding stellar population. The Crab is interesting because of the apparently low energy and mass of the supernova remnant. We also know it was not a binary at death and that the explosion formed a neutron star. Using Gaia EDR3 parallaxes and photometry, we analyze stars inside a cylinder with a projected radius of 100 pc and spanning distances from ∼1600 to 2300 pc set by the 2σ uncertainties in the Crab’s parallax. We also individually model the most luminous stars local to the Crab. The two most luminous stars are blue, roughly main sequence stars with masses of ∼11M⊙. We estimate the stellar population’s age distribution using Solar metallicity PARSEC isochrones. The estimated age distribution of the 205 MG < 0 stars modestly favor lower mass stars, consistent with an AGB star or a lower mass binary merger as the progenitor, but statistically we cannot rule out higher masses. This may be driven by contamination due to the ∼700 pc span of the cylinder in distance.
Structures of the cyanobacterial nitrogen regulators NtcA and PipX complexed to DNA shed light on DNA binding by NtcA and implicate PipX in the recruitment of RNA polymerase
Authors: Forcada-Nadal Alicia , Bibak Sirine , Salinas Paloma , Contreras Asunción , Rubio Vicente , Llácer José L
Published: February 2025

The CRP-FNR (cAMP receptor protein-fumarate/nitrate reductase regulator) superfamily of transcriptional regulators includes the cyanobacterial master regulator NtcA, which orchestrates large responses of cyanobacteria to nitrogen scarcity. NtcA uses as allosteric activator 2-oxoglutarate (2OG), a signal of nitrogen poorness and carbon richness, and binds a co-activating protein (PipX) that shuttles between the signaling protein PII and NtcA depending on nitrogen richness, thus connecting PII signaling and gene expression regulation. Here, combining structural (X-ray crystallography of six types of crystals including NtcA complexes with DNA, 2OG, and PipX), modeling, and functional [electrophoretic mobility shift assays and bacterial two-hybrid (BACTH)] studies, we clarify the reasons for the exquisite specificity for the binding of NtcA to its target DNA, its mechanisms of activation by 2OG, and its co-activation by PipX. Our crystal structures of PipX–NtcA–DNA complexes prove that PipX does not interact with DNA, although it increases NtcA–DNA contacts, and that it stabilizes the active, DNA-binding-competent conformation of NtcA. Superimposition of this complex on a very recently reported cryo-electron microscopy structure of NtcA in a transcription activity complex with RNA polymerase (RNAP), shows that PipX binding helps recruit RNAP by PipX interaction with RNAP, particularly with its gamma and sigma (region 4) subunits, a structural prediction supported here by BACTH experiments.
Synapsin III promotes neuronal-like transdifferentiation of glioblastoma stem cells by disrupting JAG1-Notch1 interaction
Authors: Deng Yilin , Yuan Zheng , Jin Xiong , Wang Zekun , Gong Rui , Ren Shuai , Park Jong Bae , Shi Bingyang , Yin Jinlong
Published: February 2025

Background

Glioblastoma (GBM), a formidable and highly aggressive form of brain cancer, is predominantly driven by GBM stem cells (GSCs), which are characterized by their ability for self-renewal and aberrant differentiation. Targeting the terminal differentiation of GSCs represents a promising therapeutic strategy. This study aimed to elucidate the role of synapsin III (SYN3) in driving the differentiation of GSCs into neuron-like cells and its effect on the tumor-suppressive pathways in GBM.

Method

Proliferation assays, limited dilution assays, immunocytochemistry, western blot, RT-qPCR, and GSC tumor models were used to determine gene function and assess the role of γ-secretase inhibitors. Co-immunoprecipitation and microscale thermophoresis were conducted to explore the underlying regulatory mechanisms. Intracranial orthotopic injection of adeno-associated virus (AAV) was performed to evaluate therapeutic potential.

Results

We demonstrate that SYN3, uniquely within the synapsin family, acts as a tumor suppressor by steering GSCs toward neuronal-like transdifferentiation. Mechanistically, SYN3 enhances the expression of Neuregulin 3 (NRG3), which serves as a non-canonical antagonist of Notch signaling by competitively binding to specific epitopes within the EGF-like domain of JAG1, a critical site for the canonical engagement of Notch receptors. This critical interaction disrupts the JAG1-Notch1 signaling pathway, a key mechanism driving GSCs toward neuronal-like transdifferentiation, thereby reducing their stemness. Furthermore, SYN3 demonstrated significant antineoplastic activity in a mouse model harboring GSCs. AAV-mediated overexpression of SYN3 markedly impeded GBM progression.

Conclusion

Our research reveals the therapeutic potential of SYN3 in regulating GSC fate and offers a novel differentiation-based approach for GBM therapy.
Under cover of darkness: Refuge from artificial light at night may mitigate risks to stranded seabirds
Authors: Brown Taylor M , Baker Kaitlyn , Wilhelm Sabina I , Burness Gary
Published: February 2025

Artificial light at night is an anthropogenic pollutant that has wide-ranging effects on wildlife. Fledgling seabirds of order Procellariiformes exhibit phototaxis toward artificial lights on their first flights from the nest, causing them to become grounded in human settlements, where they are subject to increased predation risk. Limited evidence suggests certain light types may be less attractive than others, yet there is also evidence for an aversion to light under certain circumstances. We investigated differences in phototactic behavior, activity level, and shelter-seeking behavior of grounded Hydrobates leucorhous (Leach’s Storm-Petrel) fledglings exposed to artificial light in 3 experiments: a Y-maze choice experiment, an open field test, and a modified open field test with a hide box provided (“safe haven test”). When provided with combinations of different light types in the Y-maze, storm-petrels typically remained stationary in the darkest parts of the apparatus (farthest from light stimuli) and exhibited no preferred response toward one light type over another. This was consistent with results from the open field test: individuals were less active in darkness than when exposed to 2 of 3 light conditions (warm white light-emitting diode and high-pressure sodium). More than half of individuals entered the hide box in light conditions, compared to none in darkness. Considered together, our results indicate that most (but not all) H. leucorhous fledglings exhibit photophobic behavior after stranding, which may be part of a behavioral strategy to avoid predation. Further, we demonstrate the utility of providing hide boxes to protect stranded seabird fledglings in locations where lighting cannot be eliminated or where rescue efforts are limited in spatial or temporal coverage. However, hide boxes would have limited utility in dark locations. Hide boxes constitute a novel mitigation measure that merits future testing for its ability to reduce stranding-induced mortality, especially in imperiled procellariiform species.
The Big Green Button: Stratospheric Aerosol Injection as a Geopolitical Dilemma During Strategic Competition Between the United States and China, and Implications for Expanding Aerosol Injection Near-term Research
Authors: Nielsen Jeffrey
Published: February 2025

This research examines stratospheric aerosol injection (SAI) policy options through a dyadic international relations framework between the United States and People’s Republic of China (China). Deploying large-scale SAI to manage solar radiation presents states with a novel source of geopolitical influence through influencing global climate systems. While multiple political bodies like the United Nations, European Union, United States, China, and India could feasibly deploy SAI without full global consent, the United States and China are powerful enough to deploy large-scale SAI unilaterally. The United States and China currently perceive themselves as locked in “great power competition” with each other which exposes a mutual SAI national security gap and accompanying policy dilemma. Given their divergent global power strategies but mutual global climate interests, this research assesses how the United States and China could compete or cooperate on SAI strategies. This research’s dyadic analysis of four policy scenarios provides three conclusions. First, the United States and China could each benefit from SAI cooperation whether they are cooperating to deter or deploy SAI. Second, SAI cooperation presents a potential political off-ramp from great power competition that aligns with each state’s mutual climate security interests. Third, expanding SAI research and conventional mitigation could support near-term United States and China policymaking regardless of whether they ultimately pursue SAI deployment or deterrence strategies. SAI advocates and critics alike can use these scenarios and conclusions to better discuss SAI as a geopolitical security dilemma.