bluuebunny/crossref_metadata_2025_split huggingface dataset:
DDO1002, an NRF2–KEAP1 inhibitor, improves hematopoietic stem cell aging and stress response
Authors: Li Yuwen , Wu Aiwei , Jin Xinrong , Shen Haiping , Zhao Chenyan , Yi Xiao , Nie Hui , Wang Mingwei , Yin Shouchun , Zuo Hongna , Ju Zhenyu , Jiang Zhenyu , Wang Hu 
Published: December 2024

Abstract
Oxidative stress diminishes the functionality of hematopoietic stem cells (HSCs) as age advances, with heightened reactive oxygen species (ROS) levels exacerbating DNA damage, cellular senescence, and hematopoietic impairment. DDO1002, a potent inhibitor of the NRF2–KEAP1 pathway, modulates the expression of antioxidant genes. Yet, the extent to which it mitigates hematopoietic decline post-total body irradiation (TBI) or in the context of aging remains to be elucidated. Our study has elucidated the role of DDO1002 in modulating NRF2 activity, which, in turn, activates the NRF2-driven antioxidant response element (ARE) signaling cascade. This activation can diminish intracellular levels of ROS, thereby attenuating cellular senescence. In addition, DDO1002 has been demonstrated to ameliorate DNA damage and avert HSC apoptosis, underscoring its potential to mitigate hematopoietic injury precipitated by TBI. Competitive transplantation assay revealed that the administration of DDO1002 can improve the reconstitution and self-renewal capacity of HSCs in aged mice. Single-cell sequencing analysis elucidated that DDO1002 treatment attenuated intracellular inflammatory signaling pathways and mitigated ROS pathway in aged HSCs, suggesting its potential to restore the viability of these cells. Consequently, DDO1002 effectively activated the NRF2–ARE pathway, delaying cellular senescence and ameliorating impaired hematopoiesis, thereby demonstrating its potential as a therapeutic agent for age-related hematopoietic disorders.
A Brief Report on Sex-Specific Differences in Persistent Depression, Anxiety, and Loneliness Among Canadian Veterans During the COVID-19 Pandemic
Authors: Webber Colleen , Mahar Alyson L , St Cyr Kate , Cramm Heidi , Reppas-Rindlisbacher Christina , Siddhpuria Shailee , Hallet Julie , Rochon Paula A , Fear Nicola T 
Published: December 2024

ABSTRACT

Introduction
Older adults are at increased risk of severe illness and mortality from Coronavirus disease of 2019 (COVID-19) infection. However, public health strategies aimed at reducing spread of COVID-19 may have resulted in increased mental health symptoms, particularly among older adults. Currently, little is known about whether older Veterans were more likely to experience persistent mental health symptoms during the COVID-19 pandemic than non-Veterans. The objectives of the current study were to (1) compare differences in persistent symptoms of anxiety, depression, and loneliness among a sample of Canadian Armed Forces Veterans and non-Veterans ≥55 years of age and (2) to evaluate potential sex-specific differences in persistent mental health symptoms.

Material and Methods
The data for this study are drawn from a longitudinal survey of Canadian adults (55 years and older) during the COVID-19 pandemic. Ethical approval was received from the Women’s College Hospital Research Ethics Board. Participants completed a baseline survey of sociodemographic, mental health–related, and COVID-19–related variables in May 2020 and 8 follow-up surveys monthly between May 2020 and January 2021. Modified Poisson regression models with robust standard errors were used to estimate risk of persistent symptoms of anxiety, depression, and loneliness.

Results
Eight hundred twenty-nine participants (13.7% [n = 114] Veterans) were included in the analysis of persistent depressive symptoms, 859 participants (14.0% [n = 120] Veterans) were included in the analysis of persistent anxiety symptoms, and 862 (13.9% [n = 120] Veterans) were included in the analysis of persistent symptoms of loneliness. When comparing male Veterans and non-Veterans, there were small but statistically insignificant differences in persistent symptoms of anxiety (adjusted relative risk [aRR], 0.59; 95% confidence interval [CI], 0.24-1.46), depression (aRR, 1.54; 95% CI, 0.63-3.77), or loneliness (aRR, 0.79; 95% CI, 0.36-1.75); similar small but statistically insignificant differences were observed in persistent symptoms of anxiety (aRR, 1.26; 95% CI, 0.51-3.09), depression (aRR, 1.16; 95% CI, 0.49-2.73), and loneliness (aRR, 1.33; 95% CI, 0.61-2.90) when comparing female Veterans to female non-Veterans.

Conclusions
Qualitative, but statistically nonsignificant sex-specific differences in persistent symptoms of anxiety, depression, and loneliness during the early months of the COVID-19 pandemic were observed in this study comparing Veterans and non-Veterans. Additional sex-stratified analyses using larger samples or qualitative interviews may be useful in understanding the unique mental health experiences of older men, women, and gender diverse Veterans during the COVID-19 pandemic.
Why do some ultra diffuse Galaxies have rich globular cluster systems?
Authors: Forbes Duncan A , Buzzo Maria Luisa , Ferre-Mateu Anna , Romanowsky Aaron J , Gannon Jonah , Brodie Jean P , Collins Michelle L M 
Published: December 2024

ABSTRACT
Some ultra diffuse galaxies (UDGs) reveal many more globular clusters (GCs) than classical dwarf galaxies of the same stellar mass. These UDGs, with a mass in their GC system ($M_{\rm GC}$) approaching 10 per cent of their host galaxy stellar mass ($M_{\ast }$), are also inferred to have high halo mass to stellar mass ratios ($M_{\rm halo}/M_{\ast }$). They have been dubbed Failed Galaxies. It is unknown what role high GC formation efficiencies and/or low destruction rates play in determining the high $M_{\rm GC}/M_{\ast }$ ratios of some UDGs. Here we present a simple model, which is informed by recent JWST observations of lensed galaxies and by a simulation in the literature of GC mass loss and tidal disruption in dwarf galaxies. With this simple model, we aim to constrain the effects of GC efficiency/destruction on the observed GC richness of UDGs and their variation with the integrated stellar populations of UDGs. We assume no ongoing star formation (i.e. quenching at early times) and that the disrupted GCs contribute their stars to those of the host galaxy. We find that UDGs, with high $M_{\rm GC}/M_{\ast }$ ratios today, are most likely the result of very high GC formation efficiencies combined with modest rates of GC destruction. The current data loosely follow the model that ranges from the mean stellar population of classical dwarfs to that of metal-poor GCs as $M_{\rm GC}/M_{\ast }$ increases. As more data becomes available for UDGs, our simple model can be refined and tested further.
Impact of the shape of the prestellar density fluctuations on the core mass function
Authors: Dumond Pierre , Chabrier Gilles 
Published: December 2024

ABSTRACT
It is well known that departure from sphericity in the geometry of primordial dark matter haloes modifies their mass function. The ellipsoidal collapse model yields a better agreement with simulations of hierarchical clustering than the original spherical model. In this paper, we examine the same issue in the context of star formation by studying the impact of non-sphericity of density perturbations in a gravoturbulent medium on the prestellar core mass function (CMF). An important question, notably, is to find out how ellipsoidal, instead of spherical, initial density fluctuations modify both the high-mass and low-mass tails of the CMF. Our study shows that triaxial density fluctuations indeed depart from a purely spherical form but the deformation (prolateness and ellipticity) remains modest, suggesting that the usual hypothesis of spherical collapse in existing theories of the IMF is reasonable. We find that, as in the cosmological case, the departure from sphericity increases the collapse barrier, stabilizing the prestellar cores. The striking difference between the stellar case and the cosmological one for the ellipsoidal collapse model is that, although in both cases the less dense structures are the most deformed, they correspond to small scales, thus low-mass haloes in cosmology but to large scales, thus large mass cores in star formation. As a result, the high-mass range of the CMF is the most affected by the ellipsoidal collapse, resulting in a slightly less steep slope than the one predicted with the spherical hypothesis and a peak slightly shifted towards lower masses.
Ultraviolet scattering polarization from space particles entering Earth’s atmosphere
Authors: López-Viejobueno Jennifer , Gómez de Castro Ana I 
Published: December 2024

ABSTRACT
Space material from leftovers of comets and asteroids is daily entering the Earth’s atmosphere. Traditionally, this influx has been characterized from ground-based observations or through meteorite searches. However, cosmic dust and small meteoroids (below a grain size of 1 cm) are not easily detectable with the current facilities and there is scant information about them. In this work, we analyse the feasibility of characterizing the low-mass end of the dust size distribution using observations at ultraviolet wavelengths from space. For this purpose, we have computed the expected scattered ultraviolet radiation and polarization produced by space dust falling on Earth using the Monte Carlo code radmc-3d. We have built a density model attending to the features and parameters obtained from measurements of meteorites, meteor showers, and cometary dust observations. We show that silicate grains will be easily distinguishable from carbonates and irons based on polarization measurements. Moreover, the polarization reversals produced in the resonance scattering regime can be used to study the details of the size distribution of small dust grains. We point out the dependence of the modelled polarization on the way of discretizing the particle size distribution.
A case report of a 14-year-old male patient with large vessel vasculitis following COVID-19
Authors: Nemoto Hiroki , Nozaki Yoshihiro , Matsumoto Takashi , Kiyoki Kaori , Ishiodori Takumi , Morita Atsushi , Imagawa Kazuo , Murakami Takashi , Takahashi Miho , Imai Hironori , Takada Hidetoshi 
Published: December 2024

ABSTRACT
Most reported cases of large vessel vasculitis (LVV) following coronavirus disease 2019 (COVID-19) have involved adults, with paediatric cases being rare. We present the case of a 14-year-old boy who developed LVV following COVID-19. Initially, he presented with fever and cough, and nasopharyngeal polymerase chain reaction testing confirmed COVID-19. His symptoms spontaneously resolved without specific COVID-19 treatments. However, 10 days after contracting COVID-19, his fever recurred and his inflammatory markers were significantly elevated. His condition did not meet the criteria for Kawasaki disease or multisystem inflammatory syndrome in children associated with COVID-19. Contrast-enhanced computed tomography revealed arterial wall thickening in the aorta and carotid arteries, indicative of LVV. Upon initiation of high-dose immunoglobulin therapy and aspirin, his fever subsided and his inflammatory markers and imaging findings normalised. Differential diagnosis ruled out infections, immune disorders, and Takayasu arteritis (TAK), a common cause of aortitis in children. Over a 1-year follow-up period, there were no recurrence and no stenotic lesions in large vessels. This finding suggests that the patient experienced transient LVV following COVID-19. Cytokine profile analysis performed before and after treatment revealed elevated levels of interleukin (IL)-6, IL-8, and IL-12/IL-23p40, typically associated with the active phase of TAK. Importantly, IL-17A and tumour necrosis factor-α levels were normal, as elevations in these cytokines have been linked to TAK recurrence. Notably, some cases of LVV following COVID-19 do not respond well to treatment; further research, including case accumulation and cytokine profile analysis, is needed to better predict prognosis.
Automated pediatric brain tumor imaging assessment tool from CBTN: Enhancing suprasellar region inclusion and managing limited data with deep learning
Authors: Gandhi Deep B , Khalili Nastaran , Familiar Ariana M , Gottipati Anurag , Khalili Neda , Tu Wenxin , Haldar Shuvanjan , Anderson Hannah , Viswanathan Karthik , Storm Phillip B , Ware Jeffrey B , Resnick Adam , Vossough Arastoo , Nabavizadeh Ali , Fathi Kazerooni Anahita 
Published: December 2024

Abstract

Background
Fully automatic skull-stripping and tumor segmentation are crucial for monitoring pediatric brain tumors (PBT). Current methods, however, often lack generalizability, particularly for rare tumors in the sellar/suprasellar regions and when applied to real-world clinical data in limited data scenarios. To address these challenges, we propose AI-driven techniques for skull-stripping and tumor segmentation.

Methods
Multi-institutional, multi-parametric MRI scans from 527 pediatric patients (n = 336 for skull-stripping, n = 489 for tumor segmentation) with various PBT histologies were processed to train separate nnU-Net-based deep learning models for skull-stripping, whole tumor (WT), and enhancing tumor (ET) segmentation. These models utilized single (T2/FLAIR) or multiple (T1-Gd and T2/FLAIR) input imaging sequences. Performance was evaluated using Dice scores, sensitivity, and 95% Hausdorff distances. Statistical comparisons included paired or unpaired 2-sample t-tests and Pearson’s correlation coefficient based on Dice scores from different models and PBT histologies.

Results
Dice scores for the skull-stripping models for whole brain and sellar/suprasellar region segmentation were 0.98 ± 0.01 (median 0.98) for both multi- and single-parametric models, with significant Pearson’s correlation coefficient between single- and multi-parametric Dice scores (r &gt; 0.80; P &lt; .05 for all). Whole tumor Dice scores for single-input tumor segmentation models were 0.84 ± 0.17 (median = 0.90) for T2 and 0.82 ± 0.19 (median = 0.89) for FLAIR inputs. Enhancing tumor Dice scores were 0.65 ± 0.35 (median = 0.79) for T1-Gd+FLAIR and 0.64 ± 0.36 (median = 0.79) for T1-Gd+T2 inputs.

Conclusion
Our skull-stripping models demonstrate excellent performance and include sellar/suprasellar regions, using single- or multi-parametric inputs. Additionally, our automated tumor segmentation models can reliably delineate whole lesions and ET regions, adapting to MRI sessions with missing sequences in limited data context.
Consequentialism and the separateness of persons
Authors: Fischer Jessica J T 
Published: December 2024

Abstract
It is often said that consequentialism violates the separateness of persons. But what does this mean? Existing interpretations are often unclear, or let consequentialism off easy: because they target amendable parts of the consequentialist framework, they can be sidestepped by more subtle versions of the theory. Consequentialism's opponents, however, might hope for a stronger interpretation––one which suggests that the separateness of persons objection presses a distinct and powerful charge against consequentialist theory. This paper proposes such an interpretation. It starts from the fact that, unlike other moral theories, consequentialism determines how to act by looking at features such as states of affairs or outcomes. Yet, crucially, states of affairs or outcomes often make reference to, or extend across, more than one person. Thus, they implicitly and necessarily group together different individuals. In the proposal of this paper, it is this part of consequentialism which violates the separateness of persons.
Coronary artery calcium and atherosclerotic cardiovascular disease risk scores in patients with calcium pyrophosphate deposition disease
Authors: Tedeschi Sara K , Hayashi Keigo , Guan Hongshu , Solomon Daniel H , Weber Brittany 
Published: December 2024

Abstract

Objective
Calcium pyrophosphate deposition (CPPD) disease is associated with an increased risk for cardiovascular (CV) events. We examined the atherosclerotic burden by coronary artery calcium (CAC) scores (Agatston score) and compared 10-year atherosclerotic CV disease (ASCVD) risk scores in patients with vs without chondrocalcinosis, a radiographic marker of CPPD.

Methods
We performed a cross-sectional analysis at an academic medical centre, 1991–2022. Among all patients with an Agatston score in routine care, we defined a cohort with chondrocalcinosis detected before the CAC scan. Comparators without chondrocalcinosis were matched 2:1 on age and sex—the primary analysis excluded statin users. We compared Agatston scores between the chondrocalcinosis cohort and comparators. We also tested for differences between cohorts in 10-year ASCVD risk score frequencies (low, borderline/intermediate or high).

Results
756 patients with chondrocalcinosis were matched to 1554 comparators (mean age 68 years, 53% female). CV risk factor burden was high in both cohorts, and statin use was infrequent. The unadjusted Agatston score was non-significantly higher in the chondrocalcinosis cohort (mean 359.1, s.d. 737.9) than in matched comparators (mean 297.1, s.d. 644.9) (P = 0.08). High 10-year ASCVD risk scores were significantly more common in the chondrocalcinosis cohort than comparators (P &lt; 0.01).

Conclusion
Coronary atherosclerosis burden by CAC was not significantly different between patients with chondrocalcinosis and matched comparators, though 10-year ASCVD risk scores were higher in the chondrocalcinosis cohort, suggesting that factors beyond coronary artery calcification contribute to the increased CV event rate in patients with CPPD disease.
Compression ratio: a novel method to quantify compressibility as a diagnostic measurement in giant cell arteritis
Authors: Khurshid Muhammad Asim , Mynors-Wallis Daniel , Richards Selwyn , Barclay Charlotte , Fox Christine , Budka Marcin , Hopkinson Neil , Young-Min Steven 
Published: December 2024

Abstract

Objectives
Ultrasonographic assessment of giant cell arteritis (GCA) relies on the demonstration of a non-compressible halo. Several ultrasonographic methods have been developed to quantify arterial wall thickness; however, arterial compressibility has not been quantified. This study presents a possible solution for quantifying compressibility to assist in diagnosing GCA.

Methods
Cross-sectional areas of uncompressed and compressed arteries were measured ultrasonographically, and their ratio was calculated [compression ratio (CR)]. The values obtained were tested for a relationship with the diagnosis of GCA and diagnostic performance was compared against halo count (HC).

Results
Ultrasound findings from 304 patients (65.8% females) were divided into GCA arm (n = 72) and Not-GCA arm (n = 232). The CR values for patients in the GCA arm were significantly lower than the Not-GCA arm whether compared as the individual patient mean or lowest CR value (Mann–Whitney U test P &lt;0.001). The CR values observed in this study from a single skilled clinician suggest a threshold CR value of ≤2.3 for predicting a diagnosis of GCA. If confirmed in other studies this would effectively provide a quantitative measure that might help training sonographers confirm a visually identified halo sign and enhance objectivity in ultrasonographic assessment of GCA.

Conclusion
Compression ratio (CR) is a novel quantifiable measure that contributes to the ultrasound assessment of GCA. It is worthy of further research and in clinical application, it is a measurement that may enhance diagnostic certainty.
Identification and validation of a novel autophagy-related biomarker in obstructive sleep apnea syndrome
Authors: Li Zhiyong , Yi Huijie , Li Yuxi , Yang Jie , Guo Peng , Han Fang 
Published: December 2024

Abstract

Study objectives
Obstructive sleep apnea syndrome is closely associated with tumor growth. Chronic intermittent hypoxia promotes autophagy and is related to malignant tumor development. However, the role of autophagy in obstructive sleep apnea syndrome progression remains unclear.

Methods
obstructive sleep apnea syndrome datasets (GSE135917 and GSE38792) from Gene Expression Omnibus were analyzed to identify differentially expressed genes and autophagy-related differentially expressed genes. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analysis were conducted, and a protein–protein interaction network identified hub genes. Colorectal cancer datasets from The Cancer Genome Atlas were used for differential expression and survival analyses, along with gene set enrichment analysis and immune infiltration analysis. Chronic intermittent hypoxia-induced autophagy and oxidative stress were investigated in Sprague-Dawley rats using reactive oxygen species assays. Hub genes were validated in rats and obstructive sleep apnea syndrome patient samples.

Results
Gene set enrichment analysis revealed significant differences in autophagy-related gene expression among obstructive sleep apnea syndrome patients. Hub genes ATG5, CASP1, MAPK8, EIF4G1, and TANK-binding kinase 1 were identified, with ATG5 and TANK-binding kinase 1 validated. Autophagy-related differentially expressed genes were predominantly upregulated in colorectal cancer tissues. TANK-binding kinase 1 expression in colorectal cancer patients was associated with enhanced sensitivity to immunotherapy and CD8 + T cell, macrophage, and regulatory T cell infiltration, potentially influencing the immune microenvironment. The animal experiments showed that chronic intermittent hypoxia increased reactive oxygen species levels, suggesting that chronic intermittent hypoxia plays a role in autophagy. TANK-binding kinase 1 expression was significantly higher in obstructive sleep apnea syndrome patients than in controls, and continuous positive airway pressure did not alter TANK-binding kinase 1 levels.

Conclusions
This study is the first to describe the potential contribution of TANK-binding kinase 1 to the development of obstructive sleep apnea syndrome and its potential as a novel biomarker and potential therapeutic target for obstructive sleep apnea syndrome.
Orthologs of Drosophila pointed and Arginine kinase 1 impact sleep in mice
Authors: Harbison Susan T , Peiravi Morteza , Zhang Fan , Yimam Shemsiya , Noguchi Audrey , Springer Danielle 
Published: December 2024

Abstract
Model organisms such as Drosophila are powerful tools to study the genetic basis of sleep. Previously, we identified the genes pointed and Arginine kinase 1 using selective breeding for long and short sleep duration in an outbred population of Drosophila. pointed is a transcription factor that is part of the epidermal growth factor receptor signaling pathway, while Arginine kinase 1 is involved in proline and arginine metabolism. Conserved orthologs of these genes exist in mice, leading us to hypothesize that they would also impact sleep in a murine model. We generated mutations in the murine orthologs Ets1 and Ckm using CRISPR in a C57BL/6N background and used video analysis to measure sleep in the mice. Both mutations affected sleep parameters, and the effects were observed predominantly in female mice, with males showing fewer differences from littermate controls. The study of natural populations in flies therefore leads to candidate genes with functional conservation on sleep in mammals.