bluuebunny/crossref_metadata_2025 huggingface dataset:
Extracellular vesicle proteome unveils cathepsin B connection to Alzheimer’s disease pathogenesis
Authors: Yuyama Kohei , Sun Hui , Fujii Risa , Hemmi Isao , Ueda Koji , Igeta Yukifusa
Published: December 2023

Extracellular vesicles (EVs) are membrane vesicles that are released extracellularly and considered to be implicated in the pathogenesis of neurodegenerative diseases including Alzheimer’s disease. Here, CSF EVs of 16 ATN-classified cases were subjected to quantitative proteome analysis. In these CSF EVs, levels of 11 proteins were significantly altered during the ATN stage transitions (P < 0.05 and fold-change > 2.0). These proteins were thought to be associated with Alzheimer’s disease pathogenesis and represent candidate biomarkers for pathogenic stage classification. Enzyme-linked immunosorbent assay analysis of CSF and plasma EVs revealed altered levels of cathepsin B (CatB) during the ATN transition (seven ATN groups in validation set, n = 136). The CSF and plasma EV CatB levels showed a negative correlation with CSF amyloid-β42 concentrations. This proteomic landscape of CSF EVs in ATN classifications can depict the molecular framework of Alzheimer’s disease progression, and CatB may be considered a promising candidate biomarker and therapeutic target in Alzheimer’s disease amyloid pathology.
Cost-effectiveness of screening for chronic kidney disease: existing evidence and knowledge gaps
Authors: van Mil Dominique , Pouwels Xavier G L V , Heerspink Hiddo J L , Gansevoort Ron T
Published: December 2023

It is well known that the worldwide prevalence of chronic kidney disease (CKD) has risen to over 10% of the general population during the past decades. Patients with CKD are at increased risk of both kidney failure and cardiovascular disease (CVD), posing a substantial health challenge. Therefore, screening for CKD is warranted to identify and treat patients early to prevent progression and complications. In this issue of the Journal, Yeo and colleagues provide an updated systematic review of the cost-effectiveness of screening for CKD in the general adult population. They show that screening for CKD in high-risk populations is cost-effective and that there is limited evidence for screening the general population. It should be noted that most studies they discuss do not consider the benefit of screening to prevent CVD in addition to preventing kidney failure, the treatment effect of novel therapeutic agents such as SGLT2 inhibitors, and the possibility of screening in a home-based setting. These three aspects will likely improve the cost-effectiveness of CKD screening, making it feasible to move towards general population screening for CKD.
The Mayflower and Historical Culture in Britain, 1620–2020
Authors: Downey Edmund , Hulme Tom , Vandrei Martha
Published: December 2023

In 2020 the Anglo-American world marked the 400th anniversary of the trans-Atlantic Mayflower voyage with a programme of activities. Intensive and focused interest in the story of the Mayflower is not a new phenomenon—especially in the United States, where it is the bedrock of the nation’s ‘origin story’. But the tale of the Pilgrims has historically also captured the British imagination. This article outlines a chronology for understanding the cultural importance in Britain of this voyage, from the New England chroniclers to the postcolonial critiques of historians today. In between, it offers a thematic analysis of the different groups which could use the story in their construction of morality and identity, from Romanticists and abolitionists to Anglo-American diplomats and civic boosters. Understanding the afterlife of the voyage in this long perspective, we argue, provides us with a more nuanced understanding of how ideas of history develop and evolve within broader arenas of politics and civil society. We use the concept of historical culture: an approach that is attuned to the interplay between memory, public history, heritage and popular history, and across forms of media (novels, plays, film) and spaces of interaction (cities, politics, movements). As the vogue for commemoration continues to exert power in Britain and beyond, and so does an increasing demand for more critical approaches to historical redress, we thus develop a critical framework that understands the powerful draw of ‘history’—both past and present.
Patients’ perception of orthodontic retainers: a systematic review
Authors: Moda Larissa Barbosa , Bastos Renata Travassos da Rosa Moreira , Flores-Mir Carlos , Normando David
Published: December 2023

Background

Orthodontic retainers are widely used to prevent relapses after orthodontic treatment; however, evidence about patients' perceptions of retainers is lacking.

Objective

To assess patients’ perception of orthodontic retainers.

Search Methods

PubMed, Web of Science, Scopus, LILACS, LIVIVO, Cochrane Library, and gray literature (Google Scholar) were searched without date or language restrictions. A manual search of the reference lists of the included articles was also performed.

Selection criteria

Studies comparing patients’ perceptions of wearing orthodontic retainers were included.

Data collection and analysis

According to the study design, the risk of bias (RoB) assessment was performed using RoB 2.0 or ROBINS-I. The level of evidence was assessed through the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) tool.

Results

Seventeen studies met the eligibility criteria. After the RoB assessment, 12 randomized controlled trials presented a high RoB, and 4 non-randomized controlled trials presented a moderate RoB. The certainty of evidence was classified as very low for the four assessed outcomes. The studies generally reported an initial temporary negative impact of orthodontic retainers. Different esthetic, functional, and ease-of-use advantages are reported using removable and fixed retainers. A quantitative analysis was not performed due to the considerable clinical and methodological heterogeneity among the studies.

Conclusion

The current evidence, although very limited, suggests that orthodontic retainers have an initial negative impact related to discomfort and functional limitations, but they seem to regress over time. There is a preference for thermoplastic over Hawley-type retainers. However, thermoplastic retainers cause different functional difficulties, and bonded retainers present the advantage of affecting speech function less than orthodontic removable retainers, although they can facilitate oral hygiene problems.

Registration

PROSPERO (CRD42022306665).
Gender-specific treatment effects and outcomes reported in orthodontic research. A cross-sectional empirical study
Authors: Kummer Géraldine , Eliades Theodore , Koletsi Despina
Published: December 2023

Aim

To identify practices of assessment of gender effects in research articles in orthodontics and detect whether there were significant differences in the treatment effects on outcomes according to gender.

Materials and Methods

Four major orthodontic journals were sought over a 3-year period to identify publications which included assessment of gender effects on outcomes in their reporting. Data were extracted on the following characteristics: journal, year of publication, region of authorship, and study design. For the studies including reporting of gender effects, whether a significant effect existed was further documented. Additionally, for these studies, data were extracted on population, sample size per gender, treatment, comparison, outcome type, and nature and whether gender analysis was based on subgroup testing or included as a main effect. Descriptive statistics, cross-tabulations, univariable, and multivariable regression models were utilized as appropriate.

Results

A total of 718 research articles were eligible for inclusion out of a pool of 1,132 screened articles. Of those, 95 reported on any type of analysis on gender effects (95/718; 13.2%). In the 95 studies that reported assessment of gender effects, it was clear that the majority did not detect significant gender-related differences across the documented outcomes (range of frequency distribution for significant gender differences across all outcomes: 0–50%). Twenty-two articles overall (22/95; 23.2%) described a significant gender effect classified by outcome, 12 favoring female and 10 favoring male participants. Patterns of efficacy and adverse outcomes were schemed either favoring female (root resorption: 4/10; 40.0%, periodontal outcomes: 3/11; 27.3%) or male (cephalometric/growth changes following orthodontic treatment: 4/17; 23.5%) patients across the 22 studies with significant effects. Appropriately designed and adequately powered statistical analyses, with gender effect assessment as a main effect in a multivariable regression model was associated with 6.53 times higher odds for identifying significant gender effects (OR = 6.53; 95% CI: 2.15, 19.8; P = .001).

Conclusions

A very small proportion of research studies included gender effect assessment in their analyses. Of those, a quarter described significant effects. Nevertheless, careful analysis planning and strategies should be prioritized to allow for any meaningful interpretation.
Sounding passions and therapeutic performance in Thomas Weelkes’s songs
Authors: Butler Katherine
Published: December 2023

This article explores a group of Thomas Weelkes’s songs where the usually light-hearted, playful and often suggestive fa-la refrain is juxtaposed with melancholic lyrics. The contrasting passions in these texts provide inspiration for typically madrigalian musical expression, often involving chromatic writing for melancholic passages; however, the nonsense syllables in the fa-la refrains function differently. With no semantic text, the expression of these passages depends on the musical setting and the decisions taken by the performers, which might align or jar with prior expectations of fa-la refrains. Such passages are ambiguous and malleable, and the signification of the fa-las might change from stanza to stanza.

Weelkes’s experimentation with how fa-la refrains might communicate a range of passions engages with contemporary debates about the extent to which music’s affective powers were reliant on, amplified by, or independent of text. Moreover, several of Weelkes’s songs enact a therapeutic purging of melancholy attributed to non-verbal or instrumental music. Given Weelkes’s interest in exploring sonic effects which are both onomatopoeic and utilize conventions of musical expression, these songs can be interpreted as not merely representations of the passions but as potential acts of musical therapy.
The interaction mechanism between zein and folic acid in alkaline aqueous solutions: an experimental and molecular simulation study
Authors: Zhu Jun , Yao Yiling , Liao Yuying , Cai Lala , Zhang Wenqi , Hong Nuo , Sun Wenlin , Xiong Chunhua , Yao Lanying
Published: December 2023

Objectives

Folic acid is a vitamin that is not highly soluble in water and is sensitive to the environment. Therefore, it is important to find suitable carriers. This study aimed to exemplify the interaction of folic acid with zein in alkaline aqueous solutions and shed light on how zein can be used as a carrier for folic acid.

Materials and Methods

Zein and folic acid were separately dissolved in NaOH solutions with a PH of 11.5. Zein solution and folic acid solution were combined in specific ratios. Various methods including multi-spectroscopy, dynamic light scattering, and electron microscopy combining with molecular dynamics simulations were used to study the interaction mechanism between zein and folic acid in alkaline aqueous solutions.

Results

Fluorescence spectroscopy showed that the quenching of zein by folic acid was mainly static, and the main driving force behind this interaction was van der Waals forces and hydrogen bonds. The formation of zein–folic acid complexes was confirmed by ultraviolet–visible spectroscopy, Fourier transform infrared spectroscopy, and circular dichroism spectroscopy. The results also showed that the structure of zein changed when it interacted with folic acid. Dynamic light scattering analysis revealed that the addition of folic acid caused proteins to aggregate. The aggregates of the complexes had an irregular shape and were large, as observed by scanning electron microscopy and transmission electron microscopy. Molecular simulation was used to further investigate the interaction mechanisms. According to these findings, the folic acid molecule interacted with zein in a shallow recess near the protein surface. The dominant forces at play in the zein–folic acid interaction were van der Waals forces and electrostatic forces, including hydrogen bonding.

Conclusion

The zein alkali-soluble system is very suitable for folic acid delivery.
Variation in Home Healthcare Use by Dementia Status Among a National Cohort of Older Adults
Authors: Burgdorf Julia G , Ornstein Katherine A , Liu Bian , Leff Bruce , Brody Abraham A , McDonough Catherine , Ritchie Christine S
Published: December 2023

Background

Medicare-funded home healthcare (HHC) delivers skilled nursing, therapy, and related services through visits to the patient’s home. Nearly one-third (31%) of HHC patients have diagnosed dementia, but little is currently known regarding how HHC utilization and care delivery differ for persons living with dementia (PLwD).

Methods

We drew on linked 2012–2018 Health and Retirement Study and Medicare claims for a national cohort of 1 940 community-living older adults. We described differences in HHC admission, length of stay, and referral source by patient dementia status and used weighted, multivariable logistic and negative binomial models to estimate the relationship between dementia and HHC visit type and intensity while adjusting for sociodemographic characteristics, health and functional status, and geographic/community factors.

Results

PLwD had twice the odds of using HHC during a 2-year observation period, compared to those without dementia (odds ratio [OR]: 2.03; p < .001). They were more likely to be referred to HHC without a preceding hospitalization (49.4% vs 32.1%; p < .001) and incurred a greater number of HHC episodes (1.4 vs 1.0; p < .001) and a longer median HHC length of stay (55.8 days vs 40.0 days; p < .001). Among post-acute HHC patients, PLwD had twice the odds of receiving social work services (unadjusted odds ratio [aOR]: 2.15; p = .008) and 3 times the odds of receiving speech-language pathology services (aOR: 2.92; p = .002).

Conclusions

Findings highlight HHC’s importance as a care setting for community-living PLwD and indicate the need to identify care delivery patterns associated with positive outcomes for PLwD and design tailored HHC clinical pathways for this patient subpopulation.
Temporal Patterns of Change in Physical and Cognitive Performance
Authors: Desai Pankaja , Halloway Shannon , Krueger Kristin R , Rajan Kumar B , Evans Denis A
Published: December 2023

Background

This study examined the relation between declines in physical and cognitive performance in older people.

Methods

A population-based cohort of 7 483 adults (average age 72 years) were interviewed. Physical performance was assessed with 3 standardized tests and a combination of 4 cognitive tests was used to assess cognitive function. Rate of change in physical and cognitive performance was determined for each interval between interviews. In mixed effects linear regression models adjusted for age, sex, race, and study time, and change in each factor was used to predict change in the other factor. We examined time associations by using changes in the predictor measured at 1, 2, or 3 intervals before the outcome change.

Results

Decline in cognitive function was most strongly predicted by physical decline in the same 3-year interval. The decline in cognitive function was weaker in the 1-time interval after the decline in physical function and was not significant in later intervals. When a decline in cognitive function was used to predict a decline in physical function, the results were similar. The strongest association occurred in the same time interval so that declines in cognitive and physical performance tend to occur together.

Conclusions

Decline in cognition and physical function seem to occur together in a short timeframe. It is important to investigate the reasons for these changes that are short-term to guide the development of interventions.
Sobre fracaso constitucional, constitucionalismo transformador y utopismoOn constitutional failure, Transformative Constitutionalism, and Utopianism
Authors: Landau David , Dixon Rosalind
Published: December 2023

In this brief epilogue, we reflect on the articles in this symposium to ask two questions that are particularly important to transformative constitutionalism. First, what is constitutional failure? While this symposium focuses on constitution-making episodes that never result in a final text, projects might be seen as failures even if they formally go into effect, because they fail to produce on the ground change. Transformative constitutional projects often pay more attention to the articulation of rights than the pathways through which these rights are implemented. Such a text can fall prey to structural utopian constitutionalism, where there is no path to implement ambitious programmatic content. Second, we ask: what causes constitutional failure? The essays in this symposium highlight essentially political reasons, particularly the failure to build sufficient political support from parties and other stakeholders. Constitution-making without such support from political insiders, such as the 2022 Chilean draft or the Icelandic draft, risks falling into sociological utopian constitutionalism and may fail to launch. Examining the failures in this symposium, particularly the overwhelming loss of the 2022 Chilean draft, may help avoid situations where transformation slides into utopianism.
Extent of community pharmacists’ care of clients with depression in Enugu, Nigeria: a cross-sectional survey
Authors: Anosike Chibueze , Adibe Maxwell Ogochukwu , Ani Desmond Nnia
Published: December 2023

Background

Community pharmacists play a crucial role in the care of people with depression. This study aimed to evaluate the level of care provided by community pharmacists for clients with depression in Enugu, Nigeria.

Methods

A cross-sectional survey was conducted among randomly selected community pharmacists in Enugu, Nigeria. The data obtained were analysed descriptively.

Key findings

Approximately 25% of pharmacists perform depression screening, and 14.4% refer clients to psychiatrists. Pharmacists rarely provide information on antidepressant dosage, side effects, frequency, and duration.

Conclusion

Community pharmacists in Enugu are not providing effective care to depressed patients. Thus, appropriate interventions are recommended.
The Securitization of Asylum: A Review of UK Asylum Laws Post-Brexit
Authors: Saenz Perez Cristina
Published: December 2023

Understanding the role of external actors is essential to understanding the United Kingdom’s (UK) securitization agenda in the field of asylum. Whilst the internal dynamics of securitization in migration and asylum and its links to the Brexit referendum have been extensively analysed, the externalization of asylum and its connection to the so-called ‘hostile environment’ policy have received less attention. This article addresses this gap, and focuses on how the Nationality and Borders Act 2022 and the UK–Rwanda Memorandum of Understanding for the relocation of asylum seekers advance the externalization of asylum post-Brexit. It examines how these reforms reinforce the securitization that characterizes the UK’s asylum and migration policy and evaluates how they exclude asylum seekers from access to basic human rights, in violation of the 1951 Refugee Convention and the European Convention on Human Rights.
The shape of an axisymmetric meniscus in a static liquid pool: effective implementation of the Euler transformation
Authors: Naghshineh Nastaran , Reinberger W Cade , Barlow Nathaniel S , Samaha Mohamed A , Weinstein Steven J
Published: December 2023

We examine the classical problem of the height of a static liquid interface that forms on the outside of a solid vertical cylinder in an unbounded stagnant pool exposed to air. Gravitational and surface tension forces compete to affect the interface shape as characterized by the Bond number. Here, we provide a convergent power series solution for interface shapes that rise above or fall below the horizontal pool as a function of contact angle and Bond number. We find that the power series solution expressed in terms of the radial distance from the wall is divergent, and thus rewrite the divergent series as a new power series expressed as powers of an Euler transformed variable; this series is modified to match the large distance asymptotic behaviour of the meniscus. The Euler transformation maps non-physical singularities to locations that do not restrict series convergence in the physical domain, while the asymptotic modification increases the rate of convergence of the series overall. We demonstrate that when the divergent series coefficients are used to implement the Euler transformation, finite precision errors are incurred, even for a relatively small number of terms. To avoid such errors, the independent variable in the governing differential equation is changed to that of the Euler transform, and the power series is developed directly without using the divergent series. The resulting power series solution is validated by comparison with a numerical solution of the interface shape and the small Bond number matched asymptotic solution for the height of the interface along the cylinder developed by Lo (1983, J. Fluid Mech., 132, p.65-78). The convergent power series expansion has the ability to exceed the accuracy of the matched asymptotic solution for any Bond number given enough terms, and the recursive nature of the solution makes it straightforward to implement.
Using deep learning to accurately detect sow vulva size in a group pen with a single camera
Authors: Chang Shen-Chang , Wu Xin-Ru , Kuan Hao-Yuan , Peng Shao-Yu , Chang Chia-Ying
Published: December 2023

This paper presents a non-contact method for the detection of changes in sow vulva size in a group pen. The traditional approach to estrus detection is manually pressing down on the back of the sow to elicit standing responses; however, this method causes undue distress for sows not in estrus. When a sow is in estrus, the vulva is red and swollen due to the presence of endocrine. Monitoring changes in vulva size to detect estrus with as little impact on the sow as possible is the focus of this study. This is achieved using a single camera combined with a deep learning framework. Our approach comprises two steps: vulva detection and vulva size conversion. Images of sows of Yorkshire, Landrace, and Duroc breeds were collected in group housing, and the vulva was detected through artificial markers and the network architecture of YOLO v4. Based on the internal and external parameters of the camera, the detected size was converted into millimeters and the results of manual measurement (MM) and automatic calculation combined to calculate the size of the vulva. Analysis of the calculated size compared with MM indicates that the object recognition rate of the system exceeds 97.06%, with a size error of only + 1.70 to −4.47 mm and high-calculation efficiency (>2.8 frames/s). Directions for future research include the automatic detection of pig width.
Much work to do about measuring work
Authors: Bradley Cathy J , Kitchen Sara , Owsley Kelsey M
Published: December 2023

Work ability is a critical economic and well-being indicator in cancer care. Yet, work ability is understudied in clinical trials and observational research and is often undocumented in medical records. Despite agreement on the importance of work from well-being, health insurance, and financial perspectives, standardized approaches for collecting, measuring, and analyzing work outcomes are lacking in the health-care setting. The necessary components for closing the gap in patient and caregiver employment research in health-care settings involve a common set of measures, including those that replace or translate generic measures of mental and physical functioning into work outcomes in observational and clinical trial research, standardized approaches to data collection and documentation, and the use of longitudinal data to understand the consequences of reduced work ability over time. We present a conceptual framework for the inclusion of work ability in outcomes research. We cover constructs for employment and work ability measurement that can be adopted in research, recorded as patient-level data, and used to guide treatment decisions. The inclusion of return to work and hours worked, productivity, and ability to perform in a similar job can support conversations that guide treatment decisions and minimize economic consequences. Our hope is that by considering impact on work ability, improved treatments will be developed, health inequities reduced, and resources directed toward aiding patients and their caregivers in balancing work and health demands.
The effects of third-party intervention in the adjudication of maritime delimitation disputes
Authors: Aw Stephany
Published: December 2023

Although the adjudication of a maritime boundary dispute is usually a bilateral process, it is also often the case that third States have an interest in the delimitation to be carried out. Coupled with the potential for the delimitation decisions of courts and tribunals to impact their maritime claims or entitlements, this raises the concern that third State interests could be prejudiced by such a dispute settlement process, without their participation. While third-party intervention has been suggested as a possible means of recourse for such third States, this article argues that third States may, in practice, be hesitant of resorting to intervention. This is because attempts to intervene, whether successful or unsuccessful, are likely to entail the court or tribunal’s eventual decision having some legally binding effects on the third State. Further, alternative options remain available to third States desirous of a platform to make their interests known.
Science fiction and self-transcendence: evidence from retrospective, experimental, and longitudinal studies
Authors: Wu Fuzhong , Zhang Zheng
Published: December 2023

This study proposes that science fiction (sci-fi), a specific entertainment genre or theme, can facilitate self-transcendence (i.e., moving beyond self-boundaries) by inducing epistemic humility (i.e., awareness of one’s epistemic limits accompanied by epistemic openness). Through increasing self-transcendence, sci-fi engagement can further promote prosocial intentions in a real-world context. We conducted three studies with different paradigms to test our hypotheses. Through a retrospective design, Study 1 found that sci-fi (vs. comedy or romance) films were recalled as eliciting stronger self-transcendence. Studies 2a and 2b, using an experimental design, revealed that sci-fi (vs. realistic) narratives induced stronger epistemic humility, and consequently led to heightened self-transcendence. Study 3, extending the findings in the pandemic context through a three-wave longitudinal design, demonstrated that sci-fi engagement within one month predicted the subsequent increase in self-transcendence, which in turn promoted coronavirus disease (COVID)-related prosocial intention over time. The potential of sci-fi to foster self-transcendence and prosociality is discussed.
A novel tetratricopeptide-repeat protein, TTP1, forms complexes with glutamyl-tRNA reductase and protochlorophyllide oxidoreductase during tetrapyrrole biosynthesis
Authors: Herbst Josephine , Pang Xiaoqing , Roling Lena , Grimm Bernhard
Published: December 2023

The biosynthesis of the tetrapyrrole end-products chlorophyll and heme depends on a multifaceted control mechanism that acts primarily at the post-translational level upon the rate-limiting step of 5-aminolevulinic acid synthesis and upon light-dependent protochlorophyllide oxidoreductase (POR). These regulatory processes require auxiliary factors that modulate the activity, stability, complex formation, and subplastidal localization of the relevant proteins. Together, they ensure optimal metabolic flow during the day and at night. As an Arabidopsis homolog of the POR-interacting tetratricopeptide-repeat protein (Pitt) first reported in Synechocystis, we characterize tetrapyrrole biosynthesis-regulating tetratricopeptide-repeat protein1 (TTP1). TTP1 is a plastid-localized, membrane-bound factor that interacts with POR, the Mg protoporphyrin monomethylester cyclase CHL27, glutamyl-tRNA reductase (GluTR), GluTR-binding protein, and FLUORESCENCE IN BLUE LIGHT. Lack of TTP1 leads to accumulation of GluTR, enhanced 5-aminolevulinic acid synthesis and lower levels of POR. Knockout mutants show enhanced sensitivity to reactive oxygen species and a slower greening of etiolated seedlings. Based on our studies, the interaction of TTP1 with GluTR and POR does not directly inhibit their enzymatic activity and contribute to the control of 5-aminolevulinic acid synthesis. Instead, we propose that TTP1 sequesters a fraction of these proteins on the thylakoid membrane, and contributes to their stability.
‘Are you a refugee like us? Oh then we have hope!’ Affective discursive encounters in doing insider Other research
Authors: Sereke Wegahta B
Published: December 2023

In this article, I reflect on how paying attention to the flow of affect between participants and the researcher during interviews unveils knowledge that highlights inequalities and advances a decolonial approach. I specifically discuss the capacity of productive discomfort in revealing valuable insights about the lived experiences of forced migrants and in uncovering knowledge that might otherwise stay hidden. In doing so, I demonstrate how my positionality as an ‘insider Other’ and my approach to interviews as affective encounters open up profound layers of experiences and sense-making. Expanding upon this, the study presents a unique framework that combines the method of interviews, conceptualized as situated affective encounters, with an affective-discursive analytical framework that views affect as intertwined with meaning and discourse. This fusion emphasizes the significance of emotions as a source of knowledge in the research process. The study highlights how this approach contributes to the reflexivity turn in migration studies and elucidates how the combined framework can guide researchers to work with discomfort. This can be a source of insight, as demonstrated by reflecting on my own research on the lived experiences of Eritrean migrants. I use several excerpts from my data to demonstrate how viewing emotions as meaningful leads to nuanced interpretations, thereby enriching insights into the living conditions of those who arrived as forced migrants.
Modelling the orbital histories of satellites of Milky Way-mass galaxies: testing static host potentials against cosmological simulations
Authors: Santistevan Isaiah B , Wetzel Andrew , Tollerud Erik , Sanderson Robyn E , Moreno Jorge , Patel Ekta
Published: December 2023

Understanding the evolution of satellite galaxies of the Milky Way (MW) and M31 requires modelling their orbital histories across cosmic time. Many works that model satellite orbits incorrectly assume or approximate that the host halo gravitational potential is fixed in time and is spherically symmetric or axisymmetric. We rigorously benchmark the accuracy of such models against the FIRE-2 cosmological baryonic simulations of MW/M31-mass haloes. When a typical surviving satellite fell in ($3.4\!-\!9.7\, \rm {Gyr}$ ago), the host halo mass and radius were typically 26–86 per cent of their values today, respectively. Most of this mass growth of the host occurred at small distances, $r\lesssim 50\, \rm {kpc}$, opposite to dark matter only simulations, which experience almost no growth at small radii. We fit a near-exact axisymmetric gravitational potential to each host at z = 0 and backward integrate the orbits of satellites in this static potential, comparing against the true orbit histories in the simulations. Orbital energy and angular momentum are not well conserved throughout an orbital history, varying by 25 per cent from their current values already $1.6\!-\!4.7\, \rm {Gyr}$ ago. Most orbital properties are minimally biased, ≲10 per cent, when averaged across the satellite population as a whole. However, for a single satellite, the uncertainties are large: recent orbital properties, like the most recent pericentre distance, typically are ≈20 per cent uncertain, while earlier events, like the minimum pericentre or the infall time, are ≈40–80 per cent uncertain. Furthermore, these biases and uncertainties are lower limits, given that we use near-exact host mass profiles at z = 0.
Generating images of the M87* black hole using GANs
Authors: Mohan Arya , Protopapas Pavlos , Kunnumkai Keerthi , Garraffo Cecilia , Blackburn Lindy , Chatterjee Koushik , Doeleman Sheperd S , Emami Razieh , Fromm Christian M , Mizuno Yosuke , Ricarte Angelo
Published: December 2023

In this paper, we introduce a novel data augmentation methodology based on Conditional Progressive Generative Adversarial Networks (CPGAN) to generate diverse black hole (BH) images, accounting for variations in spin and electron temperature prescriptions. These generated images are valuable resources for training deep learning algorithms to accurately estimate black hole parameters from observational data. Our model can generate BH images for any spin value within the range of [−1, 1], given an electron temperature distribution. To validate the effectiveness of our approach, we employ a convolutional neural network to predict the BH spin using both the GRMHD images and the images generated by our proposed model. Our results demonstrate a significant performance improvement when training is conducted with the augmented data set while testing is performed using GRMHD simulated data, as indicated by the high R2 score. Consequently, we propose that GANs can be employed as cost-effective models for black hole image generation and reliably augment training data sets for other parametrization algorithms.
The SAMI-Fornax Dwarfs Survey – IV. Star formation histories of dwarf and early-type galaxies: insights from full spectral fitting
Authors: Romero-Gómez J , Aguerri J A L , Peletier Reynier F , Mieske Steffen , van de Ven Glenn , Falcón-Barroso Jesús
Published: December 2023

We present a study on the star formation histories (SFHs) of galaxies covering the range 104 < M⋆/M⊙ < 1012, leveraging full spectral fitting algorithms. Our sample consists of 31 dwarf galaxies from the SAMI-Fornax Survey with stellar masses between 107–$10^{9.5} \, {\rm M}_{\odot }$, early-type galaxies from the ATLAS3D project with stellar masses between 1010–$10^{12} \, {\rm M}_{\odot }$, and dwarf galaxies that are satellites of Andromeda and the Milky Way, with 104 < M⋆/M⊙ < 108. We find that galaxies from 107–$10^{8} \, {\rm M}_{\odot }$ exhibit the smallest star formation rates (SFRs), while the SFR increase as we move down or up in mass. In this sense, we find that some $10^{5} \, {\rm M}_{\odot }$ galaxies have cumulative SFHs that are comparable to those of $10^{12} \, {\rm M}_{\odot }$ galaxies. Our study shows that the evolution of giant galaxies is primarily governed by their internal properties, with time-scales that do not depend on their environmental location. In contrast, dwarf galaxies below $10^{8} \, {\rm M}_{\odot }$ can be significantly affected in dense environments, such as the inner regions of a cluster, that severely quench the galaxies before the assembly of their 50 per cent present-day mass. We find that, only dwarfs with stellar masses between 107–$10^{9} \, {\rm M}_{\odot }$ actively form stars nowadays, while less massive galaxies seem to remain unaffected by the environment due to the expulsion of most of their gas at an early stage in their evolution. Our study highlights and corroborates a critical threshold around $10^{8}-10^{9} \, {\rm M}_{\odot }$ in galaxy evolution from previous studies, separating more massive galaxies minimally impacted by the environment from those less massive galaxies quenched by it.
Cholesterol homeostasis confers glioma malignancy triggered by hnRNPA2B1-dependent regulation of SREBP2 and LDLR
Authors: Zhang Juan , Liu Bei , Xu Changwei , Ji Chenchen , Yin Anan , Liu Yifeng , Yao Yan , Li Bowen , Chen Tangdong , Shen Liangliang , Wu Yuanming
Published: December 2023

Background

Dysregulation of cholesterol metabolism is a significant characteristic of glioma, yet the underlying mechanisms are largely unknown. N6-methyladenosine (m6A) modification has been implicated in promoting tumor development and progression. The aim of this study was to determine the key m6A regulatory proteins involved in the progression of glioma, which is potentially associated with the reprogramming of cholesterol homeostasis.

Methods

Bioinformatics analysis was performed to determine the association of m6A modification with glioma malignancy from The Cancer Genome Atlas and Genotype-Tissue Expression datasets. Glioma stem cell (GSC) self-renewal was determined by tumor sphere formation and bioluminescence image assay. RNA sequencing and lipidomic analysis were performed for cholesterol homeostasis analysis. RNA immunoprecipitation and luciferase reporter assay were performed to determine hnRNPA2B1-dependent regulation of sterol regulatory element-binding protein 2 (SREBP2) and low-density lipoprotein receptor (LDLR) mRNA. The methylation status of hnRNPA2B1 promoter was determined by bioinformatic analysis and methylation-specific PCR assay.

Results

Among the m6A-regulatory proteins, hnRNPA2B1 was demonstrated the most important independent prognostic risk factor for glioma. hnRNPA2B1 ablation exhibited a significant tumor-suppressive effect on glioma cell proliferation, GSC self-renewal and tumorigenesis. hnRNPA2B1 triggers de novo cholesterol synthesis by inducing HMGCR through the stabilization of SREBP2 mRNA. m6A modification of SREBP2 or LDLR mRNA is required for hnRNPA2B1-mediated mRNA stability. The hypomethylation of cg21815882 site on hnRNPA2B1 promoter confers elevated expression of hnRNPA2B1 in glioma tissues. The combination of targeting hnRNPA2B1 and cholesterol metabolism exhibited remarkable antitumor effects, suggesting valuable clinical implications for glioma treatment.

Conclusions

hnRNPA2B1 facilitates cholesterol uptake and de novo synthesis, thereby contributing to glioma stemness and malignancy.
Defining interventions and metrics to improve diversity in CNS clinical trial participation: A SNO and RANO effort
Authors: Budhu Joshua A , Chukwueke Ugonma N , Jackson Sadhana , Lee Eudocia Q , McFaline-Figueroa J Ricardo , Willmarth Nicole , Dalmage Mahalia , Kawachi Ichiro , Arons David , Chang Susan M , Galanis Evanthia , Hervey-Jumper Shawn L , Wen Patrick Y , Porter Alyx B
Published: December 2023

Despite major strides in cancer research and therapy, these advances have not been equitable across race and ethnicity. Historically marginalized groups (HMG) are more likely to have inadequate preventive screening, increased delays in diagnosis, and poor representation in clinical trials. Notably, Black, Hispanic, and Indigenous people represent 30% of the population but only 9% of oncology clinical trial participants. As a result, HMGs lack equitable access to novel therapies, contradicting the principle of distributive justice, as enshrined in the Belmont report, which demands the equitable selection of subjects in research involving human subjects. The lack of clinical trial diversity also leads to low generalizability and potentially harmful medical practices. Specifically, patients with brain cancer face unique barriers to clinical trial enrollment and completion due to disease-specific neurologic and treatment-induced conditions. Collectively, the intersection of these disease-specific conditions with social determinants of health fosters a lack of diversity in clinical trials. To ameliorate this disparity in neuro-oncology clinical trial participation, we present interventions focused on improving engagement of HMGs. Proposals range from inclusive trial design, decreasing barriers to care, expanding trial eligibility, access to tumor profiling for personalized medical trials, setting reasonable metrics and goals for accrual, working with patient community stakeholders, diversifying the neuro-oncology workforce, and development of tools to overcome biases with options to incentivize equity. The diversification of participation amongst neuro-oncology clinical trials is imperative. Equitable access and inclusion of HMG patients with brain tumors will not only enhance research discoveries but will also improve patient care.
10000-SPE-1 STEM CELL-BASED GENE THERAPY FOR MALIGNANT GLIOMA USING GENOME-EDITED HUMAN INDUCED PLURIPOTENT STEM CELLS
Authors: Tamura Ryota , Yo Masahiro , Imai Ryotaro , Okano Hideyuki , Toda Masahiro
Published: December 2023

Glioblastoma is the most aggressive primary brain tumor, and is characterized by diffuse infiltration into the normal brain parenchyma. New therapeutic approaches targeting invasive biological behaviour are warranted. In the present study, we show that neural stem cells (NSCs) derived from CRISRP/Cas9-edited induced pluripotent stem cells (iPSCs) have high tumor-trophic migratory capacity and stable constitutive therapeutic transgene expression, which leads to strong anti-tumor effects against glioma stem cell (GSC) models. The present study provides answers to some important research questions associated with stem cell-based gene therapy. First, the tumor-trophic migratory capacities of human iPSC-derived NSCs (iPSC-NSCs), fetal NSCs, and mesenchymal stem cells (MSCs) were quantitatively evaluated by spatiotemporal methodologies. We demonstrated that iPSC-NSCs have a higher tumor-trophic migratory capacity than MSCs in the brain. Self-repulsive action and pathotropism were important for the migration of iPSC-NSCs: ephrin ligand/receptor mediated repulsion of iPSC-NSCs and CXCL12-CXCR4 interactions between GSCs and iPSC-NSCs. Second, a prodrug converting enzyme fusion gene was selected as a therapeutic gene in human iPSCs. In general, stable constitutive transgene expression by viral vectors was difficult in human iPSCs. Furthermore, viral vectors integrate randomly into the host genome, which raises concerns about transgene silencing, insertional mutagenesis, and oncogene activation. In the present study, several common insertion sites including GAPDH, ACTB, and AAVS1, were compared. The most appropriate gene locus that achieved stable constitutive transgene expression was determined via CRISPR/Cas9-mediated genome editing. Third, we revealed the novel mechanism of action using iPSC-NSCs expressing CD-UPRT, in which ferroptosis was associated with enhanced anti-tumor immune responses. We demonstrated that the established iPSC-NSCs had strong therapeutic efficacy in GSC animal models. Finally, predictive biomarkers for the efficacy of the present treatment strategy were established. We will conduct a clinical trial of this treatment strategy. This research concept can disseminate biological, medical and engineering advances.
10015-NI-1 PREDICTION OF MGMT PROMOTOR METHYLATION STATUS IN GLIOBLASTOMA BY CONTRAST-ENHANCED T1-WEIGHTED IMAGE
Authors: Sanada Takahiro , Kinoshita Manabu , Sasaki Takahiro , Yamamoto Shota , Fujikawa Seiya , Fukuyama Shusei , Hayashi Nobuhide , Fukai Junya , Okita Noriko , Nonaka Masahiro , Uda Takehiro , Arita Hideyuki , Mori Kanji , Ishibashi Kenichi , Takano Koji , Nishida Namiko , Shofuda Tomoko , Yoshioka Ema , Kanematsu Daisuke , Tanino Mishie , Kodama Yoshinori , Mano Masayuki , Kanemura Yonehiro
Published: December 2023

PURPOSE

The study aims to explore MRI phenotypes that predict the methylation status of the promoter region of MGMT (pMGMT) in glioblastoma.

MATERIALS AND METHODS

202 histologically and molecularly confirmed glioblastoma patients (pMGMT methylated: 103, unmethylated: 99) at the Kansai Network for Molecular Diagnosis of Central Nervous Tumors (KNBTG) were used as a test cohort. 104 patients from the Cancer Imaging Archive (TCIA) / Cancer Genome Atlas (TCGA) dataset (pMGMT methylated: 103, unmethylated: 99) were used as a validation cohort. "Thickened structure" was defined when the solid component of the tumor had either a circumferential extension or occupied more than 50% of the entire volume of the tumor. "Methylated contrast phenotype" was defined by imaging findings with one of the following three features: indistinct enhancing circumferential border, heterogenous enhancement, and nodular enhancement. The inter-rater agreement between three independent blinded raters was first evaluated, and then the relationship between the image findings and pMGMT methylation status was investigated.

RESULTS

Fleiss's Kappa coefficient for "Thickened structure" was 0.68 for the KNBTG cohort and 0.56 for the TCIA cohort and for " Methylated contrast phenotype", 0.32 and 0.35, respectively. The odds ratio of "Methylated contrast phenotype" detecting pMGMT hypermethylation was 2.4 (p = 0.003) for the KNBTG cohort. The odds ratio of "Methylated contrast phenotype" associated with pMGMT methylation was 4.5 (p = 0.001) for those restricted to tumors presenting a "Thickened structure". The odds ratio for pMGMT methylation detected by "Methylated contrast phenotype" was 3.4 (p = 0.005) for the TCIA cohort. It was 7.1 (p = 0.009) when restricting to tumors presenting a "Thickened structure".

CONCLUSION

Glioblastoma showing both a "Thickened structure" structure and "Methylated contrast phenotype" is associated with pMGMT methylation, which may be a clinically useful imaging feature.
10020-ML-1 SENTINEL LESION PRECEDING PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA
Authors: Sasaki Takahiro , Yamoto Toshikazu , Fukai Junya , Nishibayashi Hiroki , Nakao Naoyuki
Published: December 2023

It has been reported that there are rare cases of spontaneous resolution, which are referred to as sentinel lesions in the early stages of primary malignant lymphoma of the central nervous system (PCNSL). In this study, we examined cases of PCNSL that presented with a sentinel lesion. Of the 43 PCNSL cases biopsied at our institution between 2011 and 2022, three cases were difficult to diagnose on initial biopsy. No preoperative steroids were used in all patients, and postoperative CT or MRI confirmed that the lesions were appropriately sampled from the targeted lesions. Since the diagnosis was not confirmed by the initial biopsy and symptoms were stable, the patients were followed up without chemotherapy, but symptoms worsened around 6 months later, and MRI showed recurrent large lesions. Another biopsy was performed in all patients, and a definitive diagnosis of diffuse large B-cell lymphoma (DLBCL) was finally obtained. It has been reported that sentinel lesions in PCNSL are characterized by demyelination or nonspecific inflammation on initial pathology and spontaneous resolution of lesions, which are estimated to be changes mediated by immunological mechanisms. In the present study, the course of symptoms was characterized by a relatively slow progression, and diffusion-weighted images at the initial onset did not show as high a signal as in usual PCNSL. Multiple biopsies are required to make a definitive diagnosis, and careful follow-up of symptoms and images and determination of the appropriate timing of biopsy are important.