bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring marginalized indigenous communities’ expectations and experiences with the national school education system in Nepal: a study of Kham Magars
Authors: Khanal Jeevan , Khatri Chhetri Gopi Ram , Ghimire Som Nath
Published: September 2023

Limited information is available on the expectations and experiences of the Kham Magars, an indigenous community in Nepal, regarding the value of school education. This study delves into the expectations and experiences of school education among the indigenous Kham Magar community in Nepal, using the Expectation Value Theory as a framework. Through qualitative analysis of narratives from community members, multifaceted expectations emerge, including access to education, employment opportunities, active participation, teacher respect, and equal representation. The study further highlights that the Kham Magar community initially places a high value on education, driven by their efforts in establishing schools and their deep respect for teachers. However, over time, challenges arise due to diminished realization of expected benefits, language barriers, and a focus on traditional agricultural practices, all of which impact the sustainability of formal education. Despite valuing education, the community’s aspirations may not always align perfectly with formal schooling, underscoring the importance of incorporating cultural integration into the curriculum. Ultimately, the findings of this study contribute to a better understanding of indigenous expectations towards education, thus emphasizing the necessity for implementing inclusive and sustainable development policies.
Business politicians and fiscal consolidation
Authors: Nones Nicola
Published: September 2023

What explains the variation in countries’ propensity to engage in austerity policy? Economic and political country-level factors are the paramount explanations in the literature. Nevertheless, variation in fiscal preferences at the executive level remains underexplored, except for ideology. Moreover, budget decisions are endogenous to the state of the economy, thus casting doubt on standard measures based on the debt and/or deficit ratio. This article contributes to the literature in two ways. First, I turn to the individual level of analysis and suggest that leaders with business experience are more likely to pursue a balanced budget and tend to implement fiscal consolidation policies based on spending cuts. Second, I ease concerns about individuals’ self-selection into office by relying on fiscal adjustments that are weakly orthogonal to the economic cycle. The statistical analysis of a panel of 17 OECD countries between 1978 and 2014 confirms the theoretical expectations. The results are robust to a variety of specification and statistical methodologies and hold for a subset of as-if random leadership transitions following close elections. A case study of Brian Mulroney's governments in Canada (1984–93) further illustrates the argument.
Examining the effect of ice dynamic changes on subglacial hydrology through modelling of a synthetic Antarctic glacier
Authors: Hayden Anna-Mireilla , Dow Christine F.
Published: September 2023

Hydrologic pathways beneath ice sheets and glaciers play an important role in regulating ice flow. Antarctica has experienced, and will continue to experience, changes in ice dynamics and geometry, but the associated changes in subglacial hydrology have received less attention. Here, we use the GlaDS subglacial hydrology model to examine drainage evolution beneath an idealised Antarctic glacier in response to steepening ice surface slopes, accelerating ice velocities and subglacial lake drainages. Ice surface slope changes exerted a dominant influence, redirecting basal water to different outlet locations and substantially increasing channelised discharge crossing the grounding line. Faster ice velocities had comparatively negligible effects. Subglacial lake drainage results indicated that lake refilling times play a key role in drainage system evolution, with lake flux more readily accommodated following shorter refilling times. Our findings are significant for vulnerable Antarctic regions currently experiencing dynamic thinning since subglacial water re-routing could destabilise ice shelves through enhanced sub-shelf melting, potentially hastening irreversible retreat. These changes could also affect subglacial lake activity. We, therefore, emphasise that including a nuanced and complex representation of subglacial hydrology in ice-sheet models could provide critical information on the timing and magnitude of sea-level change contributions from Antarctica.
A Smothering Embrace? Hermeneutical Issues in Catholic Discourse about Jews and Judaism
Authors: Polyakov Emma O’Donnell
Published: September 2023

This article examines how Jews and Judaism are envisioned in the Catholic imagination, through a critical reading of contemporary Catholic discourse on Judaism. It identifies three problematic areas. The first concerns the tendency of Catholic discourse to project a specifically Christian vision of salvation history onto the Jewish people, which reflects Christian rather than Jewish self-understanding. Second, this article analyzes patterns in language and imagery in Vatican documents about Judaism, alert to troubling allusions implicit in the texts. The third area concerns a hermeneutical obstacle to deep interreligious understanding, one which may be ultimately insurmountable: namely, the challenges of understanding the religious other according to its own self-understanding. This article reaches an ambivalent conclusion, conceding that the goal of recognizing the self-understanding of another religious tradition may ultimately be impossible.
Parental homeownership and education: the implications for offspring wealth inequality in Great Britain
Authors: Gregg Paul , Kanabar Ricky
Published: September 2023

The rapid widening of wealth inequalities has led to sharp differences in living standards in Great Britain. Understanding whether and separately the rate at which individuals accumulate particular types of wealth by family background is important for improving wealth and social mobility. We show offspring wealth inequality is driven by housing wealth, and holding such wealth is becoming increasingly associated with early life circumstances relating to parental housing tenure and education, even after controlling for adult offspring’s own characteristics. Importantly, we find adult offspring whose parents hold a degree and are homeowners are no less likely to report homeownership and housing wealth compared to older cohorts from the same background. Our findings infer the intergenerational rank correlation in housing wealth is set to double in approximately three decades.
The role of diet in the management of psoriasis: a scoping review
Authors: Hawkins Poppy , Earl Kate , Tektonidis Thanasis G. , Fallaize Rosalind
Published: September 2023

Psoriasis is a chronic, systemic, immune-mediated, inflammatory skin disease associated with significant comorbidities. Globally, there are an estimated 60 million people living with psoriasis (PLwP). There is a growing body of evidence on the role of diet in psoriasis management, and demand for dietary advice is high. However, there are no specific, evidence-based dietary guidelines. This scoping review summarises the literature on use and effectiveness of diet in the management of psoriasis to improve understanding of the evidence and assist PLwP and healthcare professionals (HCPs) to discuss diet. The findings were categorised into three themes: (1) dietary intakes of PLwP, (2) the perceived role of diet in psoriasis management and (3) dietary approaches to manage psoriasis symptoms. In cross-sectional studies PLwP were reported to have higher fat and lower fibre intakes compared with controls, and lower psoriasis severity was associated with higher fibre intake. However, research is limited. PLwP perceive diet to have an impact on symptoms and make dietary modifications which are often restrictive. Systematic reviews and RCTs found certain dietary approaches improved symptoms, but only in specific populations (e.g. PLwP with obesity and PLwP with coeliac disease), and evidence for supplement use is inconclusive. The grey literature provides limited guidance to PLwP; focusing on weight loss and associated comorbidities. Larger, controlled trials are required to determine dietary approaches for psoriasis management, especially in PLwP without obesity and non-coeliac PLwP. Further understanding of diet modification, information acquisition and experiences among PLwP will enhance holistic care for psoriasis management.
Interrogating multisystem intended pathways to youth thriving and resilience: Benefits of inclusive human development theoretical framing
Authors: Spencer Margaret Beale
Published: September 2023

Moving more deeply into the 21st century and acknowledging the ongoing patterned needs of children, there continues to be broadly voiced sentiments about the importance of all children’s thriving, adaptive coping, and resiliency. This paper notes that social science more broadly and developmental science specifically is a major resource determinative of the nature of remedies conceptualized, designed, and implemented. Evident is that the harms experienced by children and the solutions implemented by delivery systems are frequently unaligned. Efficacy and impact do not appear to be improved by multisystem integration delivery. This paper explores the benefits of incorporating inclusive and shared human development theory. As well, it examines the need to question the character virtue of the multisystem integration efforts intended to afford supportive solutions required for youths’ thriving and resiliency. Specifically, it addresses whether democratic and equity relevant character values are integrated into public and privately funded intended supportive systems. The position taken is that whether considered under conditions of trauma illustrated by the global COVID pandemic or the efficacy of systems intended to aid the most vulnerable youngsters, the character of the content of support and its delivery matter and can benefit from inclusive human development interrogation and theorizing.
Perceptional and actional enrichment for metaphor detection with sensorimotor norms
Authors: Wan Mingyu , Su Qi , Ahrens Kathleen , Huang Chu-Ren
Published: September 2023

Understanding the nature of meaning and its extensions (with metaphor as one typical kind) has been one core issue in figurative language study since Aristotle’s time. This research takes a computational cognitive perspective to model metaphor based on the assumption that meaning is perceptual, embodied, and encyclopedic. We model word meaning representation for metaphor detection with embodiment information obtained from behavioral experiments. Our work is the first attempt to incorporate sensorimotor knowledge into neural networks for metaphor detection, and demonstrates superiority, consistency, and interpretability compared to peer systems based on two general datasets. In addition, with cross-sectional analysis of different feature schemas, our results suggest that metaphor, as a device of cognitive conceptualization, can be ‘learned’ from the perceptual and actional information independent of several more explicit levels of linguistic representation. The access to such knowledge allows us to probe further into word meaning mapping tendencies relevant to our conceptualization and reaction to the physical world.
Maternal childhood maltreatment: associations to offspring brain volume and white matter connectivity
Authors: Lugo-Candelas Claudia , Chang Le , Dworkin Jordan D. , Aw Natalie , Fields Andrea , Reed Hannah , Spann Marisa , Gilchrist Michelle A. , Hinds Walter , Marsh Rachel , Fifer William P. , Weissman Myrna , Foerster Bernd Uwe , Manin Marina Giorgi , Silva Ivaldo , Peterson Bradley , Coelho Milani Ana Carolina , Gingrich Jay , Monk Catherine , Duarte Cristiane S. , Jackowski Andrea , Posner Jonathan
Published: September 2023

The deleterious effects of adversity are likely intergenerational, such that one generation’s adverse experiences can affect the next. Epidemiological studies link maternal adversity to offspring depression and anxiety, possibly via transmission mechanisms that influence offspring fronto-limbic connectivity. However, studies have not thoroughly disassociated postnatal exposure effects nor considered the role of offspring sex. We utilized infant neuroimaging to test the hypothesis that maternal childhood maltreatment (CM) would be associated with increased fronto-limbic connectivity in infancy and tested brain-behavior associations in childhood. Ninety-two dyads participated (32 mothers with CM, 60 without; 52 infant females, 40 infant males). Women reported on their experiences of CM and non-sedated sleeping infants underwent MRIs at 2.44 ± 2.74 weeks. Brain volumes were estimated via structural MRI and white matter structural connectivity (fiber counts) via diffusion MRI with probabilistic tractography. A subset of parents (n = 36) reported on children’s behaviors at age 5.17 ± 1.73 years. Males in the maltreatment group demonstrated greater intra-hemispheric fronto-limbic connectivity (b = 0.96, p= 0.008, [95%CI 0.25, 1.66]), no differences emerged for females. Fronto-limbic connectivity was related to somatic complaints in childhood only for males (r = 0.673, p = 0.006). Our findings suggest that CM could have intergenerational associations to offspring brain development, yet mechanistic studies are needed.
Balancing may be everywhere, but the proportionality test is not
Authors: da Silva Virgílio Afonso
Published: September 2023

The relationship between balancing and proportionality has not always been clear. Because part of the literature falls short of adequately differentiating between the two tools, many people have become conditioned to see an instance of proportionality whenever the word ‘balancing’ is dropped. As a consequence, the ubiquity of balancing brought about the feeling that proportionality is equally ubiquitous. In this article, I show that the proportionality test is necessarily linked to judicial review and how this link is key to understanding why not every instance of balancing is part of the proportionality test and that proportionality cannot be as ubiquitous as many have claimed. This has not only analytical relevance, but also institutional consequences.
Extension event attendance increases adoption of weed management practices by sports field managers
Authors: Frisvold George B. , Agme Chandrakant , Ervin David , Allen Jennifer , Askew Shawn , Bowling Rebecca Grubbs , Brosnan James , Elmore Matthew , Gannon Travis , Kaminski John , McCarty Lambert , McCurdy James D. , Patton Aaron J. , Taylor Jacob , Unruh J. Bryan , Bagavathiannan Muthukumar
Published: September 2023

Data from a national survey of 348 U.S. sports field managers were used to examine the effects of participation in Cooperative Extension events on the adoption of turfgrass weed management practices. Of the respondents, 94% had attended at least one event in the previous 3 yr. Of this 94%, 97% reported adopting at least one practice as a result of knowledge gained at an Extension turfgrass event. Half of the respondents had adopted four or more practices; a third adopted five or more practices. Nonchemical, cultural practices were the most-adopted practices (65% of respondents). Multiple regression analysis was used to examine factors explaining practice adoption and Extension event attendance. Compared to attending one event, attending three events increased total adoption by an average of one practice. Attending four or more events increased total adoption by two practices. Attending four or more events (compared to one event) increased the odds of adopting six individual practices by 3- to 6-fold, depending on the practice. This suggests that practice adoption could be enhanced by encouraging repeat attendance among past Extension event attendees. Manager experience was a statistically significant predictor of the number of Extension events attended but a poor direct predictor of practice adoption. Experience does not appear to increase adoption directly, but indirectly, via its impact on Extension event attendance. In addition to questions about weed management generally, the survey asked questions specifically about annual bluegrass management. Respondents were asked to rank seven sources of information for their helpfulness in managing annual bluegrass. There was no single dominant information source, but Extension was ranked more than any other source as the most helpful (by 22% of the respondents) and was ranked among the top three by 53%, closely behind field representative/local distributor sources at 54%.
European Summer Synoptic Circulations and Their Observed 2022 and Projected Influence on Hot Extremes and Dry Spells
Authors: Herrera‐Lormendez Pedro , Douville Hervé , Matschullat Jörg
Published: September 2023

In 2022, western Europe experienced its hottest summer on record and widespread dry conditions, with substantial impacts on health, water and vegetation. We use a reanalysis to classify daily mean sea level pressure fields and to investigate the influence of synoptic circulations on the occurrence of temperature extremes and dry days. Summer 2022 featured an above‐normal occurrence of anticyclones extending from the British Isles to the Baltic countries, as well as enhanced easterly, southerly and low‐flow conditions which contributed to the observed extremes over southern and western Europe. While the hot summer of 2022 is only partially explained by circulation anomalies, such anomalies played a key role in the exceptional occurrence of dry days. The comparison with summer circulation anomalies projected by twenty global climate models moreover suggests that future circulation changes will further exacerbate hot and dry extremes over Europe.
Fracture Permeability Enhancement During Fluid Injection Modulated by Pressurization Rate and Surface Asperities
Authors: Ji Yinlin , Zhang Wei , Hofmann Hannes , Cappa Frédéric , Zhang Supeng
Published: September 2023

We present a series of controlled fluid injection experiments in the laboratory on a pre‐stressed natural rough fracture with a high initial permeability (∼10−13 m2) in granite using different fluid pressurization rates. Our results show that fluid injection on a fracture with a slight velocity‐strengthening frictional behavior exhibits dilatant slow slip in association with a permeability increase up to ∼41 times attained at the maximum slip velocity of 0.085 mm/s for the highest‐rate injection case. Under these conditions, the slip velocity‐dependent change in hydraulic aperture is a dominant process to explain the transient evolution of fracture permeability, which is modulated by fluid pressurization rate and fracture surface asperities. This leads to the conclusion that permeability evolution can be engineered for subsurface geoenergy applications by controlling the fluid pressurization rate on slowly slipping fractures.
The Hydrologic Cycle and Atmospheric Rivers in CESM2 Simulations of the Last Glacial Maximum
Authors: Lora J. M. , Skinner C. B. , Rush W. D. , Baek S. H.
Published: September 2023

Proxy reconstructions and model simulations of precipitation during Earth's glacial periods suggest that the locations and mechanisms of atmospheric moisture transport have changed considerably during Earth's past. We investigate the hydroclimate of the Last Glacial Maximum (LGM) using simulations with the Community Earth System Model, with a focus on the extratropics and the influence of atmospheric rivers (ARs), a key driver of modern‐day moisture transport globally. Mean and extreme precipitation increase significantly over southwestern Patagonia, Iberia, and southwestern North America—mid‐latitude regions affected by ARs in the modern climate—despite overall decreases elsewhere. In each, the associated moisture transport changes are different, with increased transport and AR activity mainly occurring in the North Atlantic. The overall LGM response is dominated by the response to ice sheets, with other forcings causing additional cooling and drying over the extratropics and a strong decrease of moisture transport over the subpolar North Atlantic.
A copper-iodide cluster microcube-based X-ray scintillator
Authors: Qiu Jian , Liu Xiaogang
Published: September 2023

Newly developed copper-iodide cluster microcubes offer a solution to the issues commonly faced by powder scintillation screens. These problems include inadequate scintillation performance and significant light scattering, resulting in poor image quality. With the advent of monodisperse copper-iodide cluster microparticle scintillators, efficient and long-term stable scintillation is achieved, while ensuring biocompatibility. Moreover, they enable high-resolution static and dynamic X-ray imaging, providing high image quality.
Polarization patterns of light enable geolocalization in oceans
Authors: Wang Lihong V.
Published: September 2023

The deep ocean, characterized by its immense depths and absence of global positioning system (GPS) functionality, presents considerable challenges for search and rescue missions. Inspired by the geolocalization capabilities of migratory marine animals, Bai et al. present a novel method for underwater geolocalization using the polarization patterns of light in the underwater environment. Emulating a sextant using these underwater polarization patterns, the study determines geolocation in underwater settings. Despite prior skepticism, even in low-visibility waters, these patterns, learned through a deep neural network, provide geolocation accuracies of 55 km at 8 m and 255 km at 50 m. This pioneering approach offers implications for search and rescue and hints at navigation mechanisms in marine animals.
Long non-coding RNA SNHG8 drives stress granule formation in tauopathies
Authors: Bhagat Reshma , Minaya Miguel A. , Renganathan Arun , Mehra Muneshwar , Marsh Jacob , Martinez Rita , Eteleeb Abdallah M. , Nana Alissa L. , Spina Salvatore , Seeley William W. , Grinberg Lea T. , Karch Celeste M.
Published: September 2023

Tauopathies are a heterogenous group of neurodegenerative disorders characterized by tau aggregation in the brain. In a subset of tauopathies, rare mutations in the MAPT gene, which encodes the tau protein, are sufficient to cause disease; however, the events downstream of MAPT mutations are poorly understood. Here, we investigate the role of long non-coding RNAs (lncRNAs), transcripts >200 nucleotides with low/no coding potential that regulate transcription and translation, and their role in tauopathy. Using stem cell derived neurons from patients carrying a MAPT p.P301L, IVS10 + 16, or p.R406W mutation and CRISPR-corrected isogenic controls, we identified transcriptomic changes that occur as a function of the MAPT mutant allele. We identified 15 lncRNAs that were commonly differentially expressed across the three MAPT mutations. The commonly differentially expressed lncRNAs interact with RNA-binding proteins that regulate stress granule formation. Among these lncRNAs, SNHG8 was significantly reduced in a mouse model of tauopathy and in FTLD-tau, progressive supranuclear palsy, and Alzheimer’s disease brains. We show that SNHG8 interacts with tau and stress granule-associated RNA-binding protein TIA1. Overexpression of mutant tau in vitro is sufficient to reduce SNHG8 expression and induce stress granule formation. Rescuing SNHG8 expression leads to reduced stress granule formation and reduced TIA1 levels in immortalized cells and in MAPT mutant neurons, suggesting that dysregulation of this non-coding RNA is a causal factor driving stress granule formation via TIA1 in tauopathies.
Amphiregulin normalizes altered circuit connectivity for social dominance of the CRTC3 knockout mouse
Authors: Park Ji-Seon , Heo Hwon , Kim Min-Seok , Lee Seung-Eun , Park Sukyoung , Kim Ki-Hyun , Kang Young-Ho , Kim Je Seong , Sung Young Hoon , Shim Woo Hyun , Kim Dong-Hou , Song Youngsup , Yoon Seung-Yong
Published: September 2023

Social hierarchy has a profound impact on social behavior, reward processing, and mental health. Moreover, lower social rank can lead to chronic stress and often more serious problems such as bullying victims of abuse, suicide, or attack to society. However, its underlying mechanisms, particularly their association with glial factors, are largely unknown. In this study, we report that astrocyte-derived amphiregulin plays a critical role in the determination of hierarchical ranks. We found that astrocytes-secreted amphiregulin is directly regulated by cAMP response element-binding (CREB)-regulated transcription coactivator 3 (CRTC3) and CREB. Mice with systemic and astrocyte-specific CRTC3 deficiency exhibited a lower social rank with reduced functional connectivity between the prefrontal cortex, a major social hierarchy center, and the parietal cortex. However, this effect was reversed by astrocyte-specific induction of amphiregulin expression, and the epidermal growth factor domain was critical for this action of amphiregulin. These results provide evidence of the involvement of novel glial factors in the regulation of social dominance and may shed light on the clinical application of amphiregulin in the treatment of various psychiatric disorders.
Sex- and suicide-specific alterations in the kynurenine pathway in the anterior cingulate cortex in major depression
Authors: Brown Samara J. , Christofides Katerina , Weissleder Christin , Huang Xu-Feng , Shannon Weickert Cynthia , Lim Chai K. , Newell Kelly A.
Published: September 2023

Major depressive disorder (MDD) is a serious psychiatric disorder that in extreme cases can lead to suicide. Evidence suggests that alterations in the kynurenine pathway (KP) contribute to the pathology of MDD. Activation of the KP leads to the formation of neuroactive metabolites, including kynurenic acid (KYNA) and quinolinic acid (QUIN). To test for changes in the KP, postmortem anterior cingulate cortex (ACC) was obtained from the National Institute of Health NeuroBioBank. Gene expression of KP enzymes and relevant neuroinflammatory markers were investigated via RT-qPCR (Fluidigm) and KP metabolites were measured using liquid chromatography-mass spectrometry in tissue from individuals with MDD (n = 44) and matched nonpsychiatric controls (n = 36). We report increased IL6 and IL1B mRNA in MDD. Subgroup analysis found that female MDD subjects had significantly decreased KYNA and a trend decrease in the KYNA/QUIN ratio compared to female controls. In addition, MDD subjects that died by suicide had significantly decreased KYNA in comparison to controls and MDD subjects that did not die by suicide, while subjects that did not die by suicide had increased KYAT2 mRNA, which we hypothesise may protect against a decrease in KYNA. Overall, we found sex- and suicide-specific alterations in the KP in the ACC in MDD. This is the first molecular evidence in the brain of subgroup specific changes in the KP in MDD, which not only suggests that treatments aimed at upregulation of the KYNA arm in the brain may be favourable for female MDD sufferers but also might assist managing suicidal behaviour.
Neoadjuvant botensilimab plus balstilimab response pattern in locally advanced mismatch repair proficient colorectal cancer
Authors: Kasi Pashtoon Murtaza , Hidalgo Manuel , Jafari Mehraneh D. , Yeo Heather , Lowenfeld Lea , Khan Uqba , Nguyen Alana T. H. , Siolas Despina , Swed Brandon , Hyun Jini , Khan Sahrish , Wood Madeleine , Samstein Benjamin , Rocca Juan P. , Ocean Allyson J. , Popa Elizabeta C. , Hunt Daniel H. , Uppal Nikhil P. , Garrett Kelly A. , Pigazzi Alessio , Zhou Xi Kathy , Shah Manish A. , Hissong Erika
Published: September 2023

In patients with locally advanced cancer without distant metastases, the neoadjuvant setting presents a platform to evaluate new drugs. For mismatch repair proficient/microsatellite stable (pMMR/MSS) colon and rectal cancer, immunotherapy has shown limited efficacy. Herein, we report exceptional responses observed with neoadjuvant botensilimab (BOT), an Fc-enhanced next-generation anti–CTLA-4 antibody, alongside balstilimab (BAL; an anti-PD-1 antibody) in two patients with pMMR/MSS colon and rectal cancer. The histological pattern of rapid immune response observed (“inside-out” (serosa-to-mucosa) tumor regression) has not been described previously in this setting. Spatial biology analyses (RareCyte Inc.) reveal mechanisms of actions of BOT, a novel innate-adaptive immune activator. These observations have downstream implications for clinical trial designs using neoadjuvant immunotherapy and potentially sparing patients chemotherapy.
The role of cell death in SARS-CoV-2 infection
Authors: Yuan Cui , Ma Zhenling , Xie Jiufeng , Li Wenqing , Su Lijuan , Zhang Guozhi , Xu Jun , Wu Yaru , Zhang Min , Liu Wei
Published: September 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), showing high infectiousness, resulted in an ongoing pandemic termed coronavirus disease 2019 (COVID-19). COVID-19 cases often experience acute respiratory distress syndrome, which has caused millions of deaths. Apart from triggering inflammatory and immune responses, many viral infections can cause programmed cell death in infected cells. Cell death mechanisms have a vital role in maintaining a suitable environment to achieve normal cell functionality. Nonetheless, these processes are dysregulated, potentially contributing to disease pathogenesis. Over the past decades, multiple cell death pathways are becoming better understood. Growing evidence suggests that the induction of cell death by the coronavirus may significantly contributes to viral infection and pathogenicity. However, the interaction of SARS-CoV-2 with cell death, together with its associated mechanisms, is yet to be elucidated. In this review, we summarize the existing evidence concerning the molecular modulation of cell death in SARS-CoV-2 infection as well as viral-host interactions, which may shed new light on antiviral therapy against SARS-CoV-2.
Dispersal, habitat filtering, and eco-evolutionary dynamics as drivers of local and global wetland viral biogeography
Authors: ter Horst Anneliek M , Fudyma Jane D , Sones Jacqueline L , Emerson Joanne B
Published: September 2023

Wetlands store 20–30% of the world’s soil carbon, and identifying the microbial controls on these carbon reserves is essential to predicting feedbacks to climate change. Although viral infections likely play important roles in wetland ecosystem dynamics, we lack a basic understanding of wetland viral ecology. Here 63 viral size-fraction metagenomes (viromes) and paired total metagenomes were generated from three time points in 2021 at seven fresh- and saltwater wetlands in the California Bodega Marine Reserve. We recovered 12,826 viral population genomic sequences (vOTUs), only 4.4% of which were detected at the same field site two years prior, indicating a small degree of population stability or recurrence. Viral communities differed most significantly among the seven wetland sites and were also structured by habitat (plant community composition and salinity). Read mapping to a new version of our reference database, PIGEONv2.0 (515,763 vOTUs), revealed 196 vOTUs present over large geographic distances, often reflecting shared habitat characteristics. Wetland vOTU microdiversity was significantly lower locally than globally and lower within than between time points, indicating greater divergence with increasing spatiotemporal distance. Viruses tended to have broad predicted host ranges via CRISPR spacer linkages to metagenome-assembled genomes, and increased SNP frequencies in CRISPR-targeted major tail protein genes suggest potential viral eco-evolutionary dynamics in response to both immune targeting and changes in host cell receptors involved in viral attachment. Together, these results highlight the importance of dispersal, environmental selection, and eco-evolutionary dynamics as drivers of local and global wetland viral biogeography.
Feasibility of mass cytometry proteomic characterisation of circulating tumour cells in head and neck squamous cell carcinoma for deep phenotyping
Authors: Payne Karl , Brooks Jill , Batis Nikolaos , Khan Naeem , El-Asrag Mohammed , Nankivell Paul , Mehanna Hisham , Taylor Graham
Published: September 2023

Background

Circulating tumour cells (CTCs) are a potential cancer biomarker, but current methods of CTC analysis at single-cell resolution are limited. Here, we describe high-dimensional single-cell mass cytometry proteomic analysis of CTCs in HNSCC.

Methods

Parsortix microfluidic-enriched CTCs from 14 treatment-naïve HNSCC patients were analysed by mass cytometry analysis using 41 antibodies. Immune cell lineage, epithelial-mesenchymal transition (EMT), stemness, proliferation and immune checkpoint expression was assessed alongside phosphorylation status of multiple signalling proteins. Patient-matched tumour gene expression and CTC EMT profiles were compared. Standard bulk CTC RNAseq was performed as a baseline comparator to assess mass cytometry data.

Results

CTCs were detected in 13/14 patients with CTC counts of 2–24 CTCs/ml blood. Unsupervised clustering separated CTCs into epithelial, early EMT and advanced EMT groups that differed in signalling pathway activation state. Patient-specific CTC cluster patterns separated into immune checkpoint low and high groups. Patient tumour and CTC EMT profiles differed. Mass cytometry outperformed bulk RNAseq to detect CTCs and characterise cell phenotype.

Discussion

We demonstrate mass cytometry allows high-plex proteomic characterisation of CTCs at single-cell resolution and identify common CTC sub-groups with potential for novel biomarker development and immune checkpoint inhibitor treatment stratification.
Sheptide A: an antimalarial cyclic pentapeptide from a fungal strain in the Herpotrichiellaceae
Authors: Shepherd Robert A. , Earp Cody E. , Cank Kristof B. , Raja Huzefa A. , Burdette Joanna , Maher Steven P. , Marin Adriana A. , Ruberto Anthony A. , Mai Sarah Lee , Darveaux Blaise A. , Kyle Dennis E. , Pearce Cedric J. , Oberlies Nicholas H.
Published: September 2023

As part of ongoing efforts to isolate biologically active fungal metabolites, a cyclic pentapeptide, sheptide A (1), was discovered from strain MSX53339 (Herpotrichiellaceae). The structure and sequence of 1 were determined primarily by analysis of 2D NMR and HRMS/MS data, while the absolute configuration was assigned using a modified version of Marfey’s method. In an in vitro assay for antimalarial potency, 1 displayed a pEC50 value of 5.75 ± 0.49 against malaria-causing Plasmodium falciparum. Compound 1 was also tested in a counter screen for general cytotoxicity against human hepatocellular carcinoma (HepG2), yielding a pCC50 value of 5.01 ± 0.45 and indicating a selectivity factor of ~6. This makes 1 the third known cyclic pentapeptide biosynthesized by fungi with antimalarial activity.
Diagnostic accuracy of self-reported age-related macular degeneration in the ASPREE Longitudinal Study of Older Persons
Authors: McGuinness Myra B. , Robman Liubov , Hodgson Lauren A. B. , Tran Cammie , Woods Robyn L. , Owen Alice J. , McNeil John J. , Makeyeva Galina , Abhayaratna Walter P. , Guymer Robyn H.
Published: September 2023

Background

The validity of findings from epidemiological studies using self-report of ophthalmic conditions depends on several factors. We assessed the diagnostic accuracy of self-reported age-related macular degeneration (AMD) among older Australians enroled in a primary prevention clinical trial and compared diagnostic accuracy between demographic subgroups.

Methods

At baseline (2010–2015), Australian sub-study participants of the ASPirin in Reducing Events in the Elderly (ASPREE) trial, underwent bilateral two-field, 45° non-mydriatic colour retinal photography. Beckman classification of any-stage AMD was used as the reference standard diagnosis. Participants were asked whether a doctor had ever diagnosed them with “macular degeneration” (the index test) via a paper-based questionnaire as part of the ASPREE Longitudinal Study of Older Persons (ALSOP) within the first year of enrolment.

Results

In total, 4193 participants were included (aged 70–92 years, 50.8% female). Of those, 262 (6.3%) reported having AMD and 92 (2.2%) were unsure. Retinal grading detected 2592 (61.8%) with no AMD, 867 (20.7%) with early, 686 (16.4%) with intermediate and 48 (1.1%) with late AMD (n = 1601 with any-stage AMD, 38.2%). Self-reported AMD had 11.4% sensitivity (95% CI 9.9–13.1) and 96.9% specificity (95% CI 96.2–97.6) for any-stage AMD, with 69.8% and 63.9% positive and negative predictive values. Sensitivity was higher among participants with late-stage AMD (87.5%), older participants (26.8%), and those with poorer vision (41.0%).

Conclusions

Although most participants with late-stage AMD were aware of having AMD, the majority with early and intermediate AMD were not. Therefore, findings from studies that rely on disease self-report should be interpreted with caution.
A subset of viruses thrives following microbial resuscitation during rewetting of a seasonally dry California grassland soil
Authors: Nicolas Alexa M. , Sieradzki Ella T. , Pett-Ridge Jennifer , Banfield Jillian F. , Taga Michiko E. , Firestone Mary K. , Blazewicz Steven J.
Published: September 2023

Viruses are abundant, ubiquitous members of soil communities that kill microbial cells, but how they respond to perturbation of soil ecosystems is essentially unknown. Here, we investigate lineage-specific virus-host dynamics in grassland soil following “wet-up”, when resident microbes are both resuscitated and lysed after a prolonged dry period. Quantitative isotope tracing, time-resolved metagenomics and viromic analyses indicate that dry soil holds a diverse but low biomass reservoir of virions, of which only a subset thrives following wet-up. Viral richness decreases by 50% within 24 h post wet-up, while viral biomass increases four-fold within one week. Though recent hypotheses suggest lysogeny predominates in soil, our evidence indicates that viruses in lytic cycles dominate the response to wet-up. We estimate that viruses drive a measurable and continuous rate of cell lysis, with up to 46% of microbial death driven by viral lysis one week following wet-up. Thus, viruses contribute to turnover of soil microbial biomass and the widely reported CO2 efflux following wet-up of seasonally dry soils.
epiAneufinder identifies copy number alterations from single-cell ATAC-seq data
Authors: Ramakrishnan Akshaya , Symeonidi Aikaterini , Hanel Patrick , Schmid Katharina T. , Richter Maria L. , Schubert Michael , Colomé-Tatché Maria
Published: September 2023

Single-cell open chromatin profiling via scATAC-seq has become a mainstream measurement of open chromatin in single-cells. Here we present epiAneufinder, an algorithm that exploits the read count information from scATAC-seq data to extract genome-wide copy number alterations (CNAs) for individual cells, allowing the study of CNA heterogeneity present in a sample at the single-cell level. Using different cancer scATAC-seq datasets, we show that epiAneufinder can identify intratumor clonal heterogeneity in populations of single cells based on their CNA profiles. We demonstrate that these profiles are concordant with the ones inferred from single-cell whole genome sequencing data for the same samples. EpiAneufinder allows the inference of single-cell CNA information from scATAC-seq data, without the need of additional experiments, unlocking a layer of genomic variation which is otherwise unexplored.
Organisation of the orthobunyavirus tripodal spike and the structural changes induced by low pH and K+ during entry
Authors: Hover Samantha , Charlton Frank W. , Hellert Jan , Swanson Jessica J. , Mankouri Jamel , Barr John N. , Fontana Juan
Published: September 2023

Following endocytosis, enveloped viruses employ the changing environment of maturing endosomes as cues to promote endosomal escape, a process often mediated by viral glycoproteins. We previously showed that both high [K+] and low pH promote entry of Bunyamwera virus (BUNV), the prototypical bunyavirus. Here, we use sub-tomogram averaging and AlphaFold, to generate a pseudo-atomic model of the whole BUNV glycoprotein envelope. We unambiguously locate the Gc fusion domain and its chaperone Gn within the floor domain of the spike. Furthermore, viral incubation at low pH and high [K+], reminiscent of endocytic conditions, results in a dramatic rearrangement of the BUNV envelope. Structural and biochemical assays indicate that pH 6.3/K+ in the absence of a target membrane elicits a fusion-capable triggered intermediate state of BUNV GPs; but the same conditions induce fusion when target membranes are present. Taken together, we provide mechanistic understanding of the requirements for bunyavirus entry.
Blue organic light-emitting diode with a turn-on voltage of 1.47 V
Authors: Izawa Seiichiro , Morimoto Masahiro , Fujimoto Keisuke , Banno Koki , Majima Yutaka , Takahashi Masaki , Naka Shigeki , Hiramoto Masahiro
Published: September 2023

Among the three primary colors, blue emission in organic light-emitting diodes (OLEDs) are highly important but very difficult to develop. OLEDs have already been commercialized; however, blue OLEDs have the problem of requiring a high applied voltage due to the high-energy of blue emission. Herein, an ultralow voltage turn-on at 1.47 V for blue emission with a peak wavelength at 462 nm (2.68 eV) is demonstrated in an OLED device with a typical blue-fluorescent emitter that is widely utilized in a commercial display. This OLED reaches 100 cd/m2, which is equivalent to the luminance of a typical commercial display, at 1.97 V. Blue emission from the OLED is achieved by the selective excitation of the low-energy triplet states at a low applied voltage by using the charge transfer (CT) state as a precursor and triplet-triplet annihilation, which forms one emissive singlet from two triplet excitons.
Disentangling age, gender, and racial/ethnic disparities in multiple myeloma burden: a modeling study
Authors: Huber John H. , Ji Mengmeng , Shih Yi-Hsuan , Wang Mei , Colditz Graham , Chang Su-Hsin
Published: September 2023

Multiple myeloma (MM) is a hematological malignancy that is consistently preceded by an asymptomatic condition, monoclonal gammopathy of undetermined significance (MGUS). Disparities by age, gender, and race/ethnicity in both MGUS and MM are well-established. However, it remains unclear whether these disparities can be explained by increased incidence of MGUS and/or accelerated progression from MGUS to MM. Here, we fit a mathematical model to nationally representative data from the United States and showed that the difference in MM incidence can be explained by an increased incidence of MGUS among male and non-Hispanic Black populations. We did not find evidence showing differences in the rate of progression from MGUS to MM by either gender or race/ethnicity. Our results suggest that screening for MGUS among high-risk groups (e.g., non-Hispanic Black men) may hold promise as a strategy to reduce the burden and MM health disparities.
Microrollers flow uphill as granular media
Authors: Wilson-Whitford Samuel R. , Gao Jinghui , Roffin Maria Chiara , Buckley William E. , Gilchrist James F.
Published: September 2023

Pour sand into a container and only the grains near the top surface move. The collective motion associated with the translational and rotational energy of the grains in a thin flowing layer is quickly dissipated as friction through multibody interactions. Alternatively, consider what will happen to a bed of particles if one applies a torque to each individual particle. In this paper, we demonstrate an experimental system where torque is applied at the constituent level through a rotating magnetic field in a dense bed of microrollers. The net result is the grains roll uphill, forming a heap with a negative angle of repose. Two different regimes have been identified related to the degree of mobility or fluidisation of the particles in the bulk. Velocimetry of the near surface flowing layer reveals the collective motion of these responsive particles scales in a similar way to flowing bulk granular flows. A simple granular model that includes cohesion accurately predicts the apparent negative coefficient of friction. In contrast to the response of active or responsive particles that mimic thermodynamic principles, this system results in macroscopic collective behavior that has the kinematics of a purely dissipative granular system.
Capturing dynamical correlations using implicit neural representations
Authors: Chitturi Sathya R. , Ji Zhurun , Petsch Alexander N. , Peng Cheng , Chen Zhantao , Plumley Rajan , Dunne Mike , Mardanya Sougata , Chowdhury Sugata , Chen Hongwei , Bansil Arun , Feiguin Adrian , Kolesnikov Alexander I. , Prabhakaran Dharmalingam , Hayden Stephen M. , Ratner Daniel , Jia Chunjing , Nashed Youssef , Turner Joshua J.
Published: September 2023

Understanding the nature and origin of collective excitations in materials is of fundamental importance for unraveling the underlying physics of a many-body system. Excitation spectra are usually obtained by measuring the dynamical structure factor, S(Q, ω), using inelastic neutron or x-ray scattering techniques and are analyzed by comparing the experimental results against calculated predictions. We introduce a data-driven analysis tool which leverages ‘neural implicit representations’ that are specifically tailored for handling spectrographic measurements and are able to efficiently obtain unknown parameters from experimental data via automatic differentiation. In this work, we employ linear spin wave theory simulations to train a machine learning platform, enabling precise exchange parameter extraction from inelastic neutron scattering data on the square-lattice spin-1 antiferromagnet La2NiO4, showcasing a viable pathway towards automatic refinement of advanced models for ordered magnetic systems.
Fgf signalling triggers an intrinsic mesodermal timer that determines the duration of limb patterning
Authors: Sedas Perez Sofia , McQueen Caitlin , Stainton Holly , Pickering Joseph , Chinnaiya Kavitha , Saiz-Lopez Patricia , Placzek Marysia , Ros Maria A. , Towers Matthew
Published: September 2023

Complex signalling between the apical ectodermal ridge (AER - a thickening of the distal epithelium) and the mesoderm controls limb patterning along the proximo-distal axis (humerus to digits). However, the essential in vivo requirement for AER-Fgf signalling makes it difficult to understand the exact roles that it fulfils. To overcome this barrier, we developed an amenable ex vivo chick wing tissue explant system that faithfully replicates in vivo parameters. Using inhibition experiments and RNA-sequencing, we identify a transient role for Fgfs in triggering the distal patterning phase. Fgfs are then dispensable for the maintenance of an intrinsic mesodermal transcriptome, which controls proliferation/differentiation timing and the duration of patterning. We also uncover additional roles for Fgf signalling in maintaining AER-related gene expression and in suppressing myogenesis. We describe a simple logic for limb patterning duration, which is potentially applicable to other systems, including the main body axis.