bluuebunny/crossref_metadata_2025 huggingface dataset:
Children in Uniform
Authors: Hurl-Eamon Jennine
Published: January 2025

After assuming command of the Army in the 1790s, the Duke of York simultaneously limited boys under 16 from becoming officers while increasing the number of boys permitted to serve in the other ranks. Though on the surface this suggests that the Army cared more about protecting elite boys from war’s dangers, boys of all ranks had much in common. The Army saw all boys as useless in comparison to their adult counterparts. Their advantage consisted in their higher willingness to enlist and their lower pay. For civilians, boys’ entry into the Army reduced the potential for youthful misrule. Military commanders promised to treat younger soldiers with compassion, but rarely delivered. Dressed in ill-fitting uniforms, boys received less rations than men, though the calorie needs of growing lads were actually higher. They were also vulnerable to the hazing and immoral influences of the men around them. Officers sometimes exercised more leniency on younger courts martial defendants, but this was not guaranteed. Boy soldiers experienced combat similar to their older counterparts, and were more likely to engage in dangerous acts of bravery to defy those who denounced them for their youth. The Enlightenment might have tasked adults with protecting child innocence, but it also advocated training youngsters to realize their full potential. The Army shared this focus on the future adult, ignoring the needs of the child in order to get the most out of the man he would become.
Thematic Dative Plurals in Early Greek Hexameter Poetry
Authors: McConnell Tom
Published: January 2025

This chapter focusses on thematic dative plurals. For this linguistic feature perhaps most of all, it is found that dialect is the probably the most relevant factor, and that chronology is hard to establish. Having set out the dialectal situation, it is argued that once again, formulae are very important, and also metre—so much so, that the analysis can only be carried out by splitting up the data into groups based on metrical shape, like for the genitives. Here also it is found that it is difficult to maintain a chronological interpretation of the data, and that a dialectal one appears much more likely.
Homeric Speech, Narrative, and Style
Authors: McConnell Tom
Published: January 2025

This chapter picks up on the chapter on tmesis, and goes into much more detail about how and why Homeric speech and narrative act differently in how they use this linguistic feature. After some preliminaries and definitions, it is argued that the degree of continuity between performances is crucial for how the poets created different linguistic registers for different kinds of poetry, given recomposition-in-performance. The arguments made here will go on to be used in a similar fashion in the subsequent chapter, which will expand the scope of the analysis to include different genres of early Greek hexameter poetry. The concept of recomposition-in-performance is therefore key, and discussed at length here.
Register in Early Greek Hexameter Poetry
Authors: McConnell Tom
Published: January 2025

This chapter follows on from the previous, but expands the scope of the discussion, in that it thinks about how different sub-genres of early Greek hexameter poetry might have been composed with more or less consistency diachronically. After some discussion and definitions, the chapter discusses what we can know about our main non-heroic sub-genres and their prehistory—cosmogony, didactic, and hymnic hexameter. It then turns to a second argument, picking up a recurring theme of Part 1, which concerns formulae. It is argued that formulae exert a significant analogical pressure in terms of the linguistic archaisms often contained within, and therefore that poems with relatively fewer formulae are therefore less likely to exhibit linguistic archaisms.
Conclusion
Authors: McConnell Tom
Published: January 2025

The concluding chapter ties together all the threads of all the preceding chapters. It argues that there are a great many factors in understanding the distribution of the artificial language of the corpus. Chronology is almost certainly an operant factor, but there are so many complications (both ‘external’, i.e. dialect and stylistic and ‘internal’, i.e. formulae and meter) that it is extremely difficult to draw meaningful chronological conclusions about the texts, and therefore that glottochronology is extremely difficult for early Greek hexameter poetry. It is also argued that style is a much more important factor than previously realized, and that this is tied to the prehistory of the different performance traditions.
The Topography of Nonviolence
Authors: Devji Faisal
Published: January 2025

As the father of his nation Gandhi is naturally associated with India’s territory. From his ideas about home rule and village republics to mobilizing peasants in the country’s heartland, the Mahatma’s mission was linked with the vast landmass of India. Yet Gandhi was born in a port city that served as a gateway for Gujarat’s commerce across the Indian Ocean, a trail which he followed first as a student to London and then as a lawyer in South Africa. Moving between land and sea, Gandhi was able to unsettle the territorial foundations of India’s colonial society with new ideas and practices from everywhere and nowhere. Even his manifesto of 1909, Hind Swaraj, was written on board a ship. Rather than vanishing into the great territorial expanses of the subcontinent, this shifting and even liquid world of ideas, images, and practices allowed Indians to free and transform themselves, even while their land was in the possession of others.
A Rasātmaka Journey
Authors: Shukla-Bhatt Neelima
Published: January 2025

In the vast scholarship on M. K. Gandhi, his aesthetic sensibility has received little attention compared to his political action and thought on nonviolence. Yet an examination of his writings and communications reveals that his aesthetic sensibility was integrally linked to them. Contrary to the general perception about his indifference or utilitarian approach to art, he, in fact, saw life itself as art. He searched for a unity of truth, goodness, and beauty in all aspects of life. Nonviolence, expressed through moral action, was a path to realize that unity. Taking a cue from Gandhi’s reference to his ‘Experiments with Truth’ as a source of rasa (aesthetic relishing) in his ‘autobiography’, this chapter examines how the aesthetic and the moral were woven in Gandhi’s quest. It proposes that of the various interpretations of rasa in Indian aesthetics, the one sought by Gandhi comes closest to śāntarasa (tranquil mood) as expounded by the eleventh-century mystic Abhinavagupta, who compared it to the bliss experienced in meditation.
The Number Sense of Nineteenth-Century British Literature
Authors: Markovits Stefanie
Published: January 2025

The Number Sense of Nineteenth-Century British Literature considers how the avalanche of printed numbers characterizing the period affected its literature. While it touches on the rise of statistics and developments in politics and mathematics, this book takes as its starting point the presence of actual numbers—ordinal and cardinal, Arabic, Roman, or spelled out in words—within the century’s literary texts. It is through the deployment of such figures that texts display their number sense; similarly, readers develop the faculty of number sense by paying attention to their presence. And while it often takes us back to a specific historical context, attention to a text’s use of numbers also enables more fundamental recognitions about how literature makes meaning. The book asks what kinds of work, intellectual and ethical, literature’s numerical figures perform. Why are some writers especially numbery? What affordances do numbers wield in various literary environments and against a specific historical backdrop? How do they relate to aspects like plot and character, narrative and lyric? How do they interact with seriality, so central to nineteenth-century publication? When do the numbers really count, and when do they ask us to keep count? Lingering over texts’ measures illuminates the way numbers help shape literary works into the recognizable forms we call genres; one marks both lyric and the Bildungsroman but looks very different in each setting. Number sense uncovers how numbers can serve both as valves, releasing cultural pressures, and as fulcrums, places where pressures coincide to create new forms of literary agency.
Byron’s Counts
Authors: Markovits Stefanie
Published: January 2025

Romantic poets are very numbery. William Wordsworth is a renowned poet of number; his “egotistical sublime” manifests not only in a lyric devotion to the singularity that is one but also in a wider deployment of counts. Yet the measures and tallies in his verse generally reveal a distrust of number. In contrast, while Byron’s numbers in Don Juan may occasionally mislead, they also yield positive forms of meaning. Byron uses the generic affordances of narrative verse to encourage counting in order to manage the challenge, in the age of Malthus, that experiences of proliferation pose to a sympathy-based, Enlightenment ethics—especially in the case of collective disasters such as war. Don Juan teaches readers how to get a feel for counting, a process that can lead from the one toward the many. This lesson is delivered formally, through the poem’s use of ottava rima, as it addresses issues of number, genre, and naming.
Jane Austen, by Half
Authors: Markovits Stefanie
Published: January 2025

The novels of the notoriously numbery Jane Austen exhibit a surprising preponderance of the fraction half. Chapter 2 considers this “rational number” as a kind of generic marker of the matching processes undergirding the courtship or marriage plot and as a measure of Austen’s ontology. Looking at Austen’s interest in halves reveals her ambivalence regarding the perfect fit of wholes, which, while the telos and ultimate source happiness in her writing, also represent structures of disciplinary containment (broadly social and, via the novel, generic) that arise in response to a scarcity economics that Austen knows well to fear. The chapter ends by tracking these same forces at play in George Gissing’s The Odd Women, another peculiarly half-rich text the from later in the century that engages both issues of money and the Woman Question.
Figuring Character in Dickens
Authors: Markovits Stefanie
Published: January 2025

Chapter 3 focuses broadly on how numbers have intersected with characterological description before homing in on how Charles Dickens’s treatment of name, number, and character offers a rejoinder to the novel numberiness of liberal democracy. Dickens’s novels have long been recognized as testing grounds for ideas of character (flat and round, major and the minor) as they present the struggle of The One vs. the Many, in Alex Woloch’s formulation. But A Tale of Two Cities has proved especially fertile in this regard in recent years. This fact relates to this novel’s unusual numerical saturation. A Tale reveals that the politics of character is always, on some level, a politics of number. A coda turns to Lewis Carroll’s Alice in Wonderland, reflecting on its modes of characterization in relation to those of Dickens’s revolutionary novel—and to the preeminent genre of individualist singularity, the Bildungsroman.
Conclusion
Authors: Markovits Stefanie
Published: January 2025

The Conclusion reprises the Introduction via an exploration of two more sets of threes, in Wilkie Collins’s Armadale and Thomas Hardy’s first published novel, Desperate Remedies. In these novels, the third time is not so much a charm as the ultimate proof of a pattern or series. Both sensation novels thus use this figure to think through ancient ideas of fate, chance, and agency against the numbery backdrop of modernity. The novels’ numbers reflect the development of “statistical fatalism” or “statistical determinism,” as modern causalities of risk coexist with other, older modes. They thereby demonstrate the how the Law of Large Numbers was sometimes misapplied to smaller ones. Their prominent threes thus operate at the weird convergence of old and new, emotional and rational, and scientific and aesthetic methods of signification, offering a perfect opportunity to exercise readers’ number sense.
Does Amsterdam criteria applied to largely unsubmitted term placentas with favorable fetal outcomes show significant maternal clinicopathologic correlation?
Authors: Fortes Precious Ann , Janzen Carla , Lei Margarida Y Y , Vangala Sitaram , Sung Kyunghyun , Devaskar Sherin U , Sullivan Peggy S
Published: January 2025

Objectives

Before the Amsterdam Placental Workshop Group Consensus Statement, standardization in placental pathology assessment did not exist. This study evaluated the Amsterdam criteria’s utility in correlating ischemic placental disease (IPD) with placental pathologic lesions in a cohort of largely unsubmitted term placentas with favorable outcomes.

Methods

In this prospective case-controlled study at a single institution, all placentas were examined using Amsterdam protocols for gross sampling and microscopic review by 2 reviewers who were blinded to clinical history. Pathologic findings including hypoxic and chronic villitis of unknown etiology (VUE) scores were correlated with IPD status and whether the placenta was submitted to pathology using either a χ² test or Fisher exact test, as appropriate.

Results

A total of 172 placentas collected between 2017 and 2020 were included. Approximately 18.6% (n = 32) were in the IPD group, and 81.4% (n = 140) were in the non-IPD group. No statistically significant differences in microscopic findings were seen in ascending infection, maternal vascular malperfusion, fetal vascular malperfusion, or VUE between groups or by submission status. When tabulated as a hypoxic score, placentas from the IPD group were associated with greater hypoxic scores compared to non-IPD placentas (P = .011). A positive association was observed between greater VUE scores and hypoxic scores (P = .007).

Conclusions

In largely unsubmitted term placentas, the microscopic findings per Amsterdam criteria may be nonspecific. When tabulated as hypoxic or VUE scores, however, some clinicopathologic correlation may be seen in the setting of IPD. Further work is needed to refine the thresholds of meaningful reporting of placental pathology using the Amsterdam criteria.
Evidence Supports the Validity and Reliability of Response Times from a Brief Survey as a Digital Biomarker for Processing Speed in a Large Panel Study
Authors: Hernandez Raymond , Stone Arthur A , Zelinski Elizabeth , Meijer Erik , Galama Titus , Faul Jessica , Kapteyn Arie , Junghaenel Doerte U , Jin Haomiao , Gatz Margaret , Lee Pey-Jiuan , Maupin Daniel , Gao Hongxin , Orriens Bart , Schneider Stefan
Published: January 2025

Survey response times (RTs) have hitherto untapped potential to allow researchers to gain more detailed insights into the cognitive performance of participants in online panel studies. We examined if RTs recorded from a brief online survey could serve as a digital biomarker for processing speed. Data from 9,893 adults enrolled in the nationally representative Understanding America Study were used in the analyses. Hypotheses included that people’s average survey RTs would have a large correlation with an established processing speed test, small to moderate correlations with other cognitive tests, and associations with functional impairment. We also hypothesized that survey RTs would have sensitivity to various participant characteristics comparable to the established processing speed test’s sensitivity (e.g., similar standardized means by gender). Overall, results support the validity and reliability of people’s average RTs to survey items as a digital biomarker for processing speed. The correlation between survey RTs (reverse scored) and the formal processing speed test was 0.61 (p<0.001), and small to moderate associations with most other cognitive and functional status measures were observed. Sensitivity of survey RTs to various participant characteristics was nearly identical to the formal processing speed test. Survey RTs may be useful as proxies for processing speed.
Trends in use of tobacco and cannabis across different alcohol consumption levels in the United States, 2010–19
Authors: Pham Huyen , Bui Thanh C , Glass Joseph E , Back Sudie E , Le Phuc
Published: January 2025

Aims

People often drink alcohol and use other substances concurrently, increasing the risk of adverse health outcomes. Our aims were to: (i) assess temporal trends in tobacco and/or cannabis use by varying alcohol consumption levels and (ii) identify associated factors of polysubstance use in high-risk alcohol users.

Methods

We conducted a repeated cross-sectional study combining 2010–19 U.S. National Survey of Drug Use and Health (NSDUH). Alcohol consumption was categorized as no use, low-risk use, and high-risk use. Outcomes include past-month tobacco and/or cannabis use, nicotine dependence, and/or frequent cannabis use. We employed linear time trends and multivariable logistic regressions.

Results

We included 395 256 participants aged ≥18 years. From 2010 to 2019, the prevalence of tobacco use and nicotine dependence decreased while that of any and frequent cannabis use increased (P < .05). Tobacco use decreased faster in people with low−/high-risk alcohol use than no use (24% and 22% vs. 16%), whereas any cannabis use increased more rapidly in the no use group (155% vs. 77% in low- and 31% increase in high-risk groups). Among those with high-risk alcohol use, Hispanic individuals were less likely to use tobacco, cannabis, and both tobacco and cannabis, while non-Hispanic Black (NH Black) were more likely to use cannabis and both tobacco and cannabis than NH White counterparts (P < .05).

Conclusion

Past-month tobacco use decreased, while cannabis use increased significantly across all alcohol consumption levels. Sociodemographic subgroups, such as NH Black individuals and those with psychiatric comorbidities, showed increased odds of polysubstance use, underscoring the need for targeted public health interventions.
Estimating the time-varying emission rate of peracetic acid
Authors: Hines Ryan , Chen Chun-Yu , Nicas Mark , Ramachandran Gurumurthy
Published: January 2025

The use of peracetic acid (PAA) as a general disinfectant has seen increasing usage in recent years, and although it is a strong irritant, exposure monitoring for PAA may often be difficult due to relatively high costs and the potential for interferences by other co-occurring chemicals such as hydrogen peroxide. These issues with exposure monitoring make modeling a potentially useful tool in exposure assessment of PAA if model parameters can be accurately determined. This study estimates the time-varying mass emission rate of PAA for use in exposure modeling by using the small spill model and examines the effect of various environmental conditions on the PAA evaporation rate, including surface roughness/substrate, general ventilation rate, and local wind speed. The relatively high evaporation rate constant (1.18 min−1) determined did not vary significantly with these parameters, suggesting it is applicable across a wide range of common environmental conditions. In addition, in a controlled chamber setting, the first-order decay rate constant for PAA in air was determined to be 0.5 h−1. The corresponding half-life of 83 min is approximately 4 times longer than previous estimates. This decay rate should be accounted for in future modeling and exposure assessments. To evaluate the estimated evaporation rate, trials were conducted in a highly controlled exposure chamber using conditions similar to those found in healthcare settings to compare predicted modeled concentrations to those made by a real-time detection instrument, SafeCide 2.0 (ChemDAQ, Inc.). The results of the trials indicate that the evaporation rate constant and well-mixed room model perform well in predicting the concentration of PAA over a range of conditions. Moreover, the modeling results and measured concentrations across all trials indicate a high potential for overexposure to PAA. Therefore, exposure controls must be adequate when considering the use of PAA as a general disinfectant.
Crypt4GH-JS: securely storing sensitive data online with client-side encryption
Authors: Thelen Fabienne , Hochmuth Jannis , Griep Sven , Schwab Benedikt , Goesmann Alexander , Förster Frank
Published: January 2025

Motivation and Results

Crypt4GH-JS is a browser-ready implementation of the Crypt4GH file encryption standard written in JavaScript. While having minimal to no impact on data upload and download throughput this library enables on-the-fly encryption of arbitrary data in web applications, regardless of whether on the client or server side. As development moves more and more toward cloud-native applications, this library represents a significant step forward for flexible data security in the context of opaque cloud storage systems.

Availability and implementation

Crypt4GH-JS can be installed via Node Package Manager (https://www.npmjs.com/package/crypt4gh_js) or through its public GitHub Repository (https://github.com/fathelen/crypt4ghJS), where the source code is available. Crypt4GH-JS can be tested in the browser using our demonstration website, which can be found at: https://fathelen.github.io/crypt4ghJS/.
Unveiling Schizophrenia: a study with generalized functional linear mixed model via the investigation of functional random effects
Authors: Rui Rongxiang , Xiong Wei , Pan Jianxin , Tian Maozai
Published: January 2025

Previous studies have identified attenuated pre-speech activity and speech sound suppression in individuals with Schizophrenia, with similar patterns observed in basic tasks entailing button-pressing to perceive a tone. However, it remains unclear whether these patterns are uniform across individuals or vary from person to person. Motivated by electroencephalographic (EEG) data from a Schizophrenia study, we develop a generalized functional linear mixed model (GFLMM) for repeated measurements by incorporating subject-specific functional random effects associated with multiple functional predictors. To assess the significance of these functional effects, we employ two different multivariate functional principal component analysis methods, which transform the GFLMM into a conventional generalized linear mixed model, thereby facilitating its implementation with standard software. Furthermore, we introduce a cutting-edge testing approach utilizing working responses to detect both subject-specific and predictor-specific functional random effects. Monte Carlo simulation studies demonstrate the effectiveness of our proposed testing method. Application of the proposed methods to the Schizophrenia data reveals significant subject-specific effects of human brain activity in the frontal zone (Fz) and the central zone (Cz), providing valuable insights into the potential variations among individuals, from healthy controls to those diagnosed with Schizophrenia.
Evaluation of the Foot Function Index in pachyonychia congenita
Authors: Oldham Jaimie , Stuart Beth L , McCarthy Rebecca L , Schwartz Janice , Evans Holly , Hansen David , O’Toole Edel A
Published: January 2025

Pachyonychia congenita has a significant impact on the Foot Function Index (FFI) comparable with that seen in rheumatoid arthritis. Some genotypes have a greater impact than others. The FFI will be a helpful tool for clinical research in this area.
Contributions of connectional pathways to shaping Alzheimer’s disease pathologies
Authors: Bougacha Salma , Roquet Daniel , Landeau Brigitte , Saul Elise , Naveau Mikaël , Sherif Siya , Bejanin Alexandre , Dhenain Marc , Raj Ashish , Vivien Denis , Chetelat Gaël
Published: January 2025

Four important imaging biomarkers of Alzheimer’s disease, namely grey matter atrophy, glucose hypometabolism and amyloid-β and tau deposition, follow stereotypical spatial distributions shaped by the brain network of structural and functional connections. In this case-control study, we combined several predictors reflecting various possible mechanisms of spreading through structural and functional pathways to predict the topography of the four biomarkers in amyloid-positive patients while controlling for the effect of spatial distance along the cortex. For each biomarker, we quantified the relative contribution of each predictor to the variance explained by the model. We also compared the contribution between apolipoprotein E-ɛ4 carriers and non-carriers. We found that topological proximity to areas of maximal pathology through the functional connectome explained significant parts of variance for all biomarkers and that functional pathways totalized more than 30% of contributions for hypometabolism and amyloid load. By contrast, atrophy and tau load were mainly predicted by structural pathways, with major contributions from inter-regional diffusion. The ɛ4 allele modulated contributions to the four biomarkers in a way consistent with compromised brain connectomics in carriers. Our approach can be used to assess the contribution of concurrent mechanisms in other neurodegenerative diseases and the possible modifying impact of relevant factors on this contribution.
A multi-centre UK-based survey on angioedema secondary to acquired C1 inhibitor deficiency
Authors: Morsi Hadeil , Huissoon Aarnoud , Grammatikos Alexandros , Whyte Andrew , Manson Ania , Ekbote Anjali , Sivadasan Anju , Boulton Anne Pacita Rosillo , Herwadkar Archana , Anantharachagan Ariharan , Price Arthur , Steele Cathal , Stroud Catherine , Chopra Charu , Arnold Dilani , Eren Efrem , Cleave Elizabeth , Drewe Elizabeth , Moon Emily , Zinser Emily , Hayman Grant , Alachkar Hana , Ghanta Harichandana , Bourne Helen , Abdelhakam Intisar , Dempster John , Townsend Katie , Sooriyakumar Kavitha , Lorenzo Lorena , Dziadzio Magdalena , Ahuja Manisha , Prasinou Maria , Frleta-Gilchrist Marina , Zhang Michael , Thomas Moira , Vijayadurai Pavaladurai , Vaitla Prashantha Madhuri , Sargur Ravishankar , Herriot Richard , Yellon Robert L , Murng Sai Hurng Kham , Drinkwater Sara , Denness Sarah , Denman Sarah , Elkhalifa Shuayb , Savic Sinisa , Kiani-Alikhan Sorena , Coulter Tanya I , El-Shanawany Tariq , Rahman Tasneem , Garcez Tomaz , Yong Patrick F K , Jain Rashmi
Published: January 2025

Background

Acquired angioedema due to C1-inhibitor deficiency (AAE-C1-INH) is very rare compared to its prototype, hereditary angioedema. An updated characterisation of the AAE-C1-INH cohort in UK is required to inform management.

Objectives

To describe the disease burden of AAE-C1-INH, long-term prophylaxis (LTP) and the clinical, immunochemical and treatment profiles of AAE-associated diseases in UK.

Method

Retrospective data on 117 AAE-C1-INH patients were collected using a national survey proforma across 25/34 Adult Clinical Immunology and Allergy centres in UK. Other European cohorts were compared.

Results

Median age at AAE-C1-INH diagnosis was 65 years with 3.4% of patients diagnosed below 40 years. The median delay in diagnosis was one year. Antifibrinolytics and attenuated androgens showed comparable efficacy as LTP 88.9% and 89.5%, respectively. A haematological disorder was identified in 83.8% AAE-C1-INH patients compared to 3.4% autoimmune diseases. The predominant haematological disorders were splenic marginal zone lymphoma (SZL) 34% followed by MGUS 16%. The severity of angioedema did not depend on the associated disease. Anti-C1INH-autoantibodies testing was limited at 23.1%. Rituximab monotherapy was effective in treating 9/9 SZL and 1/2 MGUS-associated AAE-C1-INH. Rituximab efficacy was independent of anti-C1INH-autoantibodies detection with response in 3/3 seronegative and 4/4 seropositive patients

Conclusion

The diagnosis of AAE-C1-INH should not be overlooked below the age of 40 years. The choice of oral LTP should be informed by propensity to side-effects. B-cell depletion could be considered in treating monoclonal B cell disorder-associated-AAE-C1-INH in the absence of haematological indications. Further studies are required to address the clinical utility of anti-C1INH-autoantibodies.
The changes in the ratio of Dicer1 transcripts can participate in the neuronal hypoxic response by regulating miR-29b
Authors: Liu Linan , Liu Yingxin , Sun Yongfeng , Lu Xian , Ji Yong , Zhao Xiujuan , Li Jun , Liu Chuncheng
Published: January 2025

The nervous system is highly dependent on the supply of oxygen and nutrients, so when demand for oxygen exceeds its supply, hypoxia is induced. The hippocampus is very important in the nervous system. It has the ability to control human behavior, memory, emotion, and so on. Therefore, when the hippocampus is damaged by hypoxia, it may cause nervous system diseases such as Alzheimer’s disease, Parkinson’s disease, and stroke. Alternative splicing plays an important regulatory role in the processes of growth and disease occurrence and development. However, the function of hypoxia-induced alternative splicing in neurological diseases needs to be further studied. Therefore, we performed hypoxia stress on mouse hippocampal neuron HT22 cells and then analyzed differentially expressed genes and differential alternative splicing events by next-generation sequencing. Through bioinformatics analysis and verification, it was found that hypoxia stress regulated the expression of Rbm15 and the ratio of Dicer1 transcripts in HT22 cells. The change in the ratio of Dicer1 transcripts may be related to the upregulation of miR-29b under hypoxia stress. This study can provide multiple time point sequencing results and a theoretical basis for the study of hypoxia-related gene alternative splicing.
The hemispheric differences in prefrontal function of Internet game disorder and non-Internet game disorder: an activation likelihood estimation meta-analysis
Authors: Xue Rui , Li Jiaqi , Yang Haibo
Published: January 2025

This study explored the differences in brain activation between individuals with and without Internet gaming disorder (IGD) through activation likelihood estimation analysis. In total, 39 studies were included based on the inclusion and exclusion criteria by searching the literature in the PubMed and Web of Science databases, as well as reading other reviews. The analysis revealed that the activated brain regions in IGD were the right inferior frontal gyrus, left cingulate gyrus, and left lentiform nucleus. In comparison, the activated brain regions in non-IGD were the left middle frontal, left inferior frontal, left anterior cingulate, left precentral, and right precentral gyri. The results of the present study on differences in activation further confirm existing theoretical hypotheses. Future studies should explore hemispheric differences in prefrontal brain function between IGD and non-IGD.
Reactivating and reorganizing activity-silent working memory: two distinct mechanisms underlying pinging the brain
Authors: Yang Can , He Xianhui , Cai Ying
Published: January 2025

Recent studies have proposed that visual information in working memory (WM) can be maintained in an activity-silent state and reactivated by task-irrelevant high-contrast visual impulses (“ping”). Although pinging the brain has become a popular tool for exploring activity-silent WM, its underlying mechanisms remain unclear. In the current study, we directly compared the neural reactivation effects and behavioral consequences of spatial-nonmatching and spatial-matching pings to distinguish the noise-reduction and target-interaction hypotheses of pinging the brain. Initially, in an electroencephalogram study, our neural decoding results showed that spatial-nonmatching pings reactivated activity-silent WM transiently without changing the original WM representations or recall performance. Conversely, spatial-matching pings reactivated activity-silent WM more durably and further reorganized WM information by decreasing neural representations’ dynamics. Notably, only the reactivation strength of spatial-matching pings correlated with recall performance and was modulated by the location of memorized items, with neural reactivation occurring only when both items and pings were presented horizontally. Consistently, in a follow-up behavioral study, we found that only spatial-matching, horizontal pings impaired recall performance compared to no ping. Together, our results demonstrated two distinct mechanisms underlying pinging the brain, highlighting the critical role of the ping’s context (i.e. spatial information) in reactivating and reorganizing activity-silent WM.
Neural correlates of reciprocity bias: social debts modulate unfairness perception of violation during third-party observation
Authors: Zhang Yinling , Chen Rongrong , Liu Siqi , Chen Peiqi , Mai Xiaoqin
Published: January 2025

The phenomenon of beneficiaries ignoring benefactors’ violations, ranging from everyday favors to bribes, is widespread yet lacks targeted theoretical and empirical attention. We propose a conceptual framework that includes “social debt” and “reciprocity bias,” where “social debt” is defined as information about benefits bestowed by benefactors and “reciprocity bias” as the influence of social debt on beneficiaries’ perceptions and decisions in situations involving the benefactor. To investigate this bias in moral perception and its cognitive–neural mechanisms, we manipulated three levels of social debt (none, less, more) by varying the amount of unasked benefits that benefactors bestowed upon participants. Participants then observed the distributor’s fair or unfair allocation of resources to another person, while their electroencephalography (EEG) was recorded. Results indicate that more (vs. none/less) social debt reduces perceptions of unfairness toward benefactors’ violations and enhances fairness perceptions of their norm adherence. This was, accompanied by the diminished fairness effect on fronto-centered P2 and a reversal fairness effect on the power of theta oscillations (4 to 7 Hz). These findings support a multilevel reciprocity bias in fairness perception, suggesting that strong social debt may heighten concern for benefactor’s interests and increase the adaptive value of their violations at the cognitive–neural level.
Characterization of LTBP2 mutation causing mitral valve prolapse
Authors: Shpitzen Shoshi , Rosen Haim , Ben-Zvi Ayal , Meir Karen , Levin Galina , Gudgold Amichay , Ben Dor Shifra , Haffner Rebecca , Zwas Donna R , Leibowitz David , Slaugenhaupt Susan A , Banin Eyal , Mizrachi Rotem , Obolensky Alexey , Levine Robert A , Gilon Dan , Leitersdorf Eran , Tessler Idit , Reshef Noga , Durst Ronen
Published: January 2025

Aims

Mitral valve prolapse (MVP) is a common valvular disorder associated with significant morbidity and mortality, with a strong genetic basis. This study aimed to identify a mutation in a family with MVP and to characterize the valve phenotype in LTBP2 knockout (KO) mice.

Methods and results

Exome sequencing and segregation analysis were performed on a large family with MVP. Two mouse strains were generated: a complete KO of the LTBP2 gene and a knockin (KI) of the human mutation. At 6 months, phenotyping was conducted using echocardiography, histology, eye optical coherence tomography, and quantitative polymerase chain reaction analysis for TGF-β signalling targets (periostin/POSTN, RUNX2, and CTGF) in valve tissues. LTBP2 rs117800773 V1506M mutation exhibited segregation with MVP. LTBP2 KO mice had a higher incidence of myxomatous changes by histology (7 of 9 of KO vs. 0 of 7 control animals, P = 0.00186) and echocardiography (7 of 9 vs. 0 of 8, P = 0.0011). LTBP2 KI mice for the human mutation showed a significantly elevated myxomatous histological phenotype (8 of 8 vs. 0 of 9, P = 0.00004) as well as by echocardiography (6 of 8 vs. 0 of 9, P = 0.00123). Knockout mice demonstrated an increase in the depth of the anterior chamber as well as reduced visual acuity. LTBP2 KO mice demonstrated overexpression of both TGF-β signalling targets RUNX2 and periostin (P = 0.0144 and P = 0.001826, respectively).

Conclusion

We report a KO mouse strain with an LTBP2 mutation, demonstrating a valve phenotype, alongside a family with a novel mutation linked to MVP.
Bumblebees prefer sulfoxaflor-contaminated food and show caste-specific differences in sulfoxaflor sensitivity
Authors: Orr Sarah E , Xu Jixiang , Juneau Wanvimol C , Goodisman Michael A D
Published: January 2025

More than 30% of human food crop yield requires animal pollination. In addition, successful crop production depends on agrochemicals to control pests. However, agrochemicals can have negative consequences on beneficial insect pollinators, such as bees. We investigated the effects of an emerging class of pesticides, sulfoximines, on the common eastern bumblebee, Bombus impatiens. We performed a series of 96-hour toxicity tests on microcolonies of laboratory-reared B. impatiens. Our data showed that sulfoxaflor (SFX) is significantly less toxic to B. impatiens than historically used neonicotinoid pesticides, such as thiamethoxam. Further, for the first time, we found significant differences among castes in sensitivity to SFX; workers and drones were more sensitive than queens. These findings are notable because they reveal both caste and sex-specific differences in bumblebee sensitivity to pesticides. Interestingly, we found no evidence that bumblebees avoid SFX-contaminated sugar syrup. To the contrary, B. impatiens workers had an apparent preference for SFX-contaminated sugar syrup over sugar syrup alone. Overall, our investigation provides novel information on an important pesticide and may help inform regulatory decisions regarding pesticide use.
Assessment of responses of cultured benthic foraminiferal communities to copper pollution through environmental RNA metabarcoding analysis
Authors: Qiao Ling , Zhao Anran , Yuan Tao , Guo Yuanming , Chen Ye , Li Tiejun , Ren Chengzhe
Published: January 2025

Copper (Cu) is an essential trace element and can accumulate in sedimentary environments. However, beyond a certain concentration threshold, Cu can pose toxicity risks to biota. Benthic foraminifera are widely distributed and exhibit characteristics such as high biodiversity, short life cycle, good preservation potential, and high pollutant sensitivity, making them good bioindicators. In this study, we investigated the responses of benthic foraminiferal communities to various Cu concentrations through environmental RNA metabarcoding under controlled laboratory conditions. Some foraminiferal genera—Glandulina, Pyrgo, Quinqueloculina, Sorites, and Vellaria—exhibited sensitivity to high Cu concentrations. Other genera—Ammonia, Operculina, Reophax, Bolivina, Glabratella, Miliammina, and Parasorites—displayed tolerance to high Cu concentrations. Moreover, high Cu levels led to reduced living benthic foraminifera abundance and interspecific interactions, albeit without inducing test deformities. Our findings provide a novel and efficient approach for exploring the responses of benthic foraminiferal communities to heavy metal pollution.
Chronic toxicity of dissolved barium and sodium chloride to the water flea Ceriodaphnia dubia: implications for unconventional gas flowback–produced waters
Authors: Willems Daniel J , Kumar Anupama , Nugegoda Dayanthi
Published: January 2025

Unconventional gas flowback–produced waters, particularly those of marine origin from shale gas, can contain elevated concentrations of barium (Ba) and sodium chloride (NaCl). There are limited Ba water quality guideline values to help assess the potential risk of Ba exposure to freshwater biota. Barium toxicity is heavily influenced by sulfate concentrations as Ba and sulfate react, forming the highly water-insoluble and thus less bioavailable Ba sulfate. To determine survival and reproductive impacts, the water flea Ceriodaphnia dubia was exposed to dissolved Ba, NaCl, and binary combinations of dissolved Ba and NaCl. No chronic lethal concentration (LC) endpoints could be determined for dissolved Ba-only exposure up to 16 mg/L due to near 100% parent survivorship across all treatments. The NaCl LC50 (95% credible intervals) = 708 (502–939) mg/L. The dissolved Ba reproductive effect concentration (EC) at EC20 was 0.95 (0.19–3.22) mg/L. Meanwhile, for NaCl, the EC10 and EC20 concentrations were 365 (149–651) mg/L and 510 (282–760) mg/L, respectively. The binary exposure of Ba and NaCl had limited meaningful data due to some experimental shortcomings (lack of Ba-only and NaCl-only controls). Despite this, at 410 mg/L NaCl, the dissolved Ba reproductive EC10 and EC20 were determined to be 8.87 [3.58–11.7] mg/L and 10.1 (5.64–11.8) mg/L, respectively. These results suggest that marginally increased NaCl concentrations alleviate Ba toxicity, particularly when Ba is at low concentrations. Further chronic studies are needed to account for Ba toxicity in dissolved and precipitated forms and derive a Ba guideline value for freshwater biota.
Bioconcentration, maternal transfer, and toxicokinetics of PFOS in a multi-generational zebrafish exposure
Authors: Gust Kurt A , Kimble Ashley N , Mylroie J Erik , Mayo Michael L , Wilbanks Mitch S , Steward Catherine S C , Chapman Kacy A , Lotufo Guilherme R , Garcia-Reyero Natalia , Moore David W
Published: January 2025

To enable risk characterization of perfluorooctane sulfonic acid (PFOS) in extended chronic and multi-generational exposures, we assessed PFOS bioconcentration in zebrafish (Danio rerio) exposed continuously to environmentally-relevant PFOS concentrations (0, 0.1, 0.6, 3.2, 20, and 100 µg/L PFOS) through 180 days postfertilization (dpf) in parental (P) and first filial generation (F1) fish. Exposures included five replicate tanks per treatment where whole-body PFOS concentrations were measured using 20–35 fish per replicate at 14 and 29 dpf in the P generation and one fish of each sex per replicate at 180 dpf for the P and F1 generations. Perfluorooctane sulfonic acid accumulation reached an apparent steady state at ≤ 14 dpf where whole-body wet-weight concentrations remained constant through 180 dpf in the P and F1 generations. The median bioconcentration factor (BCF) of 934 L/kg was observed for all PFOS exposures with a range from 255 to 2,136 L/kg which varied with PFOS exposure concentration and sex of adult fish. Significantly lower BCFs were observed in 20 and 100 µg/L PFOS exposures versus 0.1 and 0.6 µg/L indicating exposure-concentration dependance. Additionally, males had significantly increased (∼2×) PFOS accumulation and BCFs versus females in both P and F1 generations. Maternal transfer of PFOS was observed from P females to F1 eggs where maternal whole-body and egg PFOS burdens were equivalent, suggesting PFOS transfer to eggs was not a depuration pathway. Finally, a toxicokinetic model was developed that reliably reproduced PFOS whole-body burdens (data within 1.64-fold of predicted values) across all exposure durations spanning the P and F1 generations, providing a tool for PFOS bioaccumulation predictions relevant for risk assessment of acute, chronic, and multi-generational exposures.
Effects of heavy metal accumulation mediated by floral rewards on key stages of growth and development of bumblebees (Bombus terrestris L.)
Authors: Wu Lei , Sun Qi , Zhao Jimin , Wang Xing , Wang Deli , Zhang Yanwen
Published: January 2025

Whether soil heavy metal pollution contributes to the decline in pollinator populations remains inconclusive. Based on the detection of heavy metals in the nectar, pollen, and bodies of pollinating insects in areas affected by heavy metal pollution, this study aimed to investigate the impact of adding four heavy metals—zinc (Zn), lead (Pb), copper (Cu), and nickel (Ni)—at realistic concentrations to the diet on the pre-oviposition period, larval development period, production of adult bees, and weight of worker bees. The study sought to evaluate the influence of heavy metal accumulation mediated by floral rewards on key stages of growth and development of bumblebee (Bombus terrestris L.). Results revealed that Zn, Pb, and Cu significantly extended the pre-oviposition period of queen bees, with Pb doubling the time at high concentrations and Ni showing no significant effect at moderate to low concentrations. Lead, Cu, and Ni significantly extended the larval development period at medium and high concentrations, whereas Zn only had a significant effect at high concentrations. The four heavy metals significantly reduced the adult bee yield and the body weight of worker bees at different concentrations, among which the high concentrations of Pb and Cu significantly reduced the adult bee yield by 25%–40%. The effect of a high concentration of copper on the body weight of worker bees was the most obvious, a reduction by 30%. Our findings support the hypothesis that heavy metal pollution, mediated by floral rewards, can have serious impact on some key stages of growth and development of bumblebees.
Advancing the quantitative understanding of adverse outcome pathways: current status, methodologies, and future directions
Authors: Jeong Jaeseong , Gasparyan Manvel , Choi Jinhee
Published: January 2025

An adverse outcome pathway (AOP) framework maps the sequence of events leading to adverse outcomes from chemical exposures, providing a mechanistic understanding often absent in traditional methods. The quantitative AOP (qAOP) advances AOP by integrating quantitative data and mathematical modeling, thereby providing a more precise comprehension of relationships between molecular initiating events, key events, and adverse outcomes. This review critically examines three primary methodologies: systems toxicology, regression modeling, and Bayesian network modeling, highlighting their strengths, limitations, and specific data requirements within toxicology. Through an analysis of current methodologies and challenges, this review emphasizes the integration of experimental and computational approaches to elucidate key event relationships and proposes strategies for overcoming limitations through standardized protocols and advanced computational tools. By outlining future research directions and the potential of qAOPs to transform chemical risk assessment, this review aims to contribute to the advancement of regulatory science and the protection of public health and the environment.
Identifying potential trace metal contamination impacts of a coal ash landfill on the largest Chesapeake Bay tributary (Chester, VA, USA)
Authors: Frankel Tyler E , Crowell Catherine , Orledge Summer , Giancarlo Leanna , Odhiambo Ben Kisila
Published: January 2025

Coal fly ash is a highly heterogeneous waste product that becomes concentrated with metals after combustion that have been shown to act as neurotoxins and/or carcinogens in both wildlife and humans. As such, increased understanding of the presence, concentrations, and potential ecosystem impacts is needed. The Chesterfield power station contains more than 15 million tons of ash and is located adjacent to the James River, which serves as a tributary to the Chesapeake Bay. Our study investigated (1) the presence and concentrations of aluminum (Al), aresnic (As), cadmium (Cd), chromium (Cr), copper (Cu), iron (Fe), magnesium (Mg), manganese (Mn), lead (Pb), selenium (Se), and zinc (Zn) in surface water, deep water, and sediment samples obtained from the surrounding area and (2) the presence of various teleost species, using environmental DNA (eDNA) sampling. Universal cokriging was used to estimate the spatial variability of metals in sediments and the extent of pollution interpreted using enrichment factors (EF). Little contamination was observed in water samples compared to sediment samples. Elevated concentrations of Al, As, Cd, Cr, Fe, Pb, and Zn were observed in areas immediately adjacent to the coal ash landfills. Arsenic, Cd, and Pb showed increased EF in sites adjacent to the landfills, suggesting that the contamination observed is due to anthropogenic factors. Environmental DNA analyses revealed the presence of 22 teleost species, several of which have been identified as threatened, endangered, diadromous, and/or consumed by anglers who use the James River. Collectively, our results provide novel insight regarding the impacts of coal ash on an important Chesapeake Bay watershed and guidance for future risk assessment.