bluuebunny/crossref_metadata_2025 huggingface dataset:
Longitudinal change in the adjective intensifier system of Hexagonal French
Authors: Kunkel Scott
Published: November 2024

Intensifiers are known for their dynamic nature, due in part to the expressive function they serve. However, while the quantitative patterning of English intensifiers has been studied extensively, the intensifier system of French has yet to be well documented. This study therefore examines intensifier use from a variationist sociolinguistic perspective in the ESLO corpus of spoken Hexagonal French. The quantitative distributions of adjective intensifiers are compared across two corpora collected in 1970 and 2010. Results show a significant decrease in intensification rate over time. Analysis of individual intensifiers show some to have decreased in use over time (e.g. très, tellement), others to have increased (e.g. vraiment, tout), and others to appear only in the later sample (e.g. super, hyper). Longitudinal change is also found in the adjectival function (predicative vs. attributive) and collocational width of intensifiers. Relating to social factors, no significant gender difference is found between female and male speakers’ intensification rate over time. Furthermore, très dominates as the preferred intensifier among older generations, while younger speakers favour more varied intensifiers. Analyzing such changes in the use of intensifiers over the past half century contributes to a better understanding of the structure and development of the French intensifier system.
Power line density and habitat quality: key factors in Canarian houbara bustard decline
Authors: Ucero Alberto , Alonso Juan C. , Palacín Carlos , Abril-Colón Inmaculada , Álvarez-Martínez José M.
Published: November 2024

Species’ declines are caused by a combination of factors that affect survival and/or breeding success. We studied the effects of a set of environmental and anthropogenic variables on the disappearance of Canarian Houbara Bustards Chlamydotis undulata fuertaventurae on Fuerteventura (Canary Islands), once the main stronghold of this endangered bird. Of 83 male display sites detected in 1997–1998, only 29 remained occupied in 2020–2021 (a 65% decrease in only 23 years). We compared habitat quality, density of conspecifics, other steppe birds and crows, presence of human infrastructure, and degree of environmental protection between these 29 extant sites and the 54 extinct sites using univariate analyses and generalised linear models (GLMs). The most influential variable in the abandonment of display sites was the Normalised Difference Vegetation Index (NDVI), an indicator of green vegetation productivity, which suggests a strong effect of habitat aridification due to climate change on the population’s extinction process. Powerline density was the second most important factor. This suggests that houbaras have survived where a greater abundance of food resources has enabled a higher breeding success, and where powerline fatalities have caused lower mortality over the years. Higher densities of houbaras, and other steppe birds and crows at extant display sites confirmed the better habitat quality in these areas. Extant display sites, located generally in protected areas, also had lower densities of human infrastructure (e.g. buildings, roads). We discuss the conservation implications of these results and provide management recommendations for this endangered subspecies.
The effect of rapamycin treatment on mouse ovarian follicle development in dehydroepiandrosterone-induced polycystic ovary syndrome mouse model
Authors: Yildirim Ecem , Onel Tugce , Agus Sami , Gunalan Elif , Yilmaz Bayram , Aydin Mehmet Serif , Yaba Aylin
Published: November 2024

Polycystic ovary syndrome (PCOS) is a complex reproductive and endocrine disorder affecting 5–10% of women of reproductive age, but the pathophysiology of PCOS still remains unknown. Here, the aim of our study was to analyze the effects of rapamycin treatment that may regulate impaired hormonal levels and folliculogenesis in dehydroepiandrosterone (DHEA)-treated PCOS mouse. We hypothesized that rapamycin may ameliorate the negative effects of PCOS in DHEA-induced PCOS mouse model. The target of rapamycin (TOR) gene product is a serine/threonine kinase that has been implicated in the control of cell growth, proliferation and autophagy, and rapamycin is a potent inhibitor of mTORC1 pathway. In this study, for the first time, mTORC1 and activation products are presented at protein and mRNA levels after rapamycin treatment in DHEA-induced PCOS mouse ovary. We showed that rapamycin treatment may regulate follicular development, hormonal levels and provide ovulation in DHEA-induced PCOS mouse. Additionally, we assessed decreased primordial follicle reserve, increased number of primary and secondary follicles, corpus luteum structure forms again after 10 days of rapamycin treatment. This study presented here suggests rapamycin treatment regulates hormonal phenotype and folliculogenesis in the ovary and also mTOR signalling pathway in granulosa cells of DHEA-induced PCOS mouse ovary which may have potential to attenuate understanding the mechanism of dominant follicle selection and anovulatory infertility.
Identification of clinical risk factors for coronary artery lesions in children with Kawasaki disease: a retrospective cohort study
Authors: Yang Xiangna , Zou Jiayi , Nie Hao , Zhang Gang , Liao Yin , Deng Jian , Wang Yanfei
Published: November 2024

Background:

Coronary artery lesions are the most severe complications of Kawasaki disease. Despite recent advances, evidence of the association between risk factors and coronary artery lesion is lacking. In this study, we demonstrated the potential clinical indicators that could assist to evaluate the prevalence of coronary artery lesion among paediatric patients with Kawasaki disease.

Methods:

We retrospectively enrolled 260 paediatric patients with Kawasaki disease. Patients with coronary dilation, coronary aneurysm, and intimal thickening of coronary arteries were included in this study. Medical records of each patient were collected. Logistic regression analysis was performed to explore risk factors and the occurrence of coronary artery lesion in patients with Kawasaki disease.

Results:

Respectively, 64 (24.6%), 39 (15%), and 56 patients (21.5%) of the participants had coronary dilation, coronary aneurysm, and intimal thickening of coronary arteries. Univariate analysis revealed that age, gender, duration of fever, time of initial use of intravenous immunoglobulin, erythrocyte sedimentation rate, white blood cell counts, time of platelet increase, the maximum value of platelet, albumin, and immunoglobulin G level was associated with coronary artery lesion. In multivariable logistic analysis, those younger and mainly males were associated with all three outcomes of coronary artery lesion, lower serum albumin levels, and later initial use of intravenous immunoglobulin were linked to a higher risk of coronary dilation and coronary aneurysm.

Conclusions:

The potential risk factors that could be used to estimate the occurrence of coronary artery lesion in Kawasaki disease patients are young age, male, lower serum albumin lever, and later initial use of intravenous immunoglobulin. However, long-term follow-up and multi-centre studies are required to verify our findings in the future.
Victorian Municipal Waste Management
Authors: Thielman Frances
Published: November 2024

Municipal solid waste management shapes public life at every moment, and it did so for the Victorians as much as it does for us today. Victorians were concerned about the sanitary risk unruly trash posed, but profit, not conservation or fear of hazardous waste, was the primary motivator behind all Victorian municipal waste management. Though the Victorian period is often characterized as a time when government and public works were becoming centralized, this was not the case with municipal solid waste management. Instead, a focus on the individual pursuit of profit meant that Victorian waste management was dispersed across society, with homemakers, recycling entrepreneurs, dustmen, and the very poorest members of society all playing a role. The structures Victorians built (or failed to build) to attend to their trash can help us understand how they ordered society. Waste management practices provide a microcosm of nineteenth-century British capitalism, class, gender roles, and imperial nationalism.
Pensions as Infrastructure
Authors: Hunt Aeron
Published: November 2024

Pensions were a means of social provisioning long before they became a cornerstone of state welfare policies in the early twentieth century. The multifarious pension forms that persisted and were reshaped during the Victorian period offer occasions to glimpse how social bonds and obligations across time were imagined and contested. The pensions of Charles Dickens's Bleak House (1852–53) suggest how the infrastructural potential of a form might flicker within the literary text, even as it is unacknowledged and left behind.
An Empire of Red Weed: Environmental Infrastructure in H. G. Wells's The War of the Worlds
Authors: Bowden Mary
Published: November 2024

This article argues that natural environments should be seen as life-sustaining infrastructures. Countering a tendency to see infrastructures as human-engineered, I show how environmental infrastructures are shaped by humans and nonhumans alike, with their life-sustaining roles often only revealed by their disruption. I demonstrate how infrastructures might be shaped by nonhumans by highlighting the career of Elodea canadensis, or Canadian waterweed, an introduced plant that wrought havoc on Britain's watery environments in the mid- to late nineteenth century. Red weed, the plant introduced by the Martians in H. G. Wells's The War of the Worlds, echoes Elodea in its course through the British environment. But while Elodea and similar introduced species prompted nascent critiques of imperial plant movement, I show how Wells avoids such critiques by deleting red weed, and any further environmental consequences following from its introduction, from his novel's end. Instead, Wells endorses a natural-selection-driven explanation for the British environment's superior fitness—an explanation that affirms rather than critiques ecological imperialism and mitigates the role of nonhumans in reshaping environmental infrastructures.
Photography as Knowledge Infrastructure
Authors: Tange Andrea Kaston
Published: November 2024

Photography may seem primarily a technology of image-making, but it was in fact a powerful mode of meaning-making in the nineteenth century, and its operation as such was actively under negotiation from its invention. This essay examines the photograph's status as both documentary object and artistic expression, drawing on examples including journalistic, political, and familial uses of the medium as well as the forms of entertainment it provided. As a force of knowledge production—whether helping consolidate emerging sentimental ideals of family relations, forwarding anthropological understandings of the world, or supporting the work of spiritualists claiming to commune with the dead—photography was used to clarify and shape people's ideas about phenomena they did not understand and often otherwise could not see. As such, it became a vital infrastructure for the transmission of culture and the consolidation of national identity.
Extreme comovements and downside/upside risk spillovers between oil prices and exchange rates
Authors: Ning Cathy , Xu Dinghai
Published: November 2024

This paper examines the dependence structure and risk spillovers between oil prices and exchange rates in both oil-exporting and oil-importing countries. Using a flexible dependence switching copula model, we analyze both positive and negative dependence and transitions between the dependence regimes. Additionally, we investigate the directional risk spillovers between oil and currency markets in both their downsides and upsides. Based on empirical data from 1999 to 2024 for major oil-exporting and oil-importing countries, we find that oil price-currency dependence is predominantly positive for oil-exporting countries, with infrequent transitions, but mainly negative for oil-importing countries, with frequent transitions between the two dependence regimes. These transitions often occur around crisis or war times. Furthermore, we observe that during downturns in the oil market, tail dependence between oil prices and currencies becomes more pronounced than during upturns. Our results indicate the presence of risk spillovers between oil and currency markets, with the downside spillover effects outweighing the upside ones. Moreover, we find that risk spillover is stronger from oil markets to currency markets than the reverse direction. These insights substantially enrich the existing literature and would offer valuable implications for effective risk management strategies and policymaking.
Bacteria Acidithiobacillus ferrooxidans, terrestrial analogue of extraterrestrial microorganisms?
Authors: Slowik Grzegorz Piotr , Richer Renee , Stryjska Aleksandra Zofia , Dabrowski Pawel
Published: November 2024

In this comprehensive review, Acidithiobacillus ferrooxidans, an acidophilic bacterium, has been thoroughly examined as a plausible analogue for microbial life in Venus's lower cloud layer. Given its ability to adapt to extreme conditions, including low pH environments and metal-rich settings, Acidithiobacillus ferrooxidans is considered a promising candidate for studying life analogues in Venus's clouds. This article comprehensively analyses the bacterium's distinctive phenotypic and genotypic features, investigating its metabolic pathways, adaptive strategies and potential ecological niche within Venusian cloud ecosystems. After careful consideration of the environmental parameters characterizing Venus, the unidentified UV absorber in its clouds, and the prospects for microbial life, this review underscores the imperative nature of future Venus missions and the pivotal role that Acidithiobacillus ferrooxidans may play in exploring the possible habitability of Venus and advancing astrobiological research.
Greening‐Induced Biophysical Impacts Lead to Earlier Spring and Autumn Phenology in Temperate and Boreal Forests
Authors: Guo Jing , Wang Jinmei , Qiao Yuxin , Huang Xu , Smith Nicholas G. , Liu Zhiyong , Zhang Rui , Chen Xiuzhi , Wu Chaoyang , Peñuelas Josep , Chen Lei
Published: November 2024

Tree phenology, the timing of periodic biological events in trees, is highly sensitive to climate change. Previous studies have indicated that forest greening can impact the local climate by modifying the seasonal surface energy budget. However, the understanding of tree phenological responses to forest greening at large spatial scales remains limited. Utilizing satellite‐derived phenological and leaf area index data spanning from 2001 to 2021, herein we show that forest greening led to earlier spring and autumn phenology in both temperate and boreal forests. Our findings demonstrated that forest greening during winter and spring contributed to a reduction in surface albedo, resulting in biophysical warming and consequently advancing spring leaf phenology. Conversely, forest greening in summer and autumn induced biophysical cooling through increased evapotranspiration, leading to an earlier onset of autumn leaf phenology. Our findings highlight the significant impact of forest greening‐induced local seasonal climate changes on shaping tree phenology in temperate and boreal forests. It is crucial to consider these greening‐induced alterations in microclimate conditions when modeling changes in tree phenology under future climate warming scenarios.
Weather Extremes Influence Human Migration Between Mexico and the United States
Authors: van Deelen Grace
Published: November 2024

Undocumented immigrants from agricultural areas in Mexico are most vulnerable to drought and seasonal weather patterns.
The Multi‐Segment Complexity of the 2024 MW ${M}_{W}$ 7.5 Noto Peninsula Earthquake Governs Tsunami Generation
Authors: Kutschera Fabian , Jia Zhe , Oryan Bar , Wong Jeremy Wing Ching , Fan Wenyuan , Gabriel Alice‐Agnes
Published: November 2024

The 1 January 2024, moment magnitude 7.5 Noto Peninsula earthquake ruptured in complex ways, challenging analysis of its tsunami generation. We present tsunami models informed by a 6‐subevent centroid moment tensor (CMT) model obtained through Bayesian inversion of teleseismic and strong motion data. We identify two distinct bilateral rupture episodes. Initial, onshore rupture toward the southwest is followed by delayed re‐nucleation at the hypocenter, likely aided by fault weakening, causing significant seafloor uplift to the northeast. We construct a complex multi‐fault uplift model, validated against geodetic observations, that aligns with known fault system geometries and is critical in modeling the observed tsunami. The simulations can explain tsunami wave amplitude, timing, and polarity of the leading wave, which are crucial for tsunami early warning. Upon comparison with alternative source models and analysis of 2000 multi‐CMT ensemble solutions, we highlight the importance of incorporating complex source effects for realistic tsunami simulations.
Proton Cyclotron Waves and Pickup Ion Ring Distribution Instabilities Upstream of Mars
Authors: Cheng Kun , Liu Kaijun , Mousavi Ameneh , Cowee Misa , Zheng Xianming , Zhou Jingyi , Wang Yan , Liu Yuqi , Wang Xinye
Published: November 2024

Proton cyclotron waves (PCWs) upstream of Mars are thought to be associated with the instabilities of pickup ions. The instabilities of pickup ions of ring distributions have larger maximum growth rates compared with beam distributions. However, observations revealed a notably‐reduced occurrence rate of PCWs for pickup ions of ring distributions. Linear instability analysis and a corresponding two‐dimensional particle‐in‐cell (PIC) simulation are performed to investigate the instabilities of pickup ion ring distributions upstream of Mars. Linear instability analysis indicates that a pickup ion ring distribution is unstable to the ion cyclotron, ion Bernstein, and mirror instabilities. The corresponding PIC simulation confirms the linear analysis results and further demonstrates that the pickup ions are scattered toward an isotropic shell distribution by the waves excited. Interestingly, the saturation energy of the waves is much lower than that driven by a corresponding pickup ion beam distribution, and mirror waves eventually dominate the system.
The Relative Importance of Ocean Advection and Surface Heat Fluxes During the Madden–Julian Oscillation in a Coupled Ocean–Atmosphere Model
Authors: Karlowska E. , Matthews A. J. , Webber B. G. M. , Graham T. , Xavier P.
Published: November 2024

Intraseasonal variability of ocean surface mixed layer temperature (MLT) in the tropics can be linked to the Madden–Julian Oscillation (MJO), the main source of intraseasonal atmospheric variability in the tropics. Here, we conduct a boreal winter mixed layer heat budget using 10‐day forecast composites of a coupled ocean–atmosphere Numerical Weather Prediction model of the UK Met Office to reveal that ocean advection plays a major role in modulating intraseasonal anomalies of MLT over the tropical Indian Ocean and the Maritime Continent. Large scale ( 10) intraseasonal anomalies of MLT ( 0.1 C) are driven by net surface heat flux. Ocean advection dominates at smaller horizontal scales ( 1), contributing up to 0.5 C to the intraseasonal MLT anomaly. Prior to the development of the enhanced MJO convection in the western Indian Ocean (phases 8 and 1), ocean advection reinforces the net heat flux warming in this region. However, ocean advection opposes the net heat flux warming in the Maritime Continent prior to the development of suppressed MJO convection in this region. When the MJO convection develops over the central Indian Ocean (phase 3), ocean advection (net surface heat flux) drives the intraseasonal MLT anomalies in the western Indian Ocean (central Indian Ocean and the Maritime Continent). Our results demonstrate the importance of ocean dynamics during the initiation and growth of the MJO, and raise implications for models that do not resolve these processes.
Evaluation of two different self-disinfection alginate impression material
Authors: Bendary Islam M. , Omar Alaa A. , Goda Reham M. , Ali Ahmed A. , Lotfy Kareem A. , Shohayeb Mohamed M.
Published: November 2024

Objective

This study was conducted to evaluate the antimicrobial efficacy and mechanical properties of two experimental self-disinfecting alginate preparations utilising two different antimicrobial agents; povidone-iodine and silver nanoparticles.

Methods

Alginate moulds were assigned into three groups. Additives-free control group, povidone-iodine-containing group, and silver nanoparticle-containing group. Discs from each group were obtained and assessed for their antimicrobial activities by the disc diffusion method against Staphylococcus aureus, Escherichia coli, and Candida albicans. For the elastic recovery analysis, each group was divided into 6 samples. Each sample was mixed according to its group specification and subjected to surface detail reproduction and elastic recovery according to ISO 1563:1990 specifications. All data were expressed as mean ± standard deviation for each group at the significance level of P < 0.05.

Results

Results revealed that the experimental self-disinfection alginate possessed broad-spectrum antimicrobial activities against the tested microorganisms, compared to the control group. No statistically significant differences in elastic recovery values between all tested groups (P < 0.05) were observed. For surface detail reproduction, all samples reproduced the 50 μm line.

Conclusion

Povidone-iodine as well as silver nanoparticles could be used efficiently for the sanitization of alginate moulds without adverse effects on detail accuracy or elastic recovery of the impression material.
OTUB1 regulation of ferroptosis and the protective role of ferrostatin-1 in lupus nephritis
Authors: Liu Chen , Gan Yu-hui , Yong Wei-jing , Xu Hong-de , Li Yong-chun , Hu Hui-miao , Zhao Zhan-zheng , Qi Yuan-yuan
Published: November 2024

Lupus nephritis (LN) is a prevalent and severe manifestation of systemic lupus erythematosus (SLE), leading to significant morbidity and mortality. OTUB1, a deubiquitinating enzyme, has emerged as a potential therapeutic target due to its role in cellular protection and regulation of ferroptosis, a form of cell death linked to LN. Our study revealed significantly reduced OTUB1 expression in the glomeruli of LN patients and podocytes, correlated with disease severity. CRISPR/Cas9-mediated OTUB1 knockout in podocytes resulted in pronounced injury, indicated by decreased levels of nephrin and podocin. Ferrostatin-1 treatment effectively mitigated this injury, restoring SLC7A11 expression and significantly reducing MDA levels, Fe2+ levels, BODIPY C11 expression, and normalized cysteine and glutathione expression. In the MRL/lpr mouse model, Ferrostatin-1 significantly improved renal function decreased proteinuria, and ameliorated renal histopathological changes, including reduced glomerular endothelial swelling, mesangial cell proliferation, and leukocyte infiltration. These results underscore the protective role of Ferrostatin-1 in modulating the pathogenesis of LN. OTUB1 plays a crucial protective role against podocyte injury in LN by regulating ferroptosis. Ferrostatin-1 effectively mitigates podocyte damage induced by OTUB1 deficiency, suggesting that targeting ferroptosis could be a promising therapeutic strategy for LN.
Stem cell transplantation extends the reproductive life span of naturally aging cynomolgus monkeys
Authors: Yan Long , Tu Wan , Zhao Xuehan , Wan Haifeng , Wu Jiaqi , Zhao Yan , Wu Jun , Sun Yingpu , Zhu Lan , Qin Yingying , Hu Linli , Yang Hua , Ke Qiong , Zhang Wenzhe , Luo Wei , Xiao Zhenyu , Chen Xueyu , Wu Qiqian , He Beijia , Teng Man , Dai Shanjun , Zhai Jinglei , Wu Hao , Yang Xiaokui , Guo Fan , Wang Hongmei
Published: November 2024

The ovary is crucial for female reproduction and health, as it generates oocytes and secretes sex hormones. Transplantation of mesenchymal stem cells (MSCs) has been shown to alleviate pathological ovarian aging. However, it is unclear whether MSCs could benefit the naturally aging ovary. In this study, we first examined the dynamics of ovarian reserve of Chinese women during perimenopause. Using a naturally aging cynomolgus monkey (Macaca fascicularis) model, we found that transplanting human embryonic stem cells-derived MSC-like cells, which we called M cells, into the aging ovaries significantly decreased ovarian fibrosis and DNA damage, enhanced secretion of sex hormones and improved fertility. Encouragingly, a healthy baby monkey was born after M-cell transplantation. Moreover, single-cell RNA sequencing analysis and in vitro functional validation suggested that apoptosis, oxidative damage, inflammation, and fibrosis were mitigated in granulosa cells and stromal cells following M-cell transplantation. Altogether, these findings demonstrate the beneficial effects of M-cell transplantation on aging ovaries and expand our understanding of the molecular mechanisms underlying ovarian aging and stem cell-based alleviation of this process.
Bacterial toxins induce non-canonical migracytosis to aggravate acute inflammation
Authors: Li Diyin , Yang Qi , Luo Jianhua , Xu Yangyushuang , Li Jingqing , Tao Liang
Published: November 2024

Migracytosis is a recently described cellular process that generates and releases membrane-bound pomegranate-like organelles called migrasomes. Migracytosis normally occurs during cell migration, participating in various intercellular biological functions. Here, we report a new type of migracytosis induced by small GTPase-targeting toxins. Unlike classic migracytosis, toxin-induced migrasome formation does not rely on cell migration and thus can occur in both mobile and immobile cells. Such non-canonical migracytosis allows the cells to promptly respond to microbial stimuli such as bacterial toxins and effectors and release informative cellular contents in bulk. We demonstrated that C. difficile TcdB3 induces liver endothelial cells and Kupffer cells to produce migrasomes in vivo. Moreover, the migracytosis-defective Tspan9‒/‒ mice show less acute inflammation and lower lethality rate in the toxin challenge assay. Therefore, we propose that the non-canonical migracytosis acts as a new mechanism for mammalian species to sense and exacerbate early immune response upon microbial infections.
A generalised computer vision model for improved glaucoma screening using fundus images
Authors: Chaurasia Abadh K. , Liu Guei-Sheung , Greatbatch Connor J. , Gharahkhani Puya , Craig Jamie E. , Mackey David A. , MacGregor Stuart , Hewitt Alex W.
Published: November 2024

Importance

Worldwide, glaucoma is a leading cause of irreversible blindness. Timely detection is paramount yet challenging, particularly in resource-limited settings. A novel, computer vision-based model for glaucoma screening using fundus images could enhance early and accurate disease detection.

Objective

To develop and validate a generalised deep-learning-based algorithm for screening glaucoma using fundus image.

Design, setting and participants

The glaucomatous fundus data were collected from 20 publicly accessible databases worldwide, resulting in 18,468 images from multiple clinical settings, of which 10,900 were classified as healthy and 7568 as glaucoma. All the data were evaluated and downsized to fit the model’s input requirements. The potential model was selected from 20 pre-trained models and trained on the whole dataset except Drishti-GS. The best-performing model was further trained to classify healthy and glaucomatous fundus images using Fastai and PyTorch libraries.

Main outcomes and measures

The model’s performance was compared against the actual class using the area under the receiver operating characteristic (AUROC), sensitivity, specificity, accuracy, precision and the F1-score.

Results

The high discriminative ability of the best-performing model was evaluated on a dataset comprising 1364 glaucomatous discs and 2047 healthy discs. The model reflected robust performance metrics, with an AUROC of 0.9920 (95% CI: 0.9920–0.9921) for both the glaucoma and healthy classes. The sensitivity, specificity, accuracy, precision, recall and F1-scores were consistently higher than 0.9530 for both classes. The model performed well on an external validation set of the Drishti-GS dataset, with an AUROC of 0.8751 and an accuracy of 0.8713.

Conclusions and relevance

This study demonstrated the high efficacy of our classification model in distinguishing between glaucomatous and healthy discs. However, the model’s accuracy slightly dropped when evaluated on unseen data, indicating potential inconsistencies among the datasets—the model needs to be refined and validated on larger, more diverse datasets to ensure reliability and generalisability. Despite this, our model can be utilised for screening glaucoma at the population level.
Opportunities for retrieval and tool augmented large language models in scientific facilities
Authors: Prince Michael H. , Chan Henry , Vriza Aikaterini , Zhou Tao , Sastry Varuni K. , Luo Yanqi , Dearing Matthew T. , Harder Ross J. , Vasudevan Rama K. , Cherukara Mathew J.
Published: November 2024

Upgrades to advanced scientific user facilities such as next-generation x-ray light sources, nanoscience centers, and neutron facilities are revolutionizing our understanding of materials across the spectrum of the physical sciences, from life sciences to microelectronics. However, these facility and instrument upgrades come with a significant increase in complexity. Driven by more exacting scientific needs, instruments and experiments become more intricate each year. This increased operational complexity makes it ever more challenging for domain scientists to design experiments that effectively leverage the capabilities of and operate on these advanced instruments. Large language models (LLMs) can perform complex information retrieval, assist in knowledge-intensive tasks across applications, and provide guidance on tool usage. Using x-ray light sources, leadership computing, and nanoscience centers as representative examples, we describe preliminary experiments with a Context-Aware Language Model for Science (CALMS) to assist scientists with instrument operations and complex experimentation. With the ability to retrieve relevant information from facility documentation, CALMS can answer simple questions on scientific capabilities and other operational procedures. With the ability to interface with software tools and experimental hardware, CALMS can conversationally operate scientific instruments. By making information more accessible and acting on user needs, LLMs could expand and diversify scientific facilities’ users and accelerate scientific output.
Microstructure and radiation shielding capabilities of Al-Cu and Al-Mn alloys
Authors: El-Samrah Moamen G. , Nabil Islam M. , Shamekh Mohamed E. , Elmasry M. , Osman M.
Published: November 2024

In this study, the microstructure and elemental analysis of aluminum-copper alloy type-2024, Al-2024, and aluminum-manganese alloy type-3003, Al-3003, have been investigated by using a scanning electron microscope (SEM) equipped with Energy dispersive spectroscopy (EDS) detector. Experimental and theoretical radiation shielding studies were performed to assess the radiation shielding capabilities of the studied alloys. Considering the radiation shielding theoretical assessment, some reliable software tools were used, such as Phy-X/PSD, MCNP5, NXCom, and MRCsC. The microstructural observations and results have shown the presence of second phases rich with the main alloying elements in both alloys. Considering Al-2024 alloy, coarse second-phase particles, having a size range of 8–15 μm, were found aligning in lines parallel to the rolling direction, whereas smaller ones, having a size range of 2–8 μm, were found decorated the grain boundaries. Also, dark holes represent the pull-out large particles separated during preparation indicated poor adhesion with the main matrix that could be a result of losing particle coherency with the matrix where the misorientation in-between the atomic planes increase. However, better adhesion of the second-phase particles with the matrix, which were found possessing smaller particle size, have been observed in the Al-3003 alloy indicating good coherency and better manufacturing process for the non-heat-treatable alloy. The second-phase particles in case of Al-2024 alloy were found containing significant content of high-Z elements like Cu with greater volume fraction equals 7.5%. On the other side, Al-3003 alloy has possessed second-phase particles which lack of high-Z elements with only volume fraction equals 3.5%. All the former besides the higher density and content of high-Z elements like copper in Al-2024 alloy in compare to Al-3003 alloy and pure aluminum, led to relatively better radiation shielding capabilities against energetic photons, the highest in the low energy band and decreases with the increase of the photon energy, and slight superiority in the case of fast neutrons with only 3%inc. over pure aluminum. For instance, the radiation protection efficiency (RPE) values dropped from about; 23.2, 21.6, and 20.8% at 0.100 MeV to only 5.7, 5.9, and 5.6% at Eγ = 2 MeV, for; Al-2024, Al-3003, and Al-Pure, respectively."Please check and confirm that the authors and their respective affiliations have been correctly identified and amend if necessary.""confirmed"
Therapeutic potential of hyaluronic acid hydrogel combined with bone marrow stem cells-conditioned medium on arthritic rats’ TMJs
Authors: Assi Mai M. , Grawish Mohammed E. , Elsabaa Heba Mahmoud , Helal Mohamad E. , Ezzat Samah K.
Published: November 2024

Conditioned media (CM) is derived from mesenchymal stem cells (MSC) culture and contains biologically active components. CM is easy to handle and reduces inflammation while repairing injured joints. Combination therapy of the CM with cross-linked hyaluronic acid (HA) could ameliorate the beneficial effect of HA in treating degenerative changes of articulating surfaces associated with arthritic rats’ temporomandibular joints (TMJs). This study aimed to evaluate the therapeutic potential of HA hydrogel combined with bone marrow stem cells-conditioned medium (BMSCs-CM) on the articulating surfaces of TMJs associated with complete Freund’s adjuvant (CFA)-induced arthritis. Fifty female Sprague-Dawley rats were divided randomly into five equal groups. Rats of group I served as the negative controls and received intra-articular (IA) injections of 50 µl saline solution, whereas rats of group II were subjected to twice IA injections of 50 µg CFA in 50 µl; on day 1 of the experiment to induce persistent inflammation and on day 14 to induce arthritis. Rats of group III and IV were handled as group II and instead, they received an IA injection of 50 µl HA hydrogel and 50 µl of BMSCs-CM, respectively. Rats of group V were given combined IA injections of 50 µl HA hydrogel and BMSCs-CM. All rats were euthanized after the 4th week of inducing arthritis. The joints were processed for sectioning and histological staining using hematoxylin and eosin, Masson’s trichrome and toluidine blue special staining, and immunohistochemical staining for nuclear factor-kappa B (NF-κB). SPSS software was used to analyze the data and one-way analysis of variance followed by post-hoc Tukey statistical tests were used to test the statistical significance at 0.05 for alpha and 0.2 for beta. In the pooled BMSC-CM, 197.14 pg/ml of platelet-derived growth factor and 112.22 pg/ml of interleukin-10 were detected. Compared to TMJs of groups III and IV, TMJs of group V showed significant improvements (P = 0.001) in all parameters tested as the disc thickness was decreased (331.79 ± 0.73), the fibrocartilaginous layer was broadened (0.96 ± 0.04), and the amount of the trabecular bone was distinctive (19.35 ± 1.07). The mean values for the collagen amount were increased (12.29 ± 1.38) whereas the mean values for the NF-κB expression were decreased (0.62 ± 0.15). Combination therapy of HA hydrogel and BMSCs-CM is better than using HA hydrogel or BMSCs-CM, separately to repair degenerative changes in rats’ TMJs associated with CFA-induced arthritis.
Regulation of neutrophil associated RNASET2 expression in rheumatoid arthritis
Authors: Passari Mauro , Scutera Sara , Schioppa Tiziana , Tiberio Laura , Piantoni Silvia , Tamassia Nicola , Bugatti Mattia , Vermi William , Angeli Fabrizio , Caproli Alessia , Salvi Valentina , Sozio Francesca , Gismondi Angela , Stabile Helena , Franceschini Franco , Bosisio Daniela , Acquati Francesco , Vermeren Sonja , Sozzani Silvano , Andreoli Laura , Del Prete Annalisa , Musso Tiziana
Published: November 2024

Neutrophils (PMNs) are key players of innate immune responses through the release of cytoplasmic granule content and the formation of neutrophil extracellular traps (NETs). RNASET2 is an acidic ribonuclease, recently proposed as an alarmin signal associated with inflammatory responses. Here we show that, along the neutrophil maturation cascade, RNASET2 is expressed in segmented and mature PMNs. In human PMNs, RNASET2 colocalized with primary and tertiary granules and was found to be associated with NETs following PMA or Nigericin stimulation. Similarly, activation of PMNs by soluble immune complexes, a hallmark of several autoimmune diseases, also induced RNASET2-associated NETs. Genome-wide association studies recently identified RNASET2 among a cluster of genes associated with increased susceptibility to develop autoimmune diseases, including rheumatoid arthritis (RA). RNASET2 was found expressed by PMNs and macrophages infiltrating inflamed joints in a murine model of RA (K/BxN Serum-Transfer-Induced Arthritis, STIA), by immunostaining. Similar results were found in synovial biopsies of RA patients with active disease. In addition, we demonstrate that RNASET2 circulating levels correlated with the onset and the severity of disease in two mouse models of inflammatory arthritis, STIA and CIA (Collagen-Induced Arthritis) and in serum of RA patients. These results show that PMNs are an important source of RNASET2 and that its circulating levels are associated with RA development suggesting a role for RNASET2 in the pathogenesis of immune-mediated diseases.
Prevalence and aggravation of cervical spine instabilities in rheumatoid arthritis during over 10 years: a prospective multicenter cohort study
Authors: Kanda Yutaro , Yurube Takashi , Hirata Hiroaki , Sumi Masatoshi
Published: November 2024

We designed a prospective multicenter cohort study to clarify a long-term, > 10-year prevalence and aggravation of cervical spine instabilities in rheumatoid arthritis (RA). In 2001–2002, 634 outpatients were enrolled, and 233 (36.8%) were followed for > 10 years. Cervical spine instability was defined as atlantoaxial subluxation (AAS, > 3-mm atlantodental interval), vertical subluxation (VS, < 13-mm Ranawat value), and subaxial subluxation (SAS, ≥ 2-mm irreducible vertebral translation). The aggravation was determined as ≥ 2 mm decrease of the Ranawat value in VS, ≥ 2-mm increase of slippage in SAS, and these new developments. The prevalence of VS and SAS increased during both the initial and last > 5 years (all, p ≤ 0.049). While VS aggravation was associated with pre-existing AAS (p = 0.007) and VS (p = 0.002), SAS aggravation correlated with pre-existing VS (p = 0.002). Multivariable analysis found hand mutilating changes (odds ratio [OR] = 4.048, p = 0.008), RA duration ≥ 5 years (OR = 3.711, p = 0.013), C-reactive protein (CRP) level ≥ 3.8 mg/dL (OR = 2.187, p = 0.044), and previous joint surgery (OR = 2.147, p = 0.021) as predictors for VS aggravation. Pre-existing VS (OR = 2.252, p = 0.024) and CRP ≥ 1.0 mg/dL (OR = 2.139, p = 0.013) were disclosed as predictors for SAS aggravation. Low disease activity and clinical remission before the development of VS and advanced peripheral joint destruction are essential to prevent progressive cervical spine instability in RA.
CCDC28A deficiency causes head-tail coupling defects and immotility in murine spermatozoa
Authors: Stojanovic Nena , Hernández Rosario Ortiz , Ramírez Nayeli Torres , Martínez Olga Margarita Echeverría , Hernández Abrahan Hernández , Shibuya Hiroki
Published: November 2024

Male infertility presents a substantial challenge in reproductive medicine, often attributed to impaired sperm motility. The present study investigates the role of CCDC28A, a protein expressed specifically in male germ cells, whose paralog CCDC28B has been implicated in ciliogenesis. We identify unique expression patterns for CCDC28A and CCDC28B within the mouse testes, where CCDC28A is expressed in germ cells, whereas CCDC28B is expressed in supporting somatic cells. Through knockout mouse models and histological analyses, we reveal that CCDC28A deficiency results in diminished sperm motility and structural aberrations in sperm tails, notably affecting the head-tail coupling apparatus (HTCA), thereby causing male infertility. Fine structural analyses by transmission electron microscopy reveal disruptions at the capitulum-basal plate junction of the HTCA in the CCDC28A mutants. This results in the bending of the head within the neck region, often accompanied by thickening of the tail midpiece. Our discovery demonstrates that CCDC28A plays an essential role in male fertility and sperm tail morphogenesis through the formation of HTCA.
Bridging organ transcriptomics for advancing multiple organ toxicity assessment with a generative AI approach
Authors: Li Ting , Chen Xi , Tong Weida
Published: November 2024

Translational research in toxicology has significantly benefited from transcriptomic profiling, particularly in drug safety. However, its application has predominantly focused on limited organs, notably the liver, due to resource constraints. This paper presents TransTox, an innovative AI model using a generative adversarial network (GAN) method to facilitate the bidirectional translation of transcriptomic profiles between the liver and kidney under drug treatment. TransTox demonstrates robust performance, validated across independent datasets and laboratories. First, the concordance between real experimental data and synthetic data generated by TransTox was demonstrated in characterizing toxicity mechanisms compared to real experimental settings. Second, TransTox proved valuable in gene expression predictive models, where synthetic data could be used to develop gene expression predictive models or serve as “digital twins” for diagnostic applications. The TransTox approach holds the potential for multi-organ toxicity assessment with AI and advancing the field of precision toxicology.
An engineered aldolase enables the biocatalytic synthesis of 2′-functionalized nucleoside analogues
Authors: Willmott Matthew , Finnigan William , Birmingham William R. , Derrington Sasha R. , Heath Rachel S. , Schnepel Christian , Hayes Martin A. , Smith Peter D. , Falcioni Francesco , Turner Nicholas J.
Published: November 2024

Nucleosides functionalized at the 2′-position play a crucial role in therapeutics, serving as both small-molecule drugs and modifications in therapeutic oligonucleotides. However, the synthesis of these molecules often presents substantial synthetic challenges. Here we present an approach to the synthesis of 2′-functionalized nucleosides based on enzymes from the purine nucleoside salvage pathway. Initially, active-site variants of deoxyribose-5-phosphate aldolase were generated for the highly stereoselective synthesis of d-ribose-5-phosphate analogues with a broad range of functional groups at the 2-position. Thereafter, these 2-modified pentose phosphates were converted into 2′-modified purine analogues by construction of one-pot multienzyme cascade reactions, leading to the synthesis of guanosine (2′-OH) and adenosine (2′-OH, 2′-Me, 2′-F) analogues. This cascade allows for the control of the 2′-functional group alongside 2-stereochemistry. Our findings demonstrate the capability of these biocatalytic cascades to efficiently generate 2′-functionalized nucleosides, starting from simple starting materials.
Impact of blue light on cutaneous barrier structures and properties: NPLC/HR-MSn and Raman analyses
Authors: Habib Léa , Michael-Jubeli Rime , Abboud Marie , Lteif Roger , Tfayli Ali
Published: November 2024

Blue light alters lipids and proteins in the reconstructed human epidermis.
Rapid neurostimulation at the micron scale with an optically controlled thermal-capture technique
Authors: Romshin Alexey M. , Aseyev Nikolay A. , Idzhilova Olga S. , Koryagina Alena A. , Zeeb Vadim E. , Vlasov Igor I. , Balaban Pavel M.
Published: November 2024

Thermal-capture mode (TCM), a new form of local heat action on living cells, is discovered with diamond-heater thermometer (DHT). In TCM, 50 °C heat steps elicit enhanced depolarization up to 20 mV, enabling precise modulation of neuron excitability.
The thermal instability of hydrogen-substituted graphdiyne and its role in lithium–sulfur batteries
Authors: Eeso Karam , Wygant Bryan R. , Chen Zhitao , Sarswat Akriti , Lambert Timothy N. , Liu Nian
Published: November 2024

This study reveals the role of thermal instability in hydrogen-substituted graphdiyne (HsGDY) and its impact on lithium–sulfur (Li–S) battery performance.
Water-resistant boronic ester vitrimer with hydrophobic side chain protection
Authors: Mah Justin Jian Qiang , Feng Hongzhi , Surat'man Nayli Erdeanna Binte , Li Bofan , Wang Sheng , Li Zibiao
Published: November 2024

A boronic ester vitrimer with high hydrolytic stability afforded by fluorinated side-chain protection is reported.
Cereblon-recruiting proteolysis targeting chimeras (PROTACs) can determine the selective degradation of HDAC1 over HDAC3
Authors: Pavan Aline R. , Smalley Joshua P. , Patel Urvashi , Pytel Wiktoria A. , dos Santos Jean Leandro , Cowley Shaun M. , Schwabe John W. R. , Hodgkinson James T.
Published: November 2024

Cereblon-recruiting PROTACs can degrade HDAC1 with selectivity over HDAC3.
Intramolecular cyclization of N-aryl amides for the synthesis of 3-amino oxindoles
Authors: Yang Haitao , Pan Yu , Tian Yijing , Yu Kaili , Bai Yifeng , Jiang Yonggang , Zhang Hongbin , Deng Guogang , Yang Xiaodong
Published: November 2024

A mild and efficient strategy to synthesize pharmaceutically important 3-amino oxindoles from readily available N-aryl amides has been developed.
Investigations of the interactions between ZnO nanorods and H2 with 17O NMR spectroscopy
Authors: Song Benteng , Wang Fang , Zhu Qin , Xie Ling-Hai , Peng Luming
Published: November 2024

Schematic diagram for the interaction of H2 with ZnO nanorods under different conditions.
A high affinity and selective DNA aptamer for copper ions
Authors: Wang Jin , Liu Yibo , Li Xiangmei , Lei Hongtao , Liu Juewen
Published: November 2024

A high affinity aptamer for Cu2+ with a dissociation constant value of 14.2 nM was isolated using the capture-SELEX method, and it was used to develop a strand-displacement fluorescent biosensor with a limit of detection of 2.1 nM.
Structural properties and lattice phonons evolution in phenothiazine/iminostilbene solid solutions
Authors: Giunchi Andrea , Pandolfi Lorenzo , Della Valle Raffaele G. , Salzillo Tommaso , Venuti Elisabetta , Demitri Nicola , Riegler Hans , Petschacher Christina , Liu Jie , Werzer Oliver
Published: November 2024

Solid solutions of APIs phenothiazine and iminostilbene are structurally characterized in bulk and thin films. Low-frequency Raman and DFT analyses reveal how the loss of periodicity impacts lattice dynamics.
The impact of side-chain fluorination on proton-bound phenylalanine dimers: a cryogenic infrared spectroscopic study
Authors: Safferthal Marc , Greis Kim , Chang Rayoon , Chang Chun-Wei , Hoffmann Waldemar , Meijer Gerard , von Helden Gert , Pagel Kevin
Published: November 2024

In this study, a combination of cryogenic gas-phase infrared spectroscopy and ab initio calculations is used to show the influence of side-chain fluorination on the structures and interaction types in proton-bound phenylalanine homodimers.