bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultra-low photodamage three-photon microscopy assisted by neural network for monitoring regenerative myogenesis
Authors: Li Yifei , Li Keying , He Mubin , Liang Chenlin , Xie Xin , Qian Jun 
Published: August 2024

ABSTRACTThree-photon microscopy (3PM) enables high-resolution three-dimensional (3D) imaging in deeply situated and highly scattering biological specimens, facilitating precise characterization of biological morphology and cellular-level physiologyin vivo. However, the use of fluorescent probes with relatively low three-photon absorption cross-sections necessitates high-peak-power lasers for excitation, which poses inherent risks of light-induced damage. Additionally, the low repetition frequency of these lasers prolongs scanning time per pixel, hampering imaging speed and exacerbating the potential for photodamage. Such limitations hinder the application of 3PM in studying vulnerable tissues, including muscle regeneration. To address this critical issue, we developed the Multi-Scale Attention Denoising Network (MSAD-Net), a precise and versatile denoising network suitable for diverse structures and varying noise levels. Our network enables the use of lower excitation power (1/4-1/2 of the common power) and shorter scanning time (1/6-1/4 of the common time) in 3PM while preserving image quality and tissue integrity. It achieves an impressive structural similarity index (SSIM) of up to 0.9932 and an incredibly fast inference time of just 80 milliseconds per frame which ensured both high fidelity and practicality for downstream applications. By utilizing MSAD-Net-assisted imaging, we comprehensively characterize the biological morphology and functionality of muscle regeneration processes through deepin vivofive-channel imaging under extremely low excitation power and short scanning time, while maintaining a high signal-to-background ratio (SBR) and excellent axial spatial resolution. Furthermore, we conducted high axial-resolution dynamic imaging of vascular microcirculation, macrophages, and ghost fibers. Our findings provide a deeper understanding of the mechanisms underlying muscle regeneration at the cellular and tissue levels.
A Self-Assembling Immune-Featured Osteosarcoma Patient/PDX Derived Organoid Model and Biobank for Personalized Immune Therapy
Authors: Mu Haoran , Tao Yining , Wang Jinzeng , He Xin , Zhang Qi , Chen Weixi , Yao Bing , Ding Sen , Yang Xiyu , Zhang Liyuan , Wang Hongsheng , Zuo Dongqing , Shen Jiakang , Sun Mengxiong , Wang Haoyu , Jiao Ming , Jin Xinmeng , Jin Yinhui , Liang Youzhi , Gong Yuyan , Mao Winfred , Liu Qian , Wang Zhuoying , Lv Yu , Xu Jing , Zhang Tao , Yang Yuqin , Lin Jun , Asward Fred J. , Joseph James D. , Li Mingxi , Cai Zhengdong , Sun Wei , Yang Liu , Hua Yingqi 
Published: August 2024

AbstractOsteosarcoma (OS) exhibit intra- and inter-heterogeneity, complicating the exploration of effective therapeutic strategies. Traditionalin vitroandin vivomodels are limited in inheriting biological and genomic heterogeneities of OS patients, even in inheriting the features on tumor microenvironment. The prolonged generation time of current models makes the drug development of OS slow and is not suitable to clinically rapid timing. Here, we introduce methods for generating and biobanking patient/PDX-derived osteosarcoma organoids (OS PD(X)Os) that recapitulate the histological, biological and genomic features of their paired OS patients. OS PD(X)Os can be generated quickly with high reliabilityin vitroor transplanted to immunodeficient mice. We further demonstrate an immune-featured OS PD(X)O (named iOS) model and its method for testing personalized chemotherapy response, personalized immune therapeutic strategy and target drug development, such as a novel PRMT5MTAinhibitor ARPN2169 on MTAP-deleted OS. Our studies show that iOS models maintain many typical features of OS and could be rapidly employed to investigate patient-specific therapeutic strategies. Additionally, our biobank establishes a rich resource for basic, translational and even clinical OS researches.
Exploiting functional regions in the viral RNA genome as druggable entities
Authors: Luo Dehua , Zheng Yingge , Huang Zhiyuan , Wen Zi , Guo Lijun , Deng Yingxiang , Li Qingling , Bai Yuqing , Haider Shozeb , Wei Dengguo 
Published: August 2024

ABSTRACTRNA-targeting compounds or small interfering RNAs (siRNAs) offer a potent means for controlling viral infections. An essential prerequisite to their design depends on identifying conserved and functional viral RNA structures in cells. Techniques that probe RNA structuresin situhave been developed recently including SHAPE-MaP, which has been helpful in analyzing the secondary structures of RNA. In this study, we report on the application of SHAPE-MaP to the Porcine Epidemic Diarrhoea Virus (PEDV) RNA genome to categorize different functional regions including potential quadruplex forming sequence and target sites of small interfering RNA (siRNA). Our results show that these structures can be exploited to inhibit viral proliferation and that SHAPE-MaP is an effective method to the identification of secondary structures in RNA genomes.
Continuous emergence of phototaxis inDictyostelium discoideum
Authors: Genettais Damien , Bernard Charles , Geoffroy Felix , Nizak Clément , Adiba Sandrine 
Published: August 2024

AbstractThe evolutionary transition from uni- to multicellularity is associated with new properties resulting from collective cell behavior. The social amoebaDictyostelium discoideumalternating between individual cells and multicellular forms of varying size provides a powerful biological system to characterize such emergent properties. Multicellular forms coined slugs have long been described as chemotactic towards cAMP, and also as phototactic. While chemotaxis is also well-documented at the single-cell level, which merely explains slug chemotaxis, we asked whether slug phototaxis is an emergent property of multicellularity. For this, we developed an automated microscopy setup to quantify and compare the migration trajectories of single cells and slugs moving in the dark or illuminated with lateral light. We find that single cells, either extracted from phototactic slugs or taken prior to multicellular aggregation, are not phototactic, implying that slug phototaxis results from interactions between cells that lack this property. Further, by analysing slugs composed of a varying number of cells, we find that phototaxis efficiency increases continuously with slug size. Cell-cell interactions combined with self-organization are thus key elements for this property to emerge.
AmygdalaGo-BOLT3D: A boundary learning transformer for tracing human amygdala
Authors: Dong Bo , Zhou Quan , Gao Peng , Wei Jintao , Xiao Jiale , Wang Wei , Liang Peipeng , Lin Danhua , He Hongjian , Zuo Xi-Nian 
Published: August 2024

AbstractAutomated amygdala segmentation is one of the most common tasks in human neuroscience research. However, due to the small volume of the human amygdala, especially in developing brains, the precision and consistency of the segmentation results are often affected by individual differences and inconsistencies in data distribution. To address these challenges, we propose an algorithm for learning boundary contrast of 427 manually traced amygdalae in children and adolescents to generate a transformer, AmygdalaGo-BOLT3D, for automatic segmentation of human amygdala. This method focuses on the boundary to effectively address the issue of false positive recognition and inaccurate edges due to small amygdala volume. Firstly, AmygdalaGo-BOLT3D develops a basic architecture for an adaptive cooperation network with multiple granularities. Secondly, AmygdalaGo-BOLT3D builds the self-attention-based consistency module to address generalizability problems arising from individual differences and inconsistent data distributions. Third, AmygdalaGo-BOLT3D adapts the original sample-mask model for the amygdala scene, which consists of three parts, namely a lightweight volumetric feature encoder, a 3D cue encoder, and a volume mask decoder, to improve the generalized segmentation of the model. Finally, AmygdalaGo-BOLT3D implements a boundary contrastive learning framework that utilizes the interaction mechanism between a prior cue and the embedded magnetic resonance images to achieve effective integration between the two. Experimental results demonstrate that predictions of the overall structure and boundaries of the human amygdala exhibit highly improved precision and help maintain stability in multiple age groups and imaging centers. This verifies the stability and generalization of the algorithm designed for multiple tasks. AmygdalaGo-BOLT3D has been deployed for the community (GITHUB LINK) to provide an open science foundation for its applications in population neuroscience.
Early life challenge enhances cortisol regulation in zebrafish larvae
Authors: Castillo-Ramírez Luis A. , Herget Ulrich , Ryu Soojin , De Marco Rodrigo J. 
Published: August 2024

ABSTRACTThe hypothalamic-pituitary-adrenal (HPA) axis in mammals and the hypothalamic-pituitary-interrenal (HPI) axis in fish are open systems that adapt to the environment during development. Little is known about how this adaptation begins and regulates early stress responses. We used larval zebrafish to examine the impact of prolonged forced swimming at 5 days post-fertilization (dpf), termed early-life challenge (ELC), on cortisol responses, neuropeptide expression in the nucleus preopticus (NPO), and gene transcript levels. At 6 dpf, ELC-exposed larvae showed normal baseline cortisol but reduced reactivity to an initial stressor. Conversely, they showed increased reactivity to a second stressor within the 30-minute refractory period, when cortisol responses are typically suppressed. ELC larvae had fewer corticotropin-releasing hormone (crh), arginine vasopressin (avp), and oxytocin (oxt)-positive cells in the NPO, with reduced crh and avp co-expression. Gene expression analysis revealed upregulation of genes related to cortisol metabolism (hsd11b2,cyp11c1), steroidogenesis (star), and stress modulation (crh,avp,oxt). These results suggest that early environmental challenge initiates adaptive plasticity in the HPI axis, tuning cortisol regulation to balance responsiveness and protection during repeated stress. Future studies should explore the broader physiological effects of prolonged forced swimming and its long-term impact on cortisol regulation and stress-related circuits.SummaryThis study explores how early-life challenges in zebrafish affect stress responses and hormone regulation, offering insights into developmental adaptability and stress management mechanisms.
Efficient modular system identification provides a high-resolution assay of temporal processing and reveals the multilevel effects of attention along the human auditory pathway
Authors: Singh Ravinderjit , Bharadwaj Hari 
Published: August 2024

AbstractHuman studies of auditory temporal processing and the effects therein of aging, hearing loss, musicianship, and other auditory processing disorders have conventionally employed brainstem evoked potentials (e.g., FFRs/EFRs targeting specific modulation frequencies). Studies of temporal processing in forebrain structures are fewer and are often restricted to the 40 Hz steady-state response. One factor contributing to the limited investigation is the lack of a fast and reliable method to characterize temporal processing non-invasively in humans over a wide range of modulation frequencies. Here, we use a system-identification approach where white noise, modulated using an extended maximum-length sequence (em-seq), is employed to target stimulus energy toward a modulation-frequency range of interest and efficiently obtain a robust auditory modulation-temporal response function or ‘mod-TRF’. The mod-TRF can capture activity from sources in the early processing pathway (5-7 ms latency), middle-latency region (MLR), and late latency region (LLR). The mod-TRF is a high-resolution, modular assay of the temporal modulation transfer function (tMTF) in that the distinct neural components contributing to the tMTF can be separated on the basis of their latency, modulation frequency band, and scalp topography. This decomposition provides the insight that the seemingly random individual variation in the shape of the tMTF can be understood as arising from individual differences in the weighting and latency of similar underlying neural sources in the composite scalp response. We measured the mod-TRF under different states of attention and found a reduction in latency or enhancement of amplitude of the response from specific sources. Surprisingly, we found that attention effects can extend to the earliest parts of the processing pathway (5ms) in highly demanding tasks. Taken together, the mod-TRF is a promising tool for dissecting auditory temporal processing and obtain further insight into a variety of phenomenon such as aging, hearing loss, and neural pathology.
Rapid depletion and super-resolution microscopy reveal an unexpected role of the nuclear-speckle protein SRSF5 in paraspeckle assembly and dynamics during cellular stress
Authors: Arnold Benjamin , Kessler Laurell , Okuda Ellen Kazumi , Riegger Ricarda J. , Cañás Maria Clara Hernández , Zebrowska Ewelina , Bakisoglu Cem , Nagasse Helder Y. , Stanek David , Dormann Dorothee , Zarnack Kathi , Heilemann Mike , Müller-McNicoll Michaela 
Published: August 2024

AbstractNuclear speckles (NS) and paraspeckles (PS) are adjacent condensates with distinct protein composition, with serine-arginine-rich splicing factors (SRSFs) concentrated in NS. Surprisingly, we find that SRSF5 is present in both. Combining super-resolution imaging, proximity proteomics and iCLIP, we show that SRSF5 binds with PS core proteins to the PS-scaffold RNANEAT1and locates between PS spheres. Acute SRSF5 depletion results in reduced PS with differently packagedNEAT1. Under stress, SRSF5’s association with PS increases, and without SRSF5, PS cluster assembly is impaired. Interfering with binding to purine-rich RNAs even causes PS-NS fusion. In an intriguing over-compensation, longer SRSF5 depletion reduces TDP-43 levels via premature polyadenylation, leading toNEAT1isoform switching and more PS. We propose that SRSF5 forms a stress-specific PS shell and acts as a glue for PS clusters. Additionally, we uncover SRSF5 as a novel regulator of TDP-43 and demonstrate how acute depletion distinguishes direct from compensatory effects.HighlightsNS protein SRSF5 associates with PS shells and enriches between PS spheresSRSF5 binds the PS-scaffold RNANEAT1and ensures properNEAT1packagingSRSF5 association with PS increases under stress and promotes cluster formationInterfering with binding to purine-rich RNAs causes the fusion of PS and NSAcute SRSF5 depletion reveals compensatory effects on PS assembly and dynamicsSRSF5 regulates TDP-43 levels via premature polyadenylation
Immunotherapeutic strategy to prevent progression and complications of acute rheumatic fever
Authors: Rafeek Rukshan Ahamed Mohamed , Ketheesan Natkunam , Good Michael F. , Pandey Manisha , Lepletier Ailin 
Published: August 2024

AbstractAcute rheumatic fever (ARF) is an autoimmune disease triggered by antibodies and T-cells targeting the Group A streptococcal (GAS, Strep A) bacterium, often leading to rheumatic heart disease (RHD). Long-term antibiotic therapy is recognized as a cornerstone of public health programs to prevent reinfection and progression of ARF. However, better tools to slow disease progression, and mitigate its lifelong consequences are required. Evidence obtained in a preclinical model suggests that this can be achieved. Using the rat autoimmune valvulitis model, we explored the potential of low-dose interleukin 2 (LD-IL-2) as an immunotherapeutic intervention. In this model injection of recombinant Strep A M5 protein (rM5) to Lewis rats induce autoimmune complications, cardiac tissue inflammation and conduction abnormalities. In animals injected with rM5 and treated with LD-IL-2, no cardiac functional or histological changes were observed. LD-IL-2 therapy effectively reduced the production of cross-reactive antibodies against cardiac tissue and induced a significant increase in classical regulatory T-cells (Treg) and CD8+Tregs in the mediastinal (heart-draining) lymph nodes. These novel findings suggest LD-IL-2 will be an effective immunotherapeutic agent for treating ARF/RHD.
Quantifying the impact of a broadly protective sarbecovirus vaccine in a future SARS-X pandemic
Authors: Whittaker Charles , Barnsley Gregory , Olivera Mesa Daniela , Laydon Daniel J , Tan Chee Wah , Zhu Feng , Johnson Rob , Doohan Patrick , Nedjati-Gilani Gemma , Winskill Peter , Hogan Alexandra B. , Deol Arminder , Mukandavire Christinah , Hauck Katharina , Lye David Chien Boon , Wang Lin-Fa , Watson Oliver J. , Ghani Azra C 
Published: August 2024

AbstractCOVID-19 has underscored the need for more timely access to vaccines during future pandemics. This has motivated development of broad-spectrum vaccines providing protection against viral families, which could be stockpiled ahead of an outbreak and deployed rapidly following detection. We use mathematical modelling to evaluate the utility of a broadly protective sarbecovirus vaccine (BPSV) during a hypothetical SARS-X outbreak, including ring-vaccination, spatial targeting and mass vaccination of high-risk populations. Our results show BPSV ring- or spatially-targeted vaccination strategies are unlikely to contain a SARS-CoV-2-like virus but could contain or slow the spread of a SARS-CoV-1-like virus. Vaccination of high-risk populations with the BPSV ahead of a virus-specific vaccine (VSV) becoming available could substantially reduce mortality. For a 250-day VSV development timeline, BPSV availability reduced infection-related deaths in our model by 54% on average, though exact impact depended on the non-pharmaceutical intervention (NPI) scenario considered. We further show that BPSV availability enables shorter and less stringent NPIs to be imposed whilst limiting disease burden to that observed in the VSV-only scenario, though results are sensitive to vaccine properties (e.g. efficacy), health system capabilities (e.g. vaccination rollout speed) and the assumed timeline to VSV availability. Our modelling suggests that availability of a BPSV for those aged 60+ years could have averted 40-65% of COVID-19 deaths during the pandemic’s first year, with exact impact depending on the size of the maintained stockpile. Our work highlights significant potential impact of a BPSV, but that achieving this depends on investment into health systems enabling rapid and equitable access during future SARS-X pandemics.
Lack of Epistatic Interaction ofSNCAwithAPOEin Synucleinopathies
Authors: Saini Prabhjyot , Yu Eric , Estiar Mehrdad A. , Krohn Lynne , Mufti Kheireddin , Rudakou Uladzislau , Ruskey Jennifer A. , Asayesh Farnaz , Laurent Sandra B. , Spiegelman Dan , Arnulf Isabelle , Montplaisir Jacques Y. , Gagnon Jean-François , Desautels Alex , Dauvilliers Yves , Gigli Gian Luigi , Valente Mariarosaria , Janes Francesco , Bernardini Andrea , Sonka Karel , Kemlink David , Oertel Wolfgang , Kaivola Karri , Janzen Annette , Plazzi Giuseppe , Antelmi Elena , Biscarini Francesco , Figorilli Michela , Puligheddu Monica , Mollenhauer Brit , Trenkwalder Claudia , Sixel-Döring Friederike , De Cock Valérie Cochen , Monaca Christelle Charley , Heidbreder Anna , Ferini-Strambi Luigi , Dijkstra Femke , Viaene Mineke , Abril Beatriz , Boeve Bradley F. , Postuma Ronald B. , Rouleau Guy A. , Anselmi Victoria , Ibrahim Abubaker , Stefani Ambra , Högl Birgit , Hu Michele T.M. , Scholz Sonja W. , Gan-Or Ziv 
Published: August 2024

AbstractTwo recent studies suggested that theAPOEε4 haplotype was associated with increased α-synuclein pathology in cell and mouse models. Genetic variants in theSNCAregion have strong association with Parkinson’s disease (PD), Dementia with Lewy Bodies (DLB), and idiopathic REM Sleep Behavior Disorder (iRBD), whileAPOEis a genetic risk determinant for only DLB. To determine if genetic-level interactions betweenSNCAandAPOEexists that can explain the protein-level association, we investigated the genotypic interaction ofAPOEandSNCAin cohorts of PD, DLB, and iRBD. We analyzed genome-wide association study (GWAS) data from 5,229 PD patients and 5,480 controls, 2,610 DLB patients and 1,920 controls, and 1,055 iRBD patients and 3,667 controls. We used logistic regression interaction models across all 3 cohorts independently between the 1) top GWAS signals ofSNCASNPs andAPOEhaplotypes, 2) SNP x SNP and 3-way SNP interaction across the entire coding region plus 200kb flanking each gene. No significant interactions were found to be associated with any of the synucleinopathies after correction for multiple testing. Our results do not support a role for genetic interactions betweenAPOEandSNCAacross PD, DLB, and iRBD. Since the tested genetic variants affect the expression and function of these proteins, it is likely that any interactions between them does not affect the risk of PD, DLB and iRBD.
Intestinal Parasites among Primary School Children in Aden, Yemen
Authors: Gubran Ali N. M. , Al-Haidary Naif Mohammed , Bajubair Marwa Faisal M. , Algibary Afrah Mohsen Ali , Ali Manal Galeb Mhmad , Ali Marwa Fuad Othman 
Published: August 2024

AbstractBackgroundIntestinal parasite infection is a significant public health problem worldwide. This study aimed to determine the prevalence of intestinal parasites among primary school children, identify the most common types of parasites, and identify the risk factors contributing to infection in Aden, Yemen.Methodology/Principal FindingsAn analytical cross-sectional study was conducted on 201 school children in Aden, Yemen. Stool specimens were collected and tested using direct methods (saline and iodine preparations) and sedimentation concentration techniques. Data analysis was performed using SPSS (Version 21) with p ≤ 0.05 considered statistically significant. The overall prevalence of intestinal parasites was 47.3%; 35.8% had a single parasite and 11.5% had multiple parasites. Higher rates were observed among female schoolchildren (51.2%), children whose mothers had primary education (51.3%), secondary education (50%), housewives (48.5%), and children aged >9 years (50%). The most predominant parasite was Entamoeba histolytica/dispar (36.3%). There was no significant association between the identified risk factors and intestinal parasitic infections.Conclusions/SignificanceThe prevalence rate of intestinal parasites is high in Aden, Yemen, with Entamoeba histolytica/dispar being the most dominant parasite. The highest rates were found among female schoolchildren, those whose mothers were housewives with primary or secondary education, and children aged >9 years.Author SummaryIntestinal parasite infections are a major health issue in many parts of the world, especially in developing countries like Yemen. This study investigated the prevalence of these infections among primary school children in Aden, Yemen. By analyzing stool samples from 201 children, we found that nearly half were infected with at least one type of parasite. The most common parasite was Entamoeba histolytica/dispar, affecting more than a third of the children. We also discovered that certain groups of children were more likely to be infected, such as older children, girls, and those whose mothers had lower levels of education or were housewives. Understanding these patterns can help in developing targeted interventions to reduce the spread of these infections and improve children’s health and educational outcomes.