bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of Wnt/β-catenin signaling is critical for the tumorigenesis of choroid plexus
Authors: Ho Kim Hoa , Trapp Marleen , Guida Catello , Ivanova Ekaterina L , De Jaime-Soguero Anchel , Jabali Ammar , Thomas Christian , Salasova Alena , Bernatík Ondřej , Salio Chiara , Horschitz Sandra , Hasselblatt Martin , Sassoè-Pognetto Marco , Čajánek Lukáš , Ishikawa Hiroshi , Schroten Horst , Schwerk Christian , Acebrón Sergio P , Angel Peter , Koch Philipp , Patrizi Annarita 
Published: August 2024

Abstract

Background
The choroid plexus (ChP) is the secretory epithelial structure located in the brain ventricles. Choroid plexus tumors (CPTs) are rare neoplasms predominantly occurring in young patients with intensified malignancy in children. CPT treatment is hindered by insufficient knowledge of tumor pathology and the limited availability of valid models.

Methods
Genomic and transcriptomic data from CPT patients were analyzed to identify the putative pathological pathway. Cellular and molecular techniques were employed to validate bioinformatic results in CPT patient samples. Pharmacologic inhibition of Wnt/β-catenin signaling was assessed in CPT cells. Cell-based assays of ChP cell lines were performed following CRISPR-Cas9-derived knockout and overexpression of Wnt/β-catenin pathway genes. A 3D CPT model was generated through CRISPR-Cas9-derived knockout of APC.

Results
We discovered that Wnt/β-catenin signaling is activated in human CPTs, likely as a consequence of large-scale chromosomal instability events of the CPT genomes. We demonstrated that CPT-derived cells depend on autocrine Wnt/β-catenin signaling for survival. Constitutive Wnt/β-catenin pathway activation, either through knockout of the negative regulator APC or overexpression of the ligand WNT3A, induced tumorigenic properties in ChP 2D in vitro models. Increased activation of the Wnt/β-catenin pathway in ChP organoids, through treatment with a potent GSK3β inhibitor, reduced the differentiation of mature ChP epithelial cells. Remarkably, the depletion of APC was sufficient to induce the oncogenic transformation of ChP organoids.

Conclusions
Our research identifies Wnt/β-catenin signaling as a critical driver of CPT tumorigenesis and provides the first 3D in vitro model for future pathological and therapeutic studies of CPT.
Radiocatalytic ammonia synthesis from nitrogen and water
Authors: Mu Bo-Shuai , Xu Yang , Tu Zhiyu , Zhang Yugang , Liang Weiqiu , Li Jiahao , Wang Xianglin , Shen Siyong , Chen Junyi , Liu Zhibo 
Published: August 2024

ABSTRACT
The development of alternative methods to the Haber–Bosch process for ammonia (NH3) synthesis is a pressing and formidable challenge. Nuclear energy represents a low-carbon, efficient and stable source of power. The harnessing of nuclear energy to drive nitrogen (N2) reduction not only allows ‘green’ NH3 synthesis, but also offers the potential for the storage of nuclear energy as a readily transportable zero-carbon fuel. Herein, we explore radiocatalytic N2 fixation to NH3 induced by γ-ray radiation. Hydrated electrons (e−aq) that are generated from water radiolysis enable N2 reduction to produce NH3. Ru-based catalysts synthesized by using γ-ray radiation with excellent radiation stability substantially improve NH3 production in which the B5 sites of Ru particles may play an important role in the activation of N2. By benefitting from the remarkable penetrating power of γ-ray radiation, radiocatalytic NH3 synthesis can proceed in an autoclave under appropriate pressure conditions, resulting in an NH3 concentration of ≤5.1 mM. The energy conversion efficiency of the reaction is as high as 563.7 mgNH3·MJ−1. This radiocatalytic chemistry broadens the research scope of catalytic N2 fixation while offering promising opportunities for converting nuclear energy into chemical energy.
Heritable Tissue-Culture-Free Gene Editing in Nicotiana benthamiana through Viral Delivery of SpCas9 and sgRNA
Authors: Yoshida Tetsuya , Ishikawa Masayuki , Toki Seiichi , Ishibashi Kazuhiro 
Published: August 2024

Abstract
Conventional plant gene editing requires laborious tissue-culture-mediated transformation, which restricts the range of applicable plant species. In this study, we developed a heritable and tissue-culture-free gene editing method in Nicotiana benthamiana using tobacco ringspot virus (TRSV) as a vector for in planta delivery of Cas9 and single-guide RNA (sgRNA) to shoot apical meristems. Agrobacterium-mediated inoculation of the TRSV vector induced systemic and heritable gene editing in Nicotiana benthamiana PHYTOENE DESATURASE. Transient downregulation of RNA silencing enhanced gene editing efficiency, resulting in an order of magnitude increase (0.8–13.2%) in the frequency of transgenerational gene editing. While the TRSV system had a preference for certain sgRNA sequences, co-inoculation of a TRSV vector carrying only Cas9 and a tobacco rattle virus vector carrying sgRNA successfully introduced systemic mutations with all five tested sgRNAs. Extensively gene-edited lateral shoots occasionally grew from plants inoculated with the virus vectors, the transgenerational gene editing frequency of which ranged up to 100%. This virus-mediated heritable gene editing method makes plant gene editing easy, requiring only the inoculation of non-transgenic plants with a virus vector(s) to obtain gene-edited individuals.
Optimizing intervention dissemination at scale: A qualitative study of multi-sector partner organization experiences
Authors: Cassar Samuel , Salmon Jo , Timperio Anna , Powell Byron J , Della Gatta Jacqueline , Ma Jiani , Koorts Harriet 
Published: August 2024

Abstract
For population-wide impact of interventions, evidence-based programs must be successfully disseminated and adopted at scale. Research–practice partnerships can legitimize programs and support organizational adoption, however, ways of leveraging the contributions of partners during dissemination processes are less clear. TransformUs is a school-based physical activity and sedentary behaviour program, and since 2018, has been disseminated at scale to all primary schools in Victoria, Australia, in partnership with 16 state and national organizations. The study objective was to investigate the experiences of partner organizations disseminating TransformUs within their networks, and factors associated with awareness and adoption of the program in schools, from the perspective of partner organizations. Semi-structured interviews with representatives from 15 (out of 16) partner organizations in 2019 involved in disseminating TransformUs state-wide. An interview guide was informed by the RE-AIM framework. Interviews were audio-recorded, transcribed, and coded anonymously. Data were analysed thematically. Four themes (and 13 sub-themes) were identified: (i) organizational barriers and facilitators to dissemination; (ii) implementation support for partners; (iii) overall research experience; and (iv) dissemination strategy. Partners used multiple dissemination channels to increase adoption, and strong alignment between TransformUs and the partner organization’s goals appeared to enable dissemination. Partners outlined several local, regional, and state organizations to partner with, and offered suggestions regarding preferred content and timing of dissemination activities for their networks. Researchers planning research–practice partnerships should proactively consider organizational barriers partners may face during dissemination. Regular communication and feedback on dissemination outcomes may contribute to positive research–practice experiences and allow for tailored dissemination strategies.
Cryptic transmission and novel introduction of Dengue 1 and 2 genotypes in Colombia
Authors: Martínez David , Gómez Marcela , Hernández Carolina , Campo-Palacio Sandra , González-Robayo Marina , Montilla Marcela , Pavas-Escobar Norma , Tovar-Acero Catalina , Geovo-Arias Lillys , Valencia-Urrutia Esilda , Córdoba-Renteria Nayade , Carrillo-Hernandez Marlen Y , Ruiz-Saenz Julian , Martinez-Gutierrez Marlen , Paniz-Mondolfi Alberto , Patiño Luz H , Muñoz Marina , Ramírez Juan David 
Published: August 2024

Abstract
Dengue fever remains as a public health challenge in Colombia, standing as the most prevalent infectious disease in the country. The cyclic nature of dengue epidemics, occurring approximately every 3 years, is intricately linked to meteorological events like El Niño Southern Oscillation (ENSO). Therefore, the Colombian system faces challenges in genomic surveillance. This study aimed to evaluate local dengue virus (DENV) transmission and genetic diversity in four Colombian departments with heterogeneous incidence patterns (department is first-level territorial units in Colombia). For this study, we processed 266 serum samples to identify DENV. Subsequently, we obtained 118 genome sequences by sequencing DENV genomes from serum samples of 134 patients infected with DENV-1 and DENV-2 serotypes. The predominant serotype was DENV-2 (108/143), with the Asian-American (AA) genotype (91/118) being the most prevalent one. Phylogenetic analysis revealed concurrent circulation of two lineages of both DENV-2 AA and DENV-1 V, suggesting ongoing genetic exchange with sequences from Venezuela and Cuba. The continuous migration of Venezuelan citizens into Colombia can contribute to this exchange, emphasizing the need for strengthened prevention measures in border areas. Notably, the time to most recent common ancestor analysis identified cryptic transmission of DENV-2 AA since approximately 2015, leading to the recent epidemic. This challenges the notion that major outbreaks are solely triggered by recent virus introductions, emphasizing the importance of active genomic surveillance. The study also highlighted the contrasting selection pressures on DENV-1 V and DENV-2 AA, with the latter experiencing positive selection, possibly influencing its transmissibility. The presence of a cosmopolitan genotype in Colombia, previously reported in Brazil and Peru, raises concerns about transmission routes, emphasizing the necessity for thorough DENV evolution studies. Despite limitations, the study underscores genomic epidemiology’s crucial role in early detection and comprehension of DENV genotypes, recommending the use of advanced sequencing techniques as an early warning system to help prevent and control dengue outbreaks in Colombia and worldwide.
Intrahost evolution leading to distinct lineages in the upper and lower respiratory tracts during SARS-CoV-2 prolonged infection
Authors: El Moussaoui Majdouline , Bontems Sebastien , Meex Cecile , Hayette Marie-Pierre , Lejeune Marie , Hong Samuel L , Dellicour Simon , Moutschen Michel , Cambisano Nadine , Renotte Nathalie , Bours Vincent , Darcis Gilles , Artesi Maria , Durkin Keith 
Published: August 2024

Abstract
Accumulating evidence points to persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in immunocompromised individuals as a source of novel lineages. While intrahost evolution of the virus in chronically infected patients has previously been reported, existing knowledge is primarily based on samples from the nasopharynx. In this study, we investigate the intrahost evolution and genetic diversity that accumulated during a prolonged SARS-CoV-2 infection with the Omicron BF.7 sublineage, which is estimated to have persisted for &gt;1 year in an immunosuppressed patient. Based on the sequencing of eight samples collected at six time points, we identified 87 intrahost single-nucleotide variants, 2 indels, and a 362-bp deletion. Our analysis revealed distinct viral genotypes in the nasopharyngeal (NP), endotracheal aspirate, and bronchoalveolar lavage samples. This suggests that NP samples may not offer a comprehensive representation of the overall intrahost viral diversity. Our findings not only demonstrate that the Omicron BF.7 sublineage can further diverge from its already exceptionally mutated state but also highlight that patients chronically infected with SARS-CoV-2 can develop genetically specific viral populations across distinct anatomic compartments. This provides novel insights into the intricate nature of viral diversity and evolution dynamics in persistent infections.
Abundance and distribution of ringed and bearded seals in the Chukchi Sea: a reference for future trends
Authors: Boveng Peter L. , Chernook Vladimir I. , Moreland Erin E. , Conn Paul B. , Trukhanova Irina S. , Cameron Michael F. , Christman Cynthia L. , Crawford Justin A. , Harwood Lois , Hou Benjamin X. , Koslovsky Stacie M. , Lindsay Jessica M. , Litovka Denis I. , London Josh M. , McClintock Brett T. , Platonov Nikita , Quakenbush Lori , Richmond Erin L. , Vasiliev Alexander , Von Duyke Andrew L. , Willoughby Amy 
Published: August 2024

AbstractRinged (Pusa hispida) and bearded (Erignathus barbatus) seals are vulnerable to decreasing sea ice habitat in the rapidly warming Arctic. In April and May of 2016, we conducted an aerial survey over the ice-covered areas of the Chukchi Sea using thermal and color cameras to detect and count these seals on sea ice. We related the seal counts to environmental variables, and used the relationships to estimate the species’ distributions and abundance throughout the Chukchi Sea. We accounted for incomplete detection due to seals missed by sensors or image processing errors, behavioral responses to aircraft, or incomplete availability (i.e. seals that are in water or in snow dens on the ice, called lairs). For the latter, we used wet/dry records from satellite-linked bio-loggers, and remotely sensed snow melt dates to estimate the proportion of ringed seal individuals that were visible on ice for each day and location surveyed. To our knowledge, this is the first study where use of lairs by ringed seals has been formally addressed while estimating abundance from aerial surveys. Ringed seal abundance was estimated as= 592,577 (95% CI: 478,448–733,929), with highest densities near Kotzebue Sound, Alaska, USA. Bearded seal abundance was estimated as= 147,421 (95% CI: 114,155–190,380), with highest densities in broken pack ice near Bering Strait. The influence of environmental variables, such as snow depth and ice type, was consistent with prior studies of the species’ natural history, particularly ringed seals’ preference for snow of adequate depth for lairs. Our study provides the first comprehensive abundance estimates for ringed and bearded seals in the Chukchi Sea and establishes a reference for monitoring how their populations respond to Arctic warming.
Ubie Symptom Checker: A Clinical Vignette Simulation Study
Authors: Taylor N. Kenji , Nishibayashi Takashi 
Published: August 2024

AbstractBackgroundAI-driven symptom checkers (SC) are increasingly adopted in healthcare for their potential to provide users with accessible and immediate preliminary health education. These tools, powered by advanced artificial intelligence algorithms, assist patients in quickly assessing their symptoms. Previous studies using clinical vignette approaches have evaluated SC accuracy, highlighting both strengths and areas for improvement.ObjectiveThis study aims to evaluate the performance of the Ubie Symptom Checker (Ubie SC) using an innovative large language model-assisted (LLM) simulation method.MethodsThe study employed a three-phase methodology: gathering 400 publicly available clinical vignettes, medical entity linking these vignettes to the Ubie SC using large language models and physician supervision, and evaluation of accuracy metrics. The analysis focused on 328 vignettes that were within the scope of the Ubie SC with accuracy measured by Top-5 hit rates.ResultsUbie achieved a Top-5 hit accuracy of 63.4% and a Top-10 hit accuracy of 71.6%, indicating its effectiveness in providing relevant information based on symptom input. The system performed particularly well in domains such as the nervous system and respiratory conditions, though variability in accuracy was observed across different ICD groupings, highlighting areas for further refinement. When compared to physicians and comparator SC’s that used the same clinical vignettes set, Ubie compared favorably to the median physician hit accuracy.ConclusionsThe Ubie Symptom Checker shows considerable promise as a supportive education tool in healthcare. While the study highlights the system’s strengths, it also identifies areas for improvement suggesting continued refinement and real-world testing are essential to fully realize Ubie’s potential in AI-assisted healthcare.
Extracellular Vesicle-Mediated Delivery of HIF1α Reprograms Macrophages for resolutive response in Sepsis
Authors: Lee Yeji , Goo Jiyoung , Cho Seongeon , Kim Seong A , Nam Gi-Hoon , Kim Iljin , Park Jong-Wan , Jeong Cherlhyun , Kim In-San 
Published: August 2024

AbstractIn sepsis, the liver functions as a central filter organ, where hepatic macrophages form a primary antimicrobial defense layer by eliminating bacteria and regulating immune responses. Therefore, precise regulation of the immune response in hepatic macrophages is crucial for triggering effective defense mechanisms. We aim to modulate the defense immune response by delivering transcription factor HIF1α, a key regulator of monocyte/macrophage reprogramming in sepsis. Transcription factors are promising candidates because they dynamically modulate gene expression across diverse conditions, though delivering them remains challenging. In this study, we suggest a novel method for loading HIF1α into extracellular vesicles (EVs) to enhance immune defense and resolve sepsis. By delivering HIF1α to macrophages during sepsis, we promoted the differentiation of Nr1h3-dependent pro-efferocytic MoMFs and C/ebpβ-dependent pro-survival MoMFs. Pro-efferocytic MoMFs eliminate damaged hepatocytes and immune cells and pro-survival MoMFs withstand inflammatory conditions and trigger innate memory responses. Particularly, the zonation of these macrophages in the periportal region ensures effective pathogen clearance and minimizes tissue damage. These findings suggest that EV-mediated HIF1α delivery could be a promising therapeutic option for managing sepsis.
MorphoCellSorter: An Andrews plot-based sorting approach to rank microglia according to their morphological features
Authors: Benkeder Sarah , Dinh Son-Michel , Marchal Paul , Gea Priscille De , Thoby-Brisson Muriel , Hubert Violaine , Hristovska Ines , Pitollat Gabriel , Combet Kassandre , Cardoit Laura , Pillot Bruno , Léon Christelle , Wiart Marlène , Marty Serge , Honnorat Jérôme , Pascual Olivier , Comte Jean-Christophe 
Published: August 2024

AbstractMicroglia exhibit diverse morphologies reflecting environmental conditions, maturity or functional states. Thus, morphological characterization provides important information to understand microglial roles and functions. Most recent morphological analysis relies on classifying cells based on morphological parameters. However, this classification may lack biological relevance, as microglial morphologies represent a continuum rather than distinct, separate groups, and do not correspond to mathematically defined, clusters irrelevant of microglial cells function. Instead, we propose a new open-source tool, MorphoCellSorter, which assesses microglial morphology by automatically computing morphological criteria, using principal component analysis and Andrews plots to rank cells. MorphoCellSorter properly ranked cells from various microglia datasets in mice and rats of different age, fromin vivo,in vitroandex vivomodels, that were acquired using diverse imaging techniques. This approach allowed for the discrimination of cell populations in various pathophysiological conditions. Finally, MorphoCellSorter offers a versatile, easy and ready-to-use method to evaluate microglial morphological diversity that could easily be generalized to standardize practices across laboratories.
Detailed delineation of the fetal brain in diffusion MRI via multi-task learning
Authors: Karimi Davood , Calixto Camilo , Snoussi Haykel , Cortes-Albornoz Maria Camila , Velasco-Annis Clemente , Rollins Caitlin , Jaimes Camilo , Gholipour Ali , Warfield Simon K. 
Published: August 2024

AbstractDiffusion-weighted MRI is increasingly used to study the normal and abnormal development of fetal brain inutero. Recent studies have shown that dMRI can offer invaluable insights into the neurodevelopmental processes in the fetal stage. However, because of the low data quality and rapid brain development, reliable analysis of fetal dMRI data requires dedicated computational methods that are currently unavailable. The lack of automated methods for fast, accurate, and reproducible data analysis has seriously limited our ability to tap the potential of fetal brain dMRI for medical and scientific applications. In this work, we developed and validated a unified computational framework to (1) segment the brain tissue into white matter, cortical/subcortical gray matter, and cerebrospinal fluid, (2) segment 31 distinct white matter tracts, and (3) parcellate the brain’s cortex and delineate the deep gray nuclei and white matter structures into 96 anatomically meaningful regions. We utilized a set of manual, semi-automatic, and automatic approaches to annotate 97 fetal brains. Using these labels, we developed and validated a multi-task deep learning method to perform the three computations. Our evaluations show that the new method can accurately carry out all three tasks, achieving a mean Dice similarity coefficient of 0.865 on tissue segmentation, 0.825 on white matter tract segmentation, and 0.819 on parcellation. The proposed method can greatly advance the field of fetal neuroimaging as it can lead to substantial improvements in fetal brain tractography, tract-specific analysis, and structural connectivity assessment.
Erythropoietin-dependent Acquisition of CD71hiCD105hiPhenotype within CD235a−Early Erythroid Progenitors
Authors: Schippel Natascha , Wei Jing , Ma Xiaokuang , Kala Mrinalini , Qiu Shenfeng , Stoilov Peter , Sharma Shalini 
Published: August 2024

AbstractThe development of committed erythroid progenitors and their continued maturation into mature erythrocytes requires the cytokine erythropoietin (Epo). Here, we describe the immunophenotypic identification of a unique Epo-dependent colony-forming unit-erythroid (CFU-E) cell subtype that forms during early erythropoiesis (EE). This previously undescribed CFU-E subtype, termed late-CFU-E (lateC), lacks surface expression of the characteristic erythroid marker CD235a (glycophorin A) but has high levels of CD71 and CD105. LateCs could be prospectively detected in human bone marrow (BM) cells and, upon isolation and reculture, exhibited the potential to form CFU-E colonies in medium containing only Epo (no other cytokines) and continued differentiation along the erythroid trajectory. Analysis ofex vivocultures of BM CD34+cells showed that acquisition of the CD7hiCD105hiphenotype in lateCs is gradual and occurs through the formation of four EE cell subtypes. Of these, two are CD34+burst-forming unit-erythroid (BFU-E) cells, distinguishable as CD7loCD105loearly BFU-E and CD7hiCD105lolate BFU-E, and two are CD34−CFU-Es, also distinguishable as CD71loCD105loearly CFU-E and CD7hiCD105lomid-CFU-E. The transition of these EE populations is accompanied by a rise in CD36 expression, such that all lateCs are CD36+. Single cell RNA-sequencing analysis confirmed Epo-dependent formation of a CFU-E cluster that exhibits high coexpression of CD71, CD105, and CD36 transcripts. Gene set enrichment analysis revealed the involvement of genes specific to fatty acid and cholesterol metabolism in lateC formation. Overall, in addition to identifying a key Epo-dependent EE cell stage, this study provides a framework for investigation into mechanisms underlying other erythropoiesis-stimulating agents.