tbuckley/cabot-search huggingface dataset:
Multi-omics approaches reveal that diffuse midline gliomas present altered DNA replication and are susceptible to replication stress therapy
Authors: Anastasia E. Hains, Kashish Chetal, Tsunetoshi Nakatani, Joana G. Marques, Andreas Ettinger, Carlos A. O. Biagi Junior, Adriana Gonzalez-Sandoval, Renjitha Pillai, Mariella G. Filbin, Maria-Elena Torres-Padilla, Ruslan I. Sadreyev, Capucine Van Rechem
Journal: Genome biology (2024)

Abstract Background The fatal diffuse midline gliomas (DMG) are characterized by an undruggable H3K27M mutation in H3.1 or H3.3. K27M impairs normal development by stalling differentiation. The identification of targetable pathways remains very poorly explored. Toward this goal, we undertake a multi-omics approach to evaluate replication timing profiles, transcriptomics, and cell cycle features in DMG cells from both H3.1K27M and H3.3K27M subgroups and perform a comparative, integrative data analysis with healthy brain tissue. Results DMG cells present differential replication timing in each subgroup, which, in turn, correlates with significant differential gene expression. Differentially expressed genes in S phase are involved in various pathways related to DNA replication. We detect increased expression of DNA replication genes earlier in the cell cycle in DMG cell lines compared to normal brain cells. Furthermore, the distance between origins of replication in DMG cells is smaller than in normal brain cells and their fork speed is slower, a read-out of replication stress. Consistent with these findings, DMG tumors present high replication stress signatures in comparison to normal brain cells. Finally, DMG cells are specifically sensitive to replication stress therapy. Conclusions This whole genome multi-omics approach provides insights into the cell cycle regulation of DMG via the H3K27M mutations and establishes a pharmacologic vulnerability in DNA replication, which resolves a potentially novel therapeutic strategy for this non-curable disease.
Predicting the replicability of social and behavioural science claims in COVID-19 preprints
Authors: Alexandru Marcoci, David P. Wilkinson, Ans Vercammen, Bonnie C. Wintle, Anna Lou Abatayo, Ernest Baskin, Henk Berkman, Erin M. Buchanan, Sara Capitán, Tabaré Capitán, Ginny Chan, Kent Jason G. Cheng, Tom Coupé, Sarah Dryhurst, Jianhua Duan, John E. Edlund, Timothy M. Errington, Anna Fedor, Fiona Fidler, James G. Field, Nicholas Fox, Hannah Fraser, Alexandra L. J. Freeman, Anca Hanea, Felix Holzmeister, Sanghyun Hong, Raquel Huggins, Nick Huntington-Klein, Magnus Johannesson, Angela M. Jones, Hansika Kapoor, John Kerr, Melissa Kline Struhl, Marta Kołczyńska, Yang Liu, Zachary Loomas, Brianna Luis, Esteban Méndez, Olivia Miske, Fallon Mody, Carolin Nast, Brian A. Nosek, E. Simon Parsons, Thomas Pfeiffer, W. Robert Reed, Jon Roozenbeek, Alexa R. Schlyfestone, Claudia R. Schneider, Andrew Soh, Zhongchen Song, Anirudh Tagat, Melba Tutor, Andrew H. Tyner, Karolina Urbanska, Sander van der Linden
Journal: Nature Human Behaviour (2024)
Acoustic-pressure-driven ultrasonic activation of the mechanosensitive receptor RET and of cell proliferation in colonic tissue
Authors: Laura Zamfirov, Ngoc-Minh Nguyen, Maria Elena Fernández-Sánchez, Paula Cambronera Ghiglione, Eliott Teston, Alexandre Dizeux, Thomas Tiennot, Emmanuel Farge, Charlie Demené, Mickael Tanter
Journal: Nature Biomedical Engineering (2024)
Human AI collaboration for unsupervised categorization of live surgical feedback
Authors: Rafal Kocielnik, Cherine H. Yang, Runzhuo Ma, Steven Y. Cen, Elyssa Y. Wong, Timothy N. Chu, J. Everett Knudsen, Peter Wager, John Heard, Umar Ghaffar, Anima Anandkumar, Andrew J. Hung
Journal: npj Digital Medicine (2024)
Activation of Imprinted Gene <i>PW1</i> Promotes Cardiac Fibrosis After Ischemic Injury
Authors: Shan Kou, Zhengkai Lu, Defang Deng, Min Ye, Yu Sui, Lieyang Qin, Teng Feng, Zhen Jiang, Jufeng Meng, Chao-Po Lin, Xiajun Li, Chen Liu, Juan Tang, Hui Zhang
Journal: Circulation (2024)

BACKGROUND: Cardiac fibrosis, characterized by excessive extracellular matrix (ECM) deposition in the myocardium, is an important target for heart disease treatments. Pw1 (paternally expressed gene 3) is an imprinted gene expressed from the paternal allele, and de novo purine biosynthesis (DNPB) is a crucial pathway for nucleotide synthesis. However, the roles of PW1 and DNPB in ECM production by cardiac fibroblasts during myocardial ischemia are not yet understood. METHODS: To induce myocardial damage, we performed left anterior descending coronary artery ligation. We generated Pw1 CreER-2A-eGFP and Pw1 2A-CreER knock-in mouse lines to evaluate the expression of the 2 Pw1 alleles in normal and injured hearts. Bisulfite sequencing was used to analyze the DNA methylation of the Pw1 imprinting control region. We identified the phosphoribosylformylglycinamidine synthase ( Pfas ) gene, encoding the DNPB enzyme PFAS, as a direct target of PW1 using chromatin immunoprecipitation sequencing and real-time quantitative polymerase chain reaction. The role of DNPB in ECM production and cardiac fibrosis after injury was examined in vitro using cultured cardiac fibroblasts and in vivo with Pfas -deficient mice. RESULTS: Our study demonstrates that myocardial infarction reduces DNA methylation at the imprinting control region of the maternally imprinted gene Pw1 , triggering a switch from monoallelic imprinting to biallelic expression of Pw1 in cardiac fibroblasts. In activated cardiac fibroblasts, increased Pw1 expression promotes purine biosynthesis and induces ECM production by transcriptionally activating the DNPB factor Pfas . We identified that DNPB is essential for ECM production in activated fibroblasts and that loss of Pfas in fibroblasts limits cardiac fibrosis and improves heart function after injury. CONCLUSIONS: This study demonstrates that Pw1 imprinting is disrupted after injury and reveals a novel role for the downstream target PFAS in ECM production and cardiac fibrogenesis. Targeting the PW1/PFAS signaling pathway presents a promising therapeutic strategy for improving cardiac repair after injury.
T cells regulate intestinal motility and shape enteric neuronal responses to intestinal microbiota
Authors: Patricia Rodrigues Marques de Souza, Catherine M. Keenan, Laurie E. Wallace, Yasaman Bahojb Habibyan, Marcela Davoli-Ferreira, Christina Ohland, Fernando A. Vicentini, Kathy D. McCoy, Keith A. Sharkey
Journal: Gut Microbes (2024)

How the gut microbiota and immune system maintain intestinal homeostasis in concert with the enteric nervous system (ENS) remains incompletely understood. To address this gap, we assessed small intestinal transit, enteric neuronal density, enteric neurogenesis, intestinal microbiota, immune cell populations and cytokines in wildtype and T-cell deficient germ-free mice colonized with specific pathogen-free (SPF) microbiota, conventionally raised SPF and segmented filamentous bacteria (SFB)-monocolonized mice. SPF microbiota increased small intestinal transit in a T cell-dependent manner. SPF microbiota increased neuronal density in the myenteric and submucosal plexuses of the ileum and colon, similar to conventionally raised SPF mice, independently of T cells. SFB increased neuronal density in the ileum in a T cell-dependent manner, but independently of T cells in the colon. SPF microbiota stimulated enteric neurogenesis (Sox2 expression in enteric neurons) in the ileum in a T cell-dependent manner, but in the colon this effect was T cell-independent. T cells regulated nestin expression in the ENS. SPF colonization increased Th17 cells, RORγT+ Treg cells, and IL-1β and IL-17A levels in the ileum and colon. By neutralizing IL-1β and IL-17A, we observed that they control microbiota-mediated enteric neurogenesis but were not involved in the regulation of motility. Together, these findings provide new insights into the microbiota-neuroimmune dialog that regulates intestinal physiology.
α‐Synuclein in Parkinson's Disease: From Bench to Bedside
Authors: Gabriele Bellini, Vanessa D'Antongiovanni, Giovanni Palermo, Luca Antonioli, Matteo Fornai, Roberto Ceravolo, Nunzia Bernardini, Pascal Derkinderen, Carolina Pellegrini
Journal: Medicinal Research Reviews (2024)

ABSTRACT α‐Synuclein (α‐syn), a pathological hallmark of PD, is emerging as a bridging element at the crossroads between neuro/immune‐inflammatory responses and neurodegeneration in PD. Several evidence show that pathological α‐syn accumulates in neuronal and non‐neuronal cells (i.e., neurons, microglia, macrophages, skin cells, and intestinal cells) in central and peripheral tissues since the prodromal phase of the disease, contributing to brain pathology. Indeed, pathological α‐syn deposition can promote neurogenic/immune‐inflammatory responses that contribute to systemic and central neuroinflammation associated with PD. After providing an overview of the structure and functions of physiological α‐syn as well as its pathological forms, we review current studies about the role of neuronal and non‐neuronal α‐syn at the crossroads between neuroinflammation and neurodegeneration in PD. In addition, we provide an overview of the correlation between the accumulation of α‐syn in central and peripheral tissues and PD, related symptoms, and neuroinflammation. Special attention was paid to discussing whether targeting α‐syn can represent a suitable therapeutical approach for PD.
Next generation brain health: transforming global research and public health to promote prevention of dementia and reduce its risk in young adult populations
Authors: Francesca R Farina, Katie Bridgeman, Sarah Gregory, Lucía Crivelli, Isabelle F Foote, Otto-Emil I Jutila, Ludmila Kucikova, Luciano I Mariano, Kim-Huong Nguyen, Tony Thayanandan, Funmi Akindejoye, Joe Butler, Ismael L Calandri, Giedrė Čepukaitytė, Scott T Chiesa, Walter D Dawson, Kay Deckers, Vanessa De la Cruz-Góngora, Maria-Eleni Dounavi, Ishtar Govia, Edmarie Guzmán-Vélez, Shimaa A Heikal, Tanisha G Hill-Jarrett, Agustín Ibáñez, Bryan D James, Eimear McGlinchey, Donncha S Mullin, Graciela Muniz-Terrera, Maritza Pintado Caipa, Esraa M Qansuwa, Louise Robinson, Antonella Santuccione Chadha, Oliver M Shannon, Li Su, Wendy Weidner, Laura Booi
Journal: The Lancet Healthy Longevity (2024)
Visualization of endogenous p27 and Ki67 reveals the importance of a c-Myc-driven metabolic switch in promoting survival of quiescent cancer cells: Erratum
Authors: Ting La, Song Chen, Tao Guo, Xiao Hong Zhao, Liu Teng, Dandan Li, Michael Carnell, Yuan Yuan Zhang, Yu Chen Feng, Nicole Cole, Alexandra C. Brown, Didi Zhang, Qihan Dong, Jenny Y. Wang, Huixia Cao, Tao Liu, Rick F. Thorne, Feng-Min Shao, Xu Dong Zhang, Lei Jin
Journal: Theranostics (2024)

[This corrects the article DOI: 10.7150/thno.63763.].
AI model using CT-based imaging biomarkers to predict hepatocellular carcinoma in patients with chronic hepatitis B
Authors: Hyunjae Shin, Moon Haeng Hur, Byeong Geun Song, Soo Young Park, Gi-Ae Kim, Gwang Hyun Choi, Joon Yeul Nam, Minseok Albert Kim, Youngsu Park, Yunmi Ko, Jeayeon Park, Han Ah Lee, Sung Won Chung, Na Ryung Choi, Min Kyung Park, Yun Bin Lee, Dong Hyun Sinn, Seung Up Kim, Hwi Young Kim, Jong-Min Kim, Sang Joon Park, Hyung-Chul Lee, Dong Ho Lee, Jin Wook Chung, Yoon Jun Kim, Jung-Hwan Yoon, Jeong-Hoon Lee
Journal: Journal of Hepatology (2024)
A Single Center Retrospective Cohort Study of Hydroxychloroquine-Related Adverse Events in Adults with Lymphocytic Cicatricial Alopecia
Authors: Katelyn J Rypka, Zachary Wendland, Hannah Schull, Ora Raymond, James T Pathoulas, Rumbi Ngonyama, Bisma Khalid, Justin Yamanuha, Michael Evans, Ronda Farah, Maria Hordinsky
Journal: Journal of the American Academy of Dermatology (2024)
Tertiary amine modification enables triterpene nanoparticles to target the mitochondria and treat glioblastoma via pyroptosis induction
Authors: Xingchun Gao, Xiangjun Tang, Zewei Tu, Jiang Yu, Youmei Bao, Gretchen Long, Wendy C Sheu, Haoan Wu, Jia Liu, Jiangbing Zhou
Journal: Biomaterials (2024)
A Microenvironment‐Responsive Graphdiyne‐Iron Nanozyme Hydrogel with Antibacterial and Anti‐Inflammatory Effect for Periodontitis Treatment
Authors: Xiaojie Wu, Lu Wang, Yaning Lu, Meng‐Hao Li, Shuwei Liu, Yimeng Yang, Yulian Song, Sunzhuo Chen, Jing Kang, Alideertu Dong, Ying‐Wei Yang
Journal: Advanced Healthcare Materials (2024)

Periodontitis is a chronic inflammatory disease caused by dental plaque, which leads to tooth loosening and shifting or even tooth loss. Current treatments, including mechanical debridement and antibiotics, often fail to eradicate recalcitrant biofilms and mitigate excessive inflammation. Moreover, these interventions can disrupt the oral microbiome, potentially compromising long-term treatment outcomes. To address these limitations, an injectable nanoenzyme hydrogel composed of a dopamine (DA)-modified hyaluronic acid (HA) scaffold and a graphdiyne-iron (GDY-Fe) complex, named GDY-Fe@HA-DA, exhibits excellent tissue adhesion, self-healing, antibacterial properties, and biocompatibility. Under near-infrared laser irradiation, GDY-Fe@HA-DA effectively eradicates a variety of pathogens, including Escherichia coli, Staphylococcus aureus, and Porphyromonas gingivalis, through a synergistic combination of chemodynamical and photothermal therapies. The hydrogel's efficacy is further validated in both bacterial-infected skin wounds and rat periodontitis models. It effectively alleviates the inflammatory environment and promotes wound healing and periodontal tissue recovery. This findings highlight the potential of GDY-Fe@HA-DA as a promising therapeutic material for periodontitis and other tissue injuries.
Changes in skin research funding: the emergence of environmental sustainability criteria in the research competition assessment process
Authors: Hannah Badawy, Jane Harvey, Neil Rajan, Beth Stuart, Simon Tso
Journal: British Journal of Dermatology (2024)

Our study highlighted a drive for funders to embed (or consider incorporating) environmental sustainability criteria in their research competition assessment process. This development is highly relevant to skin research communities in the UK and internationally. Funders are in the unique position to shape the direction of research and mandate potential applicants to engage with all aspects of the research competition assessment process, including environmental impact. Our study highlights the need for research communities, especially early career researchers, to increase their preparedness to integrate environmental sustainability in designing, delivering and disseminating their research.
Remodeling the Inflammatory and Immunosuppressive Tumor Microenvironment for Enhancing Antiangiogenic Gene Therapy of Colorectal Cancer
Authors: Niu Jiazhen, Su Meihui, Liu De‐E, Li Na, Xin Youtao, Chen Qixian, Yu Yunjian, Ma Feihe, Elsabahy Mahmoud, Gao Hui
Journal: Advanced Healthcare Materials (2024)

Abstract Fusobacterium nucleatum ( Fn ), as an intestinal pathogenic bacterium, is closely related to the occurrence, progression, and limited therapeutic efficacy of colorectal cancer (CRC). The presence of Fn within CRC communities induces an inflammatory and immunosuppressive microenvironment while promoting new vessel formation. Therefore, developing novel methods to efficiently eliminate Fn and enhance the therapeutic outcomes against Fn ‐associated CRC is of great significance. Herein, a nanosystem named AFGTs‐PEG , which integrates antimicrobial agent lauric acid (LA), an antiangiogenic gene (sFlt‐1), a targeted polymer (OEI‐LA/PBA, OLP), and DSPE‐mPEG, to boost the gene therapy of Fn ‐infected CRC, is developed. The sFlt‐1 gene is delivered to CRC cells through lysosome escape, remarkably inhibiting new vessel formation at the CRC site and ultimately leading to CRC cell death. In principle, LA is used to eliminate Fn and its biofilms, and remodel the inflammatory and immunosuppressive microenvironment by restraining the generation of inflammatory factors and preventing polarization of M1 into M2 macrophages, thereby mitigating the adverse effects of Fn on antiangiogenic gene therapy. This study holds great promise for the treatment of bacteria‐colonized tumors.
Re: Tzoumas et al.: Improved outcomes with heavy silicone oil in complex primary retinal detachment: a large multicenter matched cohort study (Ophthalmology. 2024;131:737–740)
Authors: George Moussa, Maria Tadros, Soon Wai Ch'ng, Ash Sharma, Kim Son Lett, Arijit Mitra, Ajai K Tyagi, Walter Andreatta
Journal: Ophthalmology (2024)
Unveiling the mysteries of extrachromosomal circular DNA: from generation to clinical relevance in human cancers and health
Authors: Zilong Wang, Jiaying Yu, Wenli Zhu, Xiaoning Hong, Zhen Xu, Shuang Mao, Lei Huang, Peng Han, Chunxiao He, Changze Song, Xi Xiang
Journal: Molecular Cancer (2024)

Extrachromosomal circular DNAs (eccDNAs) are a type of circular DNAs originating from but independent of chromosomal DNAs. Nowadays, with the rapid development of sequencing and bioinformatics, the accuracy of eccDNAs detection has significantly improved. This advancement has consequently enhanced the feasibility of exploring the biological characteristics and functions of eccDNAs. This review elucidates the potential mechanisms of eccDNA generation, the existing methods for their detection and analysis, and their basic features. Furthermore, it focuses on the biological functions of eccDNAs in regulating gene expression under both physiological and pathological conditions. Additionally, the review summarizes the clinical implications of eccDNAs in human cancers and health.
Global disparities in drug-related adverse events of patients with multiple myeloma: a pharmacovigilance study
Authors: Majid Jaberi-Douraki, Xuan Xu, Danai Dima, Sikander Ailawadhi, Faiz Anwer, Sandra Mazzoni, Jason Valent, Muhammad Hamza Habib, Jim E. Riviere, Shahzad Raza
Journal: Blood Cancer Journal (2024)

Multiple myeloma (MM) is a complex hematological malignancy of clonal plasma cells driven by alterations to the chromosomal material leading to uncontrolled proliferation in the bone marrow. Ethnic and racial disparities persist in the prevalence, diagnosis, management, and outcomes of MM. These disparities are multifaceted and intersect with various factors, including demographics, geography, socioeconomic status, genetics, and access to healthcare. This study utilized the openFDA human drug adverse events (AEs) to analyze global data pertaining to MM patients and patterns of treatment-related AEs. We identified ten most frequently used drugs and drug regimens in six distinct regions, including North America (NA), Europe (EU), Asia (AS), Africa (AF), Oceania (OC), and Latin America & the Caribbean (LA). AE patterns were evaluated using the reporting odds ratio combined with a 95% confidence interval. AE reports were more prevalent in men than in women across all regions. Cardiotoxicities were more likely observed in AS and EU, while secondary neoplasms were more frequently reported in the EU. Nephropathies were prominent in OC, AF (in males), and AS (in females), while vascular toxicity, including embolism and thrombosis, was more common in NA (in males). A notable improvement in survival, particularly in AS, EU, and NA, with a significant decline in death rates was observed. Hospitalization rates displayed less variation in AS and EU but exhibited more pronounced fluctuations in AF, LA, and OC. In conclusion, this comprehensive analysis offers valuable insights into the demographic, geographic, and AE patterns of MM patients across the globe.
Language barriers in conservation: consequences and solutions
Authors: Tatsuya Amano, Violeta Berdejo-Espinola
Journal: Trends in Ecology & Evolution (2024)

Language barriers can severely hinder the advance of conservation science and its contribution to addressing the biodiversity crisis. We build a framework for understanding how language barriers can impede the evidence-based conservation of biodiversity in three ways: barriers to (i) the generation of evidence by non-native English speakers; (ii) the global synthesis of evidence scattered across different languages; and (iii) the application of English-language evidence to local decision making. We provide evidence, building on a growing body of literature, that quantifies the three consequences of language barriers in conservation. We also propose a checklist of solutions for reducing language barriers in conservation by addressing language disparities among scientists, promoting linguistic diversity in conservation, and making conservation science and its communication multilingual.
Systematically-designed mixtures outperform single fibers for gut microbiota support
Authors: T.M. Cantu-Jungles, V. Agamennone, T.J. Van den Broek, F.H.J. Schuren, B. Hamaker
Journal: Gut Microbes (2024)

Dietary fiber interventions to modulate the gut microbiota have largely relied on isolated fibers or specific fiber sources. We hypothesized that fibers systematically blended could promote more health-related bacterial groups. Initially, pooled in vitro fecal fermentations were used to design dietary fiber mixtures to support complementary microbial groups related to health. Then, microbial responses were compared for the designed mixtures versus their single fiber components in vitro using fecal samples from a separate cohort of 10 healthy adults. The designed fiber mixtures outperformed individual fibers in supporting bacterial taxa across donors resulting in superior alpha diversity and unexpected higher SCFA production. Moreover, unique shifts in community structure and specific taxa were observed for fiber mixtures that were not observed for single fibers, suggesting a synergistic effect when certain fibers are put together. Fiber mixture responses were remarkably more consistent than individual fibers across donors in promoting several taxa, especially butyrate producers from the Clostridium cluster XIVa. This is the first demonstration of synergistic fiber interactions for superior support of a diverse group of important beneficial microbes consistent across people, and unexpectedly high SCFA production. Overall, harnessing the synergistic potential of designed fiber mixtures represents a promising and more efficacious avenue for future prebiotic development.