tbuckley/cabot-search huggingface dataset:
EASL–EASD–EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD)
Authors: Frank Tacke, Paul Horn, Vincent Wai-Sun Wong, Vlad Ratziu, Elisabetta Bugianesi, Sven Francque, Shira Zelber-Sagi, Luca Valenti, Michael Roden, Fritz Schick, Hannele Yki-Järvinen, Amalia Gastaldelli, Roberto Vettor, Gema Frühbeck, Dror Dicker
Journal: Journal of Hepatology (2024)
Electrohydrodynamic Direct‐Writing Micro/Nanofibrous Architectures: Principle, Materials, and Biomedical Applications
Authors: Zhengjiang Liu, Jinqiao Jia, Qi Lei, Yan Wei, Yinchun Hu, Xiaojie Lian, Liqin Zhao, Xin Xie, Haiqing Bai, Xiaomin He, Longlong Si, Carol Livermore, Rong Kuang, Yi Zhang, Jiucun Wang, Zhaoyan Yu, Xudong Ma, Di Huang
Journal: Advanced Healthcare Materials (2024)

Electrohydrodynamic (EHD) direct-writing has recently gained attention as a highly promising additive manufacturing strategy for fabricating intricate micro/nanoscale architectures. This technique is particularly well-suited for mimicking the extracellular matrix (ECM) present in biological tissue, which serves a vital function in facilitating cell colonization, migration, and growth. The integration of EHD direct-writing with other techniques has been employed to enhance the biological performance of scaffolds, and significant advancements have been made in the development of tailored scaffold architectures and constituents to meet the specific requirements of various biomedical applications. Here, a comprehensive overview of EHD direct-writing is provided, including its underlying principles, demonstrated materials systems, and biomedical applications. A brief chronology of EHD direct-writing is provided, along with an examination of the observed phenomena that occur during the printing process. The impact of biomaterial selection and architectural topographic cues on biological performance is also highlighted. Finally, the major limitations associated with EHD direct-writing are discussed.
Genomic surveillance of SARS-CoV-2 evolution by a centralised pipeline and weekly focused sequencing, Austria, January 2021 to March 2023
Authors: Olga Frank, David Acitores Balboa, Maria Novatchkova, Ezgi Özkan, Marcus Martin Strobl, Ramesh Yelagandula, Tanino Guiseppe Albanese, Lukas Endler, Fabian Amman, Vera Felsenstein, Milanka Gavrilovic, Melanie Acosta, Timothej Patocka, Alexander Vogt, Ido Tamir, Julia Klikovits, Alexander Zoufaly, Tamara Seitz, Manuela Födinger, Andreas Bergthaler, Alexander Indra, Daniela Schmid, Peter Klimek, Alexander Stark, Franz Allerberger, Bernhard Benka, Katharina Reich, Luisa Cochella, Ulrich Elling
Journal: Eurosurveillance (2024)

Background The COVID-19 pandemic was largely driven by genetic mutations of SARS-CoV-2, leading in some instances to enhanced infectiousness of the virus or its capacity to evade the host immune system. To closely monitor SARS-CoV-2 evolution and resulting variants at genomic-level, an innovative pipeline termed SARSeq was developed in Austria. Aim We discuss technical aspects of the SARSeq pipeline, describe its performance and present noteworthy results it enabled during the pandemic in Austria. Methods The SARSeq pipeline was set up as a collaboration between private and public clinical diagnostic laboratories, a public health agency, and an academic institution. Representative SARS-CoV-2 positive specimens from each of the nine Austrian provinces were obtained from SARS-CoV-2 testing laboratories and processed centrally in an academic setting for S-gene sequencing and analysis. Results SARS-CoV-2 sequences from up to 2,880 cases weekly resulted in 222,784 characterised case samples in January 2021–March 2023. Consequently, Austria delivered the fourth densest genomic surveillance worldwide in a very resource-efficient manner. While most SARS-CoV-2 variants during the study showed comparable kinetic behaviour in all of Austria, some, like Beta, had a more focused spread. This highlighted multifaceted aspects of local population-level acquired immunity. The nationwide surveillance system enabled reliable nowcasting. Measured early growth kinetics of variants were predictive of later incidence peaks. Conclusion With low automation, labour, and cost requirements, SARSeq is adaptable to monitor other pathogens and advantageous even for resource-limited countries. This multiplexed genomic surveillance system has potential as a rapid response tool for future emerging threats.
Dissemination of extensively drug-resistant NDM-producing Providencia stuartii in Europe linked to patients transferred from Ukraine, March 2022 to March 2023
Authors: Sandra Witteveen, Jörg B Hans, Radosław Izdebski, Henrik Hasman, Ørjan Samuelsen, Laurent Dortet, Yvonne Pfeifer, Niall Delappe, Jesús Oteo-Iglesias, Dorota Żabicka, Martin Cormican, Mirco Sandfort, Felix Reichert, Anna K Pöntinen, Martin A Fischer, Nelianne Verkaik, María Pérez-Vazquez, Niels Pfennigwerth, Anette M Hammerum, Søren Hallstrøm, Marta Biedrzycka, Kati Räisänen, Cornelia CH Wielders, Paweł Urbanowicz, Angela de Haan, Karin Westmo, Fabian Landman, Han GJ van der Heide, Simon Lansu, Romy D Zwittink, Daan W Notermans, Aneta Guzek, Viacheslav Kondratiuk, Aidyn Salmanov, Sebastian Haller, Marius Linkevicius, Sören Gatermann, Anke Kohlenberg, Marek Gniadkowski, Guido Werner, Antoni PA Hendrickx
Journal: Eurosurveillance (2024)

Background The war in Ukraine led to migration of Ukrainian people. Early 2022, several European national surveillance systems detected multidrug-resistant (MDR) bacteria related to Ukrainian patients. Aim To investigate the genomic epidemiology of New Delhi metallo-β-lactamase (NDM)-producing Providencia stuartii from Ukrainian patients among European countries. Methods Whole-genome sequencing of 66 isolates sampled in 2022–2023 in 10 European countries enabled whole-genome multilocus sequence typing (wgMLST), identification of resistance genes, replicons, and plasmid reconstructions. Five bla NDM-1 -carrying- P. stuartii isolates underwent antimicrobial susceptibility testing (AST). Transferability to Escherichia coli of a bla NDM-1 -carrying plasmid from a patient strain was assessed. Epidemiological characteristics of patients with NDM-producing P. stuartii were gathered by questionnaire. Results wgMLST of the 66 isolates revealed two genetic clusters unrelated to Ukraine and three linked to Ukrainian patients. Of these three, two comprised bla NDM-1 -carrying- P. stuartii and the third bla NDM-5 -carrying- P. stuartii. The bla NDM-1 clusters (PstCluster-001, n = 22 isolates; PstCluster-002, n = 8 isolates) comprised strains from seven and four countries, respectively. The bla NDM-5 cluster (PstCluster-003) included 13 isolates from six countries. PstCluster-001 and PstCluster-002 isolates carried an MDR plasmid harbouring bla NDM-1, bla OXA-10 , bla CMY-16 , rmtC and armA , which was transferrable in vitro and, for some Ukrainian patients, shared by other Enterobacterales. AST revealed PstCluster-001 isolates to be extensively drug-resistant (XDR), but susceptible to cefiderocol and aztreonam–avibactam. Patients with data on age (n = 41) were 19–74 years old; of 49 with information on sex, 38 were male. Conclusion XDR P. stuartii were introduced into European countries, requiring increased awareness and precautions when treating patients from conflict-affected areas.
Pertussis outbreak in neonates and young infants across Italy, January to May 2024: implications for vaccination strategies
Authors: Marco Poeta, Cristina Moracas, Chiara Albano, Laura Petrarca, Marco Maglione, Luca Pierri, Maurizio Carta, Paolo Montaldo, Elisabetta Venturini, Maia De Luca, Danilo Buonsenso, Ilaria Brambilla, Vania Giacomet, Andrea Lo Vecchio, Eugenia Bruzzese, Fabio Midulla, Claudia Colomba, Alfredo Guarino
Journal: Eurosurveillance (2024)

Since January 2024, Italy experiences a pertussis outbreak, primarily affecting neonates and unvaccinated infants at high risk of severe complications and mortality; 11 major paediatric centres noted 108 hospitalisations and three deaths by 10 May. The outbreak reflects increased circulation of Bordetella pertussis and non-adherence to immunisation recommendations during pregnancy. Public health interventions, including maternal immunisation, vaccination of infants as early as possible and post-exposure prophylaxis, are critical for reducing the burden of pertussis and preventing further mortality.
Surveillance of vancomycin-resistant enterococci reveals shift in dominating clusters from vanA to vanB Enterococcus faecium clusters, Denmark, 2015 to 2022
Authors: Anette M Hammerum, Kasper Thystrup Karstensen, Louise Roer, Hülya Kaya, Mikkel Lindegaard, Lone Jannok Porsbo, Anne Kjerulf, Mette Pinholt, Barbara Juliane Holzknecht, Peder Worning, Karen Leth Nielsen, Sanne Grønvall Kjær Hansen, Marianne Clausen, Turid S Søndergaard, Esad Dzajic, Claus Østergaard, Mikala Wang, Kristoffer Koch, Henrik Hasman
Journal: Eurosurveillance (2024)

Background Vancomycin-resistant enterococci (VRE) are increasing in Denmark and Europe. Linezolid and vancomycin-resistant enterococci (LVRE) are of concern, as treatment options are limited. Vancomycin-variable enterococci (VVE) harbour the vanA gene complex but are phenotypically vancomycin-susceptible. Aim The aim was to describe clonal shifts for VRE and VVE in Denmark between 2015 and 2022 and to investigate genotypic linezolid resistance among the VRE and VVE. Methods From 2015 to 2022, 4,090 Danish clinical VRE and VVE isolates were whole genome sequenced. We extracted vancomycin resistance genes and sequence types (STs) from the sequencing data and performed core genome multilocus sequence typing (cgMLST) analysis for Enterococcus faecium . All isolates were tested for the presence of mutations or genes encoding linezolid resistance. Results In total 99% of the VRE and VVE isolates were E. faecium. From 2015 through 2019, 91.1% of the VRE and VVE were vanA E. faecium . During 2020, to the number of vanB E. faecium increased to 254 of 509 VRE and VVE isolates. Between 2015 and 2022, seven E. faecium clusters dominated: ST80-CT14 vanA , ST117-CT24 vanA , ST203-CT859 vanA, ST1421-CT1134 vanA (VVE cluster) , ST80-CT1064 vanA/vanB , ST117-CT36 vanB and ST80-CT2406 vanB. We detected 35 linezolid vancomycin-resistant E. faecium and eight linezolid-resistant VVEfm. Conclusion From 2015 to 2022, the numbers of VRE and VVE increased. The spread of the VVE cluster ST1421-CT1134 vanA E. faecium in Denmark is a concern, especially since VVE diagnostics are challenging. The finding of LVRE, although in small numbers, ia also a concern, as treatment options are limited.
OLFM4 promotes the progression of intestinal metaplasia through activation of the MYH9/GSK3β/β-catenin pathway
Authors: Hongfa Wei, Wenchao Li, Leli Zeng, Ni Ding, Kuan Li, Hong Yu, Fei Jiang, Haofan Yin, Yu Xia, Cuncan Deng, Nan Cai, Xiancong Chen, Liang Gu, Huanjie Chen, Feiran Zhang, Yulong He, Jia Li, Changhua Zhang
Journal: Molecular Cancer (2024)

Abstract Background Intestinal metaplasia (IM) is classified into complete intestinal metaplasia (CIM) and incomplete intestinal metaplasia (IIM). Patients diagnosed with IIM face an elevated susceptibility to the development of gastric cancer, underscoring the critical need for early screening measures. In addition to the complexities associated with diagnosis, the exact mechanisms driving the progression of gastric cancer in IIM patients remain poorly understood. OLFM4 is overexpressed in several types of tumors, including colorectal, gastric, pancreatic, and ovarian cancers, and its expression has been associated with tumor progression. Methods In this study, we used pathological sections from two clinical centers, biopsies of IM tissues, precancerous lesions of gastric cancer (PLGC) cell models, animal models, and organoids to explore the role of OLFM4 in IIM. Results Our results show that OLFM4 expression is highly increased in IIM, with superior diagnostic accuracy of IIM when compared to CDX2 and MUC2. OLFM4, along with MYH9, was overexpressed in IM organoids and PLGC animal models. Furthermore, OLFM4, in combination with Myosin heavy chain 9 (MYH9), accelerated the ubiquitination of GSK3β and resulted in increased β-catenin levels through the Wnt signaling pathway, promoting the proliferation and invasion abilities of PLGC cells. Conclusions OLFM4 represents a novel biomarker for IIM and could be utilized as an important auxiliary means to delimit the key population for early gastric cancer screening. Finally, our study identifies cell signaling pathways involved in the progression of IM.
A mild increase in nutrient signaling to mTORC1 in mice leads to parenchymal damage, myeloid inflammation and shortened lifespan
Authors: Ana Ortega-Molina, Cristina Lebrero-Fernández, Alba Sanz, Miguel Calvo-Rubio, Nerea Deleyto-Seldas, Lucía de Prado-Rivas, Ana Belén Plata-Gómez, Elena Fernández-Florido, Patricia González-García, Yurena Vivas-García, Elena Sánchez García, Osvaldo Graña-Castro, Nathan L. Price, Alejandra Aroca-Crevillén, Eduardo Caleiras, Daniel Monleón, Consuelo Borrás, María Casanova-Acebes, Rafael de Cabo, Alejo Efeyan
Journal: Nature Aging (2024)

Abstract The mechanistic target of rapamycin complex 1 controls cellular anabolism in response to growth factor signaling and to nutrient sufficiency signaled through the Rag GTPases. Inhibition of mTOR reproducibly extends longevity across eukaryotes. Here we report that mice that endogenously express active mutant variants of RagC exhibit multiple features of parenchymal damage that include senescence, expression of inflammatory molecules, increased myeloid inflammation with extensive features of inflammaging and a ~30% reduction in lifespan. Through bone marrow transplantation experiments, we show that myeloid cells are abnormally activated by signals emanating from dysfunctional RagC-mutant parenchyma, causing neutrophil extravasation that inflicts additional inflammatory damage. Therapeutic suppression of myeloid inflammation in aged RagC-mutant mice attenuates parenchymal damage and extends survival. Together, our findings link mildly increased nutrient signaling to limited lifespan in mammals, and support a two-component process of parenchymal damage and myeloid inflammation that together precipitate a time-dependent organ deterioration that limits longevity.
LINE-1 transcription activates long-range gene expression
Authors: Xiufeng Li, Luyao Bie, Yang Wang, Yaqiang Hong, Ziqiang Zhou, Yiming Fan, Xiaohan Yan, Yibing Tao, Chunyi Huang, Yongyan Zhang, Xueyan Sun, John Xiao He Li, Jing Zhang, Zai Chang, Qiaoran Xi, Anming Meng, Xiaohua Shen, Wei Xie, Nian Liu
Journal: Nature Genetics (2024)
A recurrent network model of planning explains hippocampal replay and human behavior
Authors: Kristopher T. Jensen, Guillaume Hennequin, Marcelo G. Mattar
Journal: Nature Neuroscience (2024)

When faced with a novel situation, people often spend substantial periods of time contemplating possible futures. For such planning to be rational, the benefits to behavior must compensate for the time spent thinking. Here, we capture these features of behavior by developing a neural network model where planning itself is controlled by the prefrontal cortex. This model consists of a meta-reinforcement learning agent augmented with the ability to plan by sampling imagined action sequences from its own policy, which we call 'rollouts'. In a spatial navigation task, the agent learns to plan when it is beneficial, which provides a normative explanation for empirical variability in human thinking times. Additionally, the patterns of policy rollouts used by the artificial agent closely resemble patterns of rodent hippocampal replays. Our work provides a theory of how the brain could implement planning through prefrontal-hippocampal interactions, where hippocampal replays are triggered by-and adaptively affect-prefrontal dynamics.
Distinct origin and region-dependent contribution of stromal fibroblasts to fibrosis following traumatic injury in mice
Authors: Daniel Holl, Wing Fung Hau, Anais Julien, Shervin Banitalebi, Jannis Kalkitsas, Soniya Savant, Enric Llorens-Bobadilla, Yann Herault, Guillaume Pavlovic, Mahmood Amiry-Moghaddam, David Oliveira Dias, Christian Göritz
Journal: Nature Neuroscience (2024)

Abstract Fibrotic scar tissue formation occurs in humans and mice. The fibrotic scar impairs tissue regeneration and functional recovery. However, the origin of scar-forming fibroblasts is unclear. Here, we show that stromal fibroblasts forming the fibrotic scar derive from two populations of perivascular cells after spinal cord injury (SCI) in adult mice of both sexes. We anatomically and transcriptionally identify the two cell populations as pericytes and perivascular fibroblasts. Fibroblasts and pericytes are enriched in the white and gray matter regions of the spinal cord, respectively. Both cell populations are recruited in response to SCI and inflammation. However, their contribution to fibrotic scar tissue depends on the location of the lesion. Upon injury, pericytes and perivascular fibroblasts become activated and transcriptionally converge on the generation of stromal myofibroblasts. Our results show that pericytes and perivascular fibroblasts contribute to the fibrotic scar in a region-dependent manner.
Developmental origin of oligodendrocytes determines their function in the adult brain
Authors: Sarah Foerster, Elisa M. Floriddia, David van Bruggen, Petra Kukanja, Bastien Hervé, Shangli Cheng, Eosu Kim, Benjamin U. Phillips, Christopher J. Heath, Richa B. Tripathi, Cody Call, Theresa Bartels, Katherine Ridley, Björn Neumann, Laura López-Cruz, Abbe H. Crawford, Cian J. Lynch, Manuel Serrano, Lisa Saksida, David H. Rowitch, Wiebke Möbius, Klaus-Armin Nave, Matthew N. Rasband, Dwight E. Bergles, Nicoletta Kessaris, William D. Richardson, Timothy J. Bussey, Chao Zhao, Gonçalo Castelo-Branco, Robin J. M. Franklin
Journal: Nature Neuroscience (2024)

In the mouse embryonic forebrain, developmentally distinct oligodendrocyte progenitor cell populations and their progeny, oligodendrocytes, emerge from three distinct regions in a spatiotemporal gradient from ventral to dorsal. However, the functional importance of this oligodendrocyte developmental heterogeneity is unknown. Using a genetic strategy to ablate dorsally derived oligodendrocyte lineage cells (OLCs), we show here that the areas in which dorsally derived OLCs normally reside in the adult central nervous system become populated and myelinated by OLCs of ventral origin. These ectopic oligodendrocytes (eOLs) have a distinctive gene expression profile as well as subtle myelination abnormalities. The failure of eOLs to fully assume the role of the original dorsally derived cells results in locomotor and cognitive deficits in the adult animal. This study reveals the importance of developmental heterogeneity within the oligodendrocyte lineage and its importance for homeostatic brain function.
Tipifarnib Reduces Extracellular Vesicles and Protects From Heart Failure
Authors: Vandana Mallaredy, Rajika Roy, Zhongjian Cheng, Charan Thej, Cindy Benedict, May Truongcao, Darukeshwara Joladarashi, Ajit Magadum, Jessica Ibetti, Maria Cimini, Carolina Gonzalez, Venkata Naga Srikanth Garikipati, Walter J. Koch, Raj Kishore
Journal: Circulation Research (2024)

Heart failure (HF) is one of the leading causes of mortality worldwide. Extracellular vesicles, including small extracellular vesicles or exosomes, and their molecular cargo are known to modulate cell-to-cell communication during multiple cardiac diseases. However, the role of systemic extracellular vesicle biogenesis inhibition in HF models is not well documented and remains unclear.
Multi-dimensional cell-free DNA-based liquid biopsy for sensitive early detection of gastric cancer
Authors: Pengfei Yu, Ping Chen, Min Wu, Guangyu Ding, Hua Bao, Yian Du, Zhiyuan Xu, Litao Yang, Jingquan Fang, Xingmao Huang, Qian Lai, Jia Wei, Junrong Yan, Shanshan Yang, Peng He, Xue Wu, Yang Shao, Dan Su, Xiangdong Cheng
Journal: Genome Medicine (2024)

Abstract Background Gastric cancer is the fifth most common cancer type. Most patients are diagnosed at advanced stages with poor prognosis. A non-invasive assay for the detection of early-stage gastric cancer is highly desirable for reducing associated mortality. Methods We collected a prospective study cohort of 110 stage I–II gastric cancer patients and 139 non-cancer individuals. We performed whole-genome sequencing with plasma samples and profiled four types of cell-free DNA (cfDNA) characteristics, fragment size pattern, copy number variation, nucleosome coverage pattern, and single nucleotide substitution. With these differential profiles, we developed an ensemble model to detect gastric cancer signals. Further, we validated the assay in an in-house first validation cohort of 73 gastric cancer patients and 94 non-cancer individuals and an independent second validation cohort of 47 gastric cancer patients and 49 non-cancer individuals. Additionally, we evaluated the assay in a hypothetical 100,000 screening population by Monte Carlo simulation. Results Our cfDNA-based assay could distinguish early-stage gastric cancer from non-cancer at an AUROC of 0.962 (95% CI: 0.942–0.982) in the study cohort, 0.972 (95% CI: 0.953–0.992) in the first validation cohort and 0.937 (95% CI: 0.890–0.983) in the second validation cohort. The model reached a specificity of 92.1% (128/139) and a sensitivity of 88.2% (97/110) in the study cohort. In the first validation cohort, 91.5% (86/94) of non-cancer individuals and 91.8% (67/73) of gastric cancer patients were correctly identified. In the second validation cohort, 89.8% (44/49) of non-cancer individuals and 87.2% (41/47) of gastric cancer patients were accurately classified. Conclusions We introduced a liquid biopsy assay using multiple dimensions of cfDNA characteristics that could accurately identify early-stage gastric cancer from non-cancerous conditions. As a cost-effective non-invasive approach, it may provide population-wide benefits for the early detection of gastric cancer. Trial registration This study was registered on ClinicalTrials.gov under the identifier NCT05269056 on March 7, 2022.