tbuckley/cabot-search huggingface dataset:
Fecal metabolite profiling identifies liver transplant recipients at risk for postoperative infection
Authors: Christopher J. Lehmann, Nicholas P. Dylla, Matthew Odenwald, Ravi Nayak, Maryam Khalid, Jaye Boissiere, Jackelyn Cantoral, Emerald Adler, Matthew R. Stutz, Mark Dela Cruz, Angelica Moran, Huaiying Lin, Ramanujam Ramaswamy, Anitha Sundararajan, Ashley M. Sidebottom, Jessica Little, Eric G. Pamer, Andrew Aronsohn, John Fung, Talia B. Baker, Aalok Kacha
Journal: Cell Host & Microbe (2023)
Plant mRNAs move into a fungal pathogen via extracellular vesicles to reduce infection
Authors: Shumei Wang, Baoye He, Huaitong Wu, Qiang Cai, Obed Ramírez-Sánchez, Cei Abreu-Goodger, Paul R.J. Birch, Hailing Jin
Journal: Cell Host & Microbe (2023)

Cross-kingdom small RNA trafficking between hosts and microbes modulates gene expression in the interacting partners during infection. However, whether other RNAs are also transferred is unclear. Here, we discover that host plant Arabidopsis thaliana delivers mRNAs via extracellular vesicles (EVs) into the fungal pathogen Botrytis cinerea. A fluorescent RNA aptamer reporter Broccoli system reveals host mRNAs in EVs and recipient fungal cells. Using translating ribosome affinity purification profiling and polysome analysis, we observe that delivered host mRNAs are translated in fungal cells. Ectopic expression of two transferred host mRNAs in B. cinerea shows that their proteins are detrimental to infection. Arabidopsis knockout mutants of the genes corresponding to these transferred mRNAs are more susceptible. Thus, plants have a strategy to reduce infection by transporting mRNAs into fungal cells. mRNAs transferred from plants to pathogenic fungi are translated to compromise infection, providing knowledge that helps combat crop diseases.
Hepatology Highlights
Journal: Hepatology (2023)

EDITORS Juan Pablo Arab, London, Ontario, Canada Sumera I. Ilyas, Rochester, MN Abbreviations: ADAR1, acting on double-stranded RNA1; LCSCs, liver cancer stem cells; MASEF, Metabolomics-advanced Steatohepatitis Fibrosis MASH, metabolic dysfunction–associated steatohepatitis; PSC, primary sclerosing cholangitis; TRM, resident memory T cells.
Combining the Tyrosine Kinase Inhibitor Cabozantinib and the mTORC1/2 Inhibitor Sapanisertib Blocks ERK Pathway Activity and Suppresses Tumor Growth in Renal Cell Carcinoma
Authors: Yige Wu, Siqi Chen, Xiaolu Yang, Kazuhito Sato, Preet Lal, Yuefan Wang, Andrew T. Shinkle, Michael C. Wendl, Tina M. Primeau, Yanyan Zhao, Alanna Gould, Hua Sun, Jacqueline L. Mudd, Jeremy Hoog, R. Jay Mashl, Matthew A. Wyczalkowski, Chia-Kuei Mo, Ruiyang Liu, John M. Herndon, Sherri R. Davies, Di Liu, Xi Ding, Yvonne A. Evrard, Bryan E. Welm, David Lum, Mei Yee Koh, Alana L. Welm, Jeffrey H. Chuang, Jeffrey A. Moscow, Funda Meric-Bernstam, Ramaswamy Govindan, Shunqiang Li, James Hsieh, Ryan C. Fields, Kian-Huat Lim, Cynthia X. Ma, Hui Zhang, Li Ding, Feng Chen
Journal: Cancer Research (2023)

Abstract Current treatment approaches for renal cell carcinoma (RCC) face challenges in achieving durable tumor responses due to tumor heterogeneity and drug resistance. Combination therapies that leverage tumor molecular profiles could offer an avenue for enhancing treatment efficacy and addressing the limitations of current therapies. To identify effective strategies for treating RCC, we selected ten drugs guided by tumor biology to test in six RCC patient-derived xenograft (PDX) models. The multitargeted tyrosine kinase inhibitor (TKI) cabozantinib and mTORC1/2 inhibitor sapanisertib emerged as the most effective drugs, particularly when combined. The combination demonstrated favorable tolerability and inhibited tumor growth or induced tumor regression in all models, including two from patients who experienced treatment failure with FDA-approved TKI and immunotherapy combinations. In cabozantinib-treated samples, imaging analysis revealed a significant reduction in vascular density, and single-nucleus RNA sequencing (snRNA-seq) analysis indicated a decreased proportion of endothelial cells in the tumors. SnRNA-seq data further identified a tumor subpopulation enriched with cell-cycle activity that exhibited heightened sensitivity to the cabozantinib and sapanisertib combination. Conversely, activation of the epithelial–mesenchymal transition pathway, detected at the protein level, was associated with drug resistance in residual tumors following combination treatment. The combination effectively restrained ERK phosphorylation and reduced expression of ERK downstream transcription factors and their target genes implicated in cell-cycle control and apoptosis. This study highlights the potential of the cabozantinib plus sapanisertib combination as a promising treatment approach for patients with RCC, particularly those whose tumors progressed on immune checkpoint inhibitors and other TKIs. Significance: The molecular-guided therapeutic strategy of combining cabozantinib and sapanisertib restrains ERK activity to effectively suppress growth of renal cell carcinomas, including those unresponsive to immune checkpoint inhibitors.
Liquid Biopsy in H3K27M Diffuse Midline Glioma
Authors: Jina Patel, Rayan Aittaleb, Robert Doherty, Ananya Gera, Benison Lau, Dana Messinger, Jack Wadden, Andrea Franson, Amanda Saratsis, Carl Koschmann
Journal: Neuro-Oncology (2023)

Abstract Diffuse midline glioma (DMG) with H3K27M mutation is an aggressive and difficult to treat pediatric brain tumor. Recurrent gain of function mutations in H3.3 (H3.3A) and H3.1 (H3C2) at the 27th lysine to methionine (H3K27M) are seen in over 2/3 of DMGs, and are associated with a worse prognosis. Due to the anatomical location of DMG, traditional biopsy carries risk for neurologic injury as it requires penetration of vital midline structures. Further, radiographic (MRI) monitoring of DMG often shows nonspecific changes, which makes therapeutic monitoring difficult. This indicates a critical need for more minimally invasive methods, such as liquid biopsy, to understand, diagnose, and monitor H3K27M DMG. Here, we review the use of all modalities to date to detect biomarkers of H3K27M in cerebrospinal fluid (CSF), blood, and urine, and compare their effectiveness in detection, diagnosis, and monitoring treatment response. We provide specific detail of recent efforts to monitor CSF and plasma H3K27M cell-free DNA in patients undergoing therapy with the imipridone ONC201. Lastly, we discuss the future of therapeutic monitoring of H3K27M-DMG, including biomarkers such as mitochondrial DNA, mutant and modified histones, and novel sequencing-based approaches for improved detection methods.
Defining what matters through core outcomes set development: uniting stakeholder perspectives, empowering patient voices
Authors: Zachary H Hopkins, Lourdes Maria Perez Chada, Kristina C Duffin
Journal: British Journal of Dermatology (2023)

Journal Article Corrected proof Defining what matters through core outcomes set development: uniting stakeholder perspectives, empowering patient voices Get access Zachary H Hopkins, Zachary H Hopkins Conceptualization, Writing - original draft, Writing - review & editing Department of Dermatology, Spencer Fox Eccles School of Medicine, University of Utah, Salt Lake City, UT, USA Correspondence: Zachary H. Hopkins. Email: zach.hopkins@hsc.utah.edu Search for other works by this author on: Oxford Academic Google Scholar Lourdes Maria Perez Chada, Lourdes Maria Perez Chada Conceptualization, Writing - original draft, Writing - review & editing Department of Dermatology, Brigham and Women's Hospital, Boston, MA, USA Search for other works by this author on: Oxford Academic Google Scholar Kristina C Duffin Kristina C Duffin Conceptualization, Writing - review & editing Department of Dermatology, Spencer Fox Eccles School of Medicine, University of Utah, Salt Lake City, UT , USA Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljad493, https://doi.org/10.1093/bjd/ljad493 Published: 11 December 2023 Article history Received: 03 December 2023 Accepted: 04 December 2023 Published: 11 December 2023 Corrected and typeset: 10 January 2024
Ursa: A Comprehensive Multiomics Toolbox for High-Throughput Single-Cell Analysis
Authors: Lu Pan, Tian Mou, Yue Huang, Weifeng Hong, Min Yu, Xuexin Li
Journal: Molecular Biology and Evolution (2023)

The burgeoning amount of single-cell data has been accompanied by revolutionary changes to computational methods to map, quantify, and analyze the outputs of these cutting-edge technologies. Many are still unable to reap the benefits of these advancements due to the lack of bioinformatics expertise. To address this issue, we present Ursa, an automated single-cell multiomics R package containing 6 automated single-cell omics and spatial transcriptomics workflows. Ursa allows scientists to carry out post-quantification single or multiomics analyses in genomics, transcriptomics, epigenetics, proteomics, and immunomics at the single-cell level. It serves as a 1-stop analytic solution by providing users with outcomes to quality control assessments, multidimensional analyses such as dimension reduction and clustering, and extended analyses such as pseudotime trajectory and gene-set enrichment analyses. Ursa aims bridge the gap between those with bioinformatics expertise and those without by providing an easy-to-use bioinformatics package for scientists in hoping to accelerate their research potential. Ursa is freely available at https://github.com/singlecellomics/ursa.
Postoperative cerebellar mutism syndrome is an acquired autism-like network disturbance
Authors: Hrishikesh Suresh, Benjamin R Morgan, Karim Mithani, Nebras M Warsi, Han Yan, Jürgen Germann, Alexandre Boutet, Aaron Loh, Flavia Venetucci Gouveia, Julia Young, Jennifer Quon, Felipe Morgado, Jason Lerch, Andres M Lozano, Bassam Al-Fatly, Andrea A Kühn, Suzanne Laughlin, Michael C Dewan, Donald Mabbott, Carolina Gorodetsky, Ute Bartels, Annie Huang, Uri Tabori, James T Rutka, James M Drake, Abhaya V Kulkarni, Peter Dirks, Michael D Taylor, Vijay Ramaswamy, George M Ibrahim
Journal: Neuro-Oncology (2023)

Abstract Background Cerebellar mutism syndrome (CMS) is a common and debilitating complication of posterior fossa tumor surgery in children. Affected children exhibit communication and social impairments that overlap phenomenologically with subsets of deficits exhibited by children with Autism spectrum disorder (ASD). Although both CMS and ASD are thought to involve disrupted cerebro-cerebellar circuitry, they are considered independent conditions due to an incomplete understanding of their shared neural substrates. Methods In this study, we analyzed postoperative cerebellar lesions from 90 children undergoing posterior fossa resection of medulloblastoma, 30 of whom developed CMS. Lesion locations were mapped to a standard atlas, and the networks functionally connected to each lesion were computed in normative adult and pediatric datasets. Generalizability to ASD was assessed using an independent cohort of children with ASD and matched controls (n = 427). Results Lesions in children who developed CMS involved the vermis and inferomedial cerebellar lobules. They engaged large-scale cerebellothalamocortical circuits with a preponderance for the prefrontal and parietal cortices in the pediatric and adult connectomes, respectively. Moreover, with increasing connectomic age, CMS-associated lesions demonstrated stronger connectivity to the midbrain/red nuclei, thalami and inferior parietal lobules and weaker connectivity to the prefrontal cortex. Importantly, the CMS-associated lesion network was independently reproduced in ASD and correlated with communication and social deficits, but not repetitive behaviors. Conclusions Our findings indicate that CMS-associated lesions may result in an ASD-like network disturbance that occurs during sensitive windows of brain development. A common network disturbance between CMS and ASD may inform improved treatment strategies for affected children.
Efficacy of cola ingestion for oesophageal food bolus impaction: open label, multicentre, randomised controlled trial
Authors: E G Tiebie, E P Baerends, T Boeije, P G Frankenmolen, H Lameijer, W van den Berg, K J van Stralen, M L Ridderikhof, A J Bredenoord
Journal: BMJ (2023)

Abstract Objective To determine the efficacy and safety of cola in resolving complete oesophageal food bolus impaction. Design Open label, multicentre, randomised controlled trial. Setting Emergency departments of five Dutch hospitals at the secondary and tertiary level, between 22 December 2019 and 16 June 2022. Participants 51 adults presenting with complete oesophageal food bolus impaction, defined as a sudden inability to pass saliva after consumption of foods. Patients who ingested meat that contained bones, and patients with an American Society of Anesthesiologists (ASA) physical status classification of IV or higher were excluded. Interventions 28 patients in the intervention group were instructed to consume 25 mL cups of cola at intervals up to a maximum total volume of 200 mL. 23 patients in the control group awaited spontaneous passage. In either group, if complete resolution of symptoms did not occur, endoscopic removal was performed following current guidelines: within 6 hours for patients with complete obstruction, and within 24 hours for partial obstruction. In case of complete resolution of symptoms, elective diagnostic endoscopy was required. Main outcome measures Improvement of oesophageal food bolus obstruction as reported by patients (ie, aggregate of complete and partial passage), and evaluation of complete passage. The secondary outcome was any intervention related adverse event. Results Cola did not have a meaningful effect on the improvement of food bolus obstruction (17/28 (61%) intervention v 14/23 (61%) control; odds ratio 1.00, 95% confidence interval 0.33 to 3.1; relative risk reduction 0.0, 95% confidence interval −0.55 to 0.36; P&gt;0.99). Complete passage was reported more often in the intervention group but this difference was not significant (12/28 (43%) intervention v 8/23 (35%) control; odds ratio 1.4 (0.45 to 4.4); relative risk reduction −0.23 (−1.5 to 0.39); P=0.58). No severe adverse events occurred. However, six (21%) patients in the intervention group experienced temporary discomfort after drinking cola. Conclusions In this study, cola consumption did not lead to a higher rate of improvement of complete oesophageal food bolus impaction. Given the lack of adverse events in the treatment group and some events of resolution after treatment, cola might be considered as a first line treatment, but should not delay any planning of endoscopic management. Trial registration Netherlands Trial Register (currently International Clinical Trial Registry Platform) NL8312.
Laser-induced vapor nanobubbles for B16-F10 melanoma cell killing and intracellular delivery of chemotherapeutics
Authors: Jana Ramon, Yanou Engelen, Herlinde De Keersmaecker, Ilia Goemaere, Deep Punj, Julián Mejía Morales, Cédric Bonte, Geert Berx, Esther Hoste, Stephan Stremersch, Ine Lentacker, Stefaan C. De Smedt, Koen Raemdonck, Kevin Braeckmans
Journal: Journal of Controlled Release (2023)
A cell-free, biomimetic hydrogel based on probiotic membrane vesicles ameliorates wound healing
Authors: Thomas Kuhn, Ahmad Aljohmani, Nicolas Frank, Lina Zielke, Mina Mehanny, Matthias W. Laschke, Marcus Koch, Jessica Hoppstädter, Alexandra K. Kiemer, Daniela Yildiz, Gregor Fuhrmann
Journal: Journal of Controlled Release (2023)

Probiotic bacteria, such as Lactobacilli, have been shown to elicit beneficial effects in various tissue regeneration applications. However, their formulation as living bacteria is challenging, and their therapeutic use as proliferating microorganisms is especially limited in immunocompromised patients. Here, we propose a new therapeutic avenue to circumvent these shortcomings by developing a bacteriomimetic hydrogel based on membrane vesicles (MVs) produced by Lactobacilli. We coupled MVs from Lactobacillus plantarum and Lactobacillus casei, respectively, to the surface of synthetic microparticles, and embedded those bacteriomimetics into a pharmaceutically applicable hydrogel matrix. The wound microenvironment changes during the wound healing process, including adaptions of the pH and changes of the oxygen supply. We thus performed proteomic characterization of the MVs harvested under different culture conditions and identified characteristic proteins related to the biological effect of the probiotics in every culture state. In addition, we highlight a number of unique proteins expressed and sorted into the MVs for every culture condition. Using different in vitro models, we demonstrated that increased cell migration and anti-inflammatory effects of the bacteriomimetic microparticles were dependent on the culture condition of the secreting bacteria. Finally, we demonstrated the bacteriomimetic hydrogel's ability to improve healing in an in vivo mouse full-thickness wound model. Our results create a solid basis for the future application of probiotic-derived vesicles in the treatment of inflammatory dispositions and stimulates the initiation of further preclinical trials.
Shifting landscape in skin cancer incidence: the rising tide of cutaneous squamous cell carcinoma and potential implications for prevention
Authors: Celeste J Eggermont, Alexander M M Eggermont
Journal: British Journal of Dermatology (2023)

Journal Article Corrected proof Shifting landscape in skin cancer incidence: the rising tide of cutaneous squamous cell carcinoma and potential implications for prevention Get access Celeste J Eggermont, Celeste J Eggermont Writing - original draft Department of Dermatology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, the Netherlands Correspondence: Celeste J. Eggermont. Email: c.eggermont@erasmusmc.nl. https://orcid.org/0000-0002-1669-0283 Search for other works by this author on: Oxford Academic Google Scholar Alexander M M Eggermont Alexander M M Eggermont Writing - original draft University Medical Center Utrecht & Princess Maxima Center, Utrecht, the NetherlandsComprehensive Cancer Center München, Technical University München & Ludwig Maximilian University, Munich, Germany https://orcid.org/0000-0002-4278-040X Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljad480, https://doi.org/10.1093/bjd/ljad480 Published: 14 December 2023 Article history Received: 21 November 2023 Accepted: 24 November 2023 Published: 14 December 2023 Corrected and typeset: 23 January 2024
Transdermal delivery of Fn14 siRNA using a novel composite ionic liquid for treatment of psoriasis-like skin lesions
Authors: Lisha Li, Xiying Wu, Junchao Wu, Xinyue Zhang, Fengze Miao, Jiandong Wang, Jiaye Lu, Jun Liu, Zhongjian Chen, Zongguang Tai, Quangang Zhu
Journal: Journal of Controlled Release (2023)
An inflammation resolution–promoting intervention prevents atrial fibrillation caused by left ventricular dysfunction
Authors: Roddy Hiram, Feng Xiong, Patrice Naud, Jiening Xiao, Deanna K Sosnowski, Ewen Le Quilliec, Arnela Saljic, Issam H Abu-Taha, Markus Kamler, Charles-Alexandre LeBlanc, Doa’a G F Al-U’Datt, Martin G Sirois, Terence E Hebert, Jean-François Tanguay, Jean-Claude Tardif, Dobromir Dobrev, Stanley Nattel
Journal: Cardiovascular Research (2023)

Abstract Aims Recent studies suggest that bioactive mediators called resolvins promote an active resolution of inflammation. Inflammatory signalling is involved in the development of the substrate for atrial fibrillation (AF). The aim of this study is to evaluate the effects of resolvin-D1 on atrial arrhythmogenic remodelling resulting from left ventricular (LV) dysfunction induced by myocardial infarction (MI) in rats. Methods and results MI was produced by left anterior descending coronary artery ligation. Intervention groups received daily intraperitoneal resolvin-D1, beginning before MI surgery (early-RvD1) or Day 7 post-MI (late-RvD1) and continued until Day 21 post-MI. AF vulnerability was evaluated by performing an electrophysiological study. Atrial conduction was analysed by using optical mapping. Fibrosis was quantified by Masson’s trichrome staining and gene expression by quantitative polymerase chain reaction and RNA sequencing. Investigators were blinded to group identity. Early-RvD1 significantly reduced MI size (17 ± 6%, vs. 39 ± 6% in vehicle-MI) and preserved LV ejection fraction; these were unaffected by late-RvD1. Transoesophageal pacing induced atrial tachyarrhythmia in 2/18 (11%) sham-operated rats, vs. 18/18 (100%) MI-only rats, in 5/18 (28%, P &amp;lt; 0.001 vs. MI) early-RvD1 MI rats, and in 7/12 (58%, P &amp;lt; 0.01) late-RvD1 MI rats. Atrial conduction velocity significantly decreased post-MI, an effect suppressed by RvD1 treatment. Both early-RvD1 and late-RvD1 limited MI-induced atrial fibrosis and prevented MI-induced increases in the atrial expression of inflammation-related and fibrosis-related biomarkers and pathways. Conclusions RvD1 suppressed MI-related atrial arrhythmogenic remodelling. Early-RvD1 had MI sparing and atrial remodelling suppressant effects, whereas late-RvD1 attenuated atrial remodelling and AF promotion without ventricular protection, revealing atrial-protective actions unrelated to ventricular function changes. These results point to inflammation resolution–promoting compounds as novel cardio-protective interventions with a particular interest in attenuating AF substrate development.
Foxp3-mediated blockage of ryanodine receptor 2 underlies contact-based suppression by regulatory T cells
Authors: Xiaobo Wang, Shuang Geng, Junchen Meng, Ning Kang, Xinyi Liu, Yanni Xu, Huiyun Lyu, Ying Xu, Xun Xu, Xinrong Song, Bin Zhang, Xin Wang, Nuerdida Nuerbulati, Ze Zhang, Di Zhai, Xin Mao, Ruya Sun, Xiaoting Wang, Ruiwu Wang, Jie Guo, S R Wayne Chen, Xuyu Zhou, Tie Xia, Hai Qi, Xiaoyu Hu, Yan Shi
Journal: Journal of Clinical Investigation (2023)

The suppression mechanism of Tregs remains an intensely investigated topic. As our focus has shifted toward a model centered on indirect inhibition of DCs, a universally applicable effector mechanism controlled by the transcription factor forkhead box P3 (Foxp3) expression has not been found. Here, we report that Foxp3 blocked the transcription of ER Ca2+-release channel ryanodine receptor 2 (RyR2). Reduced RyR2 shut down basal Ca2+ oscillation in Tregs, which reduced m-calpain activities that are needed for T cells to disengage from DCs, suggesting a persistent blockage of DC antigen presentation. RyR2 deficiency rendered the CD4+ T cell pool immune suppressive and caused it to behave in the same manner as Foxp3+ Tregs in viral infection, asthma, hypersensitivity, colitis, and tumor development. In the absence of Foxp3, Ryr2-deficient CD4+ T cells rescued the systemic autoimmunity associated with scurfy mice. Therefore, Foxp3-mediated Ca2+ signaling inhibition may be a central effector mechanism of Treg immune suppression.