tbuckley/cabot-search huggingface dataset:
Cellular communication network factor 2 regulates smooth muscle cell transdifferentiation and lipid accumulation in atherosclerosis
Authors: Qian Xu, Jisheng Sun, Claire M Holden, Hildebrando Candido Ferreira Neto, Ti Wang, Chiyuan Zhang, Zuli Fu, Giji Joseph, Ruizheng Shi, Jinhu Wang, Andrew Leask, W Robert Taylor, Zhiyong Lin
Journal: Cardiovascular Research (2024)

Abstract Aims Accruing evidence illustrates an emerging paradigm of dynamic vascular smooth muscle cell (SMC) transdifferentiation during atherosclerosis progression. However, the molecular regulators that govern SMC phenotype diversification remain poorly defined. This study aims to elucidate the functional role and underlying mechanisms of cellular communication network factor 2 (CCN2), a matricellular protein, in regulating SMC plasticity in the context of atherosclerosis. Methods and results In both human and murine atherosclerosis, an up-regulation of CCN2 is observed in transdifferentiated SMCs. Using an inducible murine SMC CCN2 deletion model, we demonstrate that SMC-specific CCN2 knockout mice are hypersusceptible to atherosclerosis development as evidenced by a profound increase in lipid-rich plaques along the entire aorta. Single-cell RNA sequencing studies reveal that SMC deficiency of CCN2 positively regulates machinery involved in endoplasmic reticulum stress, endocytosis, and lipid accumulation in transdifferentiated macrophage-like SMCs during the progression of atherosclerosis, findings recapitulated in CCN2-deficient human aortic SMCs. Conclusion Our studies illuminate an unanticipated protective role of SMC-CCN2 against atherosclerosis. Disruption of vascular wall homeostasis resulting from vascular SMC CCN2 deficiency predisposes mice to atherosclerosis development and progression.
The use of a multi-metric readout screen to identify EHMT2/G9a-Inhibition as a modulator of Cancer-Associated Fibroblast Activation State
Authors: Nila C Wu, Rene Quevedo, Michelle Nurse, Kebria Hezaveh, Haijiao Liu, Fumao Sun, Julien Muffat, Yu Sun, Craig A Simmons, Tracy L McGaha, Panagiotis Prinos, Cheryl H Arrowsmith, Laurie Ailles, Elisa D'Arcangelo, Alison P McGuigan
Journal: Biomaterials (2024)
Revolutionizing Pressure Ulcer Regeneration: Unleashing the Potential of Extracellular Matrix-Derived Temperature-Sensitive Injectable Antioxidant Hydrogel for Superior Stem Cell Therapy
Authors: Junjie Tang, Penglei Zhang, Yadong Liu, Dingyu Hou, You Chen, Lili Cheng, Yifang Xue, Jie Liu
Journal: Biomaterials (2024)
Design and conduct of theranostic trials in neuro-oncology: Challenges and opportunities
Authors: Patrick Y Wen, Matthias Preusser, Nathalie L Albert
Journal: Neuro-Oncology (2024)

Theranostics is a new treatment modality integrating molecular imaging with targeted radionuclide therapy. Theranostic agents have received regulatory approval for some systemic cancers and have therapeutic potential in neuro-oncology. As clinical trials are developed to evaluate the efficacy of theranostic agents in brain tumors, specific considerations will have to be considered, taking into account lessons learned from previous studies examining other treatment modalities in neuro-oncology. These include the need for molecular imaging or surgical window-of-opportunity studies to confirm adequate passage across the blood-brain barrier, optimize eligibility criteria, and selection of the most appropriate response criteria and endpoints to address issues such as pseudoprogression. This review will discuss some of the issues that should be considered when designing clinical trials for theranostic agents.
Complex mpox situation, 2024
Authors: Pikka Jokelainen, Anne L. Wyllie, Nitin Gupta, Aleksandra Barac, Effrossyni Gkrania-Klotsas, Casandra Bulescu, José Ramón Paño-Pardo, Marta Mora-Rillo, Martin P. Grobusch, F-Xavier Lescure
Journal: Clinical Microbiology and Infection (2024)
Recurrent Clostridioides difficile infections in solid organ transplant recipients: the international CALIPSO study
Authors: Giusy Tiseo, Dafna Yahav, Alaa Atamna, Tomer Avni, Manuel Causse, Elena Pérez-Nadales, Alessandra Mularoni, Elena Reigadas, María Olmedo-Samperio, Mario Fernández-Ruiz, Zaira R. Palacios-Baena, Jesus Rodríguez-Baño, Paolo De Simone, Giandomenico Biancofiore, Eman Fares Sabik, Mical Paul, José María Aguado, Ugo Boggi, Patricia Muñoz, Julián Torres-Cisneros, Alessio Farcomeni, Marco Falcone
Journal: Journal of Infection (2024)

<h2>Abstract</h2><h3>Objective</h3> To evaluate the risk of recurrent <i>Clostridioides difficile</i> infection (CDI) in solid-organ transplant (SOT) recipients. <h3>Methods</h3> Retrospective multicenter study including SOT recipients with a first CDI episode in the year after transplantation (Jan 2017-June 2020). The primary outcome measure was recurrence, defined as a new CDI≤56 days from the first episode. A competing risk analysis was performed using the sub-distribution hazard model multivariable analysis. <h3>Results</h3> 191 SOT recipients were included: 101 (52.9%) were kidney, 66 (34.6%) liver, 11 (5.8%) lung, 8 (4.2%) simultaneous pancreas-kidney, 4 (2.1%) heart and 1 (0.5%) pancreas alone recipients. Treatment for the first CDI were: vancomycin (n=114,59.7%), vancomycin+metronidazole (n=39,20.4%), metronidazole (n=26,13.6%), fidaxomicin (n=9,4.7%), 3 patients did not receive any therapy. After the first CDI, 17/191 (8.9%) patients died within 56-day mortality without having a recurrence, while 23/191 (12%) patients had a recurrence. Among patients with recurrent CDI, 56-day mortality rate was 30.4% (7/23 patients). On multivariable analysis, severe CDI (sHR4.01, 95% CI 1.77-9.08, p<.001) and metronidazole monotherapy (sHR 3.65, 95% CI 1.64-8.14, p=.001) were factors independently associated with recurrence. <h3>Conclusions</h3> Metronidazole monotherapy is associated with increased risk of recurrent CDI in SOT recipients. Therapeutic strategies aimed to reduce the risk of recurrence should be implemented in this setting.
Sex differences in the molecular profile of adult diffuse glioma are shaped by IDH status and tumor microenvironment
Authors: Yingbo Huang, Yuting Shan, Weijie Zhang, Christina Printzis, Lorenzo Pesce, Danielle Stover, Catherine Stanhope, Barbara E Stranger, Rong Stephanie Huang
Journal: Neuro-Oncology (2024)

Abstract Background Sex differences in adult diffuse glioma (ADG) are well established clinically, yet the underlying molecular mechanisms remain inadequately understood. Here, we aim to reveal molecular features and cellular compositions unique to each sex in ADG to comprehend the role of sex in disease etiology. Methods We quantified sex differences in the transcriptome of ADG using multiple independent glioma patient datasets. Next, we delved into the single-cell landscape to examine sex differences in gene expression and cellular composition. To explore how sex influences disease progression, we analyzed paired samples from primary and recurrent ADG cases, aiming to identify sex-specific differences in molecular and cellular features. Results Our analysis revealed that mutations in isocitrate dehydrogenase (IDH) genes and the tumor microenvironment emerged as primary influencers of sex-differential molecular enrichments. In IDHwt tumors, genes in the neuronal signaling pathway are found to be enriched in male tumors, while genes in hypoxia and inflammatory response pathways are enriched in female tumors. This pattern was reversed in IDHmut gliomas. We hypothesized that these distinctions could be attributed to heterogeneous cellular composition between sexes. Using single-cell data, we observed distinctive patterns of sex differences in cell states, cell composition, and cell–cell interaction in IDHwt and IDHmut tumors separately. Further, by comparing molecular changes in paired primary and recurrent ADG samples, we identified sex-specific differences in molecular characteristics and cellular compositions of recurrent tumors. Conclusions Our results provide a comprehensive multilevel characterization of sex differences in ADG; such findings provide novel insights into glioma disease progression in each sex.
CD151 identifies a NK cell subset that is enriched in COVID-19 patients and correlates with disease severity
Authors: Ainhoa Amarilla-Irusta, Olatz Zenarruzabeitia, Arrate Sevilla, Víctor Sandá, Ainara Lopez-Pardo, Gabirel Astarloa-Pando, Raquel Pérez-Garay, Silvia Pérez-Fernández, Susana Meijide, Natale Imaz-Ayo, Eunate Arana-Arri, Laura Amo, Francisco Borrego
Journal: Journal of Infection (2024)

Severe coronavirus disease 2019 (COVID-19) often leads to acute respiratory distress syndrome and multi-organ dysfunction, driven by a dysregulated immune response, including a cytokine storm with elevated proinflammatory cytokine levels. Natural killer (NK) cells are part of the innate immune system with a fundamental role in the defense against viral infections. However, during COVID-19 acute infection, they exhibit an altered phenotype and impaired functionality contributing to the immunopathogenesis of the disease. In this work, we have studied a cohort of patients with COVID-19 (ranging from mild to severe) by analyzing IL-15, TGF-β, PlGF and GDF-15 plasma levels and performing multiparametric flow cytometry studies. Our results revealed that severe COVID-19 patients exhibited high levels of IL-15, PlGF and GDF-15, along with an enrichment of an NK cell subset expressing the CD151 tetraspanin, which correlated with IL-15 plasma levels and disease severity. In patients, these CD151+ NK cells displayed a more activated phenotype characterized by an increased expression of HLA-DR, CD38 and granzyme B, a distinct receptor repertoire, with lower levels of CD160 and CD31 and higher levels of CD55 and, remarkably, a higher expression of tissue-resident markers CD103 and the NK cell decidual marker CD9. Last of all, in individuals with severe disease, we identified an expansion of a CD151
Artificial intelligence alphafold model for molecular biology and drug discovery: a machine-learning-driven informatics investigation
Authors: Song-Bin Guo, Yuan Meng, Liteng Lin, Zhen-Zhong Zhou, Hai-Long Li, Xiao-Peng Tian, Wei-Juan Huang
Journal: Molecular Cancer (2024)

AlphaFold model has reshaped biological research. However, vast unstructured data in the entire AlphaFold field requires further analysis to fully understand the current research landscape and guide future exploration. Thus, this scientometric analysis aimed to identify critical research clusters, track emerging trends, and highlight underexplored areas in this field by utilizing machine-learning-driven informatics methods. Quantitative statistical analysis reveals that the AlphaFold field is enjoying an astonishing development trend (Annual Growth Rate = 180.13%) and global collaboration (International Co-authorship = 33.33%). Unsupervised clustering algorithm, time series tracking, and global impact assessment point out that Cluster 3 (Artificial Intelligence-Powered Advancements in AlphaFold for Structural Biology) has the greatest influence (Average Citation = 48.36 ± 184.98). Additionally, regression curve and hotspot burst analysis highlight "structure prediction" (s = 12.40, R2 = 0.9480, p = 0.0051), "artificial intelligence" (s = 5.00, R2 = 0.8096, p = 0.0375), "drug discovery" (s = 1.90, R2 = 0.7987, p = 0.0409), and "molecular dynamics" (s = 2.40, R2 = 0.8000, p = 0.0405) as core hotspots driving the research frontier. More importantly, the Walktrap algorithm further reveals that "structure prediction, artificial intelligence, molecular dynamics" (Relevance Percentage[RP] = 100%, Development Percentage[DP] = 25.0%), "sars-cov-2, covid-19, vaccine design" (RP = 97.8%, DP = 37.5%), and "homology modeling, virtual screening, membrane protein" (RP = 89.9%, DP = 26.1%) are closely intertwined with the AlphaFold model but remain underexplored, which implies a broad exploration space. In conclusion, through the machine-learning-driven informatics methods, this scientometric analysis offers an objective and comprehensive overview of global AlphaFold research, identifying critical research clusters and hotspots while prospectively pointing out underexplored critical areas.
Integrating Phosphate Enhances Biomineralization Effect of Methacrylate Cement in Vital Pulp Treatment with Improved Human Dental Pulp Stem Cells Stimulation
Authors: Jeong‐Hyun Ryu, Utkarsh Mangal, Jae‐Sung Kwon, Ji‐Young Seo, Seong‐Yun Byun, Young‐Hee Lee, Sungil Jang, Geelsu Hwang, Hyemin Ku, Yooseok Shin, Dohyun Kim, Sung‐Hwan Choi
Journal: Advanced Healthcare Materials (2024)

Abstract Vital pulp treatment (VPT) is crucial for preserving the health and function of the tooth in cases where the pulp tissue remains vital despite exposure. Various materials are introduced for this purpose. However, challenges such as low strength, high solubility, and tooth discoloration persist. Methylmethacrylate‐based cement (MC) offers excellent sealing ability, feasibility, and mechanical properties, making it a promising alternative for VPT. Phosphate‐based glass (PBG) has the potential to promote hard tissue regeneration by releasing key inducers, phosphorus (P) and calcium (Ca), for reparative odontogenesis. This study investigates PBG‐integrated MC (PIMC) by characterizing its properties, assessing human dental pulp stem cell activity related to initial inflammatory adaptation and odontogenic differentiation, and evaluating hard tissue formation using an in vivo dog pulpotomy model. Results indicate that a 5% PBG‐integrated MC (5PIMC) maintains the physicochemical properties of MC. Furthermore, 5PIMC demonstrates cytocompatibility, excellent expression of osteo/odontogenic markers, and resistance to inflammatory markers, significantly outperforming MC. Enhanced hard tissue formation is observed in the dental pulp of mongrel dog teeth treated with 5PIMC. These findings suggest that 5PIMC could be an optimal and suitable material for reparative odontogenesis through VPT.
Educational and income inequalities across diseases in Denmark: a register-based cohort study
Authors: Anna Vera Jørring Pallesen, Jochen O Mierau, Frederik Kølby Christensen, Laust Hvas Mortensen
Journal: The Lancet Public Health (2024)

Educational attainment and income are often, but not always, associated with disease incidence. Existing research typically examines single diseases, resulting in disparate analyses with little comparability. In this study, we aimed to assess educational and income inequalities across diseases in Denmark.
Decoding Paradoxical Links of Cytokine Markers in Cognition: Cross talk between Physiology, Inflammaging, and Alzheimer’s Disease- Related Cognitive Decline
Authors: Hiba Khan, Talib Naseem, Pooja Kaushik, Jagriti Narang, Rehan Khan, Siddharth Panwar, Suhel Parvez
Journal: Ageing Research Reviews (2024)
The intersection between transgender identity and migrant background: experienced barriers and facilitators to healthcare in The Netherlands
Authors: Eline Wijstma, Alex von Vaupel-Klein, Camiel Welling, Ali Jawad, Luella W. Smith, Raagini Bora, Sabrina Sanchez, Joël Illidge, Udi Davidovich, Elske Hoornenborg, Hanne Zimmermann
Journal: International Journal of Transgender Health (2024)

Background Transgender and gender-diverse (TGD) people, particularly those with migrant backgrounds (mTGD), face health inequalities and barriers to care globally.
Alendronate-functionalized polymeric micelles target icaritin to bone for mitigating osteoporosis in a rat model
Authors: Xiaoduan Sun, Yan Lin, Xingyue Zhong, Chao Fan, Zhen Liu, Xin Chen, Zaiyi Luo, Jili Wu, Singkome Tima, Zhirong Zhang, Jun Jiang, Xingjie Du, Xiangyu Zhou, Zhirong Zhong
Journal: Journal of Controlled Release (2024)
Microenvironment-responsive nano-bioconjugated vesicles for the multi-pronged treatment of liver fibrosis
Authors: Jie-Hua Xing, Li-Shuang Hou, Kaichao Zhang, Yao-Wen Zhang, Chenxi Zheng, Zedong Cai, Bingdong Sui, Si-Yuan Zhou, Wei He, Bang-Le Zhang
Journal: Journal of Controlled Release (2024)
<i>Helicobacter pylori</i> PldA modulates TNFR1-mediated p38 signaling pathways to regulate macrophage responses for its survival
Authors: Wei Yang Sit, Mei-Ling Cheng, Tsan-Jan Chen, Chia-Jo Chen, Bo-Nian Chen, Ding-Jun Huang, Pei-Lien Chen, Yun-Ching Chen, Chi-Jen Lo, Deng-Chyang Wu, Wan-Chen Hsieh, Chung-Ting Chang, Ruey-Hwa Chen, Wen-Ching Wang
Journal: Gut Microbes (2024)

Helicobacter pylori, a dominant member of the gastric microbiota was associated with various gastrointestinal diseases and presents a significant challenge due to increasing antibiotic resistance. This study identifies H. pylori's phospholipase A (PldA) as a critical factor in modulating host macrophage responses, facilitating H. pylori 's evasion of the immune system and persistence. PldA alters membrane lipids through reversible acylation and deacylation, affecting their structure and function. We found that PldA incorporates lysophosphatidylethanolamine into macrophage membranes, disrupting their bilayer structure and impairing TNFR1-mediated p38-MK2 signaling. This disruption results in reduced macrophage autophagy and elevated RIP1-dependent apoptosis, thereby enhancing H. pylori survival, a mechanism also observed in multidrug-resistant strains. Pharmacological inhibition of PldA significantly decreases H. pylori viability and increases macrophage survival. In vivo studies corroborate PldA's essential role in H. pylori persistence and immune cell recruitment. Our findings position PldA as a pivotal element in H. pylori pathogenesis through TNFR1-mediated membrane modulation, offering a promising therapeutic target to counteract bacterial resistance.
Acetate Utilization Promotes Hormone Therapy Resistance in Prostate Cancer through Neuroendocrine Differentiation
Authors: Dajun Gao, Yanting Shen, Lingfan Xu, Yi Sun, Hailiang Hu, Bin Xu, Zhong Wang, Huan Xu
Journal: Drug Resistance Updates (2024)

Tumor fatty acid (FA) metabolic plasticity plays a pivotal role in resistance to therapy and poses limitations to anticancer strategies. In this study, our aim is to uncover the role of acetate metabolism in neurodifferentiation (NED)-mediated castration-resistant prostate cancer (CRPC).
Fibroblast-specific TGF-β signaling mediates cardiac dysfunction, fibrosis, and hypertrophy in obese diabetic mice
Authors: Izabela Tuleta, Anis Hanna, Claudio Humeres, Jennifer T Aguilan, Simone Sidoli, Fenglan Zhu, Nikolaos G Frangogiannis
Journal: Cardiovascular Research (2024)

Abstract Aims Transforming growth factor (TGF)-β is up-regulated in the diabetic myocardium and may mediate fibroblast activation. We aimed at examining the role of TGF-β-induced fibroblast activation in the pathogenesis of diabetic cardiomyopathy. Methods and results We generated lean and obese db/db mice with fibroblast-specific loss of TbR2, the Type 2 receptor-mediating signaling through all three TGF-β isoforms, and mice with fibroblast-specific Smad3 disruption. Systolic and diastolic function, myocardial fibrosis, and hypertrophy were assessed. Transcriptomic studies and in vitro experiments were used to dissect mechanisms of fibroblast activation. Fibroblast-specific TbR2 loss attenuated systolic and diastolic dysfunction in db/db mice. The protective effects of fibroblast TbR2 loss in db/db mice were associated with attenuated fibrosis and reduced cardiomyocyte hypertrophy, suggesting that in addition to their role in fibrous tissue deposition, TGF-β-stimulated fibroblasts may also exert paracrine actions on cardiomyocytes. Fibroblast-specific Smad3 loss phenocopied the protective effects of fibroblast TbR2 loss in db/db mice. Db/db fibroblasts had increased expression of genes associated with oxidative response (such as Fmo2, encoding flavin-containing monooxygenase 2), matricellular genes (such as Thbs4 and Fbln2), and Lox (encoding lysyl oxidase). Ingenuity pathway analysis (IPA) predicted that neurohumoral mediators, cytokines, and growth factors (such as AGT, TGFB1, and TNF) may serve as important upstream regulators of the transcriptomic profile of diabetic mouse fibroblasts. IPA of scRNA-seq data identified TGFB1, p53, MYC, PDGF-BB, EGFR, and WNT3A/CTNNB1 as important upstream regulators underlying fibroblast activation in db/db hearts. Comparison of the transcriptome of fibroblasts from db/db mice with fibroblast-specific Smad3 loss and db/db Smad3 fl/fl controls identified Thbs4 [encoding thrombospondin-4 (TSP-4), a marker of activated fibroblasts] as a candidate diabetes-induced fibrogenic mediator. However, in vitro experiments showed no significant activating effects of matricellular or intracellular TSP-4 on cardiac fibroblasts. Conclusion Fibroblast-specific TGF-β/Smad3 signaling mediates ventricular fibrosis, hypertrophy, and dysfunction in Type 2 diabetes.
Clarifying the Risks of Consuming Edible Cannabis
Authors: Donna M. Lisi
Journal: JAMA Internal Medicine (2024)

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Letter by Aldaas et al Regarding Article, "Direct Oral Anticoagulants for Stroke Prevention in Patients With Device-Detected Atrial Fibrillation: A Study-Level Meta-Analysis of the NOAH-AFNET 6 and ARTESiA Trials"
Authors: Omar M. Aldaas, Amer M. Aldaas, Jonathan C. Hsu
Journal: Circulation (2024)
Mex3a Protects Against Atherosclerosis: Evidence From Mice and Humans
Authors: Donato Santovito, James M. Henderson, Kiril Bidzhekov, Vasiliki Triantafyllidou, Yvonne Jansen, Zhifen Chen, Floriana M. Farina, Anastasiia Diagel, Maria Aslani, Xavier Blanchet, Heribert Schunkert, Remco T.A. Megens, Yvonne Döring, Michael Sattler, Christian Weber
Journal: Circulation (2024)
New ubiquitomic subtypes in hepatocellular carcinoma: Insights for future therapeutic approaches
Authors: Hayato Nakagawa
Journal: Hepatology (2024)

Department of Gastroenterology and Hepatology, Mie University, 2-174 Edobashi, Tsu, Mie 514-8507, Japan Correspondence Hayato Nakagawa, Department of Gastroenterology and Hepatology, Mie University, 2-174 Edobashi, Tsu, Mie 514-8507, Japan. Email: [email protected]
Response by McIntyre et al to Letter Regarding Article, “Direct Oral Anticoagulants for Stroke Prevention in Patients With Device-Detected Atrial Fibrillation: A Study-Level Meta-Analysis of the NOAH-AFNET 6 and ARTESiA Trials”
Authors: William F. McIntyre, Alexander P. Benz, Jeff S. Healey, Renato Lopes
Journal: Circulation (2024)
Non-pharmaceutical interventions: evaluating challenges and priorities for future health shocks
Authors: Azeem Majeed, Jennifer K Quint, Samir Bhatt, Firoza Davies, Nazrul Islam
Journal: BMJ (2024)

Non-pharmaceutical interventions implemented during health shocks such as the covid-19 pandemic require rapid, robust, and rigorous evaluation that can generate timely evidence to guide government policy and maintain public confidence, say <b>Azeem Majeed and colleagues</b>