tbuckley/cabot-search huggingface dataset:
LncRNA MIR181A1HG Deficiency Attenuates Vascular Inflammation and Atherosclerosis
Authors: Huaner Ni, Yulong Ge, Ying Zhuge, Xiaoqiang Liu, Hangwei Chen, Junyi Liu, Weifeng Li, Xiang Wang, Gu Shen, Qiuling Wang, Rulin Zhuang, Mark W. Feinberg, Fang Wang
Journal: Circulation Research (2025)

Endothelial cell (EC) dysfunction and vascular inflammation are critical in the initiation and progression of atherosclerosis. Long noncoding RNAs play a critical role in vascular pathology, but relatively little is known about their involvement in controlling vascular inflammation. MIR181A1HG is a conserved long noncoding RNA located in juxtaposition with miR-181a1 and miR-181b1, both involved in vascular inflammation. The study aims to investigate the role of MIR181A1HG in regulating vascular inflammation. We examined the expression of MIR181A1HG in both human and mouse atherosclerotic lesions. Loss-of-function and gain-of-function studies, and multiple RNA-protein interaction assays were used to investigate the role and molecular mechanisms of MIR181A1HG in vascular inflammation and atherosclerosis. The atherosclerotic phenotypes of MIR181A1HG-/-ApoE-/- mice were analyzed in combination with single-cell RNA sequencing. The transcriptional regulation of MIR181A1HG was verified through luciferase reporter and chromatin immunoprecipitation assays. MIR181A1HG expression was abundant in ECs and significantly increased in both human and mouse atherosclerotic lesions. MIR181A1HG-/-ApoE-/- mice had reduced NLRP (NLR family pyrin domain containing) 3 inflammasome signaling, EC activation, monocyte infiltration, and atherosclerotic lesion formation. Genetic deletion of MIR181A1HG in myeloid sells did not alter the progression of atherosclerosis. Single-cell RNA sequencing analysis revealed that MIR181A1HG deficiency reduced the proportion of immune cells and enriched anti-inflammation pathways in EC clusters in atherosclerotic lesions. In contrast, EC-specific MIR181A1HG overexpression promoted NLRP3 inflammasome signaling, EC activation, and atherosclerotic lesion formation, effects that were reversed by pharmacological inhibition of NLRP3 (MCC950). MIR181A1HG was transcriptionally activated via an NF-κB (nuclear factor kappa B)/p65-dependent pathway. Mechanistically, MIR181A1HG mediated these effects on regulating NLRP3 inflammasome and EC activation in part through decoying Foxp1 (forkhead box transcription factor 1) away from the promoters of target genes, which was independent of the miR-181a1/b1 cluster. Finally, EC-specific Foxp1 silencing reversed the antiatherosclerotic effect mediated by MIR181A1HG-deletion in vivo. These findings identify MIR181A1HG as a central driver of vascular inflammation in atherosclerosis by its ability to decoy Foxp1 away from target gene promoters and activate NLRP3 inflammasome in the vascular endothelium. Our study suggests MIR181A1HG as a future therapeutic target for vascular inflammatory disease states.
Microglial mechanisms drive amyloid-β clearance in immunized patients with Alzheimer’s disease
Authors: Lynn van Olst, Brooke Simonton, Alex J. Edwards, Anne V. Forsyth, Jake Boles, Pouya Jamshidi, Thomas Watson, Nate Shepard, Talia Krainc, Benney MR Argue, Ziyang Zhang, Joshua Kuruvilla, Lily Camp, Mengwei Li, Hang Xu, Jeanette L. Norman, Joshua Cahan, Robert Vassar, Jinmiao Chen, Rudolph J. Castellani, James AR Nicoll, Delphine Boche, David Gate
Journal: Nature Medicine (2025)

Alzheimer's disease (AD) therapies utilizing amyloid-β (Aβ) immunization have shown potential in clinical trials. Yet, the mechanisms driving Aβ clearance in the immunized AD brain remain unclear. Here, we use spatial transcriptomics to explore the effects of both active and passive Aβ immunization in the AD brain. We compare actively immunized patients with AD with nonimmunized patients with AD and neurologically healthy controls, identifying distinct microglial states associated with Aβ clearance. Using high-resolution spatial transcriptomics alongside single-cell RNA sequencing, we delve deeper into the transcriptional pathways involved in Aβ removal after lecanemab treatment. We uncover spatially distinct microglial responses that vary by brain region. Our analysis reveals upregulation of the triggering receptor expressed on myeloid cells 2 (TREM2) and apolipoprotein E (APOE) in microglia across immunization approaches, which correlate positively with antibody responses and Aβ removal. Furthermore, we show that complement signaling in brain myeloid cells contributes to Aβ clearance after immunization. These findings provide new insights into the transcriptional mechanisms orchestrating Aβ removal and shed light on the role of microglia in immune-mediated Aβ clearance. Importantly, our work uncovers potential molecular targets that could enhance Aβ-targeted immunotherapies, offering new avenues for developing more effective therapeutic strategies to combat AD.
Dietary protein restriction elevates FGF21 levels and energy requirements to maintain body weight in lean men
Authors: Trine S. Nicolaisen, Aslak E. Lyster, Kim A. Sjøberg, Daniel T. Haas, Christian T. Voldstedlund, Anne-Marie Lundsgaard, Jakob K. Jensen, Ea M. Madsen, Casper K. Nielsen, Mads Bloch-Ibenfeldt, Nicolai J. Wewer Albrechtsen, Adam J. Rose, Natalie Krahmer, Christoffer Clemmensen, Erik A. Richter, Andreas M. Fritzen, Bente Kiens
Journal: Nature Metabolism (2025)

Dietary protein restriction increases energy expenditure and enhances insulin sensitivity in mice. However, the effects of a eucaloric protein-restricted diet in healthy humans remain unexplored. Here, we show in lean, healthy men that a protein-restricted diet meeting the minimum protein requirements for 5 weeks necessitates an increase in energy intake to uphold body weight, regardless of whether proteins are replaced with fats or carbohydrates. Upon reverting to the customary higher protein intake in the following 5 weeks, energy requirements return to baseline levels, thus preventing weight gain. We also show that fasting plasma FGF21 levels increase during protein restriction. Proteomic analysis of human white adipose tissue and in FGF21-knockout mice reveal alterations in key components of the electron transport chain within white adipose tissue mitochondria. Notably, in male mice, these changes appear to be dependent on FGF21. In conclusion, we demonstrate that maintaining body weight during dietary protein restriction in healthy, lean men requires a higher energy intake, partially driven by FGF21-mediated mitochondrial adaptations in adipose tissue.
Pulmonary endarterectomy on thin ice: improving risk estimation
Authors: Bernhard Moser, Clemens Aigner
Journal: European Respiratory Journal (2025)

<title>Extract</title> Complex thoracic and cardiac procedures inevitably carry some risk of morbidity and mortality. General risk prediction models such as the EuroLung score for pulmonary resections or the EuroSCORE II for cardiac procedures have proven their value in selecting patients for frequently performed procedures. However, they do not necessarily apply for specific pathophysiological conditions. When tailored risk modelling for rare conditions or procedures is performed, sufficient patient numbers are required and applicability in real-world settings has to be carefully evaluated.
Concerns regarding cohort construction and selection bias in the study of PAP devices and cancer incidence
Authors: Xiaonu Peng, Xiaofeng Yu, Haibo Huang, Peng Hao, Wei Zhang, Wenjun Li
Journal: European Respiratory Journal (2025)

<title>Extract</title> We read with great interest the recent article written by K<sc>endzerska</sc> <italic>et al</italic>. [1] entitled "Association between a recalled positive airway pressure device and incident cancer: a population-based study," which was published recently in your esteemed journal. We are writing to express a few concerns regarding the methodology and data presentation, particularly as detailed in figure 1 of the article. While the study provides valuable insights, the cohort construction process could have resulted in potential biases that may impact the generalisability and validity of the findings.
The moving target of progressive pulmonary fibrosis: insights for future clinical trials
Authors: Vincent Cottin, Valentine Mismetti, Claudia Valenzuela, Justin Oldham
Journal: European Respiratory Journal (2025)

<title>Extract</title> Progressive pulmonary fibrosis (PPF) is a recently proposed construct to identify individuals with fibrotic interstitial lung disease (ILD) other than idiopathic pulmonary fibrosis (IPF) who develop an IPF-like trajectory, characterised by fibrotic progression despite conventional therapy [1]. PPF leads to excessive extracellular matrix deposition following injury to the alveolar epithelium, leading to architectural distortion, impaired gas exchange and functional decline [2]. Common aetiologies that develop PPF include connective tissue disease-associated ILD, unclassifiable ILD, fibrotic hypersensitivity pneumonitis and other idiopathic interstitial pneumonias [3]. Clinically, PPF typically presents with worsening dyspnoea, exercise limitation, reduced pulmonary function and hypoxaemia, negatively impacting quality of life, imparting a heavy humanistic burden on patients and caregivers, and leading to substantial economic burden [4, 5]. The disease course of PPF is comparable to that of idiopathic pulmonary fibrosis, with worse survival than most malignancies [6].
Engineered multifunctional nanoparticles for enhanced radiation therapy: three-in-one approach for cancer treatment
Authors: Tejaswini Appidi, Debarghya China, George-Răzvan Ștefan, Michele Moreau, Serena Mao, Esteban Velarde, Ngeh Toyang, Henry Lowe, Aravind Kumar Rengan, Kai Ding, Wilfred Ngwa
Journal: Molecular Cancer (2025)

Clinical cancer treatment modalities include radiation as one of the first-line therapies used for treating almost two-thirds of cancer patients. Combinational therapy for cancer is becoming extremely popular, with multiple therapies and their pharmacological effects expected to provide a synergistic outcome. The nanotechnology-based combinational therapeutic approach is emerging as a more effective strategy, for its advantages include simultaneous loading of multiple drugs, on-demand drug delivery controlled by external or internal stimulus, targeting a particular site, and the potential to combine physical treatment modalities (like radiation, thermal therapies, etc.) with chemical interventions (like chemotherapy, immunotherapy, etc.). We report a combination of radiotherapy and chemotherapy mediated by a multifunctional lipo-polymeric hybrid nanosystem coated with gold, demonstrating the three different functionalities using a single nanosystem: a) radio sensitization, b) radiation-triggered delivery of drugs, and c) application as an X-ray/CT contrast agent. The lipo-polymeric hybrid nanoparticles, synthesized using a modified hydrogel isolation method, were loaded with a natural plant-derived anti-cancer agent "Caflanone." These nanoparticles were further subjected to in-situ reduction for a surface coating of gold, which provided enhanced radiosensitivity, radiation triggered drug delivery and X-ray/CT imaging. This approach using a multifunctional nanosystem leverages the biocompatibility of the lipo-polymeric hybrid system for the loading of drugs, precise spatiotemporal controllability of radiation for drug release, and the cytotoxicity of the plant-derived anti-cancer agent "Caflanone." A significant therapeutic efficacy in vitro against breast cancer (p = 0.0002), pancreatic cancer (p < 0.0001), and glioblastoma (p < 0.0001) was demonstrated with the combinational approach. The application of the nanosystem as an X-ray/CT contrast agent has been shown in vivo in tumor-bearing mice and the safety profile and histopathology evaluated in healthy mice showed no adverse effects. A significant increase (p = 0.01) in the survival of breast tumor-bearing mice treated with a combinational approach was also demonstrated. The engineered multifunctional nanoparticles enhanced the radiation therapy and triggered the drug release at the tumor site, triggering the action of encapsulated chemotherapeutic agents while providing image guidance.
Circular RNA circCLASP2 promotes nasopharyngeal carcinoma progression through binding to DHX9 to enhance PCMT1 translation
Authors: Miao Peng, Shanshan Zhang, Pan Wu, Xiangchan Hou, Dan Wang, Junshang Ge, Hongke Qu, Chunmei Fan, Yujuan Zhou, Bo Xiang, Qianjin Liao, Ming Zhou, Ming Tan, Guiyuan Li, Wei Xiong, Pan Chen, Zhaoyang Zeng, Zhaojian Gong
Journal: Molecular Cancer (2025)

Circular RNAs (circRNAs), characterized by their covalently closed-loop structures, constitute a distinct class of non-coding RNAs. They play pivotal regulatory roles within cells and are intricately associated with the progression of malignant tumors. However, their roles and the underlying mechanisms in nasopharyngeal carcinoma (NPC) progression have yet to be fully uncovered and comprehensively understood. Employing RNA sequencing technology, high-abundance circular RNAs in NPC were identified. Expression analysis of circCLASP2 in NPC tissues was conducted using quantitative real-time polymerase chain reaction (qRT-PCR) and in situ hybridization experiments. Through in vitro and in vivo functional assays, the influence of circCLASP2 on the proliferation and metastasis of NPC was investigated. LC-MS/MS technology analyzed the binding partners of circCLASP2, its differentially regulated targets, and the associated proteins of PCMT1. Interactions among circCLASP2, DHX9 protein, and PCMT1 mRNA were elucidated through RNA immunoprecipitation and RNA pull-down techniques. The effects of circCLASP2 and DHX9 on RNA G-quadruplex (rG4) structures and PCMT1 mRNA translation were explored through immunofluorescence (IF), ribosomal gradient separation, and dual-luciferase reporter assays. Immunoprecipitation (IP) revealed the downstream effector of the circCLASP2-DHX9-PCMT1 regulatory axis and Phalloidin staining confirmed its ultimate effect on the cytoskeleton. PDS treatment was applied for interventions in NPC, demonstrating potential therapeutic avenues. Our research revealed that circCLASP2, a novel circRNA that has not been reported in tumors, is upregulated in NPC and fosters cell proliferation and metastasis both in vitro and in vivo. Mechanistically, circCLASP2 acts as a molecular scaffold, facilitating the approximation of DHX9 to PCMT1 mRNA. DHX9 unwinds the inhibitory rG4 structure near the translation initiation site on PCMT1 mRNA, increasing PCMT1 expression. PCMT1 binds to and upregulates cytoskeleton-associated proteins, modulating cytoskeleton strength and dynamics and ultimately driving NPC cell proliferation and metastasis. In both in vitro and in vivo experiments, PDS significantly inhibits NPC growth and metastasis, showcasing promising therapeutic potential. Our investigation pinpointed a circular RNA, circCLASP2, which is upregulated in NPC and augments cytoskeletal functions via the DHX9-PCMT1 axis, contributing to the malignancy progression of NPC. This pathway holds promise as a potential therapeutic target for NPC. Furthermore, these molecules could also serve as biomarkers for adjunct diagnosis and prognosis assessment in NPC.
Incidental Detection of Meningioma on 18F-Flutemetamol PET
Authors: Young-Sil An, So Young Moon, Tae Hoon Roh
Journal: Clinical Nuclear Medicine (2025)

Meningioma is typically a benign tumor that may incidentally be found on imaging. This case demonstrates the utility of 18F-flutemetamol (FMM) PET/CT in an 80-year-old woman evaluated for memory decline. Although the scan was performed for dementia assessment, it revealed an incidental mass in the frontal region. Early-phase PET showed relatively low uptake, while delayed-phase imaging displayed intense uptake of 18F-FMM. Magnetic resonance imaging and surgical pathology confirmed the lesion as a meningioma. This report may aid in interpreting incidental mass lesions on 18F-FMM PET, providing a reference for physicians who may encounter similar findings.
Accurate fully automated assessment of left ventricle, left atrium, and left atrial appendage function from computed tomography using deep learning
Authors: Lee Jollans, Mariana Bustamante, Lilian Henriksson, Anders Persson, Tino Ebbers
Journal:  (2024)

Assessment of cardiac function is essential for diagnosis and treatment planning in cardiovascular disease. Volume of cardiac regions and the derived measures of stroke volume (SV) and ejection fraction (EF) are most accurately calculated from imaging. This study aims to develop a fully automatic deep learning approach for calculation of cardiac function from computed tomography (CT). Time-resolved CT data sets from 39 patients were used to train segmentation models for the left side of the heart including the left ventricle (LV), left atrium (LA), and left atrial appendage (LAA). We compared nnU-Net, 3D TransUNet, and UNETR. Dice Similarity Scores (DSS) were similar between nnU-Net (average DSS = 0.91) and 3D TransUNet (DSS = 0.89) while UNETR performed less well (DSS = 0.69). Intra-class correlation analysis showed nnU-Net and 3D TransUNet both accurately estimated LVSV (ICCnnU-Net = 0.95; ICC3DTransUNet = 0.94), LVEF (ICCnnU-Net = 1.00; ICC3DTransUNet = 1.00), LASV (ICCnnU-Net = 0.91; ICC3DTransUNet = 0.80), LAEF (ICCnnU-Net = 0.95; ICC3DTransUNet = 0.81), and LAASV (ICCnnU-Net = 0.79; ICC3DTransUNet = 0.81). Only nnU-Net significantly predicted LAAEF (ICCnnU-Net = 0.68). UNETR was not able to accurately estimate cardiac function. Time to convergence during training and time needed for inference were both faster for 3D TransUNet than for nnU-Net. nnU-Net outperformed two different vision transformer architectures for the segmentation and calculation of function parameters for the LV, LA, and LAA. Fully automatic calculation of cardiac function parameters from CT using deep learning is fast and reliable.
Lymphoscintigraphy for Peri-Anal Squamous Cell Carcinoma: A Case Report of an Atypical Location for Sentinel Lymph Node
Authors: Faeze Rabani, Amin Saber Tanha, Nasrin Raeisi, Azadeh Jabbari Noghabi, Ramin Sadeghi
Journal: Clinical Nuclear Medicine (2025)

This case report describes a 41-year-old man with a progressively enlarging, painful vegetative lesion in the perianal region, ultimately diagnosed as squamous cell carcinoma (SCC), through a punch biopsy. Sentinel lymph node (SLN) mapping was performed via preoperative lymphoscintigraphy utilizing 99mTc-Phytate. Notably, an SLN was identified in an atypical location, below the anterior superior iliac spine (ASIS) in the subcutaneous tissue, diverging from typical drainage patterns associated with perianal SCC. Surgical excision of the SLNs revealed no evidence of tumoral involvement. This case underscores the importance of personalized assessment with preoperative lymphoscintigraphy in atypical lymphatic drainage patterns for effective staging and treatment of malignancies such as peri-anal SCC.
Prediabetes and type 2 diabetes but not obesity are associated with alterations in bile acid related gut microbe-microbe and gut microbe-host community metabolism
Authors: Kristina Schlicht, Lea Pape, Nathalie Rohmann, Carina Knappe, Johannes Epe, Corinna Geisler, Daniela Pohlschneider, Susanne Brodesser, Lucy Kruse, Maria-Elisabeth Rohlfing, Katharina Hartmann, Kathrin Türk, Jens Marquardt, Jan Beckmann, Witigo von Schönfels, Alexia Beckmann, Perdita Wietzke-Braun, Dominik M. Schulte, Tim Hollstein, Tobias Demetrowitsch, Julia Jensen-Kroll, Fynn Brix, Stefan Schreiber, Andre Franke, Karin Schwarz, Silvio Waschina, Matthias Laudes
Journal: Gut Microbes (2025)

The interplay between bile acids (BAs) and metabolic diseases has gained importance in recent years, with a variety of studies investigating their relationship with diverging results. Therefore, in the present study we performed a detailed analysis of BA metabolism in 492 subjects with different metabolic phenotypes. Besides microbiomics and metabolomics this investigation included in silico analysis of community metabolism to examine metabolic interchange between different microbes as well as microbes and the human host. Our findings revealed distinct changes in the BA profiles of patients with diabetes and prediabetes, whereas obesity alone had no influence on circulating BAs. Impaired glycemic control led to increased circulating BAs, a shift toward more secondary BAs, and an increase in the ratio of glycine to taurine-conjugated BAs. Additional analyses revealed that the ratio of glycine to taurine conjugation demonstrated variations between the single BAs, cholic acid (CA), chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA), regardless of the metabolic status, with CA having a higher fraction of taurine conjugation. Furthermore, we found that microbiome alterations are associated with BAs, independent of diabetes or obesity. Analysis of microbial community metabolism revealed differential relative pathway abundance in relation to diabetes, particularly those related to membrane and polyamine synthesis. Increased bacterial cross-feeding of polyamines, galactose, and D-arabinose also coincided with an increase in BA. Notably, our serum metabolome analysis mirrored several of the previously in silico predicted exchanged metabolites, especially amino acid metabolism. Therefore, targeting BA metabolism may be a future approach for the treatment of metabolic diseases, especially prediabetes and type 2 diabetes.