tbuckley/cabot-search huggingface dataset:
Circular RNA‐based neoantigen vaccine for hepatocellular carcinoma immunotherapy
Authors: Fei Wang, Guang Cai, Yingchao Wang, Qiuyu Zhuang, Zhixiong Cai, Yingying Li, Shaodong Gao, Fang Li, Cuilin Zhang, Bixing Zhao, Xiaolong Liu
Journal: MedComm (2024)

Abstract mRNA vaccines are regarded as a highly promising avenue for next‐generation cancer therapy. Nevertheless, the intricacy of production, inherent instability, and low expression persistence of linear mRNA significantly restrict their extensive utilization. Circular RNAs (circRNAs) offer a novel solution to these limitations due to their efficient protein expression ability, which can be rapidly generated in vitro without the need for extra modifications. Here, we present a novel neoantigen vaccine based on circRNA that induces a potent anti‐tumor immune response by expressing hepatocellular carcinoma‐specific tumor neoantigens. By cyclizing linearRNA molecules, we were able to enhance the stability of RNA vaccines and form highly stable circRNA molecules with the capacity for sustained protein expression. We confirmed that neoantigen‐encoded circRNA can promote dendritic cell (DC) activation and enhance DC‐induced T‐cell activation in vitro, thereby enhancing T‐cell killing of tumor cells. Encapsulating neoantigen‐encoded circRNA within lipid nanoparticles for in vivo expression has enabled the creation of a novel circRNA vaccine platform. This platform demonstrates superior tumor treatment and prevention in various murine tumor models, eliciting a robust T‐cell immune response. Our circRNA neoantigen vaccine offers new options and application prospects for neoantigen immunotherapy in solid tumors.
Autophagy‐mediated activation of the AIM2 inflammasome enhances M1 polarization of microglia and exacerbates retinal neovascularization
Authors: Xianyang Liu, Qian Zhou, Jiayu Meng, Hangjia Zuo, Ruonan Li, Rui Zhang, Huiping Lu, Zhi Zhang, Hongshun Li, Shuhao Zeng, Meng Tian, Hong Wang, Ke Hu, Na Li, Liming Mao, Shengping Hou
Journal: MedComm (2024)

Abstract Retinopathy of prematurity (ROP) is a retinal neovascularization (RNV) disease that is characterized by abnormal blood vessel development in the retina. Importantly, the etiology of ROP remains understudied. We re‐analyzed previously published single‐cell data and discovered a strong correlation between microglia and RNV diseases, particularly ROP. Subsequently, we found that reactive oxygen species reduced autophagy‐dependent protein degradation of absent in melanoma 2 (AIM2) in hypoxic BV2 cells, leading to increased AIM2 protein accumulation. Furthermore, we engineered AIM2 knockout mice and observed that the RNV was significantly reduced compared to wild‐type mice. In vitro vascular function assays also demonstrated diminished angiogenic capabilities following AIM2 knockdown in hypoxic BV2 cells. Mechanistically, AIM2 enhanced the M1‐type polarization of microglia via the ASC/CASP1/IL‐1β pathway, resulting in RNV. Notably, the administration of recombinant protein IL‐1β exacerbated angiogenesis, while its inhibition ameliorated the condition. Taken together, our study provides a novel therapeutic target for ROP and offers insight into the interaction between pyroptosis and autophagy.
Patient-Specific Vascularized Tumor Model: Blocking TAM Recruitment with Multispecific Antibodies Targeting CCR2 and CSF-1R
Authors: Huu Tuan Nguyen, Ellen L Kan, Mouhita Humayun, Nadia Gurvich, Giovanni S Offeddu, Zhengpeng Wan, Mark F Coughlin, Diana C Renteria, Andreas Loew, Susan Wilson, Christie Zhang, Vivian Vu, Sharon Wei Ling Lee, Seng-Lai Tan, David Barbie, Jonathan Hsu, Mark Robert Gillrie, Roger D Kamm
Journal: Biomaterials (2024)
Prevalence of clinically significant liver fibrosis in the general population: A systematic review and meta-analysis
Authors: Hee Yeon Kim, Jung Hwan Yu, Young Eun Chon, Seung Up Kim, Mi Na Kim, Ji Won Han, Han Ah Lee, Young-Joo Jin, Jihyun An, Miyoung Choi, Dae Won Jun
Journal: Clinical and Molecular Hepatology (2024)

Although important, clinically significant liver fibrosis is often overlooked in the general population. We aimed to examine the prevalence of clinically significant liver fibrosis using noninvasive tests (NITs) in the general population.
Augmentative effects of leukemia inhibitory factor reveal a critical role for TYK2 signaling in vascular calcification
Authors: Ioana Alesutan, Mehdi Razazian, Trang T.D. Luong, Misael Estepa, Lakmi Pitigala, Laura A. Henze, Jakob Obereigner, Gregor Mitter, Daniel Zickler, Mirjam Schuchardt, Christine Deisl, Manousos Makridakis, Can Gollmann-Tepeköylü, Andreas Pasch, Daniel Cejka, Susanne Suessner, Marlies Antlanger, Bernhard Bielesz, Mathias Müller, Antonia Vlahou, Johannes Holfeld, Kai-Uwe Eckardt, Jakob Voelkl
Journal: Kidney International (2024)

Medial vascular calcification in chronic kidney disease (CKD) involves pro-inflammatory pathways induced by hyperphosphatemia. Several interleukin 6 family members have been associated with pro-calcific effects in vascular smooth muscle cells (VSMCs) and are considered as therapeutic targets. Therefore, we investigated the role of leukemia inhibitory factor (LIF) during VSMC calcification. LIF expression was found to be increased following phosphate exposure of VSMCs. LIF supplementation aggravated, while silencing of endogenous LIF or LIF receptor (LIFR) ameliorated the pro-calcific effects of phosphate in VSMCs. The soluble LIFR mediated antagonistic effects towards LIF and reduced VSMC calcification. Mechanistically, LIF induced phosphorylation of the non-receptor tyrosine-protein kinase 2 (TYK2) and signal transducer and activator of transcription-3 (STAT3) in VSMCs. TYK2 inhibition by deucravacitinib, a selective, allosteric oral immunosuppressant used in psoriasis treatment, not only blunted the effects of LIF, but also interfered with the pro-calcific effects induced by phosphate. Conversely, TYK2 overexpression aggravated VSMC calcification. Ex vivo calcification of mouse aortic rings was ameliorated by Tyk2 pharmacological inhibition and genetic deficiency. Cholecalciferol-induced vascular calcification in mice was improved by Tyk2 inhibition and in the Tyk2-deficient mice. Similarly, calcification was ameliorated in Abcc6/Tyk2-deficient mice after adenine/high phosphorus-induced CKD. Thus, our observations indicate a role for LIF in CKD-associated vascular calcification. Hence, the effects of LIF identify a central pro-calcific role of TYK2 signaling, which may be a future target to reduce the burden of vascular calcification in CKD.
Renal Reinforcements
Authors: Robert L. Thomas, Dena E. Rifkin
Journal: Journal of the American Society of Nephrology (2024)

1Division of Endocrinology, University of California, San Diego and Veterans Affairs Healthcare System, San Diego, California 2Division of Nephrology, University of California, San Diego and Veterans Affairs Healthcare System, San Diego, California Correspondence: Dr. Robert L. Thomas, email: [email protected] See related article, "Effect of Avenciguat on Albuminuria in Patients with CKD: Two Randomized Placebo-Controlled Trials," on pages XXX–XXX.
Development and psychometric properties of the Functional Assessment of Cancer Therapy-Cutaneous T-Cell Lymphoma (FACT-CTCL)
Authors: Caroline Raymundo, David Cella, Lynne I Wagner, Daniel S Hippe, Mengyang Di, Joan Guitart, Steven T Rosen, Christiane Querfeld, Michi M Shinohara
Journal: British Journal of Dermatology (2024)

Abstract Background Patients with mycosis fungoides (MF)/Sézary Syndrome (SS) can experience impacted health-related quality of life (HRQoL). Objectives To validate the CTCL-S, a novel subscale of the Functional Assessment of Cancer Therapy–General (FACT-G), in patients with MF/SS. Methods Qualitative interviews were conducted with expert clinicians and patients with MF/SS. Thematic analysis identified the most common concerns, and 19 items were selected. Patients with MF/SS were recruited from a single centre. FACT-G, CTCL-S (collectively ‘FACT-CTCL’), Skindex-29 and Visual Analogue Scale–Pruritis (VAS-itch) were administered. A subset repeated FACT-CTCL and VAS-itch after ≈2 weeks. Patient demographics and clinical characteristics were obtained via review of the electronic medical records. Psychometric properties were assessed. Internal consistency was estimated using Cronbach’s α. Convergent and discriminant validity were assessed by comparing CTCL-S with disease stage, age, VAS-itch, FACT-G and Skindex-29. Exploratory factor analysis (EFA) was used to preliminarily assess CTCL-S dimensionality. Test–retest repeatability was summarized using intraclass correlation coefficient (ICC), within-subject standard deviation and within-subject coefficient of variation. Results Seventy-two patients completed the initial survey, and 35 repeated the FACT-CTCL and VAS-itch after ≈2 weeks. Two-thirds were men; most were White (78%). The majority (85%) had MF, 15% had SS and 75% early (stage IA–IIA) and 25% advanced (≥ stage IIB) disease. Preliminary EFA found a single predominant factor, supporting a hypothesis of unidimensionality of the CTCL-S. Internal consistency of the CTCL-S was high, with α = 0.95 [95% confidence interval (CI) 0.93–0.96]. There was no significant change in CTCL-S average test–retest scores [ICC 0.93 (P = 0.63)]. CTCL-S was significantly lower in advanced vs. early-stage disease [median (interquartile range) 34 (26–48) vs. 59 (44–68), P &amp;lt; 0.001] and strongly correlated with VAS-itch [Spearman’s r (rs) –0.70, 95% CI –0.81 to –0.55], FACT-G (rs 0.77, 95% CI 0.65–0.85) and Skindex-29 (rs –0.90, 95% CI –0.94 to –0.84), supporting convergent validity. CTCL-S scores had little correlation with age (rs 0.19, 95% CI –0.05 to 0.41, P = 0.12), supporting discriminant validity. Conclusions The FACT-CTCL is a disease-specific instrument for assessing HRQoL with high reproducibility and good performance in a cohort of patients with MF/SS.
Pericytes in the brain and heart: functional roles and response to ischaemia and reperfusion
Authors: Turgay Dalkara, Leif Østergaard, Gerd Heusch, David Attwell
Journal: Cardiovascular Research (2024)

In the last 20 years there has been a revolution in our understanding of how blood flow is regulated in many tissues. Whereas it used to be thought that essentially all blood flow control occurred at the arteriole level, it is now recognised that control of capillary blood flow by contractile pericytes plays a key role both in regulating blood flow physiologically and in reducing it in clinically-relevant pathological conditions. In this article we compare and contrast how brain and cardiac pericytes regulate cerebral and coronary blood flow, focusing mainly on the pathological events of cerebral and cardiac ischemia. The cerebral and coronary capillary beds differ dramatically in morphology, yet in both cases pericyte-mediated capillary constriction plays a key role in restricting blood flow after ischemia and possibly in other pathological conditions. We conclude with suggestions for therapeutic approaches to relaxing pericytes, which may prove useful in the long term for reducing pericyte-induced ischemia.
Pseudogene GSTM3P1 derived long non-coding RNA promotes ischemic acute kidney injury by target directed microRNA degradation of kidney-protective mir-668.
Authors: Qingqing Wei, Jing Huang, Man Jiang Livingston, Shixuan Wang, Guie Dong, Hongyan Xu, Jiliang Zhou, Zheng Dong
Journal: Kidney International (2024)
“All-in-one” metal polyphenol network nanocapsules integrated microneedle patches for lipophagy fueled ferroptosis-mediated multimodal therapy
Authors: Wenhao Wang, Ziqiao Zhong, Siyuan Peng, Jintao Fu, Minglong Chen, Tianqun Lang, Xiao Yue, Yanping Fu, Jingyu He, Yuzhen Jin, Ying Huang, Chuanbin Wu, Zhengwei Huang, Xin Pan
Journal: Journal of Controlled Release (2024)
Fast and accurate estimation of selection coefficients and allele histories from ancient and modern DNA
Authors: Andrew H Vaughn, Rasmus Nielsen
Journal: Molecular Biology and Evolution (2024)

We here present CLUES2, a full-likelihood method to infer natural selection from sequence data that is an extension of the method CLUES. We make several substantial improvements to the CLUES method that greatly increases both its applicability and its speed. We add the ability to use ancestral recombination graphs on ancient data as emissions to the underlying hidden Markov model, which enables CLUES2 to use both temporal and linkage information to make estimates of selection coefficients. We also fully implement the ability to estimate distinct selection coefficients in different epochs, which allows for the analysis of changes in selective pressures through time, as well as selection with dominance. In addition, we greatly increase the computational efficiency of CLUES2 over CLUES using several approximations to the forward-backward algorithms and develop a new way to reconstruct historic allele frequencies by integrating over the uncertainty in the estimation of the selection coefficients. We illustrate the accuracy of CLUES2 through extensive simulations and validate the importance sampling framework for integrating over the uncertainty in the inference of gene trees. We also show that CLUES2 is well-calibrated by showing that under the null hypothesis, the distribution of log-likelihood ratios follows a χ2 distribution with the appropriate degrees of freedom. We run CLUES2 on a set of recently published ancient human data from Western Eurasia and test for evidence of changing selection coefficients through time. We find significant evidence of changing selective pressures in several genes correlated with the introduction of agriculture to Europe and the ensuing dietary and demographic shifts of that time. In particular, our analysis supports previous hypotheses of strong selection on lactase persistence during periods of ancient famines and attenuated selection in more modern periods.
Author Correction: Anakinra in Sanfilippo syndrome: a phase 1/2 trial
Authors: Lynda E. Polgreen, Agnes H. Chen, Youngju Pak, Anna Luzzi, Adolfo Morales Garval, Jonathan Acevedo, Gal Bitan, Michelina Iacovino, Cara O’Neill, Julie B. Eisengart
Journal: Nature Medicine (2024)
Framework nucleic acid-based nanoparticles enhance temozolomide sensitivity in glioblastoma
Authors: Yufei Lan, Xiaodie Li, Boyang Liu, Jiankun Lu, Boming Zuo, Yue Wang, Shuting Cao, Xin Fu, Qu Yue, Xin Luo, Xiangyang Zhong, Yaoyuan Dong, Zhao Wang, Tao Yang, Xinyun Xie, Tianci Zeng, Manqing Zhang, Yuankai Wang, Yixiong Shen, Huaqin Zuo, Yan Zhao, Chao Zhang, Hongbo Guo
Journal: Drug Resistance Updates (2024)

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POS0623 COMPARATIVE EFFECTIVENESS OF SUBCUTANEOUS SARILUMAB, SUBCUTANEOUS TOCILIZUMAB, AND INTRAVENOUS TOCILIZUMAB IN PATIENTS WITH RHEUMATOID ARTHRITIS: THE ANSWER COHORT STUDY
Authors: A. Onishi, M. Tanaka, H. Onizawa, T. Fujii, K. Murata, K. Murakami, M. Hashimoto, R. Watanabe, Y. Nozaki, C. Ashida, W. Yamamoto, H. Yamada, S. Sendo, K. Ebina, M. Hidehiko, Y. Son, Y. Wada, K. Hata, S. Matsuda, A. Morinobu
Journal: Annals of the Rheumatic Diseases (2024)
Application of the updated International IgA Nephropathy Prediction Tool in children one- or two-years post-biopsy.
Authors: Sean J. Barbour, Rosanna Coppo, Lee Er, Maria Luisa Russo, Zhi-Hong Liu, Jie Ding, Xuhui Zhong, Ritsuko Katafuchi, Norishige Yoshikawa, Hong Xu, Shoji Kagami, Yukio Yuzawa, Francesco Emma, Alexandra Cambier, Licia Peruzzi, Robert J. Wyatt, Daniel C. Cattran, Caihong Zeng, Biage Su, Xuhui Zhong, Koichi Nakanishi, Yihui Zhai, Maki Urushihara, Motoshi Hattori, Francesca Diomedi Camassei, Antonella Barreca, Thomas Robert, Larisa Prikhodina, Ulla Berg, Rezan Topaloglu, Malgorzata Mizerska-Wasiak, Aikaterini Papagianni, Shubha S. Bellur, Ian Roberts
Journal: Kidney International (2024)

The pediatric International IgA Nephropathy (IgAN) Prediction Tool comprises two models with and without ethnicity and is the first method to predict the risk of a 30% decline in estimated glomerular filtration rate (eGFR) or kidney failure in children at the time of biopsy using clinical risk factors and Oxford MEST histology scores. However, it is unknown if the Prediction Tool can be applied after a period of observation post-biopsy. Using an international multi-ethnic cohort of 947 children with IgAN, 38% of whom were followed into adulthood, the Prediction Tool was updated for use one-year after biopsy. Compared to the original pediatric Prediction Tool, the updated post-biopsy Prediction Tool had a better model fit with higher R2D (51%/50% vs 20%), significant increase in 4-year C-statistics (0.83 vs 0.73/0.69, ΔC 0.09 [95% confidence interval 0.07-0.10] and ΔC 0.14 [0.12-0.15]) and better 4-year calibration with lower integrated calibration indices (0.74/0.54 vs 2.45/1.01). Results were similar after internal validation and when the models were applied two-years after biopsy. Trajectories of eGFR after a baseline one-year post-biopsy were non-linear and those at higher predicted risk started with a lower eGFR and experienced a more rapid decline over time. In children, eGFR had a variable rate of increase until 15-18 years old then decreased linearly with a more rapid decline in higher risk groups that was similar to young adults of comparable risk. Thus, the original pediatric Prediction Tool should be used in children at the time of biopsy, and the updated pediatric Prediction Tool should be used to revaluate risk one- or two-years after biopsy.
Risk of serious adverse events after primary shoulder replacement: development and external validation of a prediction model using linked national data from England and Denmark
Authors: Epaminondas Markos Valsamis, Marie Louise Jensen, Gillian Coward, Adrian Sayers, Rafael Pinedo-Villanueva, Jeppe V Rasmussen, Gary S Collins, Jonathan L Rees
Journal: The Lancet Rheumatology (2024)
The effect of frailty on mortality and hospital admission in patients with benign pleural disease in Wales: a cohort study
Authors: Roxanna Short, Ben Carter, Alessia Verduri, Eleanor Barton, Nick Maskell, Jonathan Hewitt
Journal: The Lancet Healthy Longevity (2024)

Pleural disease is common, representing 5% of the acute medical workload, and its incidence is rising, partly due to the ageing population. Frailty is an important feature and little is known about disease progression in patients with frailty and pleural disease. We aimed to examine the effect of frailty on mortality and other relevant outcomes in patients diagnosed with pleural disease.
Safety and efficacy of subcutaneous iscalimab (CFZ533) in two distinct populations of patients with Sjögren's disease (TWINSS): week 24 results of a randomised, double-blind, placebo-controlled, phase 2b dose-ranging study
Authors: Benjamin A Fisher, Xavier Mariette, Athena Papas, Thomas Grader-Beck, Hendrika Bootsma, Wan-Fai Ng, P L A van Daele, Stephanie Finzel, Ghaith Noaiseh, Sergio Elgueta, Josef Hermann, Sara S McCoy, Esen Akpek, Arthur Bookman, Monika Sopala, Michela Montecchi-Palmer, Wen-Lin Luo, Cornelia Scheurer, Wolfgang Hueber
Journal: The Lancet (2024)
Cognitive and psychiatric symptom trajectories 2–3 years after hospital admission for COVID-19: a longitudinal, prospective cohort study in the UK
Authors: Maxime Taquet, Zuzanna Skorniewska, Thomas De Deyn, Adam Hampshire, William R Trender, Peter J Hellyer, James D Chalmers, Ling-Pei Ho, Alex Horsley, Michael Marks, Krisnah Poinasamy, Betty Raman, Olivia C Leavy, Matthew Richardson, Omer Elneima, Hamish J C McAuley, Aarti Shikotra, Amisha Singapuri, Marco Sereno, Ruth M Saunders, Victoria C Harris, Natalie Rogers, Linzy Houchen-Wolloff, Neil J Greening, Parisa Mansoori, Ewen M Harrison, Annemarie B Docherty, Nazir I Lone, Jennifer Quint, Christopher E Brightling, Louise V Wain, Rachael A Evans, John R Geddes, Paul J Harrison
Journal: The Lancet Psychiatry (2024)
Assessing the extent and determinants of socioeconomic inequalities in epilepsy in the UK: a systematic review and meta-analysis of evidence
Authors: Kathryn J Bush, Emer Cullen, Susanna Mills, Richard F M Chin, Rhys H Thomas, Andrew Kingston, William Owen Pickrell, Sheena E Ramsay
Journal: The Lancet Public Health (2024)

BackgroundSocioeconomic inequalities in epilepsy incidence and its adverse outcomes are documented internationally, yet the extent of inequalities and factors influencing the association can differ between countries. A UK public health response to epilepsy, which prevents epilepsy without widening inequalities, is required. However, the data on UK epilepsy inequalities have not been synthesised in a review and the underlying determinants are unknown.MethodsIn this systematic review and meta-analysis, we searched six bibliographic databases (MEDLINE, Embase, PsycINFO, CINAHL, Web of Science, and Scopus) and grey literature published between Jan 1, 1980, and Feb 21, 2024, to identify UK studies reporting epilepsy incidence or epilepsy-related adverse outcomes by socioeconomic factors (individual level or area level). We included longitudinal cohort studies, studies using routinely collected health-care data, cross-sectional studies, and matched cohort studies and excluded conference abstracts and studies not reporting empirical results in the review and meta-analysis. Multiple reviewers (KJB, EC, SER, WOP, and RHT) independently screened studies, KJB extracted data from included studies and a second reviewer (SM or EC) checked data extraction. We used Critical Appraisal Skills Programme checklists to assess quality. We used random-effects meta-analysis to pool incident rate ratios (IRRs) and synthesised results on adverse outcomes narratively. This study was registered on PROPSPERO (CRD42023394143).FindingsWe identified 2471 unique studies from database searches. We included 26 studies, ten of which reported epilepsy incidence and 16 reported epilepsy-related adverse outcomes according to socioeconomic factors. Misclassification, participation, and interpretive biases were identified as study quality limitations. Meta-analyses showed an association between socioeconomic deprivation and epilepsy incidence, with greater risks of epilepsy incidence in groups of high-deprivation (IRR 1·34 [95% CI 1·16–1·56]; I2=85%) and medium-deprivation (IRR 1·23 [95% CI 1·08–1·39]; I2=63%) compared with low-deprivation groups. This association persisted in the studies that only included children (high vs low: IRR 1·36 [95% CI 1·19–1·57]; I2=0%). Only two studies examined factors influencing epilepsy incidence. There is limited evidence regarding UK inequalities in adverse outcomes.InterpretationSocioeconomic inequalities in epilepsy incidence are evident in the UK. To develop an evidence-based public health response to epilepsy, further research is needed to understand the populations affected, factors determining the association, and the extent of inequalities in adverse outcomes.FundingEpilepsy Research Institute UK.