tbuckley/cabot-search huggingface dataset:
COVID‐19 vaccine: recent advancements and future prospects
Authors: Li Xu, Min Li, Wu He
Journal: MedComm (2024)

Abstract Nowadays, although severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) epidemic has been handled with long‐term management globally, the virus strains keep continuous evolution in an uncertain direction. The newly emerged JN.1 dominated the globally circulating variants in a short time and resulted in increasing hospitalizations. Up to 2024, variant vaccines with the composition of XBB sub‐lineage were available due to the coordinated efforts of developers and regulatory agencies. The development of updated vaccines is still needed and the regular availability of coronavirus disease 2019 (COVID‐19) vaccines should be timely guaranteed. The current landscape of COVID‐19 vaccines and the strategies for accelerating vaccine development and approval are reviewed. Proposals to enhance variants monitoring and the establishment of the strain recommendation mechanism are made. This review provides suggestions about platform technology designation and application, real‐world data leveraging and modification to regulatory pathways both for the post‐pandemic era of SARS‐CoV‐2 and for the future unknown pathogen pandemic.
Gene editing therapy for cardiovascular diseases
Authors: Xinyu Wu, Jie Yang, Jiayao Zhang, Yuning Song
Journal: MedComm (2024)

The development of gene editing tools has been a significant area of research in the life sciences for nearly 30 years. These tools have been widely utilized in disease detection and mechanism research. In the new century, they have shown potential in addressing various scientific challenges and saving lives through gene editing therapies, particularly in combating cardiovascular disease (CVD). The rapid advancement of gene editing therapies has provided optimism for CVD patients. The progress of gene editing therapy for CVDs is a comprehensive reflection of the practical implementation of gene editing technology in both clinical and basic research settings, as well as the steady advancement of research and treatment of CVDs. This article provides an overview of the commonly utilized DNA-targeted gene editing tools developed thus far, with a specific focus on the application of these tools, particularly the clustered regularly interspaced short palindromic repeat/CRISPR-associated genes (Cas) (CRISPR/Cas) system, in CVD gene editing therapy. It also delves into the challenges and limitations of current gene editing therapies, while summarizing ongoing research and clinical trials related to CVD. The aim is to facilitate further exploration by relevant researchers by summarizing the successful applications of gene editing tools in the field of CVD.
Congenital heart disease: types, pathophysiology, diagnosis, and treatment options
Authors: Xiao Meng, Ming Song, Kai Zhang, Weida Lu, Yunyi Li, Cheng Zhang, Yun Zhang
Journal: MedComm (2024)

Abstract Congenital heart disease (CHD) is a structural abnormality of the heart and/or great vessels and patients with CHD are at an increased risks of various morbidities throughout their lives and reduced long‐term survival. Eventually, CHD may result in various complications including heart failure, arrhythmias, stroke, pneumonia, and sudden death. Unfortunately, the exact etiology and pathophysiology of some CHD remain unclear. Although the quality of life and prognosis of patients with CHD have significantly improved following technological advancement, the influence of CHD is lifelong, especially in patients with complicated CHD. Thus, the management of CHD remains a challenge due to its high prevalence. Finally, there are some disagreements on CHD among international guidelines. In this review, we provide an update of the pathophysiology, diagnosis, and treatment in most common type of CHD, including patent foramen ovale, atrial septal defect, ventricular septal defect, atrioventricular septal defect, patent ductus arteriosus, coarctation of the aorta, transposition of the great arteries, congenitally corrected transposition of the great arteries, coronary anomalies, left and right ventricular outflow tract obstruction, tetralogy of Fallot and Ebstein anomaly. In particular, we focus on what is known and what is unknown in these areas, aiming to improve the current understanding of various types of CHD.
Targeting cancer stem cells in multiple myeloma
Authors: Emine Gulsen Gunes, Metin Gunes, Jianhua Yu, Murali Janakiram
Journal: Trends in cancer (2024)

Multiple myeloma (MM) is a hematological malignancy of bone marrow (BM) plasma cells with excessive clonal expansion and is associated with the overproduction of light-chain or monoclonal immunoglobulins (Igs). MM remains incurable, with high rates of relapses and refractory disease after first-line treatment. Cancer stem cells (CSCs) have been implicated in drug resistance in MM; however, the evidence for CSCs in MM is not adequate, partly due to a lack of uniformity in the definitions of multiple myeloma stem cells (MMSCs). We review advances in understanding MMSCs and their role in drug resistance to MM therapies. We also discuss novel therapeutic strategies to overcome MMSC-mediated relapses and drug resistance.
Outbreak of Ralstonia pickettii associated with contamination of saline products distributed internationally, the United Kingdom, 2024
Authors: Mike Saunders, Amy Weaver, Rebecca Stretch, D Jeyaratnam, Mariyam Mirfenderesky, David Elliott, Charlotte Patterson, David Williams, Dervla TD Kenna, Jack Turton, Karen L Osman, Jane F Turton, Colin S Brown, JWT Elston
Journal: Eurosurveillance (2024)

We describe an outbreak of Ralstonia pickettii in the United Kingdom, with isolates genetically indistinguishable from a 2023 Australian outbreak linked to internationally distributed saline solutions. Confirmed cases (n = 3) had bacteraemia, clinically relevant infection, indwelling venous lines and frequent healthcare contact. Multi-stakeholder intervention was required including product recall and risk communications. We recommend a low threshold for investigating clusters of Ralstonia species and similar opportunistic pathogens, considering contaminated product sources. Effective mitigation requires multi-agency partnership and international collaboration.
Use of proxy indicators for automated surveillance of severe acute respiratory infection, the Netherlands, 2017 to 2023: a proof-of-concept study
Authors: Maaike C Swets, Annabel Niessen, Emilie P Buddingh, Ann CTM Vossen, Karin Ellen Veldkamp, Irene K Veldhuijzen, Mark GJ de Boer, Geert H Groeneveld
Journal: Eurosurveillance (2024)

BackgroundEffective pandemic preparedness requires robust severe acute respiratory infection (SARI) surveillance. However, identifying SARI patients based on symptoms is time-consuming. Using the number of reverse transcription (RT)-PCR tests or contact and droplet precaution labels as a proxy for SARI could accurately reflect the epidemiology of patients presenting with SARI.AimWe aimed to compare the number of RT-PCR tests, contact and droplet precaution labels and SARI-related International Classification of Disease (ICD)-10 codes and evaluate their use as surveillance indicators.MethodsPatients from all age groups hospitalised at Leiden University Medical Center between 1 January 2017 up to and including 30 April 2023 were eligible for inclusion. We used a clinical data collection tool to extract data from electronic medical records. For each surveillance indicator, we plotted the absolute count for each week, the incidence proportion per week and the correlation between the three surveillance indicators.ResultsWe included 117,404 hospital admissions. The three surveillance indicators generally followed a similar pattern before and during the COVID-19 pandemic. The correlation was highest between contact and droplet precaution labels and ICD-10 diagnostic codes (Pearson correlation coefficient: 0.84). There was a strong increase in the number of RT-PCR tests after the start of the COVID-19 pandemic.DiscussionAll three surveillance indicators have advantages and disadvantages. ICD-10 diagnostic codes are suitable but are subject to reporting delays. Contact and droplet precaution labels are a feasible option for automated SARI surveillance, since these reflect trends in SARI incidence and may be available real-time.
Continued circulation of mpox: an epidemiological and phylogenetic assessment, European Region, 2023 to 2024
Authors: Aisling M Vaughan, Mohammed Afzal, Priyanka Nannapaneni, Mathias Leroy, Xanthi Andrianou, Jeffrey Pires, Silvia Funke, Celine Roman, Juliana Reyes-Uruena, Stephan Aberle, Aristos Aristodimou, Gudrun Aspelund, Kirsty F Bennet, Antra Bormane, Anna Caraglia, Hannah Charles, Emilie Chazelle, Iva Christova, Orna Cohen, Costas Constantinou, Simon Couvreur, Asuncion Diaz, Kateřina Fabiánová, Federica Ferraro, Marte Petrikke Grenersen, Eva Grilc, Tuula Hannila-Handelberg, Anne Kathrine Hvass, Derval Igoe, Klaus Jansen, Denisa Janță, Styliani Kaoustou, Anders Koch, Mirjana Lana Kosanovic Licina, Stefka Krumova, Anton Labutin, Raskit Lachmann, Amaryl Lecompte, Rémi Lefrançois, Viktorija Leitena, Kirsi Liitsola, Ivan Mlinarić, Zohar Mor, Martha Neary, Alina Novacek, Magnus Wenstøp Øgle, Hana Orlíková, Kalliopi Papadima, Moa Rehn, Malgorzata Sadkowska-Todys, Anca Sîrbu, Klara Sondén, Berta Suárez, Marianna Thordardottir, Paula Vasconcelos, Joao Vieira Martins, Karolina Zakrzewska, Marc-Alain Widdowson, Céline M Gossner
Journal: Eurosurveillance (2024)

During the summer of 2023, the European Region experienced a limited resurgence of mpox cases following the substantial outbreak in 2022. This increase was characterised by asynchronous and bimodal increases, with countries experiencing peaks at different times. The demographic profile of cases during the resurgence was largely consistent with those reported previously. All available sequences from the European Region belonged to clade IIb. Sustained efforts are crucial to control and eventually eliminate mpox in the European Region.
Author Correction: Clinical implementation of artificial-intelligence-assisted detection of breast cancer metastases in sentinel lymph nodes: the CONFIDENT-B single-center, non-randomized clinical trial
Authors: C. van Dooijeweert, R. N. Flach, N. D. ter Hoeve, C. P. H. Vreuls, R. Goldschmeding, J. E. Freund, P. Pham, T. Q. Nguyen, E. van der Wall, G. W. J. Frederix, N. Stathonikos, P. J. van Diest
Journal: Nature Cancer (2024)
Saturation genome editing of BAP1 functionally classifies somatic and germline variants
Authors: Andrew J Waters, Timothy Brendler-Spaeth, Danielle Smith, Victoria Offord, Hong Kee Tan, Yajie Zhao, Sofia Obolenski, Maartje Nielsen, Remco van Doorn, Jo-Ellen Murphy, Prashant Gupta, Charlie F Rowlands, Helen Hanson, Erwan Delage, Mark Thomas, Elizabeth J Radford, Sebastian S Gerety, Clare Turnbull, John R B Perry, Matthew E Hurles, David J Adams
Journal: Nature Genetics (2024)

Abstract Many variants that we inherit from our parents or acquire de novo or somatically are rare, limiting the precision with which we can associate them with disease. We performed exhaustive saturation genome editing (SGE) of BAP1 , the disruption of which is linked to tumorigenesis and altered neurodevelopment. We experimentally characterized 18,108 unique variants, of which 6,196 were found to have abnormal functions, and then used these data to evaluate phenotypic associations in the UK Biobank. We also characterized variants in a large population-ascertained tumor collection, in cancer pedigrees and ClinVar, and explored the behavior of cancer-associated variants compared to that of variants linked to neurodevelopmental phenotypes. Our analyses demonstrated that disruptive germline BAP1 variants were significantly associated with higher circulating levels of the mitogen IGF-1, suggesting a possible pathological mechanism and therapeutic target. Furthermore, we built a variant classifier with &gt;98% sensitivity and specificity and quantify evidence strengths to aid precision variant interpretation.
Metronomic chemotherapy plus anti-PD-1 in metastatic breast cancer: a Bayesian adaptive randomized phase 2 trial
Authors: Hongnan Mo, Yongpei Yu, Xiaoying Sun, Hewei Ge, Lanlan Yu, Xiuwen Guan, Jingtong Zhai, Aihua Zhu, Yuhan Wei, Jinjing Wang, Xiaoyan Yan, Haili Qian, Binghe Xu, Fei Ma
Journal: Nature Medicine (2024)
Saturation genome editing maps the functional spectrum of pathogenic VHL alleles
Authors: Megan Buckley, Chloé Terwagne, Athina Ganner, Laura Cubitt, Reid Brewer, Dong-Kyu Kim, Christina M. Kajba, Nicole Forrester, Phoebe Dace, Joachim De Jonghe, Scott T. C. Shepherd, Chelsea Sawyer, Mairead McEwen, Sven Diederichs, Elke Neumann-Haefelin, Samra Turajlic, Evgueni A. Ivakine, Gregory M. Findlay
Journal: Nature Genetics (2024)

Abstract To maximize the impact of precision medicine approaches, it is critical to identify genetic variants underlying disease and to accurately quantify their functional effects. A gene exemplifying the challenge of variant interpretation is the von Hippel–Lindautumor suppressor ( VHL ). VHL encodes an E3 ubiquitin ligase that regulates the cellular response to hypoxia. Germline pathogenic variants in VHL predispose patients to tumors including clear cell renal cell carcinoma (ccRCC) and pheochromocytoma, and somatic VHL mutations are frequently observed in sporadic renal cancer. Here we optimize and apply saturation genome editing to assay nearly all possible single-nucleotide variants (SNVs) across VHL ’s coding sequence. To delineate mechanisms, we quantify mRNA dosage effects and compare functional effects in isogenic cell lines. Function scores for 2,268 VHL SNVs identify a core set of pathogenic alleles driving ccRCC with perfect accuracy, inform differential risk across tumor types and reveal new mechanisms by which variants impact function. These results have immediate utility for classifying VHL variants encountered clinically and illustrate how precise functional measurements can resolve pleiotropic and dosage-dependent genotype–phenotype relationships across complete genes.
NSUN6-mediated 5-methylcytosine modification of NDRG1 mRNA promotes radioresistance in cervical cancer
Authors: Min Yu, Mengdong Ni, Fei Xu, Chaohua Liu, Lihua Chen, Jiana Li, Siyu Xia, Yixin Diao, Jiaxin Chen, Jun Zhu, Xiaohua Wu, Min Tang, Jiajia Li, Guihao Ke
Journal: Molecular Cancer (2024)

Abstract Background Radioresistance is the leading cause of death in advanced cervical cancer (CC). Dysregulation of RNA modification has recently emerged as a regulatory mechanism in radiation and drug resistance. We aimed to explore the biological function and clinical significance of 5-methylcytosine (m 5 C) in cervical cancer radiosensitivity. Methods The abundance of RNA modification in radiotherapy-resistant and sensitive CC specimens was quantified by liquid chromatography-tandem mass spectrometry. The essential RNA modification-related genes involved in CC radiosensitivity were screened via RNA sequencing. The effect of NSUN6 on radiosensitivity was verified in CC cell lines, cell-derived xenograft (CDX), and 3D bioprinted patient-derived organoid (PDO). The mechanisms of NSUN6 in regulating CC radiosensitivity were investigated by integrative m 5 C sequencing, mRNA sequencing, and RNA immunoprecipitation. Results We found a higher abundance of m 5 C modification in resistant CC samples, and NSUN6 was the essential m 5 C-regulating gene concerning radiosensitivity. NSUN6 overexpression was clinically correlated with radioresistance and poor prognosis in cervical cancer. Functionally, higher NSUN6 expression was associated with radioresistance in the 3D PDO model of cervical cancer. Moreover, silencing NSUN6 increased CC radiosensitivity in vivo and in vitro. Mechanistically, NDRG1 was one of the downstream target genes of NSUN6 identified by integrated m 5 C-seq, mRNA-seq, and functional validation. NSUN6 promoted the m 5 C modification of NDRG1 mRNA, and the m 5 C reader ALYREF bound explicitly to the m 5 C-labeled NDRG1 mRNA and enhanced NDRG1 mRNA stability. NDRG1 overexpression promoted homologous recombination-mediated DNA repair, which in turn led to radioresistance in cervical cancer. Conclusions Aberrant m 5 C hypermethylation and NSUN6 overexpression drive resistance to radiotherapy in cervical cancer. Elevated NSUN6 expression promotes radioresistance in cervical cancer by activating the NSUN6/ALYREF-m 5 C-NDRG1 pathway. The low expression of NSUN6 in cervical cancer indicates sensitivity to radiotherapy and a better prognosis.
Oncogenic dependency on SWI/SNF chromatin remodeling factors in T-cell acute lymphoblastic leukemia
Authors: Hyoju Kim, Tze King Tan, Dean Zi Yang Lee, Xiao Zi Huang, Jolynn Zu Lin Ong, Michelle A. Kelliher, Allen Eng Juh Yeoh, Takaomi Sanda, Shi Hao Tan
Journal: Leukemia (2024)
A ROS-responsive hydrogel incorporated with dental follicle stem cell-derived small extracellular vesicles promotes dental pulp repair by ameliorating oxidative stress
Authors: Mengjie Li, Jun Tian, Kangkang Yu, He Liu, Xiaoqi Yu, Nan Wang, Qimei Gong, Kun Li, Ya Shen, Xi Wei
Journal: Bioactive Materials (2024)

Pulpitis, an inflammatory disease of dental pulp tissues, ultimately results in the loss of pulp defense properties. Existing clinical modalities cannot effectively promote inflamed pulp repair. Oxidative stress is a major obstacle inhibiting pulp repair. Due to their powerful antioxidative capacity, mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) exhibit potential for treating oxidative stress-related disorders. However, whether MSC-sEVs shield dental pulp tissues from oxidative damage is largely unknown. Here, we showed that dental follicle stem cell-derived sEVs (DFSC-sEVs) have antioxidative and prohealing effects on a rat LPS-induced pulpitis model by enhancing the survival, proliferation and odontogenesis of H2O2-injured dental pulp stem cells (DPSCs). Additionally, DFSC-sEVs restored the oxidative/antioxidative balance in DPSC mitochondria and had comparable effects on ameliorating mitochondrial dysfunction with the mitochondrion-targeted antioxidant Mito-Tempo. To improve the efficacy of DFSC-sEVs, we fabricated an intelligent and injectable hydrogel to release DFSC-sEVs by combining sodium alginate (SA) and the ROS sensor RhB-AC. The newly formed SA-RhB hydrogel efficiently encapsulates DFSC-sEVs and exhibits controlled release of DFSC-sEVs in a HClO/ClO− concentration-dependent manner, providing a synergistic antioxidant effect with DFSC-sEVs. These results suggest that DFSC-sEVs-loaded SA-RhB is a promising minimally invasive treatment for pulpitis by enhancing tissue repair in the pulp wound microenvironment.
Poly(phenylalanine) and poly(3,4-dihydroxy-L-phenylalanine): Promising biomedical materials for building stimuli-responsive nanocarriers
Authors: Lingcong Zeng, Dandan Kang, Linglin Zhu, Zunkang Zhou, Yichong Li, Wei Ling, Yu Zhang, Deng-Guang Yu, Il Kim, Wenliang Song
Journal: Journal of Controlled Release (2024)
Tumor cell-intrinsic MELK enhanced CCL2-dependent immunosuppression to exacerbate hepatocarcinogenesis and confer resistance of HCC to radiotherapy
Authors: Bufu Tang, Jinyu Zhu, Yueli Shi, Yajie Wang, Xiaojie Zhang, Biao Chen, Shiji Fang, Yang Yang, Liyun Zheng, Rongfang Qiu, Qiaoyou Weng, Min Xu, Zhongwei Zhao, Jianfei Tu, Minjiang Chen, Jiansong Ji
Journal: Molecular Cancer (2024)

Abstract Background The outcome of hepatocellular carcinoma (HCC) is limited by its complex molecular characteristics and changeable tumor microenvironment (TME). Here we focused on elucidating the functional consequences of Maternal embryonic leucine zipper kinase (MELK) in the tumorigenesis, progression and metastasis of HCC, and exploring the effect of MELK on immune cell regulation in the TME, meanwhile clarifying the corresponding signaling networks. Methods Bioinformatic analysis was used to validate the prognostic value of MELK for HCC. Murine xenograft assays and HCC lung metastasis mouse model confirmed the role of MELK in tumorigenesis and metastasis in HCC. Luciferase assays, RNA sequencing, immunopurification–mass spectrometry (IP-MS) and coimmunoprecipitation (CoIP) were applied to explore the upstream regulators, downstream essential molecules and corresponding mechanisms of MELK in HCC. Results We confirmed MELK to be a reliable prognostic factor of HCC and identified MELK as an effective candidate in facilitating the tumorigenesis, progression, and metastasis of HCC; the effects of MELK depended on the targeted regulation of the upstream factor miR-505-3p and interaction with STAT3, which induced STAT3 phosphorylation and increased the expression of its target gene CCL2 in HCC. In addition, we confirmed that tumor cell-intrinsic MELK inhibition is beneficial in stimulating M1 macrophage polarization, hindering M2 macrophage polarization and inducing CD8 + T-cell recruitment, which are dependent on the alteration of CCL2 expression. Importantly, MELK inhibition amplified RT-related immune effects, thereby synergizing with RT to exert substantial antitumor effects. OTS167, an inhibitor of MELK, was also proven to effectively impair the growth and progression of HCC and exert a superior antitumor effect in combination with radiotherapy (RT). Conclusions Altogether, our findings highlight the functional role of MELK as a promising target in molecular therapy and in the combination of RT therapy to improve antitumor effect for HCC.
Carcinogenicity of talc and acrylonitrile
Authors: Leslie T Stayner, Tania Carreón-Valencia, Paul A Demers, Jason M Fritz, Malcolm R Sim, Patricia Stewart, Hiroyuki Tsuda, Andres Cardenas, Dario Consonni, Laurie Davies, Sara De Matteis, Emanuela Felley-Bosco, Andrew J Ghio, Thomas Göen, Yann Grosse, Alessandro F Gualtieri, P David Josephy, Stella Koutros, Igor Linhart, Henriqueta Louro, Katie M O'Brien, Simona Panzacchi, Laura Peña, Pavel Rössner, Joellen M Schildkraut, Aleksandr B Stefaniak, Nicolas Wentzensen, Pascal Wild, Yuanyuan Xu, Aline de Conti, Caterina Facchin, Roland Wedekind, Ayat Ahmadi, Jessica Blanco, Shirisha Chittiboyina, Shalini Kulasingam, Richard MacLehose, Melitah Motlhale, Sanam Shah, Eero Suonio, Heidi Mattock, Andrew Kunzmann, Federica Madia, Elisa Pasqual, Lamia Benbrahim-Tallaa, Mary K Schubauer-Berigan
Journal: The Lancet Oncology (2024)