tbuckley/cabot-search huggingface dataset:
OGG1: An emerging multifunctional therapeutic target for the treatment of diseases caused by oxidative DNA damage
Authors: Yunxiao Zhong, Xinya Zhang, Ruibing Feng, Yu Fan, Zhang Zhang, Qing‐Wen Zhang, Jian‐Bo Wan, Yitao Wang, Hua Yu, Guodong Li
Journal: Medicinal Research Reviews (2024)

Oxidative DNA damage-related diseases, such as incurable inflammation, malignant tumors, and age-related disorders, present significant challenges in modern medicine due to their complex molecular mechanisms and limitations in identifying effective treatment targets. Recently, 8-oxoguanine DNA glycosylase 1 (OGG1) has emerged as a promising multifunctional therapeutic target for the treatment of these challenging diseases. In this review, we systematically summarize the multiple functions and mechanisms of OGG1, including pro-inflammatory, tumorigenic, and aging regulatory mechanisms. We also highlight the potential of OGG1 inhibitors and activators as potent therapeutic agents for the aforementioned life-limiting diseases. We conclude that OGG1 serves as a multifunctional hub; the inhibition of OGG1 may provide a novel approach for preventing and treating inflammation and cancer, and the activation of OGG1 could be a strategy for preventing age-related disorders. Furthermore, we provide an extensive overview of successful applications of OGG1 regulation in treating inflammatory, cancerous, and aging-related diseases. Finally, we discuss the current challenges and future directions of OGG1 as an emerging multifunctional therapeutic marker for the aforementioned challenging diseases. The aim of this review is to provide a robust reference for scientific researchers and clinical drug developers in the development of novel clinical targeted drugs for life-limiting diseases, especially for incurable inflammation, malignant tumors, and age-related disorders.
Correction: lncRNA SNHG6 regulates EZH2 expression by sponging miR-26a/b and miR-214 in colorectal cancer
Authors: Mu Xu, Xiaoxiang Chen, Kang Lin, Kaixuan Zeng, Xiangxiang Liu, Xueni Xu, Bei Pan, Tao Xu, Li Sun, Bangshun He, Yuqin Pan, Huiling Sun, Shukui Wang
Journal: Journal of Hematology & Oncology (2024)
The genetics and epidemiology of N- and O-immunoglobulin A glycomics
Authors: Alessia Visconti, Niccolò Rossi, Albert Bondt, Agnes Hipgrave Ederveen, Gaurav Thareja, Carolien A. M. Koeleman, Nisha Stephan, Anna Halama, Hannah J. Lomax-Browne, Matthew C. Pickering, Xu-jie Zhou, Manfred Wuhrer, Karsten Suhre, Mario Falchi
Journal: Genome Medicine (2024)

Abstract Background Immunoglobulin (Ig) glycosylation modulates the immune response and plays a critical role in ageing and diseases. Studies have mainly focused on IgG glycosylation, and little is known about the genetics and epidemiology of IgA glycosylation. Methods We generated, using a novel liquid chromatography-mass spectrometry method, the first large-scale IgA glycomics dataset in serum from 2423 twins, encompassing 71 N- and O- glycan species. Results We showed that, despite the lack of a direct genetic template, glycosylation is highly heritable, and that glycopeptide structures are sex-specific, and undergo substantial changes with ageing. We observe extensive correlations between the IgA and IgG glycomes, and, exploiting the twin design, show that they are predominantly influenced by shared genetic factors. A genome-wide association study identified eight loci associated with both the IgA and IgG glycomes ( ST6GAL1 , ELL2 , B4GALT1 , ABCF2 , TMEM121 , SLC38A10 , SMARCB1 , and MGAT3 ) and two novel loci specifically modulating IgA O- glycosylation ( C1GALT1 and ST3GAL1 ). Validation of our findings in an independent cohort of 320 individuals from Qatar showed that the underlying genetic architecture is conserved across ancestries. Conclusions Our study delineates the genetic landscape of IgA glycosylation and provides novel potential functional links with the aetiology of complex immune diseases, including genetic factors involved in IgA nephropathy risk.
Inferring clonal somatic mutations directed by X chromosome inactivation status in single cells
Authors: Ilke Demirci, Anton J. M. Larsson, Xinsong Chen, Johan Hartman, Rickard Sandberg, Jonas Frisén
Journal: Genome biology (2024)

Analysis of clonal dynamics in human tissues is enabled by somatic genetic variation. Here, we show that analysis of mitochondrial mutations in single cells is dramatically improved in females when using X chromosome inactivation to select informative clonal mutations. Applying this strategy to human peripheral mononuclear blood cells reveals clonal structures within T cells that otherwise are blurred by non-informative mutations, including the separation of gamma-delta T cells, suggesting this approach can be used to decipher clonal dynamics of cells in human tissues.
Genomic reproducibility in the bioinformatics era
Authors: Pelin Icer Baykal, Paweł Piotr Łabaj, Florian Markowetz, Lynn M. Schriml, Daniel J. Stekhoven, Serghei Mangul, Niko Beerenwinkel
Journal: Genome biology (2024)

In biomedical research, validating a scientific discovery hinges on the reproducibility of its experimental results. However, in genomics, the definition and implementation of reproducibility remain imprecise. We argue that genomic reproducibility, defined as the ability of bioinformatics tools to maintain consistent results across technical replicates, is essential for advancing scientific knowledge and medical applications. Initially, we examine different interpretations of reproducibility in genomics to clarify terms. Subsequently, we discuss the impact of bioinformatics tools on genomic reproducibility and explore methods for evaluating these tools regarding their effectiveness in ensuring genomic reproducibility. Finally, we recommend best practices to improve genomic reproducibility.
A β‐Lactamase Responsive Peptide Inhibits MRSA Infection through Self‐Assembled Nanonet
Authors: Minghao Wu, Yuting Li, Huaxing Shen, Yanan Zhang, Wei Cong, Xiaochun Hu, Yejiao Shi, Honggang Hu
Journal: Advanced Healthcare Materials (2024)

Abstract Gram‐positive S. aureus is one of the leading pathogens for death associated with antimicrobial resistance. The β‐lactamase (Bla) secreted by methicillin‐resistant S. aureus (MRSA) hydrolyzes nearly all β‐lactam antibiotics, leaving only a few antibiotics available for the clinical treatment of MRSA infections. Thereby, a Bla‐responsive peptide (BLAP) is designed here with the capacity of inhibiting MRSA infection through mimicking the host defense mechanism of human defensin‐6. The BLAP comprising a self‐assembling peptide sequence can respond specifically to the secreted Bla and assemble in situ surrounding MRSA. The assembled nanofibrous network is able to trap MRSA, preventing its invasion into the host cells effectively. As a consequence, the intramuscular injection of BLAP significantly restricted bacterial infection and abscess formation in mice. The biomimetic BLAP holds great potential for the efficient treatment of drug‐resistant gram‐positive bacterial infections.
Novel Genetic Loci in Early‐Onset Gout Derived From Whole‐Genome Sequencing of an Adolescent Gout Cohort
Authors: Aichang Ji, Yang Sui, Xiaomei Xue, Xiapeng Ji, Wenrui Shi, Yongyong Shi, Robert Terkeltaub, Nicola Dalbeth, Riku Takei, Fei Yan, Mingshu Sun, Maichao Li, Jie Lu, Lingling Cui, Zhen Liu, Can Wang, Xinde Li, Lin Han, Zhanjie Fang, Wenyan Sun, Yue Liang, Yuwei He, Guangmin Zheng, Xuefeng Wang, Jiayi Wang, Hui Zhang, Lei Pang, Han Qi, Yushuang Li, Zan Cheng, Zhiqiang Li, Jingfa Xiao, Changqing Zeng, Tony R. Merriman, Hongzhu Qu, Xiangdong Fang, Changgui Li
Journal: Arthritis & Rheumatology (2024)

Objective Mechanisms underlying the adolescent‐onset and early‐onset gout are unclear. This study aimed to discover variants associated with early‐onset gout. Methods We conducted whole‐genome sequencing in a discovery adolescent‐onset gout cohort of 905 individuals (gout onset 12 to 19 years) to discover common and low‐frequency single‐nucleotide variants (SNVs) associated with gout. Candidate common SNVs were genotyped in an early‐onset gout cohort of 2,834 individuals (gout onset ≤30 years old), and meta‐analysis was performed with the discovery and replication cohorts to identify loci associated with early‐onset gout. Transcriptome and epigenomic analyses, quantitative real‐time polymerase chain reaction and RNA sequencing in human peripheral blood leukocytes, and knock‐down experiments in human THP‐1 macrophage cells investigated the regulation and function of candidate gene RCOR1 . Results In addition to ABCG2 , a urate transporter previously linked to pediatric‐onset and early‐onset gout, we identified two novel loci ( P meta &lt; 5.0 × 10 −8 ): rs12887440 ( RCOR1 ) and rs35213808 ( FSTL5 ‐ MIR4454 ). Additionally, we found associations at ABCG2 and SLC22A12 that were driven by low‐frequency SNVs. SNVs in RCOR1 were linked to elevated blood leukocyte messenger RNA levels. THP‐1 macrophage culture studies revealed the potential of decreased RCOR1 to suppress gouty inflammation. Conclusion This is the first comprehensive genetic characterization of adolescent‐onset gout. The identified risk loci of early‐onset gout mediate inflammatory responsiveness to crystals that could mediate gouty arthritis. This study will contribute to risk prediction and therapeutic interventions to prevent adolescent‐onset gout.
Synergistic association of sodium-glucose cotransporter-2 inhibitor and metformin on liver and non-liver complications in patients with type 2 diabetes mellitus and metabolic dysfunction-associated steatotic liver disease
Authors: Xianhua Mao, Xinrong Zhang, Leslie Kam, Nicholas Chien, Rongtao Lai, Ka-Shing Cheung, Man-Fung Yuen, Ramsey Cheung, Wai-Kay Seto, Mindie H Nguyen
Journal: Gut (2024)

Type 2 diabetes mellitus and metabolic dysfunction-associated steatotic liver disease (diabetic MASLD) frequently coexist and worsen liver and non-liver outcomes, but effective pharmacological therapies are limited. We aimed to evaluate the long-term effect of sodium-glucose cotransporter-2 inhibitor (SGLT-2i) on liver and non-liver outcomes among patients with diabetic MASLD.
Direct toll-like receptor triggering in colorectal cancer-associated stromal cells elicits immunostimulatory properties leading to enhanced immune cell recruitment
Authors: Julija Djordjevic, Nubia Sarahi Cisneros Romero, Luciano Cascione, Valentina Mele, Eleonora Cremonesi, Elisa Sorrenti, Camilla Basso, Martina Villa, Agnese Cianfarani, Raffaello Roesel, Jacopo Galafassi, Pietro Edoardo Majno-Hurst, Giulio Spagnoli, Dimitrios Christoforidis, Giandomenica Iezzi
Journal: Gut (2024)
Mental health and well-being of elite youth athletes: a scoping review
Authors: Kate Gwyther, Vita Pilkington, Alan P Bailey, Margo Mountjoy, Michael F Bergeron, Simon M Rice, Rosemary Purcell
Journal: British Journal of Sports Medicine (2024)

Background There is increasing recognition of the prevalence and risk factors for mental health symptoms and disorders among adult elite athletes, with less research involving elite youth athletes. This scoping review aimed to characterise the mental health and well-being of elite youth athletes who travel internationally and compete for their sport. Method Four databases were searched in March 2023. Inclusion criteria were studies with elite youth athlete populations (mean age 12–17 years) reporting mental health and well-being outcomes. Data from included studies were charted by outcome, and risk/protective factors identified. Results Searches retrieved 3088 records, of which 33 studies met inclusion criteria, encapsulating data from 5826 athletes (2538 males, 3288 females). The most frequently studied issue was disordered eating (k=16), followed by anxiety (k=7), depression (k=5) and mixed anxiety/depression (k=2). Caseness estimates (a symptom level where mental health treatment is typically indicated) for disordered eating were wide ranging (0%–14% for males; 11%–41% for females), whereas only two studies estimated caseness for depression (7% in a mixed-sex sample; 14% for males, 40% for females) and one for anxiety (8% for males, 28% for females). Common risk factors for mental ill-health included sex, athlete status (compared with non-athletes) and social/relationship factors (with coaches/parents/peers). Contradictory evidence was observed for elite/competition level, which was associated with higher and lower rates of disordered eating. Conclusion Further representative research into the mental health and well-being of elite youth athletes is needed to enhance understanding and guide prevention and intervention measures.
Patient‐reported outcome measures and health economics in regenerative periodontal therapy: A systematic review and meta‐analysis
Authors: Zhaozhao Chen, Cho‐Ying Lin, Hom‐Lay Wang
Journal: Periodontology 2000 (2024)

Abstract Understanding patient responses to periodontal regeneration is crucial. This systematic review and meta‐analysis addressed two key questions: (a) the impact of periodontal regeneration on patient‐reported outcome measures (PROMs) for intrabony and furcation involvement and (b) the cost‐effectiveness of periodontal regeneration for treating periodontal defects. Twenty‐four studies were included, with 20 randomized clinical trials (RCTs) reporting patient‐reported outcomes and five (three RCTs and two economic model‐based studies) reporting cost‐effectiveness outcomes. Results favored regeneration therapy over conventional flap surgery for intrabony defects, showing improvements in qualitative (i.e., amount of regenerated attachment apparatus) and quantitative parameters (i.e., probing and radiographic parameters). In terms of PROMs, regenerative treatments involving barrier membranes resulted in longer chair times and higher rates of complications (such as membrane exposure or edema) compared to flap with biologic agents or access flap alone. Despite this, oral health‐related quality of life improved after both regenerative and extraction procedures. Economically, regeneration remained favorable compared to extraction and replacement or open flap debridement alone for periodontal defects. Single‐flap variants in open flap debridement yielded similar outcomes to regenerative treatment, offering a potentially cost‐effective option. Nevertheless, further discussion on the benefits of less‐invasive flap designs is needed due to the lack of histological evaluation.
Resuscitation on the field of play: a best-practice guideline from Resuscitation Council UK
Authors: Christopher M Smith, Fionna Moore, Jonathan A Drezner, Ryan Aird, Adam Benson Clarke, James Cant, Isabelle Hamilton-Bower, Sue Hampshire, Lisa Hodgson, Christopher Johnston, Judy O’Sullivan, Michael Patterson, David Pitcher, Andrew Smith, Jasmeet Soar, Lynn Thomas, David Anthony Zideman, Gavin D Perkins
Journal: British Journal of Sports Medicine (2024)

Sudden cardiac arrest (SCA) is the leading cause of sudden death in athletes during high-level, organised sport. Patient-related and event-related factors provide an opportunity for rapid intervention and the potential for high survival rates. The aim of this consensus was to develop a best-practice guideline for dedicated field-of-play medical teams responding to SCA during an organised sporting event. A task-and-finish group from Resuscitation Council UK identified a stakeholder group of relevant experts and cardiac arrest survivors in March and April 2022. Together, they developed a best-practice guideline using the best available evidence. A public consultation period further refined the guideline before it was finalised in December 2023. Any sudden collapse, without rapid recovery during sporting activity, should be considered an SCA until proven otherwise. Field-of-play medical teams should be empowered to access the collapsed athlete as soon as possible and perform initial essential interventions in situ. This includes a suggested minimum of three cycles of cardiopulmonary resuscitation and defibrillation in persistent shockable rhythms while other aspects of advanced life support are initiated. There should be careful organisation and practice of the medical response, including plans to transport athletes to dedicated facilities for definitive medical care. This best-practice guideline complements, rather than supersedes, existing resuscitation guidelines. It provides a clear approach to how to best treat an athlete with SCA and how to organise the medical response so treatments are delivered effectively and optimise outcomes.
Respiratory problems in rowers: outcomes from a systematic assessment of an elite squad
Authors: James H Hull, Zander J Williams, Anna R Jackson, Moses Wootten, Craig Ranson, Liz Arnold, Ann Redgrave
Journal: British Journal of Sports Medicine (2024)

To characterise the respiratory health of elite rowers using a systematic screening approach to assess respiratory health (SARAH) and identify the associations between SARAH findings and acute respiratory illness (ARI) and chest wall injury (CWI).
Subsequent musculoskeletal injury after concussion in National Football League players
Authors: Erin B Wasserman, Alexandra Chretien, Kimberly G Harmon, Margot Putukian, David Okonkwo, Gary S Solomon, Javier Cardenas, Mackenzie M Herzog, Allen Sills, Christina D Mack
Journal: British Journal of Sports Medicine (2024)

To assess whether National Football League (NFL) players diagnosed with a concussion have an increased risk of injury after return to football.
Novel benzothiazole derivatives target the Gac/Rsm two-component system as antibacterial synergists against Pseudomonas aeruginosa infections
Authors: Jun Liu, Wenfu Wu, Jiayi Hu, Siyu Zhao, Yiqun Chang, Qiuxian Chen, Yujie Li, Jie Tang, Zhenmeng Zhang, Xiao Wu, Shumeng Jiao, Haichuan Xiao, Qiang Zhang, Jiarui Du, Jianfu Zhao, Kaihe Ye, Meiyan Huang, Jun Xu, Haibo Zhou, Junxia Zheng, Pinghua Sun
Journal: Acta Pharmaceutica Sinica B (2024)

The management of antibiotic-resistant, bacterial biofilm infections in skin wounds poses an increasingly challenging clinical scenario.
Pre-transplant anti-nephrin antibodies are specific predictors of recurrent diffuse podocytopathy in the kidney allograft
Authors: Ibrahim Batal, Andrew J.B. Watts, Jean-Baptiste Gibier, Aghiles Hamroun, Isabelle Top, François Provot, Keith Keller, Xiaoyi Ye, Hilda E. Fernandez, Rita Leal, Nicole K. Andeen, Russell J. Crew, Geoffrey K. Dube, Elena-Rodica Vasilescu, Lloyd E. Ratner, Nicole Bowman, Andrew S. Bomback, Simone Sanna-Cherchi, Krzysztof Kiryluk, Astrid Weins
Journal: Kidney International (2024)
Mutilating arthropathy with skin nodules
Authors: Tsz On Lam, Edric Chi Ching Ip, Wendy Wan Hang Lau, Agnes Wai Sze Chan, Christina Man Tung Cheung, Joshua Jing Xi Li, Joanna Ka Man Ng, Lai-Shan Tam
Journal: Annals of the Rheumatic Diseases (2024)
Perspectives on the incidence of Acanthamoeba Keratitis: A Systematic Review and Meta-Analysis
Authors: Francesco Aiello, Gabriele Gallo Afflitto, Francesca Ceccarelli, Maria Vittoria Turco, Yuyi Han, Guillermo Amescua, John K. Dart, Carlo Nucci
Journal: Ophthalmology (2024)

To provide an overview on the incidence of Acanthamoeba keratitis (AK).
Efficacy and Safety of KRAS G12C Inhibitor IBI351 Monotherapy in Patients With Advanced NSCLC: Results From a Phase 2 Pivotal Study
Authors: Qing Zhou, Xiangjiao Meng, Longhua Sun, Dingzhi Huang, Nong Yang, Yan Yu, Mingfang Zhao, Wu Zhuang, Renhua Guo, Yi Hu, Yueyin Pan, Jinlu Shan, Meili Sun, Ying Yuan, Yun Fan, Jianan Huang, Lian Liu, Qian Chu, Xiuwen Wang, Chongrui Xu, Jiaxin Lin, Jingjing Huang, Mengna Huang, Jiya Sun, Sujie Zhang, Hui Zhou, Yi-Long Wu
Journal: Journal of Thoracic Oncology (2024)
ROS-responsive nanoparticle delivery of obeticholic acid mitigate primary sclerosing cholangitis
Authors: Qigu Yao, Beiduo Wang, Jiong Yu, Qiaoling Pan, Yingduo Yu, Xudong Feng, Wenyi Chen, Jinfeng Yang, Changyou Gao, Hongcui Cao
Journal: Journal of Controlled Release (2024)

Primary sclerosing cholangitis (PSC) is a challenging cholestatic liver disease marked by progressive bile duct inflammation and fibrosis that has no FDA-approved therapy. Although obeticholic acid (OCA) has been sanctioned for PSC, its clinical utility in PSC is constrained by its potential hepatotoxicity. Here, we introduce a novel therapeutic construct consisting of OCA encapsulated within a reactive oxygen species (ROS)-responsive, biodegradable polymer, further cloaked with human placenta-derived mesenchymal stem cell (hP-MSC) membrane (MPPFTU@OCA). Using PSC patient-derived organoid models, we assessed its cellular uptake and cytotoxicity. Moreover, using a PSC mouse model induced by 3,5-diethoxycarbonyl-1,4-dihydro-collidine (DDC), we demonstrated that intravenous administration of MPPFTU@OCA not only improved cholestasis via the FXR-SHP pathway but also reduced macrophage infiltration and the accumulation of intracellular ROS, and alleviated mitochondria-induced apoptosis. Finally, we verified the ability of MPPFTU@OCA to inhibit mitochondrial ROS thereby alleviating apoptosis by measuring the mitochondrial adenosine triphosphate (ATP) concentration, ROS levels, and membrane potential (ΔΨm) using H 2 O 2 -stimulated PSC-derived organoids. These results illuminate the synergistic benefits of integrating an ROS-responsive biomimetic platform with OCA, offering a promising therapeutic avenue for PSC. ROS-responsive and self-positioning biomimetic nanoparticle delivery of obeticholic acid mitigates primary sclerosing cholangitis via mitochondria-induced apoptosis. • ROS-responsive PPFTU material loaded with OCA alleviated hepatobiliary damage. • MSC membrane encapsulation enables powerful targeting of the liver and inflammation. • Organoids and animal models reveal that MPPFTU@OCA mitigates disease progression via mitochondrial-induced apoptosis.
Syphilis testing in blood donors, France, 2007 to 2022
Authors: Syria Laperche, Claire Sauvage, Sophie Le Cam, Florence Lot, Lucile Malard, Pierre Gallian, Elodie Pouchol, Pascale Richard, Pascal Morel, Philippe Grange, Pierre Tiberghien, Nadjet Benhaddou, Nicolas Dupin
Journal: Eurosurveillance (2024)

BackgroundSyphilis in blood donors (BD) has increased in many countries.AimWe aimed to describe trends in syphilis seroposivity in BD in France, to identify risk factors and assess if a non-treponemic test (NTT) could define BD having recovered from syphilis for more than 1 year.MethodsThe analysis covered the period 2007 to 2022 and 45,875,939 donations. Of the 474 BD syphilis-positive in 2022, 429 underwent additional investigations with an NTT. History of syphilis was obtained at the post-donation interview or based on serology results for repeat donors.ResultsUntil 2021, positivity rates remained stable (mean: 1.18/10,000 donations, range: 1.01-1.38). An increased rate was observed in 2022 (1.74/10,000; p = 0.02). Over the whole study period, prevalence was 2.2 times higher in male than in female BD (4.1 times higher in 2022). The proportion of males with an identified risk factor who have sex with men increased from 16.7% in 2007 to 64.9% in 2022. Based on NTT, 79 (18%) of the donors who were seropositive in 2022 were classified as having been infected in the previous year. History of syphilis was available for 30 of them. All had an infection within the previous 3 years. Among seven donors with a syphilis < 12 months before testing, one had an NTT titre ≥ 8, three a titre between 1 and 4, three were negative.ConclusionSyphilis seropositivity increased considerably in BDs in 2022, mostly in males, notably MSM. Available data did not allow appropriate evaluation of the NTT to distinguish recent from past infection.