tbuckley/cabot-search huggingface dataset:
Connection between oral health and chronic diseases
Authors: Di Fu, Xingyue Shu, Ge Zhou, Mengzhen Ji, Ga Liao, Ling Zou
Journal: MedComm (2025)

Chronic diseases have emerged as a paramount global health burden, accounting for 74% of global mortality and causing substantial economic losses. The oral cavity serves as a critical indicator of overall health and is inextricably linked to chronic disorders. Neglecting oral health can exacerbate localized pathologies and accelerate the progression of chronic conditions, whereas effective management has the potential to reduce their incidence and mortality. Nevertheless, limited resources and lack of awareness often impede timely dental intervention, delaying optimal therapeutic measures. This review provides a comprehensive analysis of the impact of prevalent chronic diseases-such as diabetes mellitus, rheumatoid arthritis, cardiovascular disorders, and chronic respiratory diseases-on oral health, along with an exploration of how changes in oral health affect these chronic conditions through both deterioration and intervention mechanisms. Additionally, novel insights into the underlying pathophysiological mechanisms governing these relationships are presented. By synthesizing these advancements, this review aims to illuminate the complex interrelationship between oral health and chronic diseases while emphasizing the urgent need for greater collaboration between dental practitioners and general healthcare providers to improve overall health outcomes.
Financial Incentives, Income Supplementation, Cash Transfer, and Universal Basic Income Interventions in Diabetes: Understanding Differences and Effectiveness: A Scoping Review
Authors: Leonard E. Egede, Jennifer A. Campbell, Sebastian Linde, Rebekah J. Walker
Journal: Diabetes Care (2025)

The objective of this review is to evaluate and summarize the evidence base for the effects of monetary intervention approaches (the use of positive monetary reinforcers and gains) on diabetes outcomes. A reproducible search using OVID Medline, PubMed, Scopus, and CINAHL was conducted. Articles published from database creation up to July 2024 were searched. Outcomes included hemoglobin A1c (HbA1c), LDL, BMI, blood pressure, quality of life (QOL), psychosocial factors, self-care behaviors, and diabetes complications. A total of 13 articles met inclusion criteria and were included for final synthesis. Looking at the monetary approach across each study, eight used financial incentives, three used a form of income supplementation, one used cash transfers, and one used a combination of income supplementation and financial incentives. Ten of the 13 studies found statistically significant and clinically meaningful changes in HbA1c. For participants receiving interventions, change in HbA1c ranged from 0.19% to 1.74% for interventions incorporating financial incentives, 0.7% to 1.3% for interventions incorporating income supplementation, and 0.2% to 0.7% for the study incorporating cash transfers. Overall, evidence supports the relationship between monetary approaches, diabetes-related outcomes, and self-care behaviors across monetary approaches. Future studies should consider comparison between different monetary approaches using designs that will allow identification of effective strategies. As these approaches are theoretically and structurally different, pathways identifying the underlying mechanisms of change are greatly needed to advance the field.
The crosstalk between senescence, tumor, and immunity: molecular mechanism and therapeutic opportunities
Authors: Zehua Wang, Chen Chen, Jiaoyu Ai, Yaping Gao, Lei Wang, Shurui Xia, Yongxu Jia, Yanru Qin
Journal: MedComm (2025)

Cellular senescence is characterized by a stable cell cycle arrest and a hypersecretory, proinflammatory phenotype in response to various stress stimuli. Traditionally, this state has been viewed as a tumor-suppressing mechanism that prevents the proliferation of damaged cells while activating the immune response for their clearance. However, senescence is increasingly recognized as a contributing factor to tumor progression. This dual role necessitates a careful evaluation of the beneficial and detrimental aspects of senescence within the tumor microenvironment (TME). Specifically, senescent cells display a unique senescence-associated secretory phenotype that releases a diverse array of soluble factors affecting the TME. Furthermore, the impact of senescence on tumor-immune interaction is complex and often underappreciated. Senescent immune cells create an immunosuppressive TME favoring tumor progression. In contrast, senescent tumor cells could promote a transition from immune evasion to clearance. Given these intricate dynamics, therapies targeting senescence hold promise for advancing antitumor strategies. This review aims to summarize the dual effects of senescence on tumor progression, explore its influence on tumor-immune interactions, and discuss potential therapeutic strategies, alongside challenges and future directions. Understanding how senescence regulates antitumor immunity, along with new therapeutic interventions, is essential for managing tumor cell senescence and remodeling the immune microenvironment.
Ginsenoside Rk2 alleviates hepatic ischemia/reperfusion injury by enhancing AKT membrane translocation and activation
Authors: Hong Shen, Jiajun Fu, Jiayue Liu, Toujun Zou, Kun Wang, Xiao‐Jing Zhang, Jian‐Bo Wan
Journal: MedComm (2025)

Hepatic ischemia-reperfusion injury (IRI) poses a significant threat to clinical outcomes and graft survival during hemorrhagic shock, hepatic resection, and liver transplantation. Current pharmacological interventions for hepatic IRI are inadequate. In this study, we identified ginsenoside Rk2 (Rk2), a rare dehydroprotopanaxadiol saponin, as a promising agent against hepatic IRI through high-throughput screening. The pharmacological effects and molecular mechanisms of Rk2 on hepatic IRI were further evaluated and elucidated in vitro and in vivo. Rk2 significantly reduced inflammation and apoptosis caused by oxygen-glucose deprivation and reperfusion in hepatocytes and dose dependently protected against hepatic I/R-induced liver injury in mice. Integrated approaches, including network pharmacology, molecular docking, transcriptome analysis, and isothermal titration calorimetry, along with experimental validation, indicated that Rk2 protects against hepatic IRI by targeting and activating the AKT (RAC serine/threonine protein kinase) signaling pathway. Pharmacological inhibition of AKT pathway or knockdown of AKT1 effectively diminished protective effects of Rk2. Rk2 directly binds to AKT1, facilitating its translocation from the cytoplasm to plasma membrane. This process markedly enhanced AKT interaction with PDPK1, promoting the activation of AKT1 and its downstream signaling. Our findings demonstrate that Rk2 protects against hepatic IRI by activating AKT signaling through direct binding to AKT1 and facilitating its membrane translocation.
Eupalinolide B inhibits periodontitis development by targeting ubiquitin conjugating enzyme UBE2D3
Authors: Wenhua Kuang, Ruishen Zhuge, Ping Song, Letai Yi, Shujie Zhang, Ying Zhang, Yin Kwan Wong, Ruixing Chen, Junzhe Zhang, Yuanbo Wang, Dandan Liu, Zipeng Gong, Peili Wang, Xiangying Ouyang, Jigang Wang
Journal: MedComm (2025)

Abstract Periodontitis is a chronic periodontal inflammatory disease caused by periodontal pathogens commonly seen in adults. Eupalinolide B (EB) is a sesquiterpenoid natural product extracted from Eupatorium lindleyanum and has been reported as a potential drug for cancers and immune disorders. Here, we explored the ameliorative effects and underlying molecular mechanism of EB on periodontitis for the first time. We demonstrated that EB ameliorates periodontal inflammation and alveolar bone resorption with a ligated periodontitis mouse model. In addition, the impact of EB on macrophages inflammation was examined in the Raw264.7 cell line. We identified ubiquitin‐conjugating enzyme, UBE2D3, as the direct covalent binding protein targets of EB by using a chemoproteomic method based on activity‐based protein profiling, biolayer interferometry method, and cellular thermal shift assay. Furthermore, the direct binding site of EB to UBE2D3 was identified using high‐resolution mass spectrometry and confirmed by experiments. Taken together, EB ameliorates periodontitis by targeting UBE2D3 to suppress the ubiquitination degradation of IκBα, leading to inactivation of nuclear transcription factor‐κB signaling pathway. And this was confirmed by siRNA‐mediated gene knockdown in inflammatory macrophages. Our results suggested that EB may be a new kind of UBE2D3 inhibitor and may become a promising therapeutic agent for anti‐periodontitis.
Pangenome mining of the Streptomyces genus redefines species’ biosynthetic potential
Authors: Omkar S. Mohite, Tue S. Jørgensen, Thomas J. Booth, Pep Charusanti, Patrick V. Phaneuf, Tilmann Weber, Bernhard O. Palsson
Journal: Genome biology (2025)

Background Streptomyces is a highly diverse genus known for the production of secondary or specialized metabolites with a wide range of applications in the medical and agricultural industries. Several thousand complete or nearly complete Streptomyces genome sequences are now available, affording the opportunity to deeply investigate the biosynthetic potential within these organisms and to advance natural product discovery initiatives. Results We perform pangenome analysis on 2371 Streptomyces genomes, including approximately 1200 complete assemblies. Employing a data-driven approach based on genome similarities, the Streptomyces genus was classified into 7 primary and 42 secondary Mash-clusters, forming the basis for comprehensive pangenome mining. A refined workflow for grouping biosynthetic gene clusters (BGCs) redefines their diversity across different Mash-clusters. This workflow also reassigns 2729 known BGC families to only 440 families, a reduction caused by inaccuracies in BGC boundary detections. When the genomic location of BGCs is included in the analysis, a conserved genomic structure, or synteny, among BGCs becomes apparent within species and Mash-clusters. This synteny suggests that vertical inheritance is a major factor in the diversification of BGCs. Conclusions Our analysis of a genomic dataset at a scale of thousands of genomes refines predictions of BGC diversity using Mash-clusters as a basis for pangenome analysis. The observed conservation in the order of BGCs’ genomic locations shows that the BGCs are vertically inherited. The presented workflow and the in-depth analysis pave the way for large-scale pangenome investigations and enhance our understanding of the biosynthetic potential of the Streptomyces genus.
Conceptualizing and Measuring Systemic Racism
Authors: Tyson H. Brown, Hedwig E. Lee, Margaret T. Hicken, Eduardo Bonilla-Silva, Patricia Homan
Journal: Annual Review of Public Health (2025)

This article provides a guide for rigorous, theory-driven measurement approaches, proposing best practices for the scientific study of systemic racism in health research. We argue that the analytical crux of measuring systemic racism-a complex, interconnected, and dynamic system-lies in operationalizing the collective logics, properties, and mechanisms that undergird racial inequities. Misalignment between measurement tools and these foundational features undermines research validity, as incongruent measures distort findings and obscure systemic racism's true impacts. To address this, we draw on interdisciplinary theories and evidence to dissect key features of systemic racism, emphasizing their implications for measurement. We further recommend incorporating temporal processes in health research by leveraging core principles of the life course perspective, which elucidate the intricate interplay of individual, historical, and societal trajectories. Our recommendations underscore the necessity of adopting robust, evidence-based methods to advance the understanding of how systemic racism operates and shapes public health.
SenPred: a single-cell RNA sequencing-based machine learning pipeline to classify deeply senescent dermal fibroblast cells for the detection of an in vivo senescent cell burden
Authors: Bethany K. Hughes, Andrew Davis, Deborah Milligan, Ryan Wallis, Federica Mossa, Michael P. Philpott, Linda J. Wainwright, David A. Gunn, Cleo L. Bishop
Journal: Genome Medicine (2025)

Abstract Background Senescence classification is an acknowledged challenge within the field, as markers are cell-type and context dependent. Currently, multiple morphological and immunofluorescence markers are required. However, emerging scRNA-seq datasets have enabled an increased understanding of senescent cell heterogeneity. Methods Here we present SenPred, a machine-learning pipeline which identifies fibroblast senescence based on single-cell transcriptomics from fibroblasts grown in 2D and 3D. Results Using scRNA-seq of both 2D and 3D deeply senescent fibroblasts, the model predicts intra-experimental fibroblast senescence to a high degree of accuracy (&gt; 99% true positives). Applying SenPred to in vivo whole skin scRNA-seq datasets reveals that cells grown in 2D cannot accurately detect fibroblast senescence in vivo. Importantly, utilising scRNA-seq from 3D deeply senescent fibroblasts refines our ML model leading to improved detection of senescent cells in vivo . This is context specific, with the SenPred pipeline proving effective when detecting senescent human dermal fibroblasts in vivo, but not the senescence of lung fibroblasts or whole skin. Conclusions We position this as a proof-of-concept study based on currently available scRNA-seq datasets, with the intention to build a holistic model to detect multiple senescent triggers using future emerging datasets. The development of SenPred has allowed for the detection of an in vivo senescent fibroblast burden in human skin, which could have broader implications for the treatment of age-related morbidities. All code for the SenPred pipeline is available at the following URL: https://github.com/bethk-h/SenPred_HDF .
Mechanisms of adaptive resistance to targeted therapy in <i>RET</i>-aberrant cancers
Authors: Sandra Ortiz-Cuaran, Camille Leonce
Journal: Clinical Cancer Research (2025)

Abstract The success of targeted therapies in oncogene-driven cancer is limited by adaptive or acquired treatment resistance, leading to disease progression. A recent study reports that YAP-dependent HER3 activation constitutes a therapeutic vulnerability of adaptive resistance to RET-targeted therapies in RET-altered cancers, highlighting a promising strategy to improve RET-inhibitor tumor responses.
FDA Approval Summary: Tovorafenib for Relapsed or Refractory BRAF-altered Pediatric Low-Grade Glioma
Authors: Sonia Singh, Diana Bradford, Somak Chatterjee, Xiaoxue Li, Stephanie L. Aungst, Amy M. Skinner, Claudia P. Miller, Sarah Kim-McOlash, Jeanne Fourie Zirkelbach, Ye Xiong, Youwei Bi, Ying-Hong Wang, Yuching Yang, Jielin Sun, Jeffrey Kraft, Rosane Charlab, Stacy S. Shord, Shenghui Tang, Barbara Scepura, Ilynn Bulatao, Opeyemi Udoka, Haleh Saber, Nam Atiqur. Rahman, Richard Pazdur, Harpreet Singh, Martha Donoghue, Nicole Drezner
Journal: Clinical Cancer Research (2025)

On April 23, 2024, FDA granted accelerated approval to tovorafenib, a type II RAF kinase inhibitor, for the treatment of patients 6 months of age and older with relapsed or refractory pediatric low-grade glioma (pLGG) harboring a BRAF fusion or rearrangement, or BRAF V600 mutation. Efficacy was evaluated in FIREFLY-1 (NCT04775485), a single-arm, open-label, multicenter trial that enrolled patients 6 months to 25 years of age with relapsed or refractory pLGG with an activating BRAF alteration who had received prior systemic therapy. The major efficacy outcome measure was radiologic overall response rate (ORR), defined as the proportion of patients with complete response, partial response, or minor response as determined by blinded independent central review using Response Assessment in Pediatric Neuro-Oncology (RAPNO) criteria. A key secondary endpoint was duration of response (DoR). In an efficacy population of 76 patients, the ORR was 51% (95% confidence interval (CI): 40, 63), and the median DoR was 13.8 months (95% CI: 11.3, not estimable). The required post-marketing clinical trial (FIREFLY-2) was well underway at the time of accelerated approval. This represents the first FDA approval of a systemic therapy for the treatment of patients with pLGG with BRAF fusions or rearrangements.
Virus-free CRISPR knock-in of a chimeric antigen receptor into KLRC1 generates potent GD2-specific natural killer cells
Authors: Keerthana Shankar, Isabelle Zingler-Hoslet, Diana M Tabima, Seth Zima, Lei Shi, Kirstan Gimse, Matthew H Forsberg, Varun Katta, Sage Z Davis, Daniel Maldonado, Brittany E Russell, Muhammed Murtaza, Shengdar Q Tsai, Jose M Ayuso, Christian M Capitini, Krishanu Saha
Journal: Molecular Therapy (2025)
WHY ARE WE NOT EXPLORING THE POTENTIAL OF LOWER LIMB MUSCLE POWER TO IDENTIFY PEOPLE WITH SARCOPENIA?
Authors: Hélio José Coelho-Júnior, Alejandro Álvarez-Bustos, Francesco Landi, Samuel da Silva Aguiar, Leocadio Rodriguez-Mañas, Emanuele Marzetti
Journal: Ageing Research Reviews (2025)
Adjuvant transarterial chemoembolization for hepatocellular carcinoma following curative resection: A randomized, open-label, phase 3 trial
Authors: Tao Ma, Xueli Bai, Qi Zhang, Wen Chen, Kaiquan Huang, Tao Qian, Yongzi Xu, Peiwei Sun, Yiwen Chen, Wenbo Xiao, Ke Sun, Shunliang Gao, Tingbo Liang
Journal: Hepatology (2025)

The role of adjuvant transarterial chemoembolization (TACE) for HCC following curative resection remains controversial. We aimed to determine the effectiveness of postoperative adjuvant TACE in patients with HCC​​​​​. In this randomized phase 3 trial, histologically confirmed patients with HCC (American Joint Committee on Cancer TNM stage I and II) were randomly assigned (1:1) to adjuvant TACE or observation groups. The primary endpoint was recurrence-free survival (RFS) in the intention-to-treat (ITT) population. The secondary endpoints included overall survival and safety. A total of 332 patients (ITT population) were randomly assigned to the TACE group (n=166) or the observation group (n=166) between March 2014 and June 2021. The RFS was comparable between the 2 groups from the ITT population (median, both unreached; HR, 0.88; 95% CI: 0.62-1.24; p =0.468). The RFS rates at 1, 3, and 5 years were 87.3% (95% CI: 81.2-91.5), 70.7% (95% CI: 63.0-77.0), and 60.6% (95% CI: 51.9-68.3) in the adjuvant TACE group and 84.8% (95% CI: 78.3-89.5), 69.3% (95% CI: 61.6-75.8), and 58.1% (95% CI: 49.5-65.8) in the observation group, respectively. The overall survival was comparable between the TACE group and the observation group in the ITT population (median, both unreached, HR, 1.06; 95% CI: 0.63-1.76; p =0.838). There was no grade ≥ 3 adverse event or treatment-related death in either group. Postoperative adjuvant TACE was not associated with prolonged RFS or overall survival in patients with American Joint Committee on Cancer TNM stage I or II HCC.
Downstaging of hepatocellular carcinoma before liver transplantation: Results from a national multi-center prospective cohort study
Authors: Edison Xu, Parissa Tabrizian, Julio Gutierrez, Maarouf Hoteit, Tara Ghaziani, Kali Zhou, Neehar Parikh, Veeral Ajmera, Elizabeth Aby, Amy Shui, Rebecca Marino, Allison Martin, Christopher Wong, Karissa Kao, Shravan Dave, Sander Florman, Francis Yao, Neil Mehta
Journal: Hepatology (2025)

Patients with hepatocellular carcinoma (HCC) meeting UNOS-downstaging (DS) criteria have excellent post-liver transplantation (LT) outcomes. Studies on HCC beyond UNOS-DS criteria ("All-comers" (AC)) have been limited by small sample size and short follow-up time, prompting this analysis. 326 patients meeting UNOS-DS and 190 meeting AC criteria from 9 LT centers across 5 UNOS regions were enrolled from 2015 to 2023 and prospectively followed. Competing risk analysis and Kaplan-Meier method were used to evaluate downstaging and LT outcomes, and Fine-and-Gray and Cox models were used to identify predictors of outcomes. AC and UNOS-DS had similar median alpha-fetoprotein (15 vs. 12 ng/mL;p=0.08), MELD (9 vs. 9;p=0.52), and Child-Pugh (A vs. A;p=0.30). At 2 years from first local regional therapy, 82% of UNOS-DS and 66% of AC were successfully downstaged (p<0.001). In AC, DS rates were 72% for tumor number plus diameter of largest lesion<10, 51% for sum 10-12, and 39% for sum>12 (p=0.01). Y-90 achieved higher DS success than transarterial chemoembolization (TACE) in AC (74% vs. 65%;p<0.001). 48% of UNOS-DS and 40% of AC underwent LT (p=0.10). 5-year post-LT survival was similar between UNOS-DS and AC (74% vs. 72%;p=0.77), although 5-year post-LT recurrence was higher in AC (30% vs. 14%;p=0.02). Despite higher HCC recurrence and lower ITT survival in AC, post-LT survival was comparable between UNOS-DS and AC. Y-90 attained higher DS success than TACE in AC. LT after downstaging is feasible in AC, though defining an upper limit in tumor burden may be necessary.
Prevention of liver cancer in the era of next-generation antivirals and obesity epidemic
Authors: Hiroyuki Suzuki, Naoto Fujiwara, Amit G. Singal, Thomas F. Baumert, Raymond T. Chung, Takumi Kawaguchi, Yujin Hoshida
Journal: Hepatology (2025)

Preventive interventions are expected to substantially improve the prognosis of patients with primary liver cancer, predominantly hepatocellular carcinoma (HCC) and cholangiocarcinoma. HCC prevention is challenging in the face of the evolving etiological landscape, particularly the sharp increase in obesity-associated metabolic disorders, including metabolic dysfunction-associated steatotic liver disease (MASLD). Next-generation anti-HCV and HBV drugs have substantially reduced, but not eliminated, the risk of HCC and have given way to new challenges in identifying at-risk patients. The recent development of new therapeutic agents and modalities has opened unprecedented opportunities to refine primary, secondary, and tertiary HCC prevention strategies. For primary prevention (before exposure to risk factors), public health policies, such as universal HBV vaccination, have had a substantial prognostic impact. Secondary prevention (after or during active exposure to risk factors) includes regular HCC screening and chemoprevention. Emerging biomarkers and imaging modalities for HCC risk stratification and detection may enable individual risk-based personalized and cost-effective HCC screening. Clinical studies have suggested the potential utility of lipid-lowering, anti-diabetic/obesity, and anti-inflammatory agents for secondary prevention, and some of them are being evaluated in prospective clinical trials. Computational and experimental studies have identified potential chemopreventive strategies directed at diverse molecular, cellular, and systemic targets for etiology-specific and/or agnostic interventions. Tertiary prevention (in conjunction with curative-intent therapies for HCC) is an area of active research with the development of new immune-based neo/adjuvant therapies. Cholangiocarcinoma prevention may advance with recent efforts to elucidate risk factors. These advances will collectively lead to substantial improvements in liver cancer mortality rates.