tbuckley/cabot-search huggingface dataset:
Sodium–Glucose Cotransporter 2 Inhibitor Use and Risk of Liver-Related Events in Patients With Type 2 Diabetes: A Meta-analysis of Observational Cohort Studies
Authors: Alessandro Mantovani, Riccardo Morandin, Maria Giovanna Lando, Veronica Fiorio, Grazia Pennisi, Salvatore Petta, Norbert Stefan, Herbert Tilg, Christopher D. Byrne, Giovanni Targher
Journal: Diabetes Care (2025)

BACKGROUND There is uncertainty regarding effect of sodium–glucose cotransporter 2 (SGLT2) inhibitors on the risk of major adverse liver-related outcomes (MALOs). PURPOSE We performed a meta-analysis of observational cohort studies to quantify the magnitude of the association between SGLT2 inhibitor use and risk of developing MALOs for people with type 2 diabetes mellitus (T2DM). DATA SOURCES We systematically reviewed three large electronic databases from inception to January 2025. STUDY SELECTION We included active-comparator, new-user cohort studies with comparison of SGLT2 inhibitors versus other glucose-lowering medications in patients with T2DM. DATA EXTRACTION The primary outcome was incidence rate of MALOs defined as a composite of hepatic decompensation events, hepatocellular carcinoma, liver transplantation, or liver-related deaths. Secondary outcomes included each of the above as individual events. Meta-analysis was performed with random-effects models. DATA SYNTHESIS We identified eight cohort studies with aggregate data on 626,104 patients with T2DM (397,806 SGLT2 inhibitor new users and 228,298 new users of other glucose-lowering agents). During a median of 2.7 years, SGLT2 inhibitor use was associated with significantly lower risk of MALOs (random-effects hazard ratio 0.83, 95% CI 0.72–0.95; I2 = 83.1%) and liver-related deaths (0.64, 0.50–0.82; I2 = 0%). The significant risk reduction in MALOs was observed in comparisons of SGLT2 inhibitors with dipeptidyl peptidase 4 inhibitors, metformin, or pioglitazone but not glucagon-like peptide 1 receptor agonists. Sensitivity analyses did not modify these results. A funnel plot did not show significant publication bias. LIMITATIONS Observational design of the cohort studies and high level of heterogeneity are the main limitations. CONCLUSIONS SGLT2 inhibitor use was associated with lower risk of MALOs for patients with T2DM.
Cost-effectiveness of Semaglutide Compared With Other Glucose-Lowering Medications in Treating Type 2 Diabetes: A Comprehensive Systematic Review and Meta-analysis
Authors: Ziyun Liu, Baoqi Zeng, Feng Sun, Qing Xia
Journal: Diabetes Care (2025)

BACKGROUND Significant clinical efficacy has been shown for semaglutide in managing type 2 diabetes (T2D); however, its cost-effectiveness remains uncertain. PURPOSE To systematically review existing evidence on cost-effectiveness of semaglutide versus other T2D medications. DATA SOURCES PubMed, Embase, and the Cost-Effectiveness Analysis Registry (by 11 June 2024). STUDY SELECTION A total of 45 articles (with 119 comparisons) from 2019 onward were included, representing Europe (n = 24), North America (n = 13), and Asia (all from China) (n = 8). DATA EXTRACTION Study characteristics and model characteristics/inputs/results were extracted. Lifetime costs and quality-adjusted life-years were evaluated. Proportions for cost-effectiveness outcomes (dominant, cost-effective, not cost-effective) were calculated. Subgroup analyses by region, sponsor type, comparator type, and model assumptions were performed. In sensitivity analysis a standard willingness-to-pay threshold was applied. DATA SYNTHESIS Of the articles included, 93.3% included adoption of a lifetime horizon and 84.4% a health care perspective and 68.9% were industry sponsored. For most studies reporting quality was high (86.7%). Overall, semaglutide was dominant/cost-effective in 73.9% of all comparisons. Notably, semaglutide was found to be dominant/cost-effective in all comparisons sponsored by Novo Nordisk versus in 50.0% of these funded by nonindustry sponsors and in none funded by other industry sponsors. Additionally, semaglutide was more cost-effective in high-income countries and in studies with adoption of a broader perspective, longer horizon, and lower discount rates. Results remained consistent with conversion with a common currency unit and willingness-to-pay threshold of US$50,000. LIMITATIONS Less detailed demographic information for more granular analyses. CONCLUSIONS Semaglutide is generally cost-effective compared with other glucose-lowering medications in evaluation against within-study willingness-to-pay thresholds; however, results varied by study sponsor type, region, and model assumptions, highlighting the need for transparent and context-sensitive economic evaluations.
Far-UVC Exposure in Patients with Photosensitivity Disorders
Authors: Evangelos Christou, Leona Fenton, Robert Dawe, Ewan Eadie, Sally H Ibbotson
Journal: British Journal of Dermatology (2025)

Far-ultraviolet C (Far-UVC) light, with its germicidal properties, shows promise in reducing the spread of infectious diseases in public and healthcare settings. Emerging evidence suggests minimal risk to human skin and eyes, but its safety for patients with photosensitivity disorders remains uncertain. This study aims to fill this gap by assessing the safety of Far-UVC exposure for individuals with these conditions.
Improving global access to genomic profiling in rare pediatric cancers
Authors: Sameer Farouk Sait, Tara J. O'Donohue, Tejus Bale, Anita Bowman, Katherine Hill, Emily Stockfisch, Alexandra Giantini-Larsen, Tina‌ ‌ Alano‌, Marc Rosenblum, Jamal Benhamida, Ira J. Dunkel, Michael Berger, Maria E. Arcila, Marc Ladanyi, Michael V. Ortiz, Julia Glade Bender, Alexandra Miller, Debyani Chakravarty, Kelly Cavender, Benjamin Preiser, Hongxin Zhang, Andrew L. Kung, David B. Solit, Matthias A. Karajannis, Neerav N. Shukla
Journal: Clinical Cancer Research (2025)

Abstract Background: To address financial barriers that limit access to genomic profiling and precision medicine, philanthropy supported clinical genomic testing was offered worldwide at no cost to patients with select rare cancers via the Make-an-IMPACT program. Herein, we report our findings in pediatric patients with solid or central nervous system (CNS) tumors. Methods: Tumor DNA or CSF-derived circulating tumor DNA (CSF ctDNA) was analyzed using the MSK-IMPACT assay, supplemented by targeted RNA panel sequencing in select cases. Results were returned to the patients/families and treating oncologists. Results: 63 patients from 11 countries had successful MSK-IMPACT testing. The results provided clinically relevant new diagnostic or prognostic information in 41% and 38% of solid and CNS tumor patients, respectively. Potentially therapeutically actionable alterations were identified in 44% of pediatric solid tumor and 21% of pediatric CSF ctDNA samples, respectively. Four patients subsequently received molecularly guided therapy, resulting in partial responses in two and prolonged stable disease in one. Serial tumor and CSF sampling identified resistance mutations in two patients, informing additional molecular targeted therapy recommendations. Conclusions: The Make-an-IMPACT program provided global access to state-of-the-art tumor and CSF genomic profiling across a diverse cohort of pediatric cancer patients, providing clinically relevant and actionable diagnostic, prognostic and therapeutic information reported in real time to patients and local physicians.
Spatial transcriptomics advances the use of canine patients in cancer research: analysis of osteosarcoma-bearing pet dogs enrolled in a clinical trial
Authors: Jessica A. Beck, Anjali Garg, Sarah Church, Christina Mazcko, Amy K. LeBlanc
Journal: Clinical Cancer Research (2025)

Abstract Purpose. Pet dogs spontaneously develop many of the same tumor types as humans including osteosarcoma. Recent advances in spatial transcriptomics have improved our ability to utilize formalin-fixed paraffin-embedded tissues collected at canine autopsy. These techniques allow the canine model to be investigated alongside murine models to inform human cancer research. Herein we present the first application of the GeoMx Canine Cancer Atlas to outcome-linked samples from canine patients enrolled in an osteosarcoma clinical trial. Experimental Design. A tissue microarray (TMA) of primary osteosarcoma samples was assayed using the GeoMx Digital Spatial Profiler. Samples were stratified by disease-free interval (DFI). Patients within the upper and lower tertiles were assigned to the High (n = 8) and Low DFI (n = 8) groups, respectively. Analyses included the identification of differentially expressed genes, pathway enrichment, and cell deconvolution. Results. Genes enriched in High DFI tumors included PTEN and CDKN1B. Low DFI tumors were enriched for NCAM1. Pathways enriched in the Low DFI group included MYC, MTORC1, and oxidative phosphorylation. High DFI tumors were enriched for interferon alpha response and allograft rejection pathways among others. Macrophages and CD8+ T cells were elevated in High DFI tumors. Conclusions. Gene and pathway enrichment found to be associated with disease-free interval in this study overlap with that described in human osteosarcoma patients underscoring the value of the canine model in metastatic osteosarcoma research.
Integrative Immune Signature of Complementary Circulating and Tumoral Biomarkers Maximizes the Predictive Power of Adjuvant Immunotherapeutic Benefits in High-Risk Melanoma
Authors: Ahmad A. Tarhini, Alyssa Obermayer, Sandra J. Lee, William A. LaFramboise, F. Stephen Hodi, Arivarasan D. Karunamurthy, Islam Eljilany, Dung-Tsa Chen, Patrick Hwu, Issam M. El Naqa, Howard Streicher, Vernon K. Sondak, Walter J. Storkus, Lisa H. Butterfield, Timothy I. Shaw, John M. Kirkwood
Journal: Clinical Cancer Research (2025)

Abstract Purpose: Ipilimumab (IPI) improved outcomes for high-risk melanoma patients compared to interferon-α2b (IFN) in E1609, a phase III adjuvant trial. We hypothesized that combining candidate immune biomarkers in both tumor and circulating blood could generate a superior predictive biomarker signature. Patients and Methods: We conducted gene expression profiling on baseline tumors of patients treated with IPI and IFN. We also performed multicolor flow cytometry to compare cellular marker expressions on thawed peripheral blood mononuclear cells and multiplex Luminex to measure serum biomarkers. We tested the expression levels of 31 genes and 40 circulating biomarkers in relation to survival outcomes. We then developed two separate multivariate Lasso-Cox regression models followed by integrative modeling of risk prediction using the prioritized biomarkers. Results: In blood, enriched populations of CXCR3+CD4+ T cells, CXCR3+CD8+ T cells, CTLA4+IFN-γ+CD8+ T cells, and higher levels of CCL3 and CXCL11 were associated with significantly improved overall survival (OS) and relapse-free survival (RFS), while high levels of CTLA4+Treg (CD3+CD4+CD25hi+CD152+) and monocytic (M)-MDSC (Lin-CD33+HLA-DrloCD14+CD15+) cells correlated with worse OS and RFS. In tumor, CXCL9, CD8A, CXCL10, and INPP5D were identified as Tier-1 (P&amp;lt;0.05) and IDO1, IGKC, IL2RB as Tier-2 (P&amp;lt;0.1) biomarkers of survival. Multivariate survival analysis identified that ~50% of the risk groups were defined by circulating and tumor biomarker models, indicating complementary features of defining risk groups in IPI-treated but not in IFN-treated patients. Conclusions: Integrating candidate blood and tumor immune-related biomarkers generated a baseline signature that maximizes the prediction of immunotherapeutic benefits in reference to the compartmental biomarker signatures.
Mogamulizumab induced lymph node enlargement mimicking mycosis fungoides progression
Authors: Lorena Calderon-Lozano, Borja Gonzalez-Rodriguez, An Wang, Concepción Postigo-Llorente, Eloy Tarin, Jose Rodriguez-Peralto, Antonia Rodriguez Izquierdo, Pablo Ortiz, Daniel Falkenhain-López
Journal: British Journal of Dermatology (2025)

We describe two cases of mogamulizumab-treated mycosis fungoides patients in complete remission who developed lymphadenopathy mimicking disease progression. Biopsies revealed non-malignant findings, suggesting a possible treatment-related reactive process. These cases highlight the importance of histological confirmation before altering therapy based solely on imaging.
ROBIN: A unified nanopore-based assay integrating intraoperative methylome classification and next-day comprehensive profiling for ultra-rapid tumor diagnosis
Authors: Simon Deacon, Inswasti Cahyani, Nadine Holmes, Graeme Fox, Rory Munro, Satrio Wibowo, Thomas Murray, Hannah Mason, Mark Housley, Daniel Martin, Abdi Sharif, Areeba Patel, Robert Goldspring, Sebastian Brandner, Felix Sahm, Stuart Smith, Simon Paine, Matthew Loose
Journal: Neuro-Oncology (2025)

Abstract Background Advances in our technological capacity to interrogate CNS tumor biology have led to the ever increasing use of genomic sequencing in diagnostic decision making. Presently, CNS tumors are classified based on their epigenetic signatures, leading to a paradigm shift in diagnostic pathways. Such testing can be performed so rapidly using nanopore sequencing that results can be provided intraoperatively. This information greatly improves the fidelity of smear diagnosis and can help surgeons tailor their approach, balancing the risks of surgery with the likely benefit. Nevertheless, full integrated diagnosis may require subsequent additional assays to detect pathognomonic somatic mutations and structural variants, thereby delaying the time to final diagnosis. Methods Here, we present ROBIN, a tool based on PromethION nanopore sequencing technology that can provide both real-time, intraoperative methylome classification and next-day comprehensive molecular profiling within a single assay. ROBIN utilizes 3 methylation classifiers to improve diagnostic performance in the intraoperative setting. Results We demonstrate classifier performance on 50 prospective intraoperative cases, achieving a diagnostic turnaround time under 2 hours and generating robust tumor classifications within minutes of sequencing. Furthermore, ROBIN can detect single nucleotide variants, copy number variants, and structural variants in real time, and is able to inform a complete integrated diagnosis within 24 hours. Classifier performance demonstrated concordance with final integrated diagnosis in 90% of prospective cases. Conclusion Nanopore sequencing can greatly improve turnaround times for standard-of-care diagnostic testing and is furthermore able to reliably provide clinically actionable intraoperative tumor classification.
Biofilm formation by the host microbiota: a protective shield against immunity and its implication in cancer
Authors: Elena Montanari, Giancarla Bernardo, Valentino Le Noci, Martina Anselmi, Serenella M Pupa, Elda Tagliabue, Michele Sommariva, Lucia Sfondrini
Journal: Molecular Cancer (2025)

Human-resident microbes typically cluster into biofilms - structurally organized communities embedded within a matrix of self-produced extracellular polymeric substance (EPS) that serves as a protective shield. These biofilms enhance microbial survival and functional adaptability, favoring a symbiotic relationship with the host under physiological conditions. However, biofilms exhibit a dual role in modulating the immune response. If their ability to promote tolerance is key to safeguarding homeostasis, by contrast, their persistence can overcome the cutting-edge balance resulting in immune evasion, chronic inflammation and development of numerous diseases such as cancer. Recent evidence highlights the significance of cancer-associated microbiota in shaping the tumor microenvironment (TME). These microbial inhabitants often exhibit biofilm-like structures, which may protect them from host immune responses and therapeutic interventions. The presence of biofilm-forming microbiota within the TME may promote chronic inflammation, and release of bioactive molecules that interfere with immune surveillance mechanisms, thereby enabling cancer cells to evade immune destruction. This review delves into the complex interplay between biofilms and cancer, with particular focus on the tumor-associated microbiota and the implications of biofilm involvement in modulating the immune landscape of the TME. Addressing this intricate relationship holds promises for innovative therapeutic approaches aimed at reprogramming the microbiota-cancer axis for better clinical outcomes.
Advances in the treatment of hepatocellular carcinoma: An overview of the current and evolving therapeutic landscape for clinicians
Authors: Dimitrios Moris, Alessandro Martinino, Sarah Schiltz, Peter J. Allen, Andrew Barbas, Debra Sudan, Lindsay King, Carl Berg, Charles Kim, Mustafa Bashir, Manisha Palta, Michael A. Morse, Michael E. Lidsky
Journal: CA A Cancer Journal for Clinicians (2025)

Abstract Hepatocellular carcinoma (HCC) is the sixth most common malignancy and the third leading cause of cancer‐related death worldwide. Contemporary advances in systemic and locoregional therapies have led to changes in peer‐reviewed guidelines regarding systemic therapy as well as the possibility of downstaging disease that may enable some patients with advanced disease to ultimately undergo partial hepatectomy or transplantation with curative intent. This review focuses on all modalities of therapy for HCC, guided by modern‐day practice‐changing randomized data where available. The surgical management of HCC, including resection and transplantation, both of which have evolving criteria for what is considered biologically resectable and transplantable, as well as locoregional therapy (i.e., therapeutic embolization, ablation, radiation, and hepatic arterial infusion), are discussed. Historical and modern‐day practice‐changing trials evaluating immunotherapy with targeted therapies for advanced disease, as well as adjuvant systemic therapy, are also summarized. In addition, this article examines the critical dimension of toxicities and patient‐oriented considerations to ensure a comprehensive and balanced discourse on treatment implications.
QT interval changes in transgender/gender diverse adolescents receiving gonadotropin-releasing hormone agonist and gender-affirming hormonal treatment
Authors: Hussein Zaitoon, Livia Kapusta, Galit Israeli, Anat Segev-Becker, Gil Beer, Alexander Lowenthal, Gili Yaeger Yarom, Asaf Oren, Liat Perl
Journal: International Journal of Transgender Health (2025)
Incidence and prevalence of dementia among US Medicare beneficiaries, 2015-21: population based study
Authors: Beau Blass, Cassie B Ford, Samir Soneji, Lindsay Zepel, Talita D'Aguiar Rosa, Brystana G Kaufman, Sneha Mantri, Fan Li, Brian Mac Grory, Ying Xian, Kim G Johnson, Richard O'Brien, Bradley G Hammill, Emily C O'Brien, Jay B Lusk
Journal: BMJ (2025)

Abstract Objective To determine the incidence and prevalence of dementia in a nationally representative cohort of US Medicare beneficiaries, stratified by important subgroups. Design Population based study. Setting Nationwide study between 2015 and 2021. Participants Fee-for-service Medicare beneficiaries aged 66 or older with at least one year of continuous enrollment. Main outcome measures Incidence and prevalence of dementia, calculated as percentage per person years or percentage of beneficiaries respectively. These metrics were also calculated in key subgroups defined by age, sex, race/ethnicity, and neighborhood socioeconomic status. Results A total of 5 025 039 incident cases of dementia were documented from 2015 to 2021. The overall age and sex standardized incidence decreased between 2015 and 2021 from 3.5% to 2.8%. Prevalence increased during this time from 10.5% to 11.8%. Male beneficiaries had a higher age standardized incidence than did female beneficiaries in 2015 (3.5% v 3.4%), a difference that widened by 2021 (2.9% v 2.6%; estimated difference-in-difference 0.94, 95% confidence interval (CI) 0.94 to 0.95; P&lt;0.001). Incidence was highest in 2015 for black beneficiaries (4.2%), followed by Hispanic beneficiaries (3.7%) and white beneficiaries (3.4%), and in 2021 for black beneficiaries (3.1%) followed by white beneficiaries (2.8%) and Hispanic beneficiaries (2.6%); the difference between white and black beneficiaries narrowed from 2015 to 2021 (difference-in-difference 0.92, 95% CI 0.91 to 0.93; P&lt;0.001) as did the difference between white and Hispanic beneficiaries (difference-in-difference 0.88, 0.87 to 0.89; P&lt;0.001). Conclusions The incidence of dementia decreased from 2015 to 2021, but the prevalence increased. Disparities in these measures by race/ethnicity, sex, and neighborhood socioeconomic status should motivate future measures to promote health equity.
Advances in Alzheimer's Therapy: Exploring Neuropathological Mechanisms to Revolutionize the Future Therapeutic Landscape
Authors: Vrashabh V Sugandhi, Dnyandev G Gadhave, Akanksha R Ugale, Nilesh Kulkarni, Sopan N Nangare, Harshal P Patil, Seepra Rath, Rahul Saxena, Amol Lavate, Apeksha T Patel, Ashish Jadhav, Keshav Raj Paudel
Journal: Ageing Research Reviews (2025)

Alzheimer's disease (AD) is still an excessively complicated neurological disorder that impacts millions of individuals globally. The ideal defensive feature of the central nervous system (CNS) is the intimate junction of endothelial cells, which functions as a biological barrier to safely control molecular transport throughout the brain. The blood-brain barrier (BBB) comprises tightly locked astrocyte cell junctions on CNS blood capillaries. This biological barrier shields the brain from hazardous toxins by preventing the entry of polar medications, cells, and ions. However, it is very challenging to provide any treatment to the brain for neurodegenerative illnesses like Alzheimer's. Different causative mechanisms, such as amyloid-β (Aβ) plaques, tubulin-associated unit (Tau) tangles, and neuroinflammation, cause neuronal dysfunction, leading to dementia and memory loss in the subject. Several treatments are approved for AD therapy, whereas most only help treat related symptoms. Disappointingly, current remedies have not been able to control the progression of AD due to associated side effects. Specific pathogenic mechanisms are involved in the initiation and development of this disease. Therefore, the expected survival of a patient with AD is limited and is approximately ten years. Hence, the pathogenic mechanism behind AD progression must be understood to better comprehend and improve the overall survival rate. This review highlighted the recent insights into AD pathogenesis, molecular mechanisms, advancements in theragnostic techniques, the existing updates of clinical trials, and emerging innovations for AD medicinal development. That has helped researchers develop other strategies to address the shortcomings of traditional medications.