tbuckley/cabot-search huggingface dataset:
Immune Checkpoint Inhibitors in Field Cancerization and Keratinocyte Cancer Prevention
Authors: Charlotte Cox, Susan Brown, Euan Walpole, Edwige Roy, Lea Dousset, Rahul Ladwa, Kiarash Khosrotehrani
Journal: JAMA Dermatology (2025)

Importance Therapies for individual keratinocyte carcinomas (KCs) do not prevent the onset of new KCs in a field of sun damage, and therefore the KC burden remains unchanged. Objective To investigate the association of immune checkpoint inhibitors (ICIs) with changes in field cancerization evaluated by the number of actinic keratoses (AKs) and KCs at baseline compared with 12 months after starting ICI therapy. Design, Setting, and Participants This prospective cohort study was performed at the outpatient oncology clinic of a single tertiary public hospital in Brisbane, Australia, from April 1, 2022, to November 30, 2023. Consecutive immunocompetent adults starting therapy with an inhibitor for programmed cell death 1 (PD-1) or programmed cell death ligand 1 (PDL-1) for any active cancer, with a planned treatment duration of at least 6 months, and who exhibited clinical AKs on their forearms were eligible. Those with immunosuppression, concurrent chemotherapy or radiotherapy, or recent topical fluorouracil use were excluded. Exposures Intravenous ICI therapy, either PD-1 or PDL-1 inhibitors with or without a cytotoxic T-lymphocyte–associated protein 4 inhibitor, with therapy duration determined by the treating oncologist. Main Outcomes and Measures Clinical AKs were counted and photographed before and 3, 6, and 12 months after starting ICI therapy. KC numbers were evaluated based on histopathology reports of all skin lesions excised 12 months before and after starting ICI therapy. Participants’ medical history, primary cancer tumor response using Response Evaluation Criteria in Solid Tumors, and adverse events were recorded. Results A total of 23 participants were recruited, of whom 17 (73.9%) were male, with a mean (SD) age of 69.7 (9.6) years. No participants withdrew; however, 4 died during the study due to disease progression. The mean (SD) AK number significantly decreased from 47.2 (33.8) at baseline to 14.3 (12.0) at 12 months ( P &amp;amp;lt; .001). Younger patients (8 of 12 [66.7%] vs 4 of 12 [33.3%]; P = .007) and those with a history of blistering sunburn (12 of 12 [100%] vs 0; P = .005) were more likely to reduce their AK numbers by 65% or greater. KC total numbers decreased from 42 in the 12 months before starting ICI therapy to 17 in the 12 months after. The number of cutaneous squamous cell carcinomas decreased from 16 to 5 in the same period. Conclusions and Relevance This pilot cohort study found that ICIs used for any cancer were associated with a significant reduction of AKs, suggesting potential as an immunopreventive strategy for high-risk individuals. Given the known effects of other chemopreventive agents on KCs, further investigation into ICIs managing field cancerization is required, especially considering toxicity and cost.
Attention-Deficit/Hyperactivity Disorder in Medicaid-Enrolled Autistic Adults
Authors: Benjamin E. Yerys, Sha Tao, Lindsay Shea, Gregory L. Wallace
Journal: JAMA Network Open (2025)

Importance Autistic adults experience suboptimal health outcomes. Likewise, attention-deficit/hyperactivity disorder (ADHD) is linked to poor health outcomes in the general population, yet little is known about co-occurring ADHD and its links with poor health outcomes among autistic adults. Objective To determine the prevalence of ADHD and ADHD medication prescriptions and to examine associations between health outcomes and both ADHD co-occurrence and ADHD medication prescriptions among autistic adults. Design, Setting, and Participants Population-based cohort study of US Medicaid-enrolled adults aged 18 years and older, including autistic adults with and without co-occurring intellectual disability (ID), adults with ID without autism, and adults from a random sample of Medicaid-enrolled individuals from 2008 to 2019. Analyses were completed September 2023 to September 2024. Exposures Autism, ADHD, and ID using validated algorithms from the Chronic Conditions Warehouse. Main Outcomes and Measures Prevalence rates of co-occurring ADHD, ADHD medication prescriptions, substance use, cardiovascular conditions, injury in autism without ID, ID without autism, autism with ID, and the general population. Results The study included 3 506 661 patients (mean [SD] age, 33.5 [15.6] years; 1 854 892 [52.9%] female; 702 694 [20.0%] Black, 587 048 [16.7%] Hispanic, and 1 786 703 [60.0%] White). Compared with the general Medicaid-enrolled population (1 846 102 patients), which had 49 523 patients (2.7%) with co-occurring ADHD diagnoses, this study found elevated rates of ADHD in autism without ID (280 195 patients [26.7%]; prevalence ratio [PR], 5.1; 95% CI, 4.4-5.9), autism with ID (261 061 patients [40.2%]; PR, 6.8; 95% CI, 6.0-7.7), and ID without autism (1 119 303 patients [19.0%]; PR, 4.4; 95% CI, 4.0-5.0). A total of 117 704 adults (26.6%) with ADHD received an ADHD medication prescription. The study identified that rates of substance use were higher among clinical groups with co-occurring ADHD. For example, 9886 of 74 675 autistic adults with ADHD (13.2%) had substance use disorder, compared with 11 782 of 205 520 autistic adults with no ADHD (5.7%). ADHD diagnoses were associated with higher rates of all health outcomes, regardless of group. Substance use was higher in both ID groups with ADHD diagnoses and ADHD medications, whereas injury and cardiovascular condition rates were lower in all ADHD groups who received ADHD medications. Conclusions and Relevance In this cohort study of Medicaid-enrolled adults, autistic adults experienced high rates of co-occurring ADHD and were more likely to receive ADHD medication prescriptions than adults in the general population. Negative health outcome rates are higher among autistic people with co-occurring ADHD, although ADHD medication prescriptions are associated with lower rates of negative health outcomes. Treating ADHD may improve health among autistic adults.
Long-term yogurt intake and colorectal cancer incidence subclassified by <i>Bifidobacterium</i> abundance in tumor
Authors: Satoko Ugai, Li Liu, Keisuke Kosumi, Hidetaka Kawamura, Tsuyoshi Hamada, Kosuke Mima, Kota Arima, Kazuo Okadome, Qian Yao, Kosuke Matsuda, Yuxue Zhong, Hiroki Mizuno, Andrew T. Chan, Wendy S. Garrett, Mingyang Song, Marios Giannakis, Edward L. Giovannucci, Xuehong Zhang, Shuji Ogino, Tomotaka Ugai
Journal: Gut Microbes (2025)

Evidence suggests a tumor-suppressive effect of the intake of yogurt, which typically contains Bifidobacterium. We hypothesized that long-term yogurt intake might be associated with colorectal cancer incidence differentially by tumor subgroups according to the amount of tissue Bifidobacterium. We utilized the prospective cohort incident-tumor biobank method and resources of two prospective cohort studies. Inverse probability weighted multivariable Cox proportional hazards regression was used to assess differential associations of yogurt intake with the incidence of colorectal carcinomas subclassified by the abundance of tumor tissue Bifidobacterium. During follow-up of 132,056 individuals, we documented 3,079 incident colorectal cancer cases, including 1,121 with available tissue Bifidobacterium data. The association between long-term yogurt intake and colorectal cancer incidence differed by Bifidobacterium abundance (P heterogeneity = 0.0002). Multivariable-adjusted hazard ratios (HRs) (with 95% confidence intervals) in individuals who consumed ≥2 servings/week (vs. <1 serving/month) of yogurt were 0.80 (0.50–1.28) for Bifidobacterium-positive tumor and 1.09 (0.81–1.46) for Bifidobacterium-negative tumor. This differential association was also observed in a subgroup analysis of proximal colon cancer (P heterogeneity = 0.018). Long-term yogurt intake may be differentially associated with the incidence of proximal colon cancer according to Bifidobacterium abundance, suggesting the antitumor effect of yogurt intake on the specific tumor subgroup.
Chemoimmunotherapy vs Immunotherapy Monotherapy Receipt in Advanced Non–Small Cell Lung Cancer
Authors: Vinayak S. Ahluwalia, Ravi B. Parikh
Journal: JAMA Network Open (2025)

This cross-sectional study examines factors that may be associated with the prescription of chemoimmunotherapy vs immunotherapy monotherapy in cases of advanced non–small cell lung cancer using nationwide data from the US.
Actinic Keratosis Incidence in Solid Organ Transplant Recipients
Authors: Lucy J. Navsaria, Kaiping Liao, Surya Veerabagu, Candice L. Hinkston, Mackenzie R. Wehner
Journal: JAMA Dermatology (2025)

This cohort study examines the incidence of actinic keratoses, which are possible precursors to skin cancer, especially squamous cell carcinoma, after solid organ transplant.
Who Should Own Americans’ Health Care?
Authors: David U. Himmelstein, Robert Kuttner, Steffie Woolhandler
Journal: JAMA (2025)

This Viewpoint discusses the collapse of the Steward Health Care system as a case in point of the salience of proprietorship in health care, the problem of private equity firms’ business models emphasizing short-term gains, and the conflict between financial ambition and clinical mission.
Long-Term Survival by Number of Immune Checkpoint Inhibitors in PD-L1–Negative Metastatic NSCLC
Authors: Ben Ponvilawan, Dhruv Bansal, Nagla Abdel Karim, Rahul Ramakrishnan, Janakiraman Subramanian
Journal: JAMA Network Open (2025)

This systematic review and meta-analysis evaluates long-term survival outcomes by number of immune checkpoint inhibitors among patients with programmed death-ligand 1 (PD-L1)–negative non–small cell lung cancer (NSCLC).
Sudan Ebola virus disease outbreak in Uganda — a role for cryptic transmission?
Authors: Henry Kyobe Bosa, Misaki Wayengera, Suzan Nabadda, Charles Olaro, Rony Bahatungire, Samuel Kalungi, Barnabas Bakamutumaho, Allan Muruta, Atek Kagirita, Haruna Muwonge, Andrew Nsawotebba, Isaac Ssewanyana, M Njenga Kariuki, Peter Elyanu, Mosoka Fallah, Carolyne Nasimiyu, Bronwyn Gunn, Elizabeth Mgamb, Patrick Okumu Abok, Andrew Niwagaba Bakainaga, Moses L. Joloba, Bruce Kirenga, Kasonde Mwinga, Diana Atwiine, Jane Ruth Aceng
Journal: Nature Medicine (2025)
Multiple-omics Analysis Reveals Dedifferentiation-Immunosuppression Loop Formed by Malignant Cell and Macrophage in Intrahepatic cholangiocarcinoma
Authors: Jian Ruan, Qiong Li, Yuzhi Jin, Jie Yin, Chanqi Ye, Fei Cheng, Shuaishuai Xu, Ruyin Chen, Chuan Liu, Xiaoxiang Rong, Ming Jiang, Wenguang Fu, Dayong Zheng, Jinzhang Chen, Xuanwen Bao, Houhong Wang, Jianpeng Sheng, Peng Zhao
Journal: Molecular Therapy (2025)
Phylogeography Analysis Reveals Rabies Epidemiology, Evolution, and Transmission in the Philippines
Authors: Liang Zhang, Jeffrey Cruz, Yao Tian, Yuyang Wang, Jianfeng Jiang, Riva Marie Gonzales, Rachel R Azul, Rainelda C Dela Peña, Sheng Sun, Yan Liu, Tao Jiang, Liqun Fang, Changchun Tu, Wenjie Gong, Ye Feng
Journal: Molecular Biology and Evolution (2025)

Abstract Rabies, caused by rabies virus, is a severe public health problem in the Philippines, where animal rabies epidemiology had been extensively investigated, but little is known about the national epidemiologic situations since 2010. Here, we report a 12-year nationwide animal rabies surveillance with systematic phylogenetic analysis, in which 353 whole genomes of rabies viruses collected from animal rabies cases between 2018 and 2022 were obtained. The phylogenetic and spatial–temporal evolutionary analyses showed that rabies viruses in the Philippines were exclusively classified into the SEA4 subclade within the Asian clade, but forming three major geographically specific lineages. Intra-island spread predominates the rabies transmission in three major island regions, while the inter-island transmission, between major island regions, is very limited, likely due to ocean barriers. Overall, our findings have provided the most comprehensive dataset on the infected animal species, geographic distribution, transmission dynamics, genetic diversity of rabies viruses, and transmission risk factors, thus established a basis to support WOAH-endorsed national control program for dog-mediated rabies in the Philippines.
Immune cells and arrhythmias
Authors: Joshua A Keefe, Jian Wang, Jiangping Song, Li Ni, Xander Wehrens
Journal: Cardiovascular Research (2025)

Abstract Cardiac arrhythmias are a significant cause of morbidity and mortality worldwide. Emerging evidence has demonstrated that resident and infiltrating cardiac immune cells play direct, mechanistic roles in arrhythmia onset and progression. In this review, we provide a comprehensive summary and expert commentary on the role of each immune cell subtype in the pathogenesis of atrial and ventricular arrhythmias.
VP1-2025: Datopotamab deruxtecan (Dato-DXd) vs chemotherapy (CT) in previously-treated inoperable or metastatic hormone receptor-positive, HER2-negative (HR+/HER2–) breast cancer (BC): Final overall survival (OS) from the phase III TROPION-Breast01 trial
Authors: B. Pistilli, K. Jhaveri, S-A. Im, S. Pernas Simon, M. De Laurentiis, S. Wang, N. Martinez, G. Santos Borges, D. Cescon, M. Hattori, Y-S. Lu, E. Hamilton, Q. Zhang, J. Tsurutani, K. Kalinsky, L. Xu, S. Khan, H.S. Rugo, B. Xu, A. Bardia
Journal: Annals of Oncology (2025)
From Prospective Evaluation to Practice: Model-Informed Dose Optimization in Oncology
Authors: Bram C. Agema, Birgit C. P. Koch, Ron H. J. Mathijssen, Stijn L. W. Koolen
Journal: Drugs (2025)

One dose does not fit all, especially in oncolytic drugs, where side effects and therapy failures highlight the need for personalized dosing approaches. In recent years, the quest to apply model-informed precision dosing to oncology drugs has gained significant momentum, reflecting its potential to revolutionize patient care by tailoring treatments to individual pharmacokinetic profiles. Despite this progress, model-informed precision dosing has not (yet) become widely integrated into routine clinical care. We aimed to explain model-informed precision dosing from a clinical viewpoint while addressing all prospective model-informed precision dosing implementation and validation studies in the field of oncology. We identified 16 different drugs for which prospective model-informed precision dosing validation/implementation has been performed. Although these studies are mostly focused on attaining adequate drug exposures and reducing inter-individual variability, improved clinical outcomes after performing model-informed precision dosing were shown for busulfan, and high-dose methotrexate. Toxicities were significantly reduced for busulfan and cyclophosphamide treatment. In contrast, for carboplatin, for which model-informed precision dosing has been used in the Calvert formula, no prospective validation on outcomes was deemed necessary as the therapeutic window had been extensively validated. Model-informed precision dosing has shown to be of added value in oncology and is expected to significantly change dosing regimens in the future.
Widespread and convergent evolution of cone monochromacy in galeomorph sharks
Authors: Nathan S Hart, Maria Pozo-Montoro, Olivia Seeger, Laura A Ryan, Louise Tosetto, Charlie Huveneers, Victor M Peddemors, Jane E Williamson, Troy F Gaston
Journal: Molecular Biology and Evolution (2025)

Abstract Colour vision is widespread in marine vertebrates but is notably lacking in whales, dolphins, seals, and apparently also sharks. All sharks studied to date possess only a single spectral class of cone and are thus potentially totally colour blind. The reason why sharks lack colour vision is unclear, but as the visual pigments of only a handful of this large and ecologically diverse taxon have been studied, more data are required to address this question. Here, we assembled the retinal transcriptomes of nine species from seven families and three orders within the superorder Galeomorphii to screen for visual opsin and phototransduction genes. We reveal that cone monochromacy is widespread in galeomorph sharks, but the type of cone opsin expressed varies, with lamniform and orectolobiform sharks expressing an LWS opsin, and carcharhiniform and heterodontiform sharks expressing an RH2 opsin. Cone monochromacy has evolved from a dichromatic ancestral state at least four times, implying strong selection pressure to prioritise achromatic over chromatic vision. While all species express the GRK1A and GRK7 isoforms of G protein-coupled receptor kinase, only sharks with the LWS cone opsin express the GRK1B isoform, which suggests that non-spectral functions of photoreception may have influenced, or result from, the opsin complement in the shark retina. Finally, we show that the shark RH1 opsin gene shows evidence of positive selection at sites known to influence pigment kinetics (i.e. metarhodopsin II stability) and that the rate of retinal release likely differs substantially between species in ways that reflect their physiology and ecology.
Uncovering mechanisms of thiazolidinediones on osteogenesis and adipogenesis using spatial fluxomics
Authors: Kristyna Brejchova, Michal Rahm, Andrea Benova, Veronika Domanska, Paul Reyes-Gutierez, Martina Dzubanova, Radka Trubacova, Michaela Vondrackova, Tomas Cajka, Michaela Tencerova, Milan Vrabel, Ondrej Kuda
Journal: Metabolism (2025)

Highlights•MSDC-0602K differentially affects BM-MSCs and AT-MSCs.•Bioorthogonal click chemistry allowed measurement of pyruvate pools.•Subcellular metabolic flux analysis revealed rewiring of pyruvate pathways.•Metabolic flux analysis of TG synthesis showed distinct adipogenic strategies.AbstractObjectiveInsulin-sensitizing drugs, despite their broad use against type 2 diabetes, can adversely affect bone health, and the mechanisms underlying these side effects remain largely unclear. Here, we investigated the different metabolic effects of a series of thiazolidinediones, including rosiglitazone, pioglitazone, and the second-generation compound MSDC-0602 K, on human mesenchymal stem cells (MSCs).MethodsWe developed 13C subcellular metabolomic tracer analysis measuring separate mitochondrial and cytosolic metabolite pools, lipidomic network-based isotopologue models, and bioorthogonal click chemistry, to demonstrate that MSDC-0602 K differentially affected bone marrow-derived MSCs (BM-MSCs) and adipose tissue-derived MSCs (AT-MSCs). In BM-MSCs, MSDC-0602 K promoted osteoblastic differentiation and suppressed adipogenesis. This effect was clearly distinct from that of the earlier drugs and that on AT-MSCs.ResultsFluxomic data reveal unexpected differences between this drug's effect on MSCs and provide mechanistic insight into the pharmacologic inhibition of mitochondrial pyruvate carrier 1 (MPC). Our study demonstrates that MSDC-0602 K retains the capacity to inhibit MPC, akin to rosiglitazone but unlike pioglitazone, enabling the utilization of alternative metabolic pathways. Notably, MSDC-0602 K exhibits a limited lipogenic potential compared to both rosiglitazone and pioglitazone, each of which employs a distinct lipogenic strategy.ConclusionsThese findings indicate that the new-generation drugs do not compromise bone structure, offering a safer alternative for treating insulin resistance. Moreover, these results highlight the ability of cell compartment-specific metabolite labeling by click reactions and tracer metabolomics analysis of complex lipids to discover molecular mechanisms within the intersection of carbohydrate and lipid metabolism.Graphical abstract
Tumor extracellular vesicle–derived PD-L1 promotes T cell senescence through lipid metabolism reprogramming
Authors: Feiya Ma, Xia Liu, Yuanqin Zhang, Yan Tao, Lei Zhao, Hazar Abusalamah, Cody Huffman, R. Alex Harbison, Sidharth V. Puram, Yuqi Wang, Guangyong Peng
Journal: Science Translational Medicine (2025)

The limited success of cancer immunotherapy has posed challenges in treating patients with cancer. However, promising strides could be made with a deeper understanding of the factors that cause T cell dysfunction within the tumor microenvironment and by developing effective strategies to counteract tumor-induced immune suppression. Here, we report that tumor-derived extracellular vesicles (tEVs) can induce senescence and suppression in T cells. Programmed death ligand 1 (PD-L1), a key component within tEVs, induced DNA damage and hyperactive lipid metabolism in both human and mouse T cells. This caused an elevated expression of lipid metabolic enzymes and an increase in cholesterol and lipid droplet formation, leading to cellular senescence. At a molecular level, PD-L1 derived from tEVs activated the cAMP-response element binding protein (CREB) and signal transducer and activator of transcription (STAT) signaling, which promoted lipid metabolism and facilitated senescence in human and mouse T cells. Inhibiting EV synthesis in tumors or blocking CREB signaling, cholesterol synthesis, and lipid droplet formation in effector T cells averted the tEV-mediated T cell senescence in vitro and in vivo in cell adoptive transfer and melanoma mouse models. The same treatments also bolstered the antitumor efficacy of adoptive transfer T cell therapy and anti–PD-L1 checkpoint immunotherapy in both human and mouse melanoma models. These studies identified mechanistic links between tumor-mediated immune suppression and potential immunotherapy resistance, and they provide new strategies for cancer immunotherapy.
Intestinal epithelium–derived IL-34 reprograms macrophages to mitigate gastrointestinal tract graft-versus-host disease
Authors: Aditya Rayasam, Alison Moe, Matthew Kudek, Ravi K. Shah, Cheng-Yin Yuan, James M. Miller, Mary Rau, Mollie Patton, Karolyn Wanat, Marco Colonna, Anthony E. Zamora, William R. Drobyski
Journal: Science Translational Medicine (2025)

Gastrointestinal (GI) tract graft-versus-host disease (GVHD) is a major complication after allogeneic hematopoietic stem cell transplantation and is attributable to dysregulation that occurs between the effector and regulatory arms of the immune system. Whereas regulatory T cells have a primary role in counterbalancing GVHD-induced inflammation, identifying and harnessing other pathways that promote immune tolerance remain major goals in this disease. Herein, we identified interleukin-34 (IL-34) as an intestinal epithelium–derived cytokine that was able to mitigate the severity of GVHD within the GI tract. Specifically, we observed that the absence of recipient IL-34 production exacerbated GVHD lethality, promoted intestinal epithelial cell death, and compromised barrier integrity. Mechanistically, the absence of host IL-34 skewed donor macrophages toward a proinflammatory phenotype and augmented the accumulation of pathogenic CD4 + granulocyte-macrophage colony-stimulating factor (GM-CSF) + T cells within the colon. Conversely, the administration of recombinant IL-34 substantially reduced GVHD mortality and inflammation, which was dependent on the expression of apolipoprotein E in donor macrophages. Complementary genetic and imaging approaches in mice demonstrated that intestinal epithelial cells were the relevant source of IL-34. These results were supported by colonic biopsies from patients with GVHD, which displayed IL-34 expression in intestinal epithelial cells and apolipoprotein E in lamina propria macrophages, validating similar cellular localization in humans. These studies indicate that IL-34 acts as a tissue-intrinsic cytokine that regulates GVHD severity in the GI tract and could serve as a potential therapeutic target for amelioration of this disease.