tbuckley/cabot-search huggingface dataset:
Low-grade systemic inflammation is associated with risk of psoriasis in a general population study of more than 100,000 individuals
Authors: Charlotte Näslund-Koch, Amanda Kvist-Hansen, Stig E Bojesen, Lone Skov, Camilla J Kobylecki, Signe Vedel-Krogh
Journal: British Journal of Dermatology (2025)

Abstract Background Biomarkers of low-grade systemic inflammation have been reported to be higher in patients with psoriasis than in healthy controls. However, it is unknown whether this low-grade systemic inflammation contributes to the development of psoriasis or is merely a consequence. Objectives To investigate if low-grade systemic inflammation, measured as systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), or C-reactive protein (CRP), is an independent risk factor for psoriasis. Methods We used data from the Copenhagen General Population Study, a prospective cohort study of the Danish general population where individuals aged 20-100 were enrolled between 2003 and 2015. Upon enrolment in the study, all individuals underwent a physical examination, completed an extensive self-reported questionnaire regarding lifestyle, and provided blood samples, from which SII, NLR, and CRP were measured. Psoriasis was identified using ICD codes by individual-linkage to the Danish National Patient Registry. Associations between SII, NLR, and CRP and psoriasis were estimated using hazard ratios from Cox proportional hazard regression models. Analyses were adjusted for potential confounders including sex, age, smoking, alcohol consumption, physical activity, educational level, hypertension, dyslipidaemia, and obesity. Results We included 105,418 individuals with a median age of 58 years of whom 55% were women. The risk of receiving a diagnose of psoriasis increased with increasing levels of SII, NLR, and CRP. In individuals with high levels (&amp;gt;90 percentile) of SII, NLR, and CRP, the multivariable adjusted hazard ratios were 1.78 (95% confidence interval 1.41-2.24), 1.56 (1.22-1.99), and 2.83 (2.27-3.51), respectively, compared with individuals with low levels. Results were similar but slightly attenuated when we used topical calcipotriol (alone or in combination with corticosteroids) for mild psoriasis. Conclusions We found that low-grade systemic inflammation, as measured by SII, NLR, and CRP, was an independent risk factor for psoriasis, especially moderate-to-severe disease. These findings support the hypothesis that low-grade systemic inflammation may contribute to the pathogenesis of psoriasis rather than simply being a consequence of the disease.
Secretome Derived From Mesenchymal Stem Cells Cultured as Monolayer Show Enhanced Bone Regeneration Compared to Secretome From 3D Spheroid – Clues From the Proteome
Authors: Shalini Raik, Bhavneet Kaur, Saroj Kumar, Vidya Rattan, Navin Kumar, Shalmoli Bhattacharyya
Journal: Advanced Healthcare Materials (2025)

Abstract Repair and reconstruction of critical‐sized bone defects present a significant challenge due to poor clinical outcomes of conventional bone repair strategies, such as autologous and allogenic bone grafts. The present study underscores the potential of human dental pulp stem cell‐derived trophic factors to promote bone repair and regeneration, thus evading the risks associated with cell‐based therapy. This study utilizes pre‐osteoblast cells to evaluate the osteogenic potential of 2 Dimensional (2D) and 3 Dimensional (3D) secretome from monolayer and spheroid cultures of dental pulp stem cells (DPSCs), respectively. In‐vitro results on pre‐osteoblast cells (MC3T3‐EI) treated with 2D and 3D secretome reveal lower mineralization and mRNA expression of osteogenic specific genes in 3D secretome in comparison to 2D secretome. Furthermore, 2D secretome shows better bone regeneration ability in rat models of calvarial bone defect compared to the 3D secretome. The proteomic profiles of 2D and 3D secretomes are also in concordance with these results and reveal key molecules governing bone regeneration potential. This data highlights the influence of culture conditions on the secretory pattern of mesenchymal stem cells and provides valuable insights for the development of a more effective secretome‐based cell‐free alternative for novel bone repair and regeneration.
Hiding in plain sight: A new lymphoid organ discovered in zebrafish
Authors: Mohamed N. Bakr, David M. Langenau
Journal: The Journal of Experimental Medicine (2025)

A small, unassuming, fleshy lobe at the base of the pectoral fin of fish has long been overlooked by scientists. In this issue of JEM, Castranova et al. (https://doi.org/10.1084/jem.20241435) describe this structure as a new secondary lymphoid organ. Translucent and externally located, the axillary lymphoid organ (ALO) shares striking structural similarities with mammalian secondary lymphoid organs. Due to its position and optical accessibility, the zebrafish ALO permitted noninvasive, high-resolution imaging of immune cell dynamics in live animals. These studies revealed likely interactions between T, B, and macrophage cells, arguing that the ALO may function in adaptive immune cell activation and provide a nexus for immune cell trafficking and communication.
Evolution of Critical Care Cardiology: An Update on Structure, Care Delivery, Training, and Research Paradigms: A Scientific Statement From the American Heart Association
Authors: Shashank S. Sinha, Bram J. Geller, Jason N. Katz, Cynthia Arslanian-Engoren, Christopher F. Barnett, Erin A. Bohula, Abdulla A. Damluji, Venu Menon, Robert O. Roswell, Saraschandra Vallabhajosyula, Amanda R. Vest, Sean van Diepen, David A. Morrow
Journal: Journal of the American College of Cardiology (2025)
Antibiotic-induced gut microbiome perturbation alters the immune responses to the rabies vaccine
Authors: Yupeng Feng, Sanne E de Jong, Ana Paula B N Oliveira, Hady Samaha, Fan Yang, Mengyun Hu, Yanli Wang, Nour Beydoun, Xia Xie, Haibo Zhang, Dmitri Kazmin, Zhuoqing Fang, Jun Zou, Andrew T Gewirtz, Scott D Boyd, Thomas Hagan, Nadine Rouphael, Bali Pulendran
Journal: Cell Host & Microbe (2025)
Mammographic classification of interval breast cancers and artificial intelligence performance
Authors: Tiffany T Yu, Anne C Hoyt, Melissa M Joines, Cheryce P Fischer, Nazanin Yaghmai, James S Chalfant, Lucy Chow, Shabnam Mortazavi, Christopher D Sears, James Sayre, Joann G Elmore, William Hsu, Hannah S Milch
Journal: JNCI Journal of the National Cancer Institute (2025)

Abstract Background European studies suggest artificial intelligence (AI) can reduce interval breast cancers (IBCs). However, research on IBC classification and AI’s effectiveness in the U.S., particularly using digital breast tomosynthesis (DBT) and annual screening, is limited. We aimed to mammographically classify IBCs and assess AI performance using a 12-month screening interval. Methods From digital mammography (DM) and DBT screening mammograms acquired 2010-2019 at a U.S. tertiary care academic center, we identified IBCs diagnosed &amp;lt;12 months after a negative mammogram. At least three breast radiologists retrospectively classified IBCs as missed-reading error, minimal signs-actionable, minimal signs-non-actionable, true interval, occult, or missed-technical error. A deep-learning AI tool assigned risk scores (1-10) to the negative index screening mammograms, with scores ≥8 considered “flagged.” Statistical analysis evaluated associations among IBC types and AI exam scores, AI markings, and patient/tumor characteristics. Results From 184,935 screening mammograms (65% DM, 35% DBT), we identified 148 IBCs in 148 women (mean age, 61±12 years). Of these, 26% were minimal signs-actionable; 24% occult; 22% minimal signs-non-actionable; 17% missed-reading error; 6% true interval; and 5% missed-technical error (p&amp;lt;.001). AI scored 131 mammograms (17 errors excluded). AI most frequently flagged exams with missed-reading errors (90%), minimal signs-actionable (89%) and minimal signs-non-actionable (72%) (p=.02). AI localized mammographically-visible types more accurately (35-68%) than non-visible types (0-50%, p=.02). Conclusion AI more frequently flagged and accurately localized IBC types that were mammographically visible at screening (missed or minimal signs), as compared to true interval or occult cancers.
Characterizing Bruch’s Membrane: State-of-the-Art Imaging, Computational Segmentation, and Biologic Models in Retinal Disease and Health
Authors: Joshua Ong, Amrish Selvam, Matthew Driban, Arman Zarnegar, Susana Isabel Morgado Mendes Antunes Da Silva, Jincy Joy, Ethan A Rossi, Jonathan Pieter Vande Geest, José-Alain Sahel, Jay Chhablani
Journal: Progress in Retinal and Eye Research (2025)
Short‐Chain Fatty Acids Modulate Anti‐ROR1 CAR T‐Cell Function and Exhaustion in an Intestinal Adenocarcinoma‐on‐Chip Model
Authors: Valentin D. Wegner, Adrian Feile, Miriam Alb, Michael Hudecek, Philip Hewitt, Alexander S. Mosig
Journal: Advanced Healthcare Materials (2025)

Abstract Chimeric antigen receptor (CAR) T‐cell therapy represents a promising approach for cancer treatment, with receptor tyrosine kinase‐like orphan receptor 1 (ROR1) emerging as a novel target in malignancies. This study investigates how short‐chain fatty acids (SCFAs), key microbiota‐derived metabolites, modulate anti‐ROR1 CAR T‐cell efficacy using a physiologically relevant intestinal adenocarcinoma‐on‐chip model that replicates the human intestinal microenvironment. The findings demonstrate that propionate and butyrate inhibit anti‐ROR1 CAR T‐cell function by reducing infiltration, cytotoxicity, and cytokine release while preserving junctional integrity within the tumor model. Mechanistically, these SCFAs inhibit histone deacetylase activity and promote a phenotype switch toward regulatory T‐cells, as indicated by increased expression of FoxP3 and RORγt. Additionally, propionate and butyrate upregulate PD‐1 and TIM‐3, markers of T‐cell exhaustion and immune tolerance, and induce a dose‐ and time‐dependent reduction in proinflammatory cytokines. In contrast, acetate and pentanoate promote a proinflammatory T helper 17 phenotype. These results highlight the immunomodulatory effects of SCFAs on CAR T‐cell function, emphasizing the need to consider microbiota‐derived metabolites in CAR T‐cell therapies.
Sport-specific concomitant injuries, return-to-sport rates and second anterior cruciate ligament (ACL) injuries in adolescents with ACL reconstruction
Authors: Philipp W Winkler, Baldur Thorolfsson, Ramana Piussi, Thorkell Snaebjörnsson, Rebecca Hamrin Senorski, Jon Karlsson, Kristian Samuelsson, Eric Hamrin Senorski
Journal: British Journal of Sports Medicine (2025)

Objective To evaluate differences in sport-specific concomitant injuries, return-to-sport (RTS), second ACL injuries and Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales after adolescent ACL reconstruction (ACLR) across popular sports. Methods This prospective cohort study included patients aged 10–18 years at ACLR. Demographic and injury-related data and KOOS subscales before ACLR and at the 1 and 2 years follow-ups were obtained. A survey to assess sport-specific outcomes and RTS was sent to eligible patients. Group comparisons were performed between the most popular sports and between females and males. Results Overall, 1392 patients with a mean age of 16.4±1.4 years at ACLR were included. The mean time between ACLR and survey completion was 9.7±4.2 years. The most prevalent type of sport was soccer, followed by handball, floor hockey/field hockey, basketball and other sports. Concomitant injuries (71%) and second ACL injuries (30%; 20% ipsilateral, 13% contralateral) were common across all sports. No significant differences were found in ipsilateral second ACL injuries across sexes and sports. 24% of patients competed at an elite level sport (highest national level of junior sport or higher) for some period after ACLR. 8% of patients did not RTS at all, with females significantly more often without RTS than males (9% vs 4%, p=0.041). Significant improvements were observed in KOOS subscales from baseline to the 1 and 2 years follow-ups for all sports. Conclusion Concomitant injuries are frequently observed after ACL injury in adolescents, with nearly one-third suffering a second ACL injury. While significant improvements in KOOS subscales and return to high-level sports can be expected, better injury prevention is needed after ACLR.
CCR8 <sup>+</sup> decidual regulatory T cells maintain maternal-fetal immune tolerance during early pregnancy
Authors: Zhuqing Li, Pinxin Si, Tingting Meng, Xiaoran Zhao, Chendi Zhu, Dunfang Zhang, Shutong Meng, Nianyu Li, Ran Liu, Tianxiang Ni, Junhao Yan, Hongchang Li, Ning Zhao, Chao Zhong, Yingying Qin, WanJun Chen, Zi-Jiang Chen, Xue Jiao
Journal: Science Immunology (2025)

Regulatory T (T reg ) cells play a vital role in maintaining maternal immune tolerance to the semiallogeneic fetus during pregnancy. T reg cell population heterogeneity and tissue-specific functions in the human decidua remain largely unknown. Here, using single-cell transcriptomic and T cell receptor sequencing of human CD4 + T cells from first-trimester deciduae and matched peripheral blood of pregnant women, we identified a highly activated, immunosuppressive CCR8 + T reg cell subset specifically enriched in the decidua (dT reg cells). CCR8 + dT reg cells were decreased in patients with recurrent pregnancy loss (RPL) and an abortion-prone mouse model. Depletion of CCR8 + dT reg cells increased susceptibility to fetal loss, with altered decidual immune profiles. Adoptive transfer of CCR8 + T reg cells rescued fetal loss in abortion-prone mice. The CCR8 ligand CCL1 was mainly produced by decidual CD49a + natural killer cells and was significantly decreased in patients with RPL. Our data demonstrate that CCR8 + dT reg cells are required to maintain maternal-fetal tolerance and highlight potential avenues for RPL therapies.
Endothelial-driven TGFβ signaling supports lung interstitial macrophage development from monocytes
Authors: Wen Peng, Domien Vanneste, David Bejarano, Joan Abinet, Margot Meunier, Coraline Radermecker, Fabienne Perin, Didier Cataldo, Fabrice Bureau, Andreas Schlitzer, Qiang Bai, Thomas Marichal
Journal: Science Immunology (2025)

Lung interstitial macrophages (IMs) are monocyte-derived parenchymal macrophages whose tissue-supportive functions remain unclear. Despite progress in understanding lung IM diversity and transcriptional regulation, the signals driving their development from monocytes and their functional specification remain unknown. Here, we found that lung endothelial cell–derived Tgfβ1 triggered a core Tgfβ receptor–dependent IM signature in mouse bone marrow–derived monocytes. Myeloid-specific impairment of Tgfβ receptor signaling severely disrupted monocyte-to-IM development, leading to the accumulation of perivascular immature monocytes, reduced IM numbers, and a loss of IM-intrinsic identity, a phenomenon similarly observed in the absence of endothelial-specific Tgfβ1. Mice lacking the Tgfβ receptor in monocytes and IMs exhibited altered monocyte and IM niche occupancy and hallmarks of aging including impaired immunoregulation, hyperinflation, and fibrosis. Our work identifies a Tgfβ signaling–dependent endothelial-IM axis that shapes IM development and sustains lung integrity, providing foundations for IM-targeted interventions in aging and chronic inflammation.
A Systematic Review of Novel Intravesical Approaches for the Treatment of Patients with Non–muscle-invasive Bladder Cancer
Authors: Saum Ghodoussipour, Trinity Bivalacqua, Richard T Bryan, Roger Li, M Carmen Mir, Joan Palou, Sarah P Psutka, Debasish Sundi, Mark D Tyson, Brant A Inman
Journal: European Urology (2025)

Intravesical therapy is central to managing non-muscle-invasive bladder cancer (NMIBC); yet, recurrence and progression remain common, underscoring the need for new treatments. This systematic review evaluates clinical trials of novel intravesical therapies for all risk categories of NMIBC. A comprehensive literature search was conducted to identify the clinical trials assessing the effectiveness, safety, and tolerability of intravesical therapies for NMIBC. The search focused on studies published from 2020 to 2024, including trials on bacillus Calmette-Guérin (BCG)-unresponsive/refractory disease as well as on BCG-naïve and intermediate-risk patients. Mechanisms of action and drug delivery methods were summarized. No statistical syntheses were performed due to limited comparative data. Out of 2998 studies identified, 36 reported on efficacy and safety, and six provided patient-reported outcomes (PROs). Intravesical therapies included BCG-based therapies, chemotherapy combinations, chemical-drug conjugates, thermogels, hyperthermic chemotherapy, osmotic pumps, and gene therapy. Initial response rates ranged from 42% to 85% for BCG-unresponsive/refractory patients and from 65% to 100% for treatment-naïve patients. The 12-mo recurrence-free survival rates ranged from 22% to 83% and 39% to 92%, respectively. Progression and severe toxicity (grade ≥3) were rare (0-17% and 0-20%, respectively). PROs were stable. The limitations included early-phase studies, heterogeneous outcome assessments, and a need for research on long-term durability, comparative effectiveness, quality of life, and cost. This systematic review highlights the promising efficacy and tolerability of novel intravesical therapies for NMIBC. However, further research is needed to refine treatment strategies and assess long-term outcomes, quality of life, and economic factors. Future studies should include multiarm, multistage designs with a focus on patient-centered outcomes.
Renal Neoplasia in Birt-Hogg-Dubé Syndrome: Integrated Histopathologic, Bulk, and Single-cell Transcriptomic Analysis
Authors: Sounak Gupta, Surendra Dasari, Rachel R Warren, Wei Shen, Rhianna M Urban, Melissa L Stanton, Christine M Lohse, Megan A Holdren, Megan F Hoenig, Beth A Pitel, Stephanie A Smoley, Stefan W Nelson, Nate R Torell, Autumn C Moon, Leah M Nelson, Joaquin J Garcia, Peter C Lucas, Kevin C Halling, Benjamin R Kipp, Stephen A Boorjian, Stijn P De Langhe, Lori A Erickson, Vidit Sharma, John C Cheville, Bradley C Leibovich
Journal: European Urology (2025)
Impact of climate change on aerobiology, rhinitis, and allergen immunotherapy: Work Group Report from the Aerobiology, Rhinitis, Rhinosinusitis &amp; Ocular Allergy, and Immunotherapy, Allergen Standardization &amp; Allergy Diagnostics Committees of the American Academy of Allergy, Asthma &amp; Immunology
Authors: Tolly E G Epstein, Andrew C Rorie, German D Ramon, Anjeni Keswani, Jonathan Bernstein, Rosa Codina, Christopher Codispoti, Timothy Craig, Mark Dykewicz, Denisa Ferastraoaru, Daniel Katz, Jean Kim, Désirée Larenas-Linnemann, Anil Nanda, Anh Nguyen, Mahesh Padukudru Anand, Amber Patterson, Punita Ponda, Elina Toskala, Anita N Wasan
Journal: Journal of Allergy and Clinical Immunology (2025)
Toxicity Within 6 Months of Heterogeneous Fluorodeoxyglucose-Guided Radiotherapy Dose Escalation for Locally Advanced Non–Small Cell Lung Cancer in the Scandinavian Randomized Phase III NARLAL2 Trial
Authors: Tine Schytte, Marianne M. Knap, Charlotte Kristiansen, Ane L. Appelt, Azza Khalil, Cecile Peucelle, Christina M. Lutz, Ditte S. Møller, Erlend P.S. Sande, Filipa Sundby, Gitte Persson, Hjørdis Schmidt, Lotte Holm Land, Lotte Rogg, Mette Pøhl, Mikkel D. Lund, Morten Nielsen, Nina Levin, Olfred Hansen, Rune S. Thing, Svetlana Borissova, Tarje Halvorsen, Tine B. Nielsen, Torben S. Hansen, Vilde Drageset Haakensen, Wiviann Ottosson, Carsten Brink, Lone Hoffmann
Journal: Journal of Clinical Oncology (2025)

PURPOSE Radiation dose escalation for locally advanced non–small cell lung cancer (LA-NSCLC) has been challenged by toxicity concerns. The Scandinavian phase III multicenter dose-escalation trial NARLAL2 (ClinicalTrials.gov identifier: NCT02354274 ) used a novel approach to dose escalation: heterogeneous escalation driven by the fluorodeoxyglucose positron emission tomography–avid region, with strict normal tissue dose constraints. We report early toxicity within 6 months of random assignment. MATERIALS AND METHODS Patients were recruited from seven institutions in Scandinavia. Eligibility criteria included performance status 0-1, NSCLC stage IIB-IIIB, and feasibility of delivering 66 Gy/33 fraction treatment plan. Patients were randomly assigned between standard (66 Gy) and heterogeneously dose-escalated radiotherapy. Two treatment plans were made for each patient before random assignment with matched mean lung dose and V 20Gy , and strict dose constraints for all normal tissues. Toxicity was evaluated weekly during radiotherapy, and every 3 months after random assignment. Concurrent chemotherapy was cisplatin/carboplatin and Navelbine. RESULTS Between January 2015 and March 2023, 350 patients were randomly assigned. The as-treated analysis included 178 patients in the standard and 172 in dose-escalated (mean tumor dose 88 Gy) arms. Median gross tumor and planning target volumes were, respectively, 54 cm 3 and 321 cm 3 (standard arm) and 61 cm 3 and 339 cm 3 (escalated arm). No difference in early toxicity between the two arms was observed. Grade 2 esophagitis during radiotherapy was 28.1% and 25.6%, grade 3 esophagitis 7.3% and 4.1%, grade 2 pneumonitis 15.7% and 20.3%, and grade 3 pneumonitis 3.9% and 5.8% in standard and escalated arms, respectively. For both arms, the maximum grade of early toxicity aggregated over all toxicities was 35% and 1% for grades ≥3 and 5, respectively. Four patients died from potential treatment-related toxicity. CONCLUSION Heterogeneous dose escalation did not increase early toxicity despite delivery of 88 Gy mean dose to the primary tumor, demonstrating this as an attractive strategy for LA-NSCLC radiotherapy dose escalation.
From Organoids to Assembloids: Experimental Approaches to Study Human Neuropsychiatric Disorders
Authors: Rebecca J. Levy, Sergiu P. Paşca
Journal: Annual Review of Neuroscience (2025)

To understand the pathophysiology and develop effective therapeutics for brain disorders, some of which may involve uniquely human features of the nervous system, scalable human models of neural cell diversity and circuit formation are essential. The discovery of cell reprogramming and the development of approaches for generating stem cell–derived neurons and glial cells in 3D preparations known as neural organoids and assembloids, both in vitro and following transplantation in vivo, provide new opportunities to tackle these challenges. Here, we outline strengths and limitations of currently available human experimental models as applied to neurological and psychiatric disorders for both environmental and genetic risk factors, and we discuss how these new tools hold promise for accelerating the development of therapeutics.
Progress in Understanding the Regulation of Glucose and Fructose Metabolism
Authors: Meng Zhao, Jameel Lone, Saranya Reghupaty, Karen Yasmin Linde-Garelli, Katrin J. Svensson
Journal: Annual Review of Nutrition (2025)

Hexoses, including glucose, fructose, and galactose, are six-carbon monosaccharides that play fundamental roles in mammalian metabolism, with glucose serving as the primary energy source and fructose and galactose metabolized through pathways converging with glucose metabolism. While glucose metabolism has been extensively studied over the past hundred years, the mechanisms of fructose metabolism and uptake, the transporters involved, and its roles in physiology and disease are far less explored. Recent data also suggest that excessive fructose intake can have detrimental effects on metabolic organs, including the liver. Emerging studies have uncovered novel regulatory mechanisms in glucose and fructose metabolism, including the role of posttranslational modifications of transporters and enzymes, and the discovery of regulators of transporters. Here, we highlight new findings on the regulation of glucose and fructose transporters and integrate recent molecular and clinical insights into how glucose and fructose contribute to metabolic diseases.