tbuckley/cabot-search huggingface dataset:
Truncated complement factor H Y402 gene therapy rescues C3 glomerulonephritis
Authors: Lindsey A Chew, Daniel Grigsby, C Garren Hester, Joshua Amason, W Kyle McPherson, Edward J Flynn, Meike Visel, Christopher R Starr, John G Flannery, Tylor R Lewis, Catherine Bowes Rickman
Journal: Molecular Therapy (2025)

There are no effective therapies for patients with dry age-related macular degeneration (AMD) or C3 glomerulonephritis (C3G). Unfortunately, past efforts to treat C3G using exogenous human CFH found limited success due to immune rejection of a foreign protein response. AMD research has also faced myriad challenges, including the absence of an ideal therapeutic target and difficulties with treatment delivery in certain preclinical models. In pursuit of an AMD therapy to overcome these obstacles, we ultimately capitalized on parallels in complement dysregulation between AMD and C3G. Here, we investigate the potential for complement factor H (CFH) supplementation as a strategy to rescue C3G. Our findings demonstrate restored inhibition of complement's alternative pathway and long-term reversal of disease without immune rejection using adeno-associated virus (AAV)-mediated delivery of truncated CFH (tCFH) in a Cfh-/- mouse model of C3G. We tested three different tCFH vectors and found significant differences in their relative transduction efficiency and therapeutic efficacy. These discoveries motivate the development of AAV-mediated tCFH replacement therapy for patients with C3G, while simultaneously demonstrating proof of concept for AAV-mediated tCFH gene augmentation therapy for patients with AMD.
Characterization of Patients with Symptoms of Gastroparesis Having Frequent Emergency Department Visits and Hospitalizations
Authors: Henry P. Parkman, Yuchen Xin, Laura A. Wilson, Helen Burton-Murray, Richard W. McCallum, Irene Sarosiek, Baha Moshiree, Kenneth L. Koch, Robert S. Bulat, Madhusudan Grover, Gianrico Farrugia, Bruno P. Chumpitazi, Robert J. Shulman, Laura A. Miriel, James Tonascia, Pankaj J. Pasricha, Braden Kuo, Thomas L. Abell
Journal: Clinical Gastroenterology and Hepatology (2025)
A novel tolerogenic antigen-specific vaccine induces VISTA-enriched regulatory T cells and protects against arthritis in DRB1*04:01 mice
Authors: Laura Romero-Castillo, Rajan Kumar Pandey, Bingze Xu, Christian M Beusch, Ana Oliveira-Coelho, Kejsi Zeqiraj, Carolin Svensson, Zhongwei Xu, Huqiao Luo, Outi Sareila, Pierre Sabatier, Changrong Ge, Lei Cheng, Vilma Urbonaviciute, Alexander Krämer, Cecilia Lindgren, Sabrina Haag, Johan Viljanen, Roman A Zubarev, Jan Kihlberg, Anna Linusson, Harald Burkhardt, Rikard Holmdahl
Journal: Molecular Therapy (2025)

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation, cartilage damage and bone erosion. Despite improvements with the introduction of biological disease-modifying anti-rheumatic drugs (DMARDs), RA remains an incurable life-lasting disease. Advancements in peptide-based vaccination may open new avenues for treating autoimmune diseases, including RA, by inducing immune tolerance while maintaining normal immune function. Previously we have already demonstrated the efficacy of a potent vaccine against RA, consisting of the mouse major histocompatibility complex class II (Aq) protein bound to the immunodominant type II collagen peptide COL2259-273, which needed to be galactosylated at position 264. To translate the vaccine to humans and to further enhance vaccine efficacy, we modified the glycine residue at position 265 and conjugated it with the human DRB1*04:01 molecule. Remarkably, this modified vaccine (named DR4-AL179) provided robust effectiveness in suppressing arthritis in DRB1*04:01-expressing mice without the need for galactosylation at position 264. DR4-AL179 vaccination induces tolerance involving multiple immunoregulatory pathways, including the activation of VISTA-positive nonconventional regulatory T cells, which contribute to a potent suppressive response preventing arthritis development in mice. This modified RA vaccine offers a novel therapeutic potential for human autoimmune diseases.
ErbB2/HER2-targeted CAR-NK cells eliminate breast cancer cells in an organoid model that recapitulates tumor progression
Authors: Jasmin Röder, Tijna Alekseeva, Anne Kiefer, Ines Kühnel, Maren Prüfer, Congcong Zhang, Malena Bodden, Sebastian Rosigkeit, Anja Waldmann, Torsten Tonn, Ernesto Bockamp, Stefan Stein, Winfried S Wels
Journal: Molecular Therapy (2025)
Recurrent Solitary Pleural Metastasis Originating From Neuroblastoma as Demonstrated by 123I-MIBG Scan
Authors: Xin Wen, Xia Lu, Yanfeng Xu, Jun Liu, Jigang Yang
Journal: Clinical Nuclear Medicine (2025)

An 8-year-old boy with high-risk neuroblastoma underwent routine follow-up 123I-MIBG scan, which revealed abnormal 123I-MIBG accumulation in right pleura, suggestive of potential metastasis. Histopathologic examination of the biopsy specimen confirmed the presence of pleural metastasis. The patient subsequently received four cycles of chemotherapy. A follow-up 123I-MIBG scan after chemotherapy demonstrated no abnormal MIBG uptake, indicating remission of the pleural metastasis. However, 6 months later, a subsequent 123I-MIBG scan revealed recurrent abnormal MIBG uptake in the right pleura at the same location as the initial recurrence. Surgical pathology confirmed the diagnosis of recurrent pleural metastasis.
Incidental Uptake of Spermatocele on I-131 Whole-body Scan
Authors: Mertcan Güven, Furkan Avci, Aziz Murat Argon
Journal: Clinical Nuclear Medicine (2025)

A 31-year-old man received radioiodine (I-131) treatment after bilateral total thyroidectomy and central lymph node dissection. After the treatment, I-131 whole-body scintigraphy showed focal activity in the right testicular region. SPECT/CT images showed focal activity localised in the right epididymis, and US images showed a hypoechoic lesion consistent with spermatocele.
Novel humanized CD19-CAR-T (Now talicabtagene autoleucel, Tali-cel™) cells in relapsed/ refractory pediatric B-acute lymphoblastic leukemia- an open-label single-arm phase-I/Ib study
Authors: Gaurav Narula, Swaminathan Keerthivasagam, Hasmukh Jain, Sachin Punatar, Akanksha Chichra, Chetan Dhamne, Prashant Tembhare, Papagudi Ganesan Subramanian, Nikhil Patkar, Minal Poojary, Anant Gokarn, Sumeet Mirgh, Nishant Jindal, Albeena Nisar, Deepali Pandit, Khushali Pandit, Alka Dwivedi, Atharva Karulkar, Ankesh Kumar Jaiswal, Aalia Khan, Shreshtha Shah, Afrin Rafiq, Moumita Basu, Juber Pendhari, Sweety Asija, Ambalika Chowdury, Ankit Banik, Nirmalya Roy Moulik, Shyam Srinivasan, Shilpushp Bhosle, Sumathi Hiregoudar, Shashank Ojha, Lingaraj Nayak, Jayshree Thorat, Bhausaheb Bagal, Manju Sengar, Navin Khattry, Shripad Banavali, Steven Highfill, Nirali N Shah, Rahul Purwar
Journal: Blood Cancer Journal (2025)
Radiomics in head and neck squamous cell carcinoma – a leap towards precision oncology
Authors: Pranjal Rai, Abhishek Mahajan
Journal: Journal for ImmunoTherapy of Cancer (2025)

Immunotherapy has revolutionized head and neck squamous cell carcinoma (HNSCC) treatment, with neoadjuvant chemoimmunotherapy showing promising pathological complete response rates (36–42%). Lin et al introduce a radiomics-clinical nomogram using MRI-derived intratumoral and peritumoral features to predict pCR, addressing a critical clinical gap. Their model, emphasizing the peritumoral region (within 3 mm), achieved high predictive accuracy area under curve (AUC) &gt;0.8. While the multicenter design enhances generalizability, standardizing imaging protocols remains a challenge. Integrating radiomics with the Neck Imaging Reporting and Data System could refine post-treatment assessment. This study advances precision oncology in HNSCC, offering a non-invasive tool for personalized treatment strategies. Future directions include artificial intelligence-driven radiomics and radiogenomics to enhance treatment response prediction and patient selection.
Gut microbiota derived indole-3-acetic acid ameliorates precancerous inflammatory intestinal milieu to inhibit tumorigenesis through IL-35
Authors: Juanjuan Wang, Yang Hao, Yazheng Yang, Yuan Zhang, Chen Xu, Rongcun Yang
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background Gut microbiota can significantly alter the risk or progression of cancer by maintaining gut immune system homeostasis. However, the exact mechanism by which the gut microbiota and its metabolites influence colorectal tumorigenesis is unclear. Methods The roles of tryptophan metabolite indole-3-acetic acid (IAA) in inflammation and tumor development were investigated in dextran sodium sulfate (DSS) and azoxymethane (AOM)-DSS mouse models with or without IAA supplementation and with or without Lactobacillus reuteri -produced IAA. Pregnane X receptor (PXR) knockout (KO) mice and aryl hydrocarbon receptor KO mice were used to explore the mechanism by which IAA regulates interleukin (IL)-35 expression. IL-35 + immune cells were stimulated in vitro and analyzed by flow cytometry. Additionally, metabolites were analyzed by liquid chromatography-mass spectrometry. Results We found that IAA, a metabolite of tryptophan produced in the gut by L. reuteri , can inhibit the development of colitis by inducing IL-35 expression in immunosuppressant cells. HuREG3α IECtg mice had high levels of intestinal microbiota-derived IAA, and these mice were resistant to AOM-DSS-induced cancer. Patients with colorectal cancer also had low peripheral blood levels of IAA. Further studies revealed that IAA-producing L. reuteri alleviated colitis symptoms and inhibited colon tumors by inducing macrophages, T cells, and B cells to produce IL-35. Finally, PXR KO completely abolished the effects of IAA on immune cells. Conclusion We demonstrate that gut microbiota-derived IAA can improve the precancerous colon inflammatory environment through IL-35, thereby inhibiting tumorigenesis, suggesting that IAA may be a preventive factor for colitis-related cancers.
Serum analytes as predictors of disease recurrence and the duration of invasive disease-free survival in patients with triple negative breast cancer enrolled in the OXEL trial treated with immunotherapy, chemotherapy, or chemoimmunotherapy
Authors: Nicole J Toney, Megan T Lynch, Filipa Lynce, Candace Mainor, Claudine Isaacs, Jeffrey Schlom, Renee N Donahue
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background The OXEL study ( NCT03487666 ) was a phase II trial of patients with triple negative breast cancer (TNBC) with residual disease following neoadjuvant chemotherapy, randomized to receive immunotherapy (anti-programmed cell death protein 1, nivolumab), chemotherapy (capecitabine), or chemoimmunotherapy. We previously reported on the primary endpoint of the OXEL trial, demonstrating that a peripheral immunoscore based on circulating immune cells reflecting immune activation was increased in patients treated with immunotherapy. However, compared with cell-based immune assays, sera assays are more cost-effective, less labor-intensive, and samples easier to obtain. Here, we report on differences in serum analytes between treatment arms and associations with clinical response. Methods Patients (n=38) were assayed for 97 serum analytes before and after 6 and 12 weeks of therapy. Serum analytes were assessed for changes with therapy, and as predictors of disease recurrence and the duration of invasive disease-free survival (iDFS) in both single analyte analyses and machine learning models. Results Levels of specific analytes at baseline and changes in levels at early time points on treatment preceding recurrence were associated with eventual development of disease recurrence and/or the duration of iDFS. These associations varied based on the therapy patients received. Immunotherapy led to enrichment in pro-inflammatory analytes following treatment, whereas chemotherapy resulted in overall decreases. Changes seen in patients receiving chemoimmunotherapy more closely resembled those observed in patients receiving immunotherapy alone as opposed to chemotherapy alone. Furthermore, logistic regression and Cox proportional hazard models, developed using machine learning methods, demonstrated that combinations of serum analytes were more predictive of disease recurrence and iDFS duration than analyses of single serum analytes. Notably, the multivariable models that predicted patient outcomes were highly specific to the class of treatment patients received. Conclusions In patients with TNBC with residual disease after neoadjuvant chemotherapy, treatment with immunotherapy alone or chemoimmunotherapy resulted in enhanced immune activation compared with chemotherapy alone as measured by changes in serum analyte levels. Distinct serum analytes, both at baseline and as changes after therapy, predicted clinical outcomes for patients receiving immunotherapy alone, chemotherapy alone, or chemoimmunotherapy. Trial registration number NCT03487666 .
CLN-619, a MICA/B monoclonal antibody that promotes innate immune cell-mediated antitumor activity
Authors: Kerry A Whalen, Catherine C Henry, Naveen K Mehta, Kavya Rakhra, Safak Yalcin, Kristan Meetze, Neil W Gibson, Patrick A Baeuerle, Jennifer S Michaelson
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background Major histocompatibility complex class I-related protein A and B (MICA/B) are ligands for the natural killer group 2 member D (NKG2D) receptor and are broadly expressed on tumor cells but minimally on normal tissues. When cytotoxic NKG2D-expressing immune cells engage MICA/B, the ligand-expressing cells are targeted for lysis. Cancer cells can evade NKG2D-mediated destruction by shedding MICA/B from their cell surface via proteases present in the tumor microenvironment. CLN-619 is a humanized IgG1 monoclonal antibody (mAb) which binds MICA/B and inhibits shedding resulting in accumulation of MICA/B on the tumor cell surface. CLN-619 may thereby have therapeutic effects in a broad range of malignancies by re-establishing the MICA/B-NKG2D axis to enable NKG2D-mediated, as well as Fc-gamma receptor-mediated, tumor cell lysis. Methods CLN-619 was characterized for binding epitope and affinity, effects on surface and soluble levels of MICA/B, and in vitro tumor cell killing. In mouse models, the mAb was tested for tumor growth inhibition. The contribution of the Fc-gamma (Fcγ) 1 domain to CLN-619 activity was also assessed. Results CLN-619 bound with high affinity to the alpha-3 domain of MICA/B without encumbering the interaction with NKG2D on natural killer cells. CLN-619 increased the level of cell surface expression of MICA/B and concomitantly decreased the levels of soluble MICA/B in cell culture assays. Treatment of cancer cell lines with CLN-619 induced antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis. CLN-619 resulted in potent inhibition of tumor growth in multiple xenograft models and increased survival of mice in a disseminated cancer model. Conclusions CLN-619 inhibited the shedding of MICA/B to effectively restore cytotoxic signaling pathways in immune cells. Potent antitumor activity of CLN-619 as a monotherapy was observed in several preclinical models. Activity of CLN-619 required a functional Fcγ1 domain, suggesting the requirement of simultaneous engagement of NKG2D and cluster of differentiation 16A (CD16A) on immune cells for optimal cytotoxicity. The preclinical data reported here support the assessment of CLN-619 in patients with cancer.
Advancing pancreatic cancer therapy by mesothelin-specific nanobody conjugation
Authors: Soyeon Yi, Kyunghee Noh, Hyeran Kim, Eunkyeong Jung, Suhyeon Kim, Jieun Lee, Kyeonghye Guk, Jinsol Choi, Eun-Kyung Lim, Seokho Kim, Hwangseo Park, Jung Hwa Lim, Cho-Rok Jung, Taejoon Kang, Juyeon Jung
Journal: Molecular Cancer (2025)

Pancreatic adenocarcinoma (PAAD) is highly challenging to treat due to its poor prognosis and limited effective treatment options. Liposomal nanotechnology has emerged as a promising drug delivery platform in oncology, but existing liposomal therapies face limitations such as systemic toxicity, insufficient tumor selectivity, and low target specificity. Mesothelin (MSLN), an antigen overexpressed in PAAD, has attracted attention as a potential target for precision therapy. Here, we present the development of an anti-MSLN nanobody (D3 Nb) with high binding affinity (KD = 2.2 nM) that can selectively bind to MSLN-positive cancer cells. Structural analysis revealed that hydrophobic and hydrogen bonds within the complementary determining region (CDR) of D3 Nb promote strong binding to MSLN, leading to significant inhibition of AKT/NF-κB signaling and downregulation of fibronectin 1 (FN1) and twist1, key drivers of PAAD oncogenicity. In vivo studies confirmed that D3 Nb alone inhibits tumor progression. Furthermore, selective delivery to MSLN-positive tumors in combination with gemcitabine-loaded liposomes (D3-LNP-GEM) significantly improved cytotoxicity and promoted tumor regression. These findings highlight the potential of the D3-LNP-GEM platform as a novel targeted therapy for MSLN-expressing malignancies, showing promising efficacy in preclinical models and paving the way for continued clinical evaluation.
Gut microbiota regulates hepatic ketogenesis and lipid accumulation in ketogenic diet-induced hyperketonemia by disrupting bile acid metabolism
Authors: Zhengzhong Luo, Yixin Huang, Kang Yong, Dan Wu, Linfeng Zheng, Xueping Yao, Liuhong Shen, Shumin Yu, Baoning Wang, Suizhong Cao
Journal: Gut Microbes (2025)

The ketogenic diet (KD) induces prolonged hyperketonemia, characterized by elevated circulating level of β-hydroxybutyrate. However, the KD can negatively affect host metabolic health by altering the gut microbial community. Despite this, the regulatory effect of the gut microbiota on hepatic ketogenesis and triacylglycerol (TAG) accumulation during a KD remains poorly understood. Here, we hypothesized that the commensal bacterium regulates hepatic lipid metabolism in association with KD-induced hyperketonemia. The KD disrupts the remodeling of the gut microbiota following antibiotic-induced depletion. The capacity for ketogenesis and the severity of TAG accumulation in the liver closely correlated with changes in the gut microbial composition and the up-regulation of hepatic farnesoid X receptor (FXR), peroxisome proliferator-activated receptor alpha (PPARα), and diacylglycerol O-acyltransferase 2 (DGAT2), which were modulated by bile acid metabolism through the gut-liver axis. The commensal bacterium Clostridium perfringens type A is particularly implicated in prolonged hyperketonemia, exacerbating hepatic ketogenesis and steatosis by disrupting secondary bile acid metabolism. The increased conversion of deoxycholic acid to 12-ketolithocholic acid represents a critical microbial pathway during C. perfringens colonization. These findings illuminate the adverse effects of the gut microbiota on hepatic adaptation to a KD and highlight the regulatory role of C. perfringens in ketonic states.
Standard breath-hold versus free-breathing real-time cine cardiac MRI - a prospective randomised comparison in patients with known or suspected cardiac disease
Authors: Mohamed Elshibly, Simran Shergill, Kelly Parke, Charley Budgeon, Rachel England, Ciaran Grafton-Clarke, Fathelrahman Elshibly, Peter Kellman, Gerry P McCann, Jayanth R Arnold
Journal:  (2025)

Cardiovascular magnetic resonance (CMR) is established as the reference standard for cardiac volumetric assessment. Despite the accuracy and robustness of steady-state free precession (SSFP) cine imaging, its use may prove challenging in patients with arrhythmia and in those who cannot perform repeated breath holds. An alternative solution may be a free-breathing electrocardiogram (ECG)-triggered, retro-gated, real-time cine sequence. This study sought to compare left ventricular volumetric, wall motion, and thickness assessment with both techniques. Consecutive patients with known or suspected cardiac disease referred for clinical CMR were studied at 3-Tesla. Participants underwent short-axis standard SSFP and real-time cine imaging in a randomized order within the same scan. Between sequence agreement and mean difference were compared for end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume, ejection fraction (EF), left ventricular mass (LVM), maximal wall thickness (MWT), and wall motion score index (WMSi). Two hundred and two patients (mean age 61 ± 14 years, 51% male and 14% irregular rhythm) were studied. All left ventricular indices showed good-excellent agreement between the two methods [intraclass correlation coefficient (95% confidence interval), EDV 0.96 (0.95-0.97), ESV 0.96 (0.94-0.97), EF 0.85 (0.81-0.88), LVM 0.93 (0.91-0.95), MWT 0.80 (0.75-0.85), and WMSi 0.93 (0.91-0.95)]. In patients with known or suspected cardiac disease, real-time cine imaging demonstrates good-excellent reproducibility of LV volumetric, wall thickness and resting wall motion assessment when compared with standard SSFP (Trial registration: NCT05221853).
Fexinidazole as a new oral treatment for human African trypanosomiasis due to Trypanosoma brucei rhodesiense: a prospective, open-label, single-arm, phase 2–3, non-randomised study
Authors: Enock Matovu, Westain Nyirenda, Anthony Eriatu, Deolinda Alves, Christelle Perdrieu, Marshal Lemerani, Charles Wamboga, Veerle Lejon, Jorge Seixas, Aita Signorell, Anne Reymondier, Elisabeth Baudin, Bruno Scherrer, Olaf Valverde Mordt
Journal: The Lancet Global Health (2025)
Co-occurrence patterns and related risk factors of ischaemic heart disease and ischaemic stroke across 203 countries and territories: a spatial correspondence and systematic analysis
Authors: Xuanqi An, Zeye Liu, Luwen Zhang, Jing Zhao, Qing Gu, Wei Han, Yaoda Hu, Fang Xue, Fengwen Zhang, Shouzheng Wang, Wenbin Ouyang, Yanmin Yang, Rui Fu, Weixian Yang, Sean X Leng, Jue Liu, Jingmei Jiang, Xiangbin Pan
Journal: The Lancet Global Health (2025)
Data gaps in prevalence rates of mental health conditions around the world: a retrospective analysis of nationally representative data
Authors: Caio B Casella, Antonis A Kousoulis, Brandon A Kohrt, Jason Bantjes, Christian Kieling, Pim Cuijpers, Sarah Kline, Konstantinos Kotsis, Guilherme V Polanczyk, Dan J Stein, Peter Szatmari, Kathleen R Merikangas, Zeina Mneimneh, Giovanni A Salum
Journal: The Lancet Global Health (2025)
Disproportionate increase in BMI of ≥60 kg/m2 in the USA
Authors: Michael Kachmar, Vance L Albaugh, Shengping Yang, Florina Corpodean, Steven B Heymsfield, Peter T Katzmarzyk, David S Freedman, Philip R Schauer
Journal: The Lancet Diabetes & Endocrinology (2025)
Policy and service delivery proposals to improve primary care services in low-income and middle-income country cities
Authors: Richard J Lilford, Benjamin Daniels, Barbara McPake, Zulfiqar A Bhutta, Robert Mash, Frances Griffiths, Akinyinka Omigbodun, Elzo Pereira Pinto, Radhika Jain, Gershim Asiki, Eika Webb, Katie Scandrett, Peter J Chilton, Jo Sartori, Yen-Fu Chen, Peter Waiswa, Alex Ezeh, Catherine Kyobutungi, Gabriel M Leung, Cristiani Machado, Kabir Sheikh, Sam I Watson, Jishnu Das
Journal: The Lancet Global Health (2025)
Incidence rates of malaria, meningitis, and mortality in children younger than 5 years: a prospective cohort study in Ghana and Kenya before the roll-out of the RTS,S/AS01E malaria vaccine from 2016 to 2022
Authors: Kwaku Poku Asante, Marie-Cécile Bozonnat, Miloje Savic, Seth Owusu-Agyei, Seyram Kaali, Walter Otieno, Owusu Boahen, Mathilda Tivura, Lucas Otieno, Prince Darko Agyapong, Patrick Odum Ansah, Valentine Sing'oei, Janet Oyieko, Elisha Adeniji, Nana Akosua Ansah, Samuel Bernard Ekow Harrison, Esther Oguk, David Dosoo, Lode Schuerman, Michael Bandasua Kaburise, Dennis Azabra Awuni, Kingsley Kayan, Cristina Cravcenco, François Roman, Valérie Haine
Journal: The Lancet Global Health (2025)