tbuckley/cabot-search huggingface dataset:
Dynamic STING repression orchestrates immune cell development and function
Authors: Kennady Knox, Devon Jeltema, Nicole Dobbs, Kun Yang, Cong Xing, Kun Song, Zhen Tang, Gustavo Torres-Ramirez, Jiefu Wang, Shan Gao, Tuoqi Wu, Chen Yao, Jian Wang, Nan Yan
Journal: Science Immunology (2025)

STING is an essential component of the innate immune system, yet homeostatic STING expression patterns and regulation are unknown. Using Sting1IRES-EGFP reporter and conditional Sting1 transgenic mice, we found that regulation of STING expression is critical for immune cell development and functionality. STING expression was repressed in neutrophils, and forced STING expression or signaling drove systemic inflammatory disease. During T lymphocyte development, STING expression was restricted at the double-positive stage via epigenetic silencing by DNA methyltransferase 1. Forced STING expression or signaling impaired T lymphocyte development independent of type I interferon and promoted lineage commitment to innate-like γδ T cells over adaptive αβ T cells. In the tumor microenvironment, CD8+ T lymphocytes repressed STING expression, correlating with features of T cell exhaustion in syngeneic mouse tumors and human colorectal cancer. Our data demonstrate the necessity of controlled, rather than ubiquitous, STING expression, uncovering a previously unappreciated dimension of STING pathobiology.
A deep-learning model for quantifying circulating tumour DNA from the density distribution of DNA-fragment lengths
Authors: Guanhua Zhu, Chowdhury Rafeed Rahman, Victor Getty, Denis Odinokov, Probhonjon Baruah, Hanaé Carrié, Avril Joy Lim, Yu Amanda Guo, Zhong Wee Poh, Ngak Leng Sim, Ahmed Abdelmoneim, Yutong Cai, Lakshmi Narayanan Lakshmanan, Danliang Ho, Saranya Thangaraju, Polly Poon, Yi Ting Lau, Anna Gan, Sarah Ng, Si-Lin Koo, Dawn Q. Chong, Brenda Tay, Tira J. Tan, Yoon Sim Yap, Aik Yong Chok, Matthew Chau Hsien Ng, Patrick Tan, Daniel Tan, Limsoon Wong, Pui Mun Wong, Iain Beehuat Tan, Anders Jacobsen Skanderup
Journal: Nature Biomedical Engineering (2025)
Sour neuronal signalling attenuates macrophage mediated liver injury
Authors: Xi Zhou, Zhibo Ma, Qi Cheng, Na Jiang, Junbo Li, Tianao Zhan, Naonao Yuan, Yanyu Chen, Lu Wang, Jingzeng Wang, Qingwen Li, Wenlong Jia, Bowen Xie, Yuanyuan Zhao, Bo Zhang, Bo Yang, Chen Dai, Lai Wei, Jing Liu, Zhishui Chen, Peixiang Lan
Journal: Journal of Hepatology (2025)
Primary Renal Neuroendocrine Tumor Demonstrated on 68Ga-FAPI-04 PET/CT and 18F-FDG PET/CT
Authors: Liu Xiao, Li Li, Yan Zhou, Shulei Pan, Wenjie Zhang
Journal: Clinical Nuclear Medicine (2025)

Primary renal neuroendocrine tumors are very rare. Herein, we report a case of imaging findings of a renal neuroendocrine tumor in a 36-year-old man. On 68Ga-FAPI-04 PET/CT and 18F-FDG PET/CT, it presented as a renal soft tissue mass with intense FAPI uptake (SUVmax: 20.8) but lower FDG uptake (SUVmax: 9.3). Postsurgical pathology supported a diagnosis of well-differentiated renal neuroendocrine tumor (G2).
Two Interesting Findings in One Case: Xanthogranulomatous Inflammation of the Colon and Isolated Widespread Liver Metastasis of Prostate Cancer on 68Ga-PSMA PET/CT
Authors: Hasan Önner, Ali Gümüş, Murat Çelik
Journal: Clinical Nuclear Medicine (2025)

Xanthogranulomatous inflammatory disease is a rare and benign condition that affects various organs. Due to their aggressive nature, the clinical and radiological findings of xanthogranulomatous inflammatory diseases are often misdiagnosed as malignant neoplasms. Prostate cancer metastases are most prevalent in lymph nodes and bones, with less common locations including the lung, liver, and brain. However, widespread liver metastasis is rare without metastatic dissemination to other sites. Herein, we present a case in which these 2 rare conditions were seen together on 68Ga-PSMA PET/CT.
Effect of spesolimab on sustained disease control in patients with generalized pustular psoriasis: Post hoc analysis of the EFFISAYIL 2 study
Authors: Kenneth B Gordon, Matthias Augustin, Jonathan Barker, Yayoi Tada, Mark G Lebwohl, Ming Tang, Patrick Hofmann, Christian Thoma, Alice B Gottlieb
Journal: Journal of the American Academy of Dermatology (2025)

Generalized pustular psoriasis (GPP) is a chronic inflammatory disease with an unpredictable disease course. Long-term treatment goals include sustained resolution of skin symptoms, prevention of new flares, and improvement in quality of life (QoL). To compare the effect of the interleukin-36 receptor monoclonal antibody spesolimab 600 mg subcutaneous (SC) loading dose (LD) followed by 300 mg SC every 4 weeks (q4w) versus placebo on skin symptoms and QoL burden in patients with GPP. A post hoc analysis of the EFFISAYIL 2 trial (NCT04399837) was conducted to assess the proportion of patients with sustained improvement of skin symptoms (GPP Physician Global Assessment total score, 0 or 1) and QoL burden (Dermatology Life Quality Index score, 0 or 1) at all visits up to week 48. Among the patients who received spesolimab 600 mg SC LD followed by 300 mg SC q4w, 63.3% had sustained improvement of skin symptoms (vs 29.0%; placebo), and 24.1% had sustained improvement of QoL burden (vs 3.2%; placebo). Retrospective, descriptive, post hoc analysis. Spesolimab 600 mg SC LD followed by 300 mg SC q4w provides sustained improvement of skin symptoms and QoL burden in a substantially higher proportion of patients with GPP versus placebo.
68Ga-PSMA Uptake of Brain Abscesses in a Patient With Prostate Cancer
Authors: Ying Huang, Bing Zhang, Dianchao Yue
Journal: Clinical Nuclear Medicine (2025)

A 56-year-old man with a history of brain abscess undergoing a 68Ga-labeled prostate-specific membrane antigen (PSMA) ligand PET/CT scan due to rising prostate-specific antigen levels. Besides the uptake of PSMA in the prostate lesion, the 68Ga-PSMA PET/CT images showed significant PSMA uptake in the abscesses in the left parietal and left temporal lobes. This highlights the necessity of cautious interpretation of PSMA PET/CT results, considering alternative diagnoses like infections.
Retroperitoneal Capillary Hemangioma Mimicking Paraganglioma on 18F-AlF-NOTA-Octreotide PET/CT
Authors: Yuanyuan Jiang, Guozhu Hou, Xuejuan Wang
Journal: Clinical Nuclear Medicine (2025)

Capillary hemangiomas are commonly encountered superficially in the cutaneous, subcutaneous, or mucosal tissues during childhood and early adulthood, but retroperitoneal capillary hemangioma is a rare occurrence. We present a case of a 61-year-old woman with incidentally detected capillary hemangioma in the retroperitoneum initially presumed to be paraganglioma based on 18F-AlF-NOTA-Octreotide PET/CT findings. Contrast-enhanced MRI revealed a hypervascular mass in the retroperitoneum. 18F-AlF-NOTA-Octreotide PET/CT performed for suspicion of paraganglioma showed intense uptake. Histopathologic examination of the retroperitoneal mass after surgical resection confirmed the diagnosis of capillary hemangioma rather than paraganglioma.
TANDEM Peptide Receptor Radionuclide Therapy Using [225Ac]Ac-/[177Lu]Lu-DOTA-LM3 in a Patient With Parotid Gland Metastasis From Pancreatic Neuroendocrine Neoplasm
Authors: Elisabetta Perrone, Kriti Ghai, Aleksandr Eismant, Richard P. Baum
Journal: Clinical Nuclear Medicine (2025)

We present the case of a young 38-year-old woman with metastatic progressive pancreatic neuroendocrine neoplasm (NEN) exhibiting an unusual metastasis to the parotid gland. After previous treatments, including radionuclide therapy with the somatostatin-receptor agonist DOTATOC and parotid metastasectomy, failed, she was referred to TANDEM peptide receptor radionuclide therapy (PRRT) using the somatostatin-receptor antagonist DOTA-LM3 labeled with Actinium-225 and Lutetium-177. Following 2 cycles of TANDEM-PRRT, she achieved partial remission in all metastatic sites, notably in the parotid gland and liver. This is the first reported case of metastatic pancreatic NEN with parotid involvement treated with TANDEM-PRRT.
68Ga-Pentixafor PET/CT–Based Response Evaluation and its Prognostic Value in Multiple Myeloma: Comparison With IMWG and 18F-FDG–Based Response
Authors: Harneet Kaur, Suraj Kumar, Ankit Watts, Charanpreet Singh, Man Updesh Singh Sachdeva, Sreejesh Sreedharanunni, Rajender Kumar, Pankaj Malhotra, Baljinder Singh
Journal: Clinical Nuclear Medicine (2025)

68Ga-Pentixafor PET/CT targets CXCR4 receptors and provides superior diagnostic accuracy in multiple myeloma (MM) compared with 18F-FDG PET/CT. However, its role in response evaluation remains unexplored. We propose a 68Ga-Pentixafor PET/CT-based response evaluation criterion and evaluate its utility compared with International Myeloma Working Group (IMWG) criteria and 18F-FDG PET/CT-based response. In this prospective single-center study, 40 treatment-naive myeloma patients were recruited between February 2021 and April 2023. Both 68Ga-Pentixafor and 18F-FDG PET/CT were performed at baseline and at follow-up (7.2 mo-median). Response to treatment was evaluated using the proposed 68Ga-Pentixafor PET/CT criteria and compared with responses assessed by IMWG and 18F-FDG PET/CT. Progression-free survival (PFS) and overall survival (OS) were analyzed and compared using Kaplan-Meier survival curves. Among the 40 newly diagnosed MM patients [median age: 56.5 years (IQR 45.25 to 63.75); 24 men], 68Ga-Pentixafor PET/CT was positive in a greater proportion of patients than 18F-FDG PET/CT [90% (36/40) vs. 67.5% (27/40); P=0.02] thus, adequately evaluated response in additional 27.5% (11/40) of cases. Using the proposed criteria for 68Ga-Pentixafor PET/CT, significant differences in PFS were observed across response categories [complete response (CR)-not reached, partial response (PR)-26.2 mo, progressive disease (PD)-15.3 mo; P=0.001]. Among patients achieving ≥very good partial response (VGPR) as per IMWG, those with positive 68Ga-Pentixafor PET/CT had shorter PFS compared with those with negative findings (median PFS: 34.2 mo vs. not reached; P=0.056), whereas no significant difference was noted with 18F-FDG PET/CT (P=0.68). In addition, on follow-up of patients with negative 18F-FDG at the response, those with discordant 68Ga-Pentixafor findings had significantly shorter PFS (17.73 mo vs. not reached; P=0.010) compared with those with concordant negative findings. 68Ga-Pentixafor PET/CT offers a more accurate assessment of treatment response and prognosis in MM patients, adding valuable information beyond the IMWG and 18F-FDG PET/CT-based criteria.
Can 99mTc-PSMA SPECT/CT Presenting Mirror Image of 68Ga-PSMA PET/CT Be Used for Response Assessment to 177Lu-PSMA in Metastatic Castration-Resistant Prostate Cancer?
Authors: Monika Hooda, Suraj Kumar, Sarika Prashar, Ravimohan Mavuduru, Baljinder Singh
Journal: Clinical Nuclear Medicine (2025)

A 69-year-old man, with a known case of metastatic castration-resistant prostate cancer (mCRPC) underwent 68Ga-PSMA PET/CT and 99mTc-PSMA for evaluation of disease burden and response assessment to 177Lu-PSMA therapy. 99mTc-PSMA provided a mirror image of 68Ga-PSMA. This suggests the potential of 99mTc-PSMA SPECT/CT for disease evaluation and response assessment to PSMA-based radioligand therapies in advanced-stage mCRPC patients, especially when 68Ga-PSMA PET/CT is not available.
A chromosome-level Dendrobium moniliforme genome assembly reveals the regulatory mechanisms of flavonoid and carotenoid biosynthesis pathways
Authors: Jiapeng Yang, Qiqian Xue, Chao Li, Yingying Jin, Qingyun Xue, Wei Liu, Zhitao Ni, Xiaoyu Ding
Journal: Acta Pharmaceutica Sinica B (2025)
Functional aptamer evolution-enabled elucidation of a melanoma migration-related bioactive epitope
Authors: Hong Xuan, Siqi Bian, Qinguo Liu, Jun Li, Shaojin Li, Sharpkate Shaker, Haiyan Cao, Tongxuan Wei, Panzhu Yao, Yifan Chen, Xiyang Liu, Ruidong Xue, YouBo Zhang, Liqin Zhang
Journal: Acta Pharmaceutica Sinica B (2025)
Acteoside ameliorates hepatocyte ferroptosis and hepatic ischemia-reperfusion injury via targeting PCBP2
Authors: Kexin Jia, Yinhao Zhang, Fanghong Li, Runping Liu, Jianzhi Wu, Jiaorong Qu, Ranyi Luo, Zixi Huang, Zhe Xu, Xiaojiaoyang Li
Journal: Acta Pharmaceutica Sinica B (2025)
The gut-skin axis: a bi-directional, microbiota-driven relationship with therapeutic potential
Authors: Maira Jimenez-Sanchez, Larissa S. Celiberto, Hyungjun Yang, Ho Pan Sham, Bruce A. Vallance
Journal: Gut Microbes (2025)

This review explores the emerging term "gut-skin axis" (GSA), describing the bidirectional signaling that occurs between the skin and the gastrointestinal tract under both homeostatic and disease conditions. Central to GSA communication are the gut and skin microbiota, the microbial communities that colonize these barrier surfaces. By influencing diverse host pathways, including innate immune, vitamin D receptor, and Aryl hydrocarbon receptor signaling, a balanced microbiota contributes to both tissue homeostasis and host defense. In contrast, microbiota imbalance, or dysbiosis at one site, can lead to local barrier dysfunction, resulting in the activation of signaling pathways that can disrupt tissue homeostasis at the other site, potentially leading to inflammatory skin conditions such as atopic dermatitis and psoriasis, or gut diseases like Inflammatory Bowel Disease. To date, most research on the GSA has examined the impact of the gut microbiota and diet on skin health, but recent studies show that exposing the skin to ultraviolet B-light can beneficially modulate both the gut microbiome and intestinal health. Thus, despite the traditional focus of clinicians and researchers on these organ systems as distinct, the GSA offers new opportunities to better understand the pathogenesis of cutaneous and gastrointestinal diseases and promote health at both sites.
Machine-learning assisted discovery unveils novel interplay between gut microbiota and host metabolic disturbance in diabetic kidney disease
Authors: I-Wen Wu, Yu-Chieh Liao, Tsung-Hsien Tsai, Chieh-Hua Lin, Zhao-Qing Shen, Yun-Hsuan Chan, Chih-Wei Tu, Yi-Ju Chou, Chi-Jen Lo, Chi-Hsiao Yeh, Chun-Yu Chen, Heng-Chih Pan, Heng-Jung Hsu, Chin-Chan Lee, Mei-Ling Cheng, Wayne Huey-Herng Sheu, Chi-Chun Lai, Huey-Kang Sytwu, Ting-Fen Tsai
Journal: Gut Microbes (2025)

Diabetic kidney disease (DKD) is a serious healthcare dilemma. Nonetheless, the interplay between the functional capacity of gut microbiota and their host remains elusive for DKD. This study aims to elucidate the functional capability of gut microbiota to affect kidney function of DKD patients. A total of 990 subjects were enrolled consisting of a control group (n = 455), a type 2 diabetes mellitus group (DM, n = 204), a DKD group (n = 182) and a chronic kidney disease group (CKD, n = 149). Full-length sequencing of 16S rRNA genes from stool DNA was conducted. Three findings are pinpointed. Firstly, new types of microbiota biomarkers have been created using a machine-learning (ML) method, namely relative abundance of a microbe, presence or absence of a microbe, and the hierarchy ratio between two different taxonomies. Four different panels of features were selected to be analyzed: (i) DM vs. Control, (ii) DKD vs. DM, (iii) DKD vs. CKD, and (iv) CKD vs. Control. These had accuracy rates between 0.72 and 0.78 and areas under curve between 0.79 and 0.86. Secondly, 13 gut microbiota biomarkers, which are strongly correlated with anthropometric, metabolic and/or renal indexes, concomitantly identified by the ML algorithm and the differential abundance method were highly discriminatory. Finally, the predicted functional capability of a DKD-specific biomarker, Gemmiger spp. is enriched in carbohydrate metabolism and branched-chain amino acid (BCAA) biosynthesis. Coincidentally, the circulating levels of various BCAAs (L-valine, L-leucine and L-isoleucine) and their precursor, L-glutamate, are significantly increased in DM and DKD patients, which suggests that, when hyperglycemia is present, there has been alterations in various interconnected pathways associated with glycolysis, pyruvate fermentation and BCAA biosynthesis. Our findings demonstrate that there is a link involving the gut-kidney axis in DKD patients. Furthermore, our findings highlight specific gut bacteria that can acts as useful biomarkers; these could have mechanistic and diagnostic implications.
Bridging epigenomics and tumor immunometabolism: molecular mechanisms and therapeutic implications
Authors: Xiaowen Xie, Weici Liu, Zhiyuan Yuan, Hanqing Chen, Wenjun Mao
Journal: Molecular Cancer (2025)

Epigenomic modifications—such as DNA methylation, histone acetylation, and histone methylation—and their implications in tumorigenesis, progression, and treatment have emerged as a pivotal field in cancer research. Tumors undergo metabolic reprogramming to sustain proliferation and metastasis in nutrient-deficient conditions, while suppressing anti-tumor immunity in the tumor microenvironment (TME). Concurrently, immune cells within the immunosuppressive TME undergo metabolic adaptations, leading to alterations in their immune function. The complicated interplay between metabolites and epigenomic modulation has spotlighted the significance of epigenomic regulation in tumor immunometabolism. In this review, characteristics of the epigenomic modification associated with tumors are systematically summarized alongside with their regulatory roles in tumor metabolic reprogramming and immunometabolism. Classical and emerging approaches are delineated to broaden the boundaries of research on the crosstalk research on the crosstalk between tumor immunometabolism and epigenomics. Furthermore, we discuss potential therapeutic strategies that target tumor immunometabolism to modulate epigenomic modifications, highlighting the burgeoning synergy between metabolic therapies and immunotherapy as a promising avenue for cancer treatment.
Genomic epidemiology and antimicrobial resistance reveal local transmission dynamics of enteric fever in Shenzhen, one of the mega cities in China
Authors: Yixiang Jiang, Min Jiang, Xin Lu, Meiying Yan, Xiaolu Shi, Qinghua Hu, Biao Kan
Journal: Journal of Infection (2025)

Highlights•Multiple imports and exports of S. Typhi and S. Paratyphi A strains exist in Shenzhen.•. Genomic clustering reveals silent outbreaks missed by epidemiological surveillance.•Antimicrobial resistance of enteric fever pathogens is not severe in Shenzhen.AbstractObjectivesOutbreak of enteric fever and the spread of antimicrobial-resistant Salmonella Typhi and S. Paratyphi pose significant public health challenges in low- and middle-income countries. Understanding the transmission dynamics of these pathogens is essential for developing effective control strategies.MethodsWe conducted phylogenomic analyses and integrated epidemiological data from 135 S. Typhi and 271 S. Paratyphi A isolates collected in Shenzhen from 2001 to 2017. Phylogenetic and temporal analyses were performed to identify prevalent genotypes and assess transmission patterns.ResultsAnalyses of S. Typhi isolates in Shenzhen revealed high genetic diversity, with genotypes 3.2.1 (37.8%) and 2.1.7 (20%) being most prevalent. Genotype 3.2.1 formed an independent lineage due to mutations in the quinolone resistance determining region (QRDR). The multidrug-resistant haplotype 58 (genotype 4.3.1) has been present since 2006. S. Paratyphi A isolates were predominantly genotype 2.3.3 (98.5%). Pathogen exchange occurred with at least four other provinces. A cutoff of ≤3 single nucleotide polymorphisms (SNPs) was effective for outbreak investigation, and 22 genomic clusters were found, suggesting undetected outbreaks or transmission events. While 80% of isolates were susceptible to first-line antibiotics, 16.9% of S. Paratyphi A isolates were multidrug-resistant.ConclusionsThis study provides insights into the transmission dynamics of enteric fever in Shenzhen, underscoring the need for ongoing genomic surveillance to manage and control outbreaks effectively.
Small extracellular vesicles and particles (sEVPs) derived from tumor-free pre-metastatic organs promote breast cancer metastasis and support organotropism
Authors: Tasneem Cheytan, Martin Schneider, Roberto Würth, Paul Schwerd-Kleine, Ewgenija Gutjahr, Verena Thewes, Laura L. Michel, Rebecca Weber, Tim Vorberg, Sabrina Lohr, Katja Nitschke, Michelle Neßling, Peter Lichter, Andreas Schneeweiss, Karsten Richter, Dominic Helm, Martin Sprick, Andreas Trumpp
Journal: Molecular Cancer (2025)

Metastatic breast cancer remains largely incurable, partly due to our incomplete understanding of its intricate underlying mechanisms. Notably, intercellular communication mediated by small extracellular vesicles and particles (sEVPs) has emerged as a key feature of metastasis. While tumor-derived sEVPs have been extensively studied and are known to be pro-metastatic, the role of sEVPs from metastasis-prone normal tissue sites remains primarily undefined. Here, we characterized and studied the function of sEVPs secreted from tumor-free pre-metastatic organs (TuFMO-sEVPs) such as the brain and lungs in both immunocompetent and patient-derived xenograft models. TuFMO-sEVPs from the brain of mammary tumor-bearing mice were found to have a distinct protein content as compared to brain-sEVPs from tumor-free mice, suggesting that the primary tumor can systemically influence the cargo of TuFMO-sEVPs. Importantly, mice orthotopically injected with breast cancer cells which had been educated with either brain or lung TuFMO-sEVPs prior to transplantation showed significantly increased metastasis to the respective organ. We further demonstrated that TuFMO-sEVPs induced the expression of the enzyme dihydrofolate reductase (DHFR) upon uptake by breast cancer cells, leading to their enhanced metastatic capacity. Organ-specific signatures generated from TuFMO-sEVP educated tumor cells were found to be increased in metastatic samples from breast cancer patients as compared to the primary tumor or normal tissue samples and these signatures also significantly correlated with poorer patient outcome. Collectively, our data reveals a novel facet of the metastatic cascade, implicating a role for TuFMO-sEVPs in directing metastasis and providing a potential therapeutic strategy for targeting this process.
Long-Term Efficacy and Safety of Rituximab in Patients With Pemphigus Foliaceus Compared With Pemphigus Vulgaris
Authors: Billal Tedbirt, Estelle Houivet, Maud Maho-Vaillant, Marie-Laure Golinski, Sébastien Calbo, Catherine Prost-Squarcioni, Bruno Labeille, Catherine Picard-Dahan, Guillaume Chaby, Marie-Aleth Richard, Emmanuelle Tancrède-Bohin, Sophie Duvert-Lehembre, Emmanuel Delaporte, Philippe Bernard, Frédéric Caux, Marina Alexandre, Philippe Musette, Saskia Ingen-Housz-Oro, Pierre Vabres, Gaëlle Quereux, Alain Dupuy, Sébastien Debarbieux, Martine Avenel-Audran, Michel D’Incan, Christophe Bédane, Nathalie Bénéton, Denis Jullien, Nicolas Dupin, Laurent Misery, Laurent Machet, Marie Beylot-Barry, Olivier Dereure, Bruno Sassolas, Nadège Cordel, Géraldine Jeudy, Jacques Benichou, Vivien Hébert, Pascal Joly
Journal: JAMA Dermatology (2025)

This cohort study examines the safety and efficacy of rituximab for patients with pempigus foliaceus.