tbuckley/cabot-search huggingface dataset:
Molecular Classification of Hepatocellular Carcinoma based on Zoned Metabolic Feature and Oncogenic Signaling Pathway
Authors: Tomoko Aoki, Naoshi Nishida, Yutaka Kurebayashi, Kazuko Sakai, Naoto Fujiwara, Masakatsu Tsurusaki, Kohei Hanaoka, Masahiro Morita, Hirokazu Chishina, Masahiro Takita, Satoru Hagiwara, Hiroshi Ida, Kazuomi Ueshima, Yasunori Minami, Atsushi Takebe, Takaaki Murase, Keiko Kamei, Takuya Nakai, Ippei Matsumoto, Kazuto Nishio, Masatoshi Kudo
Journal: Clinical and Molecular Hepatology (2025)

Previously, we advocated the importance of classifying hepatocellular carcinoma (HCC) based on physiological functions. This study aims to classify HCC by focusing on liver-intrinsic metabolism and glycolytic pathway in cancer cells. Comprehensive RNA/DNA sequencing, immunohistochemistry, and radiological evaluations were performed on HCC tissues from the training cohort (n=136) and validated in 916 public samples. HCC was classified using hierarchical clustering and compared with previous molecular, histopathological, and hemodynamic classifications. Liver-specific metabolism and glycolysis are mutually exclusive and were divided into two major subclasses: The "rich metabolism" subclass (60.3%) is characterized by enhanced bile acid and fatty acid metabolism, well-to-moderate differentiation, microtrabecular or pseudoglandular pattern, and homogeneous arterial-phase hyperenhancement (APHE), corresponding to Hoshida S3 with favorable prognosis. In IL6-JAK-STAT3-high (25.0%) conditions, upregulated ALB expression, enhanced gluconeogenesis and urea cycle activity, and an inflammatory-microenvironment are observed. Conversely, the Wnt/β-catenin-high environment (19.9%) features elevated GLUL, APOB and CYP3A4 expression, frequent CTNNB1 (D32-S37) mutations, and an immune-desert/excluded phenotype. The "glycolysis" subclass (39.7%), characterized by histopathological dedifferentiation and downregulated liver-specific metabolism, encompasses subclasses with PI3K/mTOR (20.6%) and NOTCH/TGF-β (19.1%) signaling. These often exhibit TP53 mutations, macrotrabecular massive or compact patterns, inhomogeneous/rim-APHE, and high expression of hypoxia-inducible factors and glucose transporters, corresponding to Hoshida S1/2 with poor prognosis. The loss of liver-specific metabolism correlates with morphological dedifferentiation, indicating cellular dedifferentiation may exhibit both physiological and pathological duality. Key signaling pathways involved in the maturation process from fetal to adult liver and zonation program may play a critical role in defining HCC diversity.
Bias recognition and mitigation strategies in artificial intelligence healthcare applications
Authors: Fereshteh Hasanzadeh, Colin B. Josephson, Gabriella Waters, Demilade Adedinsewo, Zahra Azizi, James A. White
Journal: npj Digital Medicine (2025)

Artificial intelligence (AI) is delivering value across all aspects of clinical practice. However, bias may exacerbate healthcare disparities. This review examines the origins of bias in healthcare AI, strategies for mitigation, and responsibilities of relevant stakeholders towards achieving fair and equitable use. We highlight the importance of systematically identifying bias and engaging relevant mitigation activities throughout the AI model lifecycle, from model conception through to deployment and longitudinal surveillance.
British Society of Gastroenterology practice guidance on the management of acute and chronic gastrointestinal symptoms and complications as a result of treatment for cancer
Authors: Jervoise Andreyev, Richard Adams, Jan Bornschein, Mark Chapman, Dave Chuter, Sally Darnborough, Andrew Davies, Fiona Dignan, Clare Donnellan, Darren Fernandes, Robert Flavel, Georgina Giebner, Alexandra Gilbert, Fiona Huddy, Mohid Shakil S Khan, Pauline Leonard, Shameer Mehta, Ollie Minton, Christine Norton, Louise Payton, Gill McGuire, Mark Pritchard, Claire Taylor, Susan Vyoral, Ana Wilson, Linda Wedlake
Journal: Gut (2025)

Background Survival rates after a diagnosis of cancer are improving. Poorly managed gastrointestinal (GI) side effects can interfere with delivery of curative cancer treatment. Long-term physical side effects of cancer therapy impinge on quality of life in up to 25% of those treated for cancer, and GI side effects are the most common and troublesome. Aim To provide comprehensive, practical guidance on the management of acute and chronic luminal gastrointestinal symptoms arising during and after treatment for cancer Methods A multidisciplinary expert group including patients treated for cancer, divided into working parties to identify, and synthesise recommendations for the optimal assessment, diagnosis and appropriate interventions for luminal GI side effects of systemic and local cancer therapies. Recommendations were developed using the principles of the BMJ AGREE II reporting. Results 103 recommendations were agreed. The importance of the patient perspective and what can be done to support patients are emphasised. Key physiological principles underlying the development of GI toxicity arising from cancer therapy are outlined. Individual symptoms or symptom clusters are poor at distinguishing the underlying cause(s), and investigations are required if empirical therapy does not lead rapidly to significant benefits. Patients frequently have multiple GI causes for symptoms; all need to be diagnosed and optimally treated to achieve resolution. Investigations and management approaches now known to be ineffective or of questionable benefit are highlighted. Conclusions The physical, emotional and financial costs to individuals, their families and society from cancer therapy can be considerable. Identifying and signposting affected patients who require specialist services is the role of all clinicians. Progress in the treatment of cancer increasingly means that patients require expert, multidisciplinary supportive care providing effective and safe treatment at every stage of the cancer journey. Development of such expertise should be prioritised as should the education of health professionals and the public in what, when and how acute and chronic gastrointestinal symptoms and complications should be managed.
Partial Adrenalectomy With Maximizing Adrenal Preservation: 68Ga-Pentixafor PET/CT-Guided Precise Resection of Aldosterone-Producing Adenoma
Authors: Kai Cheng, Yao He, Tingting Long, Longfei Liu, Yu Gan
Journal: Clinical Nuclear Medicine (2025)

68 Ga-pentixafor PET/CT is a reliable, noninvasive functional imaging technique that demonstrates high classification accuracy for subtypes of primary hyperaldosteronism (PA) and provides significant guidance for clinical treatment decisions. We report a case of the precise resection of an aldosterone-producing adenoma (APA) while maximizing the preservation of adrenal glands under the guidance of 68 Ga-pentixafor PET/CT imaging.
PSMA-based Theranostics in Advanced Non–small Cell Lung Cancer​​​​​​
Authors: Piyush Aggarwal, Anupriya Anwariya, Komalpreet Kaur, Swayamjeet Satapathy, Ashwani Sood, Navneet Singh, Amanjit Bal, Harmandeep Singh, Bhagwant Rai Mittal
Journal: Clinical Nuclear Medicine (2025)

Prostate-specific membrane antigen (PSMA) overexpression on prostate cancer cells finally led to the FDA approval of the therapeutic use of 177 Lu-PSMA-617 in metastatic castrate-resistant prostate cancer. However, PSMA is also expressed in the neovasculature of other solid tumors, such as lung and renal cancer, making the theranostic potential of 177 Lu-PSMA-617 worth exploring in this setting. Here is such a case of an 83-year-old man with advanced non–small cell lung cancer where the theranostic potential of 177 Lu-PSMA-617 was explored using dosimetric analysis.
Positive 18F-FDG PET/CT and Negative 123I-MIBG SPECT/CT Imaging in an Unusual Diaphragmatic Metastasis From Ganglioneuroblastoma
Authors: Ziang Zhou, Siqi Li, Jun Liu, Jigang Yang
Journal: Clinical Nuclear Medicine (2025)

A 7-year-old boy underwent 18 F-FDG PET/CT in the evaluation of a retroperitoneal mass. The examination revealed significant FDG accumulation in the right adrenal region and retroperitoneal lymph nodes, as well as mild FDG uptake in a diaphragmatic lesion. Histopathological analysis of the right adrenal mass was consistent with ganglioneuroblastoma. Three months later, 123 I-MIBG scintigraphy was conducted, which did not demonstrate abnormal MIBG accumulation in the diaphragmatic lesion. Histopathological examination of the diaphragmatic lesion confirmed metastatic involvement.
Nociplasticity: A Proposed Concept to Understand the Symptomatology of Systemic Lupus Erythematosus
Authors: David S. Pisetsky, Jennifer L. Rogers, Amanda M. Eudy, Katherine T. Martucci, Ru‐Rong Ji, Peter E. Lipsky
Journal: Arthritis & Rheumatology (2025)

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Intense Uptake of 68Ga-exendin-4 in a Patient With WHO Grade 3 Insulinoma and Extensive Intrahepatic Metastases
Authors: Hongzhe Zhang, Qingqing Pan, Silu Liu, Jie Feng, Yaping Luo
Journal: Clinical Nuclear Medicine (2025)

A 24-year-old woman with hyperinsulinemic hypoglycemia was found with a pancreatic mass and multiple intrahepatic lesions in CT and MRI. 68 Ga-exendin-4 PET/CT showed intense radioactivity in the pancreatic mass and all the intrahepatic lesions, suggesting a malignant insulinoma with multiple intrahepatic metastases. Subsequent fine needle biopsy confirmed the diagnosis of WHO grade 3 insulinoma. This case with extensive glucagon-like peptide-1 receptor (GLP-1R) expression in a high-grade malignant insulinoma highlighted the potential of GLP-1R-targeted PRRT in future clinical studies.
18F-Fluorocholine Uptake in Unilateral Breast Related to Breastfeeding in Patient With Primary Hyperparathyroidism
Authors: Yazan Z. Alabed, Hidayath A. Ansari
Journal: Clinical Nuclear Medicine (2025)

A 46-year-old woman with primary hyperparathyroidism and negative sestamibi parathyroid scan was referred for 18 F-fluorocholine ( 18 F-FCH) positron emission tomography (PET/CT) scan to help localize parathyroid adenoma. FCH PET/CT scan identified a hyperfunctioning parathyroid gland in the left neck. In addition, there was unusually intense unilateral FCH uptake in the right breast corresponding to dense soft tissue. Upon further questioning, the patient admitted to breastfeeding for the past year exclusively from the right breast. Breast MRI showed no corresponding abnormal signal. We present the imaging findings of unilateral breastfeeding on 18 F-FCH PET/CT.
Remarkable 99mTc-FAPI-46 Uptake in a Patient With Anaplastic Thyroid Carcinoma: A Promising Step in Theranostic Field
Authors: Mitra Ghahraman, Pegah Sahafi, Mohammad Hadi Samadi, Kamran Aryana, Atena Aghaee
Journal: Clinical Nuclear Medicine (2025)

Fibroblast activation protein (FAP)-targeted radionuclides are known as a promising step in cancer diagnosis and treatment (theranostic), although it is still a subject under investigation. We present a patient with anaplastic thyroid carcinoma who underwent 99mTc-FAPI-46 SPECT/CT for the evaluation of metastatic disease. Several metastatic sites were found with considerable 99mTc-FAPI-46 uptake. Malignant FAPI uptake was observed in the large calcified thyroid mass, mediastinal lymph node, both lungs, liver, few skeletal sites, and around knees prostheses. Given the notable uptake of lesions, the patient was considered as a candidate for FAP-targeted radionuclide therapy.
First Clinical Application of 99mTc-FAPI-46 as an Available Radiotracer to Evaluate the Cardiac Remodeling Process
Authors: Nasrin Raeisi, Amin Saber Tanha, Kamran Aryana, Sadegh Nazif, Somaye Barashki
Journal: Clinical Nuclear Medicine (2025)

We present a 67-year-old woman with a history of coronary artery bypass graft surgery, who experienced recent chest pain. Myocardial perfusion imaging and 99m Tc-FAPI-46 SPECT were performed to assess myocardial infarction. The dynamic FAPI imaging indicated sustained myocardial activity. Myocardial perfusion imaging identified extensive myocardial infarction and ischemia, while FAPI uptake slightly overestimated the infarct extension. Coronary angiography correlated well with these findings. FAPI PET/CT is increasingly being used to monitor cardiac remodeling. This pioneering experience with 99m Tc-FAPI-46 showcases comparable results to PET/CT, providing valuable insights into cardiac remodeling processes and highlighting the potential of 99m Tc-FAPI-46 in cardiac imaging.
Coronary Arteries Involvement in Giant Cell Arteritis Diagnosis Using 2-[18F]FDG-PET/CT
Authors: Julien Kunsch, Olivier Espitia, Françoise Kraeber-Bodéré, Marine Eustache, Bastien Jamet
Journal: Clinical Nuclear Medicine (2025)

Coronary artery involvement in giant cell arteritis (GCA) is rare but can lead to severe complications, including myocardial infarction and death. We present unique 2-[ 18 F]fluorodeoxyglucose positron emission tomography/computed tomography (2-[ 18 F]FDG-PET/CT) findings in a 91-year-old woman with GCA. In addition to typical aortic and supra-aortic involvement, this scan revealed intense FDG uptake in the coronary arteries, including the left main trunk, left anterior descending, circumflex, and right coronary arteries. This inflammatory pattern was consistent with GCA, with no signs of atherosclerosis on coronary CT angiography. Early identification of coronary inflammation enabled timely immunosuppressive therapy, potentially preventing fatal outcomes.
Effect of time of day and seasonal variation on bronchodilator responsiveness: the SPIRO-TIMETRY study
Authors: Ben Knox-Brown, Fu Chuen Kon, Karl Peter Sylvester, Akhilesh Jha
Journal: Thorax (2025)

We investigated the association between time of day and season of testing on the level of bronchodilator responsiveness in a hospital-based population. We found that per 1-hour increment in the working day, the odds of a positive bronchodilator response decreased by 8%. A similar effect was seen when time of day was dichotomised into morning and afternoon time periods. When stratifying by referral reason, the impact of time of day was only seen in those referred for asthma/query asthma. We also found that bronchodilator responsiveness was more common in winter months compared with the rest of the year.
CHOLECYSTECTOMY IS A RISK FACTOR FOR MICROSCOPIC COLITIS: A NATIONWIDE POPULATION-BASED MATCHED CASE CONTROL STUDY.
Authors: David Bergman, Fahim Ebrahim, Jiangwei Sun, John Maret-Ouda, Björn Lindkvist, Anne Peery, Jonas F. Ludvigsson
Journal: Clinical Gastroenterology and Hepatology (2025)
Factors Associated with Retinal Detachment Following Pediatric Cataract Surgery in the IRIS® Registry
Authors: Francisco Altamirano, Ju Hyun Jeon, Ju-Yeun Lee, Tobias Elze, Joan W Miller, Alice C Lorch, Deborah K VanderVeen, Efren Gonzalez, Isdin Oke
Journal: Ophthalmology (2025)
Plasma metabolite profiles of meat intake and their association with cardiovascular disease risk: A population-based study in Swedish cohorts
Authors: Getachew Arage, Koen F Dekkers, Luka Marko Rašo, Ulf Hammar, Ulrika Ericson, Susanna C Larsson, Hanna Engel, Gabriel Baldanzi, Kamalita Pertiwi, Sergi Sayols-Baixeras, Rikard Landberg, Johan Sundström, J Gustav Smith, Gunnar Engström, Johan Ärnlöv, Marju Orho-Melander, Lars Lind, Tove Fall, Shafqat Ahmad
Journal: Metabolism (2025)
Population-based Screening for Chronic Obstructive Pulmonary Disease Using the St. George’s Respiratory Questionnaire in Resource-limited Settings
Authors: William Checkley, Mingling Yang, Nicole M Robertson, Arun K Sharma, Ram K. Chandyo, Laxman Shrestha, Santa K. Das, Bruce Kirenga, Patricia Alupo, Gonzalo Gianella, Trishul Siddharthan, Suzanne L Pollard, Shumonta Quaderi, Natalie Rykiel, Oscar Flores-Flores, John R Hurst, Robert A. Wise
Journal: American Journal of Respiratory and Critical Care Medicine (2025)

Spirometry, while necessary for the diagnosis of COPD, remains a scarce and costly resource worldwide. Screening questionnaires may help to bridge the diagnostic gap. We evaluated the performance of the St. George's Respiratory Questionnaire (SGRQ) as a screening tool using spirometry-confirmed COPD as a gold standard. We screened adults aged ≥40 years for COPD in Bhaktapur, Nepal; Lima, Peru; and Nakaseke, Uganda. Participants completed SGRQs and pre-bronchodilator peak expiratory flow (PEF). We defined COPD as a post-bronchodilator FEV1/FVC Z-score < -1.645, evaluated the discriminative performance of the SGRQ using receiver operating characteristic curves, and identified the best threshold to screen for spirometry-confirmed COPD. We screened 10709 participants (mean age 56.3 years, 49.7% males, 15.4% current smokers). After exclusion for missing data and implausible values, we analyzed data of 10008 participants (94%). Prevalence of spirometry-confirmed COPD was 9.5%; mean (±SD) total SGRQ score was 7.9±11.9 points, and 20.3±19.4 points in participants with COPD and 6.6±9.9 points in those without COPD. The area-under-the-curve (AUC) for SGRQ as a screening tool for COPD was 0.77 (95% CI 0.75-0.79) and the best threshold was 10.75 points. When the SGRQ was combined with pre-bronchodilator PEF stratified by sex, the AUC increased to 0.84 (95% CI 0.82-0.85). A screening test that combined a total SGRQ score ≥12 points and/or pre-bronchodilator PEF <400 L/min for men and <250 L/min for women yielded a sensitivity of 91%, a specificity of 47% and negative predictive value of 98% to identify spirometry-confirmed COPD. SGRQ is an alternative screening tool for spirometry-confirmed COPD. Screening with the SGRQ in combination with PEF may help to identify people at-risk for COPD in resource-limited settings where spirometry is not readily available.
Reply to Francesco Montorsi, Giuseppe Rosiello, Giorgio Gandaglia, Andrea Salonia and Alberto Briganti’s Letter to the Editor re: Paolo Gontero, Alison Birtle, Otakar Capoun, et al. European Association of Urology Guidelines on Non–muscle-invasive Bladder Cancer (TaT1 and Carcinoma In Situ)—A Summary of the 2024 Guidelines Update. Eur Urol 2024;86:531–49
Authors: Paolo Gontero, Francesco Soria
Journal: European Urology (2025)
Re: Paolo Gontero, Alison Birtle, Otakar Capoun, et al. European Association of Urology Guidelines on Non–muscle-invasive Bladder Cancer (TaT1 and Carcinoma In Situ)—A Summary of the 2024 Guidelines Update. Eur Urol 2024;86:531–49
Authors: Francesco Montorsi, Giuseppe Rosiello, Giorgio Gandaglia, Andrea Salonia, Alberto Briganti
Journal: European Urology (2025)
T-cell Engagers in Prostate Cancer
Authors: Chadi Hage Chehade, Zeynep Irem Ozay, Micah Ostrowski, Chiara Mercinelli, Georges Gebrael, Nicolas Sayegh, Umang Swami, Arun A Azad, Emmanuel S Antonarakis, Neeraj Agarwal
Journal: European Urology (2025)
Harnessing STING Signaling and Natural Killer Cells overcomes PARP Inhibitor Resistance in Homologous Recombination Deficient Breast Cancer
Authors: Flaminia Pedretti, Mohmed Abdalfttah, Benedetta Pellegrino, Francesca Mateo, Paula Martínez-Sanz, Andrea Herencia-Ropero, Andreu Òdena, Pau Clavell-Revelles, Giorgia Casali, Heura Domenech, Laia Monserrat, Dražen Papić, Alba Mas Malavila, Anna Pascual-Reguant, Herena Eixarch, Marta Guzman, Olga Rodriguez, Judit Grueso, Sara Simonetti, Roberta Fasani, Paolo Nuciforo, Carmen Espejo, Stefan Florian, Miguel Ángel Pujana, Lara Nonell, Joan Seoane, Viia Valge-Archer, Mark J. O'Connor, Juan C. Nieto, Holger Heyn, Judith Balmaña, Alba Llop-Guevara, Violeta Serra
Journal: Cancer Research (2025)

Abstract Homologous recombination deficiency (HRD) contributes to genomic instability and leads to sensitivity to poly ADP-ribose polymerase inhibitors (PARPi). HRD also activates the cyclic GMP–AMP synthase (cGAS)-STimulator of INterferon Genes (STING)-Interferon (IFN) pathway, highlighting the need to understand the impact of cGAS-STING-IFN signaling on PARPi efficacy. In this study, we analyzed a cohort of thirty-five breast cancer (BC) patient-derived xenografts (PDX) and mouse-derived allografts (MDA). PARPi sensitivity correlated with HRD, increased genomic instability, and activation of the cGAS-STING-IFN signaling pathway. Single-cell analyses showed that IFN signaling and IFN-based immune interactions were suppressed in preclinical models with acquired resistance to PARPi, lacking concomitant clonal expansion of functional CD8+ T cells. However, the combination of PARPi and a novel STING agonist (STINGa) increased immune infiltration and resulted in superior antitumor activity in these tumors. Notably, the efficacy of PARPi monotherapy and the combination treatment with a STINGa was dependent on Natural Killer (NK) cells. In agreement, BC patients with BRCA1/BRCA2 mutations and good responses to PARPi showed higher abundancy of CD56+ NK cells in the tumor microenvironment and treatment-engaged CD56bright NK cells in the peripheral immune compartment, compared to those with poor responses. Therefore, these findings propose the combination of PARPi and STINGa as a potential novel strategy to enhance the therapeutic response in patients with acquired PARPi resistance and highlight a pivotal role of NK cells in the PARPi antitumor activity.
Pharmacokinetics and safety of once-yearly lenacapavir: a phase 1, open-label study
Authors: Vamshi Jogiraju, Pallavi Pawar, Jenna Yager, John Ling, Gong Shen, Anna Chiu, Emma Hughes, Ramesh Palaparthy, Christoph Carter, Renu Singh
Journal: The Lancet (2025)
Tumor-intrinsic and immune-related features associated with treatment failure in human papillomavirus-related oropharyngeal cancer
Authors: Malay K Sannigrahi, Lovely Raghav, Dominick J Rich, Travis P Schrank, Joseph A Califano, John N Lukens, Lova Sun, Iain M Morgan, Roger B Cohen, Alexander Lin, Xinyi Liu, Eric J Brown, Jianxin You, Lisa Mirabello, Sambit K Mishra, David Shimunov, Robert M Brody, Alexander T Pearson, Phyllis A Gimotty, Ahmed Diab, Jalal B Jalaly, Devraj Basu
Journal: JNCI Journal of the National Cancer Institute (2025)

Abstract Background Limited understanding of the biology predisposing certain human papillomavirus-related (HPV+) oropharyngeal squamous cell carcinomas (OPSCCs) to relapse impedes therapeutic personalization. We aimed to identify molecular traits that distinguish recurrence-prone tumors. Methods 50 HPV+ OPSCCs that later recurred (cases) and 50 non-recurrent controls matched for stage, therapy, and smoking history were RNA-sequenced. Groups were compared by gene set enrichment analysis, and select differences were validated by immunohistochemistry. Features discriminating groups were scored in each tumor using gene set variation analysis, and scores were evaluated for recurrence prediction ability. Results Cases downregulated pathways linked to anti-tumor immunity (FDR-adjusted p&amp;lt;.05) and contained fewer tumor-infiltrating lymphocytes (p&amp;lt;.001), including cytotoxic T-cells (p=.005). Cases also upregulated pathways related to cell division and other aspects of tumor progression. Upregulated and downregulated pathways were respectively used to define a tumor progression score (TPS) and immune suppression score (ISS) for each tumor. Correlation between TPS and ISS (r=.603, p&amp;lt;.001) was potentially explained by observed upregulation of DNA repair pathways in cases, which might enhance their progression directly and by limiting cytosolic DNA-induced inflammation. Accordingly, cases contained fewer double-strand breaks based on staining for phospho-RPA32 (p=.006) and γ-H2AX (p=.005) and downregulated the cytosolic DNA sensing pathway. A combined score derived from TPS and ISS optimized recurrence prediction and stratified survival in a manner generalizable to three external cohorts. Conclusions We describe a potential link in HPV+ OPSCCs between reduced DNA damage and other tumor-intrinsic and immune-related contributors to recurrence risk, opening opportunities to detect and target this high-risk biology.