tbuckley/cabot-search huggingface dataset:
FAP-Targeted SPECT/CT and PET/CT Imaging for Breast Cancer Patients
Authors: Jeremy McGale, Sakshi Khurana, Harrison Howell, Abanoub Nakhla, Tina Roa, Parth Doshi, Dorsa Shirini, Alice Huang, Phuong Duong, Philipp Backhaus, Matthew Liao, Harleen Kaur, Amelia McNiven Fontani, Isabella Hung, Neeta Pandit-Taskar, Uwe Haberkorn, Amit Gulati, Asmâa Naim, Mathieu Sinigaglia, Maria Bebawy, Antoine Girard, Romain-David Seban, Laurent Dercle
Journal: Clinical Nuclear Medicine (2025)

Abstract Breast cancer presents a significant global health challenge, necessitating continued innovation in diagnostic and therapeutic approaches. Recent advances have led to the identification of cancer-associated fibroblasts, which are highly prevalent in breast cancers and express fibroblast activation proteins (FAPs), as critical targets. FAP-specific radiotracers, when used with PET/CT and SPECT/CT, have significant potential for improving early breast cancer detection, staging, treatment response monitoring, and therapeutic intervention. This review provides insight into FAP-targeted molecular imaging, exploring advanced techniques for protein status assessment, development of early-phase targeted therapies, and other emerging applications. The advent of FAP-targeted imaging stands to significantly enhance personalized oncologic care, leading to improved breast cancer management and overall patient outcomes.
Remotely delivered weight management for people with long COVID and overweight: the randomized wait-list-controlled ReDIRECT trial
Authors: Emilie Combet, Laura Haag, Janice Richardson, Caroline E. Haig, Yvonne Cunningham, Heather L. Fraser, Naomi Brosnahan, Tracy Ibbotson, Jane Ormerod, Chris White, Emma McIntosh, Catherine A. O’Donnell, Naveed Sattar, Alex McConnachie, Michael E. J. Lean, David N. Blane
Journal: Nature Medicine (2025)
Tracking non-genetic evolution from primary to metastatic ccRCC: TRACERx Renal
Authors: Ángel Fernández-Sanromán, Annika Fendler, Benjy J.Y. Tan, Anne-Laure Cattin, Charlotte Spencer, Rachael Thompson, Lewis Au, Irene Lobon, Husayn Ahmed Pallikonda, Alice Martin, Fiona Byrne, Antonia Franz, Anna Mikolajczak, Haseeb Rahman, Zayd Tippu, Scott T.C. Shepherd, Hugang Feng, Daqi Deng, Andrew Rowan, Lisa Pickering, Andrew J.S. Furness, Kate Young, David Nicol, Sarah Maria Rudman, Tim O’Brien, Kim Edmonds, Ashish Chandra, Steve Hazell, Kevin Litchfield, George Kassiotis, James Larkin, Samra Turajlic
Journal: Cancer Discovery (2025)

Abstract Although the key aspects of genetic evolution and their clinical implications in clear-cell renal cell carcinoma (ccRCC) are well documented, how genetic features coevolve with the phenotype and tumor microenvironment (TME) remains elusive. Here, through joint genomic–transcriptomic analysis of 243 samples from 79 patients recruited to the TRACERx Renal study, we identify pervasive nongenetic intratumor heterogeneity, with over 40% not attributable to genetic alterations. By integrating tumor transcriptomes and phylogenetic structures, we observe convergent evolution to specific phenotypic traits, including cell proliferation, metabolic reprogramming, and overexpression of putative cGAS–STING repressors amid high aneuploidy. We also uncover a coevolution between the tumor and the T-cell repertoire, as well as a longitudinal shift in the TME from an antitumor to an immunosuppressive state, linked to the acquisition of recurrently late ccRCC drivers 9p loss and SETD2 mutations. Our study reveals clinically relevant and hitherto underappreciated nongenetic evolution patterns in ccRCC. Significance: Using joint genomic–transcriptomic analysis of 243 samples, we reveal recurrent patterns of nongenetic evolution in ccRCC not exclusively governed by genetic factors, including T-cell depletion, tumor T-cell receptor coevolution, potential cGAS–STING repression, and increased cell proliferation. These patterns can aid clinical management and guide novel treatment approaches.
Response eQTLs, chromatin accessibility, and 3D chromatin structure in chondrocytes provide mechanistic insight into osteoarthritis risk
Authors: Nicole E Kramer, Seyoun Byun, Philip Coryell, Susan D'Costa, Eliza Thulson, HyunAh Kim, Sylvie M Parkus, Marielle L Bond, Emma R Klein, Jacqueline Shine, Susanna Chubinskaya, Michael I Love, Karen L Mohlke, Brian O Diekman, Richard F Loeser, Douglas H Phanstiel
Journal: Cell Genomics (2025)
The trait-specific timing of accelerated genomic change in the human lineage
Authors: Eucharist Kun, Mashaal Sohail, Vagheesh M Narasimhan
Journal: Cell Genomics (2025)

Humans exhibit distinct characteristics compared to our primate and ancient hominin ancestors. To investigate genomic bursts in the evolution of these traits, we use two complementary approaches to examine enrichment among genome-wide association study loci spanning diseases and AI-based image-derived brain, heart, and skeletal tissue phenotypes with genomic regions reflecting four evolutionary divergence points. These regions cover epigenetic differences among humans and rhesus macaques, human accelerated regions (HARs), ancient selective sweeps, and Neanderthal-introgressed alleles. Skeletal traits such as pelvic width and limb proportions showed enrichment in evolutionary annotations that mirror morphological changes in the primate fossil record. Additionally, we observe enrichment of loci associated with the longitudinal fasciculus in human-gained epigenetic elements since macaques, the visual cortex in HARs, and the thalamus proper in Neanderthal-introgressed alleles, implying that associated cognitive functions such as language processing, decision-making, sensory signaling, and motor control are enriched at different evolutionary depths.
Towards NeuroAI: introducing neuronal diversity into artificial neural networks
Authors: Feng-Lei Fan, Yingxin Li, Tieyong Zeng, Fei Wang, Hanchuan Peng
Journal: Med-X (2025)

Abstract Throughout history, the development of artificial intelligence, especially artificial neural networks, has been continuously influenced by a deeper understanding of the brain. This influence includes the development of the neocognitron, considered a precursor to convolutional neural networks. The emerging field of NeuroAI posits that leveraging neuroscience knowledge could significantly advance AI by imbuing networks with enhanced capabilities. Unlike the human brain, which features a variety of morphologically and functionally distinct neurons, artificial neural networks typically rely on a homogeneous neuron model. In the human brain, the diversity of neurons facilitates a wide range of intelligent behaviors. Given that artificial networks aim to mimic the human brain, incorporating a diversity of neuron models could address key challenges in artificial intelligence, such as efficiency, interpretability, and memory capacity. This perspective begins by examining the basics of biological neuronal diversity and how biological neurons transmit and process information. We then explore research efforts to design novel neuron models for artificial networks and discuss the potential benefits of neuronal diversity, including applications in several critical areas. Finally, we address the challenges and future directions for integrating neuronal diversity into artificial networks, highlighting its potential to enrich NeuroAI.
Impact of comorbidities on the mortality benefits of lung cancer screening: a post-hoc analysis of PLCO and NLST trials
Authors: Sebastien Gendarme, Ehsan Irajizad, James P Long, Johannes F Fahrmann, Jennifer B Dennison, Seyyed Mahmood Ghasemi, Rongzhang Dou, Robert J Volk, Rafael Meza, Iakovos Toumazis, Florence Canoui-Poitrine, Samir M Hanash, Edwin J Ostrin
Journal: Journal of Thoracic Oncology (2025)
Tumor metabolic regulators: key drivers of metabolic reprogramming and the promising targets in cancer therapy
Authors: Kun Huang, Ying Han, Yihong Chen, Hong Shen, Shan Zeng, Changjing Cai
Journal: Molecular Cancer (2025)

Metabolic reprogramming within the tumor microenvironment (TME) is a hallmark of cancer and a crucial determinant of tumor progression. Research indicates that various metabolic regulators form a metabolic network in the TME and interact with immune cells, coordinating the tumor immune response. Metabolic dysregulation creates an immunosuppressive TME, impairing the antitumor immune response. In this review, we discuss how metabolic regulators affect the tumor cell and the crosstalk of TME. We also summarize recent clinical trials involving metabolic regulators and the challenges of metabolism-based tumor therapies in clinical translation. In a word, our review distills key regulatory factors and their mechanisms of action from the complex reprogramming of tumor metabolism, identified as tumor metabolic regulators. These regulators provide a theoretical basis and research direction for the development of new strategies and targets in cancer therapy based on tumor metabolic reprogramming. Refining the key regulatory factors and their mechanisms within the complex network of tumor metabolic reprogramming. Depicting the metabolic crosstalk between tumor cells, immune cells, and tumor stromal cells during tumor progression. Emphasizing the unresolved challenges of metabolic therapy in clinical translation and the advantages of personalized treatment. Providing theoretical support and research direction for new strategies for metabolic therapies.
Arachidonic acid synergizes with aspirin preventing myocardial ischemia-reperfusion injury and mitigates bleeding risk
Authors: Shaletanati Talabieke, Xuejian Yang, Jianfeng Yang, Qing Wan, Dekun Zhu, Haojie Rao, Yifei Wu, Zengrong Chen, Huihui Li, Pengfei Xu, Hong Chen, De-Pei Liu, Xu Zhang, Garret A FitzGerald, Miao Wang
Journal: Cardiovascular Research (2025)

Abstract Aims The therapeutic efficacy of coronary revascularization is compromised by myocardial ischemia-reperfusion (MI/R) injury. Higher levels of circulating arachidonic acid (AA) are reportedly associated with lower risk of cardiovascular disease. The cyclooxygenase (COX) pathway metabolizes AA into prostaglandins (PGs) and the platelet-activating thromboxane A2 (TXA2), which is inhibited by aspirin. We aimed to explore whether AA or its combination with aspirin modulates MI/R injury and aspirin-caused gastric bleeding. Methods and results Mice were subjected to 30min coronary artery ligation followed by reperfusion. AA reduced MI/R injury in mice, and its combination with aspirin provided further cardioprotection. Aspirin inhibited MI/R-triggered platelet activation and ameliorated microvascular obstruction immediately upon reperfusion, whereas AA improved microvascular perfusion at a later stage of reperfusion, coinciding with increased coronary vasodilatation. Co-administration of AA and aspirin markedly reduced cardiac neutrophil infiltration and vascular permeability and improved microcirculation. AA increased urinary metabolites of PGI2 and PGE2, not TXA2, and this selective augmentation was further enhanced by co-treatment with aspirin. Elevation in PGI2 and PGE2 correlated with reduced infarction and improved ventricular function, and inhibiting COX-2 attenuated the synergistic cadioprotection. Furthermore, oral administration of AA with aspirin after reperfusion provided a maximal cardioprotection and abolished aspirin-caused gastric bleeding. Conclusion AA synergizes with aspirin in protecting against MI/R injury, while minimizing the related bleeding risk, a major concern for patients with acute myocardial infarction. This is attributable to the selective augmentation of PGI2 and PGE2 that is amplified by TXA2 suppression by aspirin, underscoring improved microcirculation and ameliorated inflammation.
What’s the Gut Doing in the Chest? Interpositio Hepatodiaphragmatica (Chilaiditi Sign) Revisited on 18F-FDG PET/CT
Authors: Abhay Gondhane, Gaurav Malhotra
Journal: Clinical Nuclear Medicine (2025)

Abstract A 47-year-old woman, a diagnosed case of syndrome of inappropriate secretion of antidiuretic hormone, underwent 18 F-FDG PET/CT to detect occult malignancy for suspected paraneoplastic etiology. Abnormal FDG uptake was noted in the right lower chest region, which was correlated on corresponding CT images to be colonic activity interposed between the liver and elevated diaphragm, also known as Chilaiditi sign. Even though rare, Chilaiditi sign should be considered as a differential diagnosis of hypermetabolic activity in the right lower chest region on 18 F-FDG PET/CT scan that is done to look for occult tumor as shown in this case.
Intranodular Thyroid Metastasis of a Large Cell Neuroendocrine Carcinoma of the Endometrium
Authors: Capucine Richard, Abir Al Ghuzlan, Virginie Huchet, Vincent Cockenpot, Ségolène Hescot
Journal: Clinical Nuclear Medicine (2025)

Abstract A 64-year-old woman underwent initial 18 F-FDG PET/CT staging for a suspicious endometrial mass, which showed high uptake in the endometrial mass and a focal uptake in a known left thyroid nodule. Histology revealed a high-grade large cell neuroendocrine carcinoma of the endometrium with FIGO (International Federation of Gynecology and Obstetrics) stage Ib. Further explorations revealed a synchronous thyroid metastasis. Patient then received adjuvant immunochemotherapy. This case showed a potential pitfall in the initial assessment of this rare and aggressive malignancy on which the therapeutic approach greatly depends.
<i>Lactobacillus intestinalis</i> facilitates tumor-derived CCL5 to recruit dendritic cell and suppress colorectal tumorigenesis
Authors: Yong Sun, Qiwen Wang, Yao Jiang, Jiamin He, Dingjiacheng Jia, Man Luo, Wentao Shen, Qingyi Wang, Yadong Qi, Yifeng Lin, Ying Zhang, Lan Wang, Liangjing Wang, Shujie Chen, Lina Fan
Journal: Gut Microbes (2025)

Gut microbes play a crucial role in regulating the tumor microenvironment (TME) of colorectal cancer (CRC). Nevertheless, the deep mechanism between the microbiota-TME interaction has not been well explored. In this study, we for the first time discovered that Lactobacillus intestinalis (L. intestinalis) effectively suppressed tumor growth both in the AOM/DSS-induced CRC model and the ApcMin/+ spontaneous adenoma model. Our investigation revealed that L. intestinalis increased the infiltration of immune cells, particularly dendritic cells (DC), in the TME. Mechanically, the tumor-derived CCL5 induced by L. intestinalis recruited DC chemotaxis through the NOD1/NF-κB signaling pathway. In clinical samples and datasets, we found positive correlation between L. intestinalis, CCL5 level, and the DC-related genes. Our study provided a new strategy for microbial intervention for CRC and deepened the understanding of the interaction between tumor cells and the immune microenvironment modulated by gut microbes.
Single-cell and spatial transcriptomic profiling revealed niche interactions sustaining growth of endometriotic lesions
Authors: Song Liu, Xiaoyan Li, Zhiyue Gu, Jiayu Wu, Shuangzheng Jia, Jinghua Shi, Yi Dai, Yushi Wu, Hailan Yan, Jing Zhang, Yan You, Xiaowei Xue, Lulu Liu, Jinghe Lang, Xiaoyue Wang, Jinhua Leng
Journal: Cell Genomics (2025)

Highlights•Single-cell and spatial data reveal hierarchical microenvironment in endometriomas•Ectopic endometrial stromal cells retain menstrual cycle gene expression patterns•Distinct ovarian stromal cells (OSCs) links to fibrosis and inflammation in lesions•WNT5A signaling mediates interactions between ectopic endometrial stromal cells and OSCsSummaryEndometriosis is a chronic condition with limited therapeutic options. The molecular aberrations promoting ectopic attachment and interactions with the local microenvironment sustaining lesion growth have been unclear, prohibiting development of targeted therapies. Here, we performed single-cell and spatial transcriptomic profiling of ectopic lesions and eutopic endometrium in endometriosis. We found that ectopic endometrial stromal (EnS) cells retained cyclical gene expression patterns of their eutopic counterparts while exhibiting unique gene expression that contributes to the pathogenesis of endometriosis. We identified two distinct ovarian stromal cells (OSCs) localized at different zones of the lesion, showing differential gene expression profiles associated with fibrosis and inflammation, respectively. We also identified WNT5A upregulation and aberrant activation of non-canonical WNT signaling in endometrial stromal cells that may contribute to the lesion establishment, offering novel targets for therapeutic intervention. These data will enhance our understanding of the molecular mechanisms underlying endometriosis and paves the way for developing non-hormonal treatments.Graphical abstract
Allocation of Semaglutide According to Coronary Artery Calcium and BMI
Authors: Alexander C Razavi, Alexander M Cao Zhang, Zeina A Dardari, Khurram Nasir, Michael Khorsandi, Martin Bødtker Mortensen, Mouaz H Al-Mallah, Michael D Shapiro, Melissa A Daubert, Roger S Blumenthal, Laurence S Sperling, Seamus P Whelton, Michael J Blaha, Omar Dzaye
Journal: JACC. Cardiovascular imaging (2025)
Transcatheter Left Ventricular Reconstruction in Heart Failure Patients With Prior Anterior Myocardial Infarction
Authors: Jerry D Estep, Ori Ben-Yehuda, Andrew S Wechsler, Rishi Puri, Andrew A Kao, Jessica K Heimes, Michael P Pfeiffer, John P Boehmer, Vlasis Ninios, Azfar Zaman, Gregg W Stone
Journal: JACC Heart Failure (2025)
Molecular Stratification of Light-Chain Cardiac Amyloidosis With 18F-Florbetapir and 68Ga-FAPI-04 for Enhanced Prognostic Precision
Authors: Xuezhu Wang, Kaini Shen, Yuke Zhang, Yajuan Gao, Bowei Liu, Yubo Guo, Chao Ren, Zhenghai Huang, Xiao Li, Long Chang, Haiyan Ding, Hui Zhang, Zhuang Tian, Marcus Hacker, Shuyang Zhang, Yining Wang, Jian Li, Xiang Li, Li Huo
Journal: JACC. Cardiovascular imaging (2025)
Biophysical mapping of TREM2-ligand interactions reveals shared surfaces for engagement of multiple Alzheimer’s disease ligands
Authors: Jessica A. Greven, Joshua R. Wydra, Rory A. Greer, Cynthia Zhi, David A. Price, Jordyn D. Svoboda, Christopher L. M. Camitta, Mya Washington, Daisy W. Leung, Yuhua Song, Jen Alexander-Brett, Tom J. Brett
Journal: Molecular Neurodegeneration (2025)

Abstract TREM2 is a signaling receptor expressed on microglia that has emerged as an important drug target for Alzheimer’s disease and other neurodegenerative diseases. While a number of TREM2 ligands have been identified, little is known regarding the structural details of how they engage. To better understand this, we created a protein library of 28 different TREM2 variants that could be used to map interactions with various ligands using biolayer interferometry. The variants are located in previously identified putative binding surfaces on TREM2 called the hydrophobic site, basic site, and site 2. We found that mutations to the hydrophobic site ablated binding to apoE4 and TDP-43. Competition binding experiments indicated that apoE4 and oAβ42 share overlapping binding sites on TREM2. In contrast, binding to C1q was disrupted most strongly by mutations to the basic site, including R46, with some mutations to the hydrophobic site also attenuating binding, thus suggesting a broader mediation of binding across the two sites. Supporting this, competition experiments indicated that C1q binding could be blocked by both apoE and oAβ42. TREM2 binding to IL-34 was mediated by the basic site at a surface centering on R76. Competition binding experiments validated the unique site for IL-34, showing little to no competition with either oAβ42 or apoE4. However, competition experiments between C1q and IL34 suggest that the ligands compete for binding at the basic site. Altogether, our results suggest that TREM2 utilizes the hydrophobic site (consisting of CDR1, CDR2, and CDR3) as a common site to engage multiple ligands, and uses distinct basic sites to engage others. Our findings imply that pharmaceutical strategies targeting these surfaces might be effective to modulate TREM2 functions.
A comparison of respiratory event-related electroencephalographic activity in obstructive sleep apnea alone<i>versus</i>co-morbid insomnia and sleep apnea (COMISA)
Authors: Ali Abdulghafoor, Joshua. B. Hicks, AJ Hirsch Allen, Andrew E. Beaudin, Fredric Series, Amrit Singh, Patrick J. Hanly, Ali Azarbarzin, Najib. T. Ayas, Mohammadreza Hajipour
Journal: European Respiratory Journal (2025)

<title>Extract</title> Obstructive Sleep Apnea (OSA) and insomnia are common sleep disorders. OSA is characterized by repetitive collapse of the upper airway during sleep, leading to electroencephalogram (EEG) disruptions [1, 2]. Insomnia is characterized by difficulty falling asleep, staying asleep, or waking up frequently and is commonly associated with a state of hyperarousal, reflected by a significant increase in EEG power during sleep and wakefulness (<italic>e.g.</italic>, beta frequency band) [3]. OSA and insomnia occur together frequently; a systematic review found that 38% of OSA patients across 37 studies met insomnia criteria [4, 5].
Restrictive or Liberal Blood Transfusion in Patients with Myocardial Infarction and CKD
Authors: Jordan B. Strom, Brandon M. Herbert, Marnie Bertolet, Maria M. Brooks, Shahbaz A. Malik, Gilles Lemesle, Mina Madan, Philippe Gabriel Steg, Paul C. Hebert, Jay H. Traverse, Harvey D. White, Caroline Alsweiler, Rajesh Gupta, Luiz Eduardo F. Ritt, Mark A. Menegus, John H. Alexander, Renato D. Lopes, Bernard R. Chaitman, Jeffrey L. Carson
Journal: Journal of the American Society of Nephrology (2025)

Background: Chronic kidney disease (CKD) is associated with higher risk of myocardial infarction and anemia. Among patients with anemia and CKD who experience myocardial infarction, it remains uncertain if a liberal red blood cell transfusion threshold strategy (hemoglobin cutoff [Hgb] &lt; 10 g/dL) is superior to a restrictive transfusion threshold (Hgb 7-8 g/dL) strategy. Methods: Among the 3,504 patients enrolled in the Myocardial Ischemia and Transfusion (MINT) trial with non-missing creatinine, we compared baseline characteristics and 30-day and 6-month outcomes of patients without CKD (N = 1279), CKD with eGFR 30-60 mL/min/1.73 m 2 (N = 999), CKD with eGFR &lt; 30 mL/min/1.73 m 2 (N = 802), and CKD requiring dialysis (N = 415) by assigned transfusion strategy. Results: No statistically significant interactions were observed between CKD stage and assigned transfusion strategy. Among non-dialysis dependent patients with an eGFR &lt; 30 mL/min/1.73 m 2 , a restrictive transfusion strategy was associated with a higher risk of 30-day death or recurrent myocardial infarction (risk difference [RD], 5.8%, 95% CI 0.4% to 11.2%) compared to a liberal transfusion strategy. Among patients with an eGFR 30-60 mL/min/1.73 m 2 , a restrictive strategy was associated with a similar risk of 30-day death or recurrent myocardial infarction (RD, 3.7%, 95% CI -0.9% to 8.2%) compared to a liberal transfusion strategy. Among patients with CKD requiring dialysis, a restrictive strategy was also associated with a similar risk of 30-day death or recurrent myocardial infarction (RD, -2.6%, 95% CI -10.0% to 4.8%) compared to a liberal transfusion strategy. Conclusions: In patients with CKD included in this MINT subgroup analysis, a liberal transfusion strategy was not worse than a restrictive transfusion strategy and was associated with less harm in subgroups not receiving dialysis.