tbuckley/cabot-search huggingface dataset:
Increased Uptake of 68Ga-DOTA-IBA in Lung NUT Carcinoma
Authors: Na Zhang, Linwei Li, Huipan Liu, Tingting Xu, Yue Chen
Journal: Clinical Nuclear Medicine (2025)

Nuclear protein in testis gene rearrangement-associated midline carcinoma (NUT carcinoma) is a rare and highly invasive tumor. Here, we are reporting the image findings of a 38-year-old woman with lung NUT carcinoma. To evaluate the bone metastases, she underwent 68 Ga-labeled DOTA-ibandronic acid ( 68 Ga-DOTA-IBA) PET/CT examination. Surprisingly, the patient’s lung primary focus and subcutaneous nodule on the left side of the lower back region showed increased uptake.
PSMA PET/CT in Detecting Esophageal Cancer and Hepatocellular Carcinoma. A Report of Two Cases
Authors: Rami Chatta, Hina Shah, Saurabh Pallod
Journal: Clinical Nuclear Medicine (2025)

Prostate-specific membrane antigen (PSMA) PET/CT has improved the diagnosis, staging, and detection of recurrent and metastatic prostate cancer. Nevertheless, PSMA uptake has also been observed in non-prostatic conditions, which underscores the need to explore its broader applications and refine our understanding of its specificity in diverse clinical contexts. In cases of uptake in atypical locations, further workup is warranted to avoid premature conclusions of metastatic prostate disease. We report two cases of PSMA PET uptake: the first involves esophageal cancer, and the second details two synchronous malignancies-hepatocellular and esophageal cancer.
<i>E. coli</i> genetically modified for purine nucleobase release promotes butyrate generation and colonic wound healing during DSS insult
Authors: J. Scott Lee, Daniel J. Kao, Corey S. Worledge, Zachary F. Villamaria, Ruth X. Wang, Nichole M. Welch, Rachael E. Kostelecky, Sean P. Colgan
Journal: Gut Microbes (2025)

The gut microbiota transforms energy stored as undigestible carbohydrates into a remarkable number of metabolites that fuel intestinal bacterial communities and the host tissue. Colonic epithelial cells at the microbiota-host interface depend upon such microbiota-derived metabolites (MDMs) to satisfy their energy requisite. Microbial dysbiosis eliciting MDM loss contributes to barrier dysfunction and mucosal disease. Recent work has identified a role for microbiota-sourced purines (MSPs), notably hypoxanthine, as an MDM salvaged by the colonic epithelium for nucleotide biogenesis and energy balance. Here, we investigated the role of MSPs in mice during disease-modeled colonic energetic stress using a strain of E. coli genetically modified for enhanced purine nucleobase release (E. coli Mutant). E. coli Mutant colonization protected against DSS-induced tissue damage and permeability while promoting proliferation for wound healing. Metabolite and metagenomic analyses suggested a colonic butyrate-purine nucleobase metabolic axis, wherein the E. coli Mutant provided purine substrate for Clostridia butyrate production and host purine salvage, altogether supplying the host substrate for efficient nucleotide biogenesis and energy balance.
Novel PD-1-targeted, activity-optimized IL-15 mutein SOT201 acting in cis provides antitumor activity superior to PD1-IL2v
Authors: Hana Matuskova, Pavel Marasek, Vladyslav Mazhara, Ekaterina Simonova, Lucie Kosinova, Petr Danek, Klara Danova, Katerina Sajnerova, Iva Malatova, Klara Hrabankova, Denise Greco, Ondrej Martinec, Matej Fabisik, Nada Podzimkova, Kamila Hladikova, Katerina Behalova, Zuzana Antosova, Milada Sirova, Romana Mikyskova, Milan Reinis, Marek Kovar, David Béchard, Ulrich Moebius, Lenka Palova Jelinkova, Radek Spisek, Martin Steegmaier, Irena Adkins
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background SOT201 and its murine surrogate mSOT201 are novel cis-acting immunocytokines consisting of a humanized/murinized/, Fc-silenced anti-programmed cell death protein 1 (PD-1) monoclonal antibody (mAb) fused to an attenuated human interleukin (IL)-15 and the IL-15Rα sushi+ domain. Murine mPD1-IL2v is a conjugate of a murinized, Fc silenced anti-PD-1 mAb bearing human IL-2 with abolished IL-2Rα binding. These immunocytokines spatiotemporally reinvigorate PD-1 + CD8 + tumor-infiltrating lymphocytes (TILs) via cis-activation and concomitantly activate the innate immunity via IL-2/15Rβγ signaling. Methods Human peripheral blood mononuclear cell and cell lines were used to evaluate cis/trans activity of SOT201. Anti-PD-1 mAb responsive (MC38, CT26) and resistant (B16F10, CT26 STK11 KO) mouse tumor models were used to determine the anticancer efficacy, and the underlying immune cell activity was analyzed via single-cell RNA sequencing and flow cytometry. The expansion of tumor antigen-specific CD8 + T cells by mSOT201 or mPD1-IL2v and memory CD8 + T-cell generation in vivo was determined by flow cytometry. Results SOT201 delivers attenuated IL-15 to PD-1 + T cells via cis-presentation, reinvigorates exhausted human T cells and induces higher interferon-γ production than pembrolizumab in vitro. mSOT201 administered as a single dose exhibits strong antitumor efficacy with several complete responses in all tested mouse tumor models. While mPD1-IL2v activates CD8 + T cells with a 50-fold higher potency than mSOT201 in vitro, mSOT201 more effectively reactivates effector exhausted CD8 + T cells (Tex), which demonstrate higher cytotoxicity, lower exhaustion and lower immune checkpoint transcriptional signatures in comparison to mPD1-IL2v in MC38 tumors in vivo. This can be correlated with a higher rate of complete responses in the MC38 tumor model following mSOT201 treatment when compared with mPD1-IL2v. mSOT201 increased the relative number of tumor antigen-specific CD8 + T cells, and unlike mPD1-IL2v stimulated greater expansion of adoptively transferred ovalbumin-primed CD8 + T cells simultaneously limiting the peripheral CD8 + T-cell sink, leading to the development of memory CD8 + T cells in vivo. Conclusions SOT201 represents a promising therapeutic candidate that preferentially targets PD-1 + TILs, delivering balanced cytokine activity for reviving CD8 + Tex cells in tumors. SOT201 is currently being evaluated in the Phase I clinical study VICTORIA-01 ( NCT06163391 ) in patients with advanced metastatic cancer.
Modeling Stromal Cells Inside the Tumor Microenvironment of Ovarian Cancer: In Vitro Generation of Cancer‐Associated Fibroblast‐Like Cells and Their Impact in a 3D Model
Authors: Jacopo Romoli, Paola Chiodelli, Patrizia Bonassi Signoroni, Elsa Vertua, Clarissa Ferrari, Elisabetta Giuzzi, Alice Paini, Elisa Scalvini, Andrea Papait, Francesca Romana Stefani, Antonietta Rosa Silini, Ornella Parolini
Journal: MedComm (2025)

ABSTRACT The tumor microenvironment (TME) is the combination of cells and factors that promotes tumor progression, and cancer‐associated fibroblasts (CAFs) are a key component within TME. CAF originates from various stromal cells and is activated by factors such as transforming growth factor‐beta (TGF‐β) secreted by tumor cells, favoring chemoresistance and metastasis. Recent publications have underlined plasticity and heterogeneity and their strong contribution to the reactive stroma within the TME. Our study aimed to replicate the TME's structure by creating a 3D in vitro model of ovarian cancer (OC). By incorporating diverse tumor and stromal cells, we simulated a physiologically relevant environment for studying CAF‐like cell behavior within tumor spheroids in a context‐dependent manner. CAF‐like cells were generated by exposing human dermal fibroblasts to OC cell line conditioned media in the presence or absence of TGF‐β. Herein, we found that different stimuli induce the generation of heterogeneous populations of CAF‐like cells. Notably, we observed the ability of CAF‐like cells to shape the intratumoral architecture and to contribute to functional changes in tumor cell behavior. This study highlights the importance of precise assessment of CAF for potential therapeutic interventions and further provides a reliable model for investigating novel therapeutic targets in OC.
Tiny trouble: microplastics, nanoplastics, and their heartfelt impact on cardiovascular health
Authors: Tongyao Zhang, Yajie Liao, Jitao Ling, Jing Zhang, Deju Zhang, Xiaoping Yin, Peng Yu, Xiao Liu
Journal: Cardiovascular Research (2025)

Abstract Microplastics and nanoplastics are ubiquitous environmental pollutants that pose significant health risks. Several studies have reported the presence of these particles in various human tissues, including the heart, arterial plaques, and bloodstream of patients undergoing percutaneous coronary interventions. Emerging research suggests an association between these particles and an increased risk of cardiovascular diseases. In vitro and in vivo studies reveal that micro- and nanoplastics induce endothelial cell toxicity, disrupt lipid metabolism, promote oxidative stress, and facilitate foam cell formation, thereby exacerbating atherosclerosis. Furthermore, they activate inflammatory pathways, compromising vascular barrier integrity. These particles also influence coagulation dynamics by altering clotting cascade activation and promoting thrombus formation. Additionally, they induce hemolysis, alter red blood cell morphology, and impair immune cell functions, including those of macrophages and lymphocytes, by modulating cytokine secretion and inflammatory responses. Understanding these mechanisms is essential for devising effective public health strategies to mitigate the cardiovascular impact of micro- and nanoplastics.
ERCnet: phylogenomic prediction of interaction networks in the presence of gene duplication
Authors: Evan S Forsythe, Tony C Gatts, Linnea E Lane, Chris deRoux, Monica Berggren, Elizabeth A Rehmann, Emily N Zak, Trinity Bartel, Luna L’Argent, Daniel B Sloan
Journal: Molecular Biology and Evolution (2025)

Abstract Assigning gene function from genome sequences is a rate-limiting step in molecular biology research. A protein’s position within an interaction network can potentially provide insights into its molecular mechanisms. Phylogenetic analysis of evolutionary rate covariation (ERC) in protein sequence has been shown to be effective for large-scale prediction of functional relationships and interactions. However, gene duplication, gene loss, and other sources of phylogenetic incongruence are barriers for analyzing ERC on a genome-wide basis. Here, we developed ERCnet, a bioinformatic program designed to overcome these challenges, facilitating efficient all-vs-all ERC analyses for large protein sequence datasets. We simulated proteome datasets and found that ERCnet achieves combined false positive and negative error rates well below 10% and that our novel ‘branch-by-branch’ length measurements outperforms ‘root-to-tip’ approaches in most cases, offering a valuable new strategy for performing ERC. We also compiled a sample set of 35 angiosperm genomes to test the performance of ERCnet on empirical data, including its sensitivity to user-defined analysis parameters such as input dataset size and branch-length measurement strategy. We investigated the overlap between ERCnet runs with different species samples to understand how species number and composition affect predicted interactions and to identify the protein sets that consistently exhibit ERC across angiosperms. Our systematic exploration of the performance of ERCnet provides a roadmap for design of future ERC analyses to predict functional interactions in a wide array of genomic datasets. ERCnet code is freely available at https://github.com/EvanForsythe/ERCnet.
Genetic differentiation is constrained to chromosomal inversions and putative centromeres in locally adapted populations with higher gene flow
Authors: Maria Akopyan, Anna Tigano, Arne Jacobs, Aryn P Wilder, Nina O Therkildsen
Journal: Molecular Biology and Evolution (2025)

Abstract The impact of genome structure on adaptation is a growing focus in evolutionary biology, revealing an important role for structural variation and recombination landscapes in shaping genetic diversity across genomes and among populations. This is particularly relevant when local adaptation occurs despite gene flow, where clustering of differentiated loci can maintain locally adapted variants by reducing recombination between them. However, the limited genomic resources for non-model species, including reference genomes and recombination maps, have constrained our understanding of these patterns. In this study, we leverage the Atlantic silverside—a non-model fish with extensive local adaptation across a steep latitudinal gradient—as an ideal system to explore how genome structure influences adaptation under varying levels of gene flow, using a newly available reference genome and multiple recombination maps. Analyzing 168 genomes from four populations, we found a continuum of genome-wide differentiation increasing from south to north, reflecting higher connectivity among southern populations and reduced gene flow at northern latitudes. With increasing gene flow, the number and clustering of FST outlier loci also increased, with differentiated loci found exclusively within large haploblocks harboring inversions and smaller peaks overlapping putative centromeric regions. Notably, sequence divergence was only evident in inversions, supporting their role in adaptive divergence with gene flow, whereas centromeric regions appeared differentiated because of low recombination and diversity, with no indication of elevated divergence. Our results support the hypothesis that clustered genomic architectures evolve with high gene flow and enhance our understanding of how inversions and centromeres are linked to different evolutionary processes.
World of forms: Deformable geometric templates for one-shot surface meshing in coronary CT angiography
Authors: Rudolf L M van Herten, Ioannis Lagogiannis, Jelmer M Wolterink, Steffen Bruns, Eva R Meulendijks, Damini Dey, Joris R de Groot, José P Henriques, R Nils Planken, Simone Saitta, Ivana Išgum
Journal: Medical Image Analysis (2025)
Gut Microbiota Dysbiosis: Pathogenesis, Diseases, Prevention, and Therapy
Authors: Yao Shen, Nairui Fan, Shu‐xia Ma, Xin Cheng, Xuesong Yang, Guang Wang
Journal: MedComm (2025)

ABSTRACT Dysbiosis refers to the disruption of the gut microbiota balance and is the pathological basis of various diseases. The main pathogenic mechanisms include impaired intestinal mucosal barrier function, inflammation activation, immune dysregulation, and metabolic abnormalities. These mechanisms involve dysfunctions in the gut–brain axis, gut–liver axis, and others to cause broader effects. Although the association between diseases caused by dysbiosis has been extensively studied, many questions remain regarding the specific pathogenic mechanisms and treatment strategies. This review begins by examining the causes of gut microbiota dysbiosis and summarizes the potential mechanisms of representative diseases caused by microbiota imbalance. It integrates clinical evidence to explore preventive and therapeutic strategies targeting gut microbiota dysregulation, emphasizing the importance of understanding gut microbiota dysbiosis. Finally, we summarized the development of artificial intelligence (AI) in the gut microbiota research and suggested that it will play a critical role in future studies on gut dysbiosis. The research combining multiomics technologies and AI will further uncover the complex mechanisms of gut microbiota dysbiosis. It will drive the development of personalized treatment strategies.
The Case | A patient with multiple myeloma, heart failure, and nonresolving acute kidney injury
Authors: Míriam Montero-Estopiñá, Desirée Catalán-García, Eduardo Cortés, Valentina M Blanco-Fernández, Jordi Soler-Majoral, Gladys Ibarra Fernandez, Néstor Rodríguez-Chitiva, Javier Paúl-Martínez, Fredzzia Graterol Torres, Jordi Bover, Jordi Ara, Abhilash Koratala, Eduardo R Argaiz, Faeq Husain-Syed, Gregorio Romero-González
Journal: Kidney International (2025)
Safety and feasibility of 4-1BB co-stimulated CD19-specific CAR-NK cell therapy in refractory/relapsed large B cell lymphoma: a phase 1 trial
Authors: Wen Lei, Hui Liu, Wenhai Deng, Wei Chen, Yun Liang, Wenxia Gao, Xianggui Yuan, Shanshan Guo, Ping Li, Jinyong Wang, Xiangmin Tong, Yi Eve Sun, Aibin Liang, Wenbin Qian
Journal: Nature Cancer (2025)

Abstract Chimeric antigen receptor (CAR)-modified NK (CAR-NK) cells are candidates for next-generation cancer immunotherapies. Here we generated CD19-specific CAR-NK cells with 4-1BB and CD3ζ signaling endo-domains (CD19-BBz CAR-NK) by transduction of cord blood-derived NK cells using baboon envelope pseudotyped lentiviral vectors and demonstrated their antitumor activity in preclinical B cell lymphoma models in female mice. We next conducted a phase 1 dose-escalation trial involving repetitive administration of CAR-NK cells in 8 patients with relapsed/refractory large B cell lymphoma (NCT05472558). Primary end points were safety, maximum tolerated dose, and overall response rate. Secondary end points included duration of response, overall survival, and progression-free survival. No dose-limiting toxicities occurred, and the maximum tolerated dose was not reached. No cases of cytokine release syndrome, neurotoxicity, or graft-versus-host disease were observed. Results showed an overall response rate of 62.5% at day 30, with 4 patients (50%) achieving complete response. The median progression-free survival was 9.5 months, and the median overall survival was not reached. A post hoc exploratory single-cell RNA sequencing analysis revealed molecular features of CAR-NK cells associated with therapeutic efficacy and efficacy-related immune cell interaction networks. This study met the pre-specified end points. In conclusion, CD19-BBz CAR-NK cells were feasible and therapeutically safe, capable of inducing durable response in patients with B cell lymphoma.
Association between plausible genetic factors and weight loss from GLP1-RA and bariatric surgery
Authors: Jakob German, Mattia Cordioli, Veronica Tozzo, Sarah Urbut, Kadri Arumäe, Roelof A J Smit, Jiwoo Lee, Josephine H Li, Adrian Janucik, Yi Ding, Akintunde Akinkuolie, Henrike O Heyne, Andrea Eoli, Chadi Saad, Yasser Al-Sarraj, Rania Abdel-Latif, Shaban Mohammed, Moza Al Hail, Alexandra Barry, Zhe Wang, Tatiana Cajuso, Andrea Corbetta, Pradeep Natarajan, Samuli Ripatti, Anthony Philippakis, Lukasz Szczerbinski, Bogdan Pasaniuc, Zoltán Kutalik, Hamdi Mbarek, Ruth J F Loos, Uku Vainik, Andrea Ganna
Journal: Nature Medicine (2025)

Abstract Obesity is a major public health challenge. Glucagon-like peptide-1 receptor agonists (GLP1-RA) and bariatric surgery (BS) are effective weight loss interventions; however, the genetic factors influencing treatment response remain largely unexplored. Moreover, most previous studies have focused on race and ethnicity rather than genetic ancestry. Here we analyzed 10,960 individuals from 9 multiancestry biobank studies across 6 countries to assess the impact of known genetic factors on weight loss. Between 6 and 12 months, GLP1-RA users had an average weight change of −3.93% or −6.00%, depending on the outcome definition, with modest ancestry-based differences. BS patients experienced −21.17% weight change between 6 and 48 months. We found no significant associations between GLP1-RA-induced weight loss and polygenic scores for body mass index or type 2 diabetes, nor with missense variants in GLP1R . A higher body mass index polygenic score was modestly linked to lower weight loss after BS (+0.7% per s.d., P = 1.24 × 10 −4 ), but the effect attenuated in sensitivity analyses. Our findings suggest known genetic factors have limited impact on GLP1-RA effectiveness with respect to weight change and confirm treatment efficacy across ancestry groups.
High-resolution prosthetic hearing with a soft auditory brainstem implant in macaques
Authors: Alix Trouillet, Emilie Revol, Florent-Valéry Coen, Florian Fallegger, Aurélie Chanthany, Maude Delacombaz, Laurine Kolly, Ivan Furfaro, Florian Lanz, Vivek Kanumuri, Victor Adenis, Alejandro Garcia-Chavez, M Christian Brown, Lukas Anschuetz, Jocelyne Bloch, Daniel J Lee, Stéphanie P Lacour
Journal: Nature Biomedical Engineering (2025)

Abstract Individuals with compromised cochlear nerves are ineligible for cochlear implants and instead rely on auditory brainstem implants (ABIs). Most users of ABIs experience sound awareness, which aids in lip reading, yet not speech intelligibility. Here we engineered a dual-site (brainstem and cortex) implantable system, scaled to macaque anatomy, for the analysis of auditory perception evoked by electrical stimulation of the cochlear nucleus. A soft multichannel ABI, fabricated using thin-film processing, provided high-resolution auditory percepts, with spatially distinct stimulation sites eliciting cortical responses akin to frequency-specific tuning. Behavioural responses collected over several months were sufficiently precise to distinguish stimulations from adjacent channels. Soft multichannel ABIs may aid the rehabilitation of individuals with profound hearing loss who are ineligible for cochlear implants.
UnitedMet harnesses RNA–metabolite covariation to impute metabolite levels in clinical samples
Authors: Amy X Xie, Wesley Tansey, Ed Reznik
Journal: Nature Cancer (2025)

Comprehensively studying metabolism requires metabolite measurements. Such measurements, however, are often unavailable in large cohorts of tissue samples. To address this basic barrier, we propose a Bayesian framework ('UnitedMet') that leverages RNA-metabolite covariation to impute otherwise unmeasured metabolite levels from widely available transcriptomic data. UnitedMet is equally capable of imputing whole pool sizes and outcomes of isotope tracing experiments. We apply UnitedMet to investigate the metabolic impact of driver mutations in kidney cancer, identifying an association between BAP1 and a highly oxidative tumor phenotype. We similarly apply UnitedMet to determine that advanced kidney cancers upregulate oxidative phosphorylation relative to early-stage disease, that oxidative metabolism in kidney cancer is associated with inferior outcomes to anti-angiogenic therapy and that kidney cancer metastases demonstrate elevated oxidative phosphorylation. UnitedMet provides a scalable tool for assessing metabolic phenotypes when direct measurements are infeasible, facilitating unexplored avenues for metabolite-focused hypothesis generation.
Systemic inflammation impairs myelopoiesis and interferon type I responses in humans
Authors: Farid Keramati, Guus P Leijte, Niklas Bruse, Inge Grondman, Ehsan Habibi, Cristian Ruiz-Moreno, Wout Megchelenbrink, Annemieke M Peters van Ton, Hidde Heesakkers, Manita E Bremmers, Erinke van Grinsven, Kiki Tesselaar, Selma van Staveren, Walter J van der Velden, Frank W Preijers, Brigit Te Pas, Raoul van de Loop, Jelle Gerretsen, Mihai G Netea, Hendrik G Stunnenberg, Peter Pickkers, Matthijs Kox
Journal: Nature Immunology (2025)

Abstract Systemic inflammatory conditions are classically characterized by an acute hyperinflammatory phase, followed by a late immunosuppressive phase that elevates the susceptibility to secondary infections. Comprehensive mechanistic understanding of these phases is largely lacking. To address this gap, we leveraged a controlled, human in vivo model of lipopolysaccharide (LPS)-induced systemic inflammation encompassing both phases. Single-cell RNA sequencing during the acute hyperinflammatory phase identified an inflammatory CD163 + SLC39A8 + CALR + monocyte-like subset (infMono) at 4 h post-LPS administration. The late immunosuppressive phase was characterized by diminished expression of type I interferon (IFN)-responsive genes in monocytes, impaired myelopoiesis and a pronounced attenuation of the immune response on a secondary LPS challenge 1 week after the first. The infMono gene program and impaired myelopoiesis were also detected in patient cohorts with bacterial sepsis and coronavirus disease. IFNβ treatment restored type-I IFN responses and proinflammatory cytokine production and induced monocyte maturation, suggesting a potential treatment option for immunosuppression.