tbuckley/cabot-search huggingface dataset:
Transforming Cancer Therapy: Unlocking the Potential of Targeting Vascular and Stromal Cells in the Tumor Microenvironment
Authors: Lu Liu, Yuheng Zhang, Hanyu Liu, Jian Yang, Qi Tian, Nareekarn Chueakula, Saravana Ramasamy, Navin Kumar Verma, Christine Cheung, Anjali P. Kusumbe
Journal: Cancer Research (2025)

Abstract The tumor microenvironment (TME) orchestrates cancer progression by fostering a complex interplay between cancer cells and the surrounding cellular and acellular elements. Through dynamic interactions with cancer cells, vascular and stromal cells not only promote tumor growth but also enhance metastatic potential and restrict therapeutic responses. Vascular and stromal cells play a critical role in regulating epithelial-mesenchymal transition (EMT) and sustaining resistance pathways, making them compelling targets for innovative therapies. This review delves into the vascular and stromal components of the TME, their contributions to EMT and resistance mechanisms, and emerging strategies to target these interactions for improved cancer therapy outcomes.
Oscillometry-defined Small Airway Dysfunction in Tobacco-exposed Adults with Impaired or Preserved Airflow
Authors: Mustafa Abdo, Henrik Watz, Frederik Trinkmann, Sabine Bohnet, Miriam Annabella Marcella Guess, Johannes Roeben, Katharina May, Martin Reck, Benjamin-Alexander Bollmann, Susanne Stiebeler, Sabine Dettmer, Benjamin Waschki, Klaus F. Rabe, Klaas Frederik Franzen, Jens Vogel-Claussen
Journal: American Journal of Respiratory and Critical Care Medicine (2025)

Small airway dysfunction (SAD) is a key feature of COPD and might present in tobacco-exposed adults with normal spirometry. So far, the role of oscillometry-defined SAD in this population is largely unexplored. To investigate the prevalence of oscillometry-defined SAD and its associations with airway structural changes, quality of life (QoL), metabolic and cardiovascular disease (CVD) in tobacco-exposed adults with impaired or preserved airflow. In a sub-cohort (n=1628) nested within a lung cancer screening trial, we assessed airway disease using preBD-spirometry, oscillometry, and AI-powered CT. Impaired airflow included airflow obstruction (AFO) and preserved ratio impaired spirometry (PRISm). Subjects with preserved airflow (PA), defined as FEV1 and FEV1/FVC > LLN, were further stratified as PA with SAD (PA-SAD) or normal lung function. SAD was defined as the frequency dependence of resistance (R5-19) or reactance area (AX) > ULN. CT biomarkers included airway wall thickness (AWT-Pi10), lumen diameter, branch count, and emphysema. QoL was measured using the EQ-5D-5L. The overall prevalence of SAD was 39%. SAD was present in 26% of subjects with PA and in 60% of those with impaired airflow. The frequency of AFO, PRISm and PA-SAD was 21%, 15% and 16%, respectively. Similar to impaired airflow, subjects with PA-SAD had lower EQ-5D-5L score, greater AWT-Pi10, narrower lumen, lower branch count, and higher rate of metabolic and CVD than those with normal lung function, (all p-values <0.01). However, they had minimal emphysema and significantly higher branch count than those with AFO. Subjects with AFO or PRISm and concurrent SAD had greater structural changes and more frequent CVD than those with AFO or PRISm alone. SAD was associated with CVD, OR: 1.91 (95% CI: 1.55 - 2.36), even after adjusting for confounders and metabolic disease. SAD is highly prevalent among tobacco-exposed adults and is associated with airway structural changes, impaired QoL, and increased rate of CVD, even in those with PA. PA-SAD is distinct from AFO by its preserved airway count and minimal emphysema. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Global, Regional, and National Burden of Pulmonary Fungal Infections 1990-2021
Authors: Ying Xia, Weiwei Jiang, Xinlin Zhu, Bo Pan, Tianyang Chen, Yan Wang, Wanqing Liao, Weihua Pan
Journal: American Journal of Respiratory and Critical Care Medicine (2025)

Rationale: The lungs are the most prevalent site for invasive fungal infections, and the diagnosis and treatment of pulmonary fungal infections pose significant challenges, accompanied by a substantial disease burden. Global factors will likely enhance the risk of it in the future. Assessing the global burden of pulmonary fungal infections is crucial for implementing appropriate measures for prevention and control. Objectives: To evaluate the burden of pulmonary fungal infections at the global, regional, and national levels from 1990 to 2021 and make projections for 2024. Methods: Data on deaths and Disability-Adjusted Life Years due to pulmonary fungal infections were extracted from the Global Burden of Disease database. Linear regression, complex inequality measures, and the Nordpred model were employed for analysis and visualization. Results: In 2021, the global incidence of pulmonary fungal infections was estimated at 5.62 million cases (95% Uncertainty Interval [UI] 4.93-6.40 million), with 45,542 deaths (95% UI 39,299-51,944). The age-standardized mortality rate was 0.56 per 100,000 (95% UI 0.48-0.64). From 1990 to 2021, the estimated annual percentage change was -1.03% (95% Confidence Interval [CI]: -1.13 to -0.93), with an observed increase in mortality rates in low- and middle-income countries. The mortality rate significantly increased among individuals aged 50 and above. By 2044, over 87,000 deaths are expected from pulmonary fungal infections, at a rate of about 0.58 per 100,000. Conclusions: Pulmonary fungal infections represent a significant global challenge that warrants attention and necessitates international collaboration to collectively address this issue. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Predatory journals: What can we do to protect their prey?
Authors: Christine Laine, Dianne Babski, Vivienne C Bachelet, Till W Bärnighausen, Christopher Baethge, Kirsten Bibbins-Domingo, Frank Frizelle, Laragh Gollogly, Sabine Kleinert, Elizabeth Loder, João Monteiro, Eric J Rubin, Peush Sahni, Christina C Wee, Jin-Hong Yoo, Lilia Zakhama
Journal: PLoS Medicine (2025)

In this Editorial, representatives of the International Committee of Medical Editors discuss the need for multi-stakeholder involvement to recognize and counter the actions of predatory journals.
“Snake in the Scrotum Sign”: Reappraising the Potential of 18F-FDG PET/CT in Post–Renal Transplant Patient with Pyrexia of Unknown Origin
Authors: Srinivas Ananth Kumar, Madhur Kumar Srivastava, Gangadhar Tanduri
Journal: Clinical Nuclear Medicine (2025)

18 F-FDG PET/CT, the workhorse of oncological imaging has changed the diagnostic and management paradigm in cases of fever and inflammation of unknown origin, with diagnostic superiority over the conventional imaging modalities. Various complications like acute and chronic graft pyelonephritis, acute rejection, infections, and surgery-related complications can occur post-renal transplantation. The authors in the present study demonstrate coexisting graft pyelonephritis, prostatitis, epididymo-orchitis, and funiculitis on 18 F-FDG PET/CT in a patient, post renal transplant with clinical presentation as pyrexia of unknown origin.
[68Ga]Ga-FAPI-46 PET/MRT Unveils Lymph Node Metastases and Changes Treatment Strategy in Recurrent Advanced High-grade Serous Ovarian Carcinoma Patient
Authors: Marie Prochiner, Anna Hinterberger, Björn Wängler, Frederik Marmé, Freba Grawe
Journal: Clinical Nuclear Medicine (2025)

High-grade serous ovarian carcinoma (HGOC) is frequently diagnosed at an advanced stage, leading to high recurrence rates. This case report highlights the utility of [ 68 Ga]Ga-FAPI-46 PET/MRI in detecting previously unidentified lymph node metastases in a 75-year-old woman with recurrent HGOC, which altered the treatment strategy. The imaging revealed increased [ 68 Ga]Ga-FAPI-46 uptake in nonenlarged mediastinal and left perihilar lymph nodes, reclassifying the patient from FIGO IIIb to FIGO stage IV and prompting a change in therapeutic management.
Invasive Lobular Carcinoma of the Breast With Solid Renal Metastasis on 18F-FDG PET/CT
Authors: Guney Deniz, Dilara Denizmen Zorba, Zeynep Gozde Ozkan, Serkan Kuyumcu, Yasemin Sanli
Journal: Clinical Nuclear Medicine (2025)

Herein we present a case with recurrent invasive lobular carcinoma of the breast with solid renal metastasis detected on 18 F-FDG PET/CT. Invasive lobular carcinoma constitutes ∼5%–15% of all invasive breast cancers and is the second most common type of breast cancer. 18 F-FDG PET/CT is routinely used for staging and restaging invasive lobular carcinoma of the breast. Although distant solid organ metastasis is common, renal metastasis remains an exceptionally rare occurrence in ILC. This case highlights the importance of considering renal involvement in the metastatic spread of invasive lobular carcinoma, especially when using 18 F-FDG PET/CT.
AI differentiates radionecrosis from true progression in brain metastasis upon stereotactic radiosurgery: analysis of 124 histologically assessed lesions
Authors: Gaia Ressa, Riccardo Levi, Giovanni Savini, Luca Raspagliesi, Elena Clerici, Luisa Bellu, Luca A Cappellini, Marco Grimaldi, Saverio Pancetti, Beatrice Bono, Andrea Franzini, Marco Riva, Bethania Fernandez, Maximilian Niyazi, Federico Pessina, Giuseppe Minniti, Pierina Navarria, Marta Scorsetti, Letterio S Politi
Journal: Neuro-Oncology (2025)

Abstract Background Differentiating radionecrosis from neoplastic progression after stereotactic radiosurgery (SRS) for brain metastases is a diagnostic challenge. Previous studies have often been limited by datasets lacking histologically confirmed diagnoses. This study aimed to develop automated models for distinguishing radionecrosis from disease progression on brain MRI, utilizing cases with definitive histopathological confirmation. Methods This multi-center retrospective study included patients who underwent surgical resection for suspected brain metastasis progression after SRS. Presurgical FLAIR and post-contrast T1 (T1w-ce) were segmented using a convolutional neural network (CNN) and compared with manual segmentation by means of Dice score. Radiomics features were extracted from each lesion, and a Random Forest model was trained on 70% of the internal dataset and evaluated on the remaining 30% and the complete external dataset. A 3DResNet-CNN was trained on the same split dataset. Validation was performed on the external dataset. Post-surgical histology was available for all cases. Results 124 brain metastases were included (104 from center 1 and 20 from center 2). Sole radionecrosis was histologically detected in 34 cases (27.4%). In the internal dataset, univariate and multivariate analysis identified 131 significantly different radiomics features, including GLDM_DNUN and GLDM_SDE within the enhancing area on the T1w-ce. On the external test dataset, the Random Forest model and the 3DResNet-CNN yielded accurate results in terms of accuracy (80.0%, 85.0%), AUROC (0.830, 0.893) and sensitivity (92.8%, 100%) in radionecrosis prediction, respectively. Conclusion Artificial intelligence could be employed to differentiate between radionecrosis and brain metastasis progression upon SRS, potentially reducing unnecessary surgical interventions.
Evolutionary process underlying receptor gene expansion and cellular divergence of olfactory sensory neurons in honeybees
Authors: Weixing Zhang, Yage Nie, Tao Xu, Yiheng Li, Yicong Xu, Xiaoyong Chen, Peiyu Shi, Fang Liu, Hongxia Zhao, Qing Ma, Jin Xu
Journal: Molecular Biology and Evolution (2025)

Abstract Olfaction is crucial for animals’ survival and adaptation. Unlike the strict singular expression of odorant receptor (OR) genes in vertebrate olfactory sensory neurons (OSNs), insects exhibit complex OR gene expression patterns. In honeybee (Apis mellifera), a significant expansion of OR genes implies a selection preference for the olfactory demands of social insects. However, the mechanisms underlying receptor expression specificity and their contribution to OSN divergence remain unclear. In this study, we used single-nucleus multi-omics profiling to investigate the transcriptional regulation of OR genes and the cellular identity of OSNs in A. mellifera. We identified three distinct OR expression patterns, singular OR expression, co-expression of multiple OR genes with a single active promoter, and co-expression of multiple OR genes with multiple active promoters. Notably, ∼50% of OSNs co-expressed multiple OR genes, driven by polycistronic transcription of tandemly duplicated OR genes via a single active promoter. In these OSNs, their identity was determined by the first transcribed receptor. The divergent activation of the promoter for duplicated OR genes ensure the coordinate increased divergence of OSN population. By integrating multi-omics data with genomic architecture, we illustrate how fundamental genetic mechanisms drive OR gene expansion and influence flanking regulatory elements, ultimately contributing to the cellular divergence of OSNs. Our findings highlight the interplay between gene duplication and regulatory evolution in shaping OSN diversity, providing new insights into the evolution and adaptation of olfaction in social insects. This study also sheds light on how genetic innovations contribute to the evolution of complex traits.
Pre-ischaemic empagliflozin treatment attenuates blood–brain barrier disruption via β-catenin mediated protection of cerebral endothelial cells
Authors: Guohao Liu, Yanmei Qiu, Nanlin You, Mengchen Yu, Wenbo Chen, Tao Sun, Zhen Qin, Mengtao Han, Zhiwei Xue, Xiangjun Liang, Bo Mao, Lu Ling, Yanzhao Wu, Wenchen Xing, Quanmeng Liu, Donghai Wang
Journal: Cardiovascular Research (2025)

Abstract Aims Microvascular endothelial cells dysfunction can significantly worsen ischaemic stroke outcomes by disrupting tight junctions and increasing the acquisition of adhesion molecules, accelerating blood–brain barrier (BBB) disruption and pro-inflammatory response. The identification of drugs that improve endothelial cell function may be crucial for ischaemic stroke. It has been validated that empagliflozin (EMPA), a novel antidiabetic drug, protects endothelial cells regardless of the diabetic status of the patient. However, the impact of EMPA on stroke outcomes is unclear. We hypothesized that EMPA would exert a beneficial effect on ischaemic stroke outcome by protecting microvascular endothelial cells against tight junction disruption and the increase of adhesion molecules. Methods and results Young adult male mice were administered with EMPA or vehicle (dimethyl sulfoxide) daily for 7 days before being subjected to transient middle cerebral artery occlusion (tMCAO). Neurological deficits were evaluated for up to 28 days post-tMCAO. Infarct volume, BBB disruption, and inflammatory status were assessed 1 day after tMCAO.bEnd.3 cells and primary brain microvascular endothelial cells were treated with EMPA or vehicle under oxygen and glucose deprivation/reperfusion (OGD/R), and the lactate dehydrogenase release, transendothelial electrical resistance, leakage of fluorescein isothiocyanate-dextran, and tight junction and adhesion molecules proteins were examined. Mechanistic studies probing the effect of EMPA on endothelial cells were conducted by RNA-seq. EMPA treatment before ischaemia markedly improved infarct volume, BBB disruption, and inflammation 1-day post-tMCAO, and further enhanced neurobehavioral function up to 28 days. Pre-treatment of EMPA attenuated endothelial cell dysfunction under OGD/R conditions. In mechanistic terms, RNA-seq data from isolated cerebral microvessels revealed that the Wnt/β-catenin signalling pathway was preserved in the EMPA group, in contrast to the vehicle group. Pre-treatment with EMPA inhibited β-catenin ubiquitination and promoted β-catenin translocation from the cytoplasm to the nucleus to improve endothelial cell function. Importantly, the β-catenin inhibitor XAV-939 eliminated this protective function of EMPA. Conclusion EMPA administration before tMCAO attenuated ischaemia/reperfusion-induced BBB disruption and inflammation via β-catenin-mediated protection of cerebral microvascular endothelial cells. Therefore, EMPA shows potential for improving stroke outcomes as an adjunctive preventive strategy.
The Lancet Commission on rethinking coronary artery disease: moving from ischaemia to atheroma
Authors: Sarah Zaman, Jason H Wasfy, Vikas Kapil, Boback Ziaeian, William A Parsonage, Sira Sriswasdi, Timothy J A Chico, Davide Capodanno, Róisín Colleran, Nadia R Sutton, Lei Song, Nicole Karam, Reecha Sofat, Chiara Fraccaro, Daniel Chamié, Mirvat Alasnag, Takayuki Warisawa, Nieves Gonzalo, Walid Jomaa, Shamir R Mehta, Elizabeth E S Cook, Johan Sundström, Stephen J Nicholls, Leslee J Shaw, Manesh R Patel, Rasha K Al-Lamee
Journal: The Lancet (2025)
Clinically compliant enrichment of human pluripotent stem cell–derived islets
Authors: Bahareh Rajaei, Amadeo Muñoz Garcia, Juri Juksar, Jason B. Doppenberg, Miriam Paz-Barba, Fransje Boot, Willemijn de Vos, Aat A. Mulder, Ferdy Lambregtse, Lizanne Daleman, Anne E. de Leeuw, Maaike C. Nieveen, Marten A. Engelse, Ton Rabelink, Eelco J. P. de Koning, Françoise Carlotti
Journal: Science Translational Medicine (2025)

Human pluripotent stem cell–derived islet (SC-islet) transplantation is a promising β cell replacement therapy for patients with type 1 diabetes, offering a potential unlimited cell supply. Yet, the heterogeneity of the final cell product containing non–target cell types has relevant implications for SC-islet function, transplant volume, and cell product safety. Here, we present a clinically compliant, full three-dimensional differentiation protocol that includes a purification step of endocrine cell–rich clusters, relying on the principle of isopycnic centrifugation (density gradient separation). Enriched SC-islets displayed signs of functionality in vitro and in vivo. In contrast with antibody-based single-cell sorting approaches, this method does not destroy the islet cytoarchitecture associated with alterations of islet function and cell loss. Furthermore, it is fast, is easily scalable to large cell volumes, and can be applied during cell manufacturing. This method may also contribute to the generation of improved cell-based therapies for regenerative medicine purposes beyond the SC-islet field.
Ebola virus vaccination elicits Ebola virus–specific immune responses without substantial cross-reactivity to other filoviruses
Authors: Thembi Mdluli, Suzanne Wollen-Roberts, Mélanie Merbah, Bradley Beckman, Yifan Li, Aljawharah Alrubayyi, Daniel J. Curtis, Zhanna Shubin, Michael D. Barrera, Jacob Boeckelman, Shayla Duncan, Pallavi Thapa, Dohoon Kim, Margaret C. Costanzo, Hongjun Bai, Bethany L. Dearlove, Jay W. Hooper, Steven A. Kwilas, Dominic Paquin-Proulx, Michael A. Eller, Leigh Anne Eller, Hannah Kibuuka, Betty Mwesigwa, Josphat Kosgei, Fredrick Sawe, Janet Oyieko, Nyanda Ntinginya, Joel Mwakisisile, Ilesh Jani, Edna Viegas, Michael Iroezindu, Akindiran Akintunde, Kristopher Paolino, Merlin L. Robb, Lucy Ward, Chelsea McLean, Kerstin Luhn, Cynthia Robinson, Julie A. Ake, Morgane Rolland
Journal: Science Translational Medicine (2025)

The Janssen Ebola virus (EBOV) vaccine consists of the adenovirus type 26 vector encoding the EBOV glycoprotein (GP) (Ad26.ZEBOV) and the modified vaccinia Ankara (MVA) vector encoding GP from EBOV, Sudan virus, and Marburg virus and nucleoprotein from Tai Forest virus (MVA-BN-Filo) administered 8 weeks later. We conducted a systems immunology analysis of antibody-mediated and cellular immune responses induced after two immunizations with either vaccine used first. The response to vaccination was EBOV GP specific and defined by high antibody binding, Fc effector, and neutralizing responses with CD4 T cell responses also contributing. The vaccine-induced antibody profile did not distinguish people living with or without HIV-1. Samples from 48 survivors and 121 contacts from the 2007 Ugandan Bundibugyo virus epidemic also showed minimal cross-reactivity to other filovirus proteins after infection and exposure. The lack of cross-reactivity suggests that different multivalent vaccine candidates are required to provide broad protection across filoviruses.
Human iPSC–derived nephron progenitor cells treat acute kidney injury and chronic kidney disease in mouse models
Authors: Toshikazu Araoka, Kosuke Toyohara, Makoto Ryosaka, Chihiro Inui, Maasa Matsuura, Chen Ma, Jun Watahiki, Zhongwei Li, Mio Iwasaki, Akira Watanabe, Ryuji Yokokawa, Yasuhiko Tabata, Juan Carlos Izpisua Belmonte, Kenji Osafune
Journal: Science Translational Medicine (2025)

The number of patients requiring dialysis therapy continues to increase worldwide because of the lack of effective treatments for chronic kidney disease (CKD). Furthermore, no curative treatments for acute kidney injury (AKI) have been established. The therapeutic effects of human induced pluripotent stem cell–derived nephron progenitor cells (hiPSC-NPCs) on AKI have been reported in mice but not clinically confirmed. There are also no reports examining the therapeutic potential of hiPSC-NPCs on CKD. Although large numbers of uniform hiPSC-NPCs are required for cell therapies for AKI and CKD, effective expansion cultures remain to be developed. Here, we established a culture medium for cells that enabled more than 100-fold proliferation of hiPSC-NPCs from multiple hiPSC lines in two passages. We demonstrated that hiPSC-NPCs expanded by our medium named CFY or by their conditioned medium alone attenuated kidney injury and improved survival in cisplatin-induced AKI mice. We also observed that hiPSC-NPCs prevented kidney functional decline, interstitial fibrosis, and senescence in aristolochic acid–induced CKD mice. In addition, we found c-MET to be a specific cell surface marker for hiPSC-NPCs and confirmed that purified c-MET + hiPSC-NPCs had therapeutic effects on AKI and CKD mice. Furthermore, we found that hiPSC-NPCs exerted their therapeutic effects in AKI and CKD mice by secreting vascular endothelial growth factor A. Expanded hiPSC-NPCs may be useful cell therapies for AKI and CKD and may open avenues for treating kidney diseases.