tbuckley/cabot-search huggingface dataset:
Neutrophils in cancer: At the crucial crossroads of anti‐tumor and pro‐tumor
Authors: Wenpeng Cai, Tao Fan, Chu Xiao, Ziqin Deng, Yixiao Liu, Chunxiang Li, Jie He
Journal: Cancer Communications (2025)

Abstract Neutrophils are important components of the immune system and play a key role in defending against pathogenic infections and responding to inflammatory cues, including cancer. Their dysregulation indicates potential disease risk factors. However, their functional importance in disease progression has often been underestimated due to their short half‐life, especially as there is limited information on the role of intratumoral neutrophils. Recent studies on their prominent role in cancer have led to a paradigm shift in our understanding of the functional diversity of neutrophils. These studies highlight that neutrophils have emerged as key components of the tumor microenvironment, where they can play a dual role in promoting and suppressing cancer. Moreover, several approaches to therapeutically target neutrophils have emerged, and clinical trials are investigating their efficacy. In this review, we discussed the involvement of neutrophils in cancer initiation and progression. We summarized recent advances in therapeutic strategies targeting neutrophils and, most importantly, suggested future research directions that could facilitate the manipulation of neutrophils for therapeutic purposes in cancer patients.
Integrated role of cardiac magnetic resonance and genetics in predicting left ventricular reverse remodelling in dilated and non‐dilated cardiomyopathy
Authors: Martina Setti, Manuela Iseppi, Job A.J. Verdonschot, Jacopo G. Rizzi, Alessia Paldino, Carola Pio Loco Detto Gava, Giulia Barbati, Matteo Dal Ferro, Max F.G.H.M. Venner, Anne G. Raafs, Marta Gigli, Davide Stolfo, Antonio De Luca, Giulia De Angelis, Teresa M. Capovilla, Sharon Graw, Flavio L. Ribichini, Matthew Taylor, Luisa Mestroni, Stephane R.B. Heymans, Gianfranco Sinagra, Marco Merlo
Journal: European Journal of Heart Failure (2025)

Abstract Aims Left ventricular reverse remodelling (LVRR) is a prognostic marker in patients with dilated (DCM) and non‐dilated left ventricular cardiomyopathy (NDLVC). The utility of combining late gadolinium enhancement (LGE) and genetic testing in predicting LVRR in DCM/NDLVC remains a knowledge gap. This study aimed to assess an integrated approach including LGE data and genetics to predict LVRR in DCM/NDLVC patients. Methods and results This multicentre observational study included DCM/NDLVC patients with: (i) baseline echocardiographic left ventricular ejection fraction (LVEF) &lt;50%; (ii) genetic testing; (iii) baseline cardiac magnetic resonance (CMR); (iv) 12‐month follow‐up echocardiographic data. LVRR was defined as LVEF increase ≥10% or LVEF ≥50% (if baseline LVEF &lt;45%) at 12 months. Outcome measures were: (i) all‐cause mortality, heart transplant, or left ventricular assist device implantation (D/HT/LVAD); (ii) sudden cardiac death or major ventricular arrhythmias (SCD/MVA). Arrhythmogenic genes studied were LMNA , DSP , FLNC, and RBM20 . Among 1757 DCM/NDLVC with genetic data, 616 met eligibility (462 DCM, 154 NDLVC; age 51 ± 14 years, 34% female). LVRR occurred in 314 patients (51%): 251 (54%) in DCM and 63 (41%) in NDLVC ( p = 0.004). Independent predictors of LVRR within 1 year included titin truncating variants, absence of arrhythmogenic genes, and absence of LGE ring‐like pattern. In patients with LVEF &lt;35%, only the presence of LGE ring‐like pattern and arrhythmogenic genes remained independently related to a lower rate of LVRR and increased SCD/MVA risk. Conclusion In a large genetically and CMR characterized DCM/NDLVC cohort, arrhythmogenic genotypes and LGE ring‐like pattern were inversely related to LVRR, particularly in patients with LVEF &lt;35%.
Enzyme‐Instructed Self‐Assembly Reprograms Fatty Acid Metabolism for Cancer Therapeutics
Authors: Hongjian He, Haonan Lin, Le Wang, Xinyan Teng, Samar Aldahan, Meng Zhang, Meihui Yi, Guangrui Ding, Bing Xu, Ji‐Xin Cheng
Journal: Advanced Healthcare Materials (2025)

Abstract Enzyme‐instructed self‐assembly (EISA) is actively explored as a promising therapeutic approach for cancer treatment. However, the metabolic response of cancer cells to EISA remains under‐studied. Here, by stimulated Raman scattering (SRS) imaging in C─H, fingerprint, and silent windows, it is found that the formation of peptide assemblies within and around cancer cells significantly enhances both lipids catabolism and fatty acids (FAs) uptake. It is further found that the increased uptake of FAs aids the resistance of cancer cells under EISA treatment, likely to cope with the stress induced by the peptide assemblies. Combining EISA with FAs uptake inhibition leads to enhanced cancer suppression compared to EISA alone, while additional FAs supplementation rescue cancer cells from EISA treatment, both in vitro and in 3D‐culture spheroid models. These findings shed new light on the impact of EISA on the metabolic activities of cancer cells and suggest a new approach for improved cancer therapy.
Cyclic Enrichment of Urinary Exosomes Using a MOF‐on‐MOF‐Based Asymmetric Impinging Streams Chip for Bladder Cancer Diagnosis and Prognosis Prediction
Authors: Min Liu, Gaihua Jia, Xiangyu Meng, Yuan Rong, Yifan Xia, Yue Hu, Xin He, Jiurong He, Hongjie Shi, Tongzu Liu, Lilong Liu, Wei Zhou, Rui Liu, Guangming Bao, Cheng Liu, Zheng Liu, Fubing Wang
Journal: Advanced Healthcare Materials (2025)

Abstract Urinary exosomes are valuable biomarkers for the liquid biopsy of bladder cancer (BCa), carrying critical biomolecules associated with BCa that assist in clinical diagnosis and prognosis prediction. However, the lack of rapid, efficient, and high‐throughput techniques for urinary exosome enrichment limits their clinical application. This study presents an exosome cyclic enrichment chip based on asymmetric impinging streams and a metal‐organic framework (MOF)‐on‐MOF material. The newly synthesized MOF material exhibited excellent exosome‐enrichment capabilities. Moreover, the integration of asymmetric impinging streams and a cyclic fluidic pathway within the chip notably enhanced the collision efficiency between exosomes and MOF. Leveraging the chip, enables the rapid and efficient enrichment of exosomes from a 10 mL urine sample within 30 min, without the requirement for sample pre‐concentration. In a clinical study of 300 subjects from two centers, a BCa diagnostic model based on urinary exosomal NORAD (Exo‐NORAD) and urine sediment NORAD (Sed‐NORAD) is developed, which showed a higher detection positivity rate than BCa fluorescence in situ hybridization (FISH) and urinary cytology. Exo‐NORAD is identified as an independent prognostic factor for BCa using Cox regression analysis. In conclusion, this study provides a new approach for the noninvasive diagnosis and prognosis prediction of BCa.
Assessment of Hypoxia Before Radioembolization Treatment With 18F-FMISO PET
Authors: Cigdem Soydal, Burak Demir, Emre Can Celebioglu, Ecenur Dursun, Gizem Inal, Nuriye Ozlem Kucuk, Mehmet Sadik Bilgic
Journal: Clinical Nuclear Medicine (2025)

Background: Transarterial radioembolization (TARE) is a therapeutic option for patients with liver tumors. However, factors responsible for treatment resistance in TARE remain largely unknown. In this study, we aimed to investigate the role of hypoxia in the treatment response of liver tumors using 18 F-FMISO PET imaging before TARE. Patients and Methods: This single-center prospective study included 25 patients with primary or metastatic liver tumors imaged with 18 F-FMISO PET/CT before TARE and treated with 90 Y resin microspheres. Posttreatment response was assessed with 18 F-FDG PET imaging. Hypoxia status was evaluated by calculating the tumor-to-muscle (T/M) and tumor-to-blood pool (T/BP) ratios. Absorbed dose metrics were derived from 90 Y PET/MRI imaging post-procedure. Lesions were categorized by response as complete responders (CR), partial responders (PR), stable disease (SD), and progressive disease (PD). Statistical analyses included ROC curve analysis, χ2 tests, and regression models to determine predictors of treatment response. Results: Among 25 patients (mean age: 60.4 ± 12 y, 56% males), 54 18 F-FDG-avid lesions were evaluated. The median absorbed dose (Dmean) was 114.8 Gy for CR, 98.9 Gy for PR, 56.7 Gy for SD, and 78.3 Gy for PD. Significant differences in Dmean ( P = 0.013) and T/BP ratios ( P = 0.011) were observed between responder and nonresponder groups. High Dmean lesions (&gt;89 Gy) had a response rate of 86%, compared with 56% in low Dmean lesions. Hypoxic lesions (T/BP &gt;1.29) showed a 57% response rate, while non-hypoxic lesions (T/BP &lt;1.29) showed a 91% response rate. In combined analyses, while non-hypoxic/high Dmean lesions had the highest response rates (93%), hypoxic/low-dose had the lowest response rate (39%). Conclusions: In this study, we have observed that both mean absorbed radiation dose and hypoxia status are significant predictors of response to treatment after radioembolization of liver tumors. While larger studies are needed to confirm these findings, this pilot study may pave the way for further personalized treatments to achieve better results for radioembolization.
Plastron Appendicitis Mimicking a Malignant Adnexal Mass
Authors: Muhammet Halil Baltacioglu
Journal: Clinical Nuclear Medicine (2025)

Plastron appendicitis is a rare complication of acute appendicitis, characterized by localized and encapsulated inflammation within the surrounding tissues. It accounts for ∼4%–5% of all acute appendicitis cases. The mass-like appearance of plastron appendicitis can mimic various malignant pathologies, particularly those of the adnexal region. Due to its rarity, diagnosing plastron appendicitis can be challenging. Advanced imaging techniques, such as 18 F-FDG PET/CT, are crucial in differentiating it from other pathologies. In this case presentation, we aim to present the 18 F-FDG PET/CT and contrast-enhanced CT imaging findings of a patient with plastron appendicitis, which was initially suspected to be a malignant adnexal mass.
Superior NET Targeting by Switch From Agonist to Antagonist-mediated Somatostatin Receptor Theranostics Allowing Successful (LM3-based) PRRT of Otherwise Precluded mNET: Intraindividual Proof-of-concept
Authors: Tilman Speicher, Caroline Burgard, Florian Rosar, Moritz Bastian, Mark Bartholomä, Stephan Maus, Samer Ezziddin
Journal: Clinical Nuclear Medicine (2025)

We present a case of a 69-year-old woman with metastasized small bowel NET G2 initially treated with somatostatin analogs (SSA). Disease progression was observed under SSA, and poor tracer uptake on [ 68 Ga]Ga-DOTATOC PET/CT precluded peptide receptor radionuclide therapy (PRRT). Subsequently, evaluation with [ 68 Ga]Ga-NODAGA-LM3 PET/CT was performed, which showed markedly better and treatment-sufficient uptake, enabling initiation of PRRT with [ 177 Lu]Lu-DOTA-LM3. After 4 therapy cycles, a positive response was observed. This interesting case nicely demonstrates not only the diagnostic superiority of somatostatin receptor antagonist (over agonist) imaging but also the direct translation into successful targeted peptide-mediated radionuclide therapy.
Aggregation‐Assisted Three‐Photon Fluorescence Resonance Energy Transfer Boosts Phosphorescence for Deep‐Tissue Time‐Resolved Intravital Brain Imaging
Authors: Bingshun Wu, Yifei Li, Lan Liu, Yuchen Yang, Han Wu, Mubin He, Ben Zhong Tang, Zheng Zheng
Journal: Advanced Healthcare Materials (2025)

Abstract Three‐photon phosphorescence microscopic bioimaging holds promise for deep‐tissue time‐resolved brain imaging with high spatial resolution and contrast. However, developing probes with bright phosphorescence and strong second near‐infrared (NIR‐II) three‐photon absorption suitable for biological applications remains a formidable challenge. Herein, a kind of fluorescence resonance energy transfer (FRET)‐based nanoparticles (NPFA‐PorPt NPs) is proposed by co‐encapsulation of a three‐photon absorbing aggregation‐induced emission luminogen (NPFA), and a phosphorescent platinum octaethylporphyrin (PorPt) using 1,2‐distearoyl‐sn‐glycero‐3‐phosphoethanolamine‐N‐[methoxy(polyethylene glycol)‐2000] as the encapsulation matrix. NPFA is well designed to display superior three‐photon absorption properties in the NIR‐II region and its emission overlaps well with the absorption of PorPt, allowing efficient energy transfer to PorPt in nanoparticles. The phosphorescence of PorPt in the optimal NPFA‐2%PorPt NPs is boosted by 350‐fold as compared to that of pure PorPt aggregates upon the same excitation. The strong three‐photon excited phosphorescence enables NPFA‐2%PorPt NPs to be successfully applied for in vivo time‐resolved brain and muscle vascular imaging with deep penetration, high spatial resolution, and contrast, and even the small capillaries in the deep tissue can be recognized. This study paves the way for the development of highly efficient multiphoton‐absorbing phosphorescent probes for biomedical applications.
Role of insulinemic and inflammatory dietary patterns on gut microbial composition and circulating biomarkers of metabolic health among older American men
Authors: Sushma Nepal, Ni Shi, Rebecca Hoyd, Daniel J. Spakowicz, Eric Orwoll, James M. Shikany, Nicola Napoli, Fred K. Tabung
Journal: Gut Microbes (2025)

Chronic low-grade inflammation and hyperinsulinemia are linked with metabolic dysfunction and dysbiosis. This study investigated the role of dietary inflammatory and insulinemic potential on gut microbiome and circulating health biomarkers in older men. Data from the Osteoporotic Fractures in Men (MrOS) study were analyzed. Reversed Empirical Dietary Inflammatory Pattern (rEDIP), Empirical Dietary Index for Hyperinsulinemia (rEDIH), and Healthy Eating Index (HEI)-2020 scores were computed from food frequency questionnaire data. Stool samples were profiled using 16S rRNA sequencing. Elastic net regression identified diet-associated microbial profiles and multivariable-adjusted linear regression assessed diet-biomarker associations. Higher rEDIP, rEDIH, and HEI-2020 scores were positively associated with gut microbiota alpha diversity. Specific genera, including Intestinibacter and Lachnospira, associated positively, while Dielma, Peptococcus, Feacalitalea, and Negativibaccilus associated inversely with healthier dietary patterns. When evaluating changes in dietary patterns between baseline and visit 4 ( ~ 14 years), these genera tended to define rEDIP, rEDIH more than HEI-2020. In addition, higher dietary quality was linked to better biomarker profiles, including lower creatinine, sodium, triglycerides, and insulin resistance. Beneficial effects of higher dietary quality on health may be mediated by the ability of diet to regulate gut microbial composition and metabolic biomarker profiles.
Mechanosensory Piezo2 regulated by gut microbiota participates in the development of visceral hypersensitivity and intestinal dysmotility
Authors: Haonan Zheng, Yuzhu Chen, Siqi Lu, Zuojing Liu, Yinchao Ma, Cunzheng Zhang, Yiming Zhang, Jindong Zhang, Chang Liu, Ming Chu, Fei Pei, Shuangjiang Liu, Liping Duan
Journal: Gut Microbes (2025)

The gut microbiota plays a crucial role in the manifestation of intestinal dysfunction associated with irritable bowel syndrome (IBS). The mechanosensory Piezo2 has been implicated in the regulation of intestinal function. However, it remains unclear whether Piezo2 is modulated by the gut microbiota, thus contributing to the development of visceral hypersensitivity and gut dysmotility. The study enrolled patients with diarrhea-predominant IBS (IBS-D) alongside healthy controls (HC). Questionnaires, rectal barostat test, and colonoscopy with mucosal biopsy were conducted. Fecal microbiota transplantation (FMT) was performed using samples from HC or IBS-D patients, and interventions with Akkermansia muciniphila or Fusobacterium varium were carried out on colon- or dorsal root ganglion (DRG)- Piezo2 knockdown pseudo-germ-free mice. Visceral sensitivity and intestinal motility were assessed. Piezo2 levels were detected using western blot and immunofluorescence. Fecal 16S rRNA sequencing and cecum untargeted metabolomics analysis, followed by molecular docking predictions of Piezo2, were also performed. The ratio of Piezo2+/5-HT+ cells was lower in IBS-D patients, positively correlated with visceral sensation and intestinal dysbiosis. The mice that received FMT from IBS-D patients exhibited colonic dysmotility and visceral hypersensitivity, along with elevated Piezo2 protein levels in the colon and DRG. Knockdown of Piezo2 in the colon or DRG ameliorated the FMT-induced colonic dysmotility and visceral hypersensitivity. Fecal 16S rRNA sequencing revealed distinct microbiota composition. Notably, Fusobacterium varium, but not Akkermansia muciniphila, induced gut dysmotility and visceral hypersensitivity, effects that could be alleviated by colon or DRG Piezo2 knockdown. Additionally, Fusobacterium varium lead to increased Piezo2 protein levels, as well as elevated levels of indole-3-acetic acid and indole-3-acrylic acid, which were predicted to bind to Piezo2, causing disturbances. Piezo2 can be regulated by gut microbiota and involved in visceral hypersensitivity and colonic dysmotility, with Fusobacterium varium playing a crucial role.
Prospective phase II trial of first-line rituximab, methotrexate, and orelabrutinib (R-MO) in primary central nervous system lymphoma
Authors: Lixia Sheng, Hailing Liu, Xiaohui Zhang, Kaiyang Ding, Jie Ma, Hongling Peng, Xia Zhao, Mei Sun, Wei Shi, Feiyan Zhang, Jianyong Li, Lei Cao, Lei Fan
Journal: Blood Cancer Journal (2025)
Updated insights into the molecular networks for NLRP3 inflammasome activation
Authors: Seungwha Paik, Jin Kyung Kim, Hyo Jung Shin, Eun-Jin Park, In Soo Kim, Eun-Kyeong Jo
Journal: Cellular and Molecular Immunology (2025)

Over the past decade, significant advances have been made in our understanding of how NACHT-, leucine-rich-repeat-, and pyrin domain-containing protein 3 (NLRP3) inflammasomes are activated. These findings provide detailed insights into the transcriptional and posttranslational regulatory processes, the structural-functional relationship of the activation processes, and the spatiotemporal dynamics of NLRP3 activation. Notably, the multifaceted mechanisms underlying the licensing of NLRP3 inflammasome activation constitute a focal point of intense research. Extensive research has revealed the interactions of NLRP3 and its inflammasome components with partner molecules in terms of positive and negative regulation. In this Review, we provide the current understanding of the complex molecular networks that play pivotal roles in regulating NLRP3 inflammasome priming, licensing and assembly. In addition, we highlight the intricate and interconnected mechanisms involved in the activation of the NLRP3 inflammasome and the associated regulatory pathways. Furthermore, we discuss recent advances in the development of therapeutic strategies targeting the NLRP3 inflammasome to identify potential therapeutics for NLRP3-associated inflammatory diseases. As research continues to uncover the intricacies of the molecular networks governing NLRP3 activation, novel approaches for therapeutic interventions against NLRP3-related pathologies are emerging.
RORγt eTACs mediate oral tolerance and Treg induction
Authors: Im-Hong Sun, Anita E. Qualls, Han S. Yin, Jiaxi Wang, Matthew P. Arvedson, Joe Germino, Nolan K. Horner, Sheng Zhong, Juan Du, Martin Valdearcos, Vasilis Ntranos, Richard M. Locksley, Roberto R. Ricardo-Gonzalez, James M. Gardner
Journal: The Journal of Experimental Medicine (2025)

The immune system must distinguish pathogens from innocuous dietary antigens, but the precise mechanisms and cellular actors remain unclear. Here, we demonstrate that RORγt-lineage APCs are required for oral tolerance. Using lineage tracing and single-cell sequencing, we show these APCs consist of three principal populations: type 3 innate lymphoid cells (ILC3s), RORγt-lineage dendritic cells, and cells expressing Aire called RORγt eTACs (R-eTACs)-also known as Janus or Thetis cells. We show that R-eTACs, but not ILC3s, are required for oral tolerance induction. We find R-eTACs are of probable myeloid origin and uniquely express integrin β8 (Itgb8). Both MHCII and Itgb8 expression in RORγt-lineage cells are necessary to induce food-specific regulatory T cells. Mice lacking R-eTACs or with deletion of MHCII or Itgb8 in the RORγt lineage fail to generate Tregs and instead develop a T-follicular helper response with elevated antigen-specific antibodies. These findings establish R-eTACs as critical mediators of oral tolerance and suggest novel cellular targets to modulate immune tolerance.
Cellular Versus Acellular Matrix Products for Diabetic Foot Ulcer Treatment: The Dermagraft and Oasis Longitudinal Comparative Efficacy Study (DOLCE)—A Randomized Clinical Trial
Authors: Harrison Shawa, Ramanjot Kaur, Catherine Tchanque-Fossuo, Hadar Lev-Tov, Kaitlyn West, Pallas Sulgi Lim, Nuen Tsang Yang, Mirabel Dafinone, Rawlings Everett Lyle, Chin-Shang Li, David Rocke, Sara Dahle, Roslyn Rivkah Isseroff
Journal: Diabetes Care (2025)

OBJECTIVE To determine whether cellular matrix (CM) products result in better healing rates than acellular matrix (ACM) products for nonhealing diabetic foot ulcers. RESEARCH DESIGN AND METHODS The Dermagraft and Oasis Longitudinal Comparative Efficacy Study (DOLCE) was a randomized, single-blinded, three-arm controlled trial. Patients (aged ≥18 years) with a full-thickness nonhealing diabetic foot ulcer who met inclusion/exclusion criteria were enrolled. RESULTS Of 169 eligible patients, 138 were enrolled and 117 randomly assigned. For 12 weeks, patients received standard of care (SOC), CM, or ACM. The primary outcome was the percentage of wounds healed by 12 weeks. Of the 117 participants, 41 were in the CM group, 48 in the ACM group, and 28 in the SOC group. There were 21 withdrawals, but seven had reached the first primary end point. Complete re-epithelialization of the ulcer by 12 weeks occurred in 59% of the 117 total participants: 49% in the CM group, 69% in the ACM group, and 57% in the SOC group (P = 0.16 by χ2 test). At 28 weeks, 25 participants (61%) in the CM group, 27 (56%) in the ACM group, and 18 (64%) in the SOC group had healed (P = 0.78). No differences were found in wound recidivism or adverse event occurrence between groups. CONCLUSIONS No difference in efficacy was found between SOC, ACM, and CM, suggesting that SOC can reduce the economic burden of diabetic foot ulcer treatment.