tbuckley/cabot-search huggingface dataset:
Clinical factors influencing retreatment with anti-PD-(L)1 therapies after treatment in early-stage cancers: a modified Delphi consensus study
Authors: Lajos Pusztai, Vernon K Sondak, Raquel Aguiar-Ibáñez, Federico Cappuzzo, Christos Chouaid, Chris Elder, Yosuke Hirasawa, Masaru Ishida, Robert Jones, Seung Hyeun Lee, Ryuichi Mizuno, Masayoshi Nagata, David Okonji, Phillip Parente, Bhavesh Shah, Alexander Sun, Dominihemberg Ferreira, Carmel Spiteri, Andrea Lauer, Amrit Kaliasethi, Carol Kao, Smita Kothari, Jan McKendrick
Journal: Journal for ImmunoTherapy of Cancer (2025)

Anti-programmed death (ligand) 1 (anti-PD-(L)1) therapies were first introduced in the metastatic setting and have since been approved and reimbursed for treating early-stage cancers in the adjuvant, perioperative, and neoadjuvant settings in many cancer types. Current evidence supporting anti-PD(L)-1 retreatment after relapse with prior neoadjuvant and/or adjuvant anti-PD(L)1 therapy is limited and inconclusive. There is no guidance for clinicians on how and when to retreat with anti-PD-(L)1 therapies when anti-PD-(L)1 therapy was administered in the neoadjuvant and/or adjuvant setting. This study aimed to reach consensus on factors to guide decision-making regarding retreatment with anti-PD-(L)1 therapies after prior therapy with an anti-PD-(L)1 agent. This modified Delphi study consisted of a clinician survey across 10 countries followed by three real-time virtual Delphi panels involving clinical experts who had completed the survey. Clinical experts were experienced in using anti-PD-(L)1 treatments in early-stage cancers and/or as retreatment of patients with recurrences following early-stage treatment with anti-PD-(L)1 therapies. Of 28 clinicians providing survey responses, 20 participated in one of three Delphi panels. There was consensus that retreatment can be defined as ‘repeated treatment with the same therapeutic class following relapse after or during neoadjuvant and/or adjuvant treatment.’ All three panels agreed that decisions around retreatment should consider ‘prior immune-related adverse events/toxicity,’ ‘time-related factors’ (eg, time since completion of full treatment course and since discontinuation) and ‘previous patient response’ (often referred to by clinicians as tumor response, which may have reflected their experience with metastatic disease). Other factors identified as important included country-specific practices, treatment availability, and reimbursement. Generally, the clinical experts considered that retreatment could be considered from ≥3 to 6 months after stopping initial anti-PD-(L)1 treatment, or from ≥6 months after relapse/recurrence. In conclusion, clinicians across different regions recognized a role for retreating patients with anti-PD-(L)1 therapies after initial anti-PD-(L)1 treatment for early-stage cancers. Consensus was reached on some factors to consider regarding whether and when to retreat, although differences in clinical practice between countries/geographical regions made it difficult to achieve consensus for some more nuanced elements of retreatment. Further evidence could help better inform retreatment decisions.
Response to: Comment on “Nivolumab adjuvant to chemo-radiation in localized muscle-invasive urothelial cancer: primary analysis of a multicenter, single-arm, phase II, investigator-initiated trial (NEXT)”
Authors: Gliceida M Galarza Fortuna, Umang Swami, Sumati Gupta
Journal: Journal for ImmunoTherapy of Cancer (2025)
B7-H3 and CSPG4 co-targeting as Pan-CAR-T cell treatment of triple-negative breast cancer
Authors: Simone Stucchi, Roberto Borea, Susana Garcia-Recio, Manuela Zingarelli, Patrick D Rädler, Elena Camerini, Caroline Marnata Pellegry, Siobhan O’Connor, H Shelton Earp, Lisa A Carey, Charles M Perou, Barbara Savoldo, Gianpietro Dotti
Journal: Journal for ImmunoTherapy of Cancer (2025)

Purpose Chimeric antigen receptor T (CAR-T) cell therapy is under clinical investigation in patients with metastatic triple-negative breast cancer (TNBC). However, the identification of targetable antigens remains a high priority to avoid toxicity and prevent tumor escape. Experimental design Here we analyzed the gene expression of B7-H3 ( CD276 ) and chondroitin sulfate proteoglycan 4 ( CSPG4 ) in 98 TNBC samples identified in the AURORA US Network and Rapid Autopsy RNA sequencing data set at University of North Carolina (UNC). We then performed immunohistochemistry analysis for B7-H3 and CSPG4 protein expression in 151 TNBC samples collected at UNC. Finally, the validity of the proposed B7-H3 and CSGP4 co-targeting was tested in clinically relevant TNBC patient derived xenograft (PDX) models. Results We observed that CD276 and CSPG4 genes are broadly and comparably expressed in TNBC samples, and gene expression is generally conserved in tumor metastases. None of the TNBC analyzed met the criteria for simultaneous low expression of CSPG4 and CD276 genes. Immunohistochemistry analysis showed a median H-score of 138 (105–168, lower and upper quartile, respectively) for B7-H3 expression and a median H-score of 33 (14–78 lower and upper quartile, respectively) for CSPG4 expression. Notably, 49% of the TNBC cores with B7-H3 H-score ≤105 exhibited a CSPG4 H-score exceeding its median value, and 37% and 18% of the TNBC cores with low B7-H3 expression scored CSPG4 expression above its median H-score or exceeded its upper quartile, respectively, confirming that at least one of these two proteins is expressed in 94% of the analyzed tumors. Finally, optimized dual-specific B7-H3 and CSPG4 CAR-T cells eradicated tumors with mixed antigen expression in TNBC PDX models. Conclusions These data highlight the clinical potential of the proposed approach that could be applicable to the great majority of patients with TNBC as well as most of patients with breast cancer in general.
Peripheral blood gene expression profiling shows prognostic significance for the course of interstitial lung disease in systemic sclerosis
Authors: Shervin Assassi, Christopher P. Denton, Matthias Zwick, Ramona Schmid, Carina Ittrich, Tobias Litzenburger, Sudha Visvanathan
Journal: Arthritis & Rheumatology (2025)

Objective We used data from the placebo arm of the SENSCIS trial to determine the prognostic/predictive significance of peripheral blood cell (PBC) transcript modules for the course of forced vital capacity (FVC) in patients with systemic sclerosis‐associated interstitial lung disease (SSc‐ILD) with and without mycophenolate mofetil (MMF) treatment. Methods Patients had SSc‐ILD with first non‐Raynaud symptom within ≤7 years. MMF treatment was permitted if taken at a stable dose for ≥6 months. PBC RNA samples were taken at baseline. Global RNA sequencing was performed, followed by a modular analysis using 62 curated whole blood modules. The prognostic significance of baseline composite modular scores for decline in FVC % predicted at week 52 was analyzed using mixed models for repeated measures. Results Among patients taking MMF (n=120), higher baseline lymphoid lineage and mitochondrial/protein synthesis modules were associated with a better course of FVC % predicted, while higher baseline myeloid lineage and inflammation modules were associated with a faster decline in FVC % predicted. Among patients not taking MMF (n=118), only myeloid lineage and inflammation modules were associated with a faster decline in FVC % predicted. Conclusion Among patients with SSc‐ILD in the SENSCIS trial, PBC modules involved in myeloid lineage were associated with a faster decline in FVC regardless of MMF treatment. Higher baseline lymphoid, protein synthesis and mitochondrial module scores were associated with a better course of SSc‐ILD among patients on MMF treatment. Blood gene expression profiles might be useful prognostic/predictive biomarkers in patients with SSc‐ILD.
Recent Progress in Azobenzene‐Based In Vivo Photopharmacology
Authors: Xin Zhou, Lupei Du, Minyong Li
Journal: Medicinal Research Reviews (2025)

ABSTRACT As the most extensively studied photoswitch in photopharmacology, the azobenzene photoswitch has precision instrumental in the photoregulation of physiological processes across various animal models. Currently, it exhibits the greatest clinical potential for photosensitive retinal restoration, capable of inducing long‐term therapeutic effects following intravitreal injection, without the need for foreign gene expression or optical fiber implantation. A significant advancement in the application of azobenzene photoswitches is their integration with optical flow control technology, which facilitates the targeting of deep tissues within the mouse cerebral cortex, addressing long‐standing challenges related to tissue penetration depth in photopharmacology. With exceptional spatial and temporal resolution, photopharmacology is particularly well‐suited for precision medicine, holding substantial potential for further development. Consequently, a comprehensive summary and review of the design strategies of azobenzene photoswitches for In Vivo applications, along with their experimental outcomes, are essential for guiding future advancements in photopharmacology. This review provides an overview of the fundamental properties and design strategies of azobenzene photoswitch molecules. Additionally, we extensively summarize all azobenzene photoswitch molecules successfully applied In Vivo for photopharmacological purposes since 2006, covering species such as Caenorhabditis elegans , Xenopus tadpoles, zebrafish, mice, rats, rabbits, and canines. Finally, we discuss the challenges associated with the In Vivo implementation of azobenzene photoswitch molecules and propose potential solutions.
Impact of Interleukin‐1 Blockade on the Development of Macrophage Activation Syndrome in Still's Disease: Incidence and Diagnostic Validity of the <scp>EULAR</scp>/<scp>ACR</scp>/<scp>PRINTO</scp> 2016 <scp>MAS</scp> Classification Criteria
Authors: Remco G.A. Erkens, Greta Rogani, Laura Huber, Anouk Verwoerd, Dieneke Schonenberg‐Meinema, J. Merlijn van den Berg, Wineke Armbrust, G. Elizabeth Legger, Sylvia Kamphuis, Ellen J.H. Schatorjé, Esther P.A.H. Hoppenreijs, Joost F. Swart, Marc H.A. Jansen, Jorg van Loosdregt, Sebastiaan J. Vastert
Journal: Arthritis & Rheumatology (2025)

Objective To evaluate the applicability of the 2016 EULAR/ACR/PRINTO macrophage activation syndrome (MAS) classification criteria in patients with Still's disease (sJIA‐SD) treated with IL‐1‐targeted therapy and to assess the incidence of MAS in this context. Methods We analyzed retrospective and prospective data from Dutch sJIA‐SD patients (diagnosis 2008‐2017, n=54) and data from a nationwide prospective Dutch cohort and intervention study (diagnosis 2017‐2022, n=66). From these cohorts, MAS episodes developing in sJIA‐SD patients treated with IL‐1‐targeted therapy (anakinra or canakinumab) with at least two year follow‐up were selected. Clinical and laboratory data was extracted from the electronic patient files. Results A total of 22 patients experienced 29 MAS episodes while on IL‐1‐targeted treatment. 7 patients had recurrent MAS episodes (not all on IL‐1 blockade). The 2016 criteria for MAS in sJIA‐SD were met for 28/29 MAS episodes (97%). Within the prospective nationwide cohort, starting anakinra as first‐line monotherapy, the incidence rate of MAS in the first two years of disease was 18% (12/66 patients, with 11/12 while on IL‐1 inhibition). This incidence is comparable to that observed in historical corticosteroid‐treated patients. Half of MAS episodes occurred within 3 months after diagnosis and Epstein‐Barr virus was the most common identifiable trigger. Conclusion While first‐line anakinra in new‐onset sJIA‐SD has demonstrated high response rates, our data suggests the incidence of MAS in the first two years of disease is not reduced. Patients appear to be particularly at risk early in disease. Importantly, our data shows that the EULAR/ACR/PRINTO 2016 MAS classification criteria remain applicable to patients receiving IL‐1‐targeted therapy.
Is Regional Atrial Strain a Useful Surrogate of Regional Atrial Fibrosis in Atrial Cardiomyopathy?
Authors: Angela W C Lee, Charles Sillett, José Alonso Solis Lemus, Cassia Kessler Iglesias, Luuk H G A Hopman, Alina Hua, Peter Wheen, Abdul Qayyum, Marina Strocchi, Caroline Roney, Thomas Booth, Tevfik F Ismail, Henry Chubb, Daniel B Ennis, Andrew Jabbour, Diane Fatkin, Marco J W Götte, Steven A Niederer
Journal:  (2025)

Abstract Aims To determine whether atrial biomechanics measured using 3D regional strain, LAV and LAEF, are associated with atrial fibrosis in patients with suspected atrial cardiomyopathy. Methods and Results Cardiovascular magnetic resonance (CMR) was performed in AF patients (n=47). Healthy volunteer (n=41), and familial DCM (n=31) cohorts were acquired for normalization and validation, respectively. Fibrosis was quantified using late gadolinium enhancement (LGE)-CMR, and 3D regional strain was quantified using feature tracking. Machine learning classifiers were used to classify regional severe fibrosis (&amp;gt;30% LGE enhancement) using regional strain and global measures of atrial anatomy and function. 3D regional strain measures (peak reservoir strain or 1st/2nd strain principal component) alone were not associated with regional fibrosis (accuracies&amp;lt;=56.0%) in the AF cohort. Severe fibrosis was found primarily in the lateral (85.1% of AF patients) and posterior (66.0%) regions. In AF patients, the classifier incorporating LAV, LAEF and regional location was associated with severe regional fibrosis (AUC=0.86±0.06, accuracy=79.4±6.2%), while in familial DCM patients the accuracy was lower (62.8%). Conclusion There is a distinctive pattern of fibrosis that develops with progression of atrial cardiomyopathy, irrespective of cause. Global measures reflecting overall atrial anatomy (LAV) and function (LAEF), rather than localized regional 3D strain, were associated with severe regional fibrosis. These data suggest that regional atrial 3D strain alone is not a reliable surrogate for severe regional fibrosis.
Functional targeting of ILC2s and ILC3s reveals selective roles in intestinal fibrosis and homeostasis
Authors: Ahmed Kabil, Natalia Nayyar, Chengxi Xu, Julyanne Brassard, Lesley A. Hill, Samuel B. Shin, Sameeksha Chopra, Bernard Lo, Yicong Li, Mya Bal, Marine Theret, Fabio M.V. Rossi, T. Michael Underhill, Michael R. Hughes, Kelly M. McNagny
Journal: The Journal of Experimental Medicine (2025)

Innate lymphoid cells (ILCs) are long-lived, tissue-resident cell analogs to T helper subsets that lack antigen-specific receptors. Understanding the roles of specific ILCs in chronic inflammation and fibrosis has been limited by inadequate tools for selective targeting. Here, we used Il17rb-CreERT2-eGFP and Rorc-Cre strains to selectively delete RORα in ILC2s and ILC3/Th17 cells, respectively. RORα deletion in ILC2s caused significant loss of gastrointestinal ILC2s, increased ILC3 abundance, elevated Th17-type responses, and heightened susceptibility to Crohn’s disease–like fibrosis. Conversely, RORα deletion in ILC3/Th17 cells reduced IL-17 production, protecting against fibrosis. Using isolithocholic acid (isoLCA), a microbial secondary bile acid and RORγt inverse agonist, we confirmed the role of ILC3s/Th17 cells in fibrosis. In RORγt reporter and Th17-deficient Rag1−/− mice, isoLCA reduced IL-17 production by ILC3s and attenuated intestinal fibrosis by dampening RORγt-dependent ILC3/Th17 responses. These findings reveal a novel interplay between ILC2s and ILC3s in gut homeostasis and demonstrate the therapeutic potential of targeting RORγt in ILC3s as a strategy for preventing fibrosis.
Questions and Caveats in Antigen-Defined Membranous Nephropathy
Authors: Nicole K. Andeen, Vanderlene L. Kung, Rupali S. Avasare, Sean Barbour, Megan Griffith, Mei Lin Z. Bissonnette, Candice Roufosse
Journal: Journal of the American Society of Nephrology (2025)

Abstract Remarkable progress has been made in the discovery of autoantigens in membranous nephropathy. With increasing testing for membranous antigens in daily practice, it is important to consider the varying strength of association between certain antigens and underlying conditions. This review explores questions and caveats which arise when assessing results of membranous antigen testing. Specifically, we will discuss: 1) discrepancy between tissue antigen and clinical scenario, focusing on PLA2R; 2) one antigen ≠ one clinical condition, i.e., the heterogeneity of membranous antigens seen in one clinical condition (such as in sarcoidosis), and conversely, heterogeneity of conditions associated with one antigen (such as for neural epidermal growth factor-like 1 (NELL1)); 3) rare presence of multiple membranous associated antigens in tissue or blood (such as with anti-protocadherin 7); and 4) lupus membranous nephritis related antigens and their influence on diagnosis or treatment.
Kelp and Cartilage Acellular Matrix Hybrid Microgel Assembly Realizes Articular Cartilage Repair Via ROS Scavenging, Endogenous BMSC Recruitment and Chondrogenic Differentiation
Authors: Junlin Chen, Qingtao Li, Chuhan Lv, Hongbo Yu, Cheng Dai, Ye Hu, Hua Dong
Journal: Advanced Healthcare Materials (2025)

Abstract Articular cartilage repair remains challenging due to the inherent poor self‐healing capacity and acute inflammation resulting from the over expression of intracellular reactive oxygen species (ROS). Although microfracture is frequently used in practical surgery, the newborn cartilage always exhibits fibrosis, mainly attributed to the weak ROS scavenging and mismatched microenvironment that fails to induce chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Herein, a novel simvastatin (SIM)‐incorporated kelp and cartilage acellular matrix hybrid (labeled as SIM@KACM/CACM) microgel assembly with enhanced ROS scavenging, endogenous BMSC recruitment, and chondrogenic differentiation capabilities is constructed to improve microfracture‐based articular cartilage repair. The kelp acellular matrix exhibits low immunogenicity, high biocompatibility, and ROS scavenging properties, whilst the sustained SIM release promotes BMSC recruitment from the bone marrow cavity. Meanwhile, the microenvironment and bioactive factors conferred by CACM facilitate the BMSC proliferation and differentiation into hyaline cartilage. In addition, the construction of porous microgel assembly via dynamic Schiff's bonds endows excellent injectability and tissue adhesion, which not only enhances its retention in the defect site after injection but also provides abundant sites for BMSC anchoring and infiltration. Due to the synergetic effect of the above‐mentioned multiple factors, the articular cartilage repair is improved dramatically.
MOF‐Based Single‐Atom and Metal Cluster Catalysts by Room‐Temperature Synthesis for Tumor Therapy
Authors: Subin Yu, Haeun Kang, Seohyeon Jee, WooYeon Moon, Dohyub Jang, Wen‐Tse Huang, Dongjun Kim, Kyungwha Chung, Dong‐Il Won, Jungwon Park, Ru‐Shi Liu, Kyungmin Choi, Sehoon Kim, Luke P. Lee, Dong Ha Kim
Journal: Advanced Healthcare Materials (2025)

Abstract Metal–organic frameworks (MOFs) are widely used as substrates for creating single‐atom catalysts due to their abundance of ligands, facilitating enzyme‐like activity for biomedical applications. However, the high‐temperature calcination process for single‐atom catalysts limits economical, efficient, and large‐scale synthesis. Here, a simple room‐temperature synthesis of MOF‐based single‐atom and metal cluster catalysts is presented for tumor therapy. Fe/MOF is obtained through a coordination reaction at room temperature, while Au/MOF is synthesized from Au 3+ /MOF by introducing a reducing agent. Au/MOF effectively generates hydrogen peroxide (H 2 O 2 ) from glucose, outperforming Au 3+ /MOF, and Fe/MOF subsequently produced hydroxyl radicals (•OH) by decomposing the generated H 2 O 2 via accelerated peroxidase‐like activity in an acidic environment. In vitro and in vivo studies confirm a significantly enhanced cancer eradication ability compared to the PBS‐treated group by combining cascade enzymatic activity, destruction of oxidative homeostasis, and excessive mitochondrial‐mediated lipid peroxidation. The novel synthesis process of MOF‐based metal single‐atom catalysts establishes a new paradigm for fabricating effective enzyme‐like nanomaterials for multimodal tumor therapy.
The efficacy of diagnostic imaging for superficial soft tissue masses on a community level.
Authors: Colton Cox, Kyren Maynard, Leila Hollis, Kathryn Glaittli, Dallin Parker, Babe Westlake
Journal: Journal of Clinical Oncology (2025)

e23547 Background: Ultrasound and magnetic resonance imaging (MRI) have both demonstrated high sensitivity and specificity in the diagnosis of soft tissue masses in previous studies. However, there may be a lack of generalizability of these findings to community healthcare settings. We seek to identify the efficacy of two of the most common forms of diagnostics in cases of superficial soft tissue masses, ultrasound and MRI, as well as report the rate of implementation of diagnostic imaging at a community level. Methods: A retrospective chart review was conducted with 343 patients meeting inclusion criteria over a period of 2 years. Data was collected and organized into the various forms of diagnostic workups performed. Diagnostic accuracy was assessed by comparing ultrasound and MRI findings to pathology results, the established gold standard. Results: 56.9% (n=195) of all masses were operated on without ultrasound or MRI, with 6.2%(n=12) being malignant. Of these malignant cases, 58.3% (n=7) of them underwent surgical excision without other forms of diagnostic workup (e.g. CT, pre-surgical biopsy). Among 22 malignant masses evaluated by ultrasound, only 4.5% (n=1) was correctly identified as malignant, while 45.5% (n=10) were incorrectly characterized, and 45.5% (n=10) yielded inconclusive results. In contrast, of 88 benign masses assessed by ultrasound, 81.2% (n=72) were correctly identified, 6.8% (n=6) were incorrectly characterized, and 10.2% (n=9) had inconclusive findings. 8.8% (n=10) went on to be confirmed by MRI despite a correct diagnosis. MRI demonstrated superior accuracy in malignant mass detection, correctly identifying 67.7% (n=21) of 31 malignant cases, with 12.9% (n=4) incorrect characterizations and 19.4% (n=6) inconclusive results. For benign masses, MRI correctly identified 79.4% (n=27) of 34 cases, with 5.9% (n=2) incorrect characterizations and 14.7% (n=5) inconclusive findings. See table for diagnostic performance results. Conclusions: These findings reveal a discrepancy between the ultrasound performance demonstrated in recent studies and its performance at a community level, especially its sensitivity for malignant masses. Due to its low screening ability, 40.9% (n=45) being unable to replace the need for MRI, and the heterogeneity of diagnostic workups performed, there is a need for development of a uniform protocol in the work-up for community healthcare systems. Diagnostic performance of ultrasound and MRI for superficial soft tissue masses. Ultrasound MRI Benign Sensitivity 92.3% (CI 84.0-97.1%) 93.1% (CI 77.2-99.15%) Specificity 9.1% (CI 0.2-41.28%) 84% (CI 63.9-95.5%) Malignant Sensitivity 9.1% (CI 0.2-41.28%) 84% (CI 63.9-95.5%) Specificity 100% (CI 95.1-100%) 96.4% (CI 81.7-99.9%)