tbuckley/cabot-search huggingface dataset:
3D-printed PCL scaffolds combined with injectable sodium alginate/magnesium-doped mesoporous bioactive glass nanosphere hydrogel for meniscus regeneration: In vitro, In vivo, and multiomics-based therapeutic analyses
Authors: Hao Li, Yongkang Yang, Tianze Gao, Runmeng Li, Chao Wang, Xue Wang, Tianyuan Zhao, Qinyu Tian, Zhixing Zhang, Ruiyang Zhang, Quanyi Guo, Zhiguo Yuan, Peifu Tang
Journal: Bioactive Materials (2025)
Reply to: “Precision nutrition in aging: Enhancing frailty prevention through personalized dietary interventions”
Authors: Rosy Conforto, Valeria Rizzo, Raffaella Russo, Elisa Mazza, Samantha Maurotti, Carmelo Pujia, Elena Succurro, Franco Arturi, Yvelise Ferro, Angela Sciacqua, Arturo Pujia, Tiziana Montalcini
Journal: Metabolism (2025)
Hepatocellular carcinoma: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up
Authors: A Vogel, S L Chan, L A Dawson, R K Kelley, J M Llovet, T Meyer, J Ricke, L Rimassa, G Sapisochin, V Vilgrain, J Zucman-Rossi, M Ducreux
Journal: Annals of Oncology (2025)
RESET: A reversible TCR-coupled antigen receptor with superior targeting sensitivity and pharmacologically controlled anti-tumor activity
Authors: Jardin Leleux, Jillian Rosenberg, Olmo Sonzogni, Rebecca L Walker, Anita Venkitaraman, Sarah M Garrison, Nan Jin, Philip D Gregory, Jordan Jarjour
Journal: Molecular Therapy (2025)

Chimeric antigen receptor (CAR) T cells are effective cancer therapies, particularly in indications with high, stable, and tumor-specific antigen expression. Other settings may require improved targeting sensitivity, controllable targeting selectivity, and/or additional potency enhancements to achieve robust efficacy. Here, we describe a novel receptor architecture called RESET (rapamycin-enabled, switchable endogenous T cell receptor) that combines (1) cell surface antigen targeting, (2) small-molecule regulation, and (3) the signaling proficiency and inherent sensitivity of native T cell receptors. RESET-T cells outperformed both constitutive and drug-regulated CAR-T cells and show hallmarks of TCR activation that suggest improved fidelity to native T cell responses. Pharmacological control then increases safety through toggling T cell activation between active and resting states and may mitigate T cell exhaustion caused by continuous antigen exposure. This convergence of drug-regulated targeting and natural immune receptor signal transduction may better replicate the kinetics and physiology of a classical T cell response and potentiate more successful and safer immunotherapies.
ZP4: A Novel Target for CAR T Cell Therapy in Triple Negative Breast Cancer
Authors: Lauren K Somes, Jonathan T Lei, Xinpei Yi, Diego F Chamorro, Paul Shafer, Ahmed Z Gad, Lacey E Dobrolecki, Emily Madaras, Nabil Ahmed, Michael T Lewis, Bing Zhang, Valentina Hoyos
Journal: Molecular Therapy (2025)
Bullous pemphigoid
Authors: Hossein Akbarialiabad, Enno Schmidt, Aikaterini Patsatsi, Yen Loo Lim, Anisa Mosam, Kaisa Tasanen, Jun Yamagami, Maryam Daneshpazhooh, Dipankar De, Adela Rambi G Cardones, Pascal Joly, Dedee F Murrell
Journal: Nature Reviews Disease Primers (2025)
Skeletal muscle and subcutaneous fat quantity as prognostic indicators in cardiac amyloidosis
Authors: Joshua Longinow, Saeid Mirzai, Po‐Hao Chen, Mazen Hanna, W.H. Wilson Tang
Journal: European Journal of Heart Failure (2025)

Aims Disease‐related changes in body composition are associated with worse outcomes in chronic heart failure. In cardiac amyloidosis (CA), the prognostic value of direct body composition measures is understudied. Methods and results We identified 160 consecutive patients with CA (transthyretin [ATTR] or light chain [AL]) diagnosed between 2001 and 2021 who had chest computed tomography within 1 year before diagnosis. Skeletal muscle index (SMI), intermuscular adipose tissue percentage (IMAT%), and subcutaneous adipose tissue index (SATI) were quantified at the twelfth vertebral level and analysed continuously, in sex‐stratified tertiles, and with derived outcome‐based cutoffs. In a comprehensive model including IMAT% and SATI, only SMI independently predicted 10‐year mortality (hazard ratio 0.69 per standard deviation increase, 95% confidence interval 0.52–0.91, p = 0.010). In tertile analyses, low SMI was associated with 2 to 2.5 times higher 1‐year, 5‐year, and 10‐year mortality versus high SMI. Medium IMAT% and SATI showed approximately 1.9 times higher 5‐year and 10‐year mortality versus high tertiles. These associations were more pronounced in ATTR‐CA, with low SATI also predicting higher mortality. AL‐CA showed fewer significant associations. Interaction testing by CA type was not significant. Outcome‐based SMI cutoffs of 23.5 cm 2 /m 2 (males) and 27.8 cm 2 /m 2 (females) for 10‐year mortality were derived but need validation. Conclusion Lower SMI was associated with increased mortality risk in patients with CA, particularly ATTR‐CA. The relationship between SATI and mortality was more nuanced: in the overall cohort, medium SATI was associated with higher mortality risk, while in patients with ATTR‐CA, lower SATI predicted higher mortality risk.
Characteristics, determinants, and prognostic impact of severe tricuspid regurgitation in patients with atrial functional mitral regurgitation: Insights from the <scp>REVEAL</scp>‐<scp>AFMR</scp> registry
Authors: Tomohiro Kaneko, Azusa Murata, Masashi Amano, Yukio Sato, Yohei Ohno, Masaru Obokata, Kimi Sato, Taiji Okada, Wataru Fujita, Kojiro Morita, Tomoko Machino‐Ohtsuka, Yukio Abe, Tohru Minamino, Nobuyuki Kagiyama
Journal: European Journal of Heart Failure (2025)
EBNA1 Targeted Ultra‐Small Near‐Infrared Persistent Luminescent Nano‐Inhibitor for Theranostics of EBV‐Associated Cancer
Authors: Yanping Xie, Yunfei Zhu, Ya Wen, Siqi Hu, Ju Jiao, Yue Wu, Lijun Jiang, Bruno Viana, Ka‐Leung Wong, Jing Wang, Rui Zou
Journal: Advanced Healthcare Materials (2025)

Abstract Epstein–Barr virus (EBV) is a well‐recognized oncogenic virus that promotes several lymphoid and epithelial cancers. The Epstein–Barr nuclear antigen 1 (EBNA1), which is known to be expressed in all EBV‐positive cancers, plays a vital role in viral genome replication and maintenance and is therefore emerged as an attractive target for clinical intervention. Several EBNA1 inhibitors have shown potency in the growth inhibition of EBV‐positive cancers, yet low bioavailability and in vivo unmonitored nature hamper their further implementation. Here a novel EBNA1 nano‐inhibitor based on EBNA1‐specific peptide inhibitor (P4) functionalized ZnGa 2 O 4 :Cr 3+ ultra‐small near‐infrared persistent luminescent (NIR‐PL) nanoparticles (ZGOC‐P4) is developed. Owing to the specific binding to EBNA1, ZGOC‐P4 nano‐inhibitor can quickly achieve nuclear internalization in EBV‐positive nasopharyngeal carcinoma (NPC) cells (C666‐1) and selectively inhibit their growth. In sharp contrast, ZGOC‐P4 nano‐inhibitor shows no inhibition effect on EBV‐negative NPC cells (HK‐1). Moreover, the results indicate that the well‐designed nano‐inhibitor enables efficient tumor‐targeting accumulation in NPC xenograft model under the monitoring of autofluorescence interference‐free NIR‐PL imaging in vivo and suppresses EBV‐associated tumor growth with an inhibition rate of 61.6%. This work highlights the potency of ZGOC‐P4 on NPC treatment and may provide new sight into future research on EBV‐associated diseases.
Microneedle Assisted Melittin‐Chondroitin Sulfate Administration for the Transdermal Therapy of Rheumatoid Arthritis
Authors: Lili Jin, Zhenhui Wang, Cheng Peng, Miao He, Feng Wang, Hongyan He, Changsheng Liu
Journal: Advanced Healthcare Materials (2025)

Abstract Rheumatoid arthritis (RA), a persistent and debilitating chronic disease characterize by joint damage and deformity, significantly impairs the life quality of patients and presents challenges for conventional drug administration due to organ damage and unsatisfactory therapeutic outcomes. To address these challenges, this study introduces an innovative hydrogel cryo‐microneedle patch (CMNP)‐mediated local administration system, primarily composed of chondroitin sulfate (CS), to deliver the potent anti‐inflammatory drug melittin (MEL). This innovative approach not only circumvents organ impairment but also enhances patient compliance. The acute toxicity of MEL is effectively mitigated by electrostatic binding with CS molecules, forming MC complexes that induce apoptosis in fibroblast‐like synoviocytes (FLS). The MC‐loaded CMNPs (MC@CCMNPs) exhibit remarkable therapeutic capacity with a notably meliorated joint damage and suppressed arthritis severity in the RA rat model. Therefore, MC@CCMNPs emerge as a promising anti‐inflammatory and safe therapy for RA treatment, as well as for other inflammation related chronic diseases.
Continuous High‐Throughput Plasma Separation for Blood Biomarker Sensing Using a Hydrodynamic Microfluidic Device
Authors: Hesam Abouali, Fatemeh Keyvani, Seied Ali Hosseini, Sanjana Srikant, Mahla Poudineh
Journal: Advanced Healthcare Materials (2025)

Abstract Continuous, cost‐effective, high‐throughput with admissible yield and purity of blood plasma separation is widely needed for biomarker detection in the clinic. The existing gold standard technique (centrifugation) and microfluidic technologies fall short of meeting these criteria. In this study, a microfluidic device design is demonstrated based on passive hydrodynamic principles to achieve admissible yield and purity plasma samples. Through computational and experimental assessments, it is shown that side channels with varying lengths are required to improve the plasma extraction rate. The optimized side channels in this device design use the formed cell‐free layer regions in the expanded areas to extract plasma consistently and efficiently. These Hydrodynamic Continuous, High‐Throughput Plasma Separator (HCHPS) microfluidic devices achieve a purity in the range of 47% to 64% with whole blood and maintaining a yield of 10% to 18%, with half hemolysis compared to gold standard centrifugation. These devices also separate the plasma from diluted blood with a purity in the range of 62% to 97% with a similar yield range. Additionally, whole human blood spiked with lactate was processed through the HCHPS device, and the separated plasma is collected and analyzed using two biosensing approaches, a bead‐based fluorescence, and an electrochemical aptamer biosensing, confirming the quality of plasma for downstream biomarker detection.
A Comparison of the Mechanical Properties of ECM Components and Synthetic Self‐Assembling Peptides
Authors: Alex Hartley, Philip Michael Williams, Alvaro Mata
Journal: Advanced Healthcare Materials (2025)

Abstract The field of tissue engineering is increasingly moving away from a one‐size‐fits‐all approach of simple synthetic homogeneous gels, and embracing more tailored designs to optimize cell function and differentiation for the organ of interest. Extracellular matrix (ECM) proteins are still the optimal route for controlling cell function, while a field of great promise is that of synthetic self‐assembling peptides (SSAPs), which are fully biocompatible, biodegradable, and offer both the hierarchical structure and dynamic properties displayed by protein networks found in natural tissue. However, the mechanical properties of neither group have been comprehensively reviewed. In this review, rheological data and the Young's modulus of the most prevalent proteins involved in the ECM (collagen I, elastin, and fibronectin) are collated for the first time, and compared against the most widely researched SSAPs: peptide amphiphiles (PAs), β‐sheets, β‐hairpin peptides, and Fmoc‐based gels (with a focus on PA‐E3, RADA16, MAX1, and FmocFF, respectively).
Corrigendum to “Recommendations for the use of next-generation sequencing (NGS) for patients with advanced cancer in 2024: a report from the ESMO Precision Medicine Working Group”
Authors: M F Mosele, C B Westphalen, A Stenzinger, F Barlesi, A Bayle, I Bièche, J Bonastre, E Castro, R Dienstmann, A Krämer, A M Czarnecka, F Meric-Bernstam, S Michiels, R Miller, N Normanno, J Reis-Filho, J Remon, M Robson, E Rouleau, A Scarpa, C Serrano, J Mateo, F André
Journal: Annals of Oncology (2025)
KLF2 expression in IgG plasma cells at their induction site regulates the migration program
Authors: Wataru Ise, Takuya Koike, Nozomi Shimada, Hiromi Yamamoto, Yuki Tai, Taiichiro Shirai, Ryoji Kawakami, Mana Kuwabara, Chie Kawai, Kyoko Shida, Takeshi Inoue, Nozomi Hojo, Kenji Ichiyama, Shimon Sakaguchi, Katsuyuki Shiroguchi, Kazuhiro Suzuki, Tomohiro Kurosaki
Journal: The Journal of Experimental Medicine (2025)

Newly generated plasma cells in secondary lymphoid organs migrate to niches in the bone marrow, wherein they survive as long-lived plasma cells (LLPCs). Although LLPCs have been extensively characterized, it is still unclear what the key determinant(s) are for plasma cell longevity. One model postulates that plasma cell heterogeneity is established at the induction site, thereby instructing their longevity. Here, we found that, among newly generated IgG plasma cells, integrin β7hi marks plasma cells predisposed to home to the bone marrow, whereas integrin β7lo cells remain in secondary lymphoid organs. Mechanistically, this egress-prone fraction had a higher expression of the KLF2 transcription factor, the loss of which resulted in defective egress by downregulating S1PR1 and CD11b. Disruption of plasma cell egress results in defective antibody durability, thereby making mice more susceptible to influenza reinfection. Thus, the migration program of plasma cells established at the induction site plays a critical role in determining antibody durability.
A “second hit” impacts disease severity in a dominantly inherited genetic skin disorder
Authors: Pierre A. Coulombe
Journal: The Journal of Experimental Medicine (2025)

In this issue of JEM, Bergson et al. (https://doi.org/10.1084/jem.20240827) identified variants in HMCN1 that co-segregate with and account for variations in disease severity in individuals with a diagnosis of epidermolysis bullosa simplex (EBS) resulting from pathogenic variants in KRT14. The authors show that hemicentin-1 binds keratin 14 at the protein level and that silencing HMCN1 expression disrupts the organization of K14-containing filaments in epidermal keratinocytes and their attachment to the extracellular matrix. These findings address the clinical heterogeneity observed in EBS, a rare genetic skin disorder, with general implications for all genodermatoses.
Transforming tumors into ‘high-risk bombs’ triggers a neoantigen storm and amplifies immune responses
Authors: Yunlong Li, Quanwei Sun, Zexin Yang, None LuoMin, Wenshuo Yang, Zhengwei Song, Kang Liu, Huihui Li, Wenheng Gao, Qinghua Wu, Wei Shen, Ye Yang, Dengke Yin
Journal: Journal of Controlled Release (2025)
Body composition and checkpoint inhibitor treatment outcomes in advanced melanoma: a multicenter cohort study
Authors: Mark Schuiveling, Laurens S Ter Maat, Isabella A J Van Duin, Rik J Verheijden, Max F Troenokarso, Pim Moeskops, Joost J C Verhoeff, Sjoerd G Elias, Wouter A C Van Amsterdam, Femke Burgers, Franchette W P J Van Den Berkmortel, Marye J Boers-Sonderen, Martijn F Boomsma, Jan Willem De Groot, John B A G Haanen, Geke A P Hospers, djura Piersma, Gerard Vreugdenhil, Hans M Westgeest, Ellen Kapiteijn, Mariette Labots, Wouter B Veldhuis, Paul J Van Diest, Pim A De Jong, Josien P W Pluim, Tim Leiner, Mitko Veta, Karijn P M Suijkerbuijk
Journal: JNCI Journal of the National Cancer Institute (2025)

Abstract Introduction The association of body composition with checkpoint inhibitor outcomes in melanoma is a matter of ongoing debate. In this study, we aim to investigate body mass index (BMI) alongside CT-derived body composition metrics in the largest cohort to date. Methods Patients treated with first-line anti-PD1 ± anti-CTLA4 for advanced melanoma were retrospectively identified from 11 melanoma centers in The Netherlands. From baseline CT scans, five body composition metrics were extracted: subcutaneous adipose tissue index, visceral adipose tissue index and skeletal muscle index, density and gauge. These metrics were correlated in uni- and multivariable Cox proportional hazards analysis with progression-free, overall and melanoma-specific survival (PFS, OS and MSS). Results A total of 1471 eligible patients were included. Median PFS and OS were 9.1 and 38.1 months, respectively. Worse PFS was observed in underweight patients (multivariable HR = 1.86, 95% CI 1.14–3.06). Furthermore, prolonged OS was observed in patients with higher skeletal muscle density (multivariable HR = 0.88, 95% CI 0.81-0.97) and gauge (multivariable HR = 0.61, 95% CI 0.82-0.998), whereas higher visceral adipose tissue index was associated with worse OS (multivariable HR = 1.12, 95% CI 1.04-1.22). No association with survival outcomes was found for overweight, obesity or subcutaneous adipose tissue. Discussion Our findings suggest that underweight BMI is associated with worse PFS, whereas higher skeletal muscle density and lower visceral adipose tissue index were associated with improved OS. These associations were independent of known prognostic factors, including sex, age, performance status and extent of disease. No significant association between higher BMI and survival outcomes was observed.
Chiral nanoassembly remodels tumor microenvironment through non-oxygen-dependent depletion lactate for eﬀective photodynamic immunotherapy
Authors: Xuan Zhang, Jinwei Bai, Shihao Sun, Yu Li, Xinxin Li, Genping Meng, Wenyuan Cheng, Yuhui Yin, Zhiyi Wang, Baodui Wang
Journal: Biomaterials (2025)
Validation of a digital pathology-based multimodal artificial intelligence biomarker in a prospective, real-world prostate cancer cohort treated with prostatectomy
Authors: Anders Bjartell, Agnieszka Krzyzanowska, Vinnie Y.T. Liu, Meghan Tierney, Trevor J. Royce, Martin Sjöström, Marisol Macarena Palominos-Rivera, Emmalyn Chen, Alexandra Kraft, Andre Esteva, Felix Y. Feng
Journal: Clinical Cancer Research (2025)

A multimodal artificial intelligence (MMAI) biomarker was developed using clinical trial data from North American men with localized prostate cancer (PCa) treated with definitive radiation, using biopsy digital pathology images and key clinical information (age, PSA, T-stage) to generate prognostic scores. This study externally validates the biomarker in a prospective, real-world dataset of men who underwent radical prostatectomy (RP) for localized PCa at a tertiary referral center in Sweden. Association between the MMAI scores (continuously and categorically) and endpoints of interest were performed with Fine-Gray and cumulative incidence analyses for biochemical recurrence (BCR) and logistic regression for adverse pathology (AP) at RP. The analysis included 143 patients with evaluable biopsy pathology images and complete clinical data to generate MMAI scores. Median follow-up was 8.8 years. At diagnosis, median PSA was 7.5 ng/mL, median age 64 years, 29% had Gleason grade group ≥3, and 88 men were evaluable for AP at RP. MMAI was significantly associated with BCR (subdistribution HR 2.45 [95% CI 1.77-3.38], p<0.001) and AP at RP (OR 4.85 [95% CI 2.54-10.78], p<0.001). Estimated 5-yr BCR rates for MMAI Intermediate-High vs Low were 25% (95% CI 16%-36%) vs 4% (95% CI 1%-11%), respectively. The MMAI biomarker, previously shown to be prognostic for distant metastasis and prostate cancer-specific mortality in men receiving definitive radiation, was prognostic for post-RP endpoints: BCR and AP. This biomarker validation study further supports the use of MMAI biomarkers in men with PCa outside North America and those treated with RP.
LCK–co-receptor association ensures T cell lineage fidelity and maximizes epitope-specific TCR diversity
Authors: Justin B. Zhang, Priyanka Chaurasia, Angela Nguyen, Zijian Huang, Trang T. Nguyen, Hui Xu, Mai T. Tran, Hugh H. Reid, Claerwen M. Jones, Stefan A. Schattgen, Daniel Thiele, Paul G. Thomas, Jeanette Rientjes, Kim L. Good-Jacobson, Roland Ruscher, Dene R. Littler, Jamie Rossjohn, Pirooz Zareie, Nicole L. La Gruta
Journal: Science Immunology (2025)

The interaction between the CD4/CD8 co-receptors and LCK (an Src family tyrosine kinase) is thought to augment T cell activation upon recognition of peptide-loaded major histocompatibility complexes (pMHCs). How this interaction influences antigen-specific T cell development is unclear however, as is its impact on naïve and immune antigen-specific T cell repertoires. In mice expressing mutated endogenous LCK unable to bind co-receptors (LCK FREE mice), we show that influenza A virus (IAV)–derived pMHC-specific CD8 and CD4 T cell responses had a significantly narrowed T cell receptor (TCR) repertoire, favoring high-affinity TCRs. This narrowing was established during T cell development and was exacerbated after viral infection. The dissociation of LCK from co-receptors also resulted in the redirection of CD4-fated T cells to the CD8 lineage, with expanded pMHCII-specific cytotoxic CD8 T cells observed after IAV infection. Thus, LCK–co-receptor association is critical for ensuring T cell lineage fidelity and maximizing antigen-specific T cell repertoire diversity.
Estrogen Control of Social Behaviors
Authors: Oluwadamilola O. Lawal, Dayu Lin, Julieta E. Lischinsky
Journal: Annual Review of Neuroscience (2025)

Social behaviors, including parental care, mating, and fighting, all depend on the hormonal milieu of an organism. Decades of work highlighted estrogen as a key hormonal controller of social behaviors, exerting its influence primarily through binding to estrogen receptor alpha (Esr1). Recent technological advances in chemogenetics, optogenetics, gene editing, and transgenic model organisms have allowed for a detailed understanding of the neuronal subpopulations and circuits for estrogen action across Esr1-expressing interconnected brain regions. Focusing on rodent studies, in this review we examine classical and contemporary research demonstrating the multifaceted role of estrogen and Esr1 in regulating social behaviors in a sex-specific and context-dependent manner. We highlight gaps in knowledge, particularly a missing link in the molecular cascade that allows estrogen to exert such a diverse behavioral repertoire through the coordination of gene expression changes. Understanding the molecular and cellular basis of Esr1’s action in social behaviors provides insights into the broader mechanisms of hormone-driven behavior modulation across the lifespan.
Phase Separation–Mediated Compartmentalization Underlies Synapse Formation and Plasticity
Authors: Xiandeng Wu, Zeyu Shen, Mingjie Zhang
Journal: Annual Review of Neuroscience (2025)

The synapse is polarized and highly compartmentalized on both its pre- and postsynaptic sides. The compartmentalization of synaptic vesicles, as well as vesicle releasing and recycling machineries, allows neurotransmitters to be released with precisely controlled timing, speed, and amplitude. The compartmentalized and clustered organization of neurotransmitter receptors and their downstream signaling enzymes allows neuronal signals to be properly received and amplified. Synaptic adhesion molecules also form clustered assemblies to align pre- and postsynaptic subcompartments for synaptic formation, stability, and transmission. Recent studies indicate that such synaptic and subsynaptic compartmentalized organizations are formed via phase separation. This review discusses how such condensed subsynaptic compartments may form and function in the context of synapse formation and plasticity. We discuss how phase separation allows for the formation of multiple distinct condensates on both sides of a synapse and how such condensates communicate with each other. We also highlight how proteins display unique properties in condensed phases compared to the same proteins in dilute solutions.